Advances of N6-methyladenosine modification on circular RNA in hepatocellular carcinoma

N6-methyladenosine(m6A)is a reversible epigenetic modification, which is one of the most abundant modifiers in eukaryotic cells and has been commonly reported in messenger RNAs and non-coding RNAs. The processing modification of m6A regulates RNA transcription, processing, splicing, degradation, and translation, and plays an important role in the biological process of tumors. Circular RNA, which lacks the 5' cap structure, has been mistakenly regarded as a "junk sequence" generated by accidental shearing during the transcription process. However, it has been found that circRNAs can be involved in tumor invasion and metastasis through microRNAs, binding proteins, translated peptides, and m6A modifications. In this paper, we reviewed the role of m6A modifications in circRNA regulation and their functions in hepatocellular carcinoma and discussed their potential clinical applications and future development in this field.

Stent-assisted coiling of intracranial carotid ophthalmic segment aneurysm segment aneurysms:Long-term follow-up from a single center

Background:To evaluate the efficacy of stent-assisted coiling(SAC)for the treatment of carotid ophthalmic segment aneurysm segment aneurysms(OSAs)of the internal carotid artery(ICA)through detailed long-term follow-up of a large patient cohort.Methods:We retrospectively analyzed 88 consecutive patients with OSAs between January 2009 and January 2020 at our center.Angiographic results were evaluated using the modified Raymond grading system and clinical outcomes were evaluated using the mRS scale.The primary endpoints were major aneurysm recurrence and poor clinical outcomes for at least 18 months of follow-up.The patients were asked to attend clinical follow-up assessments and possibly undergo DSA or MR via telephone.Results:We enrolled 88 patients with 99 OSAs treated with coiling,of whom 76 were treated with SAC.The coiling procedures were successful in all 88 patients.Overall,complications occurred in 8 patients(9.1%).No procedure-related mortality was observed.67(76.1%)experienced immediate aneurysm occlusion at the end of the procedure.Long-term angiographic follow-up(18 months)was available in 45/88 aneurysms(51%)(average 18.7±5.2 months).Four patients continued their follow-up for 5 years after initial aneurysm treatment.After a clinical follow-up time of 28.7 months(range,12-51 months),85 patients(95.5%)achieved favorable clinical outcomes(mRS scores of 0-2).Conclusions:This study indicates that SAC treatment is a safe and effective therapeutic alternative for ruptured and unruptured OSAs.The procedural risks are low with relatively long-term effectiveness.

Expert consensus on interventional therapy for traumatic splenic bleeding

This study aims to introduce the diagnosis and treatment processes of traumatic splenic bleeding and explain its emergency,medical,interventional,and surgical treatments.Furthermore,this study aims to summarize the indications and contraindications of splenic artery embolization,interventional procedures,and precautions of complications.

Research progress on circulating tumor cells of hepatocellular carcinoma

Circulating tumor cells(CTCs)are the cells released from the primary tumor and found in the peripheral blood,which can colonize and develop at a distance through blood circulation.At present,the commonly used separation and detection methods of CTCs are mainly divided into physical methods,biological methods,and microfluidic chip-based methods.Monitoring CTC count and cell phenotype is of great significance for early screening and diagnosis of hepatocellular carcinoma(HCC).Moreover,the CTC count and cell phenotype are related to assessing the clinical efficacy of the treatment of HCC and the clinical stage of HCC patients.The CTCs count is also closely related to the overall survival,progression-free survival,and postoperative recurrence of patients with HCC.

Study on the mechanism of Astragalus in the treatment of diabetic cardiomyopathy based on network pharmacology and its preliminary verification study

Objective:To explore the potential active ingredients and targets of Astragalus,and also to predict the targets and mechanisms of Astragalus in the treatment of diabetic cardiomyopathy.Based on the predicted results,the key signaling pathways were validated in a diabetic cardiomyopathy model mouse.Methods:Compounds and targets in Astragalus were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The protein names to corresponding"Gene Symbol ID"was convert by STRING database.We obtained targets of diabetic cardiomyopathy data from DisGeNET datasets.The protein-protein interaction network(PPI network)was established using STRING database.Cytoscape 3.6.0 was used to construct a disease-drug-target gene network map and to screen the 10 closest target genes by Cytohuba plug-in.The overlapping genes were then subjected to gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)-based enrichment analysis.Finally,the key molecules of the MAPK signaling pathway were validated by in vitro experiments.Animal experiments were performed using 21 Kunming mice randomly divided into normal group,model group,and Chinese herbal medicine Astragalus group,with seven mice in each group.The myocardium of mice in each group was stained with HE to compare the pathological morphological changes,and Western Blot was also used to compare the key molecules of MAPK signaling pathway,ERK1 and p-p38.Results:Astragalus contained 20 active ingredients with 188 corresponding targets,220 targets related to diabetic cardiomyopathy and 37 targets acting in conjunction with Astragalus.The common targets were imported into the STRING database to obtain a PPI network graph of overlapping genes,with 37 nodes and 391 edges.The PPI network map was imported into Cytoscape 3.6.0 software,and the most significant top 10 hub genes were obtained using the MCC algorithm in the cytoHubba plugin,namely AKT1,TP53,CASP3,MMP9,EGF,IL-10,CXCL8,IL-1β,VEGFA,PPARG.GO functional enrichment analysis yielded 40 entries for biological process(BP),23 entries for cellular component(CC),22 entries for molecular function(MF)and 94 entries for KEGG pathway enrichment screening,mainly involving PI3K-AKT,MAPK,HIF-1,FOXO,TNP pathway and other inflammation or apoptosis regulatory pathways.Animal experiments showed that Astragalus can improve the inflammatory state of myocardial tissue in mice with diabetic cardiomyopathy,and the expression of ERK1 and p-p38 protein in myocardial tissue of mice in the model group was higher than that in the normal group(P<0.05,P<0.01),and after the intervention with Astragalus,the expression of ERK1 and p-p38 protein was significantly lower than that in the model group,and the difference was statistically significant(P<0.05,P<0.01).Conclusion:Astragalus has multi-target,multi-component and multi-pathway action characteristics in the treatment of diabetic cardiomyopathy,which can exert anti-inflammatory and anti-oxidative stress effects by regulating protein expression of MAPK signaling pathway ERK1,p-p38.

Progress in Diagnosis and Endoscopic Treatment of Stanford B Penetrating Aortic Ulcers

Penetrating aortic ulcers is rare in clinical practice,and it is necessary to intervene in this type of aortic perforating ulcer because it can be accompanied by major arterial dissection and intermural hematoma.With the widespread application and technical advancement of follow-up thoracic aortic endovascular repair(TEVAR),endovascular treatment has become the first choice for symptomatic aortic perforating ulcers.In this review,we will review the diagnosis,diagnosis and endovascular treatment of aortic perforating ulcer.

One-year status of hepatic venous pressure gradient measurement from 85 hospitals in China

Aims:Surveys and research on the applications of the hepatic venous pressure gradient(HVPG)are important for understanding the current status and future development of this technology in China.This article aimed to investigate the status of hepatic venous pressure gradient measurement in China in 2022.Methods:We investigated the overall status of HVPG technology in China-including hospital distribution,hospital level,annual number of cases,catheters used,average cost,indications,and current challenges by using online questionnaire.By counting the number and percentages of cases of these results,we hope to clarify the current status of HVPG measurements in China.Results:According to the survey,85 hospitals in China used HVPG technology in 2022 distributed across 29 provinces.A total of 4989 HVPG measurements were performed in all of the surveyed hospitals in 2022,of which 2813 cases(56.4%)were measured alone.The average cost of HVPG measurement was 5646.8±2327.9 CNY.Of the clinical teams who performed the measurements(sometimes multiple per hospital),94.3%(82/87)used the balloon method,and the majority of the teams(72.4%,63/87)used embolectomy catheters.Conclusions:This survey clarified the clinical application status of HVPG in China and confirmed that some medical institutions in China have established a foundation for this technology.It is still necessary to continue promoting and popularizing this technology in the future.

Cullin 4A is associated with epithelial to mesenchymal transition and poor prognosis in perihilar cholangiocarcinoma

AIM To explore the functional role of cullin 4A(CUL4A), a core subunit of E3 ubiquitin ligase, in perihilar cholangiocarcinoma(PHCC).METHODS The expression of CUL4 A in PHCC cell lines was evaluated by Western blot and quantitative reverse transcription-polymerase chain reaction. Immunohistochemistry(IHC) was adopted to investigate the relationship between CUL4 A expression and clinicopathological characteristics of PHCC. Univariate analysis and multivariate regression analysis were performed to analyze the risk factors related to overall survival(OS) and progression-free survival(PFS) of PHCC patients. Wound healing, Transwell and Matrigel assays were utilized to explore the function of CUL4 A in PHCC metastasis. Furthermore, expression of epithelial to mesenchymal transition(EMT) markers was verified in cells with CUL4 A knockdown or overexpression. The relationship between CUL4 A expression and E-cadherin expression was also analyzed by IHC assay. Finally, the role of ZEB1 in regulating CUL4 A mediated PHCC was detected by IHC, Western blot, Transwell and Matrigel assays.RESULTS CUL4 A overexpression was detected in PHCC cell lines and clinical specimens. Clinicopathological analysis revealed a close correlation between CUL4 A overexpression and tumour differentiation, T, N and TNM stages in PHCC. Kaplan-Meier analysis revealed that high CUL4 A expression was correlated with poor OS and PFS of PHCC patients. Univariate analysis identified the following four parameters as risk factors related to OS rate of PHCC: T, N, TNM stages and high CUL4 A expression; as well as three related to PFS: N stage, TNM stage and high CUL4 A expression. Further multivariate logistic regression analysis identified high CUL4 A expression as the only independent prognostic factor for PHCC. Moreover, CUL4 A silencing in PHCC cell lines dramatically inhibited metastasis and the EMT. Conversely, CUL4 A overexpression promoted these processes. Mechanistically, ZEB1 was discovered to regulate the function of CUL4 A in promoting the EMT and metastasis.CONCLUSION CUL4 A is an independent prognostic factor for PHCC, and it can promote the EMT by regulating ZEB1 expression. CUL4 A may be a potential therapeutic target for PHCC.

Radiomics: Status quo and future challenges

Noninvasive imaging(computed tomography,magnetic resonance imaging,endoscopic ultrasonography,and positron emission tomography)as an important part of the clinical workflow in the clinic,but it still provides limited information for diagnosis,treatment effect evaluation and prognosis prediction.In addition,judgment and diagnoses made by experts are usually based on multiple years of experience and subjective impression which lead to variable results in the same case.With accumulation of medical imaging data,radiomics emerges as a relatively new approach for analysis.Via artificial intelligence techniques,highthroughput quantitative data which is invisible to the naked eyes extracted from original images can be used in the process of patients’management.Several studies have evaluated radiomics combined with clinical factors,pathological,or genetic information would assist in the diagnosis,particularly in the prediction of biological characteristics,risk of recurrence,and survival with encouraging results.In various clinical settings,there are limitations and challenges needing to be overcome before transformation.Therefore,we summarize the concepts and method of radiomics including image acquisition,region of interest segmentation,feature extraction and model development.We also set forth the current applications of radiomics in clinical routine.At last,the limitations and related deficiencies of radiomics are pointed out to direct the future opportunities and development.

S-Allylmercaptocysteine improves alcoholic liver disease partly through a direct modulation of insulin receptor signaling

Alcoholic liver disease(ALD) causes insulin resistance, lipid metabolism dysfunction, and inflammation. We investigated the protective effects and direct regulating target of S-allylmercaptocysteine(SAMC) from aged garlic on liver cell injury. A chronic ethanol-fed ALD in vivo model(the NIAAA model) was used to test the protective functions of SAMC. It was observed that SAMC(300 mg/kg, by gavage method) effectively ameliorated ALD-induced body weight reduction, steatosis,insulin resistance, and inflammation without affecting the health status of the control mice, as demonstrated by histological, biochemical, and molecular biology assays. By using biophysical assays and molecular docking, we demonstrated that SAMC directly targeted insulin receptor(INSR) protein on the cell membrane and then restored downstream IRS-1/AKT/GSK3 b signaling. Liver-specific knock-down in mice and siRNA-mediated knock-down in AML-12 cells of Insr significantly impaired SAMC(250 mmol/L in cells)-mediated protection. Restoration of the IRS-1/AKT signaling partly recovered hepatic injury and further contributed to SAMC’s beneficial effects. Continuous administration of AKT agonist and recombinant IGF-1 in combination with SAMC showed hepato-protection in the mice model.Long-term(90-day) administration of SAMC had no obvious adverse effect on healthy mice. We conclude that SAMC is an effective and safe hepato-protective complimentary agent against ALD partly through the direct binding of INSR and partial regulation of the IRS-1/AKT/GSK3 b pathway.