Salmonella enterica serovar Typhimurium,the causative agent of gastroenteritis,is one of the most successful intracellular pathogens.Although certain host factors for Salmonella infection have been unveiled,the factor...Salmonella enterica serovar Typhimurium,the causative agent of gastroenteritis,is one of the most successful intracellular pathogens.Although certain host factors for Salmonella infection have been unveiled,the factors mediating Salmonella entry,particularly the invasion process,remain obscure.Here,we have unearthed β2 integrin,a crucial member of the integrin family,as an important host factor facilitating Salmonella invasion.It is demonstrated that overexpression of β2 integrin promotes Salmonella invasion,while the knockdown of β2 integrin significantly diminishes the extent of invasion.Moreover,Salmonella exhibits specific binding affinity towards β2 integrin,and the block of β2 integrin on cell surface substantially reduces the infection of cells in vitro.The ectodomain soluble protein of β2 integrin neutralized Salmonella infection both in cells(in vitro)and in mice(in vivo).Additionally,Salmonella protein YrbD directly interacts with β2 integrin to facilitate its invasion.To our knowledge,this study showed for the first time that the protein YrbD mediates Salmonella adhesion and internalization into host cells by interacting with β2 integrin.These findings not only broaden our understanding of the mechanisms underlying Salmonella entry,but also identify a prospective target for therapeutic control.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
AIM:To investigate the expressions of type I collagen, α2 integrin and β1 integrin in the posterior sclera of guinea pigs with defocus myopia and whether basic fibroblast growth factor (bFGF) injection inhibits the ...AIM:To investigate the expressions of type I collagen, α2 integrin and β1 integrin in the posterior sclera of guinea pigs with defocus myopia and whether basic fibroblast growth factor (bFGF) injection inhibits the formation and development of myopia by upregulating the expression of type I collagen, α2 integrin and β1 integrin. METHODS:After 14 days of treatment, the refractive state and axial length were measured and the levels of type I collagen, α2 integrin and β1 integrin were assayed in the posterior sclerae of groups of guinea pigs that wore a monocular-7D polymethylmethacrylate (PMMA) lens or had -7D lens wear followed by the peribulbar injection of Phosphate Buffer Solution (PBS) or bFGF. The untreated fellow eye served as a control. Guinea pigs with no treatment served as normal group. ·RESULTS:The results showed that 14 days of monocular defocus increased axial eye length and refraction, while bFGF delivery inhibited them markedly. Further, it was also found that the monocular-7D lens could decrease the levels of type I collagen, α2 integrin and β1 integrin expressions, while, unlike PBS, bFGF increased them significantly in comparison to contralateral control eyes and normal eyes. CONCLUSION:bFGF can prevent the formation anddevelopment of defocus myopia by upregulating the expressions of type I collagen, α2 integrin and β1 integrin. Taken together, our results demonstrate that bFGF promotes sclera remodeling to prevent myopia in guinea pigs.展开更多
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
基金supported by the National Key R&D Program of China(2022YFF0710500)the the National Natural Science Foundation,China(31802192,32172853 and 32373013)+2 种基金the Natural Science Foundation of Heilongjiang Province of China(C2018070)China Postdoctoral Science Foundation(2017M620076)the Central Public-interest Scientific Institution Basal Research Fund,China(1610302022001)。
文摘Salmonella enterica serovar Typhimurium,the causative agent of gastroenteritis,is one of the most successful intracellular pathogens.Although certain host factors for Salmonella infection have been unveiled,the factors mediating Salmonella entry,particularly the invasion process,remain obscure.Here,we have unearthed β2 integrin,a crucial member of the integrin family,as an important host factor facilitating Salmonella invasion.It is demonstrated that overexpression of β2 integrin promotes Salmonella invasion,while the knockdown of β2 integrin significantly diminishes the extent of invasion.Moreover,Salmonella exhibits specific binding affinity towards β2 integrin,and the block of β2 integrin on cell surface substantially reduces the infection of cells in vitro.The ectodomain soluble protein of β2 integrin neutralized Salmonella infection both in cells(in vitro)and in mice(in vivo).Additionally,Salmonella protein YrbD directly interacts with β2 integrin to facilitate its invasion.To our knowledge,this study showed for the first time that the protein YrbD mediates Salmonella adhesion and internalization into host cells by interacting with β2 integrin.These findings not only broaden our understanding of the mechanisms underlying Salmonella entry,but also identify a prospective target for therapeutic control.
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AIM:To investigate the expressions of type I collagen, α2 integrin and β1 integrin in the posterior sclera of guinea pigs with defocus myopia and whether basic fibroblast growth factor (bFGF) injection inhibits the formation and development of myopia by upregulating the expression of type I collagen, α2 integrin and β1 integrin. METHODS:After 14 days of treatment, the refractive state and axial length were measured and the levels of type I collagen, α2 integrin and β1 integrin were assayed in the posterior sclerae of groups of guinea pigs that wore a monocular-7D polymethylmethacrylate (PMMA) lens or had -7D lens wear followed by the peribulbar injection of Phosphate Buffer Solution (PBS) or bFGF. The untreated fellow eye served as a control. Guinea pigs with no treatment served as normal group. ·RESULTS:The results showed that 14 days of monocular defocus increased axial eye length and refraction, while bFGF delivery inhibited them markedly. Further, it was also found that the monocular-7D lens could decrease the levels of type I collagen, α2 integrin and β1 integrin expressions, while, unlike PBS, bFGF increased them significantly in comparison to contralateral control eyes and normal eyes. CONCLUSION:bFGF can prevent the formation anddevelopment of defocus myopia by upregulating the expressions of type I collagen, α2 integrin and β1 integrin. Taken together, our results demonstrate that bFGF promotes sclera remodeling to prevent myopia in guinea pigs.
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.
