Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is pre...Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell(Th1/Tc1) response.These chemokines consist of CCL3(macrophage inflammatory protein-1α;MIP-1α),CCL4(MIP-1β),CCL5(regulated on activation normal T cell expressed and secreted;RANTES),CXCL10(interferon-γ-inducible protein-10;IP-10),CXCL11(interferon-inducible T-cell α chemoattractant;I-TAC),and CXCL9(monokine induced by interferon γ;Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors.Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C.The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection.When the adaptive immune response fails in this task,non-specific T cells without the capacity to control the infection are also recruited to the liver,and these are ultimately responsible for the persistent hepatic damage.The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection,and to maintain liver viability during the chronic phase,by impairing non-specific T cell migration.Some chemokines and their receptors correlate with liver damage,and CXCL10(IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome.The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.展开更多
Background: In Nigeria, adolescents and young people (AYP) aged 10 - 24, comprise 22.3% of the population and with HIV prevalence of 3.5%. The AYP living with HIV enrolled at the 68 NARHY, Lagos reflects the national ...Background: In Nigeria, adolescents and young people (AYP) aged 10 - 24, comprise 22.3% of the population and with HIV prevalence of 3.5%. The AYP living with HIV enrolled at the 68 NARHY, Lagos reflects the national challenges with poor viral suppression. The OTZ program aligns with the UNAIDS 95-95-95 goals. It seeks to empower AYPLHIV to be in charge of their treatment and commit to triple zero outcomeszero missed appointments, zero missed drugs, and zero viral loads. The purpose of the study was to assess the impact of the OTZ program on viral load suppression among members of the adolescent club in 68 NARHY, Lagos. Method: A cross-sectional retrospective study to evaluate the impact of the OTZ program on the viral load of 53 AYP enrolled in the OTZ program between March 2019 to December 2019 was analyzed. The Percentage of viral load suppression before enrollment compared with 6 and 12 months after enrollment into the OTZ program. The AYP is grouped into 10 - 14, 15 - 19, and 20 - 24 years. Activities conducted were peer driven monthly meetings with the AYP during which the adolescents interacted on issues relating to improving their treatment outcomes, healthcare workers reviewed their clinical status, viral load result, provider peer counseling, and caregivers engagement to support adherence to medication and ARV refills. Results: Before OTZ, 81% aged 10 - 14 years, 75% aged 15 - 19 years, and 25% aged 20 - 24 years were virally suppressed (VL less than 1000 copies/ml). Six months after enrollment, 94% were virally suppressed95% aged 10 - 14 years, 96% aged 15 - 19 years, and 66% aged 20-24 years. Twelve months after enrollment, 96% of AYP were virally suppressed100% aged 10-14 years, 93% aged 15 - 19 years, and 100% aged 20 - 24 years. Males viral load (VL) suppression improved from 79% to 96% and 92%, while females VL suppression improved from 69% to 93% and 100% at 6 and 12 months respectively. Conclusion: The OTZ activities contributed to improved viral load suppression in the AYP of the facility.展开更多
Objective: To compare the effects of extracorporeal membrane oxygenation (ECMO) and routine mechanical ventilation on mortality and the risk of associated adverse events in patients with severe viral pneumonia. Method...Objective: To compare the effects of extracorporeal membrane oxygenation (ECMO) and routine mechanical ventilation on mortality and the risk of associated adverse events in patients with severe viral pneumonia. Methods: PubMed, the Cochrane Library, Embase, Web of Science, and other databases were searched to collect case-control or cohort studies on prognoses associated with ECMO treatment for viral pneumonia. Search terms included extracorporeal membrane oxygenation, ECMO, viral pneumonia, COVID-19, influenza, MERS, and others. According to the PICOS principle, two evaluators independently screened the literature, extracted the data, cross-checked the data, and extracted the data again. Two researchers evaluated the risk of bias in the included studies according to the Newcastle-Ottawa Scale (NOS) and cross-checked the results. Meta-analysis was performed using RevMan 5.3 software. Results: Nine studies were included for analysis, encompassing a total of 4,330 patients, which were categorized into ECMO and CMV groups. There were no significant differences between the two groups in most baseline data;however, the ECMO group had a lower oxygenation index, and some studies reported higher SOFA scores in the ECMO group compared to the CMV group. There was no significant difference in in-hospital mortality between the two groups. The length of ICU stay, total hospital stay, and total mechanical ventilation time were longer in the ECMO group than in the CMV group. In terms of adverse events, there was no significant difference in the occurrence of kidney injury between the two groups. Bleeding events were reported in two studies, with more bleeding events occurring in the ECMO group. According to the subgroup analysis of different virus types, there were no statistical differences in the above aspects among patients with swine flu, novel coronavirus, and MERS. Conclusion: ECMO has a certain degree of positive significance in the treatment of severe viral pneumonia, but there is no significant difference in the treatment outcome of ECMO across different epidemic periods. The timing of ECMO treatment, patient management, and withdrawal evaluation still need further research.展开更多
Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and bra...Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and brain parenchyma,has attracted growing attention due to its high mortality and disability rates.Understanding the infectious routes of neurotropic viruses and the mechanism underlying the host immune response is critical to reduce viral spread and improve antiviral therapy outcomes.In this review,we summarize the common categories of neurotropic viruses,viral transmission routes in the body,host immune responses,and experimental animal models used for VE study to gain a deeper understanding of recent progress in the pathogenic and immunological mechanisms under neurotropic viral infection.This review should provide valuable resources and perspectives on how to cope with pandemic infections.展开更多
BACKGROUND Alphaherpesvirus belongs to the Herpesviridae family and has large,monopartite double-stranded linear DNA.It mainly infects the skin,mucosa,and nerves,and can affect various hosts,including humans and other...BACKGROUND Alphaherpesvirus belongs to the Herpesviridae family and has large,monopartite double-stranded linear DNA.It mainly infects the skin,mucosa,and nerves,and can affect various hosts,including humans and other animals.Here,we present a case of a patient seen by the gastroenterology department at our hospital who experienced an oral and perioral herpes infection following treatment with a ven-tilator.The patient was treated with oral and topical antiviral drugs,furacilin,oral and topical antibiotics,local epinephrine injection,topical thrombin powder,and nutritional and supportive care.A wet wound healing approach was also implemented with good response.CASE SUMMARY A 73-year-old woman presented to the hospital with a chief complaint of"abdominal pain for 3 d with dizziness for 2 d."She was admitted to the intensive care unit for septic shock and spontaneous peritonitis secondary to cirrhosis and was given antiinflammatory and symptomatic supportive treatment.A ventilator was used to assist breathing for acute respiratory distress syndrome,which developed during her admission.A large area of herpes infection appeared in the perioral region 2 d following noninvasive ventilation.The patient was transferred to the gastroenterology department,at which time she had a body temperature of 37.8 C and a respiratory rate of 18/min.The patient's con-sciousness was intact,and she no longer had abdominal pain or distension,chest tightness,or asthma.At this point,the infected perioral region changed in appearance and was now accompanied by local bleeding with crusting of blood at the wounds.The surface area of the wounds measured approximately 10 cm×10 cm.A cluster blisters appeared on the patient’s right neck,and ulcers developed in her mouth.On a subjective numerical pain scale,the patient reported a pain level of 2.Overall,her diagnoses other than the oral and perioral herpes infection included:(1)Septic shock;(2)spontaneous peritonitis;(3)abdominal infection;(4)decompensated cirrhosis;and(5)hypoproteinemia.Dermatology was consulted regarding the treatment of the patient’s wounds;they suggested treatment with oral antiviral drugs,an intramuscular injection of nutritious nerve drugs,and the application of topical penciclovir and mupirocin around the lips.Stomatology was also consulted and suggested the use of nitrocilin in a local wet application around the lips.CONCLUSION Through multidisciplinary consultation,the patient’s oral and perioral herpes infection was successfully treated with the following combined approach:(1)Application of topical antviral and antibiotic treatments;(2)keeping the wound moist with a wet wound healing strategy;(3)systemic use of oral antiviral drugs;and(4)symptomatic and nutritional supportive care.The patient was discharged from the hospital after successful wound healing.展开更多
Vitamin D is a steroid hormone that is naturally produced in the body or obtained through dietary sources,primarily under the influence of UVB radiation.This essential nutrient has a vital role in numerous physiologic...Vitamin D is a steroid hormone that is naturally produced in the body or obtained through dietary sources,primarily under the influence of UVB radiation.This essential nutrient has a vital role in numerous physiological processes,encom-passing immune function,cell growth,differentiation,insulin regulation,and cardiovascular well-being,along with its pivotal role in sustaining the delicate equilibrium of calcium and phosphate concentrations in the body.Moreover,vitamin D reinforces mucosal defense and bolsters the immune system through immunomodulation,making it a critical component of overall health.Numerous studies have unveiled the profound connection between vitamin D and the predisposition to respiratory tract infections,including well-known viruses such as influenza and the novel severe acute respiratory syndrome coronavirus 2.Vita-min D deficiency has been consistently linked to increased severity of coronavirus disease 2019(COVID-19)and a heightened risk of mortality among afflicted individuals.Retrospective observational studies have further substantiated these findings,indicating that levels of vitamin D are linked with both the occurrence and severity of COVID-19 cases.Vitamin D has its influence on viral infections th-rough a multitude of mechanisms,such as promoting the release of antimicrobial peptides and fine-tuning the responses of the immune system.Additionally,vitamin D is intertwined with the intricate network of the renin–angiotensin system,suggesting a potential impact on the development of complications related to COVID-19.While further clinical trials and extensive research are warranted,the existing body of evidence strongly hints at the possible use of vitamin D as a valuable tool in the prophylaxis and management of COVID-19 and other viral infectious diseases.展开更多
BACKGROUND Hepatitis B virus(HBV)and hepatitis C virus(HCV)viral load(VL)estimation is essential for the management of both HBV and HCV infections.Due to a longer turnaround time for VL estimation,many patients drop o...BACKGROUND Hepatitis B virus(HBV)and hepatitis C virus(HCV)viral load(VL)estimation is essential for the management of both HBV and HCV infections.Due to a longer turnaround time for VL estimation,many patients drop out from the cascade of care.To achieve the global goals of reducing morbidity and mortality due to HBV/HCV and moving towards their elimination by 2030,molecular diagnostic platforms with faster and random(i.e.single sample)access are needed.AIM To evaluate the performance of the recently launched NeuMoDx 96 random access system with the conventional COBAS^(■)AmpliPrep/COBAS TaqMan system for HBV and HCV VL estimation.METHODS Archived once-thawed plasma samples were retrieved and tested on both platforms.Correlation between the assays was determined by linear regression and Bland-Altman analysis.The study included samples from 186 patients,99 for HBV of which 49 were true infected HBV cases(hepatitis B surface antigen,antihepatitis B core antibody,and HBV DNA-positive)and 87 for HCV assay in which 39 were true positives for HCV infection(anti-HCV and HCV RNA-positive).RESULTS The median VL detected by NeuMoDx for HBV was 2.9(interquartile range[IQR]:2.0-4.3)log_(10)IU/mL and by COBAS it was 3.70(IQR:2.28-4.56)log_(10)IU/mL,with excellent correlation(R2=0.98).In HCV,the median VL detected by NeuMoDx was 4.9(IQR:4.2-5.4)log_(10)IU/mL and by COBAS it was 5.10(IQR:4.07-5.80)log_(10)IU/mL with good correlation(R2=0.96).CONCLUSION The overall concordance between both the systems was 100%for both HBV and HCV VL estimation.Moreover,no genotype-specific bias for HBV/HCV VL quantification was seen in both the systems.Our findings reveal that NeuMoDx HBV and HCV quantitative assays have shown overall good clinical performance and provide faster results with 100%sensitivity and specificity compared to the COBAS AmpliPrep/COBAS TaqMan system.展开更多
Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laborat...Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing.Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing.Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing.Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.展开更多
A patient co-infected with COVID-19 and viral hepatitis B can be atmore risk of severe complications than the one infected with a single infection.This study develops a comprehensive stochastic model to assess the epi...A patient co-infected with COVID-19 and viral hepatitis B can be atmore risk of severe complications than the one infected with a single infection.This study develops a comprehensive stochastic model to assess the epidemiological impact of vaccine booster doses on the co-dynamics of viral hepatitis B and COVID-19.The model is fitted to real COVID-19 data from Pakistan.The proposed model incorporates logistic growth and saturated incidence functions.Rigorous analyses using the tools of stochastic calculus,are performed to study appropriate conditions for the existence of unique global solutions,stationary distribution in the sense of ergodicity and disease extinction.The stochastic threshold estimated from the data fitting is given by:R_(0)^(S)=3.0651.Numerical assessments are implemented to illustrate the impact of double-dose vaccination and saturated incidence functions on the dynamics of both diseases.The effects of stochastic white noise intensities are also highlighted.展开更多
Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum ph...Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.展开更多
Objective:To explore the mechanism by which icariin alleviates viral myocarditis.Methods:CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on ce...Objective:To explore the mechanism by which icariin alleviates viral myocarditis.Methods:CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on cell viability,inflammation,and apoptosis.Moreover,the effects of icariin on ferroptosis and TLR4 signaling were assessed.After AC16 cells were transfected with TLR4 overexpression plasmids,the role of TLR4 in mediating the regulatory effect of icariin in viral myocarditis was investigated.Results:Icariin significantly elevated cell viability and reduced inflammatory factors TNF-α,IL-1β,IL-6,and IL-18.Flow cytometry revealed that icariin decreased apoptosis rate,and the protein expression of Bax and cleaved caspase 3 and 9 in CVB3-induced cardiomyocytes.Additionally,it suppressed ferroptosis including lipid peroxidation and ferrous ion,as well as the TLR4 signaling.However,TLR4 overexpression abrogated the modulatory effects of icariin.Conclusions:Icariin mitigates CVB3-induced myocardial injury by inhibiting TLR4-mediated ferroptosis.Further animal study is needed to verify its efficacy.展开更多
Pulmonary macrophages,such as tissue-resident alveolar and interstitial macrophages and recruited monocyte-derived macrophages,are the major macrophages present in the lungs during homeostasis and diseased conditions....Pulmonary macrophages,such as tissue-resident alveolar and interstitial macrophages and recruited monocyte-derived macrophages,are the major macrophages present in the lungs during homeostasis and diseased conditions.While tissue-resident macrophages act as sentinels of the alveolar space and play an important role in maintaining homeostasis and immune regulation,recruited macrophages accumulate in the respiratory tract after acute viral infections.Despite sharing similar anatomical niches,these macrophages are distinct in terms of their origins,surface marker expression,and transcriptional profiles,which impart macrophages with distinguished characteristics in physi-ological and pathophysiological conditions.In this review,we summarize the current view on these macrophage populations,their shared functions,and what makes them distinct from each other in the context of homeostasis andrespiratoryviral infections.展开更多
BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nuc...BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nucleotide polymorphisms of VH,chronic hepatitis B(CHB),chronic hepatitis C(CHC)and T2D were obtained from the BioBank Japan Project,European Bioinformatics Institute,and FinnGen.Inverse variance weighted,MREgger,and weighted median were used to test exposure-outcome associations.The MR-Egger intercept analysis and Cochran’s Q test were used to assess horizontal pleiotropy and heterogeneity,respectively.Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results.RESULTS The MR analysis showed no significant causal relationship between VH and T2D in Europeans[odds ratio(OR)=1.028;95%confidence interval(CI):0.995-1.062,P=0.101].There was a negative causal association between CHB and T2D among East Asians(OR=0.949;95%CI:0.931-0.968,P<0.001),while there was no significant causal association between CHC and T2D among East Asians(OR=1.018;95%CI:0.959-1.081,P=0.551).Intercept analysis and Cochran’s Q test showed no horizontal pleiotropy or heterogeneity(P>0.05).Sensitivity analysis showed that the results were robust.CONCLUSION Among East Asians,CHB is associated with a reduced T2D risk,but this association is limited by HBV load and cirrhosis.Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D,focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHCmediated pathways of hepatic steatosis,liver fibrosis,and cirrhosis.展开更多
Objective:To investigate the mechanism of Fuyang Jiebiao granule(FYJBKL)in the treatment of viral pneumonia.Methods:Firstly,a network model was constructed using network pharmacology to study the target expression sit...Objective:To investigate the mechanism of Fuyang Jiebiao granule(FYJBKL)in the treatment of viral pneumonia.Methods:Firstly,a network model was constructed using network pharmacology to study the target expression sites of FYJBKL viral pneumonia,so as to determine the main targets and important signal transduction pathways for the treatment of viral pneumonia.Secondly,the main components of the drug and the main target are docked.Then,the fever,sweating and inflammation rat models were established to explore the antipyretic,sweating and anti-inflammatory mechanisms of FYJBKL.Finally,the contents of IL-17,IL-1β,TNF-αand IL-6 in blood samples of rats were analyzed by ELISA method,and the morphological changes of lung tissue were observed by HE staining.Results:Quercetin,luteolin,kaempferol,etc.,and the main mechanism targets are IL-17,IL-1β,TNF-α,IL-6 and so on.Thirty signal pathways were identified by KEGG enrichment analysis,including interleukin-17 signaling pathway(IL-17 signaling pathway),human cytomegalovirus infection pathway(human cytomegalovirus infection),Kaposi's sarcoma associated herpesvirus infection pathway(Kaposi's sarcoma-as-sociated herpesvirus infection)and so on.After the study of molecular docking,we found that the contact efficiency between active substances and possible key targets is good.The high and middle concentration groups of FYJBKL significantly decreased the expression of IL-17,IL-1β,TNF-αand IL-6 in the blood of rats with inflammation(P<0.05).FYJBKL significantly reduced the foot swelling induced by egg white and inhibited the increase of body temperature induced by yeast in rats(P<0.05).HE staining showed that FYJBKL improved pulmonary fibrosis and inflammatory exudation to varying degrees.Conclusion:The effects of FuyangJiebiao granules on the related signal pathways of anti-virus,anti-immune and anti-inflammation as well as biological and cellular processes may be caused by the binding of quercetin,luteolin,kaempferol and other active ingredients to their shared targets.Fuyang Jiebiao granules can improve the related symptoms caused by viral pneumonia,and its mechanism may be related to the activities of TNF,IL-17,IL-6 and other related channels,which are multiple targets of inflammation regulation.展开更多
BACKGROUND Direct-acting antivirals(DAAs)revolutionized the treatment of chronic hepatitis C virus(HCV)-associated disease achieving high rates of sustained virological response(SVR).However,whether DAAs can reduce th...BACKGROUND Direct-acting antivirals(DAAs)revolutionized the treatment of chronic hepatitis C virus(HCV)-associated disease achieving high rates of sustained virological response(SVR).However,whether DAAs can reduce the occurrence of hepatocellular carcinoma(HCC)in patients with HCV-associated cirrhosis who are at high risk have not been concluded.AIM To investigate the effect of DAAs on the occurrence of HCC in patients with HCVassociated cirrhosis after achieving SVR.METHODS Of 427 inpatients with HCV-associated cirrhosis were enrolled in Tianjin Second People's Hospital from January 2014 to April 2020.118 patients weren’t received antiviral treatment with any reasons named non-antiviral treatment group,and 236 patients obtained from the 309 DAAs treatment patients according to the propensity score matching named DAAs treatment group.Demographic information and laboratory data were collected from baseline and the following up.Kaplan-Meier curve and Log-Rank test were used to compare the incidence and cumulative incidence of HCC between the two groups.Cox proportional risk regression was used to re-evaluate the risk factors for HCC.RESULTS HCC incidence was 4.68/100PY(95%CI,3.09-6.81)in the DAAs treatment group,while it was 3.00/100PY(95%CI,1.50-5.37)in the non-antiviral treatment group,and the relative risk was 1.82(95%CI,0.93-3.53,P>0.05).The incidence of HCC at 12,24,36 and 48 months was 3.39%,6.36%,8.47%and 10.17%in the DAAs treatment group,and it was 0%,0%,3.39%and 9.32%in the non-antiviral treatment group,respectively.Age>58[hazard ratio(HR)=1.089;95%CI,1.033-1.147;P=0.002]and liver stiffness measurement>27.85 kPa(HR=1.043;95%CI,1.022-1.065;P=0.000)were risk factors for HCC in all patients(n=427),and DAAs treatment didn’t show protective efficacy.CONCLUSION DAAs treatment seems failed to reduce the incidence of HCC occurrence in HCV-associated cirrhosis in 48 months,and even increased the incidence of HCC in 36 months.展开更多
Viral infections have been considered as a major cause of morbidity and mortality after kidney transplantation in pediatric cohort.Children are at high risk of acquiring virus-related complications due to immunologica...Viral infections have been considered as a major cause of morbidity and mortality after kidney transplantation in pediatric cohort.Children are at high risk of acquiring virus-related complications due to immunological immaturity and the enhanced alloreactivity risk that led to maintenance of high immunosuppressive regimes.Hence,prevention,early detection,and prompt treatment of such infections are of paramount importance.Among all viral infections,herpes viruses(herpes simplex virus,varicella zoster virus,Epstein-Barr virus,cytomegalovirus),hepatitis B and C viruses,BK polyomavirus,and respiratory viruses(respiratory syncytial virus,parainfluenza virus,influenza virus and adenovirus)are common in kidney transplant recipients.These viruses can cause systemic disease or allograft dysfunction affecting the clinical outcome.Recent advances in technology and antiviral therapy have improved management strategies in screening,monitoring,adoption of prophylactic or preemptive therapy and precise treatment in the immunocompromised host,with significant impact on the outcome.This review discusses the etiology,screening and monitoring,diagnosis,prevention,and treatment of common viral infections in pediatric renal transplant recipients.展开更多
Chronic viral hepatitis B (HBV) remains a major public health problem in Burkina Faso. Since access to diagnostic tests and treatments is limited because of their high cost, the majority of the population turn to trad...Chronic viral hepatitis B (HBV) remains a major public health problem in Burkina Faso. Since access to diagnostic tests and treatments is limited because of their high cost, the majority of the population turn to traditional herbal treatments. This study aimed to evaluate the effectiveness of a plant recipe called Hepatib tiben. It consisted of comparing certain biochemical and molecular parameters of patients infected with HBV that were supported by the recipe. The patients were recruited in Ouagadougou by the traditional health practitioner according to the requirements of the study. Thus 44 patients aged 20 to 61 years and carrier of HBsAg for at least 06 months were treated with Hepatib tiben. The tests were performed in the laboratory before and three months after the treatment. ELISA tests were used to confirm the presence of HBsAg and search for anti-HCV antibodies;transaminases, creatinine were quantified by the “Chem 400” automaton and the viral load of HBV by Real-time PCR. The analysis of the results reveals an improvement of the biochemical and molecular parameters of the patients with the following means (ASAT: 21.02 ± 9.97;ALAT: 21.11 ± 13.27;DNA: 1571.82 ± 3990.97 with p = 0.01 for each). As for HBsAg, its disappearance was observed in 4.55% of patients after treatment. The evaluation of the creatinine parameter explained that the recipe of plants has a tolerated effect on the kidneys of treated patients. These results, while encouraging, need to be complemented by further research for the development of effective phytomedicine to treat and eliminate this viral hepatitis B virus.展开更多
BACKGROUND Respiratory viruses are increasingly detected in children with communityacquired pneumonia.Further strategies to limit antibiotic use in children with viral pneumonia are warranted.AIM To explore clinical e...BACKGROUND Respiratory viruses are increasingly detected in children with communityacquired pneumonia.Further strategies to limit antibiotic use in children with viral pneumonia are warranted.AIM To explore clinical efficacy of budesonide/formoterol inhalation powder for viral pneumonia in children and its impact on cellular immunity and inflammatory factor production.METHODS A total of 60 children with viral pneumonia were recruited:30 receiving budesonide/formoterol inhalation powder and 30 conventional symptomatic treatment.Outcome measures included peripheral blood levels of inflammatory cytokines,CD4^(+),CD8^(+),Th1,Th2,Th17 and Treg,clinical efficacy,and incidence of adverse reactions.RESULTS Compared with the control group,the observation group showed a significant reduction in interleukin-6 and high-sensitivity C-reactive protein levels after treatment.Compared with the control group,the observation group showed a significant increase in CD4^(+)/CD8^(+)and Th1/Th2 levels,and a decrease in Th17/Treg levels after treatment.The total effective rates in the observation group and the control group were 93.75%and 85.00%,respectively,which was a significant difference(P=0.003).CONCLUSION Budesonide/formoterol inhalation powder significantly improved therapeutic efficacy for viral pneumonia in children.The mechanism of action may be related to downregulation of the inflammatory response and improved cellular immune function.展开更多
The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological ...The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological response in only 45% of cases with significant side effects. The advent of direct-acting antivirals has changed the prognosis of cirrhotic patients with hepatitis C. DAAs have ensured a sustained viral response in the majority of patients. Our work aims to see the evolution of hepatitis C patients at the cirrhosis stage under DAA. We conducted a retrospective study over 15 years (January 2009, January 2024) including all patients with post-viral cirrhosis C, whom we divided into two groups: group A, cirrhotic patients who received ribavirin and interferon, and group B, patients on DAA. From January 2009 to January 2024, we conducted a study of 182 patients with viral hepatitis C, including 102 cirrhotic patients. The mean age was 55 years. 66% of patients were initially treated with the ribavirin interferon combination, while 34% received direct-acting antivirals (DAAs). Since the introduction of DAAs, the most commonly used regimens have been sofosbuvir/daclatasvir with or without ribavirin and sofosbuvir/ledipasvir with or without ribavirin. Group A achieved sustained virological response (SVR) in 60% of cases, with notable side effects. In Group B, SVR was 98.18%, with improved tolerability and fewer side effects than previous treatments. Fifteen patients developed hepatocellular carcinoma (HCC), with a significantly lower mortality rate in those treated with DAAs compared with pegylated dual therapy (p: 0.001).展开更多
The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ...The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.展开更多
基金Supported by Grants from "Fiscam" J.C.C.M (Ayuda paraproyectos de investigación en saludPI-2007/32)+7 种基金"AsociaciónCastellana de Aparato Digestivo" (Beca ACADACAD/06)"Fundación de Investigación Médica Mutua Madrilea"(Beca Ayudas a la Investigación FMMM2548/2008),Spainsupported by a research grantfrom "Fiscam" J.C.C.M ("Perfeccionamiento y movilidad deinvestigadores" MOV-2007_JI/18), Spainsupported by a research grant from "Instituto de SaludCarlos Ⅲ" (Contrato de apoyo a la investigación en el SNS"CA07/00157),Spain
文摘Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell(Th1/Tc1) response.These chemokines consist of CCL3(macrophage inflammatory protein-1α;MIP-1α),CCL4(MIP-1β),CCL5(regulated on activation normal T cell expressed and secreted;RANTES),CXCL10(interferon-γ-inducible protein-10;IP-10),CXCL11(interferon-inducible T-cell α chemoattractant;I-TAC),and CXCL9(monokine induced by interferon γ;Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors.Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C.The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection.When the adaptive immune response fails in this task,non-specific T cells without the capacity to control the infection are also recruited to the liver,and these are ultimately responsible for the persistent hepatic damage.The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection,and to maintain liver viability during the chronic phase,by impairing non-specific T cell migration.Some chemokines and their receptors correlate with liver damage,and CXCL10(IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome.The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.
文摘Background: In Nigeria, adolescents and young people (AYP) aged 10 - 24, comprise 22.3% of the population and with HIV prevalence of 3.5%. The AYP living with HIV enrolled at the 68 NARHY, Lagos reflects the national challenges with poor viral suppression. The OTZ program aligns with the UNAIDS 95-95-95 goals. It seeks to empower AYPLHIV to be in charge of their treatment and commit to triple zero outcomeszero missed appointments, zero missed drugs, and zero viral loads. The purpose of the study was to assess the impact of the OTZ program on viral load suppression among members of the adolescent club in 68 NARHY, Lagos. Method: A cross-sectional retrospective study to evaluate the impact of the OTZ program on the viral load of 53 AYP enrolled in the OTZ program between March 2019 to December 2019 was analyzed. The Percentage of viral load suppression before enrollment compared with 6 and 12 months after enrollment into the OTZ program. The AYP is grouped into 10 - 14, 15 - 19, and 20 - 24 years. Activities conducted were peer driven monthly meetings with the AYP during which the adolescents interacted on issues relating to improving their treatment outcomes, healthcare workers reviewed their clinical status, viral load result, provider peer counseling, and caregivers engagement to support adherence to medication and ARV refills. Results: Before OTZ, 81% aged 10 - 14 years, 75% aged 15 - 19 years, and 25% aged 20 - 24 years were virally suppressed (VL less than 1000 copies/ml). Six months after enrollment, 94% were virally suppressed95% aged 10 - 14 years, 96% aged 15 - 19 years, and 66% aged 20-24 years. Twelve months after enrollment, 96% of AYP were virally suppressed100% aged 10-14 years, 93% aged 15 - 19 years, and 100% aged 20 - 24 years. Males viral load (VL) suppression improved from 79% to 96% and 92%, while females VL suppression improved from 69% to 93% and 100% at 6 and 12 months respectively. Conclusion: The OTZ activities contributed to improved viral load suppression in the AYP of the facility.
文摘Objective: To compare the effects of extracorporeal membrane oxygenation (ECMO) and routine mechanical ventilation on mortality and the risk of associated adverse events in patients with severe viral pneumonia. Methods: PubMed, the Cochrane Library, Embase, Web of Science, and other databases were searched to collect case-control or cohort studies on prognoses associated with ECMO treatment for viral pneumonia. Search terms included extracorporeal membrane oxygenation, ECMO, viral pneumonia, COVID-19, influenza, MERS, and others. According to the PICOS principle, two evaluators independently screened the literature, extracted the data, cross-checked the data, and extracted the data again. Two researchers evaluated the risk of bias in the included studies according to the Newcastle-Ottawa Scale (NOS) and cross-checked the results. Meta-analysis was performed using RevMan 5.3 software. Results: Nine studies were included for analysis, encompassing a total of 4,330 patients, which were categorized into ECMO and CMV groups. There were no significant differences between the two groups in most baseline data;however, the ECMO group had a lower oxygenation index, and some studies reported higher SOFA scores in the ECMO group compared to the CMV group. There was no significant difference in in-hospital mortality between the two groups. The length of ICU stay, total hospital stay, and total mechanical ventilation time were longer in the ECMO group than in the CMV group. In terms of adverse events, there was no significant difference in the occurrence of kidney injury between the two groups. Bleeding events were reported in two studies, with more bleeding events occurring in the ECMO group. According to the subgroup analysis of different virus types, there were no statistical differences in the above aspects among patients with swine flu, novel coronavirus, and MERS. Conclusion: ECMO has a certain degree of positive significance in the treatment of severe viral pneumonia, but there is no significant difference in the treatment outcome of ECMO across different epidemic periods. The timing of ECMO treatment, patient management, and withdrawal evaluation still need further research.
基金supported by the National Natural Science Foundation of China(81825011,81930038,81961160738)Program of Shanghai Academic/Technology Research Leader(22XD1400800)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19030200)。
文摘Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and brain parenchyma,has attracted growing attention due to its high mortality and disability rates.Understanding the infectious routes of neurotropic viruses and the mechanism underlying the host immune response is critical to reduce viral spread and improve antiviral therapy outcomes.In this review,we summarize the common categories of neurotropic viruses,viral transmission routes in the body,host immune responses,and experimental animal models used for VE study to gain a deeper understanding of recent progress in the pathogenic and immunological mechanisms under neurotropic viral infection.This review should provide valuable resources and perspectives on how to cope with pandemic infections.
基金Supported by the Construction Fund of Key Medical Disciplines of Hangzhou,No.OO20200265the Basic Public Welfare Research Project of Zhejiang Province,No.LGF22H250005+1 种基金General project of Hangzhou Health Science and Technology Plan,No.A20200320Zhejiang Provincial Medical and Health Technology Project,No.2020PY016.
文摘BACKGROUND Alphaherpesvirus belongs to the Herpesviridae family and has large,monopartite double-stranded linear DNA.It mainly infects the skin,mucosa,and nerves,and can affect various hosts,including humans and other animals.Here,we present a case of a patient seen by the gastroenterology department at our hospital who experienced an oral and perioral herpes infection following treatment with a ven-tilator.The patient was treated with oral and topical antiviral drugs,furacilin,oral and topical antibiotics,local epinephrine injection,topical thrombin powder,and nutritional and supportive care.A wet wound healing approach was also implemented with good response.CASE SUMMARY A 73-year-old woman presented to the hospital with a chief complaint of"abdominal pain for 3 d with dizziness for 2 d."She was admitted to the intensive care unit for septic shock and spontaneous peritonitis secondary to cirrhosis and was given antiinflammatory and symptomatic supportive treatment.A ventilator was used to assist breathing for acute respiratory distress syndrome,which developed during her admission.A large area of herpes infection appeared in the perioral region 2 d following noninvasive ventilation.The patient was transferred to the gastroenterology department,at which time she had a body temperature of 37.8 C and a respiratory rate of 18/min.The patient's con-sciousness was intact,and she no longer had abdominal pain or distension,chest tightness,or asthma.At this point,the infected perioral region changed in appearance and was now accompanied by local bleeding with crusting of blood at the wounds.The surface area of the wounds measured approximately 10 cm×10 cm.A cluster blisters appeared on the patient’s right neck,and ulcers developed in her mouth.On a subjective numerical pain scale,the patient reported a pain level of 2.Overall,her diagnoses other than the oral and perioral herpes infection included:(1)Septic shock;(2)spontaneous peritonitis;(3)abdominal infection;(4)decompensated cirrhosis;and(5)hypoproteinemia.Dermatology was consulted regarding the treatment of the patient’s wounds;they suggested treatment with oral antiviral drugs,an intramuscular injection of nutritious nerve drugs,and the application of topical penciclovir and mupirocin around the lips.Stomatology was also consulted and suggested the use of nitrocilin in a local wet application around the lips.CONCLUSION Through multidisciplinary consultation,the patient’s oral and perioral herpes infection was successfully treated with the following combined approach:(1)Application of topical antviral and antibiotic treatments;(2)keeping the wound moist with a wet wound healing strategy;(3)systemic use of oral antiviral drugs;and(4)symptomatic and nutritional supportive care.The patient was discharged from the hospital after successful wound healing.
文摘Vitamin D is a steroid hormone that is naturally produced in the body or obtained through dietary sources,primarily under the influence of UVB radiation.This essential nutrient has a vital role in numerous physiological processes,encom-passing immune function,cell growth,differentiation,insulin regulation,and cardiovascular well-being,along with its pivotal role in sustaining the delicate equilibrium of calcium and phosphate concentrations in the body.Moreover,vitamin D reinforces mucosal defense and bolsters the immune system through immunomodulation,making it a critical component of overall health.Numerous studies have unveiled the profound connection between vitamin D and the predisposition to respiratory tract infections,including well-known viruses such as influenza and the novel severe acute respiratory syndrome coronavirus 2.Vita-min D deficiency has been consistently linked to increased severity of coronavirus disease 2019(COVID-19)and a heightened risk of mortality among afflicted individuals.Retrospective observational studies have further substantiated these findings,indicating that levels of vitamin D are linked with both the occurrence and severity of COVID-19 cases.Vitamin D has its influence on viral infections th-rough a multitude of mechanisms,such as promoting the release of antimicrobial peptides and fine-tuning the responses of the immune system.Additionally,vitamin D is intertwined with the intricate network of the renin–angiotensin system,suggesting a potential impact on the development of complications related to COVID-19.While further clinical trials and extensive research are warranted,the existing body of evidence strongly hints at the possible use of vitamin D as a valuable tool in the prophylaxis and management of COVID-19 and other viral infectious diseases.
文摘BACKGROUND Hepatitis B virus(HBV)and hepatitis C virus(HCV)viral load(VL)estimation is essential for the management of both HBV and HCV infections.Due to a longer turnaround time for VL estimation,many patients drop out from the cascade of care.To achieve the global goals of reducing morbidity and mortality due to HBV/HCV and moving towards their elimination by 2030,molecular diagnostic platforms with faster and random(i.e.single sample)access are needed.AIM To evaluate the performance of the recently launched NeuMoDx 96 random access system with the conventional COBAS^(■)AmpliPrep/COBAS TaqMan system for HBV and HCV VL estimation.METHODS Archived once-thawed plasma samples were retrieved and tested on both platforms.Correlation between the assays was determined by linear regression and Bland-Altman analysis.The study included samples from 186 patients,99 for HBV of which 49 were true infected HBV cases(hepatitis B surface antigen,antihepatitis B core antibody,and HBV DNA-positive)and 87 for HCV assay in which 39 were true positives for HCV infection(anti-HCV and HCV RNA-positive).RESULTS The median VL detected by NeuMoDx for HBV was 2.9(interquartile range[IQR]:2.0-4.3)log_(10)IU/mL and by COBAS it was 3.70(IQR:2.28-4.56)log_(10)IU/mL,with excellent correlation(R2=0.98).In HCV,the median VL detected by NeuMoDx was 4.9(IQR:4.2-5.4)log_(10)IU/mL and by COBAS it was 5.10(IQR:4.07-5.80)log_(10)IU/mL with good correlation(R2=0.96).CONCLUSION The overall concordance between both the systems was 100%for both HBV and HCV VL estimation.Moreover,no genotype-specific bias for HBV/HCV VL quantification was seen in both the systems.Our findings reveal that NeuMoDx HBV and HCV quantitative assays have shown overall good clinical performance and provide faster results with 100%sensitivity and specificity compared to the COBAS AmpliPrep/COBAS TaqMan system.
基金supported by the National Key Research and Development Program(grant number:2022YFC2305304).
文摘Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing.Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing.Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing.Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.
文摘A patient co-infected with COVID-19 and viral hepatitis B can be atmore risk of severe complications than the one infected with a single infection.This study develops a comprehensive stochastic model to assess the epidemiological impact of vaccine booster doses on the co-dynamics of viral hepatitis B and COVID-19.The model is fitted to real COVID-19 data from Pakistan.The proposed model incorporates logistic growth and saturated incidence functions.Rigorous analyses using the tools of stochastic calculus,are performed to study appropriate conditions for the existence of unique global solutions,stationary distribution in the sense of ergodicity and disease extinction.The stochastic threshold estimated from the data fitting is given by:R_(0)^(S)=3.0651.Numerical assessments are implemented to illustrate the impact of double-dose vaccination and saturated incidence functions on the dynamics of both diseases.The effects of stochastic white noise intensities are also highlighted.
基金supported by Key R&D Project in Shandong ProvinceChina(Grant number:2020CXGC010505)+2 种基金Qingdao Science and Technology Demonstration Program for the Benefit of the PeopleShandong ProvinceChina(Grant number:23-7-8-smjk-3-nsh)。
文摘Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.
基金supported by Affiliated Hospital of Youjiang Medical University for Nationalities(No.Y20212615).
文摘Objective:To explore the mechanism by which icariin alleviates viral myocarditis.Methods:CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on cell viability,inflammation,and apoptosis.Moreover,the effects of icariin on ferroptosis and TLR4 signaling were assessed.After AC16 cells were transfected with TLR4 overexpression plasmids,the role of TLR4 in mediating the regulatory effect of icariin in viral myocarditis was investigated.Results:Icariin significantly elevated cell viability and reduced inflammatory factors TNF-α,IL-1β,IL-6,and IL-18.Flow cytometry revealed that icariin decreased apoptosis rate,and the protein expression of Bax and cleaved caspase 3 and 9 in CVB3-induced cardiomyocytes.Additionally,it suppressed ferroptosis including lipid peroxidation and ferrous ion,as well as the TLR4 signaling.However,TLR4 overexpression abrogated the modulatory effects of icariin.Conclusions:Icariin mitigates CVB3-induced myocardial injury by inhibiting TLR4-mediated ferroptosis.Further animal study is needed to verify its efficacy.
基金supported by US National Institutes of Health grants Al147394,AG069264,Al112844,HL170961 and Al154598 to J.S.
文摘Pulmonary macrophages,such as tissue-resident alveolar and interstitial macrophages and recruited monocyte-derived macrophages,are the major macrophages present in the lungs during homeostasis and diseased conditions.While tissue-resident macrophages act as sentinels of the alveolar space and play an important role in maintaining homeostasis and immune regulation,recruited macrophages accumulate in the respiratory tract after acute viral infections.Despite sharing similar anatomical niches,these macrophages are distinct in terms of their origins,surface marker expression,and transcriptional profiles,which impart macrophages with distinguished characteristics in physi-ological and pathophysiological conditions.In this review,we summarize the current view on these macrophage populations,their shared functions,and what makes them distinct from each other in the context of homeostasis andrespiratoryviral infections.
基金Supported by National Natural Science Foundation of China,No.U21A20411.
文摘BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nucleotide polymorphisms of VH,chronic hepatitis B(CHB),chronic hepatitis C(CHC)and T2D were obtained from the BioBank Japan Project,European Bioinformatics Institute,and FinnGen.Inverse variance weighted,MREgger,and weighted median were used to test exposure-outcome associations.The MR-Egger intercept analysis and Cochran’s Q test were used to assess horizontal pleiotropy and heterogeneity,respectively.Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results.RESULTS The MR analysis showed no significant causal relationship between VH and T2D in Europeans[odds ratio(OR)=1.028;95%confidence interval(CI):0.995-1.062,P=0.101].There was a negative causal association between CHB and T2D among East Asians(OR=0.949;95%CI:0.931-0.968,P<0.001),while there was no significant causal association between CHC and T2D among East Asians(OR=1.018;95%CI:0.959-1.081,P=0.551).Intercept analysis and Cochran’s Q test showed no horizontal pleiotropy or heterogeneity(P>0.05).Sensitivity analysis showed that the results were robust.CONCLUSION Among East Asians,CHB is associated with a reduced T2D risk,but this association is limited by HBV load and cirrhosis.Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D,focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHCmediated pathways of hepatic steatosis,liver fibrosis,and cirrhosis.
基金Emergency Research Project for Novel Coronavirus(2019-nCoV)Prevention and Control in Shanxi Province(No.202003D31012/GZ)Jingfang Fuyang Key Laboratory of Shanxi Province(No.202104010910011)Shanxi Provincial Health Commission Key Laboratory Construction Project。
文摘Objective:To investigate the mechanism of Fuyang Jiebiao granule(FYJBKL)in the treatment of viral pneumonia.Methods:Firstly,a network model was constructed using network pharmacology to study the target expression sites of FYJBKL viral pneumonia,so as to determine the main targets and important signal transduction pathways for the treatment of viral pneumonia.Secondly,the main components of the drug and the main target are docked.Then,the fever,sweating and inflammation rat models were established to explore the antipyretic,sweating and anti-inflammatory mechanisms of FYJBKL.Finally,the contents of IL-17,IL-1β,TNF-αand IL-6 in blood samples of rats were analyzed by ELISA method,and the morphological changes of lung tissue were observed by HE staining.Results:Quercetin,luteolin,kaempferol,etc.,and the main mechanism targets are IL-17,IL-1β,TNF-α,IL-6 and so on.Thirty signal pathways were identified by KEGG enrichment analysis,including interleukin-17 signaling pathway(IL-17 signaling pathway),human cytomegalovirus infection pathway(human cytomegalovirus infection),Kaposi's sarcoma associated herpesvirus infection pathway(Kaposi's sarcoma-as-sociated herpesvirus infection)and so on.After the study of molecular docking,we found that the contact efficiency between active substances and possible key targets is good.The high and middle concentration groups of FYJBKL significantly decreased the expression of IL-17,IL-1β,TNF-αand IL-6 in the blood of rats with inflammation(P<0.05).FYJBKL significantly reduced the foot swelling induced by egg white and inhibited the increase of body temperature induced by yeast in rats(P<0.05).HE staining showed that FYJBKL improved pulmonary fibrosis and inflammatory exudation to varying degrees.Conclusion:The effects of FuyangJiebiao granules on the related signal pathways of anti-virus,anti-immune and anti-inflammation as well as biological and cellular processes may be caused by the binding of quercetin,luteolin,kaempferol and other active ingredients to their shared targets.Fuyang Jiebiao granules can improve the related symptoms caused by viral pneumonia,and its mechanism may be related to the activities of TNF,IL-17,IL-6 and other related channels,which are multiple targets of inflammation regulation.
基金Supported by Chinese Foundation for Hepatitis Prevention and Control—Tian Qing Hepatitis Research Fund,No.TQGB20210175Tianjin Key Medical Discipline(Specialty)Construction Project,TJYXZDXK-059B+1 种基金Tianjin Health Science and Technology Project Key Discipline Special,TJWJ2022XK034and Research project of Chinese Traditional Medicine and Chinese Traditional Medicine Combined With Western Medicine of Tianjin Municipal Health and Family Planning Commission,No.2021022.
文摘BACKGROUND Direct-acting antivirals(DAAs)revolutionized the treatment of chronic hepatitis C virus(HCV)-associated disease achieving high rates of sustained virological response(SVR).However,whether DAAs can reduce the occurrence of hepatocellular carcinoma(HCC)in patients with HCV-associated cirrhosis who are at high risk have not been concluded.AIM To investigate the effect of DAAs on the occurrence of HCC in patients with HCVassociated cirrhosis after achieving SVR.METHODS Of 427 inpatients with HCV-associated cirrhosis were enrolled in Tianjin Second People's Hospital from January 2014 to April 2020.118 patients weren’t received antiviral treatment with any reasons named non-antiviral treatment group,and 236 patients obtained from the 309 DAAs treatment patients according to the propensity score matching named DAAs treatment group.Demographic information and laboratory data were collected from baseline and the following up.Kaplan-Meier curve and Log-Rank test were used to compare the incidence and cumulative incidence of HCC between the two groups.Cox proportional risk regression was used to re-evaluate the risk factors for HCC.RESULTS HCC incidence was 4.68/100PY(95%CI,3.09-6.81)in the DAAs treatment group,while it was 3.00/100PY(95%CI,1.50-5.37)in the non-antiviral treatment group,and the relative risk was 1.82(95%CI,0.93-3.53,P>0.05).The incidence of HCC at 12,24,36 and 48 months was 3.39%,6.36%,8.47%and 10.17%in the DAAs treatment group,and it was 0%,0%,3.39%and 9.32%in the non-antiviral treatment group,respectively.Age>58[hazard ratio(HR)=1.089;95%CI,1.033-1.147;P=0.002]and liver stiffness measurement>27.85 kPa(HR=1.043;95%CI,1.022-1.065;P=0.000)were risk factors for HCC in all patients(n=427),and DAAs treatment didn’t show protective efficacy.CONCLUSION DAAs treatment seems failed to reduce the incidence of HCC occurrence in HCV-associated cirrhosis in 48 months,and even increased the incidence of HCC in 36 months.
文摘Viral infections have been considered as a major cause of morbidity and mortality after kidney transplantation in pediatric cohort.Children are at high risk of acquiring virus-related complications due to immunological immaturity and the enhanced alloreactivity risk that led to maintenance of high immunosuppressive regimes.Hence,prevention,early detection,and prompt treatment of such infections are of paramount importance.Among all viral infections,herpes viruses(herpes simplex virus,varicella zoster virus,Epstein-Barr virus,cytomegalovirus),hepatitis B and C viruses,BK polyomavirus,and respiratory viruses(respiratory syncytial virus,parainfluenza virus,influenza virus and adenovirus)are common in kidney transplant recipients.These viruses can cause systemic disease or allograft dysfunction affecting the clinical outcome.Recent advances in technology and antiviral therapy have improved management strategies in screening,monitoring,adoption of prophylactic or preemptive therapy and precise treatment in the immunocompromised host,with significant impact on the outcome.This review discusses the etiology,screening and monitoring,diagnosis,prevention,and treatment of common viral infections in pediatric renal transplant recipients.
文摘Chronic viral hepatitis B (HBV) remains a major public health problem in Burkina Faso. Since access to diagnostic tests and treatments is limited because of their high cost, the majority of the population turn to traditional herbal treatments. This study aimed to evaluate the effectiveness of a plant recipe called Hepatib tiben. It consisted of comparing certain biochemical and molecular parameters of patients infected with HBV that were supported by the recipe. The patients were recruited in Ouagadougou by the traditional health practitioner according to the requirements of the study. Thus 44 patients aged 20 to 61 years and carrier of HBsAg for at least 06 months were treated with Hepatib tiben. The tests were performed in the laboratory before and three months after the treatment. ELISA tests were used to confirm the presence of HBsAg and search for anti-HCV antibodies;transaminases, creatinine were quantified by the “Chem 400” automaton and the viral load of HBV by Real-time PCR. The analysis of the results reveals an improvement of the biochemical and molecular parameters of the patients with the following means (ASAT: 21.02 ± 9.97;ALAT: 21.11 ± 13.27;DNA: 1571.82 ± 3990.97 with p = 0.01 for each). As for HBsAg, its disappearance was observed in 4.55% of patients after treatment. The evaluation of the creatinine parameter explained that the recipe of plants has a tolerated effect on the kidneys of treated patients. These results, while encouraging, need to be complemented by further research for the development of effective phytomedicine to treat and eliminate this viral hepatitis B virus.
基金the Wenzhou Basic Medical and Health Science and Technology Project,No.Y20210307.
文摘BACKGROUND Respiratory viruses are increasingly detected in children with communityacquired pneumonia.Further strategies to limit antibiotic use in children with viral pneumonia are warranted.AIM To explore clinical efficacy of budesonide/formoterol inhalation powder for viral pneumonia in children and its impact on cellular immunity and inflammatory factor production.METHODS A total of 60 children with viral pneumonia were recruited:30 receiving budesonide/formoterol inhalation powder and 30 conventional symptomatic treatment.Outcome measures included peripheral blood levels of inflammatory cytokines,CD4^(+),CD8^(+),Th1,Th2,Th17 and Treg,clinical efficacy,and incidence of adverse reactions.RESULTS Compared with the control group,the observation group showed a significant reduction in interleukin-6 and high-sensitivity C-reactive protein levels after treatment.Compared with the control group,the observation group showed a significant increase in CD4^(+)/CD8^(+)and Th1/Th2 levels,and a decrease in Th17/Treg levels after treatment.The total effective rates in the observation group and the control group were 93.75%and 85.00%,respectively,which was a significant difference(P=0.003).CONCLUSION Budesonide/formoterol inhalation powder significantly improved therapeutic efficacy for viral pneumonia in children.The mechanism of action may be related to downregulation of the inflammatory response and improved cellular immune function.
文摘The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological response in only 45% of cases with significant side effects. The advent of direct-acting antivirals has changed the prognosis of cirrhotic patients with hepatitis C. DAAs have ensured a sustained viral response in the majority of patients. Our work aims to see the evolution of hepatitis C patients at the cirrhosis stage under DAA. We conducted a retrospective study over 15 years (January 2009, January 2024) including all patients with post-viral cirrhosis C, whom we divided into two groups: group A, cirrhotic patients who received ribavirin and interferon, and group B, patients on DAA. From January 2009 to January 2024, we conducted a study of 182 patients with viral hepatitis C, including 102 cirrhotic patients. The mean age was 55 years. 66% of patients were initially treated with the ribavirin interferon combination, while 34% received direct-acting antivirals (DAAs). Since the introduction of DAAs, the most commonly used regimens have been sofosbuvir/daclatasvir with or without ribavirin and sofosbuvir/ledipasvir with or without ribavirin. Group A achieved sustained virological response (SVR) in 60% of cases, with notable side effects. In Group B, SVR was 98.18%, with improved tolerability and fewer side effects than previous treatments. Fifteen patients developed hepatocellular carcinoma (HCC), with a significantly lower mortality rate in those treated with DAAs compared with pegylated dual therapy (p: 0.001).
文摘The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.