In recent years,pharmacogenetics has emerged as an important tool for choosing the right immunosuppressant drug and its appropriate dose.Indeed,pharmacogenetics may exert its action on immunosuppressant drugs at three...In recent years,pharmacogenetics has emerged as an important tool for choosing the right immunosuppressant drug and its appropriate dose.Indeed,pharmacogenetics may exert its action on immunosuppressant drugs at three levels.Pharmacogenetics identifies and studies the genes involved in encoding the proteins involved in drug pharmacokinetics and in encoding the enzymes involved in drug degradation.Pharmacogenetics is also relevant in encoding the enzymes and proteins involved in codifying the transmembrane proteins involved in transmembrane passage favoring the absorption and intracellular action of several immunosuppressants.Pharmacogenetics concern the variability of genes encoding the proteins involved as immunosuppressant triggers in the pharmacodynamic pathways.Of course,not all genes have been discovered and studied,but some of them have been clearly examined and their relevance together with other factors such as age and race has been defined.Other genes on the basis of relevant studies have been proposed as good candidates for future studies.Unfortunately,to date,clear conclusions may be drawn only for those drugs that are metabolized by CYP3A5 and its genotyping before kidney,heart and lung transplantation is recommended.The conclusions of the studies on the recommended candidate genes,together with the development of omics techniques could in the future allow us to choose the right dose of the right immunosuppressant for the right patient.展开更多
BACKGROUND Chylous ascites is caused by disruption of the lymphatic system,which is characterized by the accumulation of a turbid fluid containing high levels of triglycerides within the abdominal cavity.The two most ...BACKGROUND Chylous ascites is caused by disruption of the lymphatic system,which is characterized by the accumulation of a turbid fluid containing high levels of triglycerides within the abdominal cavity.The two most common causes are cirrhosis and tuberculosis,and colon signer ring cell carcinoma(SRCC)due to the use of immunosuppressants is extremely rare in cirrhotic patients after liver transplantation,making it prone to misdiagnosis and missed diagnosis.CASE SUMMARY A 52-year-old man who underwent liver transplantation and was administered with immunosuppressants for 8 months was admitted with a 3-month history of progressive abdominal distention.Initially,based on lymphoscintigraphy and lymphangiography,lymphatic obstruction was considered,and cystellar chyli decompression with band lysis and external membrane stripping of the lymphatic duct was performed.However,his abdominal distention was persistent without resolution.Abdominal paracentesis revealed allogenic cells in the ascites,and immunohistochemistry analysis revealed adenocarcinoma cells with phenotypic features suggestive of a gastrointestinal origin.Gastrointestinal endoscopy was performed,and biopsy showed atypical signet ring cells in the ileocecal valve.The patient eventually died after a three-month follow-up due to progression of the tumor.CONCLUSION Colon SRCC,caused by immunosuppressants,is an unusual but un-neglected cause of chylous ascites.展开更多
Prostate cancer is a malignant tumor with a high incidence in elderly men.In recent years,with the improvement of people’s living standards and the advancement of detection technology,the incidence of prostate cancer...Prostate cancer is a malignant tumor with a high incidence in elderly men.In recent years,with the improvement of people’s living standards and the advancement of detection technology,the incidence of prostate cancer has been increasing year by year.Castration-resistant prostate cancer(CRPC)is a highly challenging type of advanced prostate cancer treatment,which clinically shows resistance to hormonal deprivation therapy.The overall treatment efficacy of CRPC is currently poor and further relevant therapeutic studies are needed to improve patient survival and quality of life.Immunosuppressants can play a role in combating the immune system of tumors,and abiraterone has also achieved remarkable results in prostate cancer treatment.This study will investigate the possible clinical effects and safety of immunosuppressants combined with abiraterone in the treatment of metastatic CRPC.The population-based study will provide clinicians with more effective treatment options,as well as enhance the understanding of novel combination therapy strategies to be implemented in the future for such patients.展开更多
Objective: Observing human to mouse one-way mixed lymphocyte culture(xMLC) and the effect of new immunosuppressant-Rapamycin on XMLC. Methods: Mouse splenic lymphocyte were collected and treated by mitomycin as activa...Objective: Observing human to mouse one-way mixed lymphocyte culture(xMLC) and the effect of new immunosuppressant-Rapamycin on XMLC. Methods: Mouse splenic lymphocyte were collected and treated by mitomycin as activating cell; Human Peripheral blood lymphocytes(hPBL)were separated and gathered as reacting cell; Mouse splenic lymphocyte and hPBL wee mixed to incubate for 1 week; The researchers designed control、RPM groups,and experiment(drugs)grup have different concentration. Results: HPBL in the experiment groups (mixed mouse lymphocyte)proliferated obviously,the amount of3H-TdR in corporation increased evidently(P<0 05,The mean percentage of CD 4, CD 8, LgG, LgM positive cells rose markedly. HPBL in the experiment groups less proliferated,the amount of 3H-TdR incorporation declined,RPM's ic50(50%inhibition concentration)approximately in 1.5 nmol/L; the mean percentage of CD 4, CD 8, IgG, IgM positive cells fell obviously. Conclusion: The human to mouse one-way MLC has obvious lymphocyte proliferation. New immunosuppressants-Rapamycin have powerful effete on XMLC.展开更多
Liquid chromatography tandem mass spectrometry(LC-MS/MS) plays an important role in clinical diagnostics. Although LC-MS/MS is superior in terms of accurately quantifying molecules in complex matrices,instrument footp...Liquid chromatography tandem mass spectrometry(LC-MS/MS) plays an important role in clinical diagnostics. Although LC-MS/MS is superior in terms of accurately quantifying molecules in complex matrices,instrument footprint, operation and maintenance complexity also hinder its expansion as the analytical technique of choice. In this study, a compact LC-MS instrument was developed, in which an assembled liquid chromatograph was coupled with a miniature ion trap mass spectrometer. The overall instrument has a footprint of 69 cm × 31 cm × 31 cm, and it requires no gas supply as well as minimum maintenance. Furthermore, the use of LC-MS is in accord with conventional clinical diagnostic protocols, and the choice of ion trap offers tandem MS performance. The results showed that the use of LC could improve both mixture analysis capability and detection sensitivity of the miniature mass spectrometer. After optimization, feasibility of this instrument in clinical practice was demonstrated by the quantitation of four widely used immunosuppressants in blood samples. Relatively good linearities were obtained, which spanned the reference ranges of effective therapeutic concentrations of each immunosuppressant. Intraday and inter-day accuracy and precision of analytical method were also assessed. This work showed that a compact LC-MS instrument could be used in clinical diagnosis, either to replace conventional lab-scale instruments or to be used in POCT applications.展开更多
AIM: To assess the effectiveness of immunosuppressants in the prophylaxis of corneal allograft rejection after high-risk keratoplasty and normal-risk keratoplasty. METHODS: We searched the Cochrane Central Register of...AIM: To assess the effectiveness of immunosuppressants in the prophylaxis of corneal allograft rejection after high-risk keratoplasty and normal-risk keratoplasty. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CNKI, VIP and reference lists of articles. Date of most recent search: 18 June, 2011. All randomised controlled trials (RCTs) assessing the use of immunosupressants in the prevention of graft rejection, irrespective of publication language. Two authors assessed trial quality and extracted data independently. Only dichotomous outcomes (clear graft survival, ratio of immune reactions and side effects) were available and were expressed as relative risk (RR) and 95% confidence intervals (CI). RESULTS: Seven studies were included in this review. In the comparing of mycophenolate mofetil (MMF) with placebo, the results showed MMF could significantly reduce immune reactions compared with placebo (RR 1.08 95% Cl 0.95 to 1.21), but no effect on clear graft survival (RR 1.11 95% Cl 0.90 to 1.35). In clear graft survival and immune reactions, MMF and cyclosporine A (CsA) showed similar effect (RR 1.11 95% Cl 0.90 to 1.35, and RR 1.48, 95% Cl 0.56 to 3.93, respectively). Tacrolimus (FK506) and steroid showed similar effects on clear graft survival and immune reactions (RR 0.32, 95% CI 0.02 to 6.21, and RR 1.00, 95%CI 0.88 to 1.14, respectively). No drug relative side effect has been found. CONCLUSION: MMF may reduce immune reactions in both normal-risk and high-risk rejection of penetrating keratoplasty. CsA and FK506 showed similar effects as MMF. However, due to the lack of large clinical trials, the evidence remain weak, the quality of evidences were rated as very low to moderate. Large, properly randomised, placebo-controlled, double masked trials are needed to evaluate the effect of immunosuppressants.展开更多
BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a multi-system fibroinflammatory disorder that can involve any organ,including the salivary glands,pancreas,and biliary tree.Treatment of immunoglobulin G4-relat...BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a multi-system fibroinflammatory disorder that can involve any organ,including the salivary glands,pancreas,and biliary tree.Treatment of immunoglobulin G4-related sclerosing cholangitis(IgG4-SC)is similar to that for IgG4-RD,but progression is irreversible in some cases.We present a case of IgG4-SC in which an immuno-suppressant induced marked clinical and radiologic improvement.CASE SUMMARY A 63-year-old male presented with a prominent itching sensation and wholebody jaundice.He showed obstructive-pattern jaundice,an elevated IgG4 level,and infiltration of a large number of IgG4-positive cells in the ampulla of Vater.The imaging findings of intrahepatic duct(IHD)and common bile duct dilation,an elevated serum IgG4 level,and characteristic histological findings led to diagnosis of IgG4-SC that compatible with the 2019 ACR/EULAR classification criteria.We planned to treat the patient with high-dose glucocorticoid(GC),followed by cyclophosphamide pulse therapy.After treatment with high-dose GC and an immunosuppressant,imaging studies showed that IHD dilatation had completely resolved.CONCLUSION Prompt diagnosis and appropriate treatment of IgG4-SC are important.Because there is a risk of relapse of IgG4-SC,the GC dose should be gradually reduced,and a maintenance immunosuppressant should be given.展开更多
Objective: To evaluate the efficacy and safety of the immunosuppressant treatment among 10 post-renal transplantation recipients with malignant tumors. Methods: Conversion to sirolimus (SRL) treatment was performed fo...Objective: To evaluate the efficacy and safety of the immunosuppressant treatment among 10 post-renal transplantation recipients with malignant tumors. Methods: Conversion to sirolimus (SRL) treatment was performed for 10 cases which had found malignant tumors after kidney transplantation. During the follow-up period, the recurrence and diffusion of the tumor, the renal function and rejection were monitored. Results: All these cases despite the death had been followed up for at least 1 year. 9 cases had no recurrence and diffusion. 1 case died due to the tumor diffusion 7 months after the drug conversion. 1 case suffered once acute rejection 2 months after the drug conversion. This acute rejection had been inhibited by flushing dose MP. Conclusion: As a new immunosuppressant, SRL not only can prevent the generation of AR, but inhibit proliferation and development of malignant tumors in kidney transplantation recipients as well.展开更多
AIM To investigate the specific effects of immunosuppressants on the antiviral action of daclatasvir and asunaprevir.METHODS The antiviral activity of daclatasvir(DCV) and asunaprevir(ASV) combined with immunosuppress...AIM To investigate the specific effects of immunosuppressants on the antiviral action of daclatasvir and asunaprevir.METHODS The antiviral activity of daclatasvir(DCV) and asunaprevir(ASV) combined with immunosuppressants was tested using two in vitro models for hepatitis C virus(HCV) infection.RESULTS Tacrolimus, rapamycin and cyclosporine did not negatively affect the antiviral action of DCV or ASV. Mycophenolic acid(MPA) showed additive antiviral effects combined with these direct acting antivirals(DAAs). MPA induces interferon-stimulated genes(ISGs) and is a potent GTP synthesis inhibitor. DCV or ASV did not induce ISGs expression nor affected ISG induction by MPA. Rather, the combined antiviral effect of MPA with DCV and ASV was partly mediated via inhibition of GTP synthesis.CONCLUSION Immunosuppressants do not negatively affect the antiviral activity of DAAs. MPA has additive effect on the antiviral action of DCV and ASV. This combined benefit needs to be confirmed in prospective clinical trials.展开更多
IgA nephropathy is the most common primary glomerular disease in China and even in the world, and it is also the most common cause of end-stage renal disease. The pathogenesis of IgA nephropathy is not clear. At prese...IgA nephropathy is the most common primary glomerular disease in China and even in the world, and it is also the most common cause of end-stage renal disease. The pathogenesis of IgA nephropathy is not clear. At present, it is mainly considered that abnormal IgA immune complex deposition in glomerular mesangial area leads to a series of clinical manifestations. Therefore, at present, in addition to supporting treatment, the treatment of IgA nephropathy mainly focuses on glucocorticoids and various immunosuppressants, but the efficacy and safety of the above immunosuppressants on IgA nephropathy are still controversial. This paper reviews the current use of immunosuppressants in the treatment of IgA nephropathy.展开更多
Immunosuppression in organ transplantation was revolutionary for its time,but technological and population changes cast new light on its use.First,metabolic syndrome(MS) is increasing as a public health issue,concomit...Immunosuppression in organ transplantation was revolutionary for its time,but technological and population changes cast new light on its use.First,metabolic syndrome(MS) is increasing as a public health issue,concomitantly increasing as an issue for post-orthotopic liver transplantation patients;yet the medications regularly used for immunosuppression contribute to dysfunctional metabolism.Current mainstay immunosuppression involves the use of calcineurin inhibitors;these are potent,but nonspecifically disrupt intracellular signaling in such a way as to exacerbate the impact of MS on the liver.Second,the impacts of acute cellular rejection and malignancy are reviewed in terms of their severity and possible interactions with immunosuppressive medications.Finally,immunosuppressive agents must be considered in terms of new developments in hepatitis C virus treatment,which undercut what used to be inevitable viral recurrence.Overall,while traditional immunosuppressive agents remain the most used,the specific side-effect profiles of all immunosuppressants must be weighed in light of the individual patient.展开更多
Hepatitis C(HCV)-infected patients have a poorer survival post-liver transplantation compared to patients transplanted for other indications,since HCV recurrence post-transplant is universal and commonly follows an ag...Hepatitis C(HCV)-infected patients have a poorer survival post-liver transplantation compared to patients transplanted for other indications,since HCV recurrence post-transplant is universal and commonly follows an aggressive course.There is increasing evidence that in the non-transplant setting,induction of hepatocyte apoptosis is one of the main mechanisms by which HCV drives liver inflammation and fibrosis,and that HCV proteins directly promote apoptosis.Recent studies have shown that post-liver transplant,there is a link between high levels of HCV replication,enhanced hepatocyte apoptosis and the subsequent development of rapidly progressive liver fibrosis.Although the responsible mechanisms remain unclear,it is likely that immunosuppressive drugs play an important role.It is well known that immunosuppressants impair immune control of HCV,thereby allowing increased viral replication.However there is also evidence that immunosuppressants may directly induce apoptosis and this may be facilitated by the presence of high levels of HCV replication.Thus HCV and immunosuppressants may synergistically interact to further enhance apoptosis and drive more rapid fibrosis.These findings suggest that modulation of apoptosis within the liver either by changing immunosuppressive therapy or the use of apoptosis inhibitors may help prevent fibrosis progression in patients with post-transplant HCV disease.展开更多
Controlling the immune response with only clinically approved immunosuppressant drugs is difficult in renal heterotra ns plantation from pigs to nonhuman primates.Moreover,to the best of our knowledge,no reports exist...Controlling the immune response with only clinically approved immunosuppressant drugs is difficult in renal heterotra ns plantation from pigs to nonhuman primates.Moreover,to the best of our knowledge,no reports exist on the use of fetal pigs as kidney donors.This study aimed to compare the degree of transplant rejection between neonatal and fetal kidneys,with genetically unmodified pigs as donors and cynomolgus monkeys as recipients.The left kidneys of the recipient monkeys were removed,followed by transplantation of neonatal as well as fetal pig kidneys,which had undergone vascular anastomosis at the same site,into the retroperitoneum.Immunosuppression was performed with only US Food and Drug Administration-approved drugs.The fetal kidneys were transplanted into the omentum and paraaortic regions of cynomolgus monkeys.Consequently,the engraftment and development of the transplanted tissues were pathologically examined by sampling over time(twice in each experiment).An acute rejection was observed after a few weeks in neonatal renal grafts with vascular anastomosis.However,fetal pig kidneys were spared from rejection despite the administration of the same immunosuppressive protocol to the monkeys and the recipient blood vessels flowing into the fetal kidneys.The immunogenicity of fetal kidneys in pig-monkey renal heterotransplantation was lower than that of neonatal kidneys.展开更多
Hepatitis B viral(HBV)reactivation in the immunosuppressed is a significant problem even in patients who have achieved serological clearance due to the persistence of HBV as cccDNA.HBV reactivation will continue to po...Hepatitis B viral(HBV)reactivation in the immunosuppressed is a significant problem even in patients who have achieved serological clearance due to the persistence of HBV as cccDNA.HBV reactivation will continue to pose a significant healthcare burden given the high prevalence of HBV and increasing use of immunosuppressants.Screening of hepatitis B surface antigen,antibody to Hepatitis B core antigen antibody and HBV DNA levels should be done routinely in all patients planned for significant immunosuppressant use.We aimed to examine the factors affecting reactivation risk.This depended on HBV disease status,the underlying disease requiring immunosuppression,and the specific immunosuppressive regime.While antiviral prophylaxis can prevent reactivation,it increases cost and still has risk of delayed reactivation after stopping antivirals and close follow-up and on-demand treatment is a good alternative for patients at risk of reactivation.展开更多
Importance:It remained unclear that the efficacy comparison between low-dose immune tolerance induction(LD-ITI)incorporating immunosuppressants(IS)when severe hemophilia A(SHA)patients had inhibitor-titer≥200 Bethesd...Importance:It remained unclear that the efficacy comparison between low-dose immune tolerance induction(LD-ITI)incorporating immunosuppressants(IS)when severe hemophilia A(SHA)patients had inhibitor-titer≥200 Bethesda Units(BU)/mL(LD-ITI-IS^(200) regimen)and LD-ITI combining with IS when SHA patients had inhibitor-titer≥40 BU/mL(LD-ITI-IS^(40) regimen).Objective:To compare the efficacy of the LD-ITI-IS^(200) regimen with that of the LD-ITI-IS^(40) regimen for SHA patients with high-titer inhibitors.Methods:A prospective cohort study on patients receiving LD-ITI-IS^(200) compared to those receiving LD-ITI-IS^(40) from January 2021 to December 2023.Both received LD-ITI[FVIII 50 IU/kg every other day].IS(rituximab+prednisone)was added when peak inhibitor tier≥200 BU/mL in the LD-ITI-IS^(200) regimen and≥40 BU/mL in the LD-ITI-IS^(40) regimen.Success is defined as a negative inhibitor plus FVIII recovery≥66%of the expected.Results:We enrolled 30 patients on LD-ITI-IS^(200) and 64 patients on LD-ITI-IS^(40),with similar baseline clinical characteristics.A lower IS-use rate was discovered in the LD-ITI-IS^(200) regimen compared to the LD-ITI-IS^(40) regimen(30.0%vs.62.5%).The two regimens(LD-ITI-IS^(200) vs.LD-ITI-IS^(40))had similar success rate(70.0%vs.79.7%),median time to success(9.4 vs.10.6 months),and annualized bleeding rate during ITI(3.7 vs.2.8).The cost to success was lower for LD-ITI-IS^(200) than for LD-ITI-IS^(40)(2107 vs.3256 US Dollar/kg).Among patients with peak inhibitor-titer 40-199 BU/mL,10 non-IS-using(on LD-ITI-IS^(200) regimen)and 28 IS-using(on LD-ITI-IS^(40) regimen)had similar success rates(70.0%vs.78.6%)and time to success(9.0 vs.8.8 months).Interpretation:In LD-ITI,IS are not necessary for inhibitor titer<200 BU/mL.展开更多
BACKGROUND Second-line treatment of Crohn’s disease(CD)commonly involves immunosuppressants such as azathioprine,mercaptopurine,or methotrexate(MTX),used either alone or in combination.AIM To investigate the current ...BACKGROUND Second-line treatment of Crohn’s disease(CD)commonly involves immunosuppressants such as azathioprine,mercaptopurine,or methotrexate(MTX),used either alone or in combination.AIM To investigate the current use of MTX among French gastroenterologists.METHODS An online questionnaire was distributed between March and August 2023 to 116 French gastroenterologists managing CD.A total of 87 respondents completed the survey and were included in the analysis.RESULTS Respondents reported a mean annual caseload of 140 CD patients(median:50).Overall,71%prescribed MTX,predominantly in injectable form(92%),either as monotherapy or in combination with biologics or cyclosporin.MTX was prescribed for mild-to-moderate CD by 64%of respondents,and for severe CD by 58%,often in combination with an anti-tumor necrosis factor agent(89%and 94%,respectively).Injectable MTX was favored(84%)in specific clinical scenarios:Patients with articular manifestations(77%),Epstein-Barr virus-negative status(65%),or aged over 65 years(58%).Among the 29%of non-prescribers,the primary reason cited was lack of familiarity with MTX use(60%).Both prescribers and non-prescribers expressed the need for clearer guidelines and real-world data to support MTX use.CONCLUSION Regardless of prescribing habits,most respondents had a favorable opinion of MTX and recognized its good longterm safety profile.French learned societies and medical associations should provide consensus guidelines on MTX use,supported by validated real-world safety and effectiveness data.展开更多
BACKGROUND Autoimmune myocarditis(AM)associated with autoimmune diseases can cause complete atrioventricular block(CAVB),but the related autoantigens and the underlying mechanisms are unclear.Anti-SSA/Ro antibodies ma...BACKGROUND Autoimmune myocarditis(AM)associated with autoimmune diseases can cause complete atrioventricular block(CAVB),but the related autoantigens and the underlying mechanisms are unclear.Anti-SSA/Ro antibodies may play an important role in this process,but cases of AM with positive anti-SSA/Ro antibodies are rare.In addition,arrhythmias,such as atrioventricular block,are very common in patients with autoimmune diseases,but severe atrioventricular block requiring permanent pacemaker implantation is extremely rare.CASE SUMMARY The patient in this case had AM with anti-SSA/Ro antibody positivity,which was associated with connective tissue disease,and the patient subsequently developed CAVB.After intensive immunosuppressive therapy,the antibody test results became negative,and pulmonary hypertension significantly improved.However,the outcome of permanent pacemaker implantation did not change.CONCLUSION In clinical practice,the awareness of adult AM associated with autoimmune diseases combined with CAVB should be strengthened in clinicians,and anti-SSA/Ro antibodies may play a role in this process.Therefore,improving the detection of antibodies and early intervention,such as active immunosuppression therapy,may be very important for improving disease prognosis.For patients who do not respond to immunosuppressive therapy,implantation of a permanent pacemaker may become an essential treatment option.展开更多
Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for pati...Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”展开更多
Background and Aims:All-oral interlferon-free antivirals are highly effective in treating recurrent hepatitis C (HCV) infection in liver transplant (LT) recipients.The aim of the study was to assess immunosuppression ...Background and Aims:All-oral interlferon-free antivirals are highly effective in treating recurrent hepatitis C (HCV) infection in liver transplant (LT) recipients.The aim of the study was to assess immunosuppression needs after achieving a sustained viral response (SVR).Methods:We compared immunosuppression needs before and after achieving a SVR in adult LT recipients treated for recurrent HCV infection with alloral direct acting agents.Results:We identified 52 liver LT treated recipients who achieved a SVR.The median (25th and 75th percentile interquartile range [IQR]) age was 62 years (57.75,65).Most recipients received tacrolimus (TAC) for their immunosuppressant regimen.After achieving SVR,there was no statistically significant difference in daily dose of TAC unadjusted per weight (p > 0.05).However,there was a statistically significant decrease in daily dose of TAC adjusted per weight,serum levels of TAC,and the product of glomerular filtration rate and TAC.No statistically significant differences in cyclosporine unadjusted/adjusted per weight daily dose or serum levels were noted.Conclusions:Immunosuppression needs were increased for those patients treated with TAC but not cyclosporine.LT recipients prescribed TAC require close monitoring after treatment completion to avoid potential risk of acute rejection.展开更多
Background Optic neuritis （ON） is often the first symptom of multiple sclerosis （MS） and neuromyelitis optica （NMO） while there has been very little research reported on ON combined with Sj（o）gren＇s syndrome ...Background Optic neuritis （ON） is often the first symptom of multiple sclerosis （MS） and neuromyelitis optica （NMO） while there has been very little research reported on ON combined with Sj（o）gren＇s syndrome （SS）.The aim of this study is to provide different treatments and services for and NMO patients combined with SS.Methods Twenty-seven patients with ON combined SS were divided into two groups：corticosteroid group （C group,methylprednisolone sodium succinate,14 patients） and corticosteroid＋ immunosuppressant group （C＋I group,leflunomide,13 patients）.ON relapse times in 1 year after treatment,number of patients who relapsed to NMO/MS in 1 years,visual acuity and retina nerve fiber layer （RNFL） thickness were measured.Mann Whitney-Wilcoxon test was used to compare continuous variables and Chi-square test or Fisher＇s exact test was to compare proportions.Results ON combined with SS patients had higher incidence rates in middle-aged women who have binocular damage and heavier visual function damage or when there is an easy relapse,and the patients are often hormone dependent.The patients are more likely anti-aquaporin-4 IgG seropositive （70.4％）.They are liable to form a centrocecal scotoma and tubular vision.The times of relapse decreased in patients who used immunosuppressant,and a significant difference was found between immunosuppressant and non-immunosuppressant groups in visual acuity recovery during 6-month followup period （P ＜0.05）; however,the RNFL thickness at the four quadrants was not significantly different.Conclusions The effect of immunosuppressant plus corticosteroid on the early onset of ON combined with SS was to provide ON remedy and to prevent recurrence in clinics.This study provides a significant reference for the prevention and treatment of ON on the basis of immunosuppressant and corticosteroid.展开更多
文摘In recent years,pharmacogenetics has emerged as an important tool for choosing the right immunosuppressant drug and its appropriate dose.Indeed,pharmacogenetics may exert its action on immunosuppressant drugs at three levels.Pharmacogenetics identifies and studies the genes involved in encoding the proteins involved in drug pharmacokinetics and in encoding the enzymes involved in drug degradation.Pharmacogenetics is also relevant in encoding the enzymes and proteins involved in codifying the transmembrane proteins involved in transmembrane passage favoring the absorption and intracellular action of several immunosuppressants.Pharmacogenetics concern the variability of genes encoding the proteins involved as immunosuppressant triggers in the pharmacodynamic pathways.Of course,not all genes have been discovered and studied,but some of them have been clearly examined and their relevance together with other factors such as age and race has been defined.Other genes on the basis of relevant studies have been proposed as good candidates for future studies.Unfortunately,to date,clear conclusions may be drawn only for those drugs that are metabolized by CYP3A5 and its genotyping before kidney,heart and lung transplantation is recommended.The conclusions of the studies on the recommended candidate genes,together with the development of omics techniques could in the future allow us to choose the right dose of the right immunosuppressant for the right patient.
基金Supported by National Natural Science Foundation of China,No.82270649.
文摘BACKGROUND Chylous ascites is caused by disruption of the lymphatic system,which is characterized by the accumulation of a turbid fluid containing high levels of triglycerides within the abdominal cavity.The two most common causes are cirrhosis and tuberculosis,and colon signer ring cell carcinoma(SRCC)due to the use of immunosuppressants is extremely rare in cirrhotic patients after liver transplantation,making it prone to misdiagnosis and missed diagnosis.CASE SUMMARY A 52-year-old man who underwent liver transplantation and was administered with immunosuppressants for 8 months was admitted with a 3-month history of progressive abdominal distention.Initially,based on lymphoscintigraphy and lymphangiography,lymphatic obstruction was considered,and cystellar chyli decompression with band lysis and external membrane stripping of the lymphatic duct was performed.However,his abdominal distention was persistent without resolution.Abdominal paracentesis revealed allogenic cells in the ascites,and immunohistochemistry analysis revealed adenocarcinoma cells with phenotypic features suggestive of a gastrointestinal origin.Gastrointestinal endoscopy was performed,and biopsy showed atypical signet ring cells in the ileocecal valve.The patient eventually died after a three-month follow-up due to progression of the tumor.CONCLUSION Colon SRCC,caused by immunosuppressants,is an unusual but un-neglected cause of chylous ascites.
文摘Prostate cancer is a malignant tumor with a high incidence in elderly men.In recent years,with the improvement of people’s living standards and the advancement of detection technology,the incidence of prostate cancer has been increasing year by year.Castration-resistant prostate cancer(CRPC)is a highly challenging type of advanced prostate cancer treatment,which clinically shows resistance to hormonal deprivation therapy.The overall treatment efficacy of CRPC is currently poor and further relevant therapeutic studies are needed to improve patient survival and quality of life.Immunosuppressants can play a role in combating the immune system of tumors,and abiraterone has also achieved remarkable results in prostate cancer treatment.This study will investigate the possible clinical effects and safety of immunosuppressants combined with abiraterone in the treatment of metastatic CRPC.The population-based study will provide clinicians with more effective treatment options,as well as enhance the understanding of novel combination therapy strategies to be implemented in the future for such patients.
文摘Objective: Observing human to mouse one-way mixed lymphocyte culture(xMLC) and the effect of new immunosuppressant-Rapamycin on XMLC. Methods: Mouse splenic lymphocyte were collected and treated by mitomycin as activating cell; Human Peripheral blood lymphocytes(hPBL)were separated and gathered as reacting cell; Mouse splenic lymphocyte and hPBL wee mixed to incubate for 1 week; The researchers designed control、RPM groups,and experiment(drugs)grup have different concentration. Results: HPBL in the experiment groups (mixed mouse lymphocyte)proliferated obviously,the amount of3H-TdR in corporation increased evidently(P<0 05,The mean percentage of CD 4, CD 8, LgG, LgM positive cells rose markedly. HPBL in the experiment groups less proliferated,the amount of 3H-TdR incorporation declined,RPM's ic50(50%inhibition concentration)approximately in 1.5 nmol/L; the mean percentage of CD 4, CD 8, IgG, IgM positive cells fell obviously. Conclusion: The human to mouse one-way MLC has obvious lymphocyte proliferation. New immunosuppressants-Rapamycin have powerful effete on XMLC.
基金supported by the National Key Research and Development Program of China (No. 2020YFF01014502)the National Natural Science of Foundation of China (Nos. 21922401,201827810)。
文摘Liquid chromatography tandem mass spectrometry(LC-MS/MS) plays an important role in clinical diagnostics. Although LC-MS/MS is superior in terms of accurately quantifying molecules in complex matrices,instrument footprint, operation and maintenance complexity also hinder its expansion as the analytical technique of choice. In this study, a compact LC-MS instrument was developed, in which an assembled liquid chromatograph was coupled with a miniature ion trap mass spectrometer. The overall instrument has a footprint of 69 cm × 31 cm × 31 cm, and it requires no gas supply as well as minimum maintenance. Furthermore, the use of LC-MS is in accord with conventional clinical diagnostic protocols, and the choice of ion trap offers tandem MS performance. The results showed that the use of LC could improve both mixture analysis capability and detection sensitivity of the miniature mass spectrometer. After optimization, feasibility of this instrument in clinical practice was demonstrated by the quantitation of four widely used immunosuppressants in blood samples. Relatively good linearities were obtained, which spanned the reference ranges of effective therapeutic concentrations of each immunosuppressant. Intraday and inter-day accuracy and precision of analytical method were also assessed. This work showed that a compact LC-MS instrument could be used in clinical diagnosis, either to replace conventional lab-scale instruments or to be used in POCT applications.
文摘AIM: To assess the effectiveness of immunosuppressants in the prophylaxis of corneal allograft rejection after high-risk keratoplasty and normal-risk keratoplasty. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CNKI, VIP and reference lists of articles. Date of most recent search: 18 June, 2011. All randomised controlled trials (RCTs) assessing the use of immunosupressants in the prevention of graft rejection, irrespective of publication language. Two authors assessed trial quality and extracted data independently. Only dichotomous outcomes (clear graft survival, ratio of immune reactions and side effects) were available and were expressed as relative risk (RR) and 95% confidence intervals (CI). RESULTS: Seven studies were included in this review. In the comparing of mycophenolate mofetil (MMF) with placebo, the results showed MMF could significantly reduce immune reactions compared with placebo (RR 1.08 95% Cl 0.95 to 1.21), but no effect on clear graft survival (RR 1.11 95% Cl 0.90 to 1.35). In clear graft survival and immune reactions, MMF and cyclosporine A (CsA) showed similar effect (RR 1.11 95% Cl 0.90 to 1.35, and RR 1.48, 95% Cl 0.56 to 3.93, respectively). Tacrolimus (FK506) and steroid showed similar effects on clear graft survival and immune reactions (RR 0.32, 95% CI 0.02 to 6.21, and RR 1.00, 95%CI 0.88 to 1.14, respectively). No drug relative side effect has been found. CONCLUSION: MMF may reduce immune reactions in both normal-risk and high-risk rejection of penetrating keratoplasty. CsA and FK506 showed similar effects as MMF. However, due to the lack of large clinical trials, the evidence remain weak, the quality of evidences were rated as very low to moderate. Large, properly randomised, placebo-controlled, double masked trials are needed to evaluate the effect of immunosuppressants.
文摘BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a multi-system fibroinflammatory disorder that can involve any organ,including the salivary glands,pancreas,and biliary tree.Treatment of immunoglobulin G4-related sclerosing cholangitis(IgG4-SC)is similar to that for IgG4-RD,but progression is irreversible in some cases.We present a case of IgG4-SC in which an immuno-suppressant induced marked clinical and radiologic improvement.CASE SUMMARY A 63-year-old male presented with a prominent itching sensation and wholebody jaundice.He showed obstructive-pattern jaundice,an elevated IgG4 level,and infiltration of a large number of IgG4-positive cells in the ampulla of Vater.The imaging findings of intrahepatic duct(IHD)and common bile duct dilation,an elevated serum IgG4 level,and characteristic histological findings led to diagnosis of IgG4-SC that compatible with the 2019 ACR/EULAR classification criteria.We planned to treat the patient with high-dose glucocorticoid(GC),followed by cyclophosphamide pulse therapy.After treatment with high-dose GC and an immunosuppressant,imaging studies showed that IHD dilatation had completely resolved.CONCLUSION Prompt diagnosis and appropriate treatment of IgG4-SC are important.Because there is a risk of relapse of IgG4-SC,the GC dose should be gradually reduced,and a maintenance immunosuppressant should be given.
文摘Objective: To evaluate the efficacy and safety of the immunosuppressant treatment among 10 post-renal transplantation recipients with malignant tumors. Methods: Conversion to sirolimus (SRL) treatment was performed for 10 cases which had found malignant tumors after kidney transplantation. During the follow-up period, the recurrence and diffusion of the tumor, the renal function and rejection were monitored. Results: All these cases despite the death had been followed up for at least 1 year. 9 cases had no recurrence and diffusion. 1 case died due to the tumor diffusion 7 months after the drug conversion. 1 case suffered once acute rejection 2 months after the drug conversion. This acute rejection had been inhibited by flushing dose MP. Conclusion: As a new immunosuppressant, SRL not only can prevent the generation of AR, but inhibit proliferation and development of malignant tumors in kidney transplantation recipients as well.
文摘AIM To investigate the specific effects of immunosuppressants on the antiviral action of daclatasvir and asunaprevir.METHODS The antiviral activity of daclatasvir(DCV) and asunaprevir(ASV) combined with immunosuppressants was tested using two in vitro models for hepatitis C virus(HCV) infection.RESULTS Tacrolimus, rapamycin and cyclosporine did not negatively affect the antiviral action of DCV or ASV. Mycophenolic acid(MPA) showed additive antiviral effects combined with these direct acting antivirals(DAAs). MPA induces interferon-stimulated genes(ISGs) and is a potent GTP synthesis inhibitor. DCV or ASV did not induce ISGs expression nor affected ISG induction by MPA. Rather, the combined antiviral effect of MPA with DCV and ASV was partly mediated via inhibition of GTP synthesis.CONCLUSION Immunosuppressants do not negatively affect the antiviral activity of DAAs. MPA has additive effect on the antiviral action of DCV and ASV. This combined benefit needs to be confirmed in prospective clinical trials.
文摘IgA nephropathy is the most common primary glomerular disease in China and even in the world, and it is also the most common cause of end-stage renal disease. The pathogenesis of IgA nephropathy is not clear. At present, it is mainly considered that abnormal IgA immune complex deposition in glomerular mesangial area leads to a series of clinical manifestations. Therefore, at present, in addition to supporting treatment, the treatment of IgA nephropathy mainly focuses on glucocorticoids and various immunosuppressants, but the efficacy and safety of the above immunosuppressants on IgA nephropathy are still controversial. This paper reviews the current use of immunosuppressants in the treatment of IgA nephropathy.
文摘Immunosuppression in organ transplantation was revolutionary for its time,but technological and population changes cast new light on its use.First,metabolic syndrome(MS) is increasing as a public health issue,concomitantly increasing as an issue for post-orthotopic liver transplantation patients;yet the medications regularly used for immunosuppression contribute to dysfunctional metabolism.Current mainstay immunosuppression involves the use of calcineurin inhibitors;these are potent,but nonspecifically disrupt intracellular signaling in such a way as to exacerbate the impact of MS on the liver.Second,the impacts of acute cellular rejection and malignancy are reviewed in terms of their severity and possible interactions with immunosuppressive medications.Finally,immunosuppressive agents must be considered in terms of new developments in hepatitis C virus treatment,which undercut what used to be inevitable viral recurrence.Overall,while traditional immunosuppressive agents remain the most used,the specific side-effect profiles of all immunosuppressants must be weighed in light of the individual patient.
文摘Hepatitis C(HCV)-infected patients have a poorer survival post-liver transplantation compared to patients transplanted for other indications,since HCV recurrence post-transplant is universal and commonly follows an aggressive course.There is increasing evidence that in the non-transplant setting,induction of hepatocyte apoptosis is one of the main mechanisms by which HCV drives liver inflammation and fibrosis,and that HCV proteins directly promote apoptosis.Recent studies have shown that post-liver transplant,there is a link between high levels of HCV replication,enhanced hepatocyte apoptosis and the subsequent development of rapidly progressive liver fibrosis.Although the responsible mechanisms remain unclear,it is likely that immunosuppressive drugs play an important role.It is well known that immunosuppressants impair immune control of HCV,thereby allowing increased viral replication.However there is also evidence that immunosuppressants may directly induce apoptosis and this may be facilitated by the presence of high levels of HCV replication.Thus HCV and immunosuppressants may synergistically interact to further enhance apoptosis and drive more rapid fibrosis.These findings suggest that modulation of apoptosis within the liver either by changing immunosuppressive therapy or the use of apoptosis inhibitors may help prevent fibrosis progression in patients with post-transplant HCV disease.
基金supported by the Japan Agency for Medical Research and Development(AMED21bk0104094h0003)a grant from Sumitomo Dainippon Pharma Co.,Ltd。
文摘Controlling the immune response with only clinically approved immunosuppressant drugs is difficult in renal heterotra ns plantation from pigs to nonhuman primates.Moreover,to the best of our knowledge,no reports exist on the use of fetal pigs as kidney donors.This study aimed to compare the degree of transplant rejection between neonatal and fetal kidneys,with genetically unmodified pigs as donors and cynomolgus monkeys as recipients.The left kidneys of the recipient monkeys were removed,followed by transplantation of neonatal as well as fetal pig kidneys,which had undergone vascular anastomosis at the same site,into the retroperitoneum.Immunosuppression was performed with only US Food and Drug Administration-approved drugs.The fetal kidneys were transplanted into the omentum and paraaortic regions of cynomolgus monkeys.Consequently,the engraftment and development of the transplanted tissues were pathologically examined by sampling over time(twice in each experiment).An acute rejection was observed after a few weeks in neonatal renal grafts with vascular anastomosis.However,fetal pig kidneys were spared from rejection despite the administration of the same immunosuppressive protocol to the monkeys and the recipient blood vessels flowing into the fetal kidneys.The immunogenicity of fetal kidneys in pig-monkey renal heterotransplantation was lower than that of neonatal kidneys.
文摘Hepatitis B viral(HBV)reactivation in the immunosuppressed is a significant problem even in patients who have achieved serological clearance due to the persistence of HBV as cccDNA.HBV reactivation will continue to pose a significant healthcare burden given the high prevalence of HBV and increasing use of immunosuppressants.Screening of hepatitis B surface antigen,antibody to Hepatitis B core antigen antibody and HBV DNA levels should be done routinely in all patients planned for significant immunosuppressant use.We aimed to examine the factors affecting reactivation risk.This depended on HBV disease status,the underlying disease requiring immunosuppression,and the specific immunosuppressive regime.While antiviral prophylaxis can prevent reactivation,it increases cost and still has risk of delayed reactivation after stopping antivirals and close follow-up and on-demand treatment is a good alternative for patients at risk of reactivation.
基金Capital Health Development Research Project,Grant/Award Number:2022-2-2093Beijing Research Ward Construction Demonstration Unit Project,Grant/Award Number:BCRW202101+1 种基金National Natural Science Foundation of China,Grant/Award Number:82270133Beijing Municipal Scienceand Technology Commission,Grant/Award Number:Z221100007422067。
文摘Importance:It remained unclear that the efficacy comparison between low-dose immune tolerance induction(LD-ITI)incorporating immunosuppressants(IS)when severe hemophilia A(SHA)patients had inhibitor-titer≥200 Bethesda Units(BU)/mL(LD-ITI-IS^(200) regimen)and LD-ITI combining with IS when SHA patients had inhibitor-titer≥40 BU/mL(LD-ITI-IS^(40) regimen).Objective:To compare the efficacy of the LD-ITI-IS^(200) regimen with that of the LD-ITI-IS^(40) regimen for SHA patients with high-titer inhibitors.Methods:A prospective cohort study on patients receiving LD-ITI-IS^(200) compared to those receiving LD-ITI-IS^(40) from January 2021 to December 2023.Both received LD-ITI[FVIII 50 IU/kg every other day].IS(rituximab+prednisone)was added when peak inhibitor tier≥200 BU/mL in the LD-ITI-IS^(200) regimen and≥40 BU/mL in the LD-ITI-IS^(40) regimen.Success is defined as a negative inhibitor plus FVIII recovery≥66%of the expected.Results:We enrolled 30 patients on LD-ITI-IS^(200) and 64 patients on LD-ITI-IS^(40),with similar baseline clinical characteristics.A lower IS-use rate was discovered in the LD-ITI-IS^(200) regimen compared to the LD-ITI-IS^(40) regimen(30.0%vs.62.5%).The two regimens(LD-ITI-IS^(200) vs.LD-ITI-IS^(40))had similar success rate(70.0%vs.79.7%),median time to success(9.4 vs.10.6 months),and annualized bleeding rate during ITI(3.7 vs.2.8).The cost to success was lower for LD-ITI-IS^(200) than for LD-ITI-IS^(40)(2107 vs.3256 US Dollar/kg).Among patients with peak inhibitor-titer 40-199 BU/mL,10 non-IS-using(on LD-ITI-IS^(200) regimen)and 28 IS-using(on LD-ITI-IS^(40) regimen)had similar success rates(70.0%vs.78.6%)and time to success(9.0 vs.8.8 months).Interpretation:In LD-ITI,IS are not necessary for inhibitor titer<200 BU/mL.
文摘BACKGROUND Second-line treatment of Crohn’s disease(CD)commonly involves immunosuppressants such as azathioprine,mercaptopurine,or methotrexate(MTX),used either alone or in combination.AIM To investigate the current use of MTX among French gastroenterologists.METHODS An online questionnaire was distributed between March and August 2023 to 116 French gastroenterologists managing CD.A total of 87 respondents completed the survey and were included in the analysis.RESULTS Respondents reported a mean annual caseload of 140 CD patients(median:50).Overall,71%prescribed MTX,predominantly in injectable form(92%),either as monotherapy or in combination with biologics or cyclosporin.MTX was prescribed for mild-to-moderate CD by 64%of respondents,and for severe CD by 58%,often in combination with an anti-tumor necrosis factor agent(89%and 94%,respectively).Injectable MTX was favored(84%)in specific clinical scenarios:Patients with articular manifestations(77%),Epstein-Barr virus-negative status(65%),or aged over 65 years(58%).Among the 29%of non-prescribers,the primary reason cited was lack of familiarity with MTX use(60%).Both prescribers and non-prescribers expressed the need for clearer guidelines and real-world data to support MTX use.CONCLUSION Regardless of prescribing habits,most respondents had a favorable opinion of MTX and recognized its good longterm safety profile.French learned societies and medical associations should provide consensus guidelines on MTX use,supported by validated real-world safety and effectiveness data.
文摘BACKGROUND Autoimmune myocarditis(AM)associated with autoimmune diseases can cause complete atrioventricular block(CAVB),but the related autoantigens and the underlying mechanisms are unclear.Anti-SSA/Ro antibodies may play an important role in this process,but cases of AM with positive anti-SSA/Ro antibodies are rare.In addition,arrhythmias,such as atrioventricular block,are very common in patients with autoimmune diseases,but severe atrioventricular block requiring permanent pacemaker implantation is extremely rare.CASE SUMMARY The patient in this case had AM with anti-SSA/Ro antibody positivity,which was associated with connective tissue disease,and the patient subsequently developed CAVB.After intensive immunosuppressive therapy,the antibody test results became negative,and pulmonary hypertension significantly improved.However,the outcome of permanent pacemaker implantation did not change.CONCLUSION In clinical practice,the awareness of adult AM associated with autoimmune diseases combined with CAVB should be strengthened in clinicians,and anti-SSA/Ro antibodies may play a role in this process.Therefore,improving the detection of antibodies and early intervention,such as active immunosuppression therapy,may be very important for improving disease prognosis.For patients who do not respond to immunosuppressive therapy,implantation of a permanent pacemaker may become an essential treatment option.
基金supported by the National Natural Science Foundation of China,No.82174112(to PZ)Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine,No.22HHZYSS00015(to PZ)State-Sponsored Postdoctoral Researcher Program,No.GZC20231925(to LN)。
文摘Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”
文摘Background and Aims:All-oral interlferon-free antivirals are highly effective in treating recurrent hepatitis C (HCV) infection in liver transplant (LT) recipients.The aim of the study was to assess immunosuppression needs after achieving a sustained viral response (SVR).Methods:We compared immunosuppression needs before and after achieving a SVR in adult LT recipients treated for recurrent HCV infection with alloral direct acting agents.Results:We identified 52 liver LT treated recipients who achieved a SVR.The median (25th and 75th percentile interquartile range [IQR]) age was 62 years (57.75,65).Most recipients received tacrolimus (TAC) for their immunosuppressant regimen.After achieving SVR,there was no statistically significant difference in daily dose of TAC unadjusted per weight (p > 0.05).However,there was a statistically significant decrease in daily dose of TAC adjusted per weight,serum levels of TAC,and the product of glomerular filtration rate and TAC.No statistically significant differences in cyclosporine unadjusted/adjusted per weight daily dose or serum levels were noted.Conclusions:Immunosuppression needs were increased for those patients treated with TAC but not cyclosporine.LT recipients prescribed TAC require close monitoring after treatment completion to avoid potential risk of acute rejection.
文摘Background Optic neuritis （ON） is often the first symptom of multiple sclerosis （MS） and neuromyelitis optica （NMO） while there has been very little research reported on ON combined with Sj（o）gren＇s syndrome （SS）.The aim of this study is to provide different treatments and services for and NMO patients combined with SS.Methods Twenty-seven patients with ON combined SS were divided into two groups：corticosteroid group （C group,methylprednisolone sodium succinate,14 patients） and corticosteroid＋ immunosuppressant group （C＋I group,leflunomide,13 patients）.ON relapse times in 1 year after treatment,number of patients who relapsed to NMO/MS in 1 years,visual acuity and retina nerve fiber layer （RNFL） thickness were measured.Mann Whitney-Wilcoxon test was used to compare continuous variables and Chi-square test or Fisher＇s exact test was to compare proportions.Results ON combined with SS patients had higher incidence rates in middle-aged women who have binocular damage and heavier visual function damage or when there is an easy relapse,and the patients are often hormone dependent.The patients are more likely anti-aquaporin-4 IgG seropositive （70.4％）.They are liable to form a centrocecal scotoma and tubular vision.The times of relapse decreased in patients who used immunosuppressant,and a significant difference was found between immunosuppressant and non-immunosuppressant groups in visual acuity recovery during 6-month followup period （P ＜0.05）; however,the RNFL thickness at the four quadrants was not significantly different.Conclusions The effect of immunosuppressant plus corticosteroid on the early onset of ON combined with SS was to provide ON remedy and to prevent recurrence in clinics.This study provides a significant reference for the prevention and treatment of ON on the basis of immunosuppressant and corticosteroid.
