Dear Editor,Monkeypox is an infectious disease that is endemic in a dozen of African countries.Some imported cases have been also reported outside of Africa in the past[1].Since early May 2022,monkeypox infections inc...Dear Editor,Monkeypox is an infectious disease that is endemic in a dozen of African countries.Some imported cases have been also reported outside of Africa in the past[1].Since early May 2022,monkeypox infections including human-to-human transmission,were reported in a multi-country outbreak in non-endemic countries and declared Public Health Emergency of International Concern(PHEIC)by the World Health Organization(WHO)in July 2022[2].As of 20 September 2022,a total of at least 62,798 human cases of monkeypox with 20 deaths have been confirmed in 115 countries in five WHO regions[3].展开更多
Presently, an ongoing outbreak of the monkeypox virus infection that began in Bayelsa State of Nigeria has now spread to other parts of the country including mostly States in the South-South with the Nigerian Ministry...Presently, an ongoing outbreak of the monkeypox virus infection that began in Bayelsa State of Nigeria has now spread to other parts of the country including mostly States in the South-South with the Nigerian Ministry of Health confirming 4 samples out of the 43 sent for testing at WHO Regional Laboratory in Dakar, Senegal. This reminds us that apart from the eradicated smallpox, there are other poxviruses that pose potential threat to people in West and Central Africa. In this paper, we developed a mathematical model for the dynamics of the transmission of monkeypox virus infection with control strategies of combined vaccine and treatment interventions. Using standard approaches, we established two equilibria for the model namely: disease-free and endemic. The disease-free equilibrium was proved to be both locally and globally asymptotically stable if R0 < 1 using the next-generation matrix and the comparison theorem. While the endemic equilibrium point existed only when R0 > 1, was proved to be locally asymptotically stable if R0 > 1 using the linearization plus row-reduction method. The basic reproduction numbers for the humans and the non-human primates of the model are computed using parameter values to be R0,h = 9.1304 x 10-6 and R0,n = 3.375 x 10-3 respectively. Numerical simulations carried out on the model revealed that the infectious individuals in the human and non-human primates’ populations will die out in the course of the proposed interventions in this paper during the time of the study. Sensitivity analysis carried out on the model parameters shows that the basic reproduction numbers of the model which served as a threshold for measuring new infections in the host populations decrease with increase in the control parameters of vaccination and treatment.展开更多
The monkeypox virus(MPXV)has triggered a current outbreak globally.Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control.It is a significant challenge but necessary...The monkeypox virus(MPXV)has triggered a current outbreak globally.Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control.It is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads,as it is one of the DNA viruses with the largest genome and the most AT-biased,and has a significant number of tandem repeats.Here we evaluated the performance of metagenomic and amplicon sequencing techniques,and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese mainland.We rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical specimens.Amplicon sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV genomes.Third-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published sequences.Besides,several intra-host single nucleotide variations were identified in the first imported mpox case.This study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical specimens.The findings of this study will significantly enhance the surveillance of MPXV.展开更多
Mpox(formerly Monkeypox)is a zoonotic infection caused by Monkeypox virus(MPXV).Since 2022,Mpox epidemics have occurred in many nonendemic countries and regions,leading the World Health Organization to declare a publi...Mpox(formerly Monkeypox)is a zoonotic infection caused by Monkeypox virus(MPXV).Since 2022,Mpox epidemics have occurred in many nonendemic countries and regions,leading the World Health Organization to declare a public health emergency of international concern.With the persistent transmission and evolution of MPXV,symptoms of Mpox have become milder,with some infections being asymptomatic.In addition,MPXV has become more contagious.Therefore,rapid and accurate diagnosis and screening of MPXV is vital to prevent and control MPXV epidemics.Here,we review and summarize the technical details,application scenarios,and the advantages and disadvantages of MPXV‐specific diagnostic methods.展开更多
The monkeypox(mpox)virus has caused worldwide transmission since its initial report in England in early May 2022.Available data from the World Health Organization(WHO)show that Europe and the Americas experienced a hu...The monkeypox(mpox)virus has caused worldwide transmission since its initial report in England in early May 2022.Available data from the World Health Organization(WHO)show that Europe and the Americas experienced a huge wave of mpox virus infection.Now the number of infected cases is on the rise in Asia.Several sporadic infections have been reported in China.In this study,we obtained high‐quality whole viral genomic sequences using a mpox virus‐specific amplicon‐based sequencing strategy.Our analysis of the phylogenomic characteristics indicated that all eight mpox virus sequences from Guangzhou belonged to the clade IIb lineage B.1.3 cluster.However,we could not locate the exact origins where the virus was imported,based on all the available mpox virus sequences from the Global Initiative on Sharing Avian Influenza Data(GISAID)database(https://gisaid.org/),except for their closest sequence similarity to that was reported from Japan.Novel amino acid mutations were found among the eight cases,suggesting that a local transmission may have occurred in Guangzhou,China.展开更多
As we set into the second half of 2022,the world is still recovering from the two-year COVID-19 pandemic.However,over the past three months,the outbreak of the Monkeypox Virus(MPV)has led to fifty-two thousand confirm...As we set into the second half of 2022,the world is still recovering from the two-year COVID-19 pandemic.However,over the past three months,the outbreak of the Monkeypox Virus(MPV)has led to fifty-two thousand confirmed cases and over one hundred deaths.This caused the World Health Organisation to declare the outbreak a Public Health Emergency of International Concern(PHEIC).If this outbreak worsens,we could be looking at the Monkeypox virus causing the next global pandemic.As Monkeypox affects the human skin,the symptoms can be captured with regular imaging.Large samples of these images can be used as a training dataset for machine learning-based detection tools.Using a regular camera to capture the skin image of the infected person and running it against computer vision models is beneficial.In this research,we use deep learning to diagnose monkeypox from skin lesion images.Using a publicly available dataset,we tested the dataset on five pre-trained deep neural networks:GoogLeNet,Places365-GoogLeNet,SqueezeNet,AlexNet and ResNet-18.Hyperparameter was done to choose the best parameters.Performance metrics such as accuracy,precision,recall,f1-score and AUC were considered.Among the above models,ResNet18 was able to obtain the highest accuracy of 99.49%.The modified models obtained validation accuracies above 95%.The results prove that deep learning models such as the proposed model based on ResNet-18 can be deployed and can be crucial in battling the monkeypox virus.Since the used networks are optimized for efficiency,they can be used on performance limited devices such as smartphones with cameras.The addition of explainable artificial intelligence techniques LIME and GradCAM enables visual interpretation of the prediction made,helping health professionals using the model.展开更多
The largest monkeypox virus(MPXV)outbreak of the 21st century occurred in 2022,which caused epidemics in many countries.According to WHO,physical contact with infected persons,contaminated surfaces,or affected animals...The largest monkeypox virus(MPXV)outbreak of the 21st century occurred in 2022,which caused epidemics in many countries.According to WHO,physical contact with infected persons,contaminated surfaces,or affected animals might be a source of this virus transmission.A febrile sickness including few symptoms found in MPX disease.Skin rash,lesions,fever,headache,fatigue,and muscle aches symptoms were observed commonly for this disease.Animal and in vitro,studies have shown that the antiviral medications cidofovir and brincidofovir are effective against MPXV.The first-generation vaccinia virus vaccine was developed in 1960,and it helped to protect against MPXV with its side effects.A second-generation vaccination with limitations was launched in 2000.However,the CDC advised vaccinations for risk groups in endemic countries,including positive patients and hospital employees.The JYNNEOS vaccine,administered in 2 doses,also provides protection from MPX.This article presents concisely the most recent findings regarding epidemiology,genomic transmission,signs and symptoms,pathogenesis,diagnosis,and therapeutic interventions for MPXV,which may be helpful to researchers and practitioners.WHO declared that MPX was no longer a global health emergency due to its declining case rate,and a number of countries have reported new incidences.Further research-based investigations must be carried out based on the 2022 outbreak.展开更多
Background The objective of this paper is to analyze the current status of monkeypox worldwide.In the face of this public health threat,our purpose is to elucidate the clinical characteristics and epidemiology of monk...Background The objective of this paper is to analyze the current status of monkeypox worldwide.In the face of this public health threat,our purpose is to elucidate the clinical characteristics and epidemiology of monkeypox,the developmental progress of monkeypox-related drugs and the vaccines available.Data sources The literature review was performed in databases including PubMed,Science Direct and Google Scholar up to July 2022.Results Since May 2022,the World Health Organization has reported more than 45,000 confirmed cases from 92 nonendemic countries,including nine deaths.Although some women and children have been infected so far,most cases have occurred among men who have sex with other men,especially those with multiple sexual partners or anonymous sex.Conclusions Pediatric monkeypox infection has been associated with a higher likelihood of severe illness and mortality than in adults.Severe monkeypox illness in pediatrics often requires adjunctive antiviral therapy.It is crucial for all countries to establish sound monitoring and testing systems and be prepared with emergency preparedness.展开更多
An ongoing multi-country outbreak of monkeypox was reported in May 2022 with several deaths,affecting 107 countries of all six World Health Organization(WHO)regions.The WHO has declared the current monkeypox outbreak ...An ongoing multi-country outbreak of monkeypox was reported in May 2022 with several deaths,affecting 107 countries of all six World Health Organization(WHO)regions.The WHO has declared the current monkeypox outbreak to be a Public Health Emergency of International Concern.It is,thus,necessary to rapidly and accurately detect and distinguish different monkeypox virus(MPXV)clades.We designed primers and probes based on the alignment of 138 complete genomes of poxviruses.In Panel 1,we mixed one pair of primers and three probes to detect and differentiate the MPXV Western Africa(IIa,IIb clade)and Congo Basin(I clade)and other orthopoxviruses.In Panel 2,we mixed one pair of primers and two probes to detect the 2022 MPXV(B.1 lineage and its descendant lineages).In addition,we tested the specificity and sensitivity of the assay using real-time PCR.In Panel 1,the assay reproducibly identified various concentrations of two plasmids of the monkeypox virus,whereas other orthopoxviruses did not cross-react.In Panel 2,the probe annealed well to MPXV B.1 and showed the expected linearity.These two multiple real-time assays are inclusive and highly specific for identifying different clades of MPXV.展开更多
Nipah virus (NiV) is a highly infectious zoonotic pathogen that poses a significant threat to human and animal health. First identified in Malaysia in 1998, NiV has since caused several outbreaks in Southeast Asia, wi...Nipah virus (NiV) is a highly infectious zoonotic pathogen that poses a significant threat to human and animal health. First identified in Malaysia in 1998, NiV has since caused several outbreaks in Southeast Asia, with sporadic cases reported in Bangladesh and India. The virus is primarily transmitted to humans through direct contact with infected animals, primarily fruit bats, or through the consumption of contaminated fruits and their juices. NiV infection presents a wide spectrum of clinical features, ranging from mild respiratory illness to severe encephalitis, with a high case fatality rate. The incubation period typically ranges from 4 to 14 days, during which patients develop fever, headache, myalgia, and respiratory symptoms such as cough and sore throat. As the disease progresses, neurological signs become prominent, including altered consciousness, seizures, and focal deficits. Severe cases may exhibit acute respiratory distress syndrome and multi organ failure. Laboratory findings often include lymphocytopenia, thrombocytopenia, and elevated liver enzymes. Diagnosis of NiV infection requires specialized laboratory testing, including reverse transcription-polymerase chain reaction (RT-PCR) and serological assays. Currently, no specific antiviral treatment exists for NiV infection, and management primarily focuses on supportive care. Prevention and control strategies encompass public health interventions, surveillance, and raising awareness among healthcare providers and the general population. The emergence and re-emergence of NiV highlight the urgent need for continued research, improved diagnostic capabilities, and the development of effective vaccines and therapeutics to mitigate the impact of this deadly virus.展开更多
According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase...According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 cases.The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in China.In addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly affected.This often leads to the development of end-stage liver and kidney diseases.Therefore,organ transplantation has emerged as an important part of active treatment for HIV infected patients.However,the curative effect is not satisfactory.HIV infection has been considered a contraindication for organ transplantation.Until the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively inhibited.With prolonged survival,the failure of important organs has become the main cause of death among HIV patients.Therefore,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion.This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land China.To date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have survived.Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary complications.展开更多
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 combinat...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.展开更多
Approximately 12-72 million people worldwide are co-infected with hepatitis B virus(HBV)and hepatitis delta virus(HDV).This concurrent infection can lead to several severe outcomes with hepatic disease,such as cirrhos...Approximately 12-72 million people worldwide are co-infected with hepatitis B virus(HBV)and hepatitis delta virus(HDV).This concurrent infection can lead to several severe outcomes with hepatic disease,such as cirrhosis,fulminant hepatitis,and hepatocellular carcinoma,being the most common.Over the past few decades,a correlation between viral hepatitis and autoimmune diseases has been reported.Furthermore,autoantibodies have been detected in the serum of patients co-infected with HBV/HDV,and autoimmune features have been reported.However,to date,very few cases of clinically significant autoimmune hepatitis(AIH)have been reported in patients with HDV infection,mainly in those who have received treatment with pegylated interferon.Interestingly,there are some patients with HBV infection and AIH in whom HDV infection is unearthed after receiving treatment with immunosuppressants.Consequently,several questions remain unanswered with the challenge to distinguish whether it is autoimmune or“autoimmune-like”hepatitis being the most crucial.Second,it remains uncertain whether autoimmunity is induced by HBV or delta virus.Finally,we investigated whether the cause of AIH lies in the previous treatment of HDV with pegylated interferon.These pressing issues should be elucidated to clarify whether new antiviral treatments for HDV,such as Bulevirtide or immu-nosuppressive drugs,are more appropriate for the management of patients with HDV and AIH.展开更多
Infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV), manifests as the classic triad of fever, pharyngitis, and cervical lymphadenopathy. Severe cases may involve organ damage, most commonly...Infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV), manifests as the classic triad of fever, pharyngitis, and cervical lymphadenopathy. Severe cases may involve organ damage, most commonly affecting the liver. Diagnosis relies on a combination of clinical presentation and laboratory parameters, with commonly used indicators including EBV-specific antibodies, EBV-DNA load, and the ratio of atypical lymphocytes. Treatment primarily involves symptomatic supportive care, with a cautious approach to the routine use of antiviral medications. In recent years, significant research in traditional Chinese medicine has been conducted in China, showing promising advancements. This article provides a comprehensive review of EBV-induced infectious mononucleosis, offering insights for clinical diagnosis and treatment.展开更多
Hepatitis B virus(HBV)infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma(HCC).HBV genetics are diverse where it is classified into at least 9 genotypes(A to...Hepatitis B virus(HBV)infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma(HCC).HBV genetics are diverse where it is classified into at least 9 genotypes(A to I)and 1 putative genotype(J),each with specific geographical distribution and possible different clinical outcomes in the patient.This diversity may be associated with the precision medicine for HBV-related HCC and the success of therapeutical approaches against HCC,related to different pathogenicity of the virus and host response.This Editorial discusses recent updates on whether the classification of HBV genetic diversity is still valid in terms of viral oncogenicity to the HCC and its precision medicine,in addition to the recent advances in cellular and molecular biology technologies.展开更多
The Janus kinase/signal transducers and activators of transcription(JAK/STAT)signaling pathway play a pivotal role in innate immunity.Among invertebrates,Domeless receptors serve as the key upstream regulators of this...The Janus kinase/signal transducers and activators of transcription(JAK/STAT)signaling pathway play a pivotal role in innate immunity.Among invertebrates,Domeless receptors serve as the key upstream regulators of this pathway.In our study on Bactrocera dorsalis,we identified three cytokine receptors:BdDomeless1,BdDomeless2,and BdDomeless3.Each receptor encompasses five fibronectin-type-III-like(FN III)extracellular domains and a transmembrane domain.Furthermore,these receptors exhibit the increased responsiveness to diverse pathogenic challenges.Notably,only BdDomeless3 is upregulated during symbiont-like viral infections.Moreover,silencing BdDomeless3 enhanced the infectivity of Bactrocera dorsalis cripavirus(BdCV)and B.dorsalis picorna-like virus(BdPLV),underscoring BdDomeless3’s crucial role in antiviral defense of B.dorsalis.Following the suppression of Domeless3 expression,six antimicrobial peptide genes displayed decreased expression,potentially correlating with the rise in viral infectivity.To our knowledge,this is the first study identifying cytokine receptors associated with the JAK/STAT pathway in tephritid flies,shedding light on the immune mechanisms of B.dorsalis.展开更多
Background: Prevention is one of the safe schemes against the high prevalence of viral Hepatitis. Negative perceptions or perceptions about the risks of hepatitis B among medical students and health care workers may i...Background: Prevention is one of the safe schemes against the high prevalence of viral Hepatitis. Negative perceptions or perceptions about the risks of hepatitis B among medical students and health care workers may influence the behavioral pattern and adoption of preventive measures against the virus and can affect the uptake of the Hepatitis B vaccine. This study assesses the perception of medical students towards Hepatitis B virus infection and Hepatitis B Vaccination in a Private Tertiary Hospital in Jos North Local Government, Plateau State, Nigeria. Methods: This was a descriptive cross-sectional study done in August 2021 among 236 clinical medical students using a multistage sampling technique. Data was collected using an interviewer-administered structured questionnaire and analysed using the IBM SPSS 28 (Statistical Package for the Social Sciences). Ethical approval was granted by Bingham University Teaching Hospital, Ethics Committee, Jos, Plateau State. Results: Two-thirds of respondents were of the opinion that they are at risk of contracting HBV. Half were of the opinion that the risk is very much while a third believed the risk is moderate. Among those who think they are not at risk of contracting HBV, the majority felt so because they are vaccinated while 10.3% believe that they are safe. 43.2% of respondents think that HBV Vaccine is very effective in preventing HBV infection while 39.8% think it is slightly effective, and 7.6% think it is not effective. Almost all respondents, 99.2% are of the opinion that HBV Vaccination is important for students while 0.8% think it is not important. The majority of the respondents at 95.8% were willing to be screened for HBV. The majority (85.6%) of respondents are willing to pay for HBV Vaccine as against 14.4% of respondents who are not willing to pay. Conclusion: Summarily, 21 (8.9%) of the students had a negative perception of Hepatitis B Vaccination, and 215 (91.1%) had a positive perception of Hepatitis B Vaccination. Perception-sustaining events like seminars, workshops, road shows, and campaigns should be organized among students and health workers.展开更多
BACKGROUND Direct-acting antiviral agents(DAAs)are highly effective treatment for chronic hepatitis C(CHC)with a significant rate of sustained virologic response(SVR).The achievement of SVR is crucial to prevent addit...BACKGROUND Direct-acting antiviral agents(DAAs)are highly effective treatment for chronic hepatitis C(CHC)with a significant rate of sustained virologic response(SVR).The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression.The assessment of fibrosis degree can be performed with transient elastography,magnetic resonance elastography or shear-wave elastography(SWE).Liver elastography could function as a predictor for hepato-cellular carcinoma(HCC)in CHC patients treated with DAAs.AIM To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus(HCV).METHODS A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS At baseline and after 12 wk of follow-up,a trend was shown towards greater liver stiffness(LS)in those who go on to develop HCC compared to those who do not[baseline LS standardized mean difference(SMD):1.15,95%confidence interval(95%CI):020-2.50;LS SMD after 12 wk:0.83,95%CI:0.33-1.98].The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data.There was a statist-ically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not(0.64;95%CI:0.04-1.24).CONCLUSION SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs.Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.展开更多
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 manageme...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.展开更多
BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)infection.Previous studies have indicated an anti-HBV effect of LWWL,...BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)infection.Previous studies have indicated an anti-HBV effect of LWWL,specifically in terms of antigen inhibition,but the underlying mechanism remains unclear.AIM To investigate the potential mechanism of action of LWWL against HBV.METHODS In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell lines.The in vivo experiment involved a hydrodynamic injectionmediated mouse model with HBV replication.Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL.RESULTS In HepG2.1403F cells,LWWL(0.8 mg/mL)exhibited inhibitory effects on HBV DNA,hepatitis B surface antigen and pregenomic RNA(pgRNA)at rates of 51.36%,24.74%and 50.74%,respectively.The inhibition rates of LWWL(0.8mg/mL)on pgRNA/covalently closed circular DNA in HepG2.1403F,HepG2.2.15 and HepG2.A64 cells were 47.78%,39.51%and 46.74%,respectively.Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis(PI3K-AKT,CASP8-CASP3 and P53 pathways).Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group(CG)among HBV-replicating cell lines,including HepG2.2.15(2.92%±1.01%vs 6.68%±2.04%,P<0.05),HepG2.A64(4.89%±1.28%vs 8.52%±0.50%,P<0.05)and HepG2.1403F(3.76%±1.40%vs 7.57%±1.35%,P<0.05)(CG vs LWWL-treated group).However,there were no significant differences in apoptosis rates between the non-HBV-replicating HepG2 cells(5.04%±0.74%vs 5.51%±1.57%,P>0.05),L02 cells(5.49%±0.80%vs 5.48%±1.01%,P>0.05)and LX2 cells(6.29%±1.54%vs 6.29%±0.88%,P>0.05).TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBVreplicating mouse model,while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replicating mouse model.CONCLUSION Preliminary results suggest that LWWL exerts a potent inhibitory effect on wild-type and drug-resistant HBV,potentially involving selective regulation of apoptosis.These findings offer novel insights into the anti-HBV activities of LWWL and present a novel mechanism for the development of anti-HBV medications.展开更多
基金supported by the Benin Ministry of Health and the Institut Pasteur de Dakar Internal Funds for Research.·。
文摘Dear Editor,Monkeypox is an infectious disease that is endemic in a dozen of African countries.Some imported cases have been also reported outside of Africa in the past[1].Since early May 2022,monkeypox infections including human-to-human transmission,were reported in a multi-country outbreak in non-endemic countries and declared Public Health Emergency of International Concern(PHEIC)by the World Health Organization(WHO)in July 2022[2].As of 20 September 2022,a total of at least 62,798 human cases of monkeypox with 20 deaths have been confirmed in 115 countries in five WHO regions[3].
文摘Presently, an ongoing outbreak of the monkeypox virus infection that began in Bayelsa State of Nigeria has now spread to other parts of the country including mostly States in the South-South with the Nigerian Ministry of Health confirming 4 samples out of the 43 sent for testing at WHO Regional Laboratory in Dakar, Senegal. This reminds us that apart from the eradicated smallpox, there are other poxviruses that pose potential threat to people in West and Central Africa. In this paper, we developed a mathematical model for the dynamics of the transmission of monkeypox virus infection with control strategies of combined vaccine and treatment interventions. Using standard approaches, we established two equilibria for the model namely: disease-free and endemic. The disease-free equilibrium was proved to be both locally and globally asymptotically stable if R0 < 1 using the next-generation matrix and the comparison theorem. While the endemic equilibrium point existed only when R0 > 1, was proved to be locally asymptotically stable if R0 > 1 using the linearization plus row-reduction method. The basic reproduction numbers for the humans and the non-human primates of the model are computed using parameter values to be R0,h = 9.1304 x 10-6 and R0,n = 3.375 x 10-3 respectively. Numerical simulations carried out on the model revealed that the infectious individuals in the human and non-human primates’ populations will die out in the course of the proposed interventions in this paper during the time of the study. Sensitivity analysis carried out on the model parameters shows that the basic reproduction numbers of the model which served as a threshold for measuring new infections in the host populations decrease with increase in the control parameters of vaccination and treatment.
基金supported by the National Key Research and Development Program of China(2022YFC2303401,2022YFC2304100,2016YFD0500301,2021YFC0863300)the Beijing Science and Technology Plan(Z211100002521017)the National Natural Science Foundation of China(82241080)。
文摘The monkeypox virus(MPXV)has triggered a current outbreak globally.Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control.It is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads,as it is one of the DNA viruses with the largest genome and the most AT-biased,and has a significant number of tandem repeats.Here we evaluated the performance of metagenomic and amplicon sequencing techniques,and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese mainland.We rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical specimens.Amplicon sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV genomes.Third-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published sequences.Besides,several intra-host single nucleotide variations were identified in the first imported mpox case.This study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical specimens.The findings of this study will significantly enhance the surveillance of MPXV.
基金Shenzhen High‐level Hospital Construction Fund,Grant/Award Numbers:23250G1001,XKJS‐CRGRK‐004Sanming Project of Medicine in Shenzhen。
文摘Mpox(formerly Monkeypox)is a zoonotic infection caused by Monkeypox virus(MPXV).Since 2022,Mpox epidemics have occurred in many nonendemic countries and regions,leading the World Health Organization to declare a public health emergency of international concern.With the persistent transmission and evolution of MPXV,symptoms of Mpox have become milder,with some infections being asymptomatic.In addition,MPXV has become more contagious.Therefore,rapid and accurate diagnosis and screening of MPXV is vital to prevent and control MPXV epidemics.Here,we review and summarize the technical details,application scenarios,and the advantages and disadvantages of MPXV‐specific diagnostic methods.
基金National Key R&D Program of China(2023YFC3041500).
文摘The monkeypox(mpox)virus has caused worldwide transmission since its initial report in England in early May 2022.Available data from the World Health Organization(WHO)show that Europe and the Americas experienced a huge wave of mpox virus infection.Now the number of infected cases is on the rise in Asia.Several sporadic infections have been reported in China.In this study,we obtained high‐quality whole viral genomic sequences using a mpox virus‐specific amplicon‐based sequencing strategy.Our analysis of the phylogenomic characteristics indicated that all eight mpox virus sequences from Guangzhou belonged to the clade IIb lineage B.1.3 cluster.However,we could not locate the exact origins where the virus was imported,based on all the available mpox virus sequences from the Global Initiative on Sharing Avian Influenza Data(GISAID)database(https://gisaid.org/),except for their closest sequence similarity to that was reported from Japan.Novel amino acid mutations were found among the eight cases,suggesting that a local transmission may have occurred in Guangzhou,China.
文摘As we set into the second half of 2022,the world is still recovering from the two-year COVID-19 pandemic.However,over the past three months,the outbreak of the Monkeypox Virus(MPV)has led to fifty-two thousand confirmed cases and over one hundred deaths.This caused the World Health Organisation to declare the outbreak a Public Health Emergency of International Concern(PHEIC).If this outbreak worsens,we could be looking at the Monkeypox virus causing the next global pandemic.As Monkeypox affects the human skin,the symptoms can be captured with regular imaging.Large samples of these images can be used as a training dataset for machine learning-based detection tools.Using a regular camera to capture the skin image of the infected person and running it against computer vision models is beneficial.In this research,we use deep learning to diagnose monkeypox from skin lesion images.Using a publicly available dataset,we tested the dataset on five pre-trained deep neural networks:GoogLeNet,Places365-GoogLeNet,SqueezeNet,AlexNet and ResNet-18.Hyperparameter was done to choose the best parameters.Performance metrics such as accuracy,precision,recall,f1-score and AUC were considered.Among the above models,ResNet18 was able to obtain the highest accuracy of 99.49%.The modified models obtained validation accuracies above 95%.The results prove that deep learning models such as the proposed model based on ResNet-18 can be deployed and can be crucial in battling the monkeypox virus.Since the used networks are optimized for efficiency,they can be used on performance limited devices such as smartphones with cameras.The addition of explainable artificial intelligence techniques LIME and GradCAM enables visual interpretation of the prediction made,helping health professionals using the model.
文摘The largest monkeypox virus(MPXV)outbreak of the 21st century occurred in 2022,which caused epidemics in many countries.According to WHO,physical contact with infected persons,contaminated surfaces,or affected animals might be a source of this virus transmission.A febrile sickness including few symptoms found in MPX disease.Skin rash,lesions,fever,headache,fatigue,and muscle aches symptoms were observed commonly for this disease.Animal and in vitro,studies have shown that the antiviral medications cidofovir and brincidofovir are effective against MPXV.The first-generation vaccinia virus vaccine was developed in 1960,and it helped to protect against MPXV with its side effects.A second-generation vaccination with limitations was launched in 2000.However,the CDC advised vaccinations for risk groups in endemic countries,including positive patients and hospital employees.The JYNNEOS vaccine,administered in 2 doses,also provides protection from MPX.This article presents concisely the most recent findings regarding epidemiology,genomic transmission,signs and symptoms,pathogenesis,diagnosis,and therapeutic interventions for MPXV,which may be helpful to researchers and practitioners.WHO declared that MPX was no longer a global health emergency due to its declining case rate,and a number of countries have reported new incidences.Further research-based investigations must be carried out based on the 2022 outbreak.
文摘Background The objective of this paper is to analyze the current status of monkeypox worldwide.In the face of this public health threat,our purpose is to elucidate the clinical characteristics and epidemiology of monkeypox,the developmental progress of monkeypox-related drugs and the vaccines available.Data sources The literature review was performed in databases including PubMed,Science Direct and Google Scholar up to July 2022.Results Since May 2022,the World Health Organization has reported more than 45,000 confirmed cases from 92 nonendemic countries,including nine deaths.Although some women and children have been infected so far,most cases have occurred among men who have sex with other men,especially those with multiple sexual partners or anonymous sex.Conclusions Pediatric monkeypox infection has been associated with a higher likelihood of severe illness and mortality than in adults.Severe monkeypox illness in pediatrics often requires adjunctive antiviral therapy.It is crucial for all countries to establish sound monitoring and testing systems and be prepared with emergency preparedness.
基金supported by the National Key Research and Development Program of China(2016YFD0500301,2021YFC0863300).
文摘An ongoing multi-country outbreak of monkeypox was reported in May 2022 with several deaths,affecting 107 countries of all six World Health Organization(WHO)regions.The WHO has declared the current monkeypox outbreak to be a Public Health Emergency of International Concern.It is,thus,necessary to rapidly and accurately detect and distinguish different monkeypox virus(MPXV)clades.We designed primers and probes based on the alignment of 138 complete genomes of poxviruses.In Panel 1,we mixed one pair of primers and three probes to detect and differentiate the MPXV Western Africa(IIa,IIb clade)and Congo Basin(I clade)and other orthopoxviruses.In Panel 2,we mixed one pair of primers and two probes to detect the 2022 MPXV(B.1 lineage and its descendant lineages).In addition,we tested the specificity and sensitivity of the assay using real-time PCR.In Panel 1,the assay reproducibly identified various concentrations of two plasmids of the monkeypox virus,whereas other orthopoxviruses did not cross-react.In Panel 2,the probe annealed well to MPXV B.1 and showed the expected linearity.These two multiple real-time assays are inclusive and highly specific for identifying different clades of MPXV.
文摘Nipah virus (NiV) is a highly infectious zoonotic pathogen that poses a significant threat to human and animal health. First identified in Malaysia in 1998, NiV has since caused several outbreaks in Southeast Asia, with sporadic cases reported in Bangladesh and India. The virus is primarily transmitted to humans through direct contact with infected animals, primarily fruit bats, or through the consumption of contaminated fruits and their juices. NiV infection presents a wide spectrum of clinical features, ranging from mild respiratory illness to severe encephalitis, with a high case fatality rate. The incubation period typically ranges from 4 to 14 days, during which patients develop fever, headache, myalgia, and respiratory symptoms such as cough and sore throat. As the disease progresses, neurological signs become prominent, including altered consciousness, seizures, and focal deficits. Severe cases may exhibit acute respiratory distress syndrome and multi organ failure. Laboratory findings often include lymphocytopenia, thrombocytopenia, and elevated liver enzymes. Diagnosis of NiV infection requires specialized laboratory testing, including reverse transcription-polymerase chain reaction (RT-PCR) and serological assays. Currently, no specific antiviral treatment exists for NiV infection, and management primarily focuses on supportive care. Prevention and control strategies encompass public health interventions, surveillance, and raising awareness among healthcare providers and the general population. The emergence and re-emergence of NiV highlight the urgent need for continued research, improved diagnostic capabilities, and the development of effective vaccines and therapeutics to mitigate the impact of this deadly virus.
基金Supported by the Shenzhen Science and Technology R&D Fund,No.JCYJ20220530163011026Shenzhen Third People’s Hospital,No.G2022008 and No.G2021008.
文摘According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 cases.The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in China.In addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly affected.This often leads to the development of end-stage liver and kidney diseases.Therefore,organ transplantation has emerged as an important part of active treatment for HIV infected patients.However,the curative effect is not satisfactory.HIV infection has been considered a contraindication for organ transplantation.Until the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively inhibited.With prolonged survival,the failure of important organs has become the main cause of death among HIV patients.Therefore,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion.This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land China.To date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have survived.Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary complications.
文摘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.
文摘Approximately 12-72 million people worldwide are co-infected with hepatitis B virus(HBV)and hepatitis delta virus(HDV).This concurrent infection can lead to several severe outcomes with hepatic disease,such as cirrhosis,fulminant hepatitis,and hepatocellular carcinoma,being the most common.Over the past few decades,a correlation between viral hepatitis and autoimmune diseases has been reported.Furthermore,autoantibodies have been detected in the serum of patients co-infected with HBV/HDV,and autoimmune features have been reported.However,to date,very few cases of clinically significant autoimmune hepatitis(AIH)have been reported in patients with HDV infection,mainly in those who have received treatment with pegylated interferon.Interestingly,there are some patients with HBV infection and AIH in whom HDV infection is unearthed after receiving treatment with immunosuppressants.Consequently,several questions remain unanswered with the challenge to distinguish whether it is autoimmune or“autoimmune-like”hepatitis being the most crucial.Second,it remains uncertain whether autoimmunity is induced by HBV or delta virus.Finally,we investigated whether the cause of AIH lies in the previous treatment of HDV with pegylated interferon.These pressing issues should be elucidated to clarify whether new antiviral treatments for HDV,such as Bulevirtide or immu-nosuppressive drugs,are more appropriate for the management of patients with HDV and AIH.
文摘Infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV), manifests as the classic triad of fever, pharyngitis, and cervical lymphadenopathy. Severe cases may involve organ damage, most commonly affecting the liver. Diagnosis relies on a combination of clinical presentation and laboratory parameters, with commonly used indicators including EBV-specific antibodies, EBV-DNA load, and the ratio of atypical lymphocytes. Treatment primarily involves symptomatic supportive care, with a cautious approach to the routine use of antiviral medications. In recent years, significant research in traditional Chinese medicine has been conducted in China, showing promising advancements. This article provides a comprehensive review of EBV-induced infectious mononucleosis, offering insights for clinical diagnosis and treatment.
基金Supported by Rumah Program 2024 of Research Organization for Health,National Research and Innovation Agency of Indonesia2023 Grant of The Fondazione Veronesi,Milan,Italy(Caecilia H C Sukowati)2023/2024 Postdoctoral Fellowship of The Manajemen Talenta,Badan Riset dan Inovasi Nasional,Indonesia(Sri Jayanti).
文摘Hepatitis B virus(HBV)infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma(HCC).HBV genetics are diverse where it is classified into at least 9 genotypes(A to I)and 1 putative genotype(J),each with specific geographical distribution and possible different clinical outcomes in the patient.This diversity may be associated with the precision medicine for HBV-related HCC and the success of therapeutical approaches against HCC,related to different pathogenicity of the virus and host response.This Editorial discusses recent updates on whether the classification of HBV genetic diversity is still valid in terms of viral oncogenicity to the HCC and its precision medicine,in addition to the recent advances in cellular and molecular biology technologies.
基金This work was supported by the National Natural Science Foundation of China(32202278)the Chongqing Special Postdoctoral Science Foundation of Chinathe earmarked fund for China Agricultural Research System(CARS-26)。
文摘The Janus kinase/signal transducers and activators of transcription(JAK/STAT)signaling pathway play a pivotal role in innate immunity.Among invertebrates,Domeless receptors serve as the key upstream regulators of this pathway.In our study on Bactrocera dorsalis,we identified three cytokine receptors:BdDomeless1,BdDomeless2,and BdDomeless3.Each receptor encompasses five fibronectin-type-III-like(FN III)extracellular domains and a transmembrane domain.Furthermore,these receptors exhibit the increased responsiveness to diverse pathogenic challenges.Notably,only BdDomeless3 is upregulated during symbiont-like viral infections.Moreover,silencing BdDomeless3 enhanced the infectivity of Bactrocera dorsalis cripavirus(BdCV)and B.dorsalis picorna-like virus(BdPLV),underscoring BdDomeless3’s crucial role in antiviral defense of B.dorsalis.Following the suppression of Domeless3 expression,six antimicrobial peptide genes displayed decreased expression,potentially correlating with the rise in viral infectivity.To our knowledge,this is the first study identifying cytokine receptors associated with the JAK/STAT pathway in tephritid flies,shedding light on the immune mechanisms of B.dorsalis.
文摘Background: Prevention is one of the safe schemes against the high prevalence of viral Hepatitis. Negative perceptions or perceptions about the risks of hepatitis B among medical students and health care workers may influence the behavioral pattern and adoption of preventive measures against the virus and can affect the uptake of the Hepatitis B vaccine. This study assesses the perception of medical students towards Hepatitis B virus infection and Hepatitis B Vaccination in a Private Tertiary Hospital in Jos North Local Government, Plateau State, Nigeria. Methods: This was a descriptive cross-sectional study done in August 2021 among 236 clinical medical students using a multistage sampling technique. Data was collected using an interviewer-administered structured questionnaire and analysed using the IBM SPSS 28 (Statistical Package for the Social Sciences). Ethical approval was granted by Bingham University Teaching Hospital, Ethics Committee, Jos, Plateau State. Results: Two-thirds of respondents were of the opinion that they are at risk of contracting HBV. Half were of the opinion that the risk is very much while a third believed the risk is moderate. Among those who think they are not at risk of contracting HBV, the majority felt so because they are vaccinated while 10.3% believe that they are safe. 43.2% of respondents think that HBV Vaccine is very effective in preventing HBV infection while 39.8% think it is slightly effective, and 7.6% think it is not effective. Almost all respondents, 99.2% are of the opinion that HBV Vaccination is important for students while 0.8% think it is not important. The majority of the respondents at 95.8% were willing to be screened for HBV. The majority (85.6%) of respondents are willing to pay for HBV Vaccine as against 14.4% of respondents who are not willing to pay. Conclusion: Summarily, 21 (8.9%) of the students had a negative perception of Hepatitis B Vaccination, and 215 (91.1%) had a positive perception of Hepatitis B Vaccination. Perception-sustaining events like seminars, workshops, road shows, and campaigns should be organized among students and health workers.
文摘BACKGROUND Direct-acting antiviral agents(DAAs)are highly effective treatment for chronic hepatitis C(CHC)with a significant rate of sustained virologic response(SVR).The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression.The assessment of fibrosis degree can be performed with transient elastography,magnetic resonance elastography or shear-wave elastography(SWE).Liver elastography could function as a predictor for hepato-cellular carcinoma(HCC)in CHC patients treated with DAAs.AIM To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus(HCV).METHODS A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS At baseline and after 12 wk of follow-up,a trend was shown towards greater liver stiffness(LS)in those who go on to develop HCC compared to those who do not[baseline LS standardized mean difference(SMD):1.15,95%confidence interval(95%CI):020-2.50;LS SMD after 12 wk:0.83,95%CI:0.33-1.98].The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data.There was a statist-ically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not(0.64;95%CI:0.04-1.24).CONCLUSION SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs.Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.
文摘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.
基金Supported by National Natural Science Foundation of China,No.81930110The National Funded Postdoctoral Researcher Program of China,No.GZC20232406+2 种基金Henan Province Traditional Chinese Medicine Science Research Project,No.2023ZY3040Henan Province Medical Science and Technology Research Plan Joint Construction Project,No.LHGJ20230233National Key Research and Development Program of China,No.2022YFC2303103.
文摘BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)infection.Previous studies have indicated an anti-HBV effect of LWWL,specifically in terms of antigen inhibition,but the underlying mechanism remains unclear.AIM To investigate the potential mechanism of action of LWWL against HBV.METHODS In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell lines.The in vivo experiment involved a hydrodynamic injectionmediated mouse model with HBV replication.Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL.RESULTS In HepG2.1403F cells,LWWL(0.8 mg/mL)exhibited inhibitory effects on HBV DNA,hepatitis B surface antigen and pregenomic RNA(pgRNA)at rates of 51.36%,24.74%and 50.74%,respectively.The inhibition rates of LWWL(0.8mg/mL)on pgRNA/covalently closed circular DNA in HepG2.1403F,HepG2.2.15 and HepG2.A64 cells were 47.78%,39.51%and 46.74%,respectively.Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis(PI3K-AKT,CASP8-CASP3 and P53 pathways).Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group(CG)among HBV-replicating cell lines,including HepG2.2.15(2.92%±1.01%vs 6.68%±2.04%,P<0.05),HepG2.A64(4.89%±1.28%vs 8.52%±0.50%,P<0.05)and HepG2.1403F(3.76%±1.40%vs 7.57%±1.35%,P<0.05)(CG vs LWWL-treated group).However,there were no significant differences in apoptosis rates between the non-HBV-replicating HepG2 cells(5.04%±0.74%vs 5.51%±1.57%,P>0.05),L02 cells(5.49%±0.80%vs 5.48%±1.01%,P>0.05)and LX2 cells(6.29%±1.54%vs 6.29%±0.88%,P>0.05).TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBVreplicating mouse model,while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replicating mouse model.CONCLUSION Preliminary results suggest that LWWL exerts a potent inhibitory effect on wild-type and drug-resistant HBV,potentially involving selective regulation of apoptosis.These findings offer novel insights into the anti-HBV activities of LWWL and present a novel mechanism for the development of anti-HBV medications.
