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 complet...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.展开更多
In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B ...In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B virus(HBV)infection,the pathogenesis of hepatocellular carcinoma(HCC),and the role of antiviral therapy in treating HCC related to HBV infection.HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways,as well as by inhibiting the immune functions of macrophages,natural killer cells and dendritic cells.In addition,HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8+T cells,ultimately leading to long-term viral infection.The loss of immune cell function caused by HBV infection ultimately leads to HCC.Long-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.展开更多
Viruses are significant pathogens causing severe plant infections and crop losses globally.The resistance mechanisms of rice to viral diseases,particularly Southern rice black-streaked dwarf virus(SRBSDV),remain poorl...Viruses are significant pathogens causing severe plant infections and crop losses globally.The resistance mechanisms of rice to viral diseases,particularly Southern rice black-streaked dwarf virus(SRBSDV),remain poorly understood.In this study,we assessed SRBSDV susceptibility in 20 Xian/indica(XI)and 20 Geng/japonica(GJ)rice varieties.XI-1B accessions in the Xian subgroup displayed higher resistance than GJ accessions.Comparative transcriptome analysis revealed changes in processes like oxidoreductase activity,jasmonic acid(JA)metabolism,and stress response.JA sensitivity assays further linked antiviral defense to the JA pathway.These findings highlight a JA-mediated resistance mechanism in rice and offer insights for breeding SRBSDV-resistant varieties.展开更多
Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with t...Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.展开更多
Introduction.Respiratory Syncytial Virus (RSV) remains a significant health threat for infants, being the main cause of hospital admissions due to lower respiratory tract infections (LRTI) within this vulnerable popul...Introduction.Respiratory Syncytial Virus (RSV) remains a significant health threat for infants, being the main cause of hospital admissions due to lower respiratory tract infections (LRTI) within this vulnerable population. Each year, RSV results in nearly 3 million hospital admissions and more than 100,000 deaths among children younger than five. Infants in their first six months of life are particularly at risk, especially those born prematurely or with underlying health conditions, with an RSV-associated mortality rate of 3.6%. Although RSV is the leading cause of infant hospitalizations in high-income countries, it causes a much higher number of deaths in low- and middle-income countries (LMICs). Currently, there is no specific treatment for RSV, and hospital management focuses on providing supportive care [1].展开更多
A complex system is inherently high-dimensional.Recent studies indicate that,even without complete knowledge of its evolutionary dynamics,the future behavior of such a system can be predicted using time-series data(da...A complex system is inherently high-dimensional.Recent studies indicate that,even without complete knowledge of its evolutionary dynamics,the future behavior of such a system can be predicted using time-series data(data-driven prediction).This suggests that the essential dynamics of a complex system can be captured through a low-dimensional representation.Virus evolution and climate change are two examples of complex,time-varying systems.In this article,we show that mutations in the spike protein provide valuable data for predicting SARS-CoV-2 variants,forecasting the possible emergence of the new macro-lineage Q in the near future.Our analysis also demonstrates that carbon dioxide concentration is a reliable indicator for predicting the evolution of the climate system,extending global surface air temperature(GSAT)forecasts through 2500.展开更多
Recently,sporadic cases of Chandipura virus(CHPV,order Mononegavirale s,family Rhabdoviridae,genus Vesiculovirus)infection were detected in Gujarat state,which has triggered the Indian Union Health Ministry to send a ...Recently,sporadic cases of Chandipura virus(CHPV,order Mononegavirale s,family Rhabdoviridae,genus Vesiculovirus)infection were detected in Gujarat state,which has triggered the Indian Union Health Ministry to send a multidisciplinary expert team to conduct epidemiological,environmental and entomological assessments for better understanding of the outbreak.1 CHPV is an emerging virus that causes encephalitis,especially in pediatric populations.展开更多
Marburg virus disease(MVD)is a highly fatal illness,with a case fatality rate of up to 88%,though this rate can be significantly reduced with prompt and effective patient care.The disease was first identified in 1967 ...Marburg virus disease(MVD)is a highly fatal illness,with a case fatality rate of up to 88%,though this rate can be significantly reduced with prompt and effective patient care.The disease was first identified in 1967 during concurrent outbreaks in Marburg and Frankfurt,Germany,and in Belgrade,Serbia,linked to laboratory use of African green monkeys imported from Uganda.Subsequent outbreaks and isolated cases have been reported in various African countries,including Angola,the Democratic Republic of the Congo,Equatorial Guinea,Ghana,Guinea,Kenya,Rwanda,South Africa(in an individual with recent travel to Zimbabwe),Tanzania,and Uganda.Initial human MVD infections typically occur due to prolonged exposure to mines or caves inhabited by Rousettus aegyptiacus fruit bats,the natural hosts of the virus.展开更多
Dear Editor,In recent decades,vector-transmitted emerging and re-emerging diseases pose public health issues around the world,in which emerging tick-borne viruses(TBVs)have played a major role since they are widely di...Dear Editor,In recent decades,vector-transmitted emerging and re-emerging diseases pose public health issues around the world,in which emerging tick-borne viruses(TBVs)have played a major role since they are widely distributed.TBVs have a wide range of hosts,including humans,livestock and rodents,with some of them able to cause severe diseases in human and domestic animals,such as Jingmen tick virus(JMTV)(Qin et al.,2014),tick-borne encephalitis virus(TBEV)(Xing et al.,2017),and Alongshan virus(ALSV)(Wang et al.,2019).Of the merging TBVs,JMTV is a novel pathogen that was first identified in Rhipicephalus microplus collected from the Jingmen city of Hubei province,China in 2010(Qin et al.,2014).展开更多
In-utero exposure to Zika virus(ZIKV)could lead to miscarriage,preterm birth and congenital Zika syndrome.This study aimed at estimating the burden of ZIKV and Dengue virus(DENV)infections among pregnant women in Boju...In-utero exposure to Zika virus(ZIKV)could lead to miscarriage,preterm birth and congenital Zika syndrome.This study aimed at estimating the burden of ZIKV and Dengue virus(DENV)infections among pregnant women in Bojude,Nigeria.A total of 200 blood samples were collected from pregnant women between February and April 2022.Using the updated CDC guidelines for the diagnosis of ZIKV infections,including ELISA and microneutralization test(MNT),we found that 16.5%of participants were positive for ZIKV IgM,10%were positive for IgG,and 23%had nAb in their serum.Among the 46 ZIKV nAb-positive women,52.2%and 10.9%were recent and previous ZIKV infections,respectively,while 6.5%had previous DENV infections.Although no recent DENV infection was detected,recent and previous ZIKV/DENV co-infections were 13.0%and 17.4%,respectively.Two participants had recent secondary ZIKV infections,while 39.1%had prolonged lifelong immunity.Recent ZIKV infection rates were significantly higher among sexually active females aged 20–29 years than other age groups,with the highest risk observed in the first trimester of pregnancy.In addition,the grand-multiparous women are at higher risk of ZIKV infections than other categories.Monotypic recent,secondary and past ZIKV infections,as well as DENV and ZIKV co-infections,were detected in both the asymptomatic and symptomatic pregnant women.These findings highlight that ZIKV infection is prevalent among pregnant women in Nigeria and underscore the associated risk factors,providing evidence-based information on the burden of ZIKV infections in DENV-endemic region.展开更多
BACKGROUND Hepatitis B virus(HBV)evades the innate immunity and leads to persistent chronic infection,but the molecular mechanism is still not well known.AIM To investigate whether HBV-miR-3 is involved in HBV immune ...BACKGROUND Hepatitis B virus(HBV)evades the innate immunity and leads to persistent chronic infection,but the molecular mechanism is still not well known.AIM To investigate whether HBV-miR-3 is involved in HBV immune evasion.METHODS HBV-miR-3 agomir and antagomir were employed to verify the effectiveness of HBV-miR-3 on cGAS-Sting-IFN pathway through the experiments on relative luciferase activity,cGAS protein expression,Sting phosphorylation and interferon(IFN)production.RESULTS HBV-miR-3 down-regulates cGAS protein expression post-transcriptionally by inhibition of cGAS 3’-untranslated region(3’-UTR)activity,which results in lower Sting phosphorylation and IFN production.HBV-miR-3 antagomir rescued cGAS protein expression,Sting phosphorylation and IFN-βproduction.CONCLUSION HBV-miR-3 plays an important role in HBV immunity evasion by targeting cGAS 3’-UTR and interfering with cGAS-Sting-IFN pathway.展开更多
Minks are highly susceptible to SARS-CoV-2,and have transmitted SARS-CoV-2 to humans.Oral immunization is one of the most promising strategies to prevent SARS-CoV-2 infection and transmission in minks.Here,we generate...Minks are highly susceptible to SARS-CoV-2,and have transmitted SARS-CoV-2 to humans.Oral immunization is one of the most promising strategies to prevent SARS-CoV-2 infection and transmission in minks.Here,we generated 3 recombinant rabies viruses(RABV),rERAG_(333E)/S6P,rERAG_(333E)/DS6P and rERAG_(333E)/BA2S6P,expressing the prefusion-stabilized SARS-CoV-2 spike protein of wild-type(S6P),δ(DS6P)or BA.2(BA2S6P)strain based on an oral rabies vaccine candidate(rERAG_(333E)).Oral or inactivated immunization of the 3 RABVs monovalent or trivalent were safe,and induced robust RABV neutralizing antibody and cross-antibody responses against the three SARS-CoV-2 in mice and minks.The challenge tests showed that 2 doses of rERAG_(333E)-S6P as an oral or inactivated vaccine completely protected mice against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts,and largely prevented viral replication and lung damage caused by wild-type SARS-CoV-2infection in minks.Notably,we also confirmed that 2 doses of rERAG_(333E)-S6P as an oral or inactivated vaccine can largely protect minks against wild-type SARS-CoV-2 transmission via respiratory droplets.Our findings suggest that rERAG_(333E)-based COVID-19 vaccines appear to be suitable oral candidates to protect minks from SARS-CoV-2infection and transmission,and may serve as inactivated vaccines for further investigation in humans.展开更多
AIM:To investigate the etiology of ocular pathogens and to establish the various pathogens present in human immunodeficiency virus(HIV)patients with cytomegalovirus retinitis(CMVR).METHODS:A total of 17 HIV-infected p...AIM:To investigate the etiology of ocular pathogens and to establish the various pathogens present in human immunodeficiency virus(HIV)patients with cytomegalovirus retinitis(CMVR).METHODS:A total of 17 HIV-infected patients with concomitant eye disorders were enrolled.Patients were divided into CMVR group(10 patients,18 eyes)and non-CMVR group(7 patients,9 eyes)based on clinical manifestations and the presence of cytomegalovirus(CMV)-DNA in ocular specimens.The viral load of CMV was assessed using polymerase chain reaction in aqueous humor,vitreous fluid,and peripheral blood samples of patients in the CMVR group.Additionally,peripheral blood CD4^(+)T cell counts were measured in both groups.RESULTS:In the CMVR group,the CMV-DNA load in the vitreous and aqueous humor samples was substantially higher than in the peripheral blood samples(P<0.01).CMVDNA load in the aqueous humor and vitreous samples of the two eyes in the CMVR group was determined to be statistically significant(10 patients,16 eyes,P=0.018,0.012).Peripheral blood CD4^(+)T cell counts in the CMVR group were adversely linked with the CMV-DNA load in both the aqueous humor and peripheral blood(P=0.005,0.048).Compared with the non-CMVR group,the peripheral blood CD4^(+)T cell count in the CMVR group decreased significantly(P=0.014).The peripheral blood CD4^(+)T cell count exceeded 300 cells/μL in 85.71%of non-CMVR patients,whereas it was below 100 cells/μL in 90.00%of the CMVR group.The intraocular specimens of the patients who underwent CMVR testing did not include any additional infections.CONCLUSION:In HIV-associated CMVR patients,there may exist alternative,yet unidentified,infection pathways for intraocular CMV in addition to the conventional route.The substantial difference in CMV-DNA load between the eyes of most CMVR patients suggests that CMV may originate from different sources in each eye.The proportion of peripheral blood CD4^(+)T cells in HIV patients is negatively correlated with the quantity of CMV viruses in their eyes.The peripheral blood count of<100 cells/μL indicates a considerable increase in the risk of concurrent CMVR.Multi-ocular pathogen presentations are uncommon in HIV individuals with CMVR.展开更多
Objective:Intimate partner violence(IPV)among people living with the human immune deficiency virus(PLHIV)poses a significant threat to efforts to reduce the spread of human immune deficiency virus(HIV)and achieve the ...Objective:Intimate partner violence(IPV)among people living with the human immune deficiency virus(PLHIV)poses a significant threat to efforts to reduce the spread of human immune deficiency virus(HIV)and achieve the sustainable development goals.In Ghana,scholarly research on the forms and prevalence of IPV is available,however knowledge of the prevalence of IPV among PLHIV is limited.To understand the prevalence of IPV among PLHIV and the intersectional factors that contribute to it,this study examined the overall prevalence of IPV among PLHIV and the associated sociodemographic factors across ten regions of Ghana.Methods:We administered face-to-face survey questionnaires to 661 randomly selected antiretroviral therapy(ART)clients using Research Electronic Data Capture tools.We used descriptive statistics(mean,standard deviation,minimum,and maximum),pairwise correlation,and multivariate regression analysis to look at the data.Results:The clients of ART experienced various forms of IPV,including sexual,physical,emotional,and economic violence and controlling behaviour.The overall prevalence of IPV among PLHIV was 27.5%.This result,although on par with the global IPV average(27%),is 1.5%higher than the national rate(26%).The Upper West Region had the highest prevalence in all the categories of IPV analysed,followed by Oti Region in second place and the Upper East Region in third,except for the prevalence of sexual violence,where Greater Accra Region ranks second.In specific regions of Ghana,sociodemographic factors shaped by patriarchal and economic considerations contribute to a higher prevalence of IPV among people living with HIV.Conclusion:The findings have implications for developing policies and interventions that address the specific factors associated with HIV-induced IPV in different regions of Ghana.These interventions should also include screening PLHIV receiving ART for their IPV status regardless of gender and deploying culturally appropriate education at the community level to foster empathy towards intimate partners living with HIV.展开更多
Influenza B viruses(IBVs)primarily infect humans and are a common cause of respiratory infections in humans.Here,to systematically analyze the antigenicity of the IBVs Hemagglutinin(HA)protein,31 B/Victoria and 19 B/Y...Influenza B viruses(IBVs)primarily infect humans and are a common cause of respiratory infections in humans.Here,to systematically analyze the antigenicity of the IBVs Hemagglutinin(HA)protein,31 B/Victoria and 19 B/Yamagata representative circulating strains were selected from Global Initiative of Sharing All Influenza Data(GISAID),and pseudotyped viruses were constructed with the vesicular stomatitis virus system.Guinea pigs were immunized with three doses of vaccines(one dose of DNA vaccines following two doses of pseudotyped virus vaccines)of the seven IBV vaccine strains,and neutralizing antibodies against the pseudotyped viruses were tested.By comparing differences between various vaccine strains,we constructed several pseudotyped viruses that contained various mutations based on vaccine strainBV-21.The vaccine strains showed good neutralization levels against the epidemic virus strains of the same year,with neutralization titers ranging from 370 to 840,while the level of neutralization against viruses prevalent in previous years decreased 1–10-fold.Each of the high-frequency epidemic strains of B/Victoria andB/Yamagata not only induced high neutralizing titers,but also had broadly neutralizing effects against virus strains of different years,with neutralizing titers ranging from1000 to 7200.R141G,D197 N,and R203K were identified as affecting the antigenicity of IBV.These mutation sites provide valuable references for the selection and design of a universal IBV vaccine strain in the future.展开更多
Epstein-Barr virus(EBV),the first identified human tumor virus,is implicated in various human malignancies,infectious mononucleosis,and more recently,multiple sclerosis.Prophylactic vaccines have the potential to effe...Epstein-Barr virus(EBV),the first identified human tumor virus,is implicated in various human malignancies,infectious mononucleosis,and more recently,multiple sclerosis.Prophylactic vaccines have the potential to effectively prevent EBV infection.Glycoprotein B(gB)serves as the fusogen and plays a pivotal role in the virus entry process,making it a critical target for EBV vaccine development.Surface membrane proteins of enveloped viruses serve as native conformational antigens,making them susceptible to immune recognition.Utilizing lipid membrane-bound viral antigens is a promising strategy for effective vaccine presentation in this context.In this study,we employed a truncated design for gB proteins,observing that these truncated gB proteins prompted a substantial release of extracellular vesicles(EVs)in insect cells.We verified that EVs exhibited abundant gB proteins,displaying the typical virus particle morphology and extracellular vesicle characteristics.gB EVs demonstrated a more efficient humoral and cellular immune response compared with the gB ectodomain trimer vaccine in mice.Moreover,the antisera induced by the gB EVs vaccine exhibited robust antibody-dependent cytotoxicity.Consequently,gB EVs-based vaccines hold significant potential for preventing EBV infection and offer valuable insights for vaccine design.展开更多
Ligularia jaluensis is an important medicinal and ornamental plant in China.However,the viruses capable of infecting Ligularia jaluensis remains unknown.Here,we identified a novel carlavirus,tentatively named ligulari...Ligularia jaluensis is an important medicinal and ornamental plant in China.However,the viruses capable of infecting Ligularia jaluensis remains unknown.Here,we identified a novel carlavirus,tentatively named ligularia jaluensis carlavirus(LJCV),as well as a known iris severe mosaic virus(ISMV),in L.jaluensis plants displaying chlorosis and yellow ring spot symptoms,using RNA-seq analysis.The LJCV genome consists of an 8497 nt positive-sense,single-stranded RNA[excluding the poly(A)tail],and contains six open reading frames(ORFs).Phylogenetic analyses based on the fulllength genome and RNA-dependent RNA polymerase(RdRp)amino acid(aa)sequences revealed that LJCV clusters within an evolutionary branch alongside known viruses in the Carlavirus genus.The RdRp protein encoded by ORF1 of LJCV shared 45.38%–67.41%identity with the corresponding proteins of eight closely related carlaviruses.ORFs 2–4 constitute the triple gene block(TGB),with TGBp1 and TGBp3 localized in the endoplasmic reticulum(ER),while TGBp2 is localized at plasmodesmata(PD)and facilitates viral intercellular movement,as demonstrated by its ability to complement the potato virus X with movement-deficient mutant(PVX-Δp25-GFP).Additionally,ORF6 encodes a cysteine-rich protein(CRP)that is localized in the chloroplast and functions as a viral pathogenicity factor,inducing severe viral symptoms in the heterologous PVX expression system.Furthermore,we successfully constructed an infectious cDNA clone of LJCV,and found that it can infect Nicotiana benthamiana plants through mechanical inoculation or agrobacterium-mediated infiltration of the LJCV infectious clone.These findings enhance our understanding of the characteristics and host range of carlaviruses,as well as the viruses capable of infecting L.jaluensis.展开更多
Over the past decades,oncolytic viruses have emerged as prominent therapeutic agents with significant potential for anticancer treatment.Enteroviruses(EVs)have garnered particular attention due to their specific tropi...Over the past decades,oncolytic viruses have emerged as prominent therapeutic agents with significant potential for anticancer treatment.Enteroviruses(EVs)have garnered particular attention due to their specific tropism for various types of tumor cells.The rapid advancement of reverse genetics has enabled its application in the genetic modification of enteroviruses and the investigation of viral infection mechanisms.The utilization of reverse genetics has significantly enhanced our understanding of the infection mechanisms and pathogenesis of enteroviruses,while concurrently facilitating the development of translational therapies related to these viruses.In this review,we summarize the progress in the application of reverse genetics to oncolytic enteroviruses and their potential clinical applications.Specifically,we discuss the characteristics of EVs and the applications of reverse genetics in EV research.We review the utilization of reverse genetics in mechanistic investigations of EVs and in exploring the oncolytic potential of EVs.Further,we discuss the oncolytic roles of specific EVs including EV-A71,coxsackievirus B3(CV-B3),echovirus 7(Echo-7),CV-A21,and poliovirus.Our review highlights the advances in oncolytic therapy utilizing EVs with specific tumor tropism,which holds significant potential for immunotherapy.展开更多
BACKGROUND Currently,there is a lack of effective adjuvant therapies for patients at high-risk of recurrent hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC)after radical resection.Given the efficacy of a...BACKGROUND Currently,there is a lack of effective adjuvant therapies for patients at high-risk of recurrent hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC)after radical resection.Given the efficacy of anti-programmed death 1/anti-programmed death ligand 1 plus anti-vascular endothelial growth factor receptor agents in advanced HCC,we conducted this study to investigate the efficacy of this combination regimen in the postoperative adjuvant treatment of patients with HBV-HCC.AIM To evaluate the value of postoperative combined therapy(PCT)with anti-programmed death 1/anti-programmed death ligand 1 and anti-vascular endothelial growth factor receptor agents in patients with HBV-HCC.METHODS Patients with HBV-HCC who underwent radical resection surgery at Anhui Provincial Hospital Affiliated to Anhui Medical University between July 2020 and April 2023 were included.Recurrence-free survival(RFS)and overall survival were assessed using propensity score matching and inverse probability of treatment weighting.Cox regression analysis was used to identify factors affecting recurrence,and subgroup analysis was conducted to investigate the impact of medications on different populations.Treatment-related adverse events and liver function measurements were evaluated.RESULTS A total of 150 patients were recruited,of whom 30 underwent PCT and 120 did not.After adjusting for confounders,patients who underwent PCT had better RFS at 6 and 12 months than those who did not(P>0.05).Similar results were observed in the Kaplan-Meier curves after propensity score matching or inverse probability of treatment weighting,although the difference was not statistically significant(P>0.05).A maximum diameter of>5 cm,vascular invasion,satellite nodules,and high gamma-glutamyl transferase levels were independent risk factors for recurrence(P<0.05).No significant interaction effects were observed in subgroup analyses.The most prevalent adverse event was hypertension(66.7%).PCT was associated with an increased risk of hepatic impairment which may predict RFS rates(P=0.041).CONCLUSION The recurrence rate was not significantly reduced in patients who underwent PCT.Hepatic impairment during treatment may indicate recurrence,and close monitoring of liver function and HBV infection is recommended.展开更多
The blood-brain barrier(BBB)keeps poisons and infections out of the brain.Some viruses can pass through this barrier and replicate in the central nervous system(CNS).Velogenic Newcastle disease virus(VNDV)is a neurotr...The blood-brain barrier(BBB)keeps poisons and infections out of the brain.Some viruses can pass through this barrier and replicate in the central nervous system(CNS).Velogenic Newcastle disease virus(VNDV)is a neurotropic virus that causes avian nonsuppurative encephalitis.VNDV often develops into a chronic infection that seriously affects poultry health in partially immune birds.The routes by which the virus enters the chicken brain are poorly understood.In this study,we discovered that VNDV increased BBB permeability in vivo and in vitro by breaking the tight junction protein zona occludens-1(ZO-1)continuity of chicken brain microvascular endothelial cells(chBMECs).By investigating the susceptibility of chBMECs to NDV infection,we found that VNDV but not lentogenic NDV was detected in the basolateral compartment in transwell assays after apical infection,suggesting that efficient replication and transcellular transport of the virus across the BBB in vitro.Furthermore,viral replication and BBB permeability were reduced during the early stage of infection by using the dynamin inhibitor dynasore.Our data demonstrate that VNDV invades the chicken brain by infecting and damaging the tight junction of chBMECs directly to increase BBB permeability.VNDV could infect chBMECs via endocytosis.As a result,our findings provide compelling evidence for VNDV entrance into the brain via the BBB,paving the way for the development of medications for NDV prevention and therapy.展开更多
基金supported by UniversitàCattolica(D1 intramural funds to RP)Italian Ministry of University and Research(PRIN 2022ZYLB7B,P2022YW7BP funds to CG).
文摘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.
基金Supported by the Natural Science Foundation of China,No.81970529the Natural Science Foundation of Jilin Province,No.20230508074RC and No.YDZJ202401218ZYTS.
文摘In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B virus(HBV)infection,the pathogenesis of hepatocellular carcinoma(HCC),and the role of antiviral therapy in treating HCC related to HBV infection.HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways,as well as by inhibiting the immune functions of macrophages,natural killer cells and dendritic cells.In addition,HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8+T cells,ultimately leading to long-term viral infection.The loss of immune cell function caused by HBV infection ultimately leads to HCC.Long-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.
基金funded by the National Key Research and Development Plan of China(2023YFD1400300)National Natural Science Foundation of China(U23A6006,32270149,32272555)+1 种基金Zhejiang Provincial Natural Science Foundation(LZ22C140001)the Ningbo Major Research and Development Plan Project(2023Z124).
文摘Viruses are significant pathogens causing severe plant infections and crop losses globally.The resistance mechanisms of rice to viral diseases,particularly Southern rice black-streaked dwarf virus(SRBSDV),remain poorly understood.In this study,we assessed SRBSDV susceptibility in 20 Xian/indica(XI)and 20 Geng/japonica(GJ)rice varieties.XI-1B accessions in the Xian subgroup displayed higher resistance than GJ accessions.Comparative transcriptome analysis revealed changes in processes like oxidoreductase activity,jasmonic acid(JA)metabolism,and stress response.JA sensitivity assays further linked antiviral defense to the JA pathway.These findings highlight a JA-mediated resistance mechanism in rice and offer insights for breeding SRBSDV-resistant varieties.
文摘Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.
文摘Introduction.Respiratory Syncytial Virus (RSV) remains a significant health threat for infants, being the main cause of hospital admissions due to lower respiratory tract infections (LRTI) within this vulnerable population. Each year, RSV results in nearly 3 million hospital admissions and more than 100,000 deaths among children younger than five. Infants in their first six months of life are particularly at risk, especially those born prematurely or with underlying health conditions, with an RSV-associated mortality rate of 3.6%. Although RSV is the leading cause of infant hospitalizations in high-income countries, it causes a much higher number of deaths in low- and middle-income countries (LMICs). Currently, there is no specific treatment for RSV, and hospital management focuses on providing supportive care [1].
基金Natural science foundation of Inner Mongolia(2024LHMS06018)The basic scientific research funding for directly affiliated universities in the Inner Mongolia(JY20250094)。
文摘A complex system is inherently high-dimensional.Recent studies indicate that,even without complete knowledge of its evolutionary dynamics,the future behavior of such a system can be predicted using time-series data(data-driven prediction).This suggests that the essential dynamics of a complex system can be captured through a low-dimensional representation.Virus evolution and climate change are two examples of complex,time-varying systems.In this article,we show that mutations in the spike protein provide valuable data for predicting SARS-CoV-2 variants,forecasting the possible emergence of the new macro-lineage Q in the near future.Our analysis also demonstrates that carbon dioxide concentration is a reliable indicator for predicting the evolution of the climate system,extending global surface air temperature(GSAT)forecasts through 2500.
文摘Recently,sporadic cases of Chandipura virus(CHPV,order Mononegavirale s,family Rhabdoviridae,genus Vesiculovirus)infection were detected in Gujarat state,which has triggered the Indian Union Health Ministry to send a multidisciplinary expert team to conduct epidemiological,environmental and entomological assessments for better understanding of the outbreak.1 CHPV is an emerging virus that causes encephalitis,especially in pediatric populations.
文摘Marburg virus disease(MVD)is a highly fatal illness,with a case fatality rate of up to 88%,though this rate can be significantly reduced with prompt and effective patient care.The disease was first identified in 1967 during concurrent outbreaks in Marburg and Frankfurt,Germany,and in Belgrade,Serbia,linked to laboratory use of African green monkeys imported from Uganda.Subsequent outbreaks and isolated cases have been reported in various African countries,including Angola,the Democratic Republic of the Congo,Equatorial Guinea,Ghana,Guinea,Kenya,Rwanda,South Africa(in an individual with recent travel to Zimbabwe),Tanzania,and Uganda.Initial human MVD infections typically occur due to prolonged exposure to mines or caves inhabited by Rousettus aegyptiacus fruit bats,the natural hosts of the virus.
基金supported by Wildlife Borne Infectious Diseases Monitoring Project of the State Forestry and Grassland Administration of China(2020076060)the National Key Research and Development Program of China to Changchun Tu(32130104).
文摘Dear Editor,In recent decades,vector-transmitted emerging and re-emerging diseases pose public health issues around the world,in which emerging tick-borne viruses(TBVs)have played a major role since they are widely distributed.TBVs have a wide range of hosts,including humans,livestock and rodents,with some of them able to cause severe diseases in human and domestic animals,such as Jingmen tick virus(JMTV)(Qin et al.,2014),tick-borne encephalitis virus(TBEV)(Xing et al.,2017),and Alongshan virus(ALSV)(Wang et al.,2019).Of the merging TBVs,JMTV is a novel pathogen that was first identified in Rhipicephalus microplus collected from the Jingmen city of Hubei province,China in 2010(Qin et al.,2014).
文摘In-utero exposure to Zika virus(ZIKV)could lead to miscarriage,preterm birth and congenital Zika syndrome.This study aimed at estimating the burden of ZIKV and Dengue virus(DENV)infections among pregnant women in Bojude,Nigeria.A total of 200 blood samples were collected from pregnant women between February and April 2022.Using the updated CDC guidelines for the diagnosis of ZIKV infections,including ELISA and microneutralization test(MNT),we found that 16.5%of participants were positive for ZIKV IgM,10%were positive for IgG,and 23%had nAb in their serum.Among the 46 ZIKV nAb-positive women,52.2%and 10.9%were recent and previous ZIKV infections,respectively,while 6.5%had previous DENV infections.Although no recent DENV infection was detected,recent and previous ZIKV/DENV co-infections were 13.0%and 17.4%,respectively.Two participants had recent secondary ZIKV infections,while 39.1%had prolonged lifelong immunity.Recent ZIKV infection rates were significantly higher among sexually active females aged 20–29 years than other age groups,with the highest risk observed in the first trimester of pregnancy.In addition,the grand-multiparous women are at higher risk of ZIKV infections than other categories.Monotypic recent,secondary and past ZIKV infections,as well as DENV and ZIKV co-infections,were detected in both the asymptomatic and symptomatic pregnant women.These findings highlight that ZIKV infection is prevalent among pregnant women in Nigeria and underscore the associated risk factors,providing evidence-based information on the burden of ZIKV infections in DENV-endemic region.
基金Supported by National Natural Science Foundation of China,Key Project,No.82430071The Scientific Research Program of FuRong Laboratory,No.2023SK2108+2 种基金Clinical Medical Research Center for Viral Hepatitis of Hunan Province,No.2023SK4009Hunan Provincial Natural Science Foundation,No.2023JJ60440Hunan Provincial Health Commission Research Program,No.C202303088786.
文摘BACKGROUND Hepatitis B virus(HBV)evades the innate immunity and leads to persistent chronic infection,but the molecular mechanism is still not well known.AIM To investigate whether HBV-miR-3 is involved in HBV immune evasion.METHODS HBV-miR-3 agomir and antagomir were employed to verify the effectiveness of HBV-miR-3 on cGAS-Sting-IFN pathway through the experiments on relative luciferase activity,cGAS protein expression,Sting phosphorylation and interferon(IFN)production.RESULTS HBV-miR-3 down-regulates cGAS protein expression post-transcriptionally by inhibition of cGAS 3’-untranslated region(3’-UTR)activity,which results in lower Sting phosphorylation and IFN production.HBV-miR-3 antagomir rescued cGAS protein expression,Sting phosphorylation and IFN-βproduction.CONCLUSION HBV-miR-3 plays an important role in HBV immunity evasion by targeting cGAS 3’-UTR and interfering with cGAS-Sting-IFN pathway.
基金supported by the National Key Research and Development Program of China(2021YFC2301700)the Natural Science Foundation of Heilongjiang Province,China(YQ2022C040)。
文摘Minks are highly susceptible to SARS-CoV-2,and have transmitted SARS-CoV-2 to humans.Oral immunization is one of the most promising strategies to prevent SARS-CoV-2 infection and transmission in minks.Here,we generated 3 recombinant rabies viruses(RABV),rERAG_(333E)/S6P,rERAG_(333E)/DS6P and rERAG_(333E)/BA2S6P,expressing the prefusion-stabilized SARS-CoV-2 spike protein of wild-type(S6P),δ(DS6P)or BA.2(BA2S6P)strain based on an oral rabies vaccine candidate(rERAG_(333E)).Oral or inactivated immunization of the 3 RABVs monovalent or trivalent were safe,and induced robust RABV neutralizing antibody and cross-antibody responses against the three SARS-CoV-2 in mice and minks.The challenge tests showed that 2 doses of rERAG_(333E)-S6P as an oral or inactivated vaccine completely protected mice against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts,and largely prevented viral replication and lung damage caused by wild-type SARS-CoV-2infection in minks.Notably,we also confirmed that 2 doses of rERAG_(333E)-S6P as an oral or inactivated vaccine can largely protect minks against wild-type SARS-CoV-2 transmission via respiratory droplets.Our findings suggest that rERAG_(333E)-based COVID-19 vaccines appear to be suitable oral candidates to protect minks from SARS-CoV-2infection and transmission,and may serve as inactivated vaccines for further investigation in humans.
基金Supported by the Self-funded Research Project of the Health and Family Planning Commission of Guangxi Zhuang Autonomous Region(No.Z2016325).
文摘AIM:To investigate the etiology of ocular pathogens and to establish the various pathogens present in human immunodeficiency virus(HIV)patients with cytomegalovirus retinitis(CMVR).METHODS:A total of 17 HIV-infected patients with concomitant eye disorders were enrolled.Patients were divided into CMVR group(10 patients,18 eyes)and non-CMVR group(7 patients,9 eyes)based on clinical manifestations and the presence of cytomegalovirus(CMV)-DNA in ocular specimens.The viral load of CMV was assessed using polymerase chain reaction in aqueous humor,vitreous fluid,and peripheral blood samples of patients in the CMVR group.Additionally,peripheral blood CD4^(+)T cell counts were measured in both groups.RESULTS:In the CMVR group,the CMV-DNA load in the vitreous and aqueous humor samples was substantially higher than in the peripheral blood samples(P<0.01).CMVDNA load in the aqueous humor and vitreous samples of the two eyes in the CMVR group was determined to be statistically significant(10 patients,16 eyes,P=0.018,0.012).Peripheral blood CD4^(+)T cell counts in the CMVR group were adversely linked with the CMV-DNA load in both the aqueous humor and peripheral blood(P=0.005,0.048).Compared with the non-CMVR group,the peripheral blood CD4^(+)T cell count in the CMVR group decreased significantly(P=0.014).The peripheral blood CD4^(+)T cell count exceeded 300 cells/μL in 85.71%of non-CMVR patients,whereas it was below 100 cells/μL in 90.00%of the CMVR group.The intraocular specimens of the patients who underwent CMVR testing did not include any additional infections.CONCLUSION:In HIV-associated CMVR patients,there may exist alternative,yet unidentified,infection pathways for intraocular CMV in addition to the conventional route.The substantial difference in CMV-DNA load between the eyes of most CMVR patients suggests that CMV may originate from different sources in each eye.The proportion of peripheral blood CD4^(+)T cells in HIV patients is negatively correlated with the quantity of CMV viruses in their eyes.The peripheral blood count of<100 cells/μL indicates a considerable increase in the risk of concurrent CMVR.Multi-ocular pathogen presentations are uncommon in HIV individuals with CMVR.
基金supported by the Christian Health Association of Ghana under Global Fund New Funding Model 3(NFM 3)HIV/TB Community Systems Strengthening programme(CSS)。
文摘Objective:Intimate partner violence(IPV)among people living with the human immune deficiency virus(PLHIV)poses a significant threat to efforts to reduce the spread of human immune deficiency virus(HIV)and achieve the sustainable development goals.In Ghana,scholarly research on the forms and prevalence of IPV is available,however knowledge of the prevalence of IPV among PLHIV is limited.To understand the prevalence of IPV among PLHIV and the intersectional factors that contribute to it,this study examined the overall prevalence of IPV among PLHIV and the associated sociodemographic factors across ten regions of Ghana.Methods:We administered face-to-face survey questionnaires to 661 randomly selected antiretroviral therapy(ART)clients using Research Electronic Data Capture tools.We used descriptive statistics(mean,standard deviation,minimum,and maximum),pairwise correlation,and multivariate regression analysis to look at the data.Results:The clients of ART experienced various forms of IPV,including sexual,physical,emotional,and economic violence and controlling behaviour.The overall prevalence of IPV among PLHIV was 27.5%.This result,although on par with the global IPV average(27%),is 1.5%higher than the national rate(26%).The Upper West Region had the highest prevalence in all the categories of IPV analysed,followed by Oti Region in second place and the Upper East Region in third,except for the prevalence of sexual violence,where Greater Accra Region ranks second.In specific regions of Ghana,sociodemographic factors shaped by patriarchal and economic considerations contribute to a higher prevalence of IPV among people living with HIV.Conclusion:The findings have implications for developing policies and interventions that address the specific factors associated with HIV-induced IPV in different regions of Ghana.These interventions should also include screening PLHIV receiving ART for their IPV status regardless of gender and deploying culturally appropriate education at the community level to foster empathy towards intimate partners living with HIV.
基金supported by a grant from the National Key R&D Program of China(No.2021YFC2301700)the Ministry of Science and Technology(China)of China(No.2021YFC2302500)the Establishment of a method for detecting neutralizing antibodies with pseudotyped viruses of China Pharmacopeia[grant number 2021S03].
文摘Influenza B viruses(IBVs)primarily infect humans and are a common cause of respiratory infections in humans.Here,to systematically analyze the antigenicity of the IBVs Hemagglutinin(HA)protein,31 B/Victoria and 19 B/Yamagata representative circulating strains were selected from Global Initiative of Sharing All Influenza Data(GISAID),and pseudotyped viruses were constructed with the vesicular stomatitis virus system.Guinea pigs were immunized with three doses of vaccines(one dose of DNA vaccines following two doses of pseudotyped virus vaccines)of the seven IBV vaccine strains,and neutralizing antibodies against the pseudotyped viruses were tested.By comparing differences between various vaccine strains,we constructed several pseudotyped viruses that contained various mutations based on vaccine strainBV-21.The vaccine strains showed good neutralization levels against the epidemic virus strains of the same year,with neutralization titers ranging from 370 to 840,while the level of neutralization against viruses prevalent in previous years decreased 1–10-fold.Each of the high-frequency epidemic strains of B/Victoria andB/Yamagata not only induced high neutralizing titers,but also had broadly neutralizing effects against virus strains of different years,with neutralizing titers ranging from1000 to 7200.R141G,D197 N,and R203K were identified as affecting the antigenicity of IBV.These mutation sites provide valuable references for the selection and design of a universal IBV vaccine strain in the future.
基金supported by the National Natural Science Foundation of China(82073756).
文摘Epstein-Barr virus(EBV),the first identified human tumor virus,is implicated in various human malignancies,infectious mononucleosis,and more recently,multiple sclerosis.Prophylactic vaccines have the potential to effectively prevent EBV infection.Glycoprotein B(gB)serves as the fusogen and plays a pivotal role in the virus entry process,making it a critical target for EBV vaccine development.Surface membrane proteins of enveloped viruses serve as native conformational antigens,making them susceptible to immune recognition.Utilizing lipid membrane-bound viral antigens is a promising strategy for effective vaccine presentation in this context.In this study,we employed a truncated design for gB proteins,observing that these truncated gB proteins prompted a substantial release of extracellular vesicles(EVs)in insect cells.We verified that EVs exhibited abundant gB proteins,displaying the typical virus particle morphology and extracellular vesicle characteristics.gB EVs demonstrated a more efficient humoral and cellular immune response compared with the gB ectodomain trimer vaccine in mice.Moreover,the antisera induced by the gB EVs vaccine exhibited robust antibody-dependent cytotoxicity.Consequently,gB EVs-based vaccines hold significant potential for preventing EBV infection and offer valuable insights for vaccine design.
基金financially supported by the Hainan Province Science and Technology Special Fund(No.ZDYF2022XDNY240)the National Key Research and Development Program of China(2022YFD1401200).
文摘Ligularia jaluensis is an important medicinal and ornamental plant in China.However,the viruses capable of infecting Ligularia jaluensis remains unknown.Here,we identified a novel carlavirus,tentatively named ligularia jaluensis carlavirus(LJCV),as well as a known iris severe mosaic virus(ISMV),in L.jaluensis plants displaying chlorosis and yellow ring spot symptoms,using RNA-seq analysis.The LJCV genome consists of an 8497 nt positive-sense,single-stranded RNA[excluding the poly(A)tail],and contains six open reading frames(ORFs).Phylogenetic analyses based on the fulllength genome and RNA-dependent RNA polymerase(RdRp)amino acid(aa)sequences revealed that LJCV clusters within an evolutionary branch alongside known viruses in the Carlavirus genus.The RdRp protein encoded by ORF1 of LJCV shared 45.38%–67.41%identity with the corresponding proteins of eight closely related carlaviruses.ORFs 2–4 constitute the triple gene block(TGB),with TGBp1 and TGBp3 localized in the endoplasmic reticulum(ER),while TGBp2 is localized at plasmodesmata(PD)and facilitates viral intercellular movement,as demonstrated by its ability to complement the potato virus X with movement-deficient mutant(PVX-Δp25-GFP).Additionally,ORF6 encodes a cysteine-rich protein(CRP)that is localized in the chloroplast and functions as a viral pathogenicity factor,inducing severe viral symptoms in the heterologous PVX expression system.Furthermore,we successfully constructed an infectious cDNA clone of LJCV,and found that it can infect Nicotiana benthamiana plants through mechanical inoculation or agrobacterium-mediated infiltration of the LJCV infectious clone.These findings enhance our understanding of the characteristics and host range of carlaviruses,as well as the viruses capable of infecting L.jaluensis.
基金supported in part by funding from the National Natural Science Foundation of China(32222005,82372226,and 82172246)the Open Project of Key Laboratory of Organ Regeneration and Transplantation,Ministry of Education,Program for JLU Science and Technology Innovative Research Team(2017TD-08)the Fundamental Research Funds for Central Universities.
文摘Over the past decades,oncolytic viruses have emerged as prominent therapeutic agents with significant potential for anticancer treatment.Enteroviruses(EVs)have garnered particular attention due to their specific tropism for various types of tumor cells.The rapid advancement of reverse genetics has enabled its application in the genetic modification of enteroviruses and the investigation of viral infection mechanisms.The utilization of reverse genetics has significantly enhanced our understanding of the infection mechanisms and pathogenesis of enteroviruses,while concurrently facilitating the development of translational therapies related to these viruses.In this review,we summarize the progress in the application of reverse genetics to oncolytic enteroviruses and their potential clinical applications.Specifically,we discuss the characteristics of EVs and the applications of reverse genetics in EV research.We review the utilization of reverse genetics in mechanistic investigations of EVs and in exploring the oncolytic potential of EVs.Further,we discuss the oncolytic roles of specific EVs including EV-A71,coxsackievirus B3(CV-B3),echovirus 7(Echo-7),CV-A21,and poliovirus.Our review highlights the advances in oncolytic therapy utilizing EVs with specific tumor tropism,which holds significant potential for immunotherapy.
基金Supported by the Key Research and Development Projects of Anhui Province,No.202104j07020048National Key Research and Development Program of China,No.2022YFA1304500.
文摘BACKGROUND Currently,there is a lack of effective adjuvant therapies for patients at high-risk of recurrent hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC)after radical resection.Given the efficacy of anti-programmed death 1/anti-programmed death ligand 1 plus anti-vascular endothelial growth factor receptor agents in advanced HCC,we conducted this study to investigate the efficacy of this combination regimen in the postoperative adjuvant treatment of patients with HBV-HCC.AIM To evaluate the value of postoperative combined therapy(PCT)with anti-programmed death 1/anti-programmed death ligand 1 and anti-vascular endothelial growth factor receptor agents in patients with HBV-HCC.METHODS Patients with HBV-HCC who underwent radical resection surgery at Anhui Provincial Hospital Affiliated to Anhui Medical University between July 2020 and April 2023 were included.Recurrence-free survival(RFS)and overall survival were assessed using propensity score matching and inverse probability of treatment weighting.Cox regression analysis was used to identify factors affecting recurrence,and subgroup analysis was conducted to investigate the impact of medications on different populations.Treatment-related adverse events and liver function measurements were evaluated.RESULTS A total of 150 patients were recruited,of whom 30 underwent PCT and 120 did not.After adjusting for confounders,patients who underwent PCT had better RFS at 6 and 12 months than those who did not(P>0.05).Similar results were observed in the Kaplan-Meier curves after propensity score matching or inverse probability of treatment weighting,although the difference was not statistically significant(P>0.05).A maximum diameter of>5 cm,vascular invasion,satellite nodules,and high gamma-glutamyl transferase levels were independent risk factors for recurrence(P<0.05).No significant interaction effects were observed in subgroup analyses.The most prevalent adverse event was hypertension(66.7%).PCT was associated with an increased risk of hepatic impairment which may predict RFS rates(P=0.041).CONCLUSION The recurrence rate was not significantly reduced in patients who underwent PCT.Hepatic impairment during treatment may indicate recurrence,and close monitoring of liver function and HBV infection is recommended.
基金supported by the National Natural Science Foundation of China(32302864 and 31572533)the Shandong Provincial Natural Science Foundation,China(ZR2021QC185)the Agricultural Science and Technology Innovation Project of Shandong Academy of Agricultural Sciences,China(CXGC2023F11)。
文摘The blood-brain barrier(BBB)keeps poisons and infections out of the brain.Some viruses can pass through this barrier and replicate in the central nervous system(CNS).Velogenic Newcastle disease virus(VNDV)is a neurotropic virus that causes avian nonsuppurative encephalitis.VNDV often develops into a chronic infection that seriously affects poultry health in partially immune birds.The routes by which the virus enters the chicken brain are poorly understood.In this study,we discovered that VNDV increased BBB permeability in vivo and in vitro by breaking the tight junction protein zona occludens-1(ZO-1)continuity of chicken brain microvascular endothelial cells(chBMECs).By investigating the susceptibility of chBMECs to NDV infection,we found that VNDV but not lentogenic NDV was detected in the basolateral compartment in transwell assays after apical infection,suggesting that efficient replication and transcellular transport of the virus across the BBB in vitro.Furthermore,viral replication and BBB permeability were reduced during the early stage of infection by using the dynamin inhibitor dynasore.Our data demonstrate that VNDV invades the chicken brain by infecting and damaging the tight junction of chBMECs directly to increase BBB permeability.VNDV could infect chBMECs via endocytosis.As a result,our findings provide compelling evidence for VNDV entrance into the brain via the BBB,paving the way for the development of medications for NDV prevention and therapy.
