Preliminary results of Thymosin-a1 versus interferon-α treatment in patients with HBeAg negative and serum HBV DNA positive chronic hepatitis B

INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer .

Precise prediction model and simplified scoring system for sustained combined response to interferon-α

AIM:To establish a predictive algorithm which may serve for selecting optimal candidates for interferon-α(IFN-α) treatment.METHODS:A total of 474 IFN-α treated hepatitis B virus e antigen(HBeAg)-positive patients were enrolled in the present study.The patients' baseline characteristics,such as age,gender,blood tests,activity grading(G) of intrahepatic inflammation,score(S) of liver fibrosis,hepatitis B virus(HBV) DNA and genotype were evaluated;therapy duration and response of each patient at the 24th wk after cessation of IFN-α treatment were also recorded.A predictive algorithm and scoring system for a sustained combined response(CR) to IFN-α therapy were established.About 10% of the patients were randomly drawn as the test set.Responses to IFN-α therapy were divided into CR,partial response(PR) and non-response(NR).The mixed set of PR and NR was recorded as PR+NR.RESULTS:Stratified by therapy duration,the most significant baseline predictive factors were alanine aminotransferase(ALT),HBV DNA level,aspartate aminotransferase(AST),HBV genotype,S,G,age and gender.According to the established model,the accuracies for sustained CR and PR+NR,respectively,were 86.4% and 93.0% for the training set,81.5% and 91.0% for the test set.For the scoring system,the sensitivity and specificity were 78.8% and 80.6%,respectively.There were positive correlations between ALT and AST,and G and S,respectively.CONCLUSION:With these models,practitioners may be able to propose individualized decisions that have an integrated foundation on both evidence-based medicine and personal characteristics.

Anti-rods/rings autoantibody generation in hepatitis Cpatients during interferon-α/ribavirin therapy

Chronic inflammation associated with hepatitis C virus(HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α(IFN-α) together with a daily dose of ribavirin. HCV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies(ANA). Between 20% to 40% of HCV patients treated with IFN-α and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings(RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings(antiRR) autoantibody production by HCV patients after IFN-α/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5'-monophosphate dehydrogenase 2(IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon.

IFIT1 polymorphisms predict interferon-α treatment efficiency for hepatitis B virus infection

AIM To investigate the association between interferoninduced protein with tetratricopeptide repeats 1(IFIT1) polymorphisms and interferon-α(IFNα) treatment efficiency among Chinese hepatitis B virus(HBV) infection patients.METHODS Two hundred and twenty five newly diagnosed chronichepatitis B(CHB) patients were enrolled in the study. All of these patients received IFNα treatment for a course of 48 wk, and were followed up for 24 wk after the treatment was end. Clinical information about virological response, hepatitis B e antigen(HBe Ag) seroconversion rate and combined response at the end of the treatment, as well as the sustained response by the time of following up 24 wk after the treatment, was collected. Four tag-single nucleotide polymorphisms(SNPs) of IFIT1 were selected and assessed for their association with these clinical outcomes.RESULTS At the end of the treatment, HBe Ag seroconversion was observed in 27.1% patients. Thirty-six point nine percent patients achieved virological response, and 15.6% patients exhibited combined response. Sustained response was obtained in 26.2% patients. The main HBV genotype of the study was genotype B. Patients who infected with HBV genotype B or C showed better treatment efficiency, no matter which clinical outcome was considered. Among the four SNPs assessed, rs303218(A > G) was found to be significantly associated with the end point virological response when assuming additive model [OR = 0.64(95%CI: 0.42-0.96), P = 0.032]. Patients who carried rs303218 GG genotype had a rather higher rate of achieving virological response(response rate: 52%, OR = 0.40, 95%CI: 0.18-0.91; P = 0.028) when compared to those had AA genotype(response rate: 27%). The most significant interaction was observed in patients who had relative lower baseline aspartate transaminase. No association between SNPs and HBe Ag seroconversion, combined response or sustained response was observed.CONCLUSION IFIT1 involves in the regulation of IFNα treatment for CHB and its polymorphism rs303218 can predict the end point virological response. The finding requires further validation.

Interferon-α induced severe thrombocytopenia:A case report and review of the literature

We report a case of severe thrombocytopenia following pegylated interferon-α 2a(Peg-IFN-α 2a)treatment of hepatitis C virus infection and summarize the clinical characteristics of 16 cases of IFN-α induced severe thrombocytopenia and its immune-mediated mechanism.Discontinuation of IFN-α and early administration of immunosuppressants are the effective therapy for IFN-αinduced severe thrombocytopenia.

Hepatitis C virus genotypes, HLA-DRB alleles and their response to interferon-α and ribavirin in patients with chronic hepatitis C

BACKGROUND: Hepatitis C virus (HCV) is a worldwide common disease. Some predictive factors influencing the response to interferon alpha (IFN-α) therapy have been identified, but the conclusions differ in various counties and areas. The aim of this study was to study the associa- tions between HCV genotypes, HLA-DRB alleles and their response to IFN-α and ribavirin in Chinese patients with chronic hepatitis C in Northeast China. METHODS: HCV genotypes of 113 patients with HCV were investigated. Gene chips were used to analyze the fre- quency of HLA-DRB in 25 of these patients and their re- sponse to IFN-α and ribavirin. The associations of HCV genotypes, HLA-DRB alleles and their response to IFN-α and ribavirin were also studied. RESULTS: The response rates differed in several types of HCV, with HCV 2b being the highest (57.78% ), HCV 1a and 2a lower (46.15% and 47.62% ) and HCV 1b the low- est (11.76% ). The response rates to IFN-α and ribavirin in patients with DRB1 07 were higher than those with DRB1 04. Sex, HCV type and HLA-DRB were all related to the response. Most female patients with HCV 2b and HLA- DRB1 07 presented complete response, whereas male pa- tients with HCV 1b and HLA-DRB1 04 usually demon- strated no response. DRB1 07 allele and HCV 2b were the factors closely related to the response. CONCLUSIONS: The response rate of HCV 1b may be the lowest even IFN-α and ribavirin are combined in treat- ment. Not only virus but also the host plays an important role in anti-virus therapy. Thus, it is necessary to adjust the host's immune status to accelerate the clearance of HCV.

Antitumor Effect of Interferon-α on U937 Human Acute Leukemia Cells in vitro and Its Molecular Mechanism

In order to investigate the antitumor effect and molecular mechanism of interferon-α （IFN-α） on human acute myeloid leukemia cell line U937 cells in vitro, the proliferation of U937 cells was determined by MTT assay, the apoptosis rate was analyzed by flow cytometry （FCM）, and the mRNA expression of cell cycle regulatory protein cyclin E was detected by RT-PCR. The results showed that IFN-α could inhibit the proliferation of U937 cells significantly in a dose- and time-dependent way （P〈0.01）, and induce the apoptosis of U937 cells also in a dose- and time-dependent manner at the concentration of 1000--4000 U/L （P〈0.01）. The apoptosis rate of U937 cells was even over 50% when cultured with IFN-α for 36--48 h at the concentration of 2000 -4000 U/L. Moreover, the expression of cyclin E mRNA was markedly inhibited by the addition of IFN-α, and the inhibition was time-dependent （P〈0.01）. It was concluded that the anti-leukemia mechanism of IFN-α might be correlated with its antiproliferative and apoptotic inducing effects, and the down-regulation of the cyclin E expression might be one of its molecular mechanisms.

Heterogeneity of immune control in chronic hepatitis B virus infection:Clinical implications on immunity with interferon-αtreatment and retreatment

Hepatitis B virus(HBV)infection is a global public health issue.Interferon-α(IFN-α)treatment has been used to treat hepatitis B for over 20 years,but fewer than 5%of Asians receiving IFN-αtreatment achieve functional cure.Thus,IFN-αretreatment has been introduced to enhance antiviral function.In recent years,immune-related studies have found that the complex interactions between immune cells and cytokines could modulate immune response networks,including both innate and adaptive immunity,triggering immune responses that control HBV replication.However,heterogeneity of the immune system to control HBV infection,particularly HBV-specific CD8^(+)T cell heterogeneity,has consequential effects on T cell-based immunotherapy for treating HBV infection.Altogether,the host’s genetic variants,negative-feedback regulators and HBV components affecting the immune system's ability to control HBV.In this study,we reviewed the literature on potential immune mechanisms affecting the immune control of HBV and the clinical effects of IFN-αtreatment and retreatment.

Intracerebroventricular administration of interferon-α enhanced splenic nerve in rats

Objective: To study the effect of intracerebroventricular administration of interferon (IFN-α) on the splenic sympathetic nerve activity. Methods: IFN-α (3×104 U/rat ) was microinjected into the third cerebroven-tricle of urethane and α-chloralose anesthetized rats. Electrical activity of the splenic nerve. body temperature and blood pressure were determined simultaneously. Results: Intracerebroventricular administration of IFN-α caused amarked and long term (>120 min) increase in the splenic nerve activity, which could be reversed by naloxonetreatment. No changes in blood pressure and body temperature. which could alter the sympathetic nerve actlvity by reflex. were observed during IFN-α and naloxone treatment. Naloxone intravenous injection alone had no effecton the splenic nerve activity. Conclusion: IFN-α in the brain can activate the splenic sympathetic nerve, and thisaction is, in some way, mediated by the opioid receptor.

Influence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B

AIM: To investigate the influence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B. METHODS: HLA-DRB1*03, *07, *09, *12, *15 alleles were determined using polymerase chain reaction/sequence specific primer (PCR/SSP) technique in 126 patients with chronic hepatitis B and 76 normal control subjects in Shandong Province, and HBV genotypes were determined by nested-PCR analysis using type-specific primers in 126 patients. RESULTS: The positivity of HLA-DRB1*07 allele in chronic hepatitis B group was significantly higher than that in normal control group (X2=6.33, P<0.025, RR=2.37). Among the 126 patients, genotype B was found in 38 (30.2%), genotype C in 69 (54.8%), and mixed genotype (B+C) in 19 (15.0%), genotypes D-F were not found. Among the 46 DRB1*07(+) patients, 7 were responders and 39 were non-responders among them (X2=6.71, P<0.05). The positivity of HLA-DRB1*07 and prevalence of HBV genotype C were significantly higher in non-responders than in responders. CONCLUSION: High positivities of HLA-DRBI *07 allele and HBV genotype C are closely associated with the lower response to interferon-α therapy for chronic hepatitis B.

Inhibitory effect of interferon-α-2b on expression of cyclooxygenase-2 and vascular endothelial growth factor in human hepatocellular carcinoma inoculated in nude mice

AIM:To evaluate the effects of interferon-α-2b (IFN-α-2b) on expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in human hepatocellular carcinoma (HCC) inoculated in nude mice and to study the underlying mechanism of IFN-α-2b against HCC growth. METHODS:Thirty-two nude mice bearing human HCC were randomly divided into four groups (n = 8). On the 10th day after implantation of HCC cells,the mice in test groups (groups A,B and C) received IFN-α-2b at a serial dose (10 000 IU for group A,20 000 IU for group B,40 000 IU for group C sc daily) for 35 d. The mice in control group received normal saline (NS). The growth conditions of transplanted tumors were observed. Both genes and proteins of COX-2 and VEGF were detected by RT-PCR and Western blot. Apoptosis of tumor cells in nude mice was detected by TUNEL assay after treatment with IFN-α-2b. RESULTS:Tumors were significantly smaller and had a lower weight in the IFN-α-2b treatment groups than those in the control group (P < 0.01),and the tumor growth inhibition rate in groups A,B and C was 27.78%,65.22% and 49.64%,respectively. The expression levels of both genes and proteins of COX-2 and VEGF were much lower in the IFN-α-2b treatment groups than in the control group (P < 0.01). The apoptosis index (AI) of tumor cells in the IFN-α-2b treatment groups was markedly higher than that in the control group (P < 0.01). Group B had a higher inhibition rate of tumor growth,a lower expression level of COX-2 and VEGF and a higher AI than groups A and C (P < 0.05),but there was no significant difference between groups A and C. CONCLUSION:The inhibitory effects of IFN-α-2b on implanted tumor growth and apoptosis may be associated with the down-regulation of COX-2 and VEGF expression. There is a dose-effect relationship. The medium dose of IFN-α-2b for inhibiting tumor growth is 20 000 IU/d.

Re-evaluation of antitumor effects of combination chemotherapy with interferon-α and 5-fluorouracil for advanced hepatocellular carcinoma

AIM: To evaluate the efficacy of combination chemotherapy with interferon-α (IFNα) and 5-fluorouracil (5-FU) in patients with advanced hepatocellular carcinoma (HCC).METHODS: Twenty-eight HCC patients in advanced stage were enrolled in the study. They were treated with IFNα/5-FU combination chemotherapy. One cycle of therapy lasted for 4 wk. IFNα (3× 106 units) was subcutaneously injected thrice weekly on days 1, 3, and 5 for 3 wk, and 5-FU (500 mg/d) was administered via the proper hepatic artery for 5 consecutive days per week for 3 wk. No drugs were administered during the 4th wk. The effect of combination chemotherapy was evaluated in each patient after every cycle based on the reduction of tumor volume.RESULTS: After the 1st cycle of therapy, 16 patients showed a partial response (PR, 57.1%) but none showed a complete response (CR, 0%). At the end of therapy,the number of patients who showed a CR, PR, or no response (NR) was 1, 10, and 17, respectively. The response rate for therapy (CR+PR) was 21.5%. Biochemical tests before therapy were compared between responsive (CR+PR) and non-responsive (NR) patients, but no significant differences were found for any of the parameters examined, indicating that no reasonable predictors could be identified in our analysis.CONCLUSION: Attempts should be made to discriminate between responders and non-responders by evaluating tumor size after the first cycle of IFNα/5-FU combination chemotherapy. For non-responders, therapy should not proceed to the next cycle, and instead, different combination of anticancer drugs should be explored.

Interferon-λ3 polymorphisms in pegylated-interferon-α plus ribavirin therapy for genotype-2 chronic hepatitis C

AIM: To evaluate interferon-λ3(IFNL3) polymorphisms in response-guided pegylated interferon-α plus ribavirin(Peg-IFNα/RBV) therapy for genotype 2(G2) chronic hepatitis C.METHODS: Between January 2006 and June 2012, a total of 180 patients with chronic infections of G2 hepatitis C virus(HCV) were treated with responseguided Peg-IFNα/RBV therapy. The treatment duration was 24 wk for patients who achieved rapid virologic response(RVR), and 36 or 48 wk for patients who did not. Then, the impact of the IFNL3 single nucleotide polymorphism genotype(TT/non-TT at rs8099917) on treatment outcomes was evaluated in the 180 patients, and between patients infected with either HCV subgenotype 2a or 2b.RESULTS: Of the 180 patients evaluated, 111 achieved RVR, while the remaining 69 patients did not. In RVR patients, the sustained virologic response(SVR) rate was 96.4%, and the IFNL3 genotype did not influence the SVR rate(96.6% vs 95.8% in IFNL3 genotype TT vs non-TT). However, in non-RVR patients, the SVR rate decreased to 72.5%(P < 0.0001), and this rate was significantly different between the IFNL3 genotype TT and non-TT groups(80.0% vs 42.9%, P = 0.0146). Multivariate regression analysis in non-RVR patients identified the IFNL3 genotype TT as the only baseline-significant factor associated with SVR(OR = 5.39, 95%CI: 1.29-22.62; P = 0.0189). In analysis according to HCV sub-genotype, no significant difference in the SVR rate was found between HCV sub-genotypes 2a and 2b.CONCLUSION: In response-guided Peg-IFNα/RBV combination therapy for chronically HCV G2-infected patients, the impact of the IFNL3 genotype on SVR was limited to non-RVR patients.

High-dose interferon-α2b induction therapy in combination with ribavirin for treatment of chronic hepatitis C in patients with non-response or relapse after interferon-a monotherapy

AIM: To evaluate the daily high-dose induction therapy with interferon-α2b (IFN-α2b) in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse, based on the assumption that the viral burden would decline faster, thus increasing the likelihood of higher response rates in this diffficult-to-treat patient group.METHODS: Seventy patients were enrolled in this study.Treatment was started with 10 MU IFN-α2b daily for 3 wk,followed by IFN-α2b 5 MU/TIW in combination with ribavirin (1 000-1 200 mg/d) for 21 wk. In case of a negative HCV RNA PCR, treatment was continued until wk 48 (IFN-α2b 3 MU/TIW+1 000-1 200 mg ribavirin/daily).RESULTS: The dose of IFN-α2b or ribavirin was reduced in 16% of patients because of hematologic side effects,and treatment was discontinued in 7% of patients. An early viral response (EVR) was achieved in 60% of patients. Fifty percent of all patients achieved an end-of-treatment response (EOT) and 40% obtained a sustained viral response (SVR). Patients with no response had a significantly lower response rate than those with a former relapse (SVR 30% vs 53%; P = 0.049). Furthermore,lower response rates were observed in patients infected with genotype 1a/b than in patients with non-1-genotype (SVR 28% vs74%; P= 0.001). As a significant predictive factor for a sustained response, a rapid initial decline of HCV RNA could be identified. No patient achieving a negative HCV-RNA PCR at wk 18 or later eventually eliminated the virus.CONCLUSION: Daily high-dose induction therapy with interferon-α2b is well tolerated and effective for the treatment of non-responders and relapsers, when interferon monotherapy fails. A fast decline of viral load during the first 12 wk is strongly associated with a sustained viral response.

Interferon-lambda:New functions on intestinal symptoms in COVID-19

The tremendous public health and economic impact of coronavirus disease 2019(COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2), has become a huge challenge globally. There is increasing evidence that SARS-CoV-2 induces intestinal infections. Type Ⅲ interferon(IFN-λ) has an antiviral role in intestinal infection, with focused, long-lasting, and non-inflammatory characteristics. This review presents a summary of the structure of SARSCoV-2, including its invasion and immune escape mechanisms. Emphasis was placed on the gastrointestinal impact of SARS-CoV-2, including changes to the intestinal microbiome, activation of immune cells, and inflammatory responses.We also describe the comprehensive functions of IFN-λ in anti-enteric SARS-CoV-2 infection, and discuss the potential application of IFN-λ as a therapeutic agent for COVID-19 with intestinal symptoms.

Construction of Fluorescence Sensing Platform on the Basis of Carbon Nitride Nanosheet for the Detection of Interferon-γ

Purpose: Interferon-γ (INF-γ) is a cytokine that participates in the immune reaction of the body. Its level of secretion can reflect the immune response condition after the body is infected by pathogens, which is a significant indication of clinically-related diseases. Therefore, it is of great significance in application to develop a fluorescence biosensor to inspect INF-γ with rapidness, high sensitivity and high practicability. Method: The fluorescence sensor is made on the basis of the two-dimensional nano-material namely Carbon Nitride Nanosheet (CNNS) and the Aptamer probe to identify INF-γ (Apt&reg;INF-γ). CNNS can quickly quench the Cy5 fluorescent dye modified on the Apt&reg;INF-γ probe due to the Photoinduced Electron Transfer (PET), but when the INF-γ exists, Apt&reg;INF-γ specifically identifies and combines it. The complex of Apt&reg;INF-γ and INF-γ is away from CNNS, which can effectively block the fluorescent signal of Apt?INF-γ being quenched by CNNS. Result: The sensitive detection of IFN-γ protein can be achieved through the application of CNNS/Apt&reg;INF-γ fluorescence sensing platform. In this method, the intensity of the fluorescent signal is positively correlated with the concentration of IFN-γ, of which the liner response range is 0.5 - 100 ng/mL and the limit of detection is 0.303 ng/mL. In addition, this fluorescence sensing platform has the advantages of high specificity, simple operation and low costs. It can inspect the content of IFN-γ in clinical serum samples without interference. The actual recovery rate of serum samples is 97.11% - 106.96%. Conclusion: Therefore, the CNNS/Apt&reg;INF-γ sensing platform is expected to be implemented in the actual clinical detection, also conducive to developing a universal fluorescence biosensor to inspect other target materials.

Development and validation of a prognostic indicator for thyroid carcinoma based on interferon-γ-related gene analysis

Background:Women are mostly affected by thyroid carcinoma(THCA),an endocrine system cancer.However,the biomarkers of interferon-gamma(IFN-γ)in THCA have not been identified,so this study aimed to investigate whether IFN-γ-related genes could predict the overall prognosis of THCA patients.Methods:Transcriptome-related expression data were obtained from The Cancer Genome Atlas database.Differential expression of IFN-γ-responsive genes(DE-IFN-γ)between THCA and normal samples was determined based on the“limma”package in R.The prognostic value of the model was determined by least absolute shrinkage and selection operator,univariate Cox,and multivariate Cox analyses,as well as Kaplan-Meier curves.A nomogram was created to predict the THCA survival probabilities by combining clinicopathological features and prognostic genetic features.High-risk and low-risk groups were examined THCA-related pathways using gene set enrichment analysis.Correlations between the two groups with different scores and the immune microenvironment and immunotherapy were also explored.Finally,we verified the expression levels using real-time PCR.Results:From 48 DE-IFN-γ,4 DE-IFN-γ(METTL7B,VAMP8,CFB,IFIT3)associated with good prognosis were selected by least absolute shrinkage and selection operator and Cox co-screening.Based on these four genes,THCA patients were divided into two groups,with the high-risk group having a poorer overall survival rate.The risk score,age,and staging were identified as independent prognostic factors.The low-scoring group had significantly enriched 13 signaling pathways,according to gene set enrichment analysis.Meanwhile,the two groups delineated according to the risk score differed in terms of the immune microenvironment and immune checkpoints.Finally,our real-time PCR results corroborated previous hypotheses.Conclusion:Researchers identified four DE-IFN-γbiomarker genes with promising prognostic value for THCA patients,which may help guide immunotherapy preference.Moreover,it may subsequently influence our THCA treatment decisions.

基于miR-155/TLR4/MyD88信号通路探讨蛇伤胶囊对竹叶青蛇伤的抗炎作用

目的探讨蛇伤胶囊对竹叶青蛇伤miR-155/Toll样受体4(TLR4)/髓样分化因子88(MyD88)信号通路及炎症的影响。方法将18只雄性新西兰大白兔分为对照组、模型组和蛇伤胶囊组,每组6只。对照组正常饮食饮水,另两组注射7.5 mg/kg竹叶青蛇毒液6 h后,模型组灌胃348 mg/(kg·d)生理盐水,蛇伤胶囊组灌胃348 mg/(kg·d)蛇伤胶囊,均连续灌胃1周。观察实验兔的一般行为学,qRT-PCR检测外周血中miR-155a-5p、TLR4和MyD88表达,ELISA检测血清中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、γ干扰素(IFN-γ)和白细胞介素-4(IL-4)含量。结果与对照组比较,模型组精神和食欲变差,排便稀软带血,伤口溃烂,miR-155-5p、TLR4 mRNA、MyD88 mRNA、IL-6和TNF-α表达均显著增加(均P<0.01),IFN-γ和IL-4表达显著下降(均P<0.01)。蛇伤胶囊组较模型组情况明显好转,miR-155a-5p、TLR4 mRNA、MyD88 mRNA、IL-6和TNF-α表达显著下降(均P<0.01),IFN-γ和IL-4表达显著增加(均P<0.01)。结论蛇伤胶囊抑制竹叶青蛇伤造成的炎症反应,维持Th1/Th2细胞平衡,其作用机制可能与抑制miR-155/TLR4/MyD88轴的表达有关。

Association of T regulatory cells with natural course and response to treatment with interferon-α in patients with chronic hepatitis B infection

Background Regulatory T cell populations, particularly CD4＋CD25＋ T regulatory cells, have been implicated in the persistence of hepatitis B virus （HBV） infection. However, no clear relationship has been established between the frequency of CD4~CD25~ T regulatory cells in the peripheral blood and either the disease phases in the natural history of chronic HBV infection or in the response to interferon-a therapy. Methods In the present study, three different common markers of CD4＋CD25＋ T regulatory cells were used to determine the numbers of T regulatory cells in healthy controls and in patients with chronic HBV infection. Results No significant difference was found when samples were gated for CD25hi and CD25＋FoxP3＋ T cells. A significant correlation was found between the number of CD4＋ Treg cells that gated with CD25＋FoxP3＋ and CD25＋CD127low/- in healthy controls and in patients with chronic hepatitis B （CHB） （r=0.67, 0.59; P 〈0.01）. The percentages of Treg cells were （8.56±2.01）% in asymptomatic carriers （Asc）, （8.74±3.04）% in inactive HBsAg carriers, （10.7±2.93）% in CHB and （7.42±1.28）% in healthy controls （F=-11.1, P 〈0.001）. The percentage of Treg cells in patients with CHB was higher than in asymptomatic HBV patients, inactive HBsAg carriers, or healthy controls （P 〈0.01）. The proportion of CD4＋CD25＋CD127 low/T cells in patients who responded to interferon-（] was （11.9±3.3）%, （9.1±2.4）% and （9.0±2.9）% at baseline, week 12 and week 24 after treatment, respectively （Z=2.42, P〈0.05; Z=2.67, P〈0.01）. Conclusions These results suggest that the proportion of the CD4＋CD25＋ regulatory T cells might be affected by the application of different markers in process to detect T regulatory cells. The frequency of Treg cells was increased in patients with CHB, which might be associated with the disease activity of these patients and contribute to prevention of extensive liver damage. A decline in Treg cells at week 12 of treatment might be associated with a better response to treatment with interferon-α.

Interferon-α salvage treatment is effective for patients with acute leukemia/myelodysplastic syndrome with unsatisfactory response to minimal residual disease-directed donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation

The efficacy of salvage interferon-α(IFN-α) treatment was investigated in patients with unsatisfactory response to minimal residual disease (MRD)-directed donor lymphocyte infusion (DLI)(n=24). Patients who did not become MRD-negative at 1 month after DLI were those with unsatisfactory response and were eligible to receive salvage IFN-α treatment within 3 months of DLI. Recombinant human IFN-α-2b injections were subcutaneously administered 2–3 times a week for 6 months. Nine (37.5%), 6 (25.0%), and 3 (12.5%) patients became MRD-negative at 1, 2, and>2 months after the salvage IFN-α treatment, respectively. Two-year cumulative incidences of relapse and non-relapse mortality were 35.9% and 8.3%, respectively. Two-year probabilities of event-free survival, disease-free survival, and overall survival were 51.6%, 54.3%, and 68.0%, respectively. Outcomes of patients subjected to salvage IFN-α treatment after DLI were significantly better than those with persistent MRD without IFN-α treatment. Moreover, clinical outcomes were comparable between the salvage DLI and IFN-α treatment groups. Thus, salvage IFN-α treatment may help improve the outcome of patients with unsatisfactory responses to MRD-directed DLI and could be a potential salvage treatment for these patients after allogeneic hematopoietic stem cell transplantation.