Cholesterol is an essential molecule for the biosynthesis of cell membranes and cell proliferation and differentiation， and the liver plays a central role in cholesterol metabolism and is responsible for the synthesis， uptake， secretion， and transport of cholesterol. The initial stages of cholesterol synthesis in the liver are particularly important， and abnormalities in such stages are closely associated with the progression of various liver diseases. Studies have shown that as a key rate-limiting enzyme in cholesterol biosynthesis， 3-hydroxy-3-methylglutaryl-coenzyme A reductase （HMGCR） has well-defined regulatory properties and has been confirmed as an important target for the regulation of various liver diseases. This article reviews the process of cholesterol metabolism， the degradation and regulatory mechanisms of HMGCR， and the application of inhibitors， as well as the role of HMGCR in liver diseases， in order to provide new insights for scientific research and the clinical prevention and treatment of liver diseases.

BACKGROUND:Cervical rotation-traction manipulation is effective and safe in the treatment of cervical spondylotic radiculopathy,and has been widely used in clinical work.However,its effects on the biomechanics of cervical vertebra and intervertebral disc and the area of intervertebral foramen have not been systematically clarified. OBJECTIVE:Based on the finite element analysis technique,a relevant research and analysis were carried out to provide digital evidence for the mechanism of effect of cervical rotation-traction manipulation in the treatment of cervical spondylotic radiculopathy. METHODS:The CT image data of a volunteer with no neck diseases were selected as the finite element model material at its left-handed physiological limit position.The initial construction of the finite element model was completed by Mimics 19.0 software,Geomagic Studio 2013 software,Hypermash 14.0 software,and ANSYS Workbench 2020 R2 software,respectively.Based on the literature,the grid division of cervical structure and the assignment of elastic modulus and elastic coefficient were completed.Based on the previous work of the team,the mechanical effects of cervical rotation-traction manipulation were simulated on the model.Effects of cervical rotation-traction manipulation on the mechanical parameters of each vertebral body and intervertebral disc in C3-T1 segment and on the cervical lateral foramen area were analyzed. RESULTS AND CONCLUSION:(1)During cervical rotation-traction manipulation,the stress of bone structure was significantly higher than that of soft tissue such as intervertebral disc.(2)When operating the technique,the stress at the top of each cervical vertebra was higher,the stress at the bottom was lower,and the stress at the facet joint and transverse process was lower.The stress at the top of the intervertebral disc was lower,the stress at the bottom was higher,but the highest point of the intervertebral disc stress was outside the top.(3)In addition,after loading the lifting force,the projected area of the C6/C7 intervertebral foramen increased significantly compared with that before loading.(4)It is indicated that the cervical rotation-traction manipulation has the mechanical characteristics of changing the stress structure of the cervical spine itself,and can expand the C6/7 intervertebral cervical foramen area on the opposite side of the patient's cervical rotation,so as to achieve the purpose of treating cervical spondylotic radiculopathy.

OBJECTIVES: To investigate the effect of cardiomyocytes-derived exosomes on lipopolysaccharide (LPS)-induced cardiomyocyte injury and its mechanism. METHODS: Exosomes isolated from rat cardiomyocytes with or without LPS treatment were co-cultured with rat lymphocytes. The lymphocytes with or without exosome treatment were co-cultured with LPS-induced rat cardiomyocytes for 48 h. Cardiomyocyte apoptosis was detected using flow cytometry, and the expressions of apoptosis marker proteins and the PI3K/AKT pathway proteins were detected using Western blotting. The effects of human recombinant IL-38 protein on apoptosis and protein expressions in LPS-induced cardiomyocytes were examined. RESULTS: Compared with normal cardiomyocyte-derived exosomes, the exosomes from LPS-induced cardiomyocytes significantly enhanced proliferation and increased mRNA and protein expression levels of IL-38 in rat lymphocytes. Bioinformatics analysis suggested that miR-1275 in the exosome played a key role in LPS-induced cardiomyocyte injury, and in dual luciferase reporter gene assay, miR-1275 mimics significantly increased luciferase activity of WT-IL-38. Co-culture with lymphocytes treated with exosomes from LPS-induced cardiomyocytes significantly inhibited apoptosis of LPS-induced cardiomyocytes. Treatment with recombinant IL-38 also effectively lowered apoptosis rate of LPS-induced cardiomyocytes, reduced cellular expression of Bax protein, and increased the protein expression levels of Bcl-2, p-PI3K and p-AKT. CONCLUSIONS miR-1275 in exosomes derived from LPS-induced cardiomyocytes mediates IL-38 up-regulation expression in lymphocytes to activate the PI3K/AKT pathway and inhibit LPS-induced cardiomyocyte apoptosis.
Apoptosis/drug effects* ; MicroRNAs/metabolism* ; Myocytes, Cardiac/metabolism* ; Animals ; Lipopolysaccharides ; Rats ; Exosomes/metabolism* ; Up-Regulation ; Interleukins/metabolism* ; Lymphocytes/cytology* ; Cells, Cultured ; Signal Transduction ; Coculture Techniques ; Phosphatidylinositol 3-Kinases/metabolism* ; Rats, Sprague-Dawley ; Humans ; Proto-Oncogene Proteins c-akt/metabolism*

Objectives:To investigate the predictive factors of stroke associated-pneumonia (SAP) in patients with acute stroke, develop nomogram and neural network prediction models and verify their predictive performance.Methods:Patients with acute stroke admitted to the First Affiliated Hospital of Kunming Medical University and Zhenxiong County People's Hospital were included retrospectively. Multivariate logistic regression analysis was used to determine the independent predictive factors of SAP, and develop nomogram and neural network prediction models. Receiver operating characteristic curve (ROC) curves were used to validate and compare the predictive performances. Results:A total of 450 patients with acute stroke were enrolled, including 286 males (63.6%), aged 64.28±13.24 years; 344 patientss (76.4%) had ischemic stroke and 106 (23.6%) had hemorrhagic stroke; 128 patients (28.4%) experienced SAP. According to the random number method, they were divided into a modeling cohort ( n=300) and a validation cohort ( n=150). Multivariate logistic regression analysis in the modeling cohort showed that a higher baseline National Institutes of Health Stroke Scale (NIHSS) score, gastric tube placement, use of proton pump inhibitors, heart failure, and higher neutrophil/lymphocyte ratio (NLR) were the independent predictive factors of SAP. ROC curve analysis showed that the area under the ROC curve of the nomogram model for predicting SAP in the modeling cohort and validation cohort was 0.841 (95% confidence interval [ CI] 0.795-0.880) and 0.863 (95% CI 0.798-0.914), respectively. The sensitivity for predicting SAP were 75.00% and 70.45%, respectively, and the specificity was 81.94% and 92.45%, respectively. The area under the ROC curve of the neural network model for predicting SAP in the modeling cohort and validation cohort was 0.847 (95% CI 0.802-0.866) and 0.862 (95% CI 0.796-0.913), respectively. The sensitivity for predicting SAP were 76.19% and 72.73%, and the specificity was 79.17% and 89.62%, respectively. Conclusions:Higher NIHSS score, gastric tube placement, use of proton pump inhibitors, heart failure, and higher NLR are the independent risk factors for SAP in patients with acute stroke. The nomogram and neural network prediction model developed using the above risk factors have higher predictive value for SAP.

Objective To investigate the expression of long non-coding RNA LINC00460 in lung adenocarcino-ma(LUAD)and its effects on cell proliferation and migration.Methods Quantitative real-time polymerase chain reaction(RT-qPCR)was used to detect the expression of LINC00460 in LUAD cell lines(PC-9,A549,NCI-H1975 and H1299)and normal lung cell line(MRC-5).LINC00460 was silenced in A549 and H1299 cells using small interfering RNA(siRNA),followed by cell proliferation assessment with CCK-8 assay and evaluation of cell migration capacity through the Transwell assay.Fluorescence in situ hybridization(FISH)and RNA immunoprecipitation(RIP)assays were performed to determine the subcellular localization of LINC00460 and its interaction with EZH2.Western blot was applied to examine EZH2 and H3K27me3 ex-pression in cells.Results LINC00460 was highly expressed in LUAD cells,and the expression level was sig-nificantly decreased after silencing(P＜0.001).Silencing LINC00460 markedly inhibited the proliferation and migration of A549 and H1299 cells(P＜0.001).LINC00460 was primarily localized in the nucleus.RIP assays confirmed a significant interaction between LINC00460 and EZH2(P＜0.001).Furthermore,the silencing of LINC00460 resulted in a significant reduction in the expression of EZH2 and its downstream target H3K27me3(P＜0.001).Conclusions LINC00460 is highly expressed in LUAD cells.Silencing LINC00460 inhibits cell proliferation and migration through EZH2.This mechanism provides a basis for LINC00460 as a potential therapeutic target in lung adenocarcinoma.

Objective To investigate the effect of microRNA-146a-5p(miR-146a-5p)on high glucose-induced injury of renal tubular epithelial cells by regulating high mobility group A2(HMGA2).Methods Human renal tubular epithelial cells(HK-2)were cultured in vitro and di-vided into different groups according to various treatment methods:normal control group(Con group),high glucose group(HG group),HG+miR-146a-5p group,HG+si-HMGA2 group,HG+miR-146a-5p+pcDNA-HMGA2 group,miR-NC group,miR-146a-5p group,anti-miR-NC group,and anti-miR-146a-5p group.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the expression levels of miR-146a-5p and HMGA2 mRNA in each group.A dual-luciferase reporter assay was employed to verify the targeting relationship between miR-146a-5p and HMGA2.Western blot was utilized to detect the expression levels of cleaved-caspase3,cleaved-caspase9,and HMGA2 protein in each group.Flow cytometry was applied to determine the apoptosis rate of cells in each group.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of inflam-matory factors[interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interleukin-8(IL-8)]in each group.The levels of oxidative stress indicators[catalase(CAT),superoxide dismutase(SOD),malondialdehyde(MDA)]in each group were also measured.Results A nucleotide se-quence complementary to miR-146a-5p was found in the 3'-untranslated region(3'-UTR)of HMGA2.The expression level of HMGA2 protein in the miR-146a-5p group was lower than that in the miR-NC group,while was higher in the anti-miR-146a-5p group than that in the anti-miR-NC group(P＜0.05).The total apoptosis rate,early apoptosis rate,late apoptosis rate,and the levels of cleaved-caspase3 protein,cleaved-caspase9 protein,HMGA2 mRNA,HMGA2 protein,TNF-α,IL-6,IL-8,and MDA in the HG group were higher than those in the Con group,whereas the levels of miR-146a-5p,CAT,and SOD were lower(P＜0.05).In the HG+miR-146a-5p group,these indicators showed opposite trends compared to the HG group(P＜0.05).Similarly,in the HG+si-HMGA2 group,the total apoptosis rate,early apoptosis rate,late apoptosis rate,and the levels of cleaved-caspase3 protein,cleaved-caspase9 protein,HMGA2 mRNA,HMGA2 protein,TNF-α,IL-6,IL-8,and MDA were lower than those in the HG group,while the levels of CAT and SOD were higher(P＜0.05).In the HG+miR-146a-5p+pcDNA-HMGA2 group,the trends of these indicators were consistent with those between the HG group and the HG+miR-146a-5p group,showing statistically significant differences when compared to the HG+miR-146a-5p group(P＜0.05).Conclusion MiR-146a-5p may play a regulatory role in high glucose-induced injury of re-nal tubular epithelial cells by targeting HMGA2.

Objective:Evaluate the occurrence of repeated hospitalizations during the DRG payment reform of a tertiary general hospital and attempt to establish an operational method for evaluating decomposed hospitalization.Methods:The relevant data of inpa-tients in a tertiary public hospital in Beijing from November 1,2020,to August 31,2023,were collected,the occurrence of repeated hospitalization before and after the DRG reform were compared,and the suspicious decomposed hospitalization groups were screened and analyzed.Results:After the DRG reform,the incidence of 14-day,7-day,3-day,and same-day repeated hospitalization increased significantly compared with that before the reform(P＜0.05).Malignancies of the digestive system,a disease with a high readmission rate in the four categories,had a consistency of 6.02％in the ADRG group for two adjacent repeated hospitalizations,and the subsequent admissions of this disease may be assigned to different DRG groups for payment settlement.Conclusion:It is crucial to further enhance the medical insurance payment system,clarify criteria for"decomposed hospitalization",reduce the supervision cost of decomposed hospitalization,and prioritize management strategies targeting avoidable unplanned readmissions.

Objective:To investigate the characteristics of cortical morphology in children with attention defi-cit hyperactivity disorder(ADHD)and those with oppositional defiant disorder(ODD)from both categorical and dimensional analyses.Methods:A total of 72 children were enrolled,including 16 children with ADHD and ODD,20 children with ADHD without ODD,and 36 age-gender-matched normal children.The diagnoses were made ac-cording to the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)criteria.The Chi-nese Wechsler Intelligence Scale for Children(C-WISC)was used to access intelligence quotient.All subjects par-ticipated in the magnetic resonance imaging(MRI)scan.The features of cortical morphology were determined using FreeSurfer software.Results:Children with ADHD and ODD[(6 528.1±857.5)mm3 vs.(7 591.2±657.3)]and children with ADHD only[(6 867.2±41.3)mm3 vs.(7 591.2±657.3)mm3]had smaller volume in the left later-al superior temporal gyrus(P＜0.05)than controls.No difference was found between ADHD with ODD group and ADHD without ODD group.There was no correlation between the cortical volume of left lateral superior temporal gyrus and ODD symptoms.Conclusion:The reduced cortical volume of left lateral superior temporal gyrus may be an important indication of the abnormal brain structure of ADHD in children.And comorbid status of ODD dose not change this structural variation.

Objective:To systematically review the predictive model for de novo stress urinary incontinence (de novo SUI) after pelvic organ prolapse (POP) surgery, with the aim of providing reference for preventing the occurrence of de novo SUI.Methods:Literature on the prediction model of de novo SUI after POP surgery was electronically retrieved in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, WanFang, and VIP. The search period was from the establishment of the database to December 31, 2023, and the language was limited to Chinese and English. Two researchers independently screened literature, extracted data, and used the prediction model risk of bias assessment tool (PROBAST) to evaluate the quality of the models.Results:A total of 13 articles were included, including 13 de novo SUI risk prediction models. One literature was a prospective study, one literature was a secondary analysis of data, and the rest were retrospective studies. The area under the receiver operating characteristic curve in nine models ranged from 0.595 to 0.842, and the C-index of three models ranged from 0.710 to 0.738. Five models were not validated or only internally validated after construction. Six models were validated in one external population. The predictive performance of one model was validated in six external populations. The overall applicability of the 13 prediction models was good, but there was a certain risk of bias in all of them. Conclusions:There is a significant difference in the predictive performance of the de novo SUI risk prediction model after POP surgery, and the number is relatively small, indicating that it is still in the development stage. Future research should continuously optimize existing models and conduct external validation, and construct predictive models suitable for postoperative de novo SUI in POP patients in China.