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

Objective To evaluate the safety and efficacy of simultaneous surgical resection combined with thermal ablation in sequential treatment of patients with multiple primary lung cancer (MPLC). Methods Patients with MPLC who underwent simultaneous, sequential surgical resection combined with thermal ablation at Shangjin Branch of West China Hospital of Sichuan University from April 2023 to May 2024 were retrospectively included, and their perioperative and follow-up data were analyzed. Results A total of 23 patients with MPLC were enrolled, including 4 males and 19 females, with a mean age of (51.61±12.38) years. Cumulatively, 48 lesions were resected and 23 lesions were ablated. About half of the patients (52.17%) had surgery and ablation treatment located in the same lung. All patients completed the combined treatment without intraoperative complications. Four patients had postoperative complications, and were effectively managed and successfully discharged. The median postoperative hospital stay was 4.00 (4.00, 4.00) days. The average follow-up duration was (11.78±4.90) months, with a local control rate of 100.00% at 6 months postoperatively. No deaths or tumor occurred during the follow-up. Conclusion Simultaneous surgery with thermal ablation in sequential treatment for MPLC is safe, flexible and effective, providing a new option for this group of patients, but further studies are needed to evaluate its long-term efficacy.

OBJECTIVE: To explore the clinical presentation and genetic etiology of a case with Xeroderma pigmentosum in conjunct with basal cell carcinoma and melanoma. METHODS: A male patient with Xeroderma pigmentosum treated at Xinxiang Central Hospital in October 2022 was selected as study subject. Whole exome sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing of his family members. This study was approved by the Ethics Committee of the hospital (Ethics No.: 2021-167). RESULTS: Magnetic resonance imaging showed that the patient has a solid soft tissue mass in the anterior and lower part of his right eyeball and a small nodule on the left nasal wing. Histopathological biopsy showed that the periocular tumor was basal cell carcinoma in conjunct with malignant melanoma, and the nasal wing tumor was basal cell carcinoma. WES and Sanger sequencing revealed that he has harbored compound heterozygous variants of the XPC gene, namely c.2391delT (p.F797Lfs*11) and IVS1+1G>A, which were inherited from his father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were rated as likely pathogenic (PVS1+PM2_Supporting+PM3) and pathogenic (PVS1+PM2_Supporting+PM3+PP5), respectively. The c.2391delT variant was unreported previously. Bioinformatic analysis suggests that it could significantly affect the tertiary structure of XPC protein. CONCLUSION The c.2391delT(p.F797Lfs*11) and IVS1+1G>A compound heterozygous variants probably underlay the pathogenesis in this patient. The detection of the novel variant has enriched the mutational spectrum of the XPC gene.
Humans ; Male ; Xeroderma Pigmentosum/genetics* ; Basal Cell Carcinoma/genetics* ; DNA-Binding Proteins/genetics* ; Melanoma/genetics* ; Mutation ; Skin Neoplasms/genetics* ; Middle Aged ; Exome Sequencing ; Pedigree

Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from ¹³C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

Objective To investigate the role of lncRNA SNHG1 in homocysteine-induced pyroptosis of podocyte.Methods Cbs+/-mice were randomly divided into two groups:a normal diet group(ND)and a high me-thionine diet group(HMD).Western blotting was used to detect the protein expression levels of Caspase-1,Cleaved Caspase-1,and NLRP3.Mouse renal glomerular podocytes were cultured in vitro,and then assigned into a control group(Control,0 μmol/L Hcy)and a homocysteine intervention group(Hcy,80 μmol/L Hcy).Western blotting was used to detect the protein expression levels of Caspase-1,Cleaved Caspase-1,and NLRP3.Mouse renal glomerular podocyion group(OE-NC + Hcy)and the lncSNHG1 overexpression + homocysteine intervention group(OE-SNHG1 + Hcy)were also established.After 48 hours of intervention,Real-time fluorescence quantita-tive PCR was used to detect the expression of lncSNHG1 in podocytes after Hcy intervention.Western blot was used to detect the expressions of Caspase-1,Cleaved Caspase-3 and NLRP3.Immunofluorescence was used to de-tect the expression levels of GSDMD and GSDMD-N.ELISA was used to detect the contents of IL-1β and IL-18.Results(1)In the animal experiments,the expression levels of pyroptosis-related proteins Caspase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were all increased in the HMD group compared with the ND group.(2)In the cellular experiments,the expression levels of Caspase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were all increased in the Hcy group compared with the Control group,and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased as well.(3)In the cellular experiments,the expres-sion of lncSNHG1 was increased in the Hcy group compared with the control group.After transduction with lnc-SNHG1 lentivirus,the expression of lncSNHG1 was increased in the OE-SNHG1 group,compared with the control group and the OE-NC group.(4)In the cellular experiments,the expressions of pyroptosis-related proteins Cas-pase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were increased compared with the OE-NC+Hcy group,and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased in the OE-SNHG1+Hcy group.Conclusion These results indicate that lncSNHG1 may play a role in promoting Hcy induced podocytepyroptosis.

Objective To explore the value of automated functional imaging(AFI)in predicting coronary artery stenosis in patients without ventricular wall motion abnormalities.Methods A total of 40 patients without ventricular wall motion abnormalities under two-dimensional echocardiography and confirmed coronary artery heart diseases(CHD)(coronary stenosis≥70％)by coronary angiography(CAG)at the Xinxiang Central Hospital from July 2018 to September 2019 were selected as the research subjects.The detection rates of coronary artery stenosis ≥70％by AFI and CAG were compared.With reference to CAG as the gold standard,the predictive value of AFI for coronary artery stenosis ≥70％was evaluated.Results There was no significant difference in the detection rates of coronary artery stenosis ≥70％by AFI and CAG(x2=1.667,P＞0.05).The predictive efficacy of AFI for coronary artery stenosis ≥70％was as follows:a sensitivity of 100％,a specificity of 63.6％,the positive predictive value of 69.2％,the negative predictive value of 100％,and an accuracy of 80％for predicting stenosis ≥70％in the left anterior descending artery;a sensitivity of 56.2％,a specificity of 91.6％,the positive predictive value of 81.8％,the negative predictive value of 75.8％,and an accuracy of 77.5％for predicting stenosis ≥70％in the left circumflex artery;a sensitivity of 95.6％,a specificity of 47.0％,the positive predictive value of 70.9％,the negative predictive value of 88.0％,and an accuracy of 75.0％for predicting stenosis ≥70％in the right coronary artery;the overall sensitivity of 85.9％,the overall specificity of 69.8％,the overall positive predictive value of 72.0％,the overall negative predictive value of 84.6％,and the overall accuracy of 77.5％.Conclusion AFI can provide a sensitive,objective,non-invasive,and inexpensive examination method for the early clinical forecast of coronary artery stenosis.

In response to the limitation of some medical image segmentation models for rectal cancer auxiliary diagnosis that are only applicable to single-modality images,a medical image segmentation method based on a cross attention mechanism that is applicable to both CT and MRI modalities is presented.Considering the different feature representations of CT and MRI images,a cross attention mechanism is proposed to unify the feature representations of the two types of images.In view of the small lesions on rectal cancer images,an improved Swin Transformer segmentation network with 3 branches is established,and the cross attention mechanism is incorporated into it,enabling the model to segment lesion areas in both types of images.The proposed method is validated using CT and MRI image data from patients with rectal cancer.Compared with ADDA,CycleGAN,and SIFA methods,the proposed method improves the accuracy by 2.94%,3.05%,0.71%on CT images,and 3.31%,4.55%,1.76%on MRI images,respectively,demonstrating its superior segmentation performance for both types of images.

Objective To investigate the protective effect of miR-328-3p on oxidized low-density lipoprotein(ox-LDL)-induced coronary artery endothelial cell injury and the potentially relevant mechanisms.Methods Human coronary artery endothelial cells(HCAECs)were induced with ox-LDL,and the cells were divided into a control group consisting of normal cells,an ox-LDL group receiving ox-LDL treatment,an ox-LDL+miR-NC group transfected with miR-NC and treated with ox-LDL,an ox-LDL+miR-328-3p group transfected with miR-328-3p and treated with ox-LDL,and ox-LDL+miR-328-3p+pcDNA group co-transfected miR-328-3p and pcDNA and treated with ox-LDL,and an ox-LDL+miR-328-3p+insulin-like growth factor 2(IGF2)group co-transfected miR-328-3p and IGF2 and treated with ox-LDL.The expression level of miR-328-3p was determined with RT-qPCR.Cell proliferation was determined by MTT.Cell apoptosis was measured by flow cytometry.Western blot was conducted to examine the protein expression levels of cleaved cas-3 and IGF2.ELISA was performed to determine the levels of tumor necrosis factor α(TNF-α),interleukin(IL)-6,and IL-1β.Dual luciferase reporter experiment was performed to verify the targeting relationship between miR-328-3p and IGF2.Results Compared with those of the control group,miR-328-3p expression level and cell activity were significantly reduced in the ox-LDL group(P＜0.05),while the apoptotic rate,the protein expression levels of cleaved cas-3,IGF2,Bax,and Bcl-2,and the levels of TNF-α,IL-6,and IL-1β were significantly increased(P＜0.05).Compared with those of the ox-LDL+miR-NC group,miR-328-3p expression level and cell activity significantly increased in the ox-LDL+miR-328-3p group(P＜0.05),while the apoptosis rate,the protein expression levels of cleaved cas-3 and IGF2,and the levels of TNF-α,IL-6,and IL-1β were significantly reduced.IGF2 was a functional target of miR-328-3p.Compared with those of the ox-LDL+miR-328-3p+pcDNA co-transfection group,the IGF2 protein level was significantly increased(P＜0.05)and cell activity was significantly decreased(P＜0.05)in the ox-LDL+miR-328-3p+IGF2 co-transfection group,while the apoptosis rate,cleaved cas-3 protein level,and the levels of TNF-α,IL-6,and IL-1β were significantly elevated(P＜0.05).Conclusion miR-328-3p inhibits ox-LDL-induced apoptosis and inflammatory in coronary artery endothelial cell injury through targeted negative regulation of IGF2.

Purpose: Prostate cancer (PCa) is an epithelial malignancy that originates in the prostate gland and is generally categorized into low, intermediate, and high-risk groups. The primary diagnostic indicator for PCa is the measurement of serum prostate-specific antigen (PSA) values. However, reliance on PSA levels can result in false positives, leading to unnecessary biopsies and an increased risk of invasive injuries. Therefore, it is imperative to develop an efficient and accurate method for PCa risk stratification. Many recent studies on PCa risk stratification based on clinical data have employed a binary classification, distinguishing between low to intermediate and high risk. In this paper, we propose a novel machine learning (ML) approach utilizing a stacking learning strategy for predicting the tripartite risk stratification of PCa. Methods: Clinical records, featuring attributes selected using the lasso method, were utilized with 5 ML classifiers. The outputs of these classifiers underwent transformation by various nonlinear transformers and were then concatenated with the lasso-selected features, resulting in a set of new features. A stacking learning strategy, integrating different ML classifiers, was developed based on these new features. Results: Our proposed approach demonstrated superior performance, achieving an accuracy of 0.83 and an area under the receiver operating characteristic curve value of 0.88 in a dataset comprising 197 PCa patients with 42 clinical characteristics. Conclusions This study aimed to improve clinicians’ ability to rapidly assess PCa risk stratification while reducing the burden on patients. This was achieved by using artificial intelligence-related technologies as an auxiliary method for diagnosing PCa.

ObjectiveTo investigate the influence of sarcopenia on bone mass loss， the risk factors for bone mass loss in liver cirrhosis， and the correlation between body composition and bone mineral density （BMD） by comparing the clinical features of bone mass loss in patients with liver cirrhosis. MethodsA total of 92 patients who were hospitalized and diagnosed with liver cirrhosis in Department of Gastroenterology， The Second Affiliated Hospital of Kunming Medical University， from April to December of 2022 were enrolled， and based on the results of dual-energy X-ray absorptiometry， they were divided into bone mass loss group （osteopenia/osteoporosis） with 57 patients and normal bone mass group with 35 patients. The two groups were compared in terms of general data， laboratory examination， imaging data， and body composition analysis. The independent samples t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the continuity correction chi-square test was used for comparison of categorical data between two groups； Pearson correlation analysis and Spearman correlation analysis were used to investigate correlation； a binary logistic regression analysis was used to investigate the risk factors for bone mass loss in liver cirrhosis. ResultsCompared with the normal bone mass group， the bone mass loss group had significantly higher age （t=-3.597， P<0.05）， proportion of female patients （χ²=8.393， P<0.05）， N-terminal middle molecular fragment of osteocalcin （N-MID） （Z=-3.068， P<0.05）， β isomer of C-terminal telopeptide of type I collagen （β-CTX） （t=-2.784， P<0.05）， and proportion of patients with sarcopenia （χ²=13.884， P<0.05） and significantly lower calcitonin （CT） （Z=-2.340， P<0.05） and L3 skeletal muscle index （L3-SMI） （t=4.621， P<0.05）. Compared with the normal bone mass group， the bone mass loss group had significantly lower total muscle mass （Z=-2.952， P<0.05）， right upper limb muscle mass （Z=-2.929， P<0.05）， left upper limb muscle mass （Z=-2.680， P<0.05）， right lower limb muscle mass （Z=-3.366， P<0.05）， left lower limb muscle mass （Z=-3.374， P<0.05）， presumed bone mass （t=2.842， P<0.05）， body water mass （Z=-2.779， P<0.05）， basal metabolic rate （BMR） （Z=-3.153， P<0.05）， and BMD of L1— L4 and femoral neck （t=9.789， t=10.280， t=10.832， Z=-7.298， t=8.945， all P<0.05）. Total muscle mass， muscle mass of trunk and limbs， presumed bone mass， BMR， and body water mass in body component analysis were positively correlated with L1 — L4 BMD and femoral neck BMD （all P<0.05）， and fat mass was positively correlated with L1 — L4 BMD （all P<0.05）. Sarcopenia （odds ratio ［OR］=8.737， 95% confidence interval ［CI］： 2.237 — 34.129， P=0.002）， age （OR=1.094， 95%CI： 1.019 — 1.175， P=0.013）， and N-MID （OR=1.095， 95%CI： 1.019 — 1.176， P=0.014） were independent risk factors for bone mass loss in patients with liver cirrhosis. ConclusionOld age， female sex， sarcopenia， elevated N-MID， elevated β-CTX， reduction in CT， low muscle mass， low presumed bone mass， low BMR， and low body water mass are the features of bone mass loss in patients with liver cirrhosis， and sarcopenia， age， and N-MID are independent risk factors for bone mass loss in patients with liver cirrhosis. Detailed assessment of body composition changes can help to identify abnormal BMD in patients with liver cirrhosis.