Objective To explore the predictive value of baseline HBs Ag level and early response for HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. Methods A tota...Objective To explore the predictive value of baseline HBs Ag level and early response for HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. Methods A total of 121 patients with HBe Ag-positive chronic hepatitis B who achieved HBs Ag loss were enrolled; all patients were treated with PEG-IFNα-2a 180 μg/week. Serum HBV DNA and serological indicators (HBs Ag, anti-HBs, HBe Ag, and anti-HBe) were determined before and every 3 months during treatment. Results The median treatment time for HBs Ag loss was 84 weeks (7-273 weeks), and 74.38% (90 cases) of the patients needed extended treatment (〉 48 weeks). The correlation between baseline HBs Ag levels and the treatment time of HBs Ag loss was significant (B = 14.465, t = 2.342, P = 0.021). Baseline HBs Ag levels together with the decline range of HBs Ag at 24 weeks significantly correlated with the treatment time of HBs Ag loss (B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005). Conclusion Baseline HBs Ag levels and extended therapy are critical steps toward HBs Ag loss. Baseline HBs Ag levels together with early response determined the treatment time of HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.展开更多
Radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restr...Radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restricts the therapeutic doses of radiation that can be delivered to tumours and thereby limits the effectiveness of the treatment. The use of radioprotectors represents an obvious strategy to obtain better tumour control using a higher dose in radiotherapy. However, most of the synthetic radioprotective compounds studied have shown inadequate clinical efficacy owing to their inherent toxicity and high cost. Hence, the development of radioprotective agents with lower toxicity and an extended window of protection has attracted a great deal of attention, and the identification of alternative agents that are less toxic and highly effective is an absolute necessity. Recent studies have shown that alpha-2-macroglobulin(α2M) possesses radioprotective effects. α2M is a tetrameric, disulfide-rich plasma glycoprotein that functions as a nonselective inhibitor of different types of non-specific proteases and as a carrier of cytokines, growth factors, and hormones. α2M induces protein factors whose interplay underlies radioprotection, which supports the idea that α2M is the central effector of natural radioprotection in the rat. Pretreatment with α2M has also induced a significant reduction of irradiation-induced DNA damage and the complete restoration of liver and body weight. Mihailovi? et al. concluded that the radioprotection provided by α2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow; these authors also indicated that an important aspect of the radioprotective effect of amifostine was the result of the induction of the endogenous cytoprotective capability of α2M. The radioprotective effects of α2M are possibly due to antioxidant, antifibrosis, and anti-inflammatory functions, as well as the maintenance of homeostasis, and enhancement of the DNA repair and cell recovery processes. This review is the first to summarise the observations and elucidate the possible mechanisms responsible for the beneficial effects of α2M. The lacunae in the existing knowledge and directions for future research are also addressed.展开更多
Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B(CHB). The objective of the ...Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B(CHB). The objective of the present study was to compare the efficacy and safety of pegylated interferon(Peg-IFN) alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone(1.5 μg/kg once weekly) or Peg-IFN alpha-2b plus adefovir(10 mg daily) for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30(36.7%) patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31(25.8%) in the monotherapy group(P=0.36). In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group(76.7% vs. 29.0%, P〈0.001). Thyroid dysfunction was more frequent in the combination group than in the monotherapy group(P〈0.05). In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.展开更多
Background: Viral hepatitis C (HCV) is common in Benin. Untreated, it can be complicated by cirrhosis and hepatocarcinoma, which are sources of death. The objectives of this work were twofold: 1) to evaluate the effec...Background: Viral hepatitis C (HCV) is common in Benin. Untreated, it can be complicated by cirrhosis and hepatocarcinoma, which are sources of death. The objectives of this work were twofold: 1) to evaluate the effectiveness and safety of treatment with classic dual interferon pegylated alpha-2a (IFN) and ribavirin therapy in Benin, and 2) to present problems related to financial accessibility to this treatment. Methods: This was a cross-sectional, descriptive and analytical study, with a retrospective collection of data from November 1, 2010 to December 31, 2015 and prospective collection from January 1, 2016 to July 31, 2016 (7 months). We included all patients treated with IFN + ribavirin for hepatitis C at CNHU/HKM. Sustained virological response (SVR) was defined as undetectable viral load C 6 months after stopping treatment. Safety was appreciated by the search for clinical and hematological adverse effects. Results: One hundred and six patients were followed for HCV, of whom 58 (54.7%) undergoing treatment (26 under standard dual therapy and 32 under direct-acting antivirals). Of the 26 patients under-conventional dual therapy, 12 (46.1%) were genotype 1, 13 (50%) genotype 2 and one (3.9%) genotype 4. In conventional dual therapy, SVR was achieved in 15 (57.7%) patients, including the genotype 4 patient, 4 out of 12 (33.3%) genotype 1 patients, and 10 out of 13 (76.9%) for genotype 2 patients. The most common side effects with this treatment were severe asthenia (23 cases), flu-like symptoms (22 cases), weight loss (21 cases) and neutropenia (22 cases), anemia and thrombocytopenia (20 of 26 cases). The overall cost of treatment per patient was 11,800,624 FCFA for genotypes 1 and 4;and 7,835,048 FCFA for genotype 2. Conclusion: The treatment of HCV with IFN + ribavirin in Benin is effective for genotype 2. But its adverse effects are manifold and its cost is high. The switch to direct-acting antivirals (more effective, better tolerated and less expensive) was therefore necessary.展开更多
OBJECTIVE To evaluate the efficacy of rituximab combined with CHOP-like regimen with or without IFN in patients newly diagnosed diffuse large B-cell Non-Hodgkin's lymphoma (DLBCL).METHODS From January 2003 to July ...OBJECTIVE To evaluate the efficacy of rituximab combined with CHOP-like regimen with or without IFN in patients newly diagnosed diffuse large B-cell Non-Hodgkin's lymphoma (DLBCL).METHODS From January 2003 to July 2008, 51 patients received CHOP-like chemotherapy (cyclophosphamide 750 mg/m2, epirubicin 80 mg/m2, vindesine 2.8 mg/m2 on day 1, and prednisolone 100 mg/day on day 1 to day 5). Thirty-one patients received CHOPR-like treatment (rituximab 375 mg/m2 1 day before CHOP-like chemotherapy). Twenty patients received CHOP-like regimen in combination with peginterferon (pegIFN) (1μg/kg on day 5) and rituximab (on day 6).RESULTS -The CR (complete remission) rate in the CHOPR-like (with or without pegIFN) group and in the CHOP-like group was 78.4% and 45.1% (P = 0.005), respectively. The estimated mean time of overall survival (OS) in the CHOPR-like group and CHOP- like group was 58.7 ± 2.8 and 36.4 ±3.4 months, respectively (P = 0.002). The rates of CR and OR (overall remission) in CHOPR- like with IFN arm were 85.0% and 95.0%, and the rates of those in CHOPR-like without IFN arm were 74.2% and 87.0% (P 〉 0.05). The estimated mean time of 4-year-PFS (progression- free survival) in CHOPR-like with IFN arm and in CHOPR-like without IFN arm was 62.9 ±3.0 months and 51.0 ± 4.6 months (P = 0.092), respectively. In the CHOPR-like with IFN arm, no patient relapsed after achieving CR, while the estimated rate of 4-year- DFS (disease-free survival) in the patients who reached CR in the CHOPR-like without IFN arm was (63.4 ± 19.3)% (P = 0.061). CONCLUSION Rituximab combined with CHOP-like chemotherapy improved the prognosis of DLBCL patients. The IFN may help to improve the quality and duration of response of DLBCL patients treated with rituximab and CHOP-like regimen.展开更多
Aroma touch therapy is widely used in clinical fields for alleviating pain-related symptoms;however, few studies have reported the pain-relief mechanisms. The present study aimed to elucidate the analgesic effects of ...Aroma touch therapy is widely used in clinical fields for alleviating pain-related symptoms;however, few studies have reported the pain-relief mechanisms. The present study aimed to elucidate the analgesic effects of aroma touch therapy with Citrus junos oil based on the quantitative evaluation of deep brain network (DBN) activity using electroencephalogram (EEG) occipital alpha-2 rhythm (10-13 Hz) powers. Experimental investigations were performed with 13 healthy volunteers using the cold pressor task for simulating chronic pain in three different sessions: a baseline session with no therapies, a control session with a touch therapy, and an aroma touch therapy. We have found for the first time that the interviewed pain ratings represented by Numeric Rating Scale (NRS) scores were strongly correlated with a DBN activity index, which was derived from the slow fluctuation components of occipital EEG alpha-2 rhythm powers. The correlation was characterized by a V-shaped curve in the DBN activity index versus the pain rating, i.e., the NRS score, which provided the complete analgesic states (NRS = 0) for some subjects under aroma touch therapy at an appropriate DBN activity index. Such analgesic states were not so strongly correlated with emotional valence. In conclusion, aroma touch therapy may directly modulate DBN activity so that pain-induced outcomes are minimized.展开更多
BACKGROUND It has been suggested that serum leucine-richα-2 glycoprotein(LRG)could be a novel monitoring biomarker for the assessment of disease activity in inflammatory bowel disease.In particular,the relationship b...BACKGROUND It has been suggested that serum leucine-richα-2 glycoprotein(LRG)could be a novel monitoring biomarker for the assessment of disease activity in inflammatory bowel disease.In particular,the relationship between LRG levels and the endoscopically assessed activity of ulcerative colitis(UC)has become a matter of interest.AIM To clarify appropriate LRG cut-off values for the prediction of endoscopic and histologic remission in Japanese patients with UC.METHODS This was a cross-sectional,single-center,observational study of Japanese patients with UC.Among 213 patients with UC,in whom LRG was measured from September 2020 to February 2022,we recruited 30 patients for whom a total colonoscopy and measurements of LRG and C-reactive protein(CRP)were performed on the same day.We retrospectively analyzed correlations between the LRG and CRP levels and endoscopic indices,including the Mayo endoscopic subscore and UC endoscopic index of severity.RESULTS Correlations between the LRG values and the Mayo endoscopic subscore or UC endoscopic index of severity were significant(r=0.754,P<0.0001;r=0.778,P<0.0001,respectively).There were also significant correlations between CRP levels and Mayo endoscopic subscore or UC endoscopic index of severity(r=0.599,P=0.0005;r=0.563,P=0.0012,respectively),although the correlation coefficients were higher for LRG.The LRG cutoff value for predicting endoscopic remission was 13.4μg/mL for a Mayo endoscopic subscore of 0[area under the curve(AUC):0.871;95%confidence interval(CI):0.744-0.998],and 13.4μg/mL for an UC endoscopic index of severity of 0 or 1(AUC:0.904;95%CI:0.792-1.000).CONCLUSION LRG may be a surrogate marker for endoscopic activity in UC,with a cut-off value of around 13.4μg/mL for endoscopically inactive disease.展开更多
基金supported by Beijing Science and Technology Commission(No.D121100003912001)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding,Support(No.ZY201402)
文摘Objective To explore the predictive value of baseline HBs Ag level and early response for HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. Methods A total of 121 patients with HBe Ag-positive chronic hepatitis B who achieved HBs Ag loss were enrolled; all patients were treated with PEG-IFNα-2a 180 μg/week. Serum HBV DNA and serological indicators (HBs Ag, anti-HBs, HBe Ag, and anti-HBe) were determined before and every 3 months during treatment. Results The median treatment time for HBs Ag loss was 84 weeks (7-273 weeks), and 74.38% (90 cases) of the patients needed extended treatment (〉 48 weeks). The correlation between baseline HBs Ag levels and the treatment time of HBs Ag loss was significant (B = 14.465, t = 2.342, P = 0.021). Baseline HBs Ag levels together with the decline range of HBs Ag at 24 weeks significantly correlated with the treatment time of HBs Ag loss (B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005). Conclusion Baseline HBs Ag levels and extended therapy are critical steps toward HBs Ag loss. Baseline HBs Ag levels together with early response determined the treatment time of HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.
基金supported by grant of the Science and Technology Planning Project of Guangdong Province (2010B060900052 and 2009B030801186)the Fundamental Research Funds for the Central Universities (the Young Teacher Training Project of Sun Yat-sen University 09ykpy12)the Medical Scientific Research Project of Zhuhai City (2012003)
文摘Radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restricts the therapeutic doses of radiation that can be delivered to tumours and thereby limits the effectiveness of the treatment. The use of radioprotectors represents an obvious strategy to obtain better tumour control using a higher dose in radiotherapy. However, most of the synthetic radioprotective compounds studied have shown inadequate clinical efficacy owing to their inherent toxicity and high cost. Hence, the development of radioprotective agents with lower toxicity and an extended window of protection has attracted a great deal of attention, and the identification of alternative agents that are less toxic and highly effective is an absolute necessity. Recent studies have shown that alpha-2-macroglobulin(α2M) possesses radioprotective effects. α2M is a tetrameric, disulfide-rich plasma glycoprotein that functions as a nonselective inhibitor of different types of non-specific proteases and as a carrier of cytokines, growth factors, and hormones. α2M induces protein factors whose interplay underlies radioprotection, which supports the idea that α2M is the central effector of natural radioprotection in the rat. Pretreatment with α2M has also induced a significant reduction of irradiation-induced DNA damage and the complete restoration of liver and body weight. Mihailovi? et al. concluded that the radioprotection provided by α2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow; these authors also indicated that an important aspect of the radioprotective effect of amifostine was the result of the induction of the endogenous cytoprotective capability of α2M. The radioprotective effects of α2M are possibly due to antioxidant, antifibrosis, and anti-inflammatory functions, as well as the maintenance of homeostasis, and enhancement of the DNA repair and cell recovery processes. This review is the first to summarise the observations and elucidate the possible mechanisms responsible for the beneficial effects of α2M. The lacunae in the existing knowledge and directions for future research are also addressed.
文摘Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B(CHB). The objective of the present study was to compare the efficacy and safety of pegylated interferon(Peg-IFN) alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone(1.5 μg/kg once weekly) or Peg-IFN alpha-2b plus adefovir(10 mg daily) for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30(36.7%) patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31(25.8%) in the monotherapy group(P=0.36). In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group(76.7% vs. 29.0%, P〈0.001). Thyroid dysfunction was more frequent in the combination group than in the monotherapy group(P〈0.05). In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.
文摘Background: Viral hepatitis C (HCV) is common in Benin. Untreated, it can be complicated by cirrhosis and hepatocarcinoma, which are sources of death. The objectives of this work were twofold: 1) to evaluate the effectiveness and safety of treatment with classic dual interferon pegylated alpha-2a (IFN) and ribavirin therapy in Benin, and 2) to present problems related to financial accessibility to this treatment. Methods: This was a cross-sectional, descriptive and analytical study, with a retrospective collection of data from November 1, 2010 to December 31, 2015 and prospective collection from January 1, 2016 to July 31, 2016 (7 months). We included all patients treated with IFN + ribavirin for hepatitis C at CNHU/HKM. Sustained virological response (SVR) was defined as undetectable viral load C 6 months after stopping treatment. Safety was appreciated by the search for clinical and hematological adverse effects. Results: One hundred and six patients were followed for HCV, of whom 58 (54.7%) undergoing treatment (26 under standard dual therapy and 32 under direct-acting antivirals). Of the 26 patients under-conventional dual therapy, 12 (46.1%) were genotype 1, 13 (50%) genotype 2 and one (3.9%) genotype 4. In conventional dual therapy, SVR was achieved in 15 (57.7%) patients, including the genotype 4 patient, 4 out of 12 (33.3%) genotype 1 patients, and 10 out of 13 (76.9%) for genotype 2 patients. The most common side effects with this treatment were severe asthenia (23 cases), flu-like symptoms (22 cases), weight loss (21 cases) and neutropenia (22 cases), anemia and thrombocytopenia (20 of 26 cases). The overall cost of treatment per patient was 11,800,624 FCFA for genotypes 1 and 4;and 7,835,048 FCFA for genotype 2. Conclusion: The treatment of HCV with IFN + ribavirin in Benin is effective for genotype 2. But its adverse effects are manifold and its cost is high. The switch to direct-acting antivirals (more effective, better tolerated and less expensive) was therefore necessary.
文摘OBJECTIVE To evaluate the efficacy of rituximab combined with CHOP-like regimen with or without IFN in patients newly diagnosed diffuse large B-cell Non-Hodgkin's lymphoma (DLBCL).METHODS From January 2003 to July 2008, 51 patients received CHOP-like chemotherapy (cyclophosphamide 750 mg/m2, epirubicin 80 mg/m2, vindesine 2.8 mg/m2 on day 1, and prednisolone 100 mg/day on day 1 to day 5). Thirty-one patients received CHOPR-like treatment (rituximab 375 mg/m2 1 day before CHOP-like chemotherapy). Twenty patients received CHOP-like regimen in combination with peginterferon (pegIFN) (1μg/kg on day 5) and rituximab (on day 6).RESULTS -The CR (complete remission) rate in the CHOPR-like (with or without pegIFN) group and in the CHOP-like group was 78.4% and 45.1% (P = 0.005), respectively. The estimated mean time of overall survival (OS) in the CHOPR-like group and CHOP- like group was 58.7 ± 2.8 and 36.4 ±3.4 months, respectively (P = 0.002). The rates of CR and OR (overall remission) in CHOPR- like with IFN arm were 85.0% and 95.0%, and the rates of those in CHOPR-like without IFN arm were 74.2% and 87.0% (P 〉 0.05). The estimated mean time of 4-year-PFS (progression- free survival) in CHOPR-like with IFN arm and in CHOPR-like without IFN arm was 62.9 ±3.0 months and 51.0 ± 4.6 months (P = 0.092), respectively. In the CHOPR-like with IFN arm, no patient relapsed after achieving CR, while the estimated rate of 4-year- DFS (disease-free survival) in the patients who reached CR in the CHOPR-like without IFN arm was (63.4 ± 19.3)% (P = 0.061). CONCLUSION Rituximab combined with CHOP-like chemotherapy improved the prognosis of DLBCL patients. The IFN may help to improve the quality and duration of response of DLBCL patients treated with rituximab and CHOP-like regimen.
文摘Aroma touch therapy is widely used in clinical fields for alleviating pain-related symptoms;however, few studies have reported the pain-relief mechanisms. The present study aimed to elucidate the analgesic effects of aroma touch therapy with Citrus junos oil based on the quantitative evaluation of deep brain network (DBN) activity using electroencephalogram (EEG) occipital alpha-2 rhythm (10-13 Hz) powers. Experimental investigations were performed with 13 healthy volunteers using the cold pressor task for simulating chronic pain in three different sessions: a baseline session with no therapies, a control session with a touch therapy, and an aroma touch therapy. We have found for the first time that the interviewed pain ratings represented by Numeric Rating Scale (NRS) scores were strongly correlated with a DBN activity index, which was derived from the slow fluctuation components of occipital EEG alpha-2 rhythm powers. The correlation was characterized by a V-shaped curve in the DBN activity index versus the pain rating, i.e., the NRS score, which provided the complete analgesic states (NRS = 0) for some subjects under aroma touch therapy at an appropriate DBN activity index. Such analgesic states were not so strongly correlated with emotional valence. In conclusion, aroma touch therapy may directly modulate DBN activity so that pain-induced outcomes are minimized.
文摘BACKGROUND It has been suggested that serum leucine-richα-2 glycoprotein(LRG)could be a novel monitoring biomarker for the assessment of disease activity in inflammatory bowel disease.In particular,the relationship between LRG levels and the endoscopically assessed activity of ulcerative colitis(UC)has become a matter of interest.AIM To clarify appropriate LRG cut-off values for the prediction of endoscopic and histologic remission in Japanese patients with UC.METHODS This was a cross-sectional,single-center,observational study of Japanese patients with UC.Among 213 patients with UC,in whom LRG was measured from September 2020 to February 2022,we recruited 30 patients for whom a total colonoscopy and measurements of LRG and C-reactive protein(CRP)were performed on the same day.We retrospectively analyzed correlations between the LRG and CRP levels and endoscopic indices,including the Mayo endoscopic subscore and UC endoscopic index of severity.RESULTS Correlations between the LRG values and the Mayo endoscopic subscore or UC endoscopic index of severity were significant(r=0.754,P<0.0001;r=0.778,P<0.0001,respectively).There were also significant correlations between CRP levels and Mayo endoscopic subscore or UC endoscopic index of severity(r=0.599,P=0.0005;r=0.563,P=0.0012,respectively),although the correlation coefficients were higher for LRG.The LRG cutoff value for predicting endoscopic remission was 13.4μg/mL for a Mayo endoscopic subscore of 0[area under the curve(AUC):0.871;95%confidence interval(CI):0.744-0.998],and 13.4μg/mL for an UC endoscopic index of severity of 0 or 1(AUC:0.904;95%CI:0.792-1.000).CONCLUSION LRG may be a surrogate marker for endoscopic activity in UC,with a cut-off value of around 13.4μg/mL for endoscopically inactive disease.