Osteoporosis and diabetes represent major global public health challenges. Neutrophil extracellular traps (NETs) serve as key components of the innate immune system by capturing and eliminating pathogens. This exploratory study aimed to preliminarily identify biomarkers associated with NETs in osteoporosis with diabetes and to provide initial insights into underlying molecular mechanisms. A transcriptomic sequencing dataset was integrated to analyze the molecular profiles of comorbid osteoporosis and diabetes (OP-DM). The NETs-related genes (NETs-RGs) were curated from previous literature. As a pilot investigation, biomarkers were identified through differential analysis, machine learning, and receiver operating characteristic (ROC). These candidate biomarkers were further evaluated by qRT-PCR and ELISA. Subsequently, molecular regulatory network construction, immune infiltration analysis, enrichment analysis, and drug prediction were conducted to generate hypotheses. S100A12 and SLC25A37 were identified as potential biomarkers. Their significant upregulation at the protein level (S100A12 and SLC25A37) was observed in an independent cohort. Enrichment analysis suggested that S100A12 was significantly enriched in 68 pathways, including “ECM-receptor interaction” and “maturity onset diabetes of the young”. SLC25A37 was significantly enriched in 54 pathways, primarily including “ribosome” and “Toll-like receptor signaling pathway”. A total of 7 immune cell types exhibited differences between the two groups. Furthermore, the XIST-hsa-miR-146a-5p-S100A12 and XIST-hsa-miR-7-5-SLC25A37 axes were suggested to have potential regulatory roles. Drugs such as rimegepant and eptinezumab were associated with biomarkers. This preliminary study suggests that S100A12 and SLC25A37 may serve as candidate biomarkers associated with NETs in osteoporosis with diabetes, providing a preliminary theoretical foundation for future larger-scale studies.

Atrial fibrillation (AF) is a common arrhythmia that usually coexists with heart failure (HF). However, research into the efficacy and safety of catheter ablation with vein of Marshall ethanol infusion (VOM-EI) in patients with persistent AF and HF with reduced ejection fraction (HFrEF) is limited. In the present study, a single-center retrospective study was conducted, involving 85 patients with persistent AF and HFrEF. Patients in group A (n=40; male/female: 29/11; average age: 62.33±11.50 years) received catheter ablation plus VOM-EI treatment, while patients in group B (n=45; male/female: 34/11; average age: 59.36±10.91 years) received catheter ablation only. The study compared the two groups regarding primary endpoint events (rate of restoration of sinus rhythm after surgery and rate of postoperative AF recurrence) and secondary endpoint events [cardiac function parameters (left ventricular ejection fraction (LVEF), left atrium diameter (LAD), left ventricular end diastolic volume (LVEDV)], New York Heart Association (NYHA) classification, B-type natriuretic peptide (BNP) and rate of postoperative rehospitalization] at 6 months of follow-up. Surgery duration and perioperative adverse events were also compared between the two groups. There were no statistical differences in baseline characteristics, CHA2DS2-VASc score and HAS-BLED score between the two groups. In comparison with group B, group A had a decreased rate of postoperative AF recurrence (2.78 vs. 21.05%). Compared with preoperative levels, both groups achieved significant enhancement in postoperative LVEF, LVEDV and LAD. Group A exhibited a significantly greater improvement in postoperative LVEF, NYHA classification and BNP levels compared with group B. No significant differences were observed between the two groups in the rate of sinus rhythm restoration (90.0 vs. 84.44%) and the rate of postoperative rehospitalization (2.78 vs. 15.79). In addition, group A exhibited a significantly shorter surgical duration than group B (156.78±39.36 min vs. 181.73±52.39 min). There were no statistically significant differences in the rate of perioperative adverse events between the two groups (7.5 vs. 8.89%). In summary, the use of VOM-EI in conjunction with catheter ablation is a safe and effective strategy for treating patients with persistent AF and HFrEF. This approach results in effective cardiac function restoration, lower postoperative AF recurrence rate, and shorter surgical time.

Background:Microglia/macrophage-dominated neuroinflammation in the hypothalamic paraventricular nucleus (PVN) critically mediates sympathetic overactivation, with the underlying mechanism remained elusive. Given that protein acetylation serves as a pivotal epigenetic modifier of inflammatory responses to immune-microenvironmental changes, we aimed to explore the role of acetyltransferase p300 in the pathophysiological process of sympathetic activation post-myocardial infarction (MI). Methods and Results:Rats MI model was established by ligating LAD artery. During early stage, p300 was increased in the PVN and mainly localized on microglia. Microinjection of short-hairpin RNA (shRNA) targeting p300 into the PVN effectively knocked down p300 expression, resulting in reduced peripheral sympathetic nerve activity and decreased cardiac norepinephrine levels. Programmed electrical stimulation post-MI revealed that p300 knockdown decreased ventricular arrhythmia (VA) susceptibility. p300-regulated acetylome was analyzed using shotgun proteomics in human HCM3 cells, and 135 target acetylated proteins were identified. Bioinformatic analysis and coimmunoprecipitation assays revealed that p300 interacted with and acetylated high-mobility group protein B1 (HMGB1). P300 facilitated the cytoplasmic translocation of HMGB in microglia in vivo, thereby contributing to cardiac sympathetic activation. Protein docking analysis and brain slice patch-clamp recordings revealed the potential interaction between HMGB1 and excitatory glutamate receptor N-methyl-D-aspartate receptor (NMDAR) levels. Rescue experiments employing patch-clamp electrophysiology with a recepor-specific inhibitor confirmed direct mediation of HMGB1 in neuronal activation through NMDAR-dependent mechanisms. Conclusion:Microglial p300-mediated translocation of HMGB1 in the PVN may be a fundamental epigenetic mechanism in NMDAR-mediated central sympathetic activation post-MI, suggesting targeting p300 signaling modulation in the PVN as a potential antiarrhythmic therapy.

AIM:Sympathetic overactivation may lead to severe ventricular arrhythmias (VAs) post-myocardial infarction (MI). The superior cervical ganglion (SCG) is an extracardiac sympathetic ganglion which regulates cardiac autonomic tone. We aimed to investigate the characteristics and functional significance of SCG on neuro-cardiac communication post-MI. METHODS:Constructed MI rat model by left anterior descending coronary artery ligation, and electrophysiological, SCG sympathetic nerve activity testing, echocardiography and histology study were performed. The proteins and gene expression were detected using RNA-seq, spatial transcriptomics, quantitative PCR, and western blotting. RESULTS:The SCG neuronal remodeling was recognized by significant increase in adrenergic tyrosine hydroxylase (TH) (+) neurons and decrease in neuronal size. Top differentially expressed genes enriched in pro-inflammatory profile and nerve regulatory factor in left SCG (LSCG) post-MI. Interleukin (IL)-1β and IL-6 increased significantly at Day 3, ahead of nerve growth factor (NGF) which peaked at Day 7 post-MI. Spatial transcriptomics further identified the relativity of TH enrichment with macrophages and cytokines. Therapeutic LSCG-ectomy successfully triggered cardiac denervation and improved VA vulnerability. Eventually, cardiac denervation attenuated macrophage/mast cell infiltration at para-infarct regions, thus improved cardiac dysfunction. Mechanism study revealed that genetic knockdown of NGF receptor trkA in LSCG reversed sympathetic remodeling and cardiac inflammation, which may be partially mediated by substance P and calcitonin gene-related peptide (CGRP). CONCLUSION:Extracardiac sympathetic LSCG remodeling participated in arrhythmogenesis and cardiac inflammation/function post-MI. NGF bridged neuro-immune crosstalk between pro-inflammatory shifting and sympathetic overdrive. Targeting LSCG modification facilitated cardiac protection and prevented VAs post-MI.

BACKGROUND:Autophagy is an evolutionarily conserved cellular process that maintains homeostasis. It enables tumor cells to survive and grow, which may lead to drug resistance. The PI3K/AKT/mTOR pathway is reported to play a key role in autophagy induction. BEX2 promotes cell growth and survival in cancer cells. However, its role in autophagy remains unclear. METHODS:Human non-small cell lung cancer (NSCLC) cell lines (A549, H1792 and H1299) and 293FT cells were used to investigate the function of BEX2 in autophagy. The experimental research was conducted via western blot, co-immunoprecipitation and confocal microscopy. RESULTS:Our data show that rapamycin induces BEX2 protein levels. Western blot and confocal microscopy analysis demonstrate that BEX2 regulates autophagy. Furthermore, BEX2 impairs PI3K/AKT/mTOR signaling. Specifically, BEX2 interacts with PIK3CA (PI3K catalytic subunit). BEX2 impairs the interaction of PIK3CA and p85 (PI3K regulatory subunit), therefore inhibiting PI3K activity. In summary, BEX2 regulates autophagy through the PI3K/AKT/mTOR signaling pathway by modulating the activity of PI3K, specifically dependent on the presence of PIK3CA. CONCLUSIONS:We discovered that BEX2 promotes autophagic flux via PI3K/AKT/mTOR signaling. BEX2 interacts with PIK3CA and impairs PIK3CA and p85 interaction, which hinders activation of PI3K/AKT/mTOR signaling and promotes autophagy induction.

Inflammation-dominated sympathetic innervation adjacent to the infarcted region plays a pivotal role in the pathogenesis of severe ventricular arrhythmias (VAs) following myocardial infarction (MI). Thus, targeting inflammation process and sympathetic innervation represents a promising therapeutic approach to prevent VAs in clinical settings. Herein, we developed intelligent injectable hydrogels using boronic ester dynamic cross- linking as a pH- and reactive oxygen species (ROS)-responsive mechanism. We synthesized fluorophenylboronic acid-modified gelatin (GelPB) and combined it with polyvinyl alcohol (PVA) to create GelPB/PVA hydrogels (GP- gel) loaded with c-type natriuretic peptide (CNP) and Sema3A. The efficacy of this smart hydrogel was evaluated in an MI model induced by left anterior descending coronary artery ligation. The drug-loaded hydrogel demonstrated the excellent anti-inflammatory, pro-angiogenic, and anti-nerve sprouting effects. Specifically, it reduced macrophages infiltration, promoted M2 macrophage polarization in the early post-MI phase, and enhanced the expression of CD31 and a-SMA. As a result, sympathetic hyperinnervation was suppressed, arrhythmia susceptibility was reduced, and electrical conduction velocity was improved. Additionally, a notable improvement in cardiac function was observed. In conclusion, hydrogel co-loaded with CNP and Sema3A offers a promising therapeutic strategy for addressing both malignant arrhythmia and heart failure post-MI.

Laminin subunit alpha-5 (LAMA5) has been identified as an oncogene in many cancers, while its role and mechanism in gastric cancer (GC) remain to be explored. Here, the influences of LAMA5 knockdown on GC were investigated in vitro and in vivo. LAMA5 expression was silenced in GC cells alone or in combination with the signal transducer and activator of transcription 3 (STAT3) activator Colivelin, followed by CCK-8, colony formation, EdU, flow cytometry, wound healing assay, and Transwell assay. The regulatory relationship between Myc-associated zinc finger protein (MAZ) and LAMA5 was characterized by ChIP and luciferase reporter analysis. The effect of knockdown of MAZ alone or in combination with LAMA5 overexpression on GC was investigated in vitro and in vivo. LAMA5 was highly expressed in GC cells, and knockdown of LAMA5 inhibited GC cell malignant aggressiveness, which was reversed by the Colivelin treatment. The transcription factor MAZ bound to the promoter of LAMA5 to activate its transcription, and the anti-tumor effects of sh-MAZ on GC cells in vitro and in vivo were overturned by LAMA5 overexpression. In conclusion, MAZ promotes GC cell proliferation and migration by the LAMA5/STAT3 axis, implying that this axis can function as a target for GC therapy.

BACKGROUND:The sublingual vein (SV) is a specialized diagnostic method used in Traditional Chinese Medicine (TCM). Despite its ability to objectively reflect blood flow, SV is often overlooked in clinical practice.OBJECTIVE:This study aims to analyze the core characteristics of SV and investigate the in-depth relationship between its digital characteristics and hypertension. The goal is to find a link between SV and hypertension and break out of the current situation.METHODS:Modern digital analysis techniques were applied to the traditional SV diagnostic theory. In a controlled study with 204 participants, the digital characteristics of SV were documented using TFDA-1, and its color value was analyzed using TDAS. Morphological characteristics of SV, such as trunklength, width, and tortuosity, were examined by combining computer vision with expert interpretation. This involved the application of automatic ranging methods and a rectangular approximation algorithm, which are novel approaches in the field of TCM. The t-test and Mann-Whitney U test were used to analyze the digital characteristics of SV in hypertension. Binary logistic regression and neural network models were established using machine learning to explore the deep relationship between SV characteristics and hypertension.RESULTS:There was a significant difference of the tortuosity of SV between the two groups (Z=-2.629, p= 0.009). The results revealed thick width of SV (OR = 2.64, 95% CI: 1.02-6.79) was the risk factor for hypertension. Addition of SV characteristics improved overall percent correct for hypertension prediction to 80%.CONCLUSION:TCM method of diagnosis of SV has been greatly expanded in terms of technical means, and the close relationship between SV and hypertension has been found in clinical data.

Objective:Myocardial infarction, coronary heart disease is one of the serious types, come on urgent, case fatality rate is high, especially the front wall or extensive anterior wall myocardial infarction, easy to merge cardiac insufficiency, arrhythmia, even in patients with sudden death will happen, and life-threatening. The aim of this study was to investigate the effects of HOPE management mode on cardiac function, quality of life and in-hospital cardiovascular adverse events in patients with myocardial infarction. Methods:118 patients with myocardial infarction hospitalized in our hospital from January 2020 to March 2022 were randomly divided into study group (n=59) and control group (n=59) and carried out a prospective study. The study group was treated with HOPE management mode, the control group was treated with conventional intervention. The LVEF, GRACE, quality of life were evaluated before intervention, 1 week after, 1 month and 3 months after intervention to evaluate the improvement of clinical symptoms, cardiac function and quality of life of patients. Results:The LVEF were increased from (42.94±2.38) % to (47.03±2.62) % in control group and from (43.51±2.45) to (52.94±3.09) in sudy group; the quality of life were increased from (42.08±7.44) points to (57.00±4.49) points in control group and (43.76±6.68) points to (69.42±8.03) points in sudy group; the GRACE score were increased from (152.10±14.52) points to (110.10±9.73) points in control group and (153.63±15.11) points to (81.71±10.21) points in sudy group, the difference were statistically significant (P < .05). All indicators in study group were better than those in control group at each time point after intervention (P < .05). Kaplan-Meier curve showed that the incidence of adverse cardiovascular events in the study group was lower than that in the control group within 3 months. Within 90 days of hospitalization, the incidence of adverse cardiovascular events were 28.81% in the control group, which was higher than 15.25% in the study group (P < .05). Kaplan-meier observation showed that the incidence of adverse cardiovascular events in control group was significantly higher than that in study group (χ2=5.586, P = .018). Conclusions:The HOPE management model can effectively improve the cardiac function and quality of life of patients with myocardial infarction, and reduce GRACE scores and the incidence of in-hospital cardiovascular adverse events, which can as a comprehensive approach to improve clinical outcomes and enhance the quality of life for patients with myocardial infarction.

Brain expressed X-linked gene 2 (BEX2) encoded protein was originally identified to promote transcription by interacting with several transcription factors in the DNA-binding complexes. Recently, BEX2 was found to be localized in cytosol and/or mitochondria and regulate apoptosis in cancer cells and tumor growth. However, the molecular mechanism underlying its roles in cancer cells remains unclear. Here, we report that crotonylated BEX2 plays an important role in inhibiting chemotherapeutic agent-induced apoptosis via enhancing mitophagy in human lung cancer cells. BEX2 promotes mitophagy by facilitating interaction between NDP52 and LC3B. Moreover, BEX2 crotonylation at K59 is critical in the BEX2-mediated mitophagy in lung cancer cells. The K59R mutation of BEX2 inhibits mitophagy by affecting the interaction of NDP52 and LC3B. BEX2 expression is elevated after anticancer drug treatment, and its overexpression inhibits chemotherapy-induced apoptosis. In addition, inhibition of BEX2-regulated mitophagy sensitizes tumor cells to apoptosis. Furthermore, BEX2 promotes tumor growth and inhibits apoptosis by regulating mitophagy in vivo. We also confirm that BEX2 is overexpressed in lung adenocarcinoma and is associated with poor prognosis in lymph node metastasis-free cancer. Therefore, combination treatment with pharmaceutical approaches targeting BEX2-induced mitophagy and anticancer drugs may represent a potential strategy for NSCLC therapy.

Mutations in the ETFDH gene, encoding electron transfer flavoprotein dehydrogenase, have been identified to cause riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD) (Wen et al., 2010). We performed the generation and characterization of human induced pluripotent stem cell (iPSC) line from skin fibroblasts of a patient with RR-MADD carrying two heterozygous ETFDH mutations (p.D130V and p.A84V). Their pluripotency was verified by the expression of several pluripotency markers on RNA and protein levels and the capability to differentiate into all three germ layers.

We investigated if poly-lactic acid (PLA) nanopillar array can trigger the differentiation of human epicardial (ADSCs) (heADSCs) into cardiomyocyte-like cells and explored the effects of these cardiomyocyte-like cells on myocardial infarction (MI) in vivo. PLA nanopillar array (200 nm diameter) and plain PLA film (PLA planar) induced heADSCs were marked with carboxyfluorescein. After 7 days, the expressions of myocardiocyte-specific genes were significantly enhanced in cells seeded on PLA nanopillar array compared with that on PLA planar, especially CACNA1C, KCNH2, and MYL2 genes (p < 0.05). However, the expressions of cardiac troponin T (cTNT), KCNQ1, and KCNA5 were lower than those in PLA planar-induced heADSCs (p < 0.05), whereas GATA4 tended to increase with time. The cells with positively stained α-actinin and cTNT were elevated in heADSCs induced by PLA nanopillar array compared with those induced by PLA planar only (p < 0.05). In vivo experiments showed that cardiac function was improved after injecting PLA-nanopillar array-induced heADSCs into the ischemic heart (p < 0.05, compared with PLA planar + MI group). Furthermore, tyrosine hydroxylase density was significantly lower (p < 0.05). PLA nanopillar array directly drives the differentiation of heADSCs into cardiomyocyte-like cells, and the induced heADSCs exhibit a protective effect on ischemic myocardium by improving cardiac function in MI rats.

Background: Intellectual disability (ID) is defined by cognitive and social adaptation defects. Variants in the SYNGAP1 gene, which encodes the brain-specific cytoplasmic protein SYNGAP1, are commonly associated with ID. The aim of this study was to identify novel SYNGAP1 gene variants in Chinese individuals with ID and evaluate the pathogenicity of the detected variants.Methods: Whole exome sequencing (WES) was performed on 113 patients diagnosed with ID. In the study, two de novo variants in SYNGAP1 were identified. Sanger sequencing was used to confirm these variants. Minigene assays were used to verify whether the de novo intronic variant in SYNGAP1 influenced the normal splicing of mRNA.Results: Two de novo heterozygous pathogenic variants in SYNGAP1, c.333del and c.664-2A>G, were identified in two ID patients separately. The c.333del variant has been reported previously as a de novo finding in a child with ID, while the c.664-2A>G variant was novel de novo intronic variant, which has not been reported in the literature. Functional studies showed that c.664-2A>G could cause aberrant splicing, resulting in exon 7 skipping and a 16bp deletion within exon 7.Conclusion: We identified two de novo pathogenic heterozygous variants in SYNGAP1 in two patients with ID, among which the c.664-2A>G variant was a novel de novo pathogenic variant. Our findings further enrich the variant spectrum of the SYNGAP1 gene and provide a research basis for the genetic diagnosis of ID.

目的 对比磁共振(MRI)多序列对肛瘘形态学改变的评估价值.方法 选择肛瘘患者46例,均于术前1周行3.0T MRI检查,序列包括脂肪抑制T2加权成像(FS T2WI)+扩散加权成像(DWI)、脂肪抑制T1加权成像(FS T1WI)+对比增强(CE)、FS T2WI.两位医师对各序列图像作出一致性评价,对比各序列肛瘘内口、瘘管的显示率及清晰度评分.结果 46例肛瘘患者手术中共发现内口51个,主瘘管及初级瘘管共62个.两位医师对肛瘘内口显示清晰度评分(FS T2WI,κ=0.816;DWI,κ=0.799;FS T1WI+CE,κ=0.828;FS T2WI+DWI,κ=0.821)、内口显示率(FS T2WI,κ=0.940;DWI,κ=0.958;FS T1WI+CE,κ=0.852;FS T2WI+DWI,κ=0.812)、瘘管清晰度评分(FS T2WI,κ= 0.824;DWI,κ=0.882;FS T1WI+CE,κ=0.718;FS T2WI+DWI,κ=0.851)、瘘管显示率(FS T2WI,κ=0.783;DWI,κ= 0.816;FS T1WI+CE,κ=0.641;FS T2WI+DWI,κ=0.792)的一致性评价较好或良好.FS T2WI+DWI、FS T1WI+CE、FS T2WI序列内口显示率比较差异无统计学意义(P均>0.05),但均高于DWI序列(P均<0.05);各序列内口清晰度评分比较差异均有统计学意义(P均<0.05).各序列瘘管显示率比较差异无统计学意义(P均>0.05),各序列瘘管清晰度评分比较差异均有统计学意义(P均<0.05).结论 MRI多序列联合应用可提高诊断肛瘘的准确性,其中FS T2WI+DWI序列与FS T1WI+增强序列对肛瘘形态变化的评价效果较好.

OBJECTIVES:N6-methyladenosine (m6A) is the most prevalent post-translational modification in eukaryotic mRNA. Recently, m6A editing modified by methyltransferase-like enzyme 3 (METTL3), the core m6A methyltransferase, has been demonstrated to be involved in cardiac sympathetic hyperactivity. This study aimed to clarify the effects and underlying mechanisms of METTL3 in the paraventricular nucleus (PVN) in mediating sympathetic activity following myocardial infarction (MI).METHODS:We established rat MI models by left anterior descending coronary artery ligation. m6A quantification was performed.The expression of METTL3 and its downstream gene, tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), were determined. The functional role of METTL3 in sympathetic hyperactivity and electrical conduction stability were verified by assessing renal sympathetic nerve activity (RSNA), norepinephrine (NE) levels, and programmed electrical stimulation. Rescue experiments were also conducted. The mechanism by which m6A is involved in mitochondrial reactive oxygen species (mROS) production, mediated by TRAF6/ECSIT pathway, was explored in lipopolysaccharide (LPS) treated primary microglial cells.RESULTS:METTL3 was predominantly localized in the microglia and significantly increased within the PVN at 3 days post-MI. Inhibition of METTL3 decreased m6A levels, TRAF6 expression, and mROS production; downregulated sympathoexcitation, indicated by attenuated NE concentration and RSNA; decreased the incidence of ventricular tachycardia or fibrillation; and improved cardiac function. Mechanistically, downregulation of METTL3 prevented TRAF6 translocation to the mitochondria in the microglia and subsequent TRAF6/ECSIT pathway activation, resulting in decreased mROS production.CONCLUSIONS:This study demonstrates that METTL3-mediated m6A modification promotes sympathetic hyperactivity through TRAF6/ECSIT pathway and mitochondrial oxidative stress in the PVN, thereby leading to ventricular arrhythmias post-MI.

Polymannuronic acid (PM) possesses more pharmacological activities than sodium alginate, but there have been few studies on its absorption mechanism, tissue distribution, and pharmacokinetics. Studies of pharmacokinetics and tissue distribution are necessary to elucidate the pharmacological effects of PM. Thus, we used fluorescein isothiocyanate (FITC) to produce fluorescently labeled PM (FITC-PM) and detected the distribution and pharmacokinetics of PM in vivo via tail vein injection. The results demonstrate that the FITC-PM showed high stability in different pH solutions. After the tail vein injection, FITC-PM tended to be distributed in the kidney, followed by the liver and in the heart, spleen, and lungs at lower concentrations. Pharmacokinetic analysis showed that the elimination rate constant of FITC-PM was 0.24, the half-life time was 2.85 h, the peak concentration was 235.17 μg/mL, the area under the curve was 631.48 μg/mL·h, the area under the curve by statistical moment was 1843.15 μg/mL·h2, the mean residence time was 2.92 h, and the clearance rate was 79.18 mL/h. These results indicate that FITC-PM could be used for PM distribution and pharmacokinetic studies, and the studies of pharmacokinetics and tissue distribution provided basic information that can be used to further clarify PM pharmacodynamic mechanisms.

Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer, which is characterized by complicated etiology, excessive heterogeneity, and poor prognosis. Necroptosis is a new kind of programmed cell death, which is intently associated with the occurrence and development of tumors. Although researchers have had a deep understanding of necroptosis in recent years, the expression level of necroptosis-related genes in HCC and its relationship with the survival time of HCC patients are not clear. Methods: According to the expression of necroptosis-related genes and the survival of HCC patients, HCC patients in the TCGA database were divided into 2 groups that were relatively independent of each other. The genes related to the survival time of HCC patients were screened from the 2 groups of differentially expressed genes. By using the Least Absolute Shrinkage and Selection Operator Cox regression analysis, the optimal λ value was obtained, and the 10-gene signature model was established. Results: According to the median risk score of the TCGA cohort, HCC patients were averagely divided into high- and low-risk groups. Compared with the low-risk group, the death toll of the high-risk group was relatively higher and the survival time was relatively shorter. Principal component analysis and t-distributed stochastic neighbor embedding analysis showed that there was a significant separation between high- and low-risk groups. Through Kaplan–Meier analysis, it was found that the survival time of HCC patients in the high-risk group was significantly shorter than that in the low-risk group. Through receiver operating characteristic analysis, it was found that the sensitivity and specificity of the model were good. We also make a comprehensive analysis of the international cancer genome consortium database as a verification queue and prove the reliability of the 10-gene signature model. Gene Ontolog, Kyoto Encyclopedia of Genes and Genomes, and single-sample gene set enrichment analysis showed that many biological processes and pathways related to immunity had been enriched, and the antitumor immune function was weakened in the high-risk population. Conclusion: The risk score can be considered as an independent prognostic factor to predict the prognosis of patients with HCC, and necroptosis-related genes are also closely related to tumor immune function.

The long noncoding RNAs (lncRNAs) have been investigated in colorectal cancer (CRC). The aim of this study is to identify the biological functions of LBX2-AS1 in CRC. Quantitative real-time polymerase chain reaction was used to examine the expression of LBX2-AS1 in CRC cells. Cell counting kit-8 and colony formation assays were performed to examine cell proliferation. Wound healing and transwell invasion assays were performed to examine the cell migration and invasion. The interaction between PTBP1 and LBX2-AS1 or KAT2A was confirmed by RNA immunoprecipitation. The KAT2A messenger RNA (mRNA) stability was probed using the transcriptional inhibitor Actinomycin D. LBX2-AS1 was significantly increased in CRC tissues and cells. Knockdown of LBX2-AS1 inhibited CRC cell proliferation, migration, and invasion. The notch signaling pathway was activated by LBX2-AS1. LBX2-AS1 enhanced the mRNA stability of the histone acetyltransferase KAT2A by interacting with RNA-binding protein PTBP1. LBX2-AS1 acted as an oncogene in CRC.