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
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
Purpose: The optimal formulation of pegylated interferon a (PEG-IFa) as a part of combination therapy with ribavirin (RBV) is uncertain for patients infected with hepatitis C Genotypes 2 and 3. Methods: A multivariate...Purpose: The optimal formulation of pegylated interferon a (PEG-IFa) as a part of combination therapy with ribavirin (RBV) is uncertain for patients infected with hepatitis C Genotypes 2 and 3. Methods: A multivariate analysis of prospectively collected treatment data from two tertiary centres on 351 treatment na?ve HCV Genotype 2 or 3 patients who received PEG-IFa-2a or b plus ribavirin. Results: Univariate analyses demonstrate that PEG-IFa-2b based on regimens achieved a higher sustained virological response (SVR) than PEG-IFa-2a (77.9% versus 62.0%, P = 0.0012). On multivariate analyses, PEG-IFa-2b appeared superior to PEG-IFa-2a with an odds ratio (OR) and 95% confidence interval (CI95) for SVR of 2.19 (CI95 1.35-3.52, P = 0.0005). Genotype was a significant predictor of outcome in the multivariate model with 80% of Genotype 2 but only 67.7% of Genotype 3 subjects achieving SVR (OR 2.66 [CI95 1.35-5.92]). Increasing age was negatively associated with SVR (OR 0.97 [CI95 0.94-0.99]). Some of the differences in SVR are explained by higher relapse rates with PEG-IFa-2a (P = 0.009). Conclusions: PEG-IFa-2b and RBV achieve higher SVR rates than PEG-IFa-2a and RBV in Genotypes 2 and 3 chronic HCV infections. There is less relapse with PEG-IFa-2b. Genotype 2 infections are considerably easier to cure. SVR is higher in younger patients. These findings should influence a choice of PEG-IFa in the era of direct acting anti-viral drugs in therapy of Genotypes 2 and 3.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
Conjunctival malignant melanoma (CMM) is a potentially lethal neoplasm with a high rate of recurrence. The modality of treatment includes a wide surgical excision, cryotherapy, topical mitomycin C and Interferon alpha...Conjunctival malignant melanoma (CMM) is a potentially lethal neoplasm with a high rate of recurrence. The modality of treatment includes a wide surgical excision, cryotherapy, topical mitomycin C and Interferon alpha 2b (INF α 2b). The aim of the study is to present the treatment of a case with CMM using topical Interferon alpha 2a. We present a 38-year-old female with diffuse bulbar dark pigmentation of the conjunctiva that arises from previously primary acquired melanosis (PAM). Biopsy resulted positive for CMM and further investigations were negative for any metastasis. Treatment with topical interferon alpha 2a was started immediately and after three months melanoma disappeared. One year after follow-up there was no sign of recurrence in regional lymph nodes or distant metastasis.展开更多
BACKGROUND Poor glycaemic control in patients with type 2 diabetes mellitus(T2DM)is often accompanied by multiple complications,including diabetic nephropathy(DN),diabetic retinopathy(DR),diabetic peripheral neuropath...BACKGROUND Poor glycaemic control in patients with type 2 diabetes mellitus(T2DM)is often accompanied by multiple complications,including diabetic nephropathy(DN),diabetic retinopathy(DR),diabetic peripheral neuropathy(DPN),and cardiac structural abnormality left ventricular hypertrophy(LVH).Early identification of high-risk populations for these complications and the implementation of intervention measures are crucial for improving patient outcomes.Serum alpha-1-microglobulin(α1-MG),a multifunctional protein synthesized by the liver and lymphocytes,has been considered a potential biomarker of diabetes-related diseases in recent years.AIM To investigate the associations of serumα1-MG with DN,DR,DPN,and LVH in T2DM patients and its predictive value.METHODS This retrospective study included 5045 T2DM patients.The study participants were stratified into quartiles according to their serumα1-MG levels.Multivariate logistic regression,restricted cubic spline,and explainable machine learning models were employed for risk assessment and feature importance evaluation.RESULTS Increasedα1-MG levels were observed in patients with DN,DR,DPN,and LVH(all P<0.001).Multivariate logistic regression revealed that each standard deviation increase inα1-MG was associated with an 84%increase in DN risk(OR:1.84,95%CI:1.62-2.10,P<0.001),a 17%increase in DR risk(OR:1.17,95%CI:1.07-1.28,P<0.001),a 14%increase in DPN risk(OR:1.14,95%CI:1.03-1.27,P=0.014),and a 28%increase in LVH risk(OR:1.28,95%CI:1.18-1.38,P<0.001).Subgroup analyses and machine learning confirmed the associations of elevatedα1-MG with these complications in T2DM patients.CONCLUSION Elevated serumα1-MG levels were independently associated with increased risks of DN,DR,DPN,and LVH in T2DM patients,suggesting its potential as a predictive biomarker.展开更多
BACKGROUND Achievement of endoscopic healing(EH)is significant in the clinical practice of inflammatory bowel disease as it is correlated with improved prognosis.Existing biomarkers,including C-reactive protein(CRP),h...BACKGROUND Achievement of endoscopic healing(EH)is significant in the clinical practice of inflammatory bowel disease as it is correlated with improved prognosis.Existing biomarkers,including C-reactive protein(CRP),have relatively low accuracy for predicting EH,especially in small intestinal lesions in Crohn’s disease(CD);thus,noninvasive and more accurate biomarkers are required.Leucine-rich alpha-2 glycoprotein(LRG),a 50-kD protein,is produced under inflammatory conditions and has been reported to be useful in assessing disease activity in inflammatory bowel disease.However,the usefulness of LRG in small intestinal lesions in CD remains inconclusive.AIM To determine the usefulness of LRG for EH in small bowel lesions in CD and compare it with CRP.METHODS This study included 133 consecutive patients with CD who underwent balloonassisted enteroscopy between June 2021 and March 2024 at Shiga University of Medical Science Hospital(Otsu,Japan).We retrospectively analyzed endoscopic scores in each of the ileum and colon and four markers including LRG,CRP,albumin,and Harvey-Bradshaw index(HBI).Spearman’s rank correlation coefficient and receiver operating characteristic analysis were performed.RESULTS Either active ileal or colonic lesions exhibited significant differences in LRG,CRP,albumin,and HBI compared with EH.CRP,albumin,and HBI showed a worse correlation with endoscopic activity in the ileum than that in the colon;however,LRG did not show a worse correlation(colon,r=0.5218;ileum,r=0.5602).Receiver operating characteristic analysis revealed that LRG for EH in the ileum and colon had the same cutoff values of 12.4μg/mL.Comparing the areas under the curve of LRG and CRP for predicting EH in the ileum revealed a significantly higher areas under the curve of LRG(95%confidence interval,0.017-0.194;P=0.024),whereas the two showed no significant difference in the colon.CONCLUSION LRG is a useful biomarker in assessing the endoscopic activity of CD and is more useful than CRP in the small intestine.展开更多
The study by Ohno et al provides valuable insights into the role of leucine-rich alpha-2-glycoprotein(LRG)as a potential biomarker for identifying small bowel lesions in Crohn's disease(CD).However,several methodo...The study by Ohno et al provides valuable insights into the role of leucine-rich alpha-2-glycoprotein(LRG)as a potential biomarker for identifying small bowel lesions in Crohn's disease(CD).However,several methodological challenges hinder its immediate use in clinical practice.Notably,the current research was retrospective,lacks comparative studies with fecal calprotectin,and did not provide long-term predictive data.Further prospective studies are needed to improve the applicability of LRG.Moreover,integrating LRG with additional biomarkers and employing artificial intelligence techniques may improve its effectiveness in disease monitoring.Future research should address interobserver variability,assess LRG's cost-effectiveness,and standardize endoscopic healing definitions to ensure broader applicability.Advancing these areas is vital for establishing LRG's role in precision medicine strategies for the management of CD.展开更多
Background： Hepatitis B surfhce antigen （HBsAg） Ioss/seroconversion is considered to be the ideal endpoint of antiviral therapy and the ultimate treatment goal in chronic hepatitis B （CHB）. This study aimed to as...Background： Hepatitis B surfhce antigen （HBsAg） Ioss/seroconversion is considered to be the ideal endpoint of antiviral therapy and the ultimate treatment goal in chronic hepatitis B （CHB）. This study aimed to assess the patterns of ttBsAg kinetics in CHB patients who achieved HBsAg loss during the treatment of pegylated interferon （PEG-IFN） α-2a. Methods： A total of 150 patients were enrolled, composing of 83 hepatitis B envelope antigen （H BeAg）-positive and 67 HBeAg-negative patients. Patients were treated with PEG-IFN α-2a180 μg/week until HBsAg loss/seroconversion was achieved, which occurred within 96 weeks. Serum hepatitis B virus deoxyribonucleic acid and serological indicators （HBsAg, anti-HBs, HBeAg, and anti-HBe） were determined before and every 3 months during PEG-1FN α-2a treatment. Biochemical markers and peripheral blood neutrophil and platelet counts were tested every 1-3 months. Results： Baseline HBsAg levels were 2.5 ± 1.3 log IU/ml, and decreased rapidly at 12 and 24 weeks by 48.3%, and 88.3%, respectively. The mean time to HBsAg loss was 54.2 ± 30.4 weeks, though most patients needed extended treatment and 30.0% of HBsAg loss occurred during 72-96 weeks. Baseline HBsAg levels were significantly higher in HBeAg-positive patients （2.9 ± 1.1 log 1U/ml） compared with HBeAg-negative patients （2.0 ± 1.3 log I U/ml; t = 4.733, P 〈 0.001）, but the HBsAg kinetics were similar. Patients who achieved HBsAg loss within 48 weeks had significantly lower baseline HBsAg levels and had more rapid decline of HBsAg at 12 weeks compared to patients who needed extended treatment to achieve HBsAg loss. Conclusions： Patients with lower baseline HBsAg levels and more rapid decline during early treatment with PEG-IFN are more likely to achieve HBsAg loss during 96 weeks of treatment, and extended therapy longer than 48 weeks may be required to achieve HBsAg loss.展开更多
Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has...Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.展开更多
Introduction:Dexamethasone(Dex)caused impaired osteoblast differentiation and oxidative stress(OS)in bone marrow mesenchymal stem cells(BMSCs).This work sought to elucidate the precise molecular pathway through which ...Introduction:Dexamethasone(Dex)caused impaired osteoblast differentiation and oxidative stress(OS)in bone marrow mesenchymal stem cells(BMSCs).This work sought to elucidate the precise molecular pathway through which Dex influences osteogenic differentiation(OD)and OS in BMSCs.Methods:The expression of Runt-related transcription factor 1(RUNX1)and alpha-2 macroglobulin(A2M)was assessed in Dex-treated BMSCs using qRTPCR and Western Blot.Following the functional rescue experiments,cell proliferation was determined by MTT assay,reactive oxygen species(ROS)expression by DCFH-DA fluorescent probe,lactate dehydrogenase(LDH),superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(Gpx)expression by kits,OD by alkaline phosphatase(ALP)staining and activity quantification,and the expression of OD-related proteins RUNX2,collagen type 1 alpha 1(COL1A1),and osteocalcin(OCN)by qRT-PCR and Western Blot.The binding of RUNX1 to A2M was initially analyzed through Jaspar website and subsequently verified by dual-luciferase reporter and ChIP assays.Results:Dextreated BMSCs had low RUNX1 and A2M expression.Dex treatment apparently elevated ROS and LDH levels,diminished cell proliferation rate and SOD,CAT,and Gpx expression,lightened intensity of ALP staining,and declined calcified nodules,ALP activity,and RUNX2,COL1A1,and OCN expression in BMSCs,which was counterweighed by RUNX1 or A2M overexpression.RUNX1 positively targeted A2M.A2M knockdown effectively nullified the ameliorative effects of RUNX1 overexpression on impaired OD and OS injury in Dex-induced BMSCs.Conclusions:Overexpression of RUNX1 attenuated Dex-induced impaired OD and OS injury in BMSCs by promoting A2M transcription.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.
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Purpose: The optimal formulation of pegylated interferon a (PEG-IFa) as a part of combination therapy with ribavirin (RBV) is uncertain for patients infected with hepatitis C Genotypes 2 and 3. Methods: A multivariate analysis of prospectively collected treatment data from two tertiary centres on 351 treatment na?ve HCV Genotype 2 or 3 patients who received PEG-IFa-2a or b plus ribavirin. Results: Univariate analyses demonstrate that PEG-IFa-2b based on regimens achieved a higher sustained virological response (SVR) than PEG-IFa-2a (77.9% versus 62.0%, P = 0.0012). On multivariate analyses, PEG-IFa-2b appeared superior to PEG-IFa-2a with an odds ratio (OR) and 95% confidence interval (CI95) for SVR of 2.19 (CI95 1.35-3.52, P = 0.0005). Genotype was a significant predictor of outcome in the multivariate model with 80% of Genotype 2 but only 67.7% of Genotype 3 subjects achieving SVR (OR 2.66 [CI95 1.35-5.92]). Increasing age was negatively associated with SVR (OR 0.97 [CI95 0.94-0.99]). Some of the differences in SVR are explained by higher relapse rates with PEG-IFa-2a (P = 0.009). Conclusions: PEG-IFa-2b and RBV achieve higher SVR rates than PEG-IFa-2a and RBV in Genotypes 2 and 3 chronic HCV infections. There is less relapse with PEG-IFa-2b. Genotype 2 infections are considerably easier to cure. SVR is higher in younger patients. These findings should influence a choice of PEG-IFa in the era of direct acting anti-viral drugs in therapy of Genotypes 2 and 3.
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Conjunctival malignant melanoma (CMM) is a potentially lethal neoplasm with a high rate of recurrence. The modality of treatment includes a wide surgical excision, cryotherapy, topical mitomycin C and Interferon alpha 2b (INF α 2b). The aim of the study is to present the treatment of a case with CMM using topical Interferon alpha 2a. We present a 38-year-old female with diffuse bulbar dark pigmentation of the conjunctiva that arises from previously primary acquired melanosis (PAM). Biopsy resulted positive for CMM and further investigations were negative for any metastasis. Treatment with topical interferon alpha 2a was started immediately and after three months melanoma disappeared. One year after follow-up there was no sign of recurrence in regional lymph nodes or distant metastasis.
文摘BACKGROUND Poor glycaemic control in patients with type 2 diabetes mellitus(T2DM)is often accompanied by multiple complications,including diabetic nephropathy(DN),diabetic retinopathy(DR),diabetic peripheral neuropathy(DPN),and cardiac structural abnormality left ventricular hypertrophy(LVH).Early identification of high-risk populations for these complications and the implementation of intervention measures are crucial for improving patient outcomes.Serum alpha-1-microglobulin(α1-MG),a multifunctional protein synthesized by the liver and lymphocytes,has been considered a potential biomarker of diabetes-related diseases in recent years.AIM To investigate the associations of serumα1-MG with DN,DR,DPN,and LVH in T2DM patients and its predictive value.METHODS This retrospective study included 5045 T2DM patients.The study participants were stratified into quartiles according to their serumα1-MG levels.Multivariate logistic regression,restricted cubic spline,and explainable machine learning models were employed for risk assessment and feature importance evaluation.RESULTS Increasedα1-MG levels were observed in patients with DN,DR,DPN,and LVH(all P<0.001).Multivariate logistic regression revealed that each standard deviation increase inα1-MG was associated with an 84%increase in DN risk(OR:1.84,95%CI:1.62-2.10,P<0.001),a 17%increase in DR risk(OR:1.17,95%CI:1.07-1.28,P<0.001),a 14%increase in DPN risk(OR:1.14,95%CI:1.03-1.27,P=0.014),and a 28%increase in LVH risk(OR:1.28,95%CI:1.18-1.38,P<0.001).Subgroup analyses and machine learning confirmed the associations of elevatedα1-MG with these complications in T2DM patients.CONCLUSION Elevated serumα1-MG levels were independently associated with increased risks of DN,DR,DPN,and LVH in T2DM patients,suggesting its potential as a predictive biomarker.
基金Supported by the Grants-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science,and Technology of Japan,No.21K15947 and No.23K07435.
文摘BACKGROUND Achievement of endoscopic healing(EH)is significant in the clinical practice of inflammatory bowel disease as it is correlated with improved prognosis.Existing biomarkers,including C-reactive protein(CRP),have relatively low accuracy for predicting EH,especially in small intestinal lesions in Crohn’s disease(CD);thus,noninvasive and more accurate biomarkers are required.Leucine-rich alpha-2 glycoprotein(LRG),a 50-kD protein,is produced under inflammatory conditions and has been reported to be useful in assessing disease activity in inflammatory bowel disease.However,the usefulness of LRG in small intestinal lesions in CD remains inconclusive.AIM To determine the usefulness of LRG for EH in small bowel lesions in CD and compare it with CRP.METHODS This study included 133 consecutive patients with CD who underwent balloonassisted enteroscopy between June 2021 and March 2024 at Shiga University of Medical Science Hospital(Otsu,Japan).We retrospectively analyzed endoscopic scores in each of the ileum and colon and four markers including LRG,CRP,albumin,and Harvey-Bradshaw index(HBI).Spearman’s rank correlation coefficient and receiver operating characteristic analysis were performed.RESULTS Either active ileal or colonic lesions exhibited significant differences in LRG,CRP,albumin,and HBI compared with EH.CRP,albumin,and HBI showed a worse correlation with endoscopic activity in the ileum than that in the colon;however,LRG did not show a worse correlation(colon,r=0.5218;ileum,r=0.5602).Receiver operating characteristic analysis revealed that LRG for EH in the ileum and colon had the same cutoff values of 12.4μg/mL.Comparing the areas under the curve of LRG and CRP for predicting EH in the ileum revealed a significantly higher areas under the curve of LRG(95%confidence interval,0.017-0.194;P=0.024),whereas the two showed no significant difference in the colon.CONCLUSION LRG is a useful biomarker in assessing the endoscopic activity of CD and is more useful than CRP in the small intestine.
文摘The study by Ohno et al provides valuable insights into the role of leucine-rich alpha-2-glycoprotein(LRG)as a potential biomarker for identifying small bowel lesions in Crohn's disease(CD).However,several methodological challenges hinder its immediate use in clinical practice.Notably,the current research was retrospective,lacks comparative studies with fecal calprotectin,and did not provide long-term predictive data.Further prospective studies are needed to improve the applicability of LRG.Moreover,integrating LRG with additional biomarkers and employing artificial intelligence techniques may improve its effectiveness in disease monitoring.Future research should address interobserver variability,assess LRG's cost-effectiveness,and standardize endoscopic healing definitions to ensure broader applicability.Advancing these areas is vital for establishing LRG's role in precision medicine strategies for the management of CD.
文摘Background： Hepatitis B surfhce antigen （HBsAg） Ioss/seroconversion is considered to be the ideal endpoint of antiviral therapy and the ultimate treatment goal in chronic hepatitis B （CHB）. This study aimed to assess the patterns of ttBsAg kinetics in CHB patients who achieved HBsAg loss during the treatment of pegylated interferon （PEG-IFN） α-2a. Methods： A total of 150 patients were enrolled, composing of 83 hepatitis B envelope antigen （H BeAg）-positive and 67 HBeAg-negative patients. Patients were treated with PEG-IFN α-2a180 μg/week until HBsAg loss/seroconversion was achieved, which occurred within 96 weeks. Serum hepatitis B virus deoxyribonucleic acid and serological indicators （HBsAg, anti-HBs, HBeAg, and anti-HBe） were determined before and every 3 months during PEG-1FN α-2a treatment. Biochemical markers and peripheral blood neutrophil and platelet counts were tested every 1-3 months. Results： Baseline HBsAg levels were 2.5 ± 1.3 log IU/ml, and decreased rapidly at 12 and 24 weeks by 48.3%, and 88.3%, respectively. The mean time to HBsAg loss was 54.2 ± 30.4 weeks, though most patients needed extended treatment and 30.0% of HBsAg loss occurred during 72-96 weeks. Baseline HBsAg levels were significantly higher in HBeAg-positive patients （2.9 ± 1.1 log 1U/ml） compared with HBeAg-negative patients （2.0 ± 1.3 log I U/ml; t = 4.733, P 〈 0.001）, but the HBsAg kinetics were similar. Patients who achieved HBsAg loss within 48 weeks had significantly lower baseline HBsAg levels and had more rapid decline of HBsAg at 12 weeks compared to patients who needed extended treatment to achieve HBsAg loss. Conclusions： Patients with lower baseline HBsAg levels and more rapid decline during early treatment with PEG-IFN are more likely to achieve HBsAg loss during 96 weeks of treatment, and extended therapy longer than 48 weeks may be required to achieve HBsAg loss.
基金funded by FEDER/Ministerio de Ciencia,Innovación y Universidades Agencia Estatal de Investigación/Project(PID2020-119729GB-100,REF/AEI/10.13039/501100011033)(to EP)a predoctoral fellowship from the Spanish Ministry of Universities(FPU)and Amigos de la Universidad de Navarra(to NSS)“Programa MRR Investigo 2023”(to MGB and MMD)。
文摘Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.
基金the Natural Science Foundation of Fujian Province(No.2023J011558)the Innovation of Science and Technology of Fujian Province(No.2021Y9098)Fujian Provincial Finance Project(No.BPB-2022FSH).
文摘Introduction:Dexamethasone(Dex)caused impaired osteoblast differentiation and oxidative stress(OS)in bone marrow mesenchymal stem cells(BMSCs).This work sought to elucidate the precise molecular pathway through which Dex influences osteogenic differentiation(OD)and OS in BMSCs.Methods:The expression of Runt-related transcription factor 1(RUNX1)and alpha-2 macroglobulin(A2M)was assessed in Dex-treated BMSCs using qRTPCR and Western Blot.Following the functional rescue experiments,cell proliferation was determined by MTT assay,reactive oxygen species(ROS)expression by DCFH-DA fluorescent probe,lactate dehydrogenase(LDH),superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(Gpx)expression by kits,OD by alkaline phosphatase(ALP)staining and activity quantification,and the expression of OD-related proteins RUNX2,collagen type 1 alpha 1(COL1A1),and osteocalcin(OCN)by qRT-PCR and Western Blot.The binding of RUNX1 to A2M was initially analyzed through Jaspar website and subsequently verified by dual-luciferase reporter and ChIP assays.Results:Dextreated BMSCs had low RUNX1 and A2M expression.Dex treatment apparently elevated ROS and LDH levels,diminished cell proliferation rate and SOD,CAT,and Gpx expression,lightened intensity of ALP staining,and declined calcified nodules,ALP activity,and RUNX2,COL1A1,and OCN expression in BMSCs,which was counterweighed by RUNX1 or A2M overexpression.RUNX1 positively targeted A2M.A2M knockdown effectively nullified the ameliorative effects of RUNX1 overexpression on impaired OD and OS injury in Dex-induced BMSCs.Conclusions:Overexpression of RUNX1 attenuated Dex-induced impaired OD and OS injury in BMSCs by promoting A2M transcription.
