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.

Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of literature

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.

Clinical practice guidelines for the interventional treatment of advanced pancreatic cancer(5^(th)edition)

Pancreatic cancer has become a major disease affecting people’s health because of its insidiousness,rapid progression and poor prognosis.Based on the practical needs of clinical work,combined with domestic multi-center research and experience,this guideline provides constructive suggestions for the interventional treatment of pancreatic cancer.

Isolated superior mesenteric artery dissection:An updated review of the literature

Isolated superior mesenteric artery dissection(ISMAD)is a rare but potentially life-threatening cause of acute abdominal pain.Owing to the availability of computed tomography angiography,more cases have been detected during screening for acute abdomen in recent years.With increasing knowledge of ISMAD,a better management strategy is being developed.To enhance our understanding and improve treatment outcomes of ISMAD,a systematic literature review was conducted with a focus on diagnosis and management strategies based on existing evidence.

Angiography findings and endovascular management of acute nonvariceal gastrointestinal bleeding:A pictorial essay

Patients with acute nonvariceal gastrointestinal bleeding(GIB)not treatable via endoscopic therapy require angiography and endovascular management.If the source of the bleeding can be identified on angiography,the bleeding can be controlled with minimal complications by endovascular treatments such as intra-arterial infusion of vasopressin,embolization,covered stent placement,or a combination thereof.This pictorial essay reviews the angiographic findings for and the endovascular management of acute nonvariceal GIB.

Uterine artery embolization combined with percutaneous microwave ablation for the treatment of prolapsed uterine submucosal leiomyoma:A case report

BACKGROUND Vaginal myomectomy is the most common form of radical treatment for prolapsed submucosal leiomyoma and is typically performed under general anesthesia.However,an alternative treatment approach is needed for patients who cannot tolerate general anesthesia.We describe a case with such a patient who was successfully treated via a minimally invasive method under local anesthesia.CASE SUMMARY A 46-year-old female suffered from abnormal uterine bleeding,severe anemia,and a reduced quality of life attributed to a massive prolapsed submucosal leiomyoma.She could not tolerate general anesthesia due to a congenital thoracic malformation and cardiopulmonary insufficiency.A new individualized combined treatment,consisting uterine artery embolization(UAE),percutaneous microwave ablation(PMWA)of the pedicle and the endometrium,and transvaginal removal of the leiomyoma by twisting,was performed.The lesion was completely removed successfully under local anesthesia without any major complications.The postoperative follow-up showed complete symptom relief and a significant improvement in the quality of life.CONCLUSION UAE combined with PMWA can be performed under local anesthesia and is a promising alternative treatment for patients who cannot tolerate general anesthesia.

Application of Cone-beam Computed Tomography in Interventional Therapies for Liver Malignancy:A Consensus Statement by the Chinese College of Interventionalists

Despite its crucial role in interventional therapies for liver malignancy,cone-beam computed tomography(CBCT)has not yet been fully integrated into clinical practice due to several complicating factors,including nonstandardized operations and limited recognition of CBCT among interventional radiologists.In response,the Chinese College of Interventionalists has released a consensus statement aimed at standardizing and promoting the application of CBCT in the interventional therapies for liver malignancy.This statement summarizes CBCT scanning techniques,and operational standards,and highlights its potential applications in clinical practice.

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.

Guidelines and standards for comprehensive clinical diagnosis and interventional treatment for diabetic foot in China(Issue 7.0)

Diabetic foot(DF)is one of the most common complications of diabetes and is associated with high morbidity,disability,lethality and low cure-rate.The clinical diagnosis and treatment of DF need to be standardized.The Chinese Diabetic Foot Cell and Interventional Therapy Technology Alliance has released six editions of guidelines and standards for clinical diagnosis and interventional treatment of DF,which filled the gap in the domestic DF treatment standard and played an important role in improving the level of diagnosis and treatment in China.In line with the latest developments in diagnosis and treatment,the Alliance,along with other 89 institutions,developed and issued the new edition based on the sixth edition to help standardize the clinical diagnosis and treatment of DF in China.

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.

Exogenous FGF－2 improves biological activity of endothelial progenitor cells exposed to high glucose conditions

Purpose: To investigate the effects of exogenous basic fibroblast growth factor-2(FGF-2) on the biological activity of endothelial progenitor cells(EPCs) exposed to high glucose conditions. Materials and Methods: 1) Bone marrow EPCs from C57BL/6 mice were isolated and cultured in vitro. EPC purity was identified by flow cytometry and immunofluorescence staining. 2) Apoptosis was detected by TUNEL assay. Migration and tube formation ability was detected by Transwell chamber and Matrigel assays, respectively. The expression and activation of β-catenin was detected by Western blot. 3) Doppler flowmetry was used to detect the effect of FGF2 on blood flow recovery in ischemic hind limbs of mice. Results: 1) FGF-2 treatment reversed high glucose induced growth inhibition of EPCs. FGF-2 treatment also increased migration and tube formation ability of EPCs even in high glucose conditions. 2) Western blot analysis demonstrated that the percentage of activated β-catenin/total β-catenin in the high glucose group were significantly lower than that in the control group, while FGF-2 treatment reversed high glucose induced β-catenin inhibition. 3) In vivo experiments demonstrated that the blood flow recovery in ischemic hind limbs of mice was significantly improved after FGF-2 treatment. Conclusion: Exogenous FGF-2 could play a role in the functional repair of damaged EPC exposed to high glucose conditions, via the activation of the Wnt/β-catenin signaling pathway.

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.

Hexafluoropropylene oxide trimer acid,a perfluorooctanoic acid alternative,induces cardiovascular toxicity in zebrafish embryos

As an increasingly used alternative to perfluorooctanoic acid(PFOA),hexafluoropropylene oxide trimer acid(HFPO-TA)has been widely detected in global water environments.However,little is known regarding its toxic effects on cardiovascular development.Here,zebrafish embryos were treated with egg water containing 0,60,120,or 240 mg/L HFPO-TA.Results showed that HFPO-TA treatment led to a significant reduction in both larval survival percentage and heart rate.Furthermore,HFPO-TA exposure caused severe pericardial edema and elongation of the sinus venous to bulbus arteriosus distance(SV-BA)in Tg(myl7:GFP)transgenic larvae,disrupting the expression of genes involved in heart development and thus causing abnormal heart looping.Obvious sprouting angiogenesis was observed in the 120 and 240 mg/L exposed Tg(fli:GFP)transgenic larvae.HFPO-TA treatment also impacted the mRNA levels of genes involved in the vascular endothelial growth factor(VEGF)pathway and embryonic vascular development.HFPO-TA exposure significantly decreased erythrocyte number in Tg(gata1:DsRed)transgenic embryos and influenced gene expression associated with the heme metabolism pathway.HFPO-TA also induced oxidative stress and altered the transcriptional levels of genes related to cell cycle and apoptosis,inhibiting cell proliferation while promoting apoptosis.Therefore,HFPO-TA exposure may induce abnormal development of the cardiovascular and hematopoietic systems in zebrafish embryos,suggesting it may not be a suitable or safe alternative for PFOA.

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.

Endovascular treatment of acute proximal deep venous thrombosis secondary to iliac vein compression syndrome： a novel technique for thrombus removal

Iliac vein compression syndrome （IVCS）,also known as May-Thurner syndrome or Cockett syndrome,is caused by compression of the left common iliac vein between the right common iliac artery and the vertebrae.A recent imaging study have demonstrated that at least a 25%compression of the left iliac vein at the arterial crossover point may be present in 66% of the asymptomatic patient population.1 With the development of interventional technique,endovascular management as a less invasive means is becoming the first-line treatment,which can not only treat the thrombosis but also correct the venous anatomic abnormalities.2 In this study,we described a novel technique combining percutaneous aspiration thrombectomy （PAT） with Fogarty catheter thrombectomy （FCT） as the thrombus removal therapy without femoral venotomy in patients with acute deep vein thrombosis （DVT） due to IVCS and evaluated its technical feasibility and short-term outcomes.

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.

Ultrasound-enhanced fluorescence imaging and chemotherapy of multidrugresistant tumors using multifunctional dendrimer/carbon dot nanohybrids

Development of innovative nanomedicine enabling enhanced theranostics of multidrug-resistant(MDR)tumors remains to be challenging.Herein,we report the development of a newly designed multifunctional yellowfluorescent carbon dot(y-CD)/dendrimer nanohybrids as a platform for ultrasound(US)-enhanced fluorescence imaging and chemotherapy of MDR tumors.Generation 5(G5)poly(amidoamine)dendrimers covalently modified with efflux inhibitor of D-α-tocopheryl polyethylene glycol 1000 succinate(G5-TPGS)were complexed with one-step hydrothermally synthesized y-CDs via electrostatic interaction.The formed G5-TPGS@y-CDs complexes were then physically loaded with anticancer drug doxorubicin(DOX)to generate(G5-TPGS@y-CDs)-DOX complexes.The developed nanohybrids display a high drug loading efficiency(40.7%),strong y-CD-induced fluorescence emission,and tumor microenvironment pH-preferred DOX release profile.Attributing to the DOX/TPGS dual drug design,the(G5-TPGS@y-CDs)-DOX complexes can overcome the multidrug resistance(MDR)of cancer cells and effectively inhibit the growth of cancer cells and tumors.Furthermore,the introduction of US-targeted microbubble destruction technology was proven to render the complexes with enhanced intracellular uptake and anticancer efficacy in vitro and improved chemotherapeutic efficacy and fluorescence imaging of tumors in vivo due to the produced sonoporation effect.The developed multifunctional dendrimer/CD nanohybrids may represent an advanced design of nanomedicine for US-enhanced theranostics of different types of MDR tumors.

Growth of BiOBr/ZIF‑67 Nanocomposites on Carbon Fiber Cloth as Filter‑Membrane‑Shaped Photocatalyst for Degrading Pollutants in Flowing Wastewater

BiOBr-based nanocomposite photocatalysts are used for removing the organic pollutants,but their poor adsorption/photocatalytic performances and the low potential for recycling limit their application.To solve the issue,herein we report a large-area recyclable CFC/BiOBr/ZIF-67 filter-membrane-shaped photocatalyst prepared by in situ growth of BiOBr/ZIF-67 nanocomposites on carbon fiber cloth(CFC).Fabrication process is based on hydrothermal synthesis of BiOBr nanosheets(diameter 0.5–1μm)on carbon fiber cloth(as substrate material)and then a chemical bath route is used to grow ZIF-67 nanoparticles(diameter 300–600 nm)in situ on the surface of CFC/BiOBr.Resulted composite,CFC/BiOBr/ZIF-67,exhibits a high specific surface area(545.82 m^(2) g^(−1))and a wide photoabsorption,accompanied by an absorption edge(~620 nm).In dark condition,CFC/BiOBr/ZIF-67 adsorbs bisphenol A(BPA)and orange 7(AO7)within 60 min,respectively with 20.0% and 40.1% efficiency.This level of efficiencies are correspondingly 2.6 and 3.2 times more that of the bare CFC/BiOBr(7.6%for BPA and 12.4% for AO7).Under visible light irradiation,CFC/BiOBr/ZIF-67 can degrade 69.7% of BPA and 96.0% of AO7,in 120 min,which are,respectively,1.3 and 1.8 times higher than the absorption efficiency of bare CFC/BiOBr(53.2% for BPA,52.0% for AO7).When CFC/BiOBr/ZIF-67 is used as a filter membrane for photocatalytic removal of pollutants in flowing wastewater(AO7,rate:~1.5 L h^(−1)),92.2%of AO7 can be decomposed after 10 filtering cycles.This study suggests CFC/BiOBr/ZIF-67 as a novel highly functional,recyclable and environmental friendly photo-driven membrane filter for purification and recovery of flowing surface waste waters.