Dysregulated microRNAs as a biomarker for diagnosis and prognosis of hepatitis B virus-associated hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a malignancy with a high incidence and fatality rate worldwide.Hepatitis B virus(HBV)infection is one of the most important risk factors for its occurrence and development.Early detection of HBV-associated HCC(HBV-HCC)can improve clinical decision-making and patient outcomes.Biomarkers are extremely helpful,not only for early diagnosis,but also for the development of therapeutics.MicroRNAs(miRNAs),a subset of non-coding RNAs approximately 22 nucleotides in length,have increasingly attracted scientists’attention due to their potential utility as biomarkers for cancer detection and therapy.HBV profoundly impacts the expression of miRNAs potentially involved in the development of hepatocarcinogenesis.In this review,we summarize the current progress on the role of miRNAs in the diagnosis and treatment of HBV-HCC.From a molecular standpoint,we discuss the mechanism by which HBV regulates miRNAs and investigate the exact effect of miRNAs on the promotion of HCC.In the near future,miRNA-based diagnostic,prognostic,and therapeutic applications will make their way into the clinical routine.

Flame behavior, shock wave, and instantaneous thermal field generated by unconfined vapor-liquid propylene oxide/air cloud detonation

Energy output and heating effects are essential for vapor-liquid fuel/air cloud detonation in the fuel-air explosive(FAE) applications or explosion accidents. The purpose of this study is to examine the dynamic large-size flame behavior, shock wave propagation law, and instantaneous thermal field generated by unconfined vapor-liquid propylene oxide(PO)/air cloud detonation. Based on computational fluid dynamics(CFD) and combustion theory, a numerical simulation is used to study the detonation process of a PO/air cloud produced by a double-event fuel-air explosive(DEFAE) of 2.16 kg. The large-scale flame behavior is characterized. The flame initially spreads radially and laterally in a wing shape. Subsequently,the developed flame increases with a larger aspect ratio. Moreover, the propagation laws of shock waves at different heights are discussed. The peak pressure of 1.3 m height level with a stepwise decline is obviously different from that of the ground with an amplitude of reversed ’N’ shape. In the vast majority of the first 6.9 m, the destructive effect of the shock wave near the ground is greater than that of the shock wave at 1.3 m height. Furthermore, the dynamic instantaneous isothermal field is demonstrated.The scaling relationship of various isotherms in the instantaneous thermal field with the flame and initial cloud is summarized. The comprehensive numerical model used in this study can be applied to determine the overpressure and temperature distribution in the entire fuel/air cloud detonation field,providing guidance for assessing the extent of damage caused by DEFAE detonation.

Better performance of PIVKA-II for detecting hepatocellular carcinoma in patients with chronic liver disease with normal total bilirubin

BACKGROUND Serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) is a promising biomarker for hepatocellular carcinoma(HCC) surveillance.AIM To identify the contributing factors related to the abnormal elevation of PIVKA-Ⅱ level and assess their potential influence on the performance of PIVKA-Ⅱ in detecting HCC.METHODS This study retrospectively enrolled in 784 chronic liver disease(CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve(AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-Ⅱ for HCC, respectively.RESULTS Elevated PIVKA-Ⅱ levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase(ALP), and total bilirubin(TBIL) for CLD patients and aspartate aminotransferase(AST) and tumor size for HCC patients(all P < 0.05). Serum PIVKA-Ⅱ were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal(ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST(all P < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-Ⅱ was significantly higher compared to that in patients with TBIL > 1 × ULN(0.817 vs 0.669, P = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant(0.783 vs 0.729, P = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone.CONCLUSION Serum PIVKA-Ⅱ has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.

Effect of Zn addition on microstructure and mechanical properties of Mg-3Y-2Nd-0.5Zr alloy

The effect of 0.5wt.%Zn addition on the microstructure and mechanical properties of Mg-3Y-2Nd-0.5Zr(WE32)alloy was investigated.The results indicate that WE32-0.5Zn alloy takes 48 h to reach peak hardness after solid solution treatment at 525℃and aging at 200℃,10 h earlier than WE32 alloy,which implies an accelerated aging precipitation kinetics owing to the addition of 0.5wt.%Zn.A large quantity of finerod and rectangular block-like Zn-Zr precipitates in theα-Mg matrix are formed in the WE32-0.5Zn alloy,and numerous needle-likeβ1phases are distributed at both ends of the Zn-Zr precipitates at peak-aged condition.In peak-aged condition,the ultimate tensile strength considerably increases from 263.2 MPa(WE32)to 309.6 MPa(WE32-0.5Zn),and the elongation dramatically increases from 4.3%(WE32)to 8.9%(WE32-0.5Zn).Theβ’andβ1phases are the main precipitates of the WE32-0.5Zn alloy peak-aged at 200℃.Theβ’andβ1phases easily nucleate at the Zn-Zr precipitates,and theβ1phases are particularly likely to nucleate and grow at the interface between the two ends of the Zn-Zr precipitates,which accelerates aging precipitation kinetics and leads to a shorter time to achieve peak aging.

以急性消化道大出血为表现的青年小肠多发间质瘤1例并文献复习

背景临床诊疗中急性小肠出血无特异性,且因小肠活动度大,迂回曲折,内镜检查不易操作,故对小肠出血的诊断仍是临床上的一大挑战.病例概述本案例为一例青年患者发生小肠多发间质瘤合并急性消化道大出血,在积极纠正休克后,以腹部电子计算机断层扫描(computed tomography,CT)为导向,完善急诊小肠镜检查,而后经过多学科综合会诊讨论迅速制定合理规范治疗方案及后续治疗计划,挽救患者生命,使患者获得最大受益.结论小肠间质瘤起病隐匿,缺乏特异性临床表现,可结合特点联合应用B超,CT、磁共振成像及相关血管造影,胃肠镜,胶囊内镜等检查明确术前诊断、精确临床分期,经多学科讨论制定规范的治疗方案,改善患者预后.

Aberrant regulation of Wnt signaling in hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the most lethal malignancies in the world. Several signaling pathways,including the wingless/int-1(Wnt) signaling pathway,have been shown to be commonly activated in HCC. The Wnt signaling pathway can be triggered via both catenin β1(CTNNB1)-dependent(also known as "canonical") and CTNNB1-independent(often referred to as "non-canonical") pathways. Specifically,the canonical Wnt pathway is one of those most frequently reported in HCC. Aberrant regulation from three complexes(the cell-surface receptor complex,the cytoplasmic destruction complex and the nuclear CTNNB1/T-cell-specific transcription factor/lymphoid enhancer binding factor transcriptional complex) are all involved in HCC. Although the non-canonical Wnt pathway is rarely reported,two main non-canonical pathways,Wnt/planar cell polarity pathway and Wnt/Ca2+ pathway,participate in the regulation of hepatocarcinogenesis. Interestingly,the canonical Wnt pathway is antagonized by non-canonical Wnt signaling in HCC. Moreover,other signaling cascades have also been demonstrated to regulate the Wnt pathway through crosstalk in HCC pathogenesis. This review provides a perspective on the emerging evidence that the aberrant regulation of Wnt signaling is a critical mechanism for the development of HCC. Furthermore,crosstalk between different signaling pathways might be conducive to the development of novel molecular targets of HCC.

年龄相关性白内障患者三焦点与单焦点IOL植入术后早期视觉质量比较

目的:观察三焦点与单焦点人工晶状体对年龄相关性白内障患者术后早期视觉质量的影响。方法:采用回顾性队列研究设计。纳入2018-06/2021-01在我院白内障科行白内障超声乳化联合人工晶状体植入术的年龄相关性白内障患者119例168眼,按照所植入人工晶状体类型分为三焦点组44例61眼与单焦点组75例107眼。对两组患者术后1mo视力(LogMAR)、视觉质量检查以及明、暗适应条件下对比敏感度检查进行统计学分析。结果:三焦点组单眼裸眼远视力(UDVA)、裸眼中距离视力(UIVA)、单眼裸眼近视力(UNVA)、最佳矫正远视力(BDVA)、最佳矫正远视下的中距离视力(DIVA)、最佳矫正远视下的近视力(DNVA)均明显优于单焦点组(均P<0.001)。三焦点组在调制传递函数截止频率(MTF cutoff)、客观散射指数(OSI)和斯特尔比值(SR)方面明显优于单焦点组(均P<0.05);在暗及明适应条件下的18c/d空间频率上,单焦点组对比敏感度明显优于三焦点组(P<0.001)。基于VF/QOF量表分析的调查问卷,三焦点组在日常生活感受评分和脱镜率方面明显优于单焦点组(P<0.05),而眩光发生率二者无差异(P>0.05)。结论:植入三焦点人工晶状体可为年龄相关性白内障超声乳化术后患者提供全方位良好的视力和视觉质量,满足不同条件下的用眼需求。

Proliferating cell nuclear antigen clamp associated factor,a potential proto-oncogene with increased expression in malignant gastrointestinal tumors

Gastrointestinal(GI)cancers,including malignancies in the gastrointestinal tract and accessory organs of digestion,represent the leading cause of death worldwide due to the poor prognosis of most GI cancers.An investigation into the potential molecular targets of prediction,diagnosis,prognosis,and therapy in GI cancers is urgently required.Proliferating cell nuclear antigen(PCNA)clamp associated factor(PCLAF),which plays an essential role in cell proliferation,apoptosis,and cell cycle regulation by binding to PCNA,is a potential molecular target of GI cancers as it contributes to a series of malignant properties,including tumorigenesis,epithelial-mesenchymal transition,migration,and invasion.Furthermore,PCLAF is an underlying plasma prediction target in colorectal cancer and liver cancer.In addition to GI cancers,PCLAF is also involved in other types of cancers and autoimmune diseases.Several pivotal pathways,including the Rb/E2F pathway,NF-κB pathway,and p53-p21 cascade,are implicated in PCLAF-mediated diseases.PCLAF also contributes to some diseases through dysregulation of the p53 pathway,WNT signal pathway,MEK/ERK pathway,and PI3K/AKT/mTOR signal cascade.This review mainly describes in detail the role of PCLAF in physiological status and GI cancers.The signaling pathways involved in PCLAF are also summarized.Suppression of the interaction of PCLAF/PCNA or the expression of PCLAF might be potential biological therapeutic strategies for GI cancers.

Hepatitis B core antigen modulates exosomal miR-135a to target vesicle-associated membrane protein 2 promoting chemoresistance in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common malignant tumors.The association of hepatitis B virus(HBV)infection with HCC is hitherto documented.Exosomal miRNAs contribute to cancer progression and chemoresistance.HBV X protein has been known to modulate miRNAs that facilitate cell proliferation and the process of hepatocarcinogenesis.However,there has been no report on hepatitis B core antigen(HBc)regulating exosomal miRNAs to induce drug resistance of HCC cells.AIM To elucidate the mechanism by which HBc promotes Doxorubicin hydrochloride(Dox)resistance in HCC.METHODS Exosomes were isolated by ultracentrifugation.The morphology and size of exosomes were evaluated by Dynamic Light Scattering(DLS)and transmission electron microscopy(TEM).The miRNAs differentially expressed in HCC were identified using The Cancer Genome Atlas(TCGA)database.The level of miR-135a-5p in patient tissue samples was detected by quantitative polymerase chain reaction.TargetScan and luciferase assay were used to predict and prove the target gene of miR-135a-5p.Finally,we identified the effects of miR-135a-5p on anti-apoptosis and the proliferation of HCC in the presence or absence of Dox using flow cytometry,Cell counting kit 8(CCK-8)assay and western blot.RESULTS We found that HBc increased the expression of exosomal miR-135a-5p.Integrated analysis of bioinformatics and patient samples found that miR-135a-5p was increased in HCC tissues in comparison with paracancerous tissues.Bioinformatic analysis and in vitro validation identified vesicle-associated membrane protein 2(VAMP2)as a novel target gene of miR-135a-5p.Functional assays showed that exosomal miR-135a-5p induced apoptosis protection,cell proliferation,and chemotherapy resistance in HCC.In addition,the rescue experiment demonstrated that VAMP2 reversed apoptosis protection,cell growth,and drug resistance by miR-135a-5p.Finally,HBc promoted HCC anti-apoptosis,proliferation,and drug resistance and prevented Dox-induced apoptosis via the miR-135a-5p/VAMP2 axis.CONCLUSION These data suggested that HBc upregulated the expression of exosomal miR-135a-5p and promoted anti-apoptosis,cell proliferation,and chemical resistance through miR-135a-5p/VAMP2.Thus,our work indicated an essential role of the miR-135a-5p/VAMP2 regulatory axis in chemotherapy resistance of HCC and a potential molecular therapeutic target for HCC.

Exosomes as potential diagnosis and treatment for liver cancer

BACKGROUND Liver cancer is the fourth most significant cause of cancer-related death.Lack of early diagnosis strategy and a scarcity of efficient therapy constitute the main reasons for its lethality.Exosomes,which contain various bioactive molecules,are characterized by high biocompatibility,low immunogenicity,and high transport efficiency.As a result,exosomes have become a research hotspot and present significant potential for cancer diagnosis biomarkers,biotherapeutics,therapy targets,drug carriers and therapeutic agents.AIM To explore the potential of exosomes in the diagnosis and treatment of liver cancer.METHODS We conducted a systematic literature search via PubMed and Web of Science.The following keywords were used:"exosomal biomarkers","exosomal therapy","exosomal therapy",and"liver cancer"or"HCC".The duplicate data were deleted by EndNote software.Literature search focused on full-texts and references of each article were carefully checked.One author(Xiao-Cui Wei)screened the literature that met the following inclusion criteria:(1)Detection of exosomes or their contents in clinical samples(body fluid or tissue);or(2)Exosomes served as drug carriers or therapeutic factors.Two authors(Xiao-Cui Wei and Li-Juan Liu)independently reviewed all retained literature and analyzed the information.RESULTS A total of 1295 studies were identified using the systematic literature search.Of these,835 duplicate studies were removed.A further 402 irrelevant studies were excluded due to being irrelevant,including other diseases,review articles,the literature containing neither clinical samples nor animal experiments,exosomeindependent studies,methods for detecting exosomes,or articles in Chinese.Finally,58 published papers were retained and analyzed in the study.It showed a list of potential exosomal biomarkers that were upregulated in the blood samples of patients with liver cancer.Those downregulated in exosomes might serve as possible biotherapeutics.Some exosomes derived from cells in vitro were used for cytology or animal experiments to explore the mechanism of these exosome contents in disease.These contents might serve as potential targets for liver cancer.Additionally,we also discussed that exosomes serve as drug carriers or therapeutic factors.CONCLUSION Exosomes might serve as potential biomarkers or therapeutic biotargets in liver cancer and have the potential to act as drug carriers and self-treatment factors for liver cancer patients.

Analysis of mechanism on Indigo Naturalis in treating chronic myelocytic leukemia based on two-dimentional model of protein-protein interaction network-moleculardocking technique

运用分子对接技术探讨青黛干预CMLK562细胞的有效分子学机制.使用在线人类孟德尔遗传数据库（OMIM）筛选CML相关基因,使用String10.0用于进一步文本挖掘并构建CML可视化蛋白质相互作用网络,将数据读入Cytoscape3.4.0,通过插件CentiScaPe2.1实现网络拓扑分析.青黛活性小分子物质从第三方数据库获取,运用Chemoffice8.0与Sybyl8.1对其再构建和优化,得到青黛小分子配体结构库,通过SurflexDock模块与受体革巴点进行分子对接,打分后得到关键靶标.构建了由425个节点（蛋白质）和2799条边（相互作用）组成的蛋白质相互作用网络,分析得出关键靶标JAK2.CML是一个受多基因调控的复杂疾病,JAK2很可能是其关键节点.

Role of the scalar f_(0)(980)in the process D_(s)^(+)→π^(+)π^(0)π^(0*)

Based on BESⅢmeasurements of the reaction D_(s)^(+)→π^(+)π^(0)π^(0),we investigate this process by considering the S-wave pseudoscalar-pseudoscalar interaction within the unitary chiral approach and the contributions from the intermediate resonances f_(0)(1370)and f_(2)(1270).Our calculation can reasonably reproduce the experimental data,and our results imply that f_(0)(980),which is dynamically generated from the S-wave pseudo scalar-pseudo scalar interaction,plays an important role in this process,and the contributions from the intermediate resonances f_(0)(1370)and f_(2)(1270)are also necessary.More precise measurements of this process in future can shed light on the nature of f_(0)(1370)and f_(2)(1270).

Circulating MicroRNA-145 is Associated with Acute Myocardial Infarction and Heart Failure

Background： Recent studies show that microRNA- 145 （miRNA- 145 ） might be an attractive tumor biomarker of considerable prognostic value, but little is known about their relationship with acute myocardial infarction （AMI）. This study investigated the correlation between the level of miR-145 and AM1. Methods： One-hundred patients were divided into three groups： no coronary artery disease （CAD） group, non-ST segment elevation myocardial infarction group, and ST segment elevation myocardial infarction group. The plasma levels of miR-145 were quantified using real-time quantitative polymerase chain reaction. Logarithmic transformation of miRNA-145 levels （Ln_rniRNA-145） was used for statistical analysis due to the skewed data distribution. Results： Plasma levels of miR-145 were significantly lower in patients with AMI compared to patients in the non-CAD group （-6.38 ± 0.11 vs. -4.47 ＋ 0.17, P 〈 0.0001）. Compared to those without heart failure, the levels of miR-145 were significantly lower in patients with heart failure （-6.91 ± 0.20 vs. -5.35 ± 0.13, P 〈 0.0001）. We also found that the lower plasma levels of miRNA-145 significantly correlated with increased serum levels of B-type natriuretic peptide （Spearman ρ = -0.60, P 〈 0.0001）, troponin T （Spearman p = -0.62, P 〈 0.0001）, and decreased ejection fraction （Spearman ρ = 0.65, P 〈 0.0001）. In a multivariable linear regression analysis, AMI and heart failure were independently associated with lower Ln miRNA-145 （estimate -0.99, standard error [SE] 0.28; P = 0.001 and estimate -0.62, SE 0.21 ; P = 0.004）. Conclusions： Our results suggest that decreased plasma levels of miR-145 are associated with AMI. Circulating miR-145 may be useful in prognosticating cardiac function and the risk of developing heart failure.

SENP2 negatively regulates cellular antiviral response by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation

Transcription factor IRF3-mediated type I interferon induction is essential for antiviral innate immunity.We identified the deSUMOylating enzyme Sentrin/SUMO-specific protease(SENP)2 as a negative regulator of virus-triggered IFN-b induction.Overexpression of SENP2 caused IRF3 deSUMOylation,K48-linked ubiquitination,and degradation,whereas depletion of SENP2 had opposite effects.Both the SUMOylation and K48-linked ubiquitination of IRF3 occurred at lysines 70 and 87,and these processes are competitive.The level of virus-triggered IFN-b was markedly up-regulated and viral replication was reduced in SENP2-deficient cells comparing with wild-type controls.Our findings suggest that SENP2 regulates antiviral innate immunity by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation,and provide an example of cross-talk between the ubiquitin and SUMO pathways in innate immunity.

Low-molecular-weight photoresponsive supramulecular hydrogel based on a dicationic azobenzene-bridged pyridinium hydrogelator

Low-molecular-weight supramolecular hydrogels are of significant attractive soft materials as particular functions can be facilely introduced by the straightforward fabrication of such self-assembled systems. In this study, an azobenzene-bridged dicationic pyridinium salt was synthesized, from which photoresponsive supramolecular hydrogel could be fabricated through the π-π stacking and hydrophobic interactions in the aqueous solution. By taking advantages of the UV-vis light induced E/Z photoisomerization behaviors of the incorporated azobenzene photochromophore, reversible gel-sol transformation of such supramolecular hydrogel could be achieved under the alternating UV-vis irradiation conditions. We believed that this photoresponsive supramolecular hydrogel will be a good supplementary in the creation of intelligent soft material.

Viologen derivatives with extendedπ-conjugation structures:From supra-/molecular building blocks to organic porous materials

Recently,increasing atte ntion has been paid on extending theπ-conjugation structures ofviologens(1,1’-disubstituted-4,4’-bipyridylium salts)by incorporating planar aromatic units into the bipyridinium backbones.Various viologen derivative s with extendedπ-conjugation structures have been synthesized,including the N-termini aromatic substituted viologens,the extendedπ-conjugated viologens(denoted as ECVs)as well as theπ-conjugated oligomeric viologens(denoted as COVs).These compounds typically exhibit interesting properties distinguished from those of an isolated viologen unit,which make them as new class of electron deficient supra-/molecular building blocks in supramolecular chemistry and materials science.In this review,we would like to highlight the recent advances of viologen derivatives with extendedπ-conjugation structures in versatile applications ranging from electrochromic and energy storage materials,the ECV/COV-based supramolecular self-assembly systems including the linear supramolecular polymers and 2D/3D supramolecular organic frameworks(SOFs),to the viologen-based covalent organic frameworks(COFs)/networks.We hope this review will serve as an in-time summary worthy of referring,more importantly,to provide inspiration in the rational design of novel molecules with unexplored properties and functions.

Luminescence Regulation of Silver-Thiolate Clusters Protected by 1,2-Dithiolate-o-carborane

Engineering the surface of the metal clusters with the core structure maintained and tuning their luminescence in a wide range is still a challenge in the nanomaterial research.We modified six mono-pyridyl ligands with different electronic effects(conjugation effect or induction effect)on a superatomic silver cluster[Ag_(14)(C_(2)B_(10)H_(10)S_(2))_(6)(CH_(3)CN)_(8)](denoted as Ag_(14))through in situ site-specific surface engineering.

Clinical characteristics and risk factors of severe respiratory syncytial virus-associated acute lower respiratory tract infections in hospitalized infants

Background:To investigate the clinical characteristics and analyze risk factors for severe respiratory syncytial virus(RSV)infection in hospitalized infants with acute lower respiratory tract infections(ALRIs).Methods:A retrospective review of the medical records of infants with RSV-associated ALRIs between March 1st,2011 and February 29th,2012 was conducted.Subjects were followed up over the phone or by outpatient visit six and twelve months after discharge.Results:Among 913 RSV-associated ALRIs infants,288(31.5%)had severe infections,which accounted for 4.2%of hospitalized children.The hospital RSV mortality rate was 1.0%.The proportions of cases with tachypnea,apnea,cyanosis,and fine rales were significantly higher in the severe ALRIs group(all P<0.001).Multivariate logistic regression showed that low-birth-weight[1.698(1.028-2.805)],age less than 3 months old[3.385(2.174-5.271)],congenital heart disease[1.667(1.149-2.418)],bronchopulmonary dysplasia[8.505(1.731-41.780)],and airway abnormalities[2.246(1.008-5.005)]were independent risk factors for severe ALRIs.The incidence of bronchitis,pneumonia and readmission in the severe group was significantly higher than that of the non-severe group during the one-year follow-up(all P<0.001).Conclusions:Younger age,low birth weight and underlying disease are associated with severe RSVassociated ALRIs.Furthermore,severe RSV infections may be associated with a higher frequency of subsequent bronchitis,pneumonia and re-hospitalization in the following year.