Role of exosomal circular RNAs as microRNA sponges and potential targeting for suppressing hepatocellular carcinoma growth and progression

In this editorial,we comment on the article by Lyu et al published in the recent issue of the World Journal of Gastroenterology(2023;2219-2840).Hepatocellular carcinoma(HCC)is a frequently encountered and highly aggressive primary liver cancer,which remains the third-commonest cause of cancer-related death despite the current therapeutic modalities.There is urgency in developing novel thera-peutic approaches,such as by manipulating extracellular vesicles,which con-stitute a highly heterogeneous nanoparticle population that contains various cargoes.These cargoes have a pivotal role in cell-to-cell communication and can modify the functional level of the recipient cells via their uptake by other recipient cells.Exosomal non-coding RNAs have particular evolving significance in HCC,such as circular RNAs,which have been found differentially expressed in normal hepatic and HCC tissues.The aberrations in their expression levels have a key role in the HCC development and progression and the overall prognosis.In this editorial,we will shed light on the emerging role of exosomal circular RNAs in HCC development and progression,focusing on the oncogenic or potentially tumor suppressive effect of mesenchymal stem cells-derived exosomal non-coding RNAs.

Efficacy of balloon-occluded retrograde transvenous obliteration, percutaneous transhepatic obliteration and combined techniques for the management of gastric fundal varices

瞄准：评估为胃的静脉曲张的处理包含 transvenous 涂去的三个 interventional 处理的效果，并且比较功效和这些方法的不利效果。方法：从 1995 ～ 2004，有胃的底的静脉曲张的 93 个病人经历了 interventional 在我们的医院的放射线学的 embolotherapy。93 个病人， 75 被对待与堵塞汽球后退 transvenous 涂去(BRTO ) 过程；8 与经皮的 transhepatic 涂去(PTO ) 是过程；并且 10 与联合 BRTO 和 PTO 治疗。后续评估检验了幸存的率，复发并且胃的静脉曲张重新流血，在每个组食道的静脉曲张和复杂并发症变得更坏。结果：BRTO， PTO，和联合治疗在 81% 是技术上成功的(75/93 ) ， 44%(8/18 ) ，并且 100%(10/10 ) 病人分别地。胃的静脉曲张的复发在 PTO 组在 BRTO 组并且在 3 个病人在 3 个病人被发现。重新流血在 PTO 组在 BRTO 组并且在 1 个病人在 1 个病人被观察。没有肝细胞癌(HCC ) ， 1 年、 3 年的幸存率在在 PTO 组的 BRTO 组， 100% 和 100% 在病人是 98% 和 87% ，并且 90% 和 75% 分别地在联合治疗组织。结论：尽管有我们的学习的限制，联合 BRTO 和 PTO 治疗可以与与 BRTO 或 PTO 仍然是甚至术后疗法的控制不了的胃的底的静脉曲张救盒子，包括在在 BRTO， PTO 和联合治疗组之间的样品尺寸的回顾的自然和差异。

Clearance of hepatitis C virus after living-donor liver transplantation in spite of residual viremia on end date of interferon therapy before transplantation

Interferon (IFN) therapy is the only treatment strategy for hepatitis C virus (HCV) infection after liver transplantation (LT), but prophylactic and treatable IFN therapy after LT has been shown to be insufficient due to the adverse effects of IFN and rivabirin. In this paper, we describe the disappearance of HCV after LT without IFN therapy in the presence of residual viremia on the day of LT. We herein report our findings since this is considered an important case for the anti-HCV strategy of post LT. A 60-year old woman with LC and HCC was referred to Nagasaki University Hospital in August 2004. After she underwent LT on February 18, 2005, we injected peg- IFN-α-2a the 11th time at 18 wk and HCV-RNA was still positive in the serum at LT. The serum HCV-RNA was negative one month after operation and subsequently dissolved 15 mo after operation without IFN therapy. As a result, we speculate that if HCV-RNA is positive while HCV core antigen is negative before LT, then it may lead to clearance of HCV after LT. Therefore long acting peg-IFN- α-2a is thus considered a potentially effective agent for the treatment of HCV-related cirrhosis before LT.

Acute upper gastrointestinal bleeding in patients on long-term oral anticoagulation therapy: Endoscopic findings, clinical management and outcome

AIM: Acute gastrointestinal bleeding is a severe complication in patients receiving long-term oral anticoagulant therapy.The purpose of this study was to describe the causes and clinical outcome of these patients.METHODS: From January 1999 to October 2003, 111patients with acute upper gastrointestinal bleeding (AUGIB)were hospitalized while on oral anticoagulants. The causes and clinical outcome of these patients were compared with those of 604 patients hospitalized during 2000-2001with AUGIB who were not taking warfarin.RESULTS: The most common cause of bleeding was peptic ulcer in 51 patients (45%) receiving anticoagulants compared to 359/604 (59.4%) patients not receiving warfarin (P＜0.05). No identifiable source of bleeding could be found in 33 patients (29.7%) compared to 31/604(5.1%) patients not receiving anticoagulants (P= 0.0001).The majority of patients with concurrent use of non-steroidal anti-inflammatory drugs (NSATDs) (26/35, 74.3%) had a peptic ulcer as a cause of bleeding while 32/76 (40.8%)patients not taking a great dose of NSATDs had a negative upper and lower gastrointestinal endoscopy. Endoscopic hemostasis was applied and no complication was reported.Six patients (5.4%) were operated due to continuing or recurrent hemorrhage, compared to 23/604 (3.8%) patients not receiving anticoagulants. Four patients died, the overall mortality was 3.6% in patients with AUGIB due to anticoagulants, which was not different from that in patients not receiving anticoagulant therapy.CONCLUSION: Patients with AUGIB while on long-term anticoagulant therapy had a clinical outcome, which is not different from that of patients not taking anticoagulants.Early endoscopy is important for the management of these patients and endoscopic hemostasis can be safely applied.

Disease control by regulation of P-glycoprotein on lymphocytes in patients with rheumatoid arthritis

The main purpose of treatment of rheumatoid arthritis(RA) with disease modifying antirheumatic drugs(DMARDs) is to control activation of lymphocytes,although some patients do not respond adequately to such treatment. Among various mechanisms of multidrug resistance, P-glycoprotein(P-gp), a member of ATP-binding cassette transporters, causes drugresistance by efflux of intracellular drugs. Certain stimuli,such as tumor necrosis factor-α, activate lymphocytes and induce P-gp expression on lymphocytes, as evident in active RA. Studies from our laboratories showed spontaneous nuclear accumulation of human Y-boxbinding protein-1, a multidrug resistance 1 transcription factor, in unstimulated lymphocytes, and surface overexpression of P-gp on peripheral lymphocytes of RA patients with high disease activity. The significant correlation between P-gp expression level and RA disease activity is associated with active efflux of drugs from the lymphocyte cytoplasm and in drugresistance.However, the use of biological agents that reduce P-gp expression as well as P-gp antagonists(e.g., cyclosporine) can successfully reduce the efflux of corticosteroids from lymphocytes in vitro, suggesting that both types of drugs can be used to overcome drug-resistance and improve clinical outcome. We conclude that lymphocytes activated by various stimuli in RA patients with highly active disease acquire P-gpmediated multidrug resistance against corticosteroids and probably some DMARDs, which are substrates of P-gp. Inhibition/reduction of P-gp could overcome such drug resistance. Expression of P-gp on lymphocytes is a promising marker of drug resistance and a suitable therapeutic target to prevent drug resistance in patients with active RA.

An autopsy case of acute pancreatitis with a high serum IgG4 complicated by amyloidosis and rheumatoid arthritis

We report an autopsy case of acute pancreatitis with a high serum IgG4 concentration complicated by systemic amyloid A amyloidosis and rheumatoid arthritis (RA). The patient was a 42-year-old Japanese female with a 22-year history of rheumatoid arthritis. She was diagnosed with myasthenia gravis when she was 31-year old. At the onset of pancreatitis, the patient was anti-nuclear antibody-positive,and had high serum gamma globulin and IgG4 levels.Dexamethasone and conventional therapy induced clinical remission and significantly decreased the serum IgG4 and gamma globulin. However, despite the decreased disease parameters, the patient developed a bleeding pseudocyst and died of cardiac failure. In the autopsy examination, it was determined that pancreatitis was probably caused by ischemia due to vascular obstruction caused by amyloid deposition in the pancreas. Even though acute pancreatitis is a rare complication in RA patients, we speculate that an autoimmune pancreatitis-related mechanism and ischemia due to vascular obstruction by amyloid deposition might be attributable to a single source that leads to acute pancreatitis in our particular case.

Chinese Yellow Wine Inhibit Production of Homocysteine-induced Extracellular Matrix Metalloproteinase-2 in Cultured Rat Vascular Smooth Muscle Cells

Objectives Regular consumption of moderate amounts of Chinese yellow wine is associated with a reduced risk of coronary disease. Matrix metalloproteinases (MMPs) that participate in extracellular matrix degradation have been involved in atherosclerotic plaque growth and instability. The present research aimed to study the effects of Chinese yellow wine on the production of homocysteine-induced extracellular MMP-2 in cultured rats’ vascular smooth muscle cells. Methods The effects of different homocysteine levels (0-1000 ?滋mol/l) on MMP-2 production, and the effects of Chinese yellow wine with low alcohol concentrations (12-19%) on homocysteine-induced MMP-2 in cultured rat vascular smooth muscle cells (VSMCs) were examined using gelatin zymography and western blotting. The changes of MMP-2 under various treatments for 12 h, 24 h and 48 h were further compared. Results Homocysteine (50-1000 ?滋mol/l) increased the production of MMP-2 significantly in a dose-dependent manner. Increased production of MMP-2 induced by homocysteine was reduced by extracellularly added Chinese yellow wine. Production of MMP-2 under various treatments for 48 h increased more than 12 h and 24 h. Conclusions Extracellularly added Chinese yellow wine decreased homocysteine-induced MMP-2 secretion. The inhibitory effect of yellow wine on the activation of MMP-2 might contribute to their beneficial effects on the cardiovascular system.

Distribution Characteristics of Drug Susceptibility Test Results of Tuberculosis and Non-Tuberculous Bacilli in Patients with Opportunistic Infections of AIDS

Objective: To understand the distribution of drug susceptibility test results of opportunistic infections of tuberculosis and non-tuberculous bacilli in AIDS patients. Methods: The AIDS patients who were hospitalized in our hospital from January 2016 to June 2019 were collected as the research objects, and patients with opportunistic tuberculosis and non-tuberculous bacilli from AIDS patients were screened for drug susceptibility tests, and the distribution characteristics of drug susceptibility were analyzed. Results: 179 strains of tuberculosis and non-tuberculous mycobacteria were isolated from the specimens of AIDS patients, including 135 cases of tuberculosis mycobacteria and 44 cases of non-tuberculous mycobacteria. In the results of the drug susceptibility test, most strains of Mycobacterium tuberculosis showed sensitivity to commonly used drugs, and a few strains showed resistance;most strains of non-tuberculous mycobacteria showed resistance, and a few strains showed sensitivity. Conclusion: AIDS opportunistic infection of Mycobacterium tuberculosis and non-tuberculous mycobacteria have significant differences in drug sensitivity test results. Timely detection and analysis are of great significance to the diagnosis and treatment of the disease.

Remission of bronchial asthma after viral clearance in chronic hepatitis C

A 53-year-old man with a history of blood transfusion at the age of 20 was admitted to our hospital because of liver dysfunction. He had bronchial asthma when he was 18 years old, which naturally resolved within 2 years. However, his bronchial asthma recurred at the age of 45 and was treated with oral theophylline. He was diagnosed as having chronic hepatitis C based on the histological and clinical findings, and then interferon (IFN) therapy was administered. The frequency of bronchial asthma attack was gradually decreasing after IFN therapy with marked improvement of hypereosinophilia. He achieved sustained viral response (SVR) and his bronchial asthma did not worsen even after the cessation of IFN. Hepatitis C virus (HCV) infection and IFN therapy were considered in the remission of asthma in this case. HCV infection could be the cause of bronchial asthma, especially in patients with late appearance of asthma.

Effects of Chios mastic gum on cardiometabolic risk factors

Chios mastic gum(CMG),the resin produced by the trunk of Pistachia lentiscus var Chia,has been used for culinary and medicinal purposes since antiquity.Despite the fact that Pistacia species are widely distributed throughout the Mediterranean basin and in the circum-Mediterranean regions,CMG is a distinctive resin of the mastic trees grown exclusively in the southern part of the island of Chios.CMG has been used for centuries as a spice,a cosmetic,but its most important usage has been as a strong phytotherapeutic therapy,primarily for the management of gastrointestinal diseases.Recently,there are studies demonstrating that CMG has hypolipidemic,cardioprotective and antidiabetic properties.Therefore,the aim of the present review is to summarize the existing literature data regarding the potential beneficial effects of CMG on cardiometabolic risk factors.

Relative predictive factors for hepatocellular carcinoma after HBeAg seroconversion in HBV infection

AIM: To determine the predictive factors forhepatocellular carcinoma (HCC) development in patientsafter spontaneous or therapeutic HBeAg seroconversion.METHODS: In 48 patients who seroconverted to anti-HBe positive during follow-up, the background factors forHCC development were analyzed.RESULTS: HCC was developed in six patients duringfollow-up (average follow-up after HBeAg seroconversion:10.9±5.4 years). The incidence of HCC evaluated byKaplan-Meier analysis was significantly higher in patientswith abnormal aspartate aminotransferase (AST＞40 IU/L) level, lower platelet counts (PLT＜10×104/μL),lower albumin level (Alb＜30 g/L), positive HBV-DNA or older age at seroconversion (＞40 years). However, lower platelet count was the only predictive factor for HCC development shown by multivariate proportional-hazard analysis.CONCLUSION: Active hepatitis or advanced hepatitis at HBeAg seroconversion or progressive hepatitis even after HBeAg seroconversion would be the risk factors for HCC development. These predictive factors should be taken into account in determining the frequency of biochemical study or imaging studies for HCC surveillance.

Aspartate aminotransferase-immunoglobulin complexes in patients with chronic liver disease

AIM: To determine the complex of AST and immunoglobulin and to investigate its clinical significance in patients with liver disease.METHODS: The complex of AST and immunoglobulin was determined by encounter immunoelectrophoresis and its clinical significance was investigated in 128 patients with liver disease.RESULTS: AST was bound to immunoglobulin of antiimmunoglobulin A (IgA) class, but any binding to antiimmunoglobulin G and anti-immunoglobulin M classes was not observed. Although the incidence of ASTimmunoglobulin complex was 41.8% in chronic hepatitis (CH), the incidences in liver cirrhosis and hepatocellular carcinoma were 62.2 and 90.0%, respectively. In alcoholic liver disease with high level of serum IgA, the incidence of the complex was 66.7%, which was higher than that in CH. The ratio of binding to lambda-chain of IgA was higher than that to kappa-chain of IgA. The serum level of IgA and the ratio of AST/alanine aminotransferase (ALT) were significantly higher in patients with AST-IgA complex than in those without complex.CONCLUSION: These results suggest that AST-IgA complex in patients with progressive liver diseases and alcoholic liver injury can lead to elevation of the ratio of AST/ALT.

Subclinical synovitis detected by magnetic resonance imaging and ultrasonography following clinical remission in patients with rheumatoid arthritis:A retrospective study

Background:Subjective residual symptoms persist after clinical remission of rheumatoid arthritis(RA)in Japanese patients.Few studies have examined the relationship between these symptoms and subclinical inflammation using high-sensitivity imaging(musculoskeletal ultrasound[MSUS]and magnetic resonance imaging[MRI]).We examined the relationship between subjective residual symptoms and imaging findings in patients with RA who achieved clinical remission.Methods:We enrolled 30 patients with RA.The primary endpoint was the patients'subjective residual symptoms.The secondary endpoint was the relationship between the aforementioned symptoms and imaging findings.Results:Despite a mean Simplified Disease Activity Index of 1.3,imaging evaluation revealed inflammatory findings.In the multivariate analysis,the Health Assessment Questionnaire Disability Index(HAQ-DI)and pain visual analog scale(VAS)scores were extracted as independent related factors of subjective residual symptoms.The stratified analysis according to HAQ-DI showed a significant difference in synovitis on MRI between patients with and without residual disability(12.0±8.7 vs.5.3±5.3,respectively;p=0.0192).However,MSUS scores showed no significant difference in these two groups.In addition,no significant differences were found in MSUS and MRI scores between patients with and without residual pain VAS.Conclusions:Our findings demonstrated residual synovitis related to patientreported outcomes in patients with RA who achieved clinical remission.In particular,patients with an HAQ-DI score of>0.25 even after achieving clinical remission should be further examined by MRI and/or MSUS for the evaluation of residual synovitis.