Interleukin 1βreceptor and synaptic dysfunction in recurrent brain infection with Herpes simplex virus type-1

Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.

HBV、HCV、HIV血筛多中心研究免疫学灰区的核酸检测分析与临床特征研究

目的分析化学发光灰区标本的临床特征及核酸检测对化学发光灰区标本结果判断的指导性意义。方法收集2021年7月—12月全国不同地区的5家综合医院入院患者术前/输血前血源性传播疾病样本检测结果,对化学发光灰区检测结果的标本进行核酸检测结果及临床特征分析。结果5723例样本中总计检出HBV免疫灰区样本28例(占比0.49%),HCV灰区样本20例(占比0.35%)。经核酸检测验证,28例HBV灰区样本中,15例HBV样本核酸检测为阳性(占比53.5%),其HBcAb也均为阳性;13例HBV样本核酸检测为阴性(占比46.5%),其中HBcAb阳性4例。HBV与HCV免疫检测灰区在临床各个科室均有发现,出现HBV灰区样本最多的前三科室为骨科、妇科、泌尿科,灰区样本核酸验证假阳性最多的临床科室为妇科与骨科。HCV灰区样本最多的前三科室为泌尿、肾内、外科,且均为假阳性。HBV灰区样本患者临床诊断结果有35.7%(10/28)为肿瘤类疾病,HCV灰区样本患者临床诊断结果有40%(8/20)为肿瘤类疾病。结论化学发光法容易造成假阳性结果,应注意复检验证,且设置灰区并非必要。灰区样本可见于多个临床科室,具有一定的临床分布特征。核酸检测可以提高检测灵敏度并且更大限度保证结果的准确性,能够验证免疫检测灰区。

基于自动化提取HCV RNA荧光定量检测系统的性能验证

目的 基于Stream SP96全自动核酸提取仪、ABI7500实时荧光定量PCR仪对丙型肝炎病毒(HCV)RNA定量检测系统的性能指标进行验证。方法 依据《临床实验室对商品定量试剂盒分析性能的验证》WS/T 420-2013性能验证方案,采用Stream SP96全自动核酸提取平台及ABI7500荧光定量PCR仪检测HCV RNA,对其准确度、精密度、线性区间、检测限、定量限和抗干扰能力等进行方法学性能验证。结果 低、高浓度标准物质的均值与靶值的误差分别为0.20和0.25,均小于靶值对数值±0.4 log;低浓度样本的批内、批间不精密度变异系数值分别为0.79%、1.01%,高浓度样本的批内、批间不精密度变异系数值分别为0.52%、1.22%,均<5%;线性相关系数r>0.980,线性区间可达20~1.0×10^(8),呈良好线性(R^(2)=0.997 3);检出限为20 IU/mL,最低定量限为50 IU/mL;含胆红素(300 mg/L)、血红蛋白(300 g/L)、甘油三酯(3 000 mg/L)的干扰物质对样本检测结果无影响。结论 HCV RNA实时荧光PCR定量法检测系统准确度、精密度、线性范围、检出限、定量限、抗干扰能力均符合厂家声明,能够满足临床对HCV RNA定量检测的需求。

New combination test for hepatitis C virus genotype and viral load determination using Amplicor GT HCV MONITOR test v2.0

AIM: To develop a new sensitive and inexpensive hepatitis C virus (HCV) combination test (HCV Guideline test) that enables the determination of HCV genotypes 1, 2 and 3, and simultaneous determination of HCV viral load using commercial Amplicor GT HOV MONITOR test v2.0 (microwell version). METHODS: The HCV Guideline test used the PCR product generated in commercial Amplicor GT HCV Monitor test v2.0 for viral load measurement using microwell plate version of Amplicor HCV Monitor and also captured on separate plates containing capture probes and competitive oligonucleotide probes specific for HCV genotypes 1, 2 and 3, The HCV genotype was subsequently determined using the biotin-labeled PCR product and five biotin-labeled HCV-specific probes. RESULTS: The sensitivity of the HCV Guideline test was 0.5 KIU/mL. Specificity of the HCV Guideline test was confirmed by direct sequencing of HCV core region and molecular evolutionary analyses based on a panel of 31 samples. The comparison of the HCV Guideline test and an in-house HCV core genotyping assay using 252 samples from chronic hepatitis C patients indicated concordant results for 97.2% of samples (59.5% genotype 1, 33.7% genotype 2, 6.0% genotype 3, and 0.8% mixed genotypes). Similarly, the HCV Guideline test showed concordance with a serological test, and the serological test failed to assign any serotype in 12.7% of the samples, indicating a better sensitivity of the HCV Guideline test. CONCLUSION: Clinically, both viral load and genotypes (1, 2 and 3) have been found to be major predictors of antiviral therapy outcome regarding chronic hepatitis C based on guidelines and they are, in normal circumstances, performed as separate stand-alone assays. The HCV Guideline test is a useful method for screening large cohorts in a routine clinical setting for determining the treatment regimen and for predicting the outcome of antiviral therapy of chronic hepatitis C.

DNA immunization with fusion genes encoding different regions of hepatitis C virus E2 fused to the gene for hepatitis B surface antigen elicits immune responses to both HCV and HBV

AIM: Both Hepatitis B virus (HBV) and Hepatitis C virus(HCV) are major causative agents of transfusion-associatedand community-acquired hepatitis worldwide. Developmentof a HCV vaccine as well as more effective HBV vaccines isan urgent task. DNA immunization provides a promisingapproach to elicit protective humoral and cellular immuneresponses against viral infection. The aim of this study is toachieve immune responses against both HCV and HBV by DNAimmunization with fusion constructs comprising various HCVE2 gene fragments fused to HBsAg gane of HBV.METHODS: C57BL/6 mice were immunized with plasmid DNAexpressing five fragments of HCV E2 fused to the gene forHBsAg respectively. After one primary and one boostingimmunizations, antibodies against HCV E2 and HBsAg weretested and subtyped in ELISA. Splenic cytokine expressionof IFN-γ and IL-10 was analyzed using an RT-PCR assay.Post-immune mouse antisera also were tested for theirability to capture HCV viruses in the serum of a hepatitis Cpatient in vitro.RESUTLTS: After immunization, antibodies against bothHBsAg and HCV E2 were detected in mouse sera, withIgG2a being the dominant immunoglobulin sub-class. High-level expression of INF-γ was deuetected in cultured splenic cells.Mouse antisera against three of the five fusion constructs wereable to capture HCV viruses in an in vitro assay.CONCLUSION: The results indicate that these fusionconstructs could efficiently elicit humoral and Th1 dominantcellular immune responses against both HBV S and HCV E2antigens in DNA-immunized mice. They thus could serve ascandidates for a bivalent vaccine against HBV and HCVinfection. In addition, the capacity of mouse antisera againstthree of the five fusion constnucts to capture HCV virusses invitro suggested that neutralizing epitopes may be present inother regions of E2 besides the hypervariable region 1.

Management of hepatitis C virus infection in HIV/HCV co-infected patients: Clinical review

Nearly one fourth of individuals with human immunodeficiency virus (HIV) infection have hepatitis C virus (HCV) infection in the US and Western Europe. With the availability of highly active antiretroviral therapy and the consequent reduction in opportunistic infections, resulting in the prolongation of the life span of HIV-infected patients, HCV co-infection has emerged as a signif icant factor influencing the survival of HIV patients. Patients with HIV/HCV co-infection have a faster rate of fibrosis progression resulting in more frequent occurrences of cirrhosis, end-stage liver disease, and hepatocellular carcinoma. However, the mechanism of interaction between the two viruses is not completely understood. The treatment for HCV in co-infected patients is similar to that of HCV monoinfection; i.e., a combination of pegylated interferon and ribavirin. The presence of any barriers to antiHCV therapy should be identified and eliminated in order to recruit all eligible patients. The response to treatment in co-infected patients is inferior compared to the response in patients with HCV mono-infection. The sustained virologic response rate is only 38% for genotype-1 and 75% for genotype-2 and -3 infections. Liver transplantation is no longer considered a contraindication for end-stage liver disease in coinfected patients. However, the 5 year survival rate is lower in co-infected patients compared to patients with HCV mono-infection (33% vs 72%, P = 0.07). A better understanding of liver disease in co-infected patients is needed to derive new strategies for improving outcome and survival.

广州地区259例丙型肝炎病毒患者HCV基因分型研究

目的 了解广州地区丙型肝炎病毒患者的HCV基因型分布情况,为该地区丙型肝炎病毒的预防和诊疗提供依据。方法 选择自2019年9月至2023年4月共259例丙型肝炎病毒患者的HCV基因分型的结果,分析比较不同年龄、性别和年度各基因型感染率的差异。结果 共纳入259例患者,最常见的基因型为6a型和1b型,占42.47%和42.08%,与其他亚型差异有统计学意义(P<0.05)。其余依次为3a型占6.18%,2a型占4.63%,3b型占4.25%,2b型占0.39%,未发现亚型混合感染。1b型,青年人群(41.86%)、中年人群(31.447%)分别低于老年人群的71.93%;6a型,青年人群(44.186%)、中年人群(51.572%)分别高于老年人群的15.789%,差异有统计学意义(P<0.05)。女性1b型63.077%、2a型10.769%分别高于男性的35.052%和2.577%,女性6a型18.462%低于男性的50.516%,差异有统计学意义(P<0.05)。不同年度各基因型感染率差异无统计学意义。结论 广州地区丙型肝炎病毒患者HCV基因分型以6a型、1b型为主。1b型多见于60岁以上的老年人群和女性,6a型多见于中青年人群及男性。

2018-2022年我国18家省级血液中心献血者HCV检测结果分析

目的分析我国省级血液中心服务区域献血人群丙型肝炎病毒(hepatitis C virus,HCV)检测数据。方法对我国东中西部不同地区的18家省级血液中心,2018—2022年初次献血和重复献血者抗-HCV和HCV RNA检测数据收集整理,分析献血者中抗-HCV ELISA和抗-HCV ELISA阴性中HCV RNA检测不合格率与年度、血液中心以及初次献血和重复献血者之间的关系。结果2018年—2022年HCV总不合格率从24.61/万逐年减少至15.17/万(χ^(2)=717.71,P<0.01),西部地区为25.72/万最高,东部11.96/万最低(χ^(2)=2382.54,P<0.01);初次献血者抗-HCV ELISA不合格率(30.50/万)比重复献血者(7.42/万)高(χ^(2)=9694.63,P<0.01);各血液中心抗-HCV ELISA阴性中HCV-RNA单独不合格率范围为0~7.54/万。结论我国18家血液中心服务区域献血者的HCV检测不合格率呈逐年降低趋势;HCV检测不合格率存在明显的地域分布差异;与初次献血者相比,重复献血者为HCV检测不合格低危人群;HCV-RNA检测在血液安全方面发挥重要作用。

基于医院感染预警系统的江西省某三甲医院就诊患者HCV微消除模式探索及评价

目的探索并评价江西省某综合医院就诊患者丙型肝炎病毒(HCV)微消除模式,为省内制定消除HCV公共健康危害策略提供参考依据。方法收集该院2021年1月—2022年12月就诊并进行HCV筛查的住院患者相关数据,其中2021年为基线数据,2022年为HCV微消除模式运行数据,分析其性别、年龄、送检科室、抗-HCV阳性率、HCV-RNA阳性率等指标,以专科就诊率、治疗率、失访率分析其运行效果,以SWOT-AHP法定量评价模式发展。结果2021—2022年共有397744例住院患者进行抗-HCV筛查,男女性别比为1.34∶1,平均年龄为54岁,送检科室主要以感染科/消化科为主。62份患者标本HCV基因亚型分型主要以1b亚型(43份)为主,其次为6亚型(9份)。模式运行后首次HCV预警率为81.20%,预警后抗-HCV送检率达93.15%,后续弹窗预警抗-HCV送检率为100%。与2021年比较,2022年HCV住院患者治疗率上升,差异有统计学意义(P<0.05);而专科就诊率、患者失访率差异均无统计学意义(均P>0.05)。模式运行重心坐标计算P(X,Y)=(0.0182,0.0069),位于第一象限。结论江西省某综合医院就诊患者HCV微消除模式可行且成效明显,下一步模式优化应重视SO策略(依靠内部优势,利用外部机会)。

Relationship of hepatitis C virus infection with primary hepatic carcinoma: an investigation of serum HCV RNA in different population groups

A preliminary study on the serum hepatitis C virus(HCV)RNA in 182 pa-tients with different chronic liver diseases and 35 blood donors was carried out with“nested”polymerase chain reaction.It was found that serum HCV RNA was detected in36.6%(34/93)cases of primary hepatic carcinoma(PHC),31.7%(20/63)liver cirrhosis,15.4%(4/26)chronic hepatitis and 2.9%(1/35)blood donors;most of the HCV RNA pos-itive cases(41/58)were complicated with HBV replicating markers;the rate of single posi-tive for HCV RNA was 15.1%(14/93)in PHC,3.2%(2/63)in liver cirrhosis,and 3.8%(1/26)in chronic hepatitis.These findings imply that about 20% of PHC cases appear tobe related to the coinfection of HCV and HBV and 15% of PHC cases are related to sin-gle HCV infection.

STUDY ON THE MOTHER TO INFANT TRANSMISSIONOF HEPATITIS C VIRUS BY COMBINED ASSAYOF ANTI-HCV AND HCV-RNA

objective The mother to infant transmission of Hey was prospectively investigated.Methods Hepatitis C virus(HCV) infection was tested by the combination assay of anti-HCV andHCV- RNA. Six hundred and ten pregnant women were investigated for HCV infection, and infants from HCVinfected mothers were followed up at birth, 3, 6, 9, 12 months after birth to investigate HCV infection. HCVgenotypes were detected in all persons with HCV- RNA positive. HCV was quantified by branch DNA signalamplification assay (bDNA) in pregnant women. Results Among 610 pregnant women, 18 infected HCV, theinfection rate of HCV in pregnant women was 2.95% (18/610). Five of 18 infants from 18 HCV infected mothersinfected HCV, they had no history of operation, or blood transfusion and other risk exposure to HCV, so the HCVinfection was irc m their mothers, the rate of HCV transmission from mother to infant was 27.8%.HCVgenotype fo was found in 16 pregnant women with HCV- RNA positive, 5 infants and their mothers had the sameHCV genotype(1b) infection. All pregnant women infected HCV have low HCV titer in serum. Conclusion lnthis research, it was noted that HCV could be vertically transmitted from mother to infant even if mother had lowserum HCV titer(≤14.11 ×105/ml). The combination assay of anti - HCV and HCV- RNA was valuable ininvestigating the HCV infection in pregnant women and the transmission of HCV from mother to infant. It haspotential value in diagnosing HCV infection in other population.

丙型病毒性肝炎抗体检测与HCV高敏核酸检测对病毒性丙型肝炎的筛查价值研究

目的通过对本院2019年1月至2022年9月需进行手术、输血或其他侵入性医疗服务的住院患者的HCV血清学抗体及高敏HCV RNA筛查结果进行回顾性分析,探讨丙型病毒性肝炎抗体检测与HCV高敏核酸检测对病毒性丙型肝炎的筛查检测价值。方法对本院相关住院患者进行Elecsys Anti-HCV II或(和)高敏HCV RNA检测,统计分析其检测结果。结果HCV血清学抗体检测22443人次,阳性率为0.68%,阳性COI中位数为38.4(1.0~165)。高敏HCV RNA检测34628人次,阳性率0.30%,阳性病毒载量中位数为1.00×10^(6)IU/mL(3.50×10^(1)~4.00×10^(7)IU/mL)。两种方法学均显示45~59岁人群阳性率显著高于其他人群(P<0.001)。两种检测有重合的样本共17785人次,HCV抗体血清学阳性率为0.70%。高敏HCV RNA阳性率0.22%,如以高敏HCV RNA为丙型肝炎现症感染的标准,HCV抗体血清学检测HCV现症感染的灵敏度为100.00%(95%CI 89.09%~100.00%),特异性为99.52%(95%CI 99.41%~99.61%),现症感染阳性预测期PPV为32.00%(95%CI 23.82%~40.18%),阴性预期值为100.00%。HCV抗体血清学检测COI值与高敏HCV RNA检测的病毒载量无线性相关性,COI<10和COI>100的HCV RNA阳性率低。结论HCV抗体检测和高敏HCV RNA均为有效的丙型肝炎筛查手段,需进一步加强对重点人群的丙型肝炎感染管理。

云南595例HIV/HCV共感染者的HCV基因型及临床特征分析

目的 分析云南省传染病医院抗病毒门诊595例HIV/HCV共感染者的HCV基因型及临床特征,为HIV/HCV防治提供参考。方法 选取2022年1月~2023年7月在云南省传染病医院抗病毒门诊就诊的HIV/AIDS患者为研究对象,采用横断面研究,收集患者基本信息,检测HCV抗体、HCV RNA、HCV基因型、生化指标,并进行分析。结果 筛查5709例HIV/AIDS患者,HCV抗体阳性率10.42%(595/5709),HCV RNA检测率86.72%(516/595),HCV RNA阳性率47.09%(243/516)。95.47%HCV RNA阳性完成HCV基因检测,其中各型占比为:1b型(14.66%)、2a型(0.86%)、3a型(27.59%)、3b型(40.95%)、6型(14.66%)、未分型(1.29%)。HCV RNA阳性者中FIB-4评分> 3.25为37.86%。不同感染途径的HIV/HCV共感染者丙肝基因分型差异有统计学意义(P <0.05),基因分型为3a、3b的FIB-4指数均高于其他基因型,两两比较差异均有统计学意义(均P <0.05)。结论 HIV/AIDS患者中HCV抗体、HCV RNA阳性率较高,HCV基因型以3b型、3a型为主要流行株,发生进展性肝脏纤维化占比较高。在HIV/AIDS患者中进行HCV感染的筛查对早期诊断及早期治疗丙型肝炎具有重要意义。

Alterations in the gut microbiome after transjugular intrahepatic portosystemic shunt in patients with hepatitis B virus-related portal hypertension

BACKGROUND Gut microbiota(GM)affects the progression and response to treatment in liver diseases.The GM composition is diverse and associated with different etiologies of liver diseases.Notably,alterations in GM alterations are observed in patients with portal hypertension(PH)secondary to cirrhosis,with hepatitis B virus(HBV)infection being a major cause of cirrhosis in China.Thus,understanding the role of GM alterations in patients with HBV infection-related PH is essential.AIM To evaluate GM alterations in patients with HBV-related PH after transjugular intrahepatic portosystemic shunt(TIPS)placement.METHODS This was a prospective,observational clinical study.There were 30 patients(with a 100%technical success rate)recruited in the present study.Patients with esophagogastric variceal bleeding due to HBV infection-associated PH who underwent TIPS were enrolled.Stool samples were obtained before and one month after TIPS treatment,and GM was analyzed using 16S ribosomal RNA amplicon sequencing.RESULTS One month after TIPS placement,8 patients developed hepatic encephalopathy(HE)and were assigned to the HE group;the other 22 patients were assigned to the non-HE group.There was no substantial disparity in the abundance of GM at the phylum level between the two groups,regardless of TIPS treatment(all,P>0.05).However,following TIPS placement,the following results were observed:(1)The abundance of Haemophilus and Eggerthella increased,whereas that of Anaerostipes,Dialister,Butyricicoccus,and Oscillospira declined in the HE group;(2)The richness of Eggerthella,Streptococcus,and Bilophila increased,whereas that of Roseburia and Ruminococcus decreased in the non-HE group;and(3)Members from the pathogenic genus Morganella appeared in the HE group but not in the non-HE group.CONCLUSION Intestinal microbiota-related synergism may predict the risk of HE following TIPS placement in patients with HBVrelated PH.Prophylactic microbiome therapies may be useful for preventing and treating HE after TIPS placement.

The Impact of Human Parvovirus B19 Co-Infection on Liver Function of HCV Infected Patients

Background: Human Parvovirus B19 is most known for causing disease in the pediatric population but can also affect adults. Human co-infection with Parvovirus B19 could deteriorate the prognosis of patient with chronic ill-ness. Objectives: This paper attempts to determine the prevalence of Parvovirus B19 in HCV infected patients and to evaluate the impact of Parvovirus B19 on liver enzymes activity of Hepatitis C patients. Study Design: The study population includes 74 chronic HCV (patient group) and 49 cases without viral hepatitis (control group). Nucleic acid of Parvovirus B19 was detected in Serum samples by nested polymerase chain reaction (nested-PCR) method. Results: Parvovirus B19-DNA infection was detected in 28.0% of chronic HCV patients. Parvovirus B19-HCV co-infection caused increasing in Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) activity than in B19-negative HCV patients. Conclusion: We conclude that Parvovirus B19 acted synergistically with HCV by increasing the levels alanine ami-notransferase (ALT) and Aspartate aminotransferase (AST).

Emerging role of liquid biopsy in rat sarcoma virus mutated metastatic colorectal cancer:A case report

BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.

Advances in Zika virus vaccines and therapeutics:A systematic review

Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection:How to achieve a better outcome

BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)have been proven,researchers have not con-firmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time(at least 24 wk)and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC.AIM To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC.METHODS A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 was conducted.Considering the history of antiviral therapy,patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups.RESULTS Kaplan–Meier analysis revealed significant differences in overall survival(P<0.0001)and disease-free survival(P=0.035)between the two groups.Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival(hazard ratio=0.27;95%confidence interval:0.08-0.88;P=0.030).CONCLUSION In patients with HBV-related HCC,it is ideal to receive preoperative long-term antiviral therapy,which helps patients tolerate more extensive hepatectomy;however,remedial antiviral therapy,which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL,can also result in improved outcomes.

Substitutions of stem-loop subdomains in internal ribosome entry site of Senecavirus A:Impacts on rescue of sequence-modifying viruses

Senecavirus A(SVA)has a positive-sense,single-stranded RNA genome.Its 5´untranslated region harbors an internal ribosome entry site(IRES),comprising 10 larger or smaller stem-loop structures(including a pseudoknot)that have been demonstrated to be well conserved.However,it is still unclear whether each stem-loop subdomain,such as a single stem or loop,is also highly conserved.To clarify this issue in the present study,a set of 29 SVA cDNA clones were constructed by site-directed mutagenesis(SDM)on the IRES.The SDM-modified scenarios included:(1)stem-formed complementary sequences exchanging with each other;(2)loop transversion;(3)loop transition;and(4)point mutations.All cDNA clones were separately transfected into cells for rescuing viable viruses,whereas only four SVAs of interest could be recovered,and were genetically stable during 20 passages.One progeny grew significantly slower than the other three did.The dual-luciferase reporter assay showed that none of the SDM-modified IRESes significantly inhibited the IRES activity.Our previous study indicated that a single motif from any of the ten stem structures,if completely mutated,would cause the failure of virus recovery.Interestingly,our present study revealed three stem structures,whose individual complementary sequences could exchange with each other to rescue sequence-modifying SVAs.Moreover,one apical loop was demonstrated to have the ability to tolerate its own full-length transition,also having no impact on the recovery of sequence-modifying SVA.The present study suggested that not every stem-loop structure was strictly conserved in its conformation,while the full-length IRES itself was well conserved.This provides a new research direction on interaction between the IRES and many factors.