BACKGROUND Donor-specific antibodies(DSAs)against human leukocyte antigen(HLA)-DQ are increasingly recognized as major contributors to antibody-mediated rejection(AMR)and graft failure in kidney transplantation.Howeve...BACKGROUND Donor-specific antibodies(DSAs)against human leukocyte antigen(HLA)-DQ are increasingly recognized as major contributors to antibody-mediated rejection(AMR)and graft failure in kidney transplantation.However,their clinical impact remains understudied in Morocco.AIM To evaluate the presence and implications of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.METHODS We retrospectively analyzed the immunological profiles and clinical outcomes of kidney transplant recipients screened for anti-HLA antibodies between 2015 and 2020,who developed anti-HLA-DQ DSAs either before or after transplantation.Anti-HLA antibodies were identified using Luminex®single antigen bead technology,and clinical follow-up included graft function assessment,biopsy interpretation,and evaluation of immunosuppression.RESULTS In the pre-transplant group(n=6 with confirmed donor typing),patients with low to moderate median fluorescence intensity(MFI)anti-HLA-DQ DSAs(MFI 561-1581)underwent successful transplantation and maintained stable graft function under optimized immunosuppression.In contrast,in the post-transplant group(n=6 with confirmed donor typing),the emergence of de novo anti-HLA-DQ DSAs was consistently associated with AMR,with MFI values reaching up to 19473,with biopsy-proven AMR in 5 of 6 cases and suspicion of AMR in 1 case.Two representative cases are detailed to illustrate the clinical impact of DQ DSAs:one patient developed high-level anti-DQB1*02 de novo DSA(MFI 12029)with persistent AMR after 5 years,while another developed anti-DQA1*05:01 de novo DSA after an early AMR episode but maintained stable graft function after 5 years(creatinine 1.48 mg/dL).CONCLUSION Our findings underscore the clinical significance of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.While preformed DSAs with low immunogenicity may permit successful transplantation,de novo DSAs strongly correlate with AMR.Proactive monitoring,including routine DSA screening and HLA-DQ typing,could improve graft outcomes by enabling early intervention and better donor selection.展开更多
Chimeric antigen receptor T(CAR-T)cell therapy represents a major advance in cancer immunotherapy,offering targeted treatment options,particularly for hematologic malignancies.This review comprehensively explores the ...Chimeric antigen receptor T(CAR-T)cell therapy represents a major advance in cancer immunotherapy,offering targeted treatment options,particularly for hematologic malignancies.This review comprehensively explores the structural evolution,production processes,and cytotoxic mechanisms underlying CAR-T function.Therapy involves engineering autologous T cells with synthetic receptors that allow major histocompatibility complex-independent recognition of tumor-associated antigens.Key structural components such as antigen recognition domains,spacers,transmembrane,and intracellular domains are optimized to enhance specificity,persistence,and cytotoxicity.CAR-T therapy exerts antitumor effects via granzyme-perforin degranulation,Fas/Fas ligand signaling,and cytokine secretion.Over time,the development of second-to fifth-generation CARs has incorporated costimulatory molecules,transcriptional regulation,and logic-gated control to improve efficacy and safety.Additionally,novel engineering strategies such as dual CARs,tandem CARs,SynNotch systems,and universal or inhibitory CARs have expanded antigen targeting and reduced offtumor toxicity.Emerging gene delivery technologies,including viral vectors,transposons,CRISPR/Cas9,and RNA-based electroporation,are improving CART production.Despite notable clinical success,particularly in CD19-and B-cell maturation antigen-targeted therapies,CAR-T applications face challenges,including cell exhaustion,antigen escape,and therapy-induced toxicities,such as cytokine release syndrome and neurotoxicity.Ongoing efforts in engineering innovation,clinical trials,and regulatory support continue to shape CAR-T therapy into a safer,more precise tool for cancer treatment.This review highlights current advances while outlining the barriers and future prospects of CAR-T immunotherapy.展开更多
Immune adjuvants are extremely important in tumor vaccines,which can amplify antigen-specific immune responses and enhance anti-tumor efficacy.Nevertheless,well-designed adjuvants and rational combination of adjuvants...Immune adjuvants are extremely important in tumor vaccines,which can amplify antigen-specific immune responses and enhance anti-tumor efficacy.Nevertheless,well-designed adjuvants and rational combination of adjuvants and antigens still remain a challenge in tumor vaccines.In this study,we designed and formulated carrier-free double-adjuvant nanoparticles(FPC-NPs)by self-assembling of fluoroalkane-grafted polyethylenimide(PEI)(Toll-like receptor 4(TLR4)agonist)and cytosine-phosphateguanine(CpG)(TLR9 agonist),and then obtained personalized tumor vaccines(FPC-NPs@TAAs)by electrostatic adsorption of tumor-associated antigens(TAAs)on the surface of FPC-NPs.The results showed that FPC-NPs@TAAs could promote cellular internalization of adjuvants,deliver antigens and adjuvants to the same antigen-presenting cell,which can effectively activate dendritic cells,encourage cross-presentation of antigens,and reduce the proportion of M2-type macrophages.Our work presents a simple method to realize the dual adjuvant combination of TLR4 and TLR9 via well-designed carrier-free nanoparticles,showing great promise for developing personalized tumor vaccines to enhance the efficacy of immunotherapy.展开更多
BACKGROUND Prevalence of the main rheumatic diseases in the Republic of Sakha(Yakutia)[RS(Y)],one of the regions of the Russian Federation,differs from the other regions of the Russian Federation due to its ethnic and...BACKGROUND Prevalence of the main rheumatic diseases in the Republic of Sakha(Yakutia)[RS(Y)],one of the regions of the Russian Federation,differs from the other regions of the Russian Federation due to its ethnic and geographic features.Knowledge regarding the prevalence and structure of juvenile idiopathic arthritis(JIA)allows us to shape the work of the pediatric rheumatology service in the region correctly,and optimize the healthcare system and the need for medica-tions.AIM To describe the epidemiological,demographic,clinical,and laboratory characteristics of children with JIA in the RS(Y)and evaluate the main outcomes.METHODS This retrospective cohort study assessed all the data from the medical histories of the patients(n=225)diagnosed with JIA(2016-2023)in the Cardiorheumatology Department of the M.E.Nikolaev National Center of Medicine.Pearson'sχ²test,Fisher's exact test,Mann–Whitney and Kruskal-Wallis tests were used for statistical analyses.RESULTS The ethnic prevalence of JIA is higher in Sakha than in Russian children at 110.1 per 100000 children and 69.4 per 100000 children,respectively.The prevalence of JIA among boys and girls in Sakha was similar,unlike in Russians,where the number of girls predominated.The JIA categories were as follows:(1)Systemic arthritis:3.5%;(2)Oligoarthritis(persistent and extended):33.8%;(3)Rheumatoid factor(RF)(+)polyarthritis:0.9%;(4)RF(-)polyarthritis:14.7%;(5)Enthesitis-related arthritis(ERA):44%;and(6)Psoriatic arthritis:3.1%.Prevalence of the ERA category was 4.4 times higher in Sakha children,but the prevalence of systemic arthritis was 2.9 times lower compared to Russians(P=0.0005).The frequency of uveitis was 10.2%,and the frequency of human leukocyte antigen(HLA)B27 was 39.6%in JIA children.Biologic treatment was received by 40.4%of JIA children and 45.3%achieved remission.CONCLUSION Higher JIA prevalence,male and ERA predominance,related to a higher frequency of HLA B27 are typical in RS(Y).These data might improve the pediatric rheumatology health service.展开更多
BACKGROUND Metastatic colorectal cancer(mCRC)is a global health challenge with a poor prognosis.Prognostic markers are critical for survival prediction.METHODS This multicenter,retrospective study measured baseline ca...BACKGROUND Metastatic colorectal cancer(mCRC)is a global health challenge with a poor prognosis.Prognostic markers are critical for survival prediction.METHODS This multicenter,retrospective study measured baseline carcinoembryonic antigen and carbohydrate antigen 19-9 levels to calculate a TMI as the geometric mean of values normalized to their upper limits of normal.Receiver operating characteristic curve analysis assessed TMI’s prognostic accuracy,and patients were stratified into high-TMI(≥1.39)and low-TMI(<1.39)groups.The primary endpoint was overall survival(OS),with progression-free survival and treatment response as secondary endpoints.RESULTS The study included 305 mCRC patients with a median follow-up of 22.9 months.The median OS for high-TMI patients was 29.5 months,significantly lower than the 45.6 months observed in the low-TMI group(P=0.02).The 2-year OS rates for the high-and low-TMI groups were 59.4%and 72.9%,respectively.Median progression-free survival was also shorter for the high-TMI group(14.0 vs 16.0 months,P=0.84).High TMI is an independent prognostic factor for worse OS.CONCLUSION TMI is a simple,cost-effective prognostic tool for mCRC,with high TMI associated with poorer survival outcomes.展开更多
Hepatitis B virus(HBV)infection is a global health concern.The current sequen-tial endpoints for the treatment of HBV infection include viral suppression,hepatitis B e antigen(HBeAg)seroconversion,functional cure,and ...Hepatitis B virus(HBV)infection is a global health concern.The current sequen-tial endpoints for the treatment of HBV infection include viral suppression,hepatitis B e antigen(HBeAg)seroconversion,functional cure,and covalently closed circular DNA(cccDNA)clearance.Serum hepatitis B core-related antigen(HBcrAg)is an emerging HBV marker comprising three components:HBeAg,hepatitis B core antigen,and p22cr.It responds well to the transcriptional activity of cccDNA in the patient's liver and is a promising alternative marker for serolo-gical testing.There is a strong correlation,and a decrease in its level corresponds to sustained viral suppression.In patients with chronic hepatitis B(CHB),serum HBcrAg levels are good predictors of HBeAg seroconversion(both spontaneous and after antiviral therapy),particularly in HBeAg-positive patients.Both low baseline HBcrAg levels and decreasing levels early in antiviral therapy favored HBsAg seroconversion,which may serve as a good surrogate option for treatment endpoints.In this review,we summarize the role of serum HBcrAg in the treat-ment of CHB.Therefore,long-term continuous monitoring of serum HBcrAg levels contributes to the clinical management of patients with CHB and optimizes the choice of treatment regimen,making it a promising marker for monitoring HBV cure.展开更多
In Western countries, clinical trials on prostate cancer screening demonstrated a limited benefit for patient survival. In the Asia-Pacific region, including Japan, the rate of prostate-specific antigen （PSA） testin...In Western countries, clinical trials on prostate cancer screening demonstrated a limited benefit for patient survival. In the Asia-Pacific region, including Japan, the rate of prostate-specific antigen （PSA） testing remains very low compared with Western countries, and the benefits of population-based screening remain unclear. This review describes the current status of population screening and diagnosis for prostate cancer in Japan and discusses the efficacy of population screening for the Asian population. Since the 1990s, screening systems have been administered by each municipal government in Japan, and decreases in the prostate cancer mortality rate are expected in some regions where the exposure rate to PSA screening has increased markedly. A population-based screening cohort revealed that the proportion of metastatic disease in cancer detected by screening gradually decreased according to the increased exposure rate, and a decreasing trend in the proportion of cancer with high serum PSA levels after population screening was started. The prognosis of the prostate cancer detected by population screening was demonstrated to be more favorable than those diagnosed outside of the population screening. Recent results in screening cohorts demonstrated the efficacy of PSA. These recent evidences regarding population-based screening in Japan may contribute to establishing the optimal prostate cancer screeninK system in Asian individuals.展开更多
AIM To assess cancer-testis antigens(CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.METHODS Eighty-three gastric cancer patients were evaluated in this stu...AIM To assess cancer-testis antigens(CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.METHODS Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1(KK-LC-1), melanoma antigen(MAGE)-A1, MAGE-A3 and New York esophageal cancer-1(NYESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained. Statistical comparisons between the expression of each CTA and each clinicopathological background were performed using the χ2 test. RESULTS The expression rates of KK-LC-1, MAGE-A1, MAGE-A3, and NY-ESO-1 were 79.5%, 32.5%, 39.8%, and 15.7%, respectively. In early stage gastric cancer specimens, the expression of KK-LC-1 was 79.4%, which is comparable to the 79.6% observed in advanced stage specimens. The expression of KK-LC-1 was not significantly associated with clinicopathological factors, while there were considerable differences in the expression rates of MAGE-A1 and MAGE-A3 with vs without lymphatic invasion(MAGE-A1, 39.3% vs 13.6%, P = 0.034; MAGE-A3, 47.5% vs 18.2%, P = 0.022) and/or vascular invasion(MAGE-A1, 41.5% vs 16.7%, P = 0.028; MAGE-A3, 49.1% vs 23.3%, P = 0.035) and, particularly, MAGE-A3, in patients with early vs advanced stage(36.5% vs 49.0%, P = 0.044), respectively. Patients expressing MAGE-A3 and NYESO-1 were older than those not expressing MAGE-A3 and NY-ESO-1(MAGE-A3, 73.7 ± 7.1 vs 67.4 ± 12.3, P = 0.009; NY-ESO-1, 75.5 ± 7.2 vs 68.8 ± 11.2, P = 0.042). CONCLUSION The KK-LC-1 expression rate was high even in patients with stage I cancer, suggesting that KK-LC-1 is a useful biomarker for early diagnosis of gastric cancer.展开更多
BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of gr...BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of great significance to find reliable prog-nostic indicators to guide the treatment and management of patients with gastric cancer.AIM To explore the relationship between serum levels of five biomarkers[carcinoem-bryonic antigen(CEA),carbohydrate antigen(CA)19-9,CA72-4,CA24-2,and ferritin]and prognosis in patients with gastric cancer.METHODS This study included 200 patients with gastric adenocarcinoma,and conducted an in-depth analysis of their baseline characteristics,relationship between tumor markers and staging,and prognosis.The study found that CA19-9 has a signi-ficant correlation with tumor stage,the average levels of CA24-2,CEA,CA72-4 and ferritin were slightly increased disregarding the stage of tumor.Survival analysis showed that increases in CEA,CA19-9,CA24-2,and ferritin were all associated with shortened overall survival of patients.Further multivariate ana-lysis revealed that elevated serum CA72-4 levels were an inde-pendent adverse prognostic factor.RESULTS This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA,CA19-9,CA72-4,CA24-2 and ferritin in patients with gastric cancer and prognosis,and can be used as important indicators for prognostic evaluation of gastric cancer.In particular,markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis.CONCLUSION Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer,and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.展开更多
In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in ped...In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.展开更多
[Objective]To design and express a recombinant protein rMKIBV incorporating confirmed antigenic epitopes of infectious bronchitis virus(IBV)as a vaccine to provide comprehensive protection.Additionally,it explores the...[Objective]To design and express a recombinant protein rMKIBV incorporating confirmed antigenic epitopes of infectious bronchitis virus(IBV)as a vaccine to provide comprehensive protection.Additionally,it explores the potential of polyclonal yolk antibodies(IgY)harvested from laying hens immunized with the rMKIBV vaccine in the prevention and control of IBV.[Methods]The antigenic epitope sequences of IBV,obtained from online databases,were compared with sequences of representative IBV strains from GenBank.Flexible peptides were designed to link all antigenic peptides.The constructed amino acid sequence was analyzed,reverse-translated,codon-optimized,and then inserted into the pET-28a(+)cloning vector.The recombinant vector was introduced into Escherichia coli for expression.The purified,desalted,and endotoxin-removed rMKIBV protein was used as a vaccine to immunize animals for investigation of its immunogenicity and ability to stimulate specific IgY production in laying hens.[Results]The retrieved IBV antigenic epitope sequences showed high similarity with the published N and S protein sequences of 22 representative IBV strains.The predicted isoelectric point and molecular weight of rMKIBV were 10.25 and 63.39 kDa,respectively.The secondary structure of rMKIBV included a high proportion of random coils,which suggested strong antigenicity.High-purity rMKIBV was obtained from E.coli transformed with the recombinant plasmid pET-28a-mkibv.This protein specifically bound to anti-His-tag antibodies,N protein antibodies,and S protein antibodies.The mice immunized with this protein showed increases in the spleen index(P<0.05),elevations in the levels of serum-specific IgG antibodies(P<0.01)and IFN-γ(P<0.05),and no significant change in the IL-2 level.Immunized laying hens successfully produced IgY in egg yolks,with specific IgY antibody levels significantly increasing.Moreover,the IgY antibody titer gradually rose after immunization,reaching the peak after about 50 days and then gradually declining to reach a stable level.[Conclusion]We successfully constructed and expressed the recombinant protein rMKIBV.The protein demonstrated good immunogenicity,stimulating specific antibody production in both mice and laying hens.Notably,the IgY extracted from the yolks of immunized laying hens offers a novel approach to IBV prevention and control.These findings hold significant scientific and practical value for the development of vaccines against IBV.展开更多
Chimeric antigen receptor-T(CAR-T)cell therapy is a precise immunotherapy for lymphoma.However,its long-term efficacy faces many challenges related to tumor cell heterogeneity,interference from immunosuppressive micro...Chimeric antigen receptor-T(CAR-T)cell therapy is a precise immunotherapy for lymphoma.However,its long-term efficacy faces many challenges related to tumor cell heterogeneity,interference from immunosuppressive microenvironments,CAR-T cell exhaustion,and unmanageable adverse events.Diverse modifications have been introduced into conventional CAR-T cells to overcome these obstacles;examples include addition of recognition sites to prevent immune escape,coupling of cytokine domains to enhance killing ability,blocking of immune checkpoint signals to resist tumor microenvironments,and inclusion of suicide systems or safety switches to improve safety and flexibility.With increasing understanding of the importance of metabolism and epigenetics in cancer and cytotherapy,glycolysis,methylation,and acetylation have become crucial CAR-T cell therapeutic targets.Universal and in situ CAR-T cells are also expected to be used in clinical applications,thus providing hope to patients with relapsed/refractory lymphomas.展开更多
Mycobacterium tuberculosis(Mtb)employs multiple mechanisms,such as phagocytosis and autophagy,to evade innate immune clearance and establish infection.In the present study,we identified the ESX-1 secretion-associated ...Mycobacterium tuberculosis(Mtb)employs multiple mechanisms,such as phagocytosis and autophagy,to evade innate immune clearance and establish infection.In the present study,we identified the ESX-1 secretion-associated protein EspL,which promotes Mtb survival by inhibiting phagosome maturation and autophagy initiation.EspL knockout decreased Mtb intracellular survival,while EspL overexpression increased bacterial survival by interfering with phagocytosis and autophagy.EspL interacts with ULK1 and promotes its phosphorylation at Ser^(757),leading to the inhibition of autophagy initiation.Additionally,overexpression of EspL reduced antigen presentation and T-cell responses both in vitro and in vivo.Our findings revealed that EspL interferes with autophagy and antigen presenta-tion by suppressing ULK1 activation.These insights provide a novel understanding of Mtb pathogenicity.展开更多
BACKGROUND Gastric cancer(GC)is an aggressive malignancy of the gastrointestinal tract characterized by high recurrence rates following radical gastrectomy.To enhance treatment efficacy,reduce recurrence,and improve p...BACKGROUND Gastric cancer(GC)is an aggressive malignancy of the gastrointestinal tract characterized by high recurrence rates following radical gastrectomy.To enhance treatment efficacy,reduce recurrence,and improve patient survival,adjuvant chemotherapy is commonly administered based on established postoperative guidelines.Despite advancements in chemotherapy delivery,the overall response rate remains below 50%,primarily due to the lack of targeted therapies tailored to specific patient populations.AIM To explore sensitive biomarkers to assess the efficacy of postoperative adjuvant chemotherapy in appropriate patient subgroups.METHODS This study retrospectively analyzed 1628 patients who underwent radical gastrectomy for GC at our hospital in 2017 and 2018,with a subsequent five-year follow-up.Patients were divided based on whether they received postoperative adjuvant chemotherapy.The study aimed to determine optimal cutoff values for various biomarkersneutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio,carcinoembryonic antigen(CEA),carbohydrate antigen(CA)199,CA724,and CA242-using receiver operating characteristic(ROC)curves.Based on the optimal ROC cut-off,a novel combined metric,NLR-CEA,was developed to assess the efficacy of adjuvant chemotherapy following GC surgery.RESULTS Cox subgroup analysis demonstrated that postoperative adjuvant chemotherapy significantly improved overall survival in the NLR-CEA_Low group with a rate of 0.41(0.26-0.63).In the NLR-CEA_Middle group,the protective effect was observed at 0.69(0.54-0.87),while in the NLR-CEA_High group,it was 0.73(0.53-0.99).Notably,a 32%difference in the efficacy of chemotherapy was observed between the NLR-CEA_Low and NLR-CEA_High groups.CONCLUSION NLR-CEA is an effective biomarker for evaluating the efficacy of postoperative adjuvant chemotherapy in GC.Patients with NLR-CEA_Low exhibit significantly better responses to chemotherapy compared to those with NLRCEA_High.展开更多
BACKGROUND Serum carcinoembryonic antigen(CEA)levels and magnetic resonance imaging(MRI)findings are widely used for the diagnosis and treatment of rectal cancer;however,research investigating their correlation remain...BACKGROUND Serum carcinoembryonic antigen(CEA)levels and magnetic resonance imaging(MRI)findings are widely used for the diagnosis and treatment of rectal cancer;however,research investigating their correlation remains limited.AIM To investigate the correlation between baseline MRI features and serum CEA levels in patients diagnosed with primary rectal cancer.METHODS Eighty patients(age:42-78 years)diagnosed with primary rectal cancer were enrolled.Baseline MRI examinations were performed to evaluate tumor size,T stage,circumferential resection margin status,extramural vascular invasion(EMVI),and lymph node metastasis.Serum CEA levels were concurrently measured.Statistical methods were used to analyze correlations.RESULTS Tumor size,T stage,EMVI,and lymph node metastasis were significantly correlated with serum CEA levels(P<0.05).Multivariate analysis identified T stage and lymph node metastasis as independent factors influencing serum CEA levels.CONCLUSION This study confirmed the correlation between baseline MRI features and serum CEA levels in patients with primary rectal cancer,highlighting their potential utility for precise diagnosis,staging,and prognostic evaluation.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common malignancies,with high recurrence rates after treatment.Identifying reliable biomarkers for predicting recurrence is essential for improving patient ou...BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common malignancies,with high recurrence rates after treatment.Identifying reliable biomarkers for predicting recurrence is essential for improving patient outcomes.Hepatitis B corerelated antigen(HBcrAg)has shown potential as a predictive marker for HCC recurrence.AIM To evaluate the association between HBcrAg levels and the risk of HCC recurrence.METHODS A systematic review was conducted following PRISMA guidelines.PubMed,EMBASE,Web of Science,and the Cochrane Library were searched without restrictions on date or language.Observational studies reporting hazard ratios(HRs)for HBcrAg as a predictor of HCC recurrence were included.Data extraction and quality assessment were performed independently by two reviewers.Statistical analyses used a random-effects model to account for heterogeneity(I²≥50%),and sensitivity analysis was performed to ensure the robustness of the results.RESULTS A total of 1339 articles were initially identified,and 17 studies were included in the final meta-analysis after screening.The pooled analysis showed a significant association between elevated HBcrAg levels and HCC recurrence(HR=4.42,95%confidence interval:3.43-5.41)with substantial heterogeneity(I²=92.6%).Subgroup analysis revealed higher pooled HRs in studies with≥500 participants(HR=4.18)and HBcrAg cut-offs≥4.0 LogU/mL(HR=5.29).Studies with≥10 years of follow-up showed a lower HR(2.89)compared to those with<10 years(3.27).Patients treated with nucleos(t)ide analogs had a pooled HR of 1.98,while those without nucleos(t)ide analog had a higher HR of 3.87.Sensitivity analysis confirmed the robustness of the results,with no significant publication bias detected.CONCLUSION This meta-analysis provides strong evidence that elevated HBcrAg levels are associated with an increased risk of HCC recurrence.HBcrAg may serve as a valuable biomarker for predicting recurrence,aiding personalized management and surveillance strategies for HCC patients.展开更多
Background:The growth of the B-cell lymphoma subtype,Hodgkin lymphoma(HL),is associated with increased autophagy.A mycobacterial antigen,Ag85,has been reported to inhibit cell autophagy under a variety of conditions.W...Background:The growth of the B-cell lymphoma subtype,Hodgkin lymphoma(HL),is associated with increased autophagy.A mycobacterial antigen,Ag85,has been reported to inhibit cell autophagy under a variety of conditions.Whether Ag85 could inhibit autophagy in HL is unknown.Methods:Lymph node samples from patients with HL and healthy controls were collected to assess proliferation and autophagy.The human HL cell line,L-428,was cultured and subjected to Ag85B treatment.Autophagy in L-428 cells was evaluated through western blotting analysis,immunohistochemistry,and transmission electron microscopy.Apoptosis in these cells was measured using flow cytometry and western blotting.The associated signaling pathways were also analyzed utilizing western blotting.The in vivo impact of Ag85B was studied using BALB/c Nude mice xenografted with L-428 cells.Results:We observed increased proliferation and autophagy in primary lymphoma tissues of patients.Administration of Ag85B inhibited the proliferation and autophagy of HL cell lines.Moreover,Ag85B promoted apoptotic pathway activation in vitro,which might be associated with mitochondrial dysfunction.Mechanistically,Ag85B inhibits autophagy by activating the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B/mechanistic target of rapamycin kinase(PI3K/AKT/mTOR)and mitogen-activated protein kinase(MAPK)pathways.Ag85B also inhibited lymphoma growth in mice xenografted with HL cell lines,but no potential toxicity was observed.Conclusion:Altogether,these results suggest that Ag85B inhibits HL growth via autophagy regulation.Current treatments for HL are associated with adverse events;therefore,Ag85B-mediated autophagy inhibition might be a promising strategy in to treat HL.展开更多
BACKGROUND The World Health Organization(WHO)recommends lumbar puncture(LP)procedures to assess the diagnosis of cryptococcal meningitis(CM)among patients with advanced human immunodeficiency virus(HIV)disease(AHD)wit...BACKGROUND The World Health Organization(WHO)recommends lumbar puncture(LP)procedures to assess the diagnosis of cryptococcal meningitis(CM)among patients with advanced human immunodeficiency virus(HIV)disease(AHD)with positive serum cryptococcal antigen(CrAg)and do not have evidence of CM.AIM To estimate pooled prevalence of uptake of LP,CM and mortality among patients with AHD.METHODS PubMed,Cochrane Library and EMBASE were searched for articles published between January 2011 and December 2024.LP uptake was defined as percentage of people who underwent LP procedures among those with AHD(CD4≤200 cells/mm3 or WHO stage III/IV)and positive serum CrAg.Using random effects models,we computed the pooled estimate of LP uptake,CM and mortality and 95%CI.Stratified analyses were used to compare uptake of LP between studies that involved multiple vs single sites,and mortality analyses between patients with positive and negative serum CrAg were performed.Sensitivity analysis on LP uptake was done by excluding prospective cohort studies that reported 100%uptake.RESULTS A total of 32 studies with 46890 people with AHD screened for serum CrAg and 2730(5.8%)had positive serum CrAg.Overall,pooled prevalence of LP uptake was 67.7%(95%CI:54.0-81.5).The overall pooled prevalence of CM was 54.3%(95%CI:39.7-69.0),and mortality was 6.2%(95%CI:4.5-8.0).There is disparities in the pooled prevalence of LP uptake with studies involving multiple sites having lower prevalence compared to those that involved single sites(54.8%vs 84.7%,P=0.004).By excluding prospective cohort studies that reported 100%uptake,the overall LP uptake was 54.5%(95%CI:38.8-70.1).The pooled prevalence of CM was significantly lower among studies that involved multiple sites compared to those that involved single sites(6.8%vs 8.1%,P≤0.001).Mortality was significantly twice as high among patients who had positive serum CrAg compared to those who had negative serum CrAg[risk ratio=2.0(95%CI:1.6-2.5),P≤0.001].CONCLUSION Nearly three to five in 10 people with AHD with positive serum CrAg did not have LP procedures done,indicating significant gaps in identifying patients with CM.Establishing a confirmed diagnosis of CM is critical to avoid exposing patients to subtherapeutic levels of antifungals preemptively.Capacity to perform LP and patient refusals are among the reasons for not performing the procedure.Capacity building in training health care providers to perform LP procedures and professional counselling to obtain patient consent are critical for appropriate treatment to reduce mortality associated with CM infection.展开更多
Hepatitis B virus infection remains a significant global health challenge,particularly in endemic regions like Vietnam.This article examines the groundbreaking study by Nguyen et al,which investigates the relationship...Hepatitis B virus infection remains a significant global health challenge,particularly in endemic regions like Vietnam.This article examines the groundbreaking study by Nguyen et al,which investigates the relationship between human leukocyte antigen-DP/DQ polymorphisms and hepatitis B virus-related liver disease progression.Through advanced multi-clustering analysis,the study reveals that the A-A-A haplotype(rs2856718-rs3077-rs9277535)provides protection against disease progression,while the G-G-G haplotype correlates with increased hepatocellular carcinoma susceptibility.The integration of machine learning approaches with genetic data offers promising avenues for refined disease prediction and personalized therapeutic strategies.This article discusses the implications for expanding study populations,implementing longitudinal cohort studies,and leveraging artificial intelligence for improved patient outcomes.展开更多
Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related mortality worldwide1.The primary treatment options for this disease are surgical resection and liver transplantation.Unfortunately,most HCC ca...Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related mortality worldwide1.The primary treatment options for this disease are surgical resection and liver transplantation.Unfortunately,most HCC cases are diagnosed in advanced stages and are inoperable.Even after surgery,the long-term prognosis remains unsatisfactory,because of a high recurrence rate.展开更多
基金Supported by the National Science and Technology Research Center(Morocco)“PhD-Associate Scholarship-PASS”Program,No.88UH2C2023.
文摘BACKGROUND Donor-specific antibodies(DSAs)against human leukocyte antigen(HLA)-DQ are increasingly recognized as major contributors to antibody-mediated rejection(AMR)and graft failure in kidney transplantation.However,their clinical impact remains understudied in Morocco.AIM To evaluate the presence and implications of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.METHODS We retrospectively analyzed the immunological profiles and clinical outcomes of kidney transplant recipients screened for anti-HLA antibodies between 2015 and 2020,who developed anti-HLA-DQ DSAs either before or after transplantation.Anti-HLA antibodies were identified using Luminex®single antigen bead technology,and clinical follow-up included graft function assessment,biopsy interpretation,and evaluation of immunosuppression.RESULTS In the pre-transplant group(n=6 with confirmed donor typing),patients with low to moderate median fluorescence intensity(MFI)anti-HLA-DQ DSAs(MFI 561-1581)underwent successful transplantation and maintained stable graft function under optimized immunosuppression.In contrast,in the post-transplant group(n=6 with confirmed donor typing),the emergence of de novo anti-HLA-DQ DSAs was consistently associated with AMR,with MFI values reaching up to 19473,with biopsy-proven AMR in 5 of 6 cases and suspicion of AMR in 1 case.Two representative cases are detailed to illustrate the clinical impact of DQ DSAs:one patient developed high-level anti-DQB1*02 de novo DSA(MFI 12029)with persistent AMR after 5 years,while another developed anti-DQA1*05:01 de novo DSA after an early AMR episode but maintained stable graft function after 5 years(creatinine 1.48 mg/dL).CONCLUSION Our findings underscore the clinical significance of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.While preformed DSAs with low immunogenicity may permit successful transplantation,de novo DSAs strongly correlate with AMR.Proactive monitoring,including routine DSA screening and HLA-DQ typing,could improve graft outcomes by enabling early intervention and better donor selection.
文摘Chimeric antigen receptor T(CAR-T)cell therapy represents a major advance in cancer immunotherapy,offering targeted treatment options,particularly for hematologic malignancies.This review comprehensively explores the structural evolution,production processes,and cytotoxic mechanisms underlying CAR-T function.Therapy involves engineering autologous T cells with synthetic receptors that allow major histocompatibility complex-independent recognition of tumor-associated antigens.Key structural components such as antigen recognition domains,spacers,transmembrane,and intracellular domains are optimized to enhance specificity,persistence,and cytotoxicity.CAR-T therapy exerts antitumor effects via granzyme-perforin degranulation,Fas/Fas ligand signaling,and cytokine secretion.Over time,the development of second-to fifth-generation CARs has incorporated costimulatory molecules,transcriptional regulation,and logic-gated control to improve efficacy and safety.Additionally,novel engineering strategies such as dual CARs,tandem CARs,SynNotch systems,and universal or inhibitory CARs have expanded antigen targeting and reduced offtumor toxicity.Emerging gene delivery technologies,including viral vectors,transposons,CRISPR/Cas9,and RNA-based electroporation,are improving CART production.Despite notable clinical success,particularly in CD19-and B-cell maturation antigen-targeted therapies,CAR-T applications face challenges,including cell exhaustion,antigen escape,and therapy-induced toxicities,such as cytokine release syndrome and neurotoxicity.Ongoing efforts in engineering innovation,clinical trials,and regulatory support continue to shape CAR-T therapy into a safer,more precise tool for cancer treatment.This review highlights current advances while outlining the barriers and future prospects of CAR-T immunotherapy.
基金supported by Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0500800)National Natural Science Foundation of China(Nos.82302390,82172090 and 82072059)+4 种基金CAMS Innovation Fund for Medical Sciences(Nos.2021-I2M-1-058,2022-I2M-2-003 and 2023-I2M-2-008)China Postdoctoral Science Foundation(No.2022M720502)Tianjin Municipal Natural Science Foundation(Nos.22JCQNJC00070 and 24ZXZSSS00200)CAMS Union Young Scholars Support Program(No.2022051)Fundamental Research Funds for the Central Universities(No.2019PT320028).
文摘Immune adjuvants are extremely important in tumor vaccines,which can amplify antigen-specific immune responses and enhance anti-tumor efficacy.Nevertheless,well-designed adjuvants and rational combination of adjuvants and antigens still remain a challenge in tumor vaccines.In this study,we designed and formulated carrier-free double-adjuvant nanoparticles(FPC-NPs)by self-assembling of fluoroalkane-grafted polyethylenimide(PEI)(Toll-like receptor 4(TLR4)agonist)and cytosine-phosphateguanine(CpG)(TLR9 agonist),and then obtained personalized tumor vaccines(FPC-NPs@TAAs)by electrostatic adsorption of tumor-associated antigens(TAAs)on the surface of FPC-NPs.The results showed that FPC-NPs@TAAs could promote cellular internalization of adjuvants,deliver antigens and adjuvants to the same antigen-presenting cell,which can effectively activate dendritic cells,encourage cross-presentation of antigens,and reduce the proportion of M2-type macrophages.Our work presents a simple method to realize the dual adjuvant combination of TLR4 and TLR9 via well-designed carrier-free nanoparticles,showing great promise for developing personalized tumor vaccines to enhance the efficacy of immunotherapy.
文摘BACKGROUND Prevalence of the main rheumatic diseases in the Republic of Sakha(Yakutia)[RS(Y)],one of the regions of the Russian Federation,differs from the other regions of the Russian Federation due to its ethnic and geographic features.Knowledge regarding the prevalence and structure of juvenile idiopathic arthritis(JIA)allows us to shape the work of the pediatric rheumatology service in the region correctly,and optimize the healthcare system and the need for medica-tions.AIM To describe the epidemiological,demographic,clinical,and laboratory characteristics of children with JIA in the RS(Y)and evaluate the main outcomes.METHODS This retrospective cohort study assessed all the data from the medical histories of the patients(n=225)diagnosed with JIA(2016-2023)in the Cardiorheumatology Department of the M.E.Nikolaev National Center of Medicine.Pearson'sχ²test,Fisher's exact test,Mann–Whitney and Kruskal-Wallis tests were used for statistical analyses.RESULTS The ethnic prevalence of JIA is higher in Sakha than in Russian children at 110.1 per 100000 children and 69.4 per 100000 children,respectively.The prevalence of JIA among boys and girls in Sakha was similar,unlike in Russians,where the number of girls predominated.The JIA categories were as follows:(1)Systemic arthritis:3.5%;(2)Oligoarthritis(persistent and extended):33.8%;(3)Rheumatoid factor(RF)(+)polyarthritis:0.9%;(4)RF(-)polyarthritis:14.7%;(5)Enthesitis-related arthritis(ERA):44%;and(6)Psoriatic arthritis:3.1%.Prevalence of the ERA category was 4.4 times higher in Sakha children,but the prevalence of systemic arthritis was 2.9 times lower compared to Russians(P=0.0005).The frequency of uveitis was 10.2%,and the frequency of human leukocyte antigen(HLA)B27 was 39.6%in JIA children.Biologic treatment was received by 40.4%of JIA children and 45.3%achieved remission.CONCLUSION Higher JIA prevalence,male and ERA predominance,related to a higher frequency of HLA B27 are typical in RS(Y).These data might improve the pediatric rheumatology health service.
文摘BACKGROUND Metastatic colorectal cancer(mCRC)is a global health challenge with a poor prognosis.Prognostic markers are critical for survival prediction.METHODS This multicenter,retrospective study measured baseline carcinoembryonic antigen and carbohydrate antigen 19-9 levels to calculate a TMI as the geometric mean of values normalized to their upper limits of normal.Receiver operating characteristic curve analysis assessed TMI’s prognostic accuracy,and patients were stratified into high-TMI(≥1.39)and low-TMI(<1.39)groups.The primary endpoint was overall survival(OS),with progression-free survival and treatment response as secondary endpoints.RESULTS The study included 305 mCRC patients with a median follow-up of 22.9 months.The median OS for high-TMI patients was 29.5 months,significantly lower than the 45.6 months observed in the low-TMI group(P=0.02).The 2-year OS rates for the high-and low-TMI groups were 59.4%and 72.9%,respectively.Median progression-free survival was also shorter for the high-TMI group(14.0 vs 16.0 months,P=0.84).High TMI is an independent prognostic factor for worse OS.CONCLUSION TMI is a simple,cost-effective prognostic tool for mCRC,with high TMI associated with poorer survival outcomes.
基金Supported by The Chongqing Talents Project,No.cstc2021ycjh-bgzxm0150The First Batch of Key Disciplines on Public Health in Chongqing,The Health Commission of Chongqing,No.2022(72)+1 种基金The Remarkable Innovation-Clinical Research Project,The Second Affiliated Hospital of Chongqing Medical UniversityThe Scientific and Technological Research Program of Chongqing Municipal Education Commission,the Second Affiliated Hospital of Chongqing Medical University,No.KJZD-K202300404.
文摘Hepatitis B virus(HBV)infection is a global health concern.The current sequen-tial endpoints for the treatment of HBV infection include viral suppression,hepatitis B e antigen(HBeAg)seroconversion,functional cure,and covalently closed circular DNA(cccDNA)clearance.Serum hepatitis B core-related antigen(HBcrAg)is an emerging HBV marker comprising three components:HBeAg,hepatitis B core antigen,and p22cr.It responds well to the transcriptional activity of cccDNA in the patient's liver and is a promising alternative marker for serolo-gical testing.There is a strong correlation,and a decrease in its level corresponds to sustained viral suppression.In patients with chronic hepatitis B(CHB),serum HBcrAg levels are good predictors of HBeAg seroconversion(both spontaneous and after antiviral therapy),particularly in HBeAg-positive patients.Both low baseline HBcrAg levels and decreasing levels early in antiviral therapy favored HBsAg seroconversion,which may serve as a good surrogate option for treatment endpoints.In this review,we summarize the role of serum HBcrAg in the treat-ment of CHB.Therefore,long-term continuous monitoring of serum HBcrAg levels contributes to the clinical management of patients with CHB and optimizes the choice of treatment regimen,making it a promising marker for monitoring HBV cure.
文摘In Western countries, clinical trials on prostate cancer screening demonstrated a limited benefit for patient survival. In the Asia-Pacific region, including Japan, the rate of prostate-specific antigen （PSA） testing remains very low compared with Western countries, and the benefits of population-based screening remain unclear. This review describes the current status of population screening and diagnosis for prostate cancer in Japan and discusses the efficacy of population screening for the Asian population. Since the 1990s, screening systems have been administered by each municipal government in Japan, and decreases in the prostate cancer mortality rate are expected in some regions where the exposure rate to PSA screening has increased markedly. A population-based screening cohort revealed that the proportion of metastatic disease in cancer detected by screening gradually decreased according to the increased exposure rate, and a decreasing trend in the proportion of cancer with high serum PSA levels after population screening was started. The prognosis of the prostate cancer detected by population screening was demonstrated to be more favorable than those diagnosed outside of the population screening. Recent results in screening cohorts demonstrated the efficacy of PSA. These recent evidences regarding population-based screening in Japan may contribute to establishing the optimal prostate cancer screeninK system in Asian individuals.
基金Supported by Grant-in-Aid for research by Kitasato University Medical Center,No.H25-0006 and the JSPS,KAKENHI,No.26670609 to Futawatari Nthe JSPS,KAKENHI,No.21700510 and No.17K16578,Takeda Science Foundation and Kitasato University Research Grant for Young Researchers to Fukuyama T
文摘AIM To assess cancer-testis antigens(CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.METHODS Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1(KK-LC-1), melanoma antigen(MAGE)-A1, MAGE-A3 and New York esophageal cancer-1(NYESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained. Statistical comparisons between the expression of each CTA and each clinicopathological background were performed using the χ2 test. RESULTS The expression rates of KK-LC-1, MAGE-A1, MAGE-A3, and NY-ESO-1 were 79.5%, 32.5%, 39.8%, and 15.7%, respectively. In early stage gastric cancer specimens, the expression of KK-LC-1 was 79.4%, which is comparable to the 79.6% observed in advanced stage specimens. The expression of KK-LC-1 was not significantly associated with clinicopathological factors, while there were considerable differences in the expression rates of MAGE-A1 and MAGE-A3 with vs without lymphatic invasion(MAGE-A1, 39.3% vs 13.6%, P = 0.034; MAGE-A3, 47.5% vs 18.2%, P = 0.022) and/or vascular invasion(MAGE-A1, 41.5% vs 16.7%, P = 0.028; MAGE-A3, 49.1% vs 23.3%, P = 0.035) and, particularly, MAGE-A3, in patients with early vs advanced stage(36.5% vs 49.0%, P = 0.044), respectively. Patients expressing MAGE-A3 and NYESO-1 were older than those not expressing MAGE-A3 and NY-ESO-1(MAGE-A3, 73.7 ± 7.1 vs 67.4 ± 12.3, P = 0.009; NY-ESO-1, 75.5 ± 7.2 vs 68.8 ± 11.2, P = 0.042). CONCLUSION The KK-LC-1 expression rate was high even in patients with stage I cancer, suggesting that KK-LC-1 is a useful biomarker for early diagnosis of gastric cancer.
文摘BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of great significance to find reliable prog-nostic indicators to guide the treatment and management of patients with gastric cancer.AIM To explore the relationship between serum levels of five biomarkers[carcinoem-bryonic antigen(CEA),carbohydrate antigen(CA)19-9,CA72-4,CA24-2,and ferritin]and prognosis in patients with gastric cancer.METHODS This study included 200 patients with gastric adenocarcinoma,and conducted an in-depth analysis of their baseline characteristics,relationship between tumor markers and staging,and prognosis.The study found that CA19-9 has a signi-ficant correlation with tumor stage,the average levels of CA24-2,CEA,CA72-4 and ferritin were slightly increased disregarding the stage of tumor.Survival analysis showed that increases in CEA,CA19-9,CA24-2,and ferritin were all associated with shortened overall survival of patients.Further multivariate ana-lysis revealed that elevated serum CA72-4 levels were an inde-pendent adverse prognostic factor.RESULTS This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA,CA19-9,CA72-4,CA24-2 and ferritin in patients with gastric cancer and prognosis,and can be used as important indicators for prognostic evaluation of gastric cancer.In particular,markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis.CONCLUSION Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer,and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.
文摘In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.
文摘[Objective]To design and express a recombinant protein rMKIBV incorporating confirmed antigenic epitopes of infectious bronchitis virus(IBV)as a vaccine to provide comprehensive protection.Additionally,it explores the potential of polyclonal yolk antibodies(IgY)harvested from laying hens immunized with the rMKIBV vaccine in the prevention and control of IBV.[Methods]The antigenic epitope sequences of IBV,obtained from online databases,were compared with sequences of representative IBV strains from GenBank.Flexible peptides were designed to link all antigenic peptides.The constructed amino acid sequence was analyzed,reverse-translated,codon-optimized,and then inserted into the pET-28a(+)cloning vector.The recombinant vector was introduced into Escherichia coli for expression.The purified,desalted,and endotoxin-removed rMKIBV protein was used as a vaccine to immunize animals for investigation of its immunogenicity and ability to stimulate specific IgY production in laying hens.[Results]The retrieved IBV antigenic epitope sequences showed high similarity with the published N and S protein sequences of 22 representative IBV strains.The predicted isoelectric point and molecular weight of rMKIBV were 10.25 and 63.39 kDa,respectively.The secondary structure of rMKIBV included a high proportion of random coils,which suggested strong antigenicity.High-purity rMKIBV was obtained from E.coli transformed with the recombinant plasmid pET-28a-mkibv.This protein specifically bound to anti-His-tag antibodies,N protein antibodies,and S protein antibodies.The mice immunized with this protein showed increases in the spleen index(P<0.05),elevations in the levels of serum-specific IgG antibodies(P<0.01)and IFN-γ(P<0.05),and no significant change in the IL-2 level.Immunized laying hens successfully produced IgY in egg yolks,with specific IgY antibody levels significantly increasing.Moreover,the IgY antibody titer gradually rose after immunization,reaching the peak after about 50 days and then gradually declining to reach a stable level.[Conclusion]We successfully constructed and expressed the recombinant protein rMKIBV.The protein demonstrated good immunogenicity,stimulating specific antibody production in both mice and laying hens.Notably,the IgY extracted from the yolks of immunized laying hens offers a novel approach to IBV prevention and control.These findings hold significant scientific and practical value for the development of vaccines against IBV.
基金supported by grants from the Science Technology Department of Zhejiang Province(Grant No.2021C03117)Noncommunicable Chronic DiseasesNational Science and Technology Major Project(Grant No.2023ZD0501300)+1 种基金National Natural Science Foundation of China(Grant No.82170219)Zhejiang Provincial Natural Science Foundation of China(Grant No.LQ24H080009)。
文摘Chimeric antigen receptor-T(CAR-T)cell therapy is a precise immunotherapy for lymphoma.However,its long-term efficacy faces many challenges related to tumor cell heterogeneity,interference from immunosuppressive microenvironments,CAR-T cell exhaustion,and unmanageable adverse events.Diverse modifications have been introduced into conventional CAR-T cells to overcome these obstacles;examples include addition of recognition sites to prevent immune escape,coupling of cytokine domains to enhance killing ability,blocking of immune checkpoint signals to resist tumor microenvironments,and inclusion of suicide systems or safety switches to improve safety and flexibility.With increasing understanding of the importance of metabolism and epigenetics in cancer and cytotherapy,glycolysis,methylation,and acetylation have become crucial CAR-T cell therapeutic targets.Universal and in situ CAR-T cells are also expected to be used in clinical applications,thus providing hope to patients with relapsed/refractory lymphomas.
基金supported by the National Natural Science Foundation of China under grant number U21A20259the National Key Research and Development Program of China under grant number 2021YFD1800401.
文摘Mycobacterium tuberculosis(Mtb)employs multiple mechanisms,such as phagocytosis and autophagy,to evade innate immune clearance and establish infection.In the present study,we identified the ESX-1 secretion-associated protein EspL,which promotes Mtb survival by inhibiting phagosome maturation and autophagy initiation.EspL knockout decreased Mtb intracellular survival,while EspL overexpression increased bacterial survival by interfering with phagocytosis and autophagy.EspL interacts with ULK1 and promotes its phosphorylation at Ser^(757),leading to the inhibition of autophagy initiation.Additionally,overexpression of EspL reduced antigen presentation and T-cell responses both in vitro and in vivo.Our findings revealed that EspL interferes with autophagy and antigen presenta-tion by suppressing ULK1 activation.These insights provide a novel understanding of Mtb pathogenicity.
文摘BACKGROUND Gastric cancer(GC)is an aggressive malignancy of the gastrointestinal tract characterized by high recurrence rates following radical gastrectomy.To enhance treatment efficacy,reduce recurrence,and improve patient survival,adjuvant chemotherapy is commonly administered based on established postoperative guidelines.Despite advancements in chemotherapy delivery,the overall response rate remains below 50%,primarily due to the lack of targeted therapies tailored to specific patient populations.AIM To explore sensitive biomarkers to assess the efficacy of postoperative adjuvant chemotherapy in appropriate patient subgroups.METHODS This study retrospectively analyzed 1628 patients who underwent radical gastrectomy for GC at our hospital in 2017 and 2018,with a subsequent five-year follow-up.Patients were divided based on whether they received postoperative adjuvant chemotherapy.The study aimed to determine optimal cutoff values for various biomarkersneutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio,carcinoembryonic antigen(CEA),carbohydrate antigen(CA)199,CA724,and CA242-using receiver operating characteristic(ROC)curves.Based on the optimal ROC cut-off,a novel combined metric,NLR-CEA,was developed to assess the efficacy of adjuvant chemotherapy following GC surgery.RESULTS Cox subgroup analysis demonstrated that postoperative adjuvant chemotherapy significantly improved overall survival in the NLR-CEA_Low group with a rate of 0.41(0.26-0.63).In the NLR-CEA_Middle group,the protective effect was observed at 0.69(0.54-0.87),while in the NLR-CEA_High group,it was 0.73(0.53-0.99).Notably,a 32%difference in the efficacy of chemotherapy was observed between the NLR-CEA_Low and NLR-CEA_High groups.CONCLUSION NLR-CEA is an effective biomarker for evaluating the efficacy of postoperative adjuvant chemotherapy in GC.Patients with NLR-CEA_Low exhibit significantly better responses to chemotherapy compared to those with NLRCEA_High.
基金Supported by Zhejiang Provincial Natural Science Foundation of China,No.LTGY24H160006Jiaxing Medical Key Discipline,No.2023-ZC-015.
文摘BACKGROUND Serum carcinoembryonic antigen(CEA)levels and magnetic resonance imaging(MRI)findings are widely used for the diagnosis and treatment of rectal cancer;however,research investigating their correlation remains limited.AIM To investigate the correlation between baseline MRI features and serum CEA levels in patients diagnosed with primary rectal cancer.METHODS Eighty patients(age:42-78 years)diagnosed with primary rectal cancer were enrolled.Baseline MRI examinations were performed to evaluate tumor size,T stage,circumferential resection margin status,extramural vascular invasion(EMVI),and lymph node metastasis.Serum CEA levels were concurrently measured.Statistical methods were used to analyze correlations.RESULTS Tumor size,T stage,EMVI,and lymph node metastasis were significantly correlated with serum CEA levels(P<0.05).Multivariate analysis identified T stage and lymph node metastasis as independent factors influencing serum CEA levels.CONCLUSION This study confirmed the correlation between baseline MRI features and serum CEA levels in patients with primary rectal cancer,highlighting their potential utility for precise diagnosis,staging,and prognostic evaluation.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common malignancies,with high recurrence rates after treatment.Identifying reliable biomarkers for predicting recurrence is essential for improving patient outcomes.Hepatitis B corerelated antigen(HBcrAg)has shown potential as a predictive marker for HCC recurrence.AIM To evaluate the association between HBcrAg levels and the risk of HCC recurrence.METHODS A systematic review was conducted following PRISMA guidelines.PubMed,EMBASE,Web of Science,and the Cochrane Library were searched without restrictions on date or language.Observational studies reporting hazard ratios(HRs)for HBcrAg as a predictor of HCC recurrence were included.Data extraction and quality assessment were performed independently by two reviewers.Statistical analyses used a random-effects model to account for heterogeneity(I²≥50%),and sensitivity analysis was performed to ensure the robustness of the results.RESULTS A total of 1339 articles were initially identified,and 17 studies were included in the final meta-analysis after screening.The pooled analysis showed a significant association between elevated HBcrAg levels and HCC recurrence(HR=4.42,95%confidence interval:3.43-5.41)with substantial heterogeneity(I²=92.6%).Subgroup analysis revealed higher pooled HRs in studies with≥500 participants(HR=4.18)and HBcrAg cut-offs≥4.0 LogU/mL(HR=5.29).Studies with≥10 years of follow-up showed a lower HR(2.89)compared to those with<10 years(3.27).Patients treated with nucleos(t)ide analogs had a pooled HR of 1.98,while those without nucleos(t)ide analog had a higher HR of 3.87.Sensitivity analysis confirmed the robustness of the results,with no significant publication bias detected.CONCLUSION This meta-analysis provides strong evidence that elevated HBcrAg levels are associated with an increased risk of HCC recurrence.HBcrAg may serve as a valuable biomarker for predicting recurrence,aiding personalized management and surveillance strategies for HCC patients.
基金supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region of China(grant number 2022D01C739)the National Natural Science Foundation of China(grant numbers 82160031,82071276)the Key Research and Development Program of Xinjiang Uyghur Autonomous Region of China(grant number 2024B03038-1).
文摘Background:The growth of the B-cell lymphoma subtype,Hodgkin lymphoma(HL),is associated with increased autophagy.A mycobacterial antigen,Ag85,has been reported to inhibit cell autophagy under a variety of conditions.Whether Ag85 could inhibit autophagy in HL is unknown.Methods:Lymph node samples from patients with HL and healthy controls were collected to assess proliferation and autophagy.The human HL cell line,L-428,was cultured and subjected to Ag85B treatment.Autophagy in L-428 cells was evaluated through western blotting analysis,immunohistochemistry,and transmission electron microscopy.Apoptosis in these cells was measured using flow cytometry and western blotting.The associated signaling pathways were also analyzed utilizing western blotting.The in vivo impact of Ag85B was studied using BALB/c Nude mice xenografted with L-428 cells.Results:We observed increased proliferation and autophagy in primary lymphoma tissues of patients.Administration of Ag85B inhibited the proliferation and autophagy of HL cell lines.Moreover,Ag85B promoted apoptotic pathway activation in vitro,which might be associated with mitochondrial dysfunction.Mechanistically,Ag85B inhibits autophagy by activating the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B/mechanistic target of rapamycin kinase(PI3K/AKT/mTOR)and mitogen-activated protein kinase(MAPK)pathways.Ag85B also inhibited lymphoma growth in mice xenografted with HL cell lines,but no potential toxicity was observed.Conclusion:Altogether,these results suggest that Ag85B inhibits HL growth via autophagy regulation.Current treatments for HL are associated with adverse events;therefore,Ag85B-mediated autophagy inhibition might be a promising strategy in to treat HL.
文摘BACKGROUND The World Health Organization(WHO)recommends lumbar puncture(LP)procedures to assess the diagnosis of cryptococcal meningitis(CM)among patients with advanced human immunodeficiency virus(HIV)disease(AHD)with positive serum cryptococcal antigen(CrAg)and do not have evidence of CM.AIM To estimate pooled prevalence of uptake of LP,CM and mortality among patients with AHD.METHODS PubMed,Cochrane Library and EMBASE were searched for articles published between January 2011 and December 2024.LP uptake was defined as percentage of people who underwent LP procedures among those with AHD(CD4≤200 cells/mm3 or WHO stage III/IV)and positive serum CrAg.Using random effects models,we computed the pooled estimate of LP uptake,CM and mortality and 95%CI.Stratified analyses were used to compare uptake of LP between studies that involved multiple vs single sites,and mortality analyses between patients with positive and negative serum CrAg were performed.Sensitivity analysis on LP uptake was done by excluding prospective cohort studies that reported 100%uptake.RESULTS A total of 32 studies with 46890 people with AHD screened for serum CrAg and 2730(5.8%)had positive serum CrAg.Overall,pooled prevalence of LP uptake was 67.7%(95%CI:54.0-81.5).The overall pooled prevalence of CM was 54.3%(95%CI:39.7-69.0),and mortality was 6.2%(95%CI:4.5-8.0).There is disparities in the pooled prevalence of LP uptake with studies involving multiple sites having lower prevalence compared to those that involved single sites(54.8%vs 84.7%,P=0.004).By excluding prospective cohort studies that reported 100%uptake,the overall LP uptake was 54.5%(95%CI:38.8-70.1).The pooled prevalence of CM was significantly lower among studies that involved multiple sites compared to those that involved single sites(6.8%vs 8.1%,P≤0.001).Mortality was significantly twice as high among patients who had positive serum CrAg compared to those who had negative serum CrAg[risk ratio=2.0(95%CI:1.6-2.5),P≤0.001].CONCLUSION Nearly three to five in 10 people with AHD with positive serum CrAg did not have LP procedures done,indicating significant gaps in identifying patients with CM.Establishing a confirmed diagnosis of CM is critical to avoid exposing patients to subtherapeutic levels of antifungals preemptively.Capacity to perform LP and patient refusals are among the reasons for not performing the procedure.Capacity building in training health care providers to perform LP procedures and professional counselling to obtain patient consent are critical for appropriate treatment to reduce mortality associated with CM infection.
基金Supported by National Natural Science Foundation of China,No.82170406 and No.81970238.
文摘Hepatitis B virus infection remains a significant global health challenge,particularly in endemic regions like Vietnam.This article examines the groundbreaking study by Nguyen et al,which investigates the relationship between human leukocyte antigen-DP/DQ polymorphisms and hepatitis B virus-related liver disease progression.Through advanced multi-clustering analysis,the study reveals that the A-A-A haplotype(rs2856718-rs3077-rs9277535)provides protection against disease progression,while the G-G-G haplotype correlates with increased hepatocellular carcinoma susceptibility.The integration of machine learning approaches with genetic data offers promising avenues for refined disease prediction and personalized therapeutic strategies.This article discusses the implications for expanding study populations,implementing longitudinal cohort studies,and leveraging artificial intelligence for improved patient outcomes.
基金supported by the RGC Research Impact Fund(Grant No.R5008-22F).
文摘Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related mortality worldwide1.The primary treatment options for this disease are surgical resection and liver transplantation.Unfortunately,most HCC cases are diagnosed in advanced stages and are inoperable.Even after surgery,the long-term prognosis remains unsatisfactory,because of a high recurrence rate.
