Background:Immunosuppression compromises the host’s ability to combat pathogens,thereby increasing susceptibility to multisystem disorders.However,safe and effective curative treatments for this condition are current...Background:Immunosuppression compromises the host’s ability to combat pathogens,thereby increasing susceptibility to multisystem disorders.However,safe and effective curative treatments for this condition are currently lacking.Modulating the gut microbiota and their metabolites represents a promising therapeutic strategy.Notably,the Chinese herbal compound Yunzhi Guben Gao(YZG)has demonstrated multi-target immunomodulatory potential.Methods:A mouse model of dexamethasone-induced immunosuppression was employed to evaluate the effects of YZG.Immune organ indices(thymus,spleen),serum cytokine levels(IL-2,TNF-α),mucosal immunity markers(pulmonary/colonic SIgA),gut microbiota structure,and short-chain fatty acids(SCFAs)abundance were evaluated.Key microbial genera and metabolites were identified via Spearman correlation analysis.Pseudo-germ-free model mice established via quadruple antibiotic treatment combined with isovaleric acid intervention were employed to evaluate whether YZG efficacy depends on the intestinal microbiota and its metabolites,and whether its intrinsic mechanisms involve the promotion of isovaleric acid production.Results:YZG intervention ameliorated systemic and mucosal immune function in immunosuppressed mice.Mechanistically,YZG remodeled gut microbiota structure and significantly increased SCFAs levels.Notably,the abundance of the genus Ligilactobacillus exhibited the strongest positive correlation with isovaleric acid levels.Ligilactobacillus abundance was also positively correlated with immune-enhancing parameters and negatively correlated with the proinflammatory cytokine TNF-α,suggesting that Ligilactobacillus plays a pivotal role in the YZG regulatory network.Experiments using pseudo-germ-free mice and isovaleric acid intervention further demonstrated that the immunoprotective effects of YZG are closely related to intestinal microbiota remodeling and increased isovaleric acid production.Conclusion:YZG alleviates immunosuppression through multiple mechanisms,primarily involving the enrichment of the probiotic genus Ligilactobacillus and the consequent increase in isovaleric acid production.This process coordinately modulates mucosal immunity,cytokine networks,and immune organ function.The elucidation of this“microbiota-metabolite-immunity”axis provides both a pharmacological basis for the clinical application of YZG and novel immune-restorative strategies targeting gut microecological regulation.展开更多
Background:The absence of well-established immunosuppressed rabbit models poses a significant hurdle in xenograft experiments.Tacrolimus has been identified as a highly promising immunosuppressive agent for rabbits.Ho...Background:The absence of well-established immunosuppressed rabbit models poses a significant hurdle in xenograft experiments.Tacrolimus has been identified as a highly promising immunosuppressive agent for rabbits.However,determining the optimal dosage and route of administration to minimize toxicity while maintaining efficacy remains challenging.Methods:In this study,we investigated the effect of orally administered tacrolimus in rabbits,with an aim to achieve a whole blood target trough level of 3-10 ng/m L,and looked at signs of tissue rejection after the transplantation of a human nerve conduit to repair a severed fibular nerve.An oral dosage range of 0.25-1.5 mg/kg/d was studied for up to 1 year in 63 New Zealand rabbits.Results:We demonstrated the feasibility of long-term grafting in rabbits while maintaining safe immunosuppression,with side effects mainly limited to diarrhea.Customizing the administered dose proved crucial for graft efficacy and low toxicity,which translated into 100%individual survival.We suggest an oral tacrolimus dose of 1.0-1.5 mg/kg depending on individual heterogeneity and recommend to implement a close therapeutic drug monitoring in the rabbits to maintain a whole blood tacrolimus trough level within the range of 5-12 ng/m L,as levels below 5 ng/m L showed signs of inflammation in the graft.Conclusion:The oral administration of tacrolimus enabled efficient immunosuppression of rabbits over a 1-year period without significant side effects or loss of animals.展开更多
Florfenicol(FLO)is a chemically synthesized broad-spectrum antimicrobial agent of amide alcohols for animals,which is one of the most widely used antimicrobials in livestock,poultry,and aquaculture.With the use of FLo...Florfenicol(FLO)is a chemically synthesized broad-spectrum antimicrobial agent of amide alcohols for animals,which is one of the most widely used antimicrobials in livestock,poultry,and aquaculture.With the use of FLo,more and more attention has been paid to its hematopoietic toxicity,immunotoxicity,genotoxicity,and embryotoxicity.In this study,SPF chicks.at the age of 3 d began to drink water with the FLO at a dose of 100 mg L^(-1)for 6 consecutive days,and the growth performance of chicks was monitored,the effect of FLO on immune organs was detected by pathological examination and TdT-mediated dUTP nick-end labeling(TUNEL)apoptosis staining.In order to evaluate the level of organism immunity,the level of Newcastle disease virus antibody in serum was detected by hemagglutination inhibition test,the content of cytokines(IL-1,IL-2,IL-6,TNF-α,IFN-γ)in serum was detected by enzyme linked immunosorbent assay(ELISA),and the transcription of interferon-related genes(IRF-7,2′-5′OAS,Mx1)and cytokine genes(IL-6,TNF-α,IFN-γ)in immune organs were detected by real time fluorescence quantitative PCR.The results showed that the early application of FLO could inhibit the growth and development of chicks,and the body weight and immune organ index of the treatment group were lower than those of the control group.Histopathological examination showed that there was a decrease in the number of lymphocytes in the bursa of Fabricius in the treatment group in the early stage of drug withdrawal,and the results of TUNEL apoptosis staining in the bursa of Fabricius showed that obvious lymphocyte apoptosis occurred in the FLO treatment group.Compared with the control group,the transcription levels of interferon-related genes IRF-7,2′-5′OAS,and cytokine genes IL-6,TNF-αand IFN-γin FLO treatment group decreased to a certain extent,while the transcription level of Mx1 gene had no significant difference at all time points.The level of serum Newcastle disease virus(NDV)antibody and the contents of cytokines IL-1,IL-2 and IFN-γin the FLO treatment group were significantly lower than those in the control group in the early stage of drug withdrawal,but recovered gradually in the later stage.This study showed that FLO has a certain degree of effect on the immune function of chicks,and the results of the study laid the foundation for further research on the mechanism of FLO-induced immunotoxicity.展开更多
Objective To observe modulatory effects of electroacupuncture （EA） on hypothalamus-pituitary adrenal （HPA） axis, thymus-exponent （TE）, γ-IFN and interleukin-2 （IL-2） in rats with exercise-induced immunosuppre...Objective To observe modulatory effects of electroacupuncture （EA） on hypothalamus-pituitary adrenal （HPA） axis, thymus-exponent （TE）, γ-IFN and interleukin-2 （IL-2） in rats with exercise-induced immunosuppression. Methods Forty-three SD rats were randomly, by using digits, divided into three groups： group A, B and C. Group A （n=10） was taken as a control group. Rats in group B （n=17） accepted intense swimming exercise for 150 min each time, 6 times each week for 8 weeks. Rats in group C （n=16） accepted EA intervention following each swimming since the second week of swimming exercise with the same duration and times as those in group B. The indices reflecting functional states of the HPA axis such as hypothalamic corticotropin releasing hormone （CRH）, plasma adrenocorticotropic hormone （ACTH）, corticosterone （CORT） etc. and changes in TE, serum γ-IFN, and IL-2 were determined. Results （1） Compared with group A, the values of ACTH and CORT in group B significantly increased （P〈0.01, P〈0.05）, but no significant differences were found in group C （both P〉0.05） though they were somewhat elevated. Compared with group A, CRH values increased by 85.14% in group B and decreased by 64.09% in group C, respectively, but both differences were without statistical significance （both P〉0.05）. Serum IL-2, γ-IFN and TE values in group B were significantly lower than those in group A（P〈0.05, P〈0.01 ）, among which γ-IFN decreased by 32.19%. The values of IL-2, γ-IFN and TE in group C tended to reduce but without significance, compared with group A. （2） Compared with group B, ACTH value in group C was very significantly lowered than that in group B （P〈0.01）, and CRH value was lower while CORT value was higher than those in group B but without significance （both P〉0.05）. The values of TE and γ-IFN in group C were significantly higher than those in group B （P〈0.01, P〈0.05）. Conclusion （1） Long-term of intense exercise induces accentuation of functions of the HPA axis and sustained high level of CORT, resulting in neuroendocrine disturbance and inhibition of immune functions. （2） EA provides favorable modulation on long-term of intense exercise-induced lowering of immune function and on the HPA axis.展开更多
Dear Editor,Lymphocyte activation gene 3(LAG3),the third established target for immune checkpoint blockade therapy,suppresses T cell function by binding to major histocompatibility complex classⅡ(MHCⅡ).Despite its s...Dear Editor,Lymphocyte activation gene 3(LAG3),the third established target for immune checkpoint blockade therapy,suppresses T cell function by binding to major histocompatibility complex classⅡ(MHCⅡ).Despite its significant therapeutic potential in cancer immunotherapy and the substantial attention it has received from academia and industry,the molecular mechanisms of LAG3-mediated immunosuppression remain poorly understood,primarily because of its unique ligand-binding characteristics and intracellular domains[1].展开更多
Background and AimsAutoimmune hepatitis(AIH)frequently coexists with extrahepatic autoimmune diseases(EADs),but their prevalence,characteristics,progression,and treatment effect in the Han Chinese population remain un...Background and AimsAutoimmune hepatitis(AIH)frequently coexists with extrahepatic autoimmune diseases(EADs),but their prevalence,characteristics,progression,and treatment effect in the Han Chinese population remain unclear.This study aimed to evaluate the prevalence and spectrum of EADs and to assess their clinical features,disease course,and treatment outcomes in Han Chinese patients with AIH.MethodsMedical records of 371 Han Chinese patients with AIH(diagnosed from March 2016 to October 2023)were retrospectively analyzed.ResultsAmong the 371 AIH patients,304(81.94%)were female,with a median age of 52.5 years(interquartile range,46.0-61.0).A total of 23.98%(89/371)had at least one EAD,including 27.06%(82/303)in type 1 AIH,11.11%(7/63)in antibody-negative AIH,and none in type 2.A single EAD was the most common(20.21%,75/371).The most frequent EADs were Sjogren’s syndrome(8.63%)and autoimmune thyroid disease(8.36%).Compared with patients without EADs,those with EADs had lower alanine aminotransferase,red blood cell,and hemoglobin levels,but higher aspartate aminotransferase/alanine aminotransferase ratio and antinuclear antibody(ANA)positivity(all P<0.05).ANA positivity was independently associated with EADs(odds ratio=2.209,95%confidence interval=1.242-3.927,P=0.007).After three months of treatment,the complete biochemical response rate was lower in the EADs group than in the non-EADs group(40.0%vs.55.3%,P=0.024),whereas no significant differences were observed at 6,12,24,or 36 months(all P>0.05).ConclusionsIn the Han Chinese population,23.98%of AIH patients had EADs,with Sjogren’s syndrome and autoimmune thyroid disease being the most common.ANA positivity was a significant risk factor for EADs.EAD patients had a poorer initial treatment response at three months,but comparable long-term biochemical response from six months.展开更多
Liver transplantation is a life-saving procedure for patients with end-stage liver diseases and acute liver failure.With advances in surgical techniques and immunosuppressive regimens,patient survival rates have signi...Liver transplantation is a life-saving procedure for patients with end-stage liver diseases and acute liver failure.With advances in surgical techniques and immunosuppressive regimens,patient survival rates have significantly improved.While the systemic complications of post-transplantation are well recognized,ophthalmic manifestations remain underreported.Ophthalmic complications can significantly impair visual function and increase morbidity in these patients.Prolonged immunosuppression makes the patients susceptible to the opportunistic pathogens such as Cytomegalovirus,Candida,Aspergillus,etc.Other common findings include dry eye disease,cataracts and retinal vascular complications which further contribute to the long-term morbidity in these patients.Early ophthalmic evaluation and prompt management are essential to prevent irreversible vision loss and improve post-transplant outcomes.High index of suspicion and multidisciplinary approach is essential to facilitate early diagnosis and treatment.This review highlights the range of ophthalmic complications observed in liver transplant recipients and underscores the need for future research focused on understanding the underlying pathophysiological mechanisms and refining the prophylactic protocols to improve outcomes in this unique patient population.展开更多
BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant rec...BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.展开更多
In the pre-biologic era,immunomodulators such as azathioprine,6-mercaptopurine,and methotrexate(MTX)were widely used as first-line maintenance therapies in Crohn’s disease.However,in the current era shaped by biologi...In the pre-biologic era,immunomodulators such as azathioprine,6-mercaptopurine,and methotrexate(MTX)were widely used as first-line maintenance therapies in Crohn’s disease.However,in the current era shaped by biologics,their role has shifted toward adjunctive use,primarily in combination with anti-tumor necrosis factor agents to reduce immunogenicity.Amid growing concerns about thiopurine-associated risks,MTX is receiving renewed attention for its favorable safety profile;however,this agent remains inconsistently utilized in gastroenterology despite its frontline status in rheumatology.This discrepancy was highlighted in a recent nationwide survey by Bonnaud et al published in the World Journal of Gastroenterology,which offers timely insights into MTX prescribing behaviors among French gastroenterologists.Although 71%of respondents reported using MTX,primarily via subcutaneous injection,it is still perceived as a secondary choice after thiopurines.Importantly,this underuse appears to be driven more by clinical inertia and limited guidance rather than by lack of efficacy or safety concerns.Clinicians increasingly recognize the value of MTX,particularly in patients with joint involvement,Epstein-Barr virus negativity,or increased malignancy risk.Notably,even non-prescribers viewed the drug favorably,suggesting that usage barriers may be modifiable.In light of evolving treatment goals that prioritize safety,cost-effectiveness,and individualized care,this editorial argues that MTX should no longer be viewed as a fallback but as a strategic first-line option in well-defined high-risk populations.The survey underscores a persistent gap between guidelines and real-world practice,reinforcing the urgent need for clearer algorithms and education to support the repositioning of MTX in modern Crohn’s disease management.展开更多
基金supported by the Research Fund Project of the Education Department of Yunnan Province(No.2023Y0464)Research Project for Scientific Research Funds of Provincial Research Institutions in Heilongjiang Province(No.CZBZ2025ZR003).
文摘Background:Immunosuppression compromises the host’s ability to combat pathogens,thereby increasing susceptibility to multisystem disorders.However,safe and effective curative treatments for this condition are currently lacking.Modulating the gut microbiota and their metabolites represents a promising therapeutic strategy.Notably,the Chinese herbal compound Yunzhi Guben Gao(YZG)has demonstrated multi-target immunomodulatory potential.Methods:A mouse model of dexamethasone-induced immunosuppression was employed to evaluate the effects of YZG.Immune organ indices(thymus,spleen),serum cytokine levels(IL-2,TNF-α),mucosal immunity markers(pulmonary/colonic SIgA),gut microbiota structure,and short-chain fatty acids(SCFAs)abundance were evaluated.Key microbial genera and metabolites were identified via Spearman correlation analysis.Pseudo-germ-free model mice established via quadruple antibiotic treatment combined with isovaleric acid intervention were employed to evaluate whether YZG efficacy depends on the intestinal microbiota and its metabolites,and whether its intrinsic mechanisms involve the promotion of isovaleric acid production.Results:YZG intervention ameliorated systemic and mucosal immune function in immunosuppressed mice.Mechanistically,YZG remodeled gut microbiota structure and significantly increased SCFAs levels.Notably,the abundance of the genus Ligilactobacillus exhibited the strongest positive correlation with isovaleric acid levels.Ligilactobacillus abundance was also positively correlated with immune-enhancing parameters and negatively correlated with the proinflammatory cytokine TNF-α,suggesting that Ligilactobacillus plays a pivotal role in the YZG regulatory network.Experiments using pseudo-germ-free mice and isovaleric acid intervention further demonstrated that the immunoprotective effects of YZG are closely related to intestinal microbiota remodeling and increased isovaleric acid production.Conclusion:YZG alleviates immunosuppression through multiple mechanisms,primarily involving the enrichment of the probiotic genus Ligilactobacillus and the consequent increase in isovaleric acid production.This process coordinately modulates mucosal immunity,cytokine networks,and immune organ function.The elucidation of this“microbiota-metabolite-immunity”axis provides both a pharmacological basis for the clinical application of YZG and novel immune-restorative strategies targeting gut microecological regulation.
基金the Canadian Institutes of Health Research(CIHR),Grant/Award Number:PJT-175016the Fonds de recherche du Québec(FRQ)through the research centre grant for the CHU de Québec-UniversitéLaval Research Center,Grant/Award Number:30641+2 种基金the Quebec Cell,Tissue and Gene Therapy Network—ThéCellthe FRQS,the Fondation du CHU de Québec-UniversitéLavalNeuro Québec。
文摘Background:The absence of well-established immunosuppressed rabbit models poses a significant hurdle in xenograft experiments.Tacrolimus has been identified as a highly promising immunosuppressive agent for rabbits.However,determining the optimal dosage and route of administration to minimize toxicity while maintaining efficacy remains challenging.Methods:In this study,we investigated the effect of orally administered tacrolimus in rabbits,with an aim to achieve a whole blood target trough level of 3-10 ng/m L,and looked at signs of tissue rejection after the transplantation of a human nerve conduit to repair a severed fibular nerve.An oral dosage range of 0.25-1.5 mg/kg/d was studied for up to 1 year in 63 New Zealand rabbits.Results:We demonstrated the feasibility of long-term grafting in rabbits while maintaining safe immunosuppression,with side effects mainly limited to diarrhea.Customizing the administered dose proved crucial for graft efficacy and low toxicity,which translated into 100%individual survival.We suggest an oral tacrolimus dose of 1.0-1.5 mg/kg depending on individual heterogeneity and recommend to implement a close therapeutic drug monitoring in the rabbits to maintain a whole blood tacrolimus trough level within the range of 5-12 ng/m L,as levels below 5 ng/m L showed signs of inflammation in the graft.Conclusion:The oral administration of tacrolimus enabled efficient immunosuppression of rabbits over a 1-year period without significant side effects or loss of animals.
文摘Florfenicol(FLO)is a chemically synthesized broad-spectrum antimicrobial agent of amide alcohols for animals,which is one of the most widely used antimicrobials in livestock,poultry,and aquaculture.With the use of FLo,more and more attention has been paid to its hematopoietic toxicity,immunotoxicity,genotoxicity,and embryotoxicity.In this study,SPF chicks.at the age of 3 d began to drink water with the FLO at a dose of 100 mg L^(-1)for 6 consecutive days,and the growth performance of chicks was monitored,the effect of FLO on immune organs was detected by pathological examination and TdT-mediated dUTP nick-end labeling(TUNEL)apoptosis staining.In order to evaluate the level of organism immunity,the level of Newcastle disease virus antibody in serum was detected by hemagglutination inhibition test,the content of cytokines(IL-1,IL-2,IL-6,TNF-α,IFN-γ)in serum was detected by enzyme linked immunosorbent assay(ELISA),and the transcription of interferon-related genes(IRF-7,2′-5′OAS,Mx1)and cytokine genes(IL-6,TNF-α,IFN-γ)in immune organs were detected by real time fluorescence quantitative PCR.The results showed that the early application of FLO could inhibit the growth and development of chicks,and the body weight and immune organ index of the treatment group were lower than those of the control group.Histopathological examination showed that there was a decrease in the number of lymphocytes in the bursa of Fabricius in the treatment group in the early stage of drug withdrawal,and the results of TUNEL apoptosis staining in the bursa of Fabricius showed that obvious lymphocyte apoptosis occurred in the FLO treatment group.Compared with the control group,the transcription levels of interferon-related genes IRF-7,2′-5′OAS,and cytokine genes IL-6,TNF-αand IFN-γin FLO treatment group decreased to a certain extent,while the transcription level of Mx1 gene had no significant difference at all time points.The level of serum Newcastle disease virus(NDV)antibody and the contents of cytokines IL-1,IL-2 and IFN-γin the FLO treatment group were significantly lower than those in the control group in the early stage of drug withdrawal,but recovered gradually in the later stage.This study showed that FLO has a certain degree of effect on the immune function of chicks,and the results of the study laid the foundation for further research on the mechanism of FLO-induced immunotoxicity.
基金Supported by Guangdong Natural Science Foundation Project: 050042740
文摘Objective To observe modulatory effects of electroacupuncture （EA） on hypothalamus-pituitary adrenal （HPA） axis, thymus-exponent （TE）, γ-IFN and interleukin-2 （IL-2） in rats with exercise-induced immunosuppression. Methods Forty-three SD rats were randomly, by using digits, divided into three groups： group A, B and C. Group A （n=10） was taken as a control group. Rats in group B （n=17） accepted intense swimming exercise for 150 min each time, 6 times each week for 8 weeks. Rats in group C （n=16） accepted EA intervention following each swimming since the second week of swimming exercise with the same duration and times as those in group B. The indices reflecting functional states of the HPA axis such as hypothalamic corticotropin releasing hormone （CRH）, plasma adrenocorticotropic hormone （ACTH）, corticosterone （CORT） etc. and changes in TE, serum γ-IFN, and IL-2 were determined. Results （1） Compared with group A, the values of ACTH and CORT in group B significantly increased （P〈0.01, P〈0.05）, but no significant differences were found in group C （both P〉0.05） though they were somewhat elevated. Compared with group A, CRH values increased by 85.14% in group B and decreased by 64.09% in group C, respectively, but both differences were without statistical significance （both P〉0.05）. Serum IL-2, γ-IFN and TE values in group B were significantly lower than those in group A（P〈0.05, P〈0.01 ）, among which γ-IFN decreased by 32.19%. The values of IL-2, γ-IFN and TE in group C tended to reduce but without significance, compared with group A. （2） Compared with group B, ACTH value in group C was very significantly lowered than that in group B （P〈0.01）, and CRH value was lower while CORT value was higher than those in group B but without significance （both P〉0.05）. The values of TE and γ-IFN in group C were significantly higher than those in group B （P〈0.01, P〈0.05）. Conclusion （1） Long-term of intense exercise induces accentuation of functions of the HPA axis and sustained high level of CORT, resulting in neuroendocrine disturbance and inhibition of immune functions. （2） EA provides favorable modulation on long-term of intense exercise-induced lowering of immune function and on the HPA axis.
文摘Dear Editor,Lymphocyte activation gene 3(LAG3),the third established target for immune checkpoint blockade therapy,suppresses T cell function by binding to major histocompatibility complex classⅡ(MHCⅡ).Despite its significant therapeutic potential in cancer immunotherapy and the substantial attention it has received from academia and industry,the molecular mechanisms of LAG3-mediated immunosuppression remain poorly understood,primarily because of its unique ligand-binding characteristics and intracellular domains[1].
基金Jiangsu Province Traditional Chinese Medicine Science and Technology Development Program(YB2020037)Nanjing Infectious Disease Clinical Medical Center,Innovation Center for Infectious Disease of Jiangsu Province(NO.CXZX202232)Nanjing Health Science and Technology Development Special Fund Project(YKK22127).
文摘Background and AimsAutoimmune hepatitis(AIH)frequently coexists with extrahepatic autoimmune diseases(EADs),but their prevalence,characteristics,progression,and treatment effect in the Han Chinese population remain unclear.This study aimed to evaluate the prevalence and spectrum of EADs and to assess their clinical features,disease course,and treatment outcomes in Han Chinese patients with AIH.MethodsMedical records of 371 Han Chinese patients with AIH(diagnosed from March 2016 to October 2023)were retrospectively analyzed.ResultsAmong the 371 AIH patients,304(81.94%)were female,with a median age of 52.5 years(interquartile range,46.0-61.0).A total of 23.98%(89/371)had at least one EAD,including 27.06%(82/303)in type 1 AIH,11.11%(7/63)in antibody-negative AIH,and none in type 2.A single EAD was the most common(20.21%,75/371).The most frequent EADs were Sjogren’s syndrome(8.63%)and autoimmune thyroid disease(8.36%).Compared with patients without EADs,those with EADs had lower alanine aminotransferase,red blood cell,and hemoglobin levels,but higher aspartate aminotransferase/alanine aminotransferase ratio and antinuclear antibody(ANA)positivity(all P<0.05).ANA positivity was independently associated with EADs(odds ratio=2.209,95%confidence interval=1.242-3.927,P=0.007).After three months of treatment,the complete biochemical response rate was lower in the EADs group than in the non-EADs group(40.0%vs.55.3%,P=0.024),whereas no significant differences were observed at 6,12,24,or 36 months(all P>0.05).ConclusionsIn the Han Chinese population,23.98%of AIH patients had EADs,with Sjogren’s syndrome and autoimmune thyroid disease being the most common.ANA positivity was a significant risk factor for EADs.EAD patients had a poorer initial treatment response at three months,but comparable long-term biochemical response from six months.
文摘Liver transplantation is a life-saving procedure for patients with end-stage liver diseases and acute liver failure.With advances in surgical techniques and immunosuppressive regimens,patient survival rates have significantly improved.While the systemic complications of post-transplantation are well recognized,ophthalmic manifestations remain underreported.Ophthalmic complications can significantly impair visual function and increase morbidity in these patients.Prolonged immunosuppression makes the patients susceptible to the opportunistic pathogens such as Cytomegalovirus,Candida,Aspergillus,etc.Other common findings include dry eye disease,cataracts and retinal vascular complications which further contribute to the long-term morbidity in these patients.Early ophthalmic evaluation and prompt management are essential to prevent irreversible vision loss and improve post-transplant outcomes.High index of suspicion and multidisciplinary approach is essential to facilitate early diagnosis and treatment.This review highlights the range of ophthalmic complications observed in liver transplant recipients and underscores the need for future research focused on understanding the underlying pathophysiological mechanisms and refining the prophylactic protocols to improve outcomes in this unique patient population.
文摘BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.
文摘In the pre-biologic era,immunomodulators such as azathioprine,6-mercaptopurine,and methotrexate(MTX)were widely used as first-line maintenance therapies in Crohn’s disease.However,in the current era shaped by biologics,their role has shifted toward adjunctive use,primarily in combination with anti-tumor necrosis factor agents to reduce immunogenicity.Amid growing concerns about thiopurine-associated risks,MTX is receiving renewed attention for its favorable safety profile;however,this agent remains inconsistently utilized in gastroenterology despite its frontline status in rheumatology.This discrepancy was highlighted in a recent nationwide survey by Bonnaud et al published in the World Journal of Gastroenterology,which offers timely insights into MTX prescribing behaviors among French gastroenterologists.Although 71%of respondents reported using MTX,primarily via subcutaneous injection,it is still perceived as a secondary choice after thiopurines.Importantly,this underuse appears to be driven more by clinical inertia and limited guidance rather than by lack of efficacy or safety concerns.Clinicians increasingly recognize the value of MTX,particularly in patients with joint involvement,Epstein-Barr virus negativity,or increased malignancy risk.Notably,even non-prescribers viewed the drug favorably,suggesting that usage barriers may be modifiable.In light of evolving treatment goals that prioritize safety,cost-effectiveness,and individualized care,this editorial argues that MTX should no longer be viewed as a fallback but as a strategic first-line option in well-defined high-risk populations.The survey underscores a persistent gap between guidelines and real-world practice,reinforcing the urgent need for clearer algorithms and education to support the repositioning of MTX in modern Crohn’s disease management.
