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HBsAg is one of the oldest diagnostic markers for HBV infection, and serum HBsAg level is associated with HBV cccDNA level in hepatocytes, HBV replication capability, and host immune response. In recent years, with the development of serum HBsAg quantification and the concept of functional cure, HBsAg quantification has been taken more and more seriously in the clinical diagnosis and treatment of HBV infection. This article analyzes the role of serum HBsAg quantification from the aspects of natural disease course of chronic hepatitis B, prediction of response to antiviral therapy, and prediction of drug withdrawal.
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Objective To investigate the relationship between subclinical hypothyroidism (SCH) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).Methods A total of 792 patients of T2DM were enrolled in the study.There were 448 males and 344 females,with an average age of (54.13 ± 13.06)years.The average duration of diabetes was (8.03 4±6.70) years.The patients were grouped according to the degree of DR and thyroid function.Among them,483 patients (61.0％) were no DR,240 patients (30.3％) were mild DR,69 patients (8.7％) were severe DR.725 patients (91.5％) were normal thyroid function,67 patients (8.5％) were SCH.The prevalence of SCH among no DR group,mild DR group and severe DR group was compared.And the prevalence of DR between normal thyroid function group and SCH group was compared.Logistic regression analysis was used to estimate the association between SCH and DR.Results No significant differences among the three groups (no DR group,mild DR group,severe DR group) were found in the prevalence of SCH (x2=1.823,P=0.402).There were no significant differences in the incidences of DR between normal thyroid function group and SCH group (x2=1.618,P=0.239).Logistic regression analysis demonstrated that SCH was not significant associated with DR [mild DR:odds ratio (OR)=1.361,95％ confidence interval (CI)=0.773-2.399,P=0.286;severe DR:OR=1.326,95％CI=0.520-3.384,P=0.555;DR:OR=1.353,95％ CI=0.798-2.294,P=0.261).Conclusion SCH is not significant associated with DR in patients with T2DM.
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OBJECTIVE:To observe the efficacy and safety of Shenqi jiangtang granule in the adjuvant treatment of type 2 dia-betes knee arthritis. METHODS:62 patients with type 2 diabetes knee arthritis were randomly divided into control group(31 cas-es) and observation group (31 cases). Control group received hypoglycemic and basic treatment for arthritis,including diet con-trol,exercise therapy and health education,as well as 0.25 g Metformin hydrochloride tablet with a meal,3 times a day + 50 mg Acarbose tablet with a meal,3 times a day,chewing;patients with arthritis pain 100 mg Aspirin enteric-coated tablet after a meal, once a day (chewing or breaking apart was prohibited). Observation group additionally received 3 g Shenqi jiangtang granule half an hour before a meal with 50 ml warm water,3 times a day. The treatment course for both groups was 6 months. Clinical effica-cy,and fasting plasma glucose(FPG),2 h postprandial blood glucose(2 h PG),glycated hemoglobin(HbA1c),interleukin-1β(IL-1β),IL-6 before and after treatment,and the incidence of adverse reactions in 2 groups were observed. RESULTS:The total effective rate in observation group was significantly higher than control group,the difference was statistically significant(P0.05). After treatment,FPG,2 h PG,HbA1c,IL-1β and IL-6 in 2 groups were significantly lower than before,and observation group was lower than control group,the differences were statistically significant(P0.05). CONCLUSIONS:Based on conventional treatment,Shenqi jiangtang granule shows obvious efficacy in the adjuvant treatment of type 2 diabetes knee arthritis.,it can reduce blood glucose and inflammation cy-tokine levels,mild symptoms of adverse reactions.
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Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases across the world, but there is still no specific treatment for NAFLD. Glucogon-like peptide 1 receptor agonist (GLP-1Ra) is a novel drug for the treatment of type 2 diabetes, based on incretin hormone target. Animal and clinical studies have demonstrated that GLP-1Ra can effec?tively reduce fat deposit in liver and attenuate hepatic steatosis. Therefore, GLP-1Ra is a promising therapeutic approachagainst NAFLD. In this review, we provided an overview of the clinical and basic research evidences and mechanisms in re?lieving NAFLD.
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Objective To investigate the mechanism of a dipeptidyl-peptidase-4 (DPP-4) inhibitor, saxagliptin, pro?moting the regeneration of islet beta cells in diabetic rats. Methods The male SD rats were randomly divided into three groups including control group (NC, n=10), diabetes group (DM, n=10) and diabetes treated with saxagliptin group (DM-S, n=10). DM-S group was treated with saxagliptin 1 mg/(kg·d) for twelve weeks. The pancreaticβcell function was analysed by hyperglycemic clamps. Immunohistochemistry with anti-PCNA was performed to observe the proliferation rate of pancreaticβcells. Immunofluorescence double staining with anti-insulin, anti-glucagon, anti-DPP-4 and anti-SDF-1 were performed to observe the expression of insulin, glucagon, DPP-4 and SDF-1 in pancreatic tissue. Western blot assay was performed to test the expression of Akt, p-Akt,β-catenin and free-β-catenin protein, and RT-PCR was performed to test the expressionlevels of c-myc and cyclinD1 mRNA in pancreatic tissue. Results Compared with NC group, there were significantly in?creased blood glucose, decreased islet function andβcell mass in DM group. Compared with DM rats, saxagliptin treatment significantly inhibited the expression of DPP-4, decreased the degradation of SDF-1, stimulated the proliferation ofβcells, and ultimately improved the islet function and histopathological changes of pancreas. Conclusion DPP-4 inhibitor saxa?gliptin can significantly improve islet function, which involved in the inhibition of the expression of DPP-4, the decreased degradation of SDF-1 and the stimulation of the proliferation ofβcells.
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Objective To investigate the possible mechanisms of glucagon-like peptide 1 receptor agonists (GLP-1Ra) protection against hyperglycemic induced beta cell apoptosis through depression of NOX2-dependent ROS production. Methods The rat model of type 2 diabetes (T2DM) was established by injecting small doses of streptozotocin (STZ) fol?lowed by 8-week high fat diet. The experimental animals were divided into three groups:normal control (N) group, diabetes (T2DM) group and GLP-1Ra group [treated with liraglutide 200 μg/(kg · d)for 12 weeks]. The blood glucose levels were compared before and after modeling, before treatment and 12-week after treatment with GLP-1Ra. The level of glycosylated hemoglobin (HbA1c) was detected by high-pressure liquid chromatography. Automatic biochemical analyzer was used to de?tect levels of aspertate aminotransferase (AST), creatinine (CR) and urea nitrogen (BUN). The apoptotic rates of islets were determined by TUNEL method and cleaved caspase 3 was detected by immunohistochemistry. DCFH-DA fluorescent probe was used to detect reactive oxygen species (ROS) levels of islets. Levels of NADPH oxidase (NOX) catalytic subunit (NOX 2) in islets were measured by immunohistochemistry. Results At the end of the study, glycemic control (average blood glucose/week and HbA1c) and lipid situation were improved significantly in the GLP-1Ra group than those of N group (P0.05). After application Apocynin for inhibition, there were no significant differences between three groups (P>0.05). The level of NOX2 was significantly lower in GLP-1Ra group compared to that of T2DM group (P<0.05). Conclusion GLP-1Ra can inhibit apoptosis ofβcells in diabetes rat, and the depression of NOX2-dependent ROS may be one of the important underly?ing mechanisms.
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Objective To investigate the possible mechanisms of glucagon-like peptide 1 receptor agonists (GLP-1Ra) induced weight loss. Methods High fat diet induced obese c57BL/6 mice were divided into normal control group (N, n=8), high fat feeding group (HF, n=32) and GLP-1Ra group treated with GLP-1Ra (liraglutide 200μg/(kg·d) or 400μg/(kg·d) for 8 weeks). Changes of body weight, blood glucose and three acyl glycosides (TG) levels were observed in three groups. HE staining was used to observe the morphological changes. Immunofluorescence staining and real-time PCR were used to mea?sure the expression of UCP-1. Furthermore, the expression of PGC-1αin protein level was observed to explore the possible mechanism of GLP-1Ra induced browning in white fat (WAT). Results After 8-week liraglutide (Lira) administration, the body weights were significantly reduced in obese mice (P<0.05). The levels of blood glucose and TG were significantly high?er in HF group than those in N group, which reduced significantly in Lira (200μg·kg-1) and Lira (400μg·kg-1) administra?tion groups (P<0.05). HE staining showed adipocytes in perirenal and inguinal subcutaneous adipose tissue partly acquired brown-like morphological characteristics. The expression levels of UCP-1 protein and mRNA and PGC-1αprotein were ele?vated in adipse tissues, which increased more in Lira (400) than those in Lira (200, P<0.05). Conclusion GLP-1Ra can induce weight loss through white fat browning by activation of UCP-1.
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Objective To observe the effects of high glucose and anoxia on Amot expression in vascular endothelial cells (VECs),and explore its role in angiogenesis.Methods VECs were incubated with different glucose concentrations for 48 h,and then cultured at normal oxygen concentration or anaerobic condition for 24 h.The protein expressions of p130-Amot and p80-Amot were detected by Western blot.After Amot expression was downregulated in VECs by siRNA,wound healing experiments and angiogenesis experiments were performed to test the effect of decreased Amot expression on angiogenesis.Results pl30-Amot protein expressions in low glucose (5.5mmol/L) plus normal oxygen group and low glucose plus anaerobic group were higher than those in high glucose (30mmol/L) plus normal oxygen group,high glucose plus anaerobic group,middle glucose (15 mmol/L) plus normal oxygen group,and middle glucose plus anaerobic group (all P＜0.01).Compared with low glucose plus anaerobic group,p130-Amot expression was higher in low glucose plus normal oxygen group (P ＜ 0.01).However,the expression of p80-Amot showed no statistically significant difference among different groups (P＞0.05).Compared to the normal VECs,the cells with decreased Amot expression by siRNA exhibited an attenuated cell migration in the wound healing experiments and a lesser tube formation in the angiogenesis experiments.Conclusions High glucose exerts a more significantly negtive effect on the Amot expression than anoxia in VECs.The downregulation of Amot expression inhibits migration and angiogenesis of VECs.
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Objective To investigate the potential effect of the redox state of plasma factor Ⅺ (FXI) on the pathogenesis of elderly diabetic hypercoagulability and macroangiopathy.Methods The plasma levels of reduced FXI were detected in elderly type 2 diabetic(T2DM)patients with/without macroangiopathy (T2DM group/DMAP group) and healthy subjects (control group),and variables associated with reduced FXI were analyzed.Results Elderly patients with T2DM had higher plasma levels of reduced FXI as compared with healthy controls.The level of reduced FXI was significantly higher in patients with macroangiopathy than without macroangiopathy [control group:(80.6± 15.6) ％,T2DM group:(94.7 ± 16.0) ％,DMAP group (142.6 ± 36.5) ％,all P＜ 0.05].The multiple stepwise regression analysis showed that plasma levels of triglyceride,cholesterol and HDL-cholesterol were the independent predictors for reduced FXI.Conclusions The plasma level of reduced FXI is increased in elderly T2DM patients with macroangiopathy.The abnormality of lipid profiles may associate with the increment of reduced FXI.These findings maybe provide the novel mechanisms for diabetic hypercoagulability and macroangiopathy.
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Cardiovascular disease (CVD) is one of the major complications of type 2 diabetes mellitus (T2DM), which results in a high risk of mortality. Thus, the cardiovascular safety of new anti-diabetic agents has become an important prob?lem with wide concern. There are two classes of incretine-based medications: glucagon-like peptide-1 receptor agonist (GLP-1RA) and dipeptidyl peptidase-4 (DPP-4) inhibitor (DPP-4I). It has been demonstrated that GLP-1RA and DPP-4I possesse beneficial actions in both animal models of cardiovascular dysfunction and patients with ischemic heart diseases. However, their effects on the cardiovascular system in diabetic patients with heart diseases are still uncertain. Here, we sys?tematically reviewed the effects of GLP-1RA and DPP-4I on cardiovascular system to provide more evidence of incretin-based therapy application for diabetes and complications.
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BACKGROUND:To prepare glucose-responsive microcapsules which can control insulin release as changing the glucose concentration in the medium is of great significance to control the occurrence and development of diabetes mel itus. OBJECTIVE:To study the performance of glucose-responsive alginate/modified-chitosan/alginate microcapsules carryingβ-TC3 cells. METHODS:Glucose-responsive alginate/modified-chitosan/alginate microcapsules were prepared by layer-by-layer self-assembly method to evaluate the performance. And the glucose-responsive microcapsules carryingβ-TC3 cells were prepared to observe the cel proliferation within the microcapsules. RESULTS AND CONCLUSION:The integrity rate of glucose-responsive alginate/modified-chitosan/alginate microcapsules could be 95%after 48 hours oscil ation, and the hardness of microcapsules lowered, but the elasticity increased. The permeability test showed that microcapsules intercepted macromolecular substances such as bovine serum albumin and immuno-globulin G. The microcapsules could release more insulin with the increase of glucose concentration. As described above, the glucose-responsive alginate/modified-chitosan/alginate microcapsules had good mechanical strength, immunoisolation effect and glucose sensitivity. Theβ-TC3 cells entrapped in the glucose-responsive microcapsules could grow wel and the peak of cel proliferation lagged behind as compared with non-microencapsulated cells, indicating the glucose-responsive microcapsules had good biocompatibility.
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Objective To characterize the profile and clinical significance of hepatitis B virus (HBV) quasispecies in patients infected with hepatitis B virus based on the sequence of reverse transcriptase (RT) region.Methods Fifty HBV infected treatment-naive patients were enrolled and divided into three groups,asymptomatic carriers (ASC) group (10 cases),chronic hepatitis B (CHB) group (30 cases) and liver cirrhosis (LC) group (10 cases).HBV genomes were extracted from serum samples.The sequence of RT region was amplified by polymerase chain reaction (PCR) and cloned into vectors.Fifteen to thirty clones per sample were selected,sequenced and analyzed by bioinformatics software.The mean values among groups were compared by analysis of variance.The median values among groups were compared by nonparametric statistics.The enumeration data were analyzed by x2 test.Results Totally 1221 HBV RT region nucleotide sequences were obtained (152from ASC patients,780 from CHB patients and 289 from LC patients).Genotype distribution showed no difference among three groups.However,the quasispecies complexity showed significant differences among the three groups,LC group ＞CHB group＞ ASC group (F=33.400,P＜0.05).The quasispecies diversity was LC group ＞CHB group＞ ASC group,and that of LC group was significantly different from the other two groups (F=18.070,P＜0.05),while there was no significant difference between CHB and ASC patients.Conclusions The HBV isolated from patients in immune clearance phase have higher variability than those isolated from patients in immune tolerance phase.The longer the infection persists and the more severe the disease is,the more variable HBV quasispecies are.
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Objective To characterize serum hepatitis B virus(HBV)full-length genome quasispecies and to investigate its ralationship with severe exacerbation of chronic hepatitis B(CHB).Methods HBV full-length genome was amplified and cloned from four treatment naive CHB patients and four treatment naive CSHB patients.Fourteen to sixteen clones per sample were selected,sequenced and analyzed by bioinformatics software.The measurement data was compared by independent-samples t test and count data was analyzed by x2 test. Results Totally 120 HBV fulllength genome sequences were obtained.All the patients had either genotype B or C virus monoinfection.One hundred percent clones(60/60)from CSHB patients showed mutations including G1896A,A1762T/G1764A(one patient even carried A1762T/G1764A/C1766T mutations),T1753C/G and start codon mutations in preS2,preS1,which were more common than those from CHB patients(46/60,76.7%;x2=15.85,P<0.01).The quasispecies complexity and diversity were higher in CSHB patients than CHB patients within full-length genome,S,X,P genes and reverse transcriptase region,but lower within C gene at both nucleotide and amino acid levels.But the difference were not statistically significant in all regions.Conclusion The mutation frequency and quasispeeies heterogeneity in HBV genome are higher in CSHB patients than in CHB patients,which may play a role in the severe exacerbation of CHB and needs further investigation in large scale studies.
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Objective To construct an in vitro phenotypic analysis technology for evaluating the impact of I233V mutation in the hepatitis B virus(HBV)reverse transcriptase(rt)domain on adefovir (ADV)resistance.Methods A site-directed mutagenesis was used to construct recombinant HBV plasmid containing rtI233V,rtA181V and rtN236T.The culture solution with varied concentration ADV was added after the transient transfection of hepatocyte-derived cell lines with recombinant wild type and mutant HBV clones.Three days later,the cells were harvested and the replicable intermediate was detected by the Southern blot assay.The half maximal inhibitory concentration (IC50) and folds of resistance were calculated by the Table Curve2D software according to the Southern blot results.Results The variant harboring rtI233V mutation exhibited a 6.5-fold decrease of susceptibility to ADV with IC50 of(1.69±0.52)/μmol/L compared to the wild type HBV.Conclusion The findings suggest that the emergence of a single substitution at position rtI233V is sufficient to induce resistance to ADV.
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Objective To investigate the association of hepatitis B virus(HBV) S gene quasispecies with the outcome of HBV infection.Methods Serum samples were collected from three chronic HBV carriers, three chronic hepatitis B and three chronic severe hepatitis B patients.All subjects were male and with HBV genotype C.HBV S gene was amplified, and 20 clones of HBV fragment were randomly selected and sequenced from each sample.SPSS 15.0 software was adopted for analysis.Results Quasispecies complexity of HBV S gene in chronic HBV carriers and chronic hepatitis B tended lower than that of the severe chronic hepatitis B, but the difference was not of statistical significance (P＞0.05).In T cell epitope 45, 47, 85 amino acid sites of the HBV S gene, the constitution of quasispecies in the chronic hepatitis B was more complex than that of the HBV carriers (P=0.01), but compared with the severe chronic hepatitis, the difference was not significant (P=0.06).The computer model showed that both the dominant clones and the non dominant clones could effectively bind to the receptors of cytotoxic T lymphocytes.Conclusion Quasispecies in some T cell epitopes of HBV S gene may be related with the clinical outcome of hepatitis B.
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Objective:To observe the effect of xylitol on the cyclooxygenase(COX)-2 expression of renal tubule in diabetic rats.Methods:The Wistar rats were randomly divided into normal control group(group NC),diabetes control group(group DC),5% xylitol-treated group(group 5%),10% xylitol-treated group(group 10%)and 20% xylitol-treated group(group 20%).At the end of 8 weeks,the expression of COX-2 in kidney tissue,the level of serum uric acid,allantoin and creatinine were tested in rat groups.Results:The levels of serum uric acid and allantoin were higher in group 5% and group 10% compared with that of group DC.The differences in levels of serum uric acid and allantoin were statistical significance between group 10% and group DC(P ＜ 0.05),whereas,the lower levels of serum uric acid and allantoin were found in group 20% compared with those of group DC(P ＞ 0.05).The levels of urine uric acid and allantoin were lower in group 5% and group 10% than those of group DC(urine uric acid,P＞ 0.05 and allantoin,P＜ 0.05),whereas,group 20% had higher levels of urine uric acid and allantoin than those of group DC(P＜ 0.05).The fractional excretion of uric acid(FEUA)was lower in group 5% and group 10% compared with that of group DC(P ＜ 0.05).The FEUA was higher in group 20% than that of group DC(P ＜ 0.05).The expression of COX-2 was significantly increased in group 5% and group 10% compared with that of group DC(P ＜ 0.05),but the expression of COX-2 decreased in group 20%(P ＜ 0.05).Conclusion:The lower and mediate doses of dietary xylitol could aggravate the tubular injury through increasing the level of serum uric acid and the expression of COX-2 in renal tubule.The higher doses of xylitol could increase the excretion of uric acid and down-regulate the expression of COX-2 in renal tubule.
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Objective To construct S6K1 shRNA gene recombinant adenovirus(S6K1 Ax)and evaluate its gene silencing effects on mouse cell lines and C57 BL/6J mice level.Methods Three S6K1 shRNA gene sequences were designed and spliced from pcPUR plasmid,pcDNA3.1 plasmid to cosmid plasmid and transfected into adenovirus.S6K1 Ax which has best gene silencing effect was selected and proliferated in 293 cell.Silencing effect of S6K1Ax was checked on mice AML12,C2C12,3T3-L1 cell lines.C57BL/6J liver was obtained after S6K1 Ax was injected into mice tail vein six days later.S6K1 was evaluated by qRT-PCR and Western blot.Alanine transferanse(ALT)was examined before and after S6K1 Ax injected.Results S6K1Ax can silence S6K1 expression of mouse AML12,C2C12 and 3T3-L1 cell lines and liver of C57 BL/6J mice on Western blot.S6K1 mRNA expression of C57BL/6J liver were control group 1.39±0.21 vs S6K1Ax group 0.63±0.09,t=6.132.P<0.01.ALT of mice hepatic function did not change after S6K1Ax injected:before(15.15±4.43)U/L,after(17.32±4.22)U/L,t=1.451,P>0.05.Conclusion Construction of shS6K1 Ax can knockdown S6K1 gene on mice cell lines and C57BL/6J mice liver,it provides a good tool to study the function of S6K1.
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To study the possible mechanism of the effect of glucagon-like peptide-1 (GLP-1) on injury to neonatal rat cardiomyocytes induced by hypoxia-reoxygenation. Lactate dehydrogenase activity [(210.0±11.5) vs (101.4±6.5) U/L] ,apoptosis rate [(8. 138±1. 512) vs(0. 575±0. 168)%] ,and caspase-3 activity [(44.52± 5.69)vs(19.98±1.97) ,all P<0.01] were all increased after hypoxia-reoxygenation. GLP-1 appears to directly act on cardiomyocytes and to protect them from hypoxia-reoxygenation injury [lactate dehydrogenase (190.2±9.0) U/ L, apoptosis rate (2.688±0.580) %, caspase-3 activity 30.34±4.18] mainly by inhibiting the apoptosis probably via the PBK/Akt signaling pathways.
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Objective To explore the effect of diabetes mellitus (DM) on biological behavior of epidermal keratinocyte in rats. Methods A total of 40 Sprague-Dawley rats were randomized into control group and streptozotocin (STZ) -induced diabetes group. Of each group, 10 rats were implemented with deep partial-thickness scalding. The re-epithelialization rate was observed at the 3rd, 7th, 14th and 21th post-burn day. Histological characteristics and thickness of epidermal tissue in both groups were observed. The adhesion rate, cell cycles, apoptosis rate and migration ability of keratinocyte were measured. The accumulation of advanced glycosylation end products (AGEs) of epidermal tissue was observed. Results The percentages of re-epithelialized area at the 7th, 14th and 21th post-burn day were much lower in DM group than in control group (P<0.05). In DM group, the epidermal thickness was reduced obviously with obscure multilayered epithelium and less amount of prickle cells; The adhesion rates of 12, 24 h after culturing keratinocyte and the percentage of G2/M phase cells were lower in DM group than in control group (P<0.05). However, apoptosis rate of keratinocyte was higher, the amount of migration cell was significantly less in DM group than in control group (both P<0.05). There were lots of AGEs accumulated in epidermal tissue in DM group, while there were hardly AGEs in control group. Conclusions Re-epithelization blocked exists on non-healing wound in DM rats, which is related with the impaired keratinocyte biological behavior. A large of AGEs accumulate in the epidermal tissue of DM rats, which may be a important reason to inhibit keratinocyte function in diabetic environment.
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Rhesus retinal vascular endothelial cell line RF/6A cells were treated with human insulin. Cell proliferation, migration, and lumen formation, as well as the expressions of vascular endothelial growth factor-A ( VEGF-A ), VEGF-A receptors, and phosphorylated receptors were measured. Insulin promoted RF/6A cell proliferation, migration, and lumen formation ( all P＜0. 01 ). Insulin increased the expression of VEGF-A mRNA and improved its protein activity ( all P＜0. 05 ), and promoted the expression of VEGFR2 mRNA and its phosphorylation ( both P＜0. 01 ). There was no significant difference in the expression of VEGFR1 mRNA among the groups ( P＞0. 05 ).