Chronic active hepatitis(CAH) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma.The histological end points of CAH are chronic inflammation,fibrosis and cirr...Chronic active hepatitis(CAH) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma.The histological end points of CAH are chronic inflammation,fibrosis and cirrhosis which are coupled with increased DNA synthesis in cirrhotic vs healthy normal livers.The potential mechanism involved in CAH includes a combination of processes leading to liver cell necrosis,inflammation and cytokine production and liver scaring(fibrosis).The severity of liver damage is regulated by Hepatitis B virus genotypes and viral components.The viral and cellular factors that contribute to liver injury are discussed in this article.Liver injury caused by the viral infection affects many cellular processes such as cell signaling,apoptosis,transcription,DNA repair which in turn induce radical effects on cell survival,growth,transformation and maintenance.The consequence of such perturbations is resulted in the alteration of bile secretion,gluconeogenesis,glycolysis,detoxification and metabolism of carbohydrates,proteins,fat and balance of nutrients.The identification and elucidation of the molecular pathways perturbed by the viral proteins are important in order to design effective strategy to minimize and/or restore the hepatocytes injury.展开更多
Background:Large-nerve fiber dysfunction,as assessed by vibration perception threshold (VPT) predicts risks of ulceration,amputation,and mortality in diabetes.Serum uric acid (UA) is closely associated with various me...Background:Large-nerve fiber dysfunction,as assessed by vibration perception threshold (VPT) predicts risks of ulceration,amputation,and mortality in diabetes.Serum uric acid (UA) is closely associated with various metabolic disorders,especially diabetes.Thus,we sought to investigate the clinical relevance of UA to large-nerve fiber dysfunction,among patients with type 2 diabetes (T2D).Methods:Medical records of consecutive patients with T2D who were admitted to Beijing Friendship Hospital Pinggu Campus between May 2014 and December 2016 were collected.Data for the 824 eligible patients included in the final analysis were extracted using a structured form.A VPT value ≥15 in either foot was defined as abnormal.We compared the clinical characteristics between patients with abnormal VPT and those with normal VPT (VPT value <15 in both feet) in the overall population and in gender subgroups.Logistic regression analysis was performed to explore the association of abnormal VPT with UA level.One-way analysis of variance was used to compare VPT values across four UA quartiles.Results:UA levels were significantly lower in T2D patients with abnormal VPT than in those with normal VPT (294.5 ± 84.0 vs.314.9 ± 92.8 μmol/L,P<0.01),especially among male patients (311.7 ± 85.2 vs.336.9 ± 89.6 μmol/L,P<0.01).From the logistic regression analysis,hyperuricemia (males >420 μmol/L;females >360 μmol/L) was associated with a reduced risk of abnormal VPT (odds ratio [OR],0.60;95% confidence interval [CI],0.39–0.91;P<0.05).This association was robust in male patients (OR,0.43;95% CI,0.24–0.76;P<0.01) but not in female patients (OR,0.92;95% CI,0.47–1.82;P = 0.816),even after adjustment for confounding factors.For the younger male subgroup (age <65 years),VPT values decreased as the UA level increased (P for trend = 0.002),but this trend was not significant in older male subgroup (age ≥65 years;P for trend = 0.400).Conclusions:Low serum UA levels showed a significant association with an increased risk of large-nerve fibe展开更多
BACKGROUND Time in range(TIR),as a novel metric for glycemic control,has robust relevance with diabetic complications.Diabetic peripheral neuropathy(DPN)is characterized by sudomotor dysfunction.AIM To explore the rel...BACKGROUND Time in range(TIR),as a novel metric for glycemic control,has robust relevance with diabetic complications.Diabetic peripheral neuropathy(DPN)is characterized by sudomotor dysfunction.AIM To explore the relationship between TIR obtained from continuous glucose monitoring(CGM)and sudomotor function detected by SUDOSCAN in subjects with type 2 diabetes.METHODS The research enrolled 466 inpatients with type 2 diabetes.All subjects underwent 3-d CGM and SUDOSCAN.SUDOSCAN was assessed with electrochemical skin conductance in hands(HESC)and feet(FESC).Average feet ESC<60μS was defined as sudomotor dysfunction(+),otherwise it was sudomotor dysfunction(-).TIR refers to the percentage of time when blood glucose is between 3.9-10 mmol/L during 1 d period.RESULTS Among the enrolled subjects,135(28.97%)presented with sudomotor dysfunction.Patients with sudomotor dysfunction(+)showed a decreased level of TIR(P<0.001).Compared to the lowest tertile of TIR,the middle and the highest tertiles of TIR was associated with an obviously lower prevalence of sudomotor dysfunction(20.51%and 21.94%vs 44.52%)(P<0.001).In addition,with the increase of TIR,HESC and FESC increased(P<0.001).Regression analysis demonstrated that TIR was inversely and independently linked with the prevalence of sudomotor dysfunction after adjusting for confounding values(odds ratio=0.979,95%CI:0.971-0.987,P<0.001).CONCLUSION The tight glycemic control assessed by TIR is of vitally protective value for sudomotor dysfunction in type 2 diabetes mellitus.展开更多
Peripheral artery disease(PAD)is a common condition characterized by atherosclerosis in the peripheral arteries,associated with concomitant coronary and cerebrovascular diseases.Proprotein convertase subtilisin/kexin ...Peripheral artery disease(PAD)is a common condition characterized by atherosclerosis in the peripheral arteries,associated with concomitant coronary and cerebrovascular diseases.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors are a class of drugs that have shown potential in hypercholesterolemic patients.This review focuses on the efficacy,safety,and clinical outcomes of PCSK9 inhibitors in PAD based on the literature indexed by PubMed.Trials such as FOURIER and ODYSSEY demonstrate the efficacy of evolocumab and alirocumab in reducing cardiovascular events,offering a potential treatment option for PAD patients.Safety evaluations from trials show few adverse events,most of which are injection-site reactions,indicating the overall safety profile of PCSK9 inhibitors.Clinical outcomes show a reduction in cardiovascular events,ischemic strokes,and major adverse limb events.However,despite these positive findings,PCSK9 inhibitors are still underutilized in clinical practice,possibly due to a lack of awareness among care providers and cost concerns.Further research is needed to establish the long-term effects and cost-effectiveness of PCSK9 inhibitors in PAD patients.展开更多
Recent studies have shown the potential of artificially synthesized conduits in the repair of peripheral nerve injury. Natural biopolymers have received much attention because of their biocompatibility. To investigate...Recent studies have shown the potential of artificially synthesized conduits in the repair of peripheral nerve injury. Natural biopolymers have received much attention because of their biocompatibility. To investigate the effects of novel electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits(biopolymer nanofiber conduits) on the repair of peripheral nerve injury, we bridged 10-mm-long sciatic nerve defects with electrospun absorbable biopolymer nanofiber conduits, poly(ε-caprolactone) or silicone conduits in Sprague-Dawley rats. Rat neurologica1 function was weekly evaluated using sciatic function index within8 weeks after repair. Eight weeks after repair, sciatic nerve myelin sheaths and axon morphology were observed by osmium tetroxide staining, hematoxylin-eosin staining, and transmission electron microscopy.S-100(Schwann cell marker) and CD4(inflammatory marker) immunoreactivities in sciatic nerve were detected by immunohistochemistry. In rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits, no serious inflammatory reactions were observed in rat hind limbs, the morphology of myelin sheaths in the injured sciatic nerve was close to normal. CD4 immunoreactivity was obviously weaker in rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits than in those subjected to repair with poly(ε-caprolactone) or silicone. Rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits tended to have greater sciatic nerve function recovery than those receiving poly(ε-caprolactone) or silicone repair. These results suggest that electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits have the potential of repairing sciatic nerve defects and exhibit good biocompatibility. All experimental procedures were approved by Institutional Animal Care and Use Committee of Taichung Veteran General Hospital, Taiwan, China(La-1031218) on October 2, 2014.展开更多
文摘Chronic active hepatitis(CAH) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma.The histological end points of CAH are chronic inflammation,fibrosis and cirrhosis which are coupled with increased DNA synthesis in cirrhotic vs healthy normal livers.The potential mechanism involved in CAH includes a combination of processes leading to liver cell necrosis,inflammation and cytokine production and liver scaring(fibrosis).The severity of liver damage is regulated by Hepatitis B virus genotypes and viral components.The viral and cellular factors that contribute to liver injury are discussed in this article.Liver injury caused by the viral infection affects many cellular processes such as cell signaling,apoptosis,transcription,DNA repair which in turn induce radical effects on cell survival,growth,transformation and maintenance.The consequence of such perturbations is resulted in the alteration of bile secretion,gluconeogenesis,glycolysis,detoxification and metabolism of carbohydrates,proteins,fat and balance of nutrients.The identification and elucidation of the molecular pathways perturbed by the viral proteins are important in order to design effective strategy to minimize and/or restore the hepatocytes injury.
文摘Background:Large-nerve fiber dysfunction,as assessed by vibration perception threshold (VPT) predicts risks of ulceration,amputation,and mortality in diabetes.Serum uric acid (UA) is closely associated with various metabolic disorders,especially diabetes.Thus,we sought to investigate the clinical relevance of UA to large-nerve fiber dysfunction,among patients with type 2 diabetes (T2D).Methods:Medical records of consecutive patients with T2D who were admitted to Beijing Friendship Hospital Pinggu Campus between May 2014 and December 2016 were collected.Data for the 824 eligible patients included in the final analysis were extracted using a structured form.A VPT value ≥15 in either foot was defined as abnormal.We compared the clinical characteristics between patients with abnormal VPT and those with normal VPT (VPT value <15 in both feet) in the overall population and in gender subgroups.Logistic regression analysis was performed to explore the association of abnormal VPT with UA level.One-way analysis of variance was used to compare VPT values across four UA quartiles.Results:UA levels were significantly lower in T2D patients with abnormal VPT than in those with normal VPT (294.5 ± 84.0 vs.314.9 ± 92.8 μmol/L,P<0.01),especially among male patients (311.7 ± 85.2 vs.336.9 ± 89.6 μmol/L,P<0.01).From the logistic regression analysis,hyperuricemia (males >420 μmol/L;females >360 μmol/L) was associated with a reduced risk of abnormal VPT (odds ratio [OR],0.60;95% confidence interval [CI],0.39–0.91;P<0.05).This association was robust in male patients (OR,0.43;95% CI,0.24–0.76;P<0.01) but not in female patients (OR,0.92;95% CI,0.47–1.82;P = 0.816),even after adjustment for confounding factors.For the younger male subgroup (age <65 years),VPT values decreased as the UA level increased (P for trend = 0.002),but this trend was not significant in older male subgroup (age ≥65 years;P for trend = 0.400).Conclusions:Low serum UA levels showed a significant association with an increased risk of large-nerve fibe
基金National Natural Science Foundation of China,No.81774134 and No.81873174Natural Science Foundation of Jiangsu Province of China,No.BK20150558 and No.BK20171331+2 种基金Postdoctoral Foundation of Jiangsu Province of China,No.1501120CJiangsu Province 333 Talent Funding Project,No.BRA2017595Young Medical Key Talents Project of Jiangsu Province,No.QNRC2016902.
文摘BACKGROUND Time in range(TIR),as a novel metric for glycemic control,has robust relevance with diabetic complications.Diabetic peripheral neuropathy(DPN)is characterized by sudomotor dysfunction.AIM To explore the relationship between TIR obtained from continuous glucose monitoring(CGM)and sudomotor function detected by SUDOSCAN in subjects with type 2 diabetes.METHODS The research enrolled 466 inpatients with type 2 diabetes.All subjects underwent 3-d CGM and SUDOSCAN.SUDOSCAN was assessed with electrochemical skin conductance in hands(HESC)and feet(FESC).Average feet ESC<60μS was defined as sudomotor dysfunction(+),otherwise it was sudomotor dysfunction(-).TIR refers to the percentage of time when blood glucose is between 3.9-10 mmol/L during 1 d period.RESULTS Among the enrolled subjects,135(28.97%)presented with sudomotor dysfunction.Patients with sudomotor dysfunction(+)showed a decreased level of TIR(P<0.001).Compared to the lowest tertile of TIR,the middle and the highest tertiles of TIR was associated with an obviously lower prevalence of sudomotor dysfunction(20.51%and 21.94%vs 44.52%)(P<0.001).In addition,with the increase of TIR,HESC and FESC increased(P<0.001).Regression analysis demonstrated that TIR was inversely and independently linked with the prevalence of sudomotor dysfunction after adjusting for confounding values(odds ratio=0.979,95%CI:0.971-0.987,P<0.001).CONCLUSION The tight glycemic control assessed by TIR is of vitally protective value for sudomotor dysfunction in type 2 diabetes mellitus.
文摘Peripheral artery disease(PAD)is a common condition characterized by atherosclerosis in the peripheral arteries,associated with concomitant coronary and cerebrovascular diseases.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors are a class of drugs that have shown potential in hypercholesterolemic patients.This review focuses on the efficacy,safety,and clinical outcomes of PCSK9 inhibitors in PAD based on the literature indexed by PubMed.Trials such as FOURIER and ODYSSEY demonstrate the efficacy of evolocumab and alirocumab in reducing cardiovascular events,offering a potential treatment option for PAD patients.Safety evaluations from trials show few adverse events,most of which are injection-site reactions,indicating the overall safety profile of PCSK9 inhibitors.Clinical outcomes show a reduction in cardiovascular events,ischemic strokes,and major adverse limb events.However,despite these positive findings,PCSK9 inhibitors are still underutilized in clinical practice,possibly due to a lack of awareness among care providers and cost concerns.Further research is needed to establish the long-term effects and cost-effectiveness of PCSK9 inhibitors in PAD patients.
基金supported by grants from the Taichung Veterans General Hospital and Central Taiwan University of Science and Technology,No.TCVGH-CTUST1047701(to CCS and BSL)Taichung Veterans General Hospital,No.TCVGH-1034907C(to CCS),Taiwan,China
文摘Recent studies have shown the potential of artificially synthesized conduits in the repair of peripheral nerve injury. Natural biopolymers have received much attention because of their biocompatibility. To investigate the effects of novel electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits(biopolymer nanofiber conduits) on the repair of peripheral nerve injury, we bridged 10-mm-long sciatic nerve defects with electrospun absorbable biopolymer nanofiber conduits, poly(ε-caprolactone) or silicone conduits in Sprague-Dawley rats. Rat neurologica1 function was weekly evaluated using sciatic function index within8 weeks after repair. Eight weeks after repair, sciatic nerve myelin sheaths and axon morphology were observed by osmium tetroxide staining, hematoxylin-eosin staining, and transmission electron microscopy.S-100(Schwann cell marker) and CD4(inflammatory marker) immunoreactivities in sciatic nerve were detected by immunohistochemistry. In rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits, no serious inflammatory reactions were observed in rat hind limbs, the morphology of myelin sheaths in the injured sciatic nerve was close to normal. CD4 immunoreactivity was obviously weaker in rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits than in those subjected to repair with poly(ε-caprolactone) or silicone. Rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits tended to have greater sciatic nerve function recovery than those receiving poly(ε-caprolactone) or silicone repair. These results suggest that electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits have the potential of repairing sciatic nerve defects and exhibit good biocompatibility. All experimental procedures were approved by Institutional Animal Care and Use Committee of Taichung Veteran General Hospital, Taiwan, China(La-1031218) on October 2, 2014.
