AIM： To assess the efficacy of triple therapy （peginterferon or high dose standard interferon, plus ribavirin and amantadine） in nonresponders to prior combination therapy. METHODS： A total of 196 patients were en...AIM： To assess the efficacy of triple therapy （peginterferon or high dose standard interferon, plus ribavirin and amantadine） in nonresponders to prior combination therapy. METHODS： A total of 196 patients were enrolled in a multicenter, open, randomized study. Patients were given 180 μg/wk of peginterferon-alpha-2a （40 kD） plus ribavirin （800-1000 rag/d） and amantadine （200 rag/d） for 48 wk （group A） or interferon-alpha-2a （6 MU/d for 4 wk, 3 MU/d for 20 wk, and 3 MU tiw for 24 wk） plus ribavirin （800-1000 rag/d） and amantadine （200 rag/d） for 48 wk （group B）. RESULTS： Overall sustained virologic response （SVR） was 26.6% （32.1% and 19.5% in group A and B, P = 0.057）. Baseline ALT 〉120 UI/L （OR 2.4; 95% CI：1.11 to 5.20; P = 0.026） and HCV RNA negativity after 12 wk （OR 8.7; 95% CI： 3.87 to 19.74; P 〈 0.0001） were independently associated with SVR. Therapy discontinuation occurred less frequently in patients treated with peginterferon than standard interferon （P = 0.036）. CONCLUSION： More than 25% of nonresponders to combination therapy can eradicate HCV infection when retreated with triple therapy, especially if they have a high baseline ALT and are treated with pegylated interferon.展开更多
HIV/AIDS has become a worldwide pandemic and highly active antiretroviral therapy (HAART) is the only generally recognized effective therapy at present. However, various unresolvable problems appear with the widesprea...HIV/AIDS has become a worldwide pandemic and highly active antiretroviral therapy (HAART) is the only generally recognized effective therapy at present. However, various unresolvable problems appear with the widespread use of HAART. Traditional Chinese Medicine shows good efficacy for intervention in HIV/AIDS and could become an effective treatment option.展开更多
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 ...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 difficult-totreat patient group. METHODS： Seventy patients were enrolled in this study. Treatment was started with 10 NU IFN-α2b daily for 3 wk, followed by IFN-α2b 5 NU/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 3MU/TIW＋1000-1200 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-oftreatment response （EOT） and d0% 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 la/b than in patients with non-1-genotype （SVR 28% vs7d%; 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.展开更多
HBV infection data of so first degree relatives from hepatitis B vaccine nonresponderand hyporesponder families stere compared 'vith those of 79 first degree relatives from high responder families. For further obs...HBV infection data of so first degree relatives from hepatitis B vaccine nonresponderand hyporesponder families stere compared 'vith those of 79 first degree relatives from high responder families. For further observation of their antibody response. those without the vaccination lwfore, and negative for HBsAg, anti-HBs and anti-HBc, or 'vith isolated ic'v anti-HBs (S/N M 10 )were given three 10 ig doses of hepatitis B vaccine at 0, 1 .6 months. The results Showed that. in thefirst degree relatives of nonresponders and hyporesponders, anti-HBs seroconversion rate and GMTwere lower (P > 0. 05), and the distribution or detected anti-HBs levels was significantly differentfrom that of the rirst degree relatives or high respondrs. In addition, before the vaccination. theHBV infection rate or the former was remarkably higher (33. 75% VS 15. 19% ), and the antibodyGMT of those positive ror anti-HBs was significantly ic'ver. This finding suggested that genetic background may play an important role in the n on -a nd-typo res ponsi yeness to hepat it is B vacc me.展开更多
Both HIV infection and antiretroviral therapy(ART)affect the oral microbiome.Whether successful treatment with ART in people living with HIV(PLWH),which leads to a significant decline in viral loads and immune reconst...Both HIV infection and antiretroviral therapy(ART)affect the oral microbiome.Whether successful treatment with ART in people living with HIV(PLWH),which leads to a significant decline in viral loads and immune reconstitution,is associated with changes in or recovery of the oral microbiome remains unknown.Therefore,we performed a cross-sectional study of 118 PLWH receiving regular ART and 40 healthy controls(HCs).Among the 118 PLWH,18 immunological nonresponders(INRs;<200 CD4^(+)T cells/μL)and 30 immunological responders(IRs;≥500 CD4^(+)T cells/μL)were identified.The oral microbiota composition of all participants was analyzed using 16S rRNA gene sequencing of throat swab samples.Relative abundance of bacterial genera was compared between IRs and INRs,and Pearson correlations between bacterial abundance and peripheral blood immune cell counts were evaluated.The INR group showed lower alpha diversity than the IR and HC groups,which displayed similar alpha diversity.The genera Alloprevotella,Prevotella and Neisseria were more abundant in PLWH than in HCs,whereas the genera Rothia,Streptococcus and Fusobacterium were more abundant in HCs than in PLWH.The genus Rothia was more abundant in the INR group,whereas Prevotella,Alloprevotella,Porphyromonas and Haemophilus were more abundant in the IR group.The genera Rothia and Alloprevotella were negatively and positively associated with CD4^(+)T cell counts,respectively.Thus,an increased abundance of Rothia in the oral microbiome is associated with unfavorable outcomes regarding immune reconstitution in PLWH receiving regular ART,whereas Prevotella,Alloprevotella,Porphyromonas and Haemophilus are associated with favorable outcomes.展开更多
Objective To evaluate the role of genetic factor in the development of nonresponder or hyporesponder to hepatitis B vaccine in Chinese people from field epidemiology and experimental study Methods Six hundred and t...Objective To evaluate the role of genetic factor in the development of nonresponder or hyporesponder to hepatitis B vaccine in Chinese people from field epidemiology and experimental study Methods Six hundred and thirty four susceptible healthy students were vaccinated with three doses of plasma derived hepatitis B vaccine Twenty nine non or hypo responders (subjects) and 30 hyperresponders (controls) as well as their 80 and 79 first degree relatives were determined and recruited in the study The first degree relatives of subjects and controls were then immunized with hepatitis B vaccine and followed up On the basis of the above results, alleles of HLA A,B,C,DR and DQ locus were further detected in the two groups Results The non and hypo response rate in immunized students was 4 6% (29/634) After administered with hepatitis B vaccine, the first degree relatives of the subjects displayed a 17 9% frequency of nonresponsiveness, higher than in the controls The phenotype frequency of HLA DR7 and B54 was 52 2% and 21 7% in subjects, 9 1% and 0 0% higher than in controls, respectively The extended haplotype B54 DR7 was more frequent in the former (17 0%) than in the latter (0 0%) ( P <0 01) Conclusion These results demonstrated that the genetic factor was likely associated with the non and hypo response to hepatitis B vaccine in Chinese people展开更多
Checkpoint inhibitors act by blocking physiologic mechanisms coopted by tumor cells to evade immune surveillance,restoring the immune system’s ability to identify and kill malignant cells.These therapies have dramati...Checkpoint inhibitors act by blocking physiologic mechanisms coopted by tumor cells to evade immune surveillance,restoring the immune system’s ability to identify and kill malignant cells.These therapies have dramatically improved outcomes in multiple tumor types with durable responses in many patients,leading to FDA approval first in advanced melanoma,then in many other malignancies.However,as experience with checkpoint inhibitors has grown,populations of patients who are primary nonresponders or develop secondary resistance have been the majority of cases,even in melanoma.Mechanisms of resistance include those inherent to the tumor microenvironment,the tumor cells themselves,and the function of the patient’s native immune cells.This review will discuss resistance to checkpoint inhibitors in melanoma as well as possible methods to restore sensitivity.展开更多
基金Supported by partially MURST COFIN 2003, FIRST 2003-2004
文摘AIM： To assess the efficacy of triple therapy （peginterferon or high dose standard interferon, plus ribavirin and amantadine） in nonresponders to prior combination therapy. METHODS： A total of 196 patients were enrolled in a multicenter, open, randomized study. Patients were given 180 μg/wk of peginterferon-alpha-2a （40 kD） plus ribavirin （800-1000 rag/d） and amantadine （200 rag/d） for 48 wk （group A） or interferon-alpha-2a （6 MU/d for 4 wk, 3 MU/d for 20 wk, and 3 MU tiw for 24 wk） plus ribavirin （800-1000 rag/d） and amantadine （200 rag/d） for 48 wk （group B）. RESULTS： Overall sustained virologic response （SVR） was 26.6% （32.1% and 19.5% in group A and B, P = 0.057）. Baseline ALT 〉120 UI/L （OR 2.4; 95% CI：1.11 to 5.20; P = 0.026） and HCV RNA negativity after 12 wk （OR 8.7; 95% CI： 3.87 to 19.74; P 〈 0.0001） were independently associated with SVR. Therapy discontinuation occurred less frequently in patients treated with peginterferon than standard interferon （P = 0.036）. CONCLUSION： More than 25% of nonresponders to combination therapy can eradicate HCV infection when retreated with triple therapy, especially if they have a high baseline ALT and are treated with pegylated interferon.
文摘HIV/AIDS has become a worldwide pandemic and highly active antiretroviral therapy (HAART) is the only generally recognized effective therapy at present. However, various unresolvable problems appear with the widespread use of HAART. Traditional Chinese Medicine shows good efficacy for intervention in HIV/AIDS and could become an effective treatment option.
文摘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 difficult-totreat patient group. METHODS： Seventy patients were enrolled in this study. Treatment was started with 10 NU IFN-α2b daily for 3 wk, followed by IFN-α2b 5 NU/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 3MU/TIW＋1000-1200 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-oftreatment response （EOT） and d0% 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 la/b than in patients with non-1-genotype （SVR 28% vs7d%; 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.
文摘HBV infection data of so first degree relatives from hepatitis B vaccine nonresponderand hyporesponder families stere compared 'vith those of 79 first degree relatives from high responder families. For further observation of their antibody response. those without the vaccination lwfore, and negative for HBsAg, anti-HBs and anti-HBc, or 'vith isolated ic'v anti-HBs (S/N M 10 )were given three 10 ig doses of hepatitis B vaccine at 0, 1 .6 months. The results Showed that. in thefirst degree relatives of nonresponders and hyporesponders, anti-HBs seroconversion rate and GMTwere lower (P > 0. 05), and the distribution or detected anti-HBs levels was significantly differentfrom that of the rirst degree relatives or high respondrs. In addition, before the vaccination. theHBV infection rate or the former was remarkably higher (33. 75% VS 15. 19% ), and the antibodyGMT of those positive ror anti-HBs was significantly ic'ver. This finding suggested that genetic background may play an important role in the n on -a nd-typo res ponsi yeness to hepat it is B vacc me.
基金from Zhejiang Plan for the Special Support for Top-notch Talents in China(2022R52029)Shandong Provincial Laboratory Project(SYS202202)the Fundamental Research Funds for the Central Universities(2022ZFJH003)。
文摘Both HIV infection and antiretroviral therapy(ART)affect the oral microbiome.Whether successful treatment with ART in people living with HIV(PLWH),which leads to a significant decline in viral loads and immune reconstitution,is associated with changes in or recovery of the oral microbiome remains unknown.Therefore,we performed a cross-sectional study of 118 PLWH receiving regular ART and 40 healthy controls(HCs).Among the 118 PLWH,18 immunological nonresponders(INRs;<200 CD4^(+)T cells/μL)and 30 immunological responders(IRs;≥500 CD4^(+)T cells/μL)were identified.The oral microbiota composition of all participants was analyzed using 16S rRNA gene sequencing of throat swab samples.Relative abundance of bacterial genera was compared between IRs and INRs,and Pearson correlations between bacterial abundance and peripheral blood immune cell counts were evaluated.The INR group showed lower alpha diversity than the IR and HC groups,which displayed similar alpha diversity.The genera Alloprevotella,Prevotella and Neisseria were more abundant in PLWH than in HCs,whereas the genera Rothia,Streptococcus and Fusobacterium were more abundant in HCs than in PLWH.The genus Rothia was more abundant in the INR group,whereas Prevotella,Alloprevotella,Porphyromonas and Haemophilus were more abundant in the IR group.The genera Rothia and Alloprevotella were negatively and positively associated with CD4^(+)T cell counts,respectively.Thus,an increased abundance of Rothia in the oral microbiome is associated with unfavorable outcomes regarding immune reconstitution in PLWH receiving regular ART,whereas Prevotella,Alloprevotella,Porphyromonas and Haemophilus are associated with favorable outcomes.
文摘Objective To evaluate the role of genetic factor in the development of nonresponder or hyporesponder to hepatitis B vaccine in Chinese people from field epidemiology and experimental study Methods Six hundred and thirty four susceptible healthy students were vaccinated with three doses of plasma derived hepatitis B vaccine Twenty nine non or hypo responders (subjects) and 30 hyperresponders (controls) as well as their 80 and 79 first degree relatives were determined and recruited in the study The first degree relatives of subjects and controls were then immunized with hepatitis B vaccine and followed up On the basis of the above results, alleles of HLA A,B,C,DR and DQ locus were further detected in the two groups Results The non and hypo response rate in immunized students was 4 6% (29/634) After administered with hepatitis B vaccine, the first degree relatives of the subjects displayed a 17 9% frequency of nonresponsiveness, higher than in the controls The phenotype frequency of HLA DR7 and B54 was 52 2% and 21 7% in subjects, 9 1% and 0 0% higher than in controls, respectively The extended haplotype B54 DR7 was more frequent in the former (17 0%) than in the latter (0 0%) ( P <0 01) Conclusion These results demonstrated that the genetic factor was likely associated with the non and hypo response to hepatitis B vaccine in Chinese people
文摘Checkpoint inhibitors act by blocking physiologic mechanisms coopted by tumor cells to evade immune surveillance,restoring the immune system’s ability to identify and kill malignant cells.These therapies have dramatically improved outcomes in multiple tumor types with durable responses in many patients,leading to FDA approval first in advanced melanoma,then in many other malignancies.However,as experience with checkpoint inhibitors has grown,populations of patients who are primary nonresponders or develop secondary resistance have been the majority of cases,even in melanoma.Mechanisms of resistance include those inherent to the tumor microenvironment,the tumor cells themselves,and the function of the patient’s native immune cells.This review will discuss resistance to checkpoint inhibitors in melanoma as well as possible methods to restore sensitivity.
