AIM:To investigate the effect of paeoniflorin(PF)on TLR4/MyD88 signaling pathway in liver of rats with metabolic dysfunction-associated fatty liver disease.METHODS:SPF grade male SD rats were randomly divid-ed into four groups:normal control(NC)group,model control(MC)group,low-dose paeoniflorin(PL)group,and high-dose paeoniflorin(PH)group.The normal group was given standard diet,and the other three groups were given high-fat diet for 8 weeks.From the fifth week,rats in paeoniflorin groups were given low dose(25 mg·kg-1·d-1)or high dose(50 mg·kg-1·d-1)paeoniflorin for 4 weeks.Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC)and triglyceride(TG)were measured by biochemical method.The levels of tumor necrosis factor(TNF)-α was detected by ELISA.Pathological change of the liver was detected with hematoxylin-eosin(HE)staining and oil red O staining,and evaluated semi-quantitatively with the nonalcoholic fatty liver disease activity score(NAS).The expres-sion levels of TLR4,MyD88 and phosphorylated nuclear factor(p-NF)-κB p65 in liver tissues were detected by immuno-histochemistry and Western blot.RESULTS:Compared with the NC group,rats in the MC group showed increased TC,TG,ALT,AST and TNF-α in serum(P<0.05),and more lipid droplets in hepatocytes and inflammatory cell infiltration in the portal area,with higher NAS,TLR4,MyD88 and p-NF-κB p65 proteins in liver tissue(P<0.05).However,pae-oniflorin could reduce TC,TG,ALT,AST and TNF-α in serum(P<0.05),improve histopathological changes of liver,decrease the NAS scoring(P<0.05),and inhibit hepatic TLR4/MyD88/p-NF-κB p65 expressions(P<0.05).CONCLU-SION:Paeoniflorin could improve the lipid metabolism disorder and reduce liver inflammation during MAFLD,and the latter effect might be in part related to the inhibition of TLR4/MyD88 signaling pathway.

OBJECTIVETo report on a Chinese family from Wenzhou with genetically confirmed Kennedy disease and describe its clinical and genetic features.

METHODSThe clinical phenotype and the level of relevant biochemical markers were assessed. To determine the number of CAG repeats in the exon 1 of androgen receptor (AR) gene, genomic DNA was extracted from peripheral blood samples of the family members, amplified by PCR and identified by DNA sequencing.

RESULTSThe proband showed predominantly proximal limb weakness, fasciculation, muscle atrophy, gynecomastia, sexual dysfunction and increased serum creatine kinase. Myopathy and neuropathy were identified by electromyography. Two other affected males and 2 affected female carriers were identified to carry an expanded CAG repeat in the AR gene. The numbers of CAG repeats were found to be 43 in the proband, 43 and 42 in the other two affected males, one of which had similar clinical symptoms to the proband.

CONCLUSIONThe family was diagnosed with Kennedy disease by analysis of the AR gene.

Adolescent ; Adult ; Base Sequence ; Bulbo-Spinal Atrophy, X-Linked ; blood ; diagnosis ; genetics ; Creatine Kinase ; blood ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Pedigree ; Receptors, Androgen ; genetics ; Trinucleotide Repeat Expansion ; Young Adult

[Objective] To investigate the clinical characteristics and risk factors of lower-extremity arterial disease in the patients with newly diagnosed type 2 diabetes mellitus combined with nonalcoholic fatty liver disease (NAFLD). [Methods] One hundred fifty-one patients were investigated respectively. The patients were divided into two groups (NAFLD-Group and non-NAFLD group) by liver ultrasonography and disease history, then their clinical data were collected and compared in order to find the differences of biochemical indicators and the morbidity of lower-extremity arterial disease between two groups. [Results] Ninety-two cases (60.93%) were complicated with NAFLD. NAFLD group had higher levels of fast insulin and C peptide level, postprandial insulin and C peptide level, uric acid, body mass index (BMI), homeostasis model assessment (HOMA-IR) and lower level of high-density lipoprotein cholesterol and insulin sensitive index than those of without NAFLD (P<0.05). One hundred and one cases(66.89%) were complicated with lower-extremity arterial disease. The morbidity of lower-extremity arterial diseases was higher in NAFLD group than that of without NAFLD group (75% vs. 54.24%, P<0.01). [Conclusion] Both lower-extremity arterial disease and NAFLD are common complicated with type 2 diabetes. The morbidity of lower-extremity arterial diseases was higher in NAFLD group than that of without NAFLD group.

Objective To study the effects of sulodexide on islet B-cell function in streptozocin induced di-abetic rats. Methods Sprague-Dawley(SD) rats were randomly divided into normal control group (group C), dia-betic group without treatment(group D), and suledexide treatment group(group S), a single dose of streptozotocin were abdominally injected to establish the diabetic rat models. Each animal in sulodexide treated group was addition-ally fed with sulodexide of 10 mg/(kg·d) for 12 weeks,while the remained group (group C and D) were given normal water in the same period. After 12 weeks of treatment, fasting plasma glucose(FPG),fasting plasma insulin (FINS), activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), triglyceride (TG), Low-density lipoprotein cholesterol (LDL-C), serum creatinine rates (SCr) and alanine aminotransferase (ALT) were measured. Insulin sensitivity index(ISI) and insulin resistant index (HOMA-IR) were calculated. Results After 12 weeks, the levels of TG, LDL-C and ALT had no significant difference between group D and group S, but were higher than those in group C (P <0.05);There were no significant difference of SCr levels among the three groups. Compared with the group C, APTT, PT, TT and ISI in group D and S were significantly decreased, HOMA-IR were significantly increased (P < 0.05). APTT, PT, TT and ISI in group S had significantly increased compared with that in group D, HOMA-IR was significantly decreased in group S compared with that in group D (P < 0.01). Conclusions Sulodexide can reduce insulin resistant, improve hypercoagulability and insulin sensitiv-ity in streptozocin induced diabetic rats. The effects to blood lipid, liver and renal functions in diabetic rats are not obvious.

Objective To investigate the relationship between dyslipidemia,obesity,insulin resistance (IR)and various degrees of non.alcoholic fatty liver disease(NAFLD)in patients with type 2 diabetes mellitus (T2DM), and the risk factors of NAFLD.Methods Two hundred and sixty-eight patients were divided into three groups(non-NAFLD group,mild NAFLD group,moderate and severe NAFLD group)by liver ultrasonography.Body height(H),weight(W),waist circumference(WC),hip circumference(H)were measured.The levels of fasting blood glucose (FBG),glycosylated hemoglobin A_1c(GHbA_1C),serum total cholesterol(TC),serunl high density lipoprotein(HDL-C),serum low density lipoprotein(LDL-C),serum triglyceride (TG),alanine aminotransferase (ALT)and fasting serum insulin(FINS)were measured.Body mass index(BMI),the waist to hip ratio(WHR)and insulin resistance index(HOMA-IR)were calculated.Unconditional logistic regression model was used to test for the risk factors of NAFLD.Results BMI、WC、WHR、HNS、HOMA.IR、TC、LDL-C、TG and ALT in NAFLD group were significantly higher than those in non-NAFLD group (P<0.05).The levels of BMI、WC、WHR、HNS、HOMA-IR、 TG and ALT increased significantly in moderate and severe NAFLD group compared with mild NAFLD group(P<0.05).TG、WHR and HOMA.IR were the risk factors of NAFLD(P<0.05,OR=2.394,3.273,5.256).Conclusions NAFLD in patients with T2DM had remarkable dyslipidemia,overweight,central obesity and insulin resistance.TG、WHR and HOMA.IR were risk factors of NAFLD.

Objective To investigate the effects of different dialysates on expression of protein kinase C-δ (PKCδ) and apoptosis of U937 cell line. Methods Different dialysates were added into culture fluid with U937 cell line at exponential phase of growth, and groups were divided: fluid A+fluid B group (dialysate A+dialysate B), fluid A+fluid B+rottlerin (PKCδ specific inhibitor)group, fluid A+powder B group (dialysate A+powder B) and fluid A+powder B + rottlerin group. Besides, blank control group and normal control group were established. Cells were harvested 24 h and 48 h after treatment, morphological changes were observed by Hoechst33258 fluorescence staining, cell apoptosis was measured by Annexin-V-FITC/PI double staining, and expression of PKCδ mRNA and protein was detected by RT-PCR and Western blotting, respectively. Results Cell apoptosis significantly increased in fluid A+powder B group, with typical morphology of apoptosis. After treatment for 24 h and 48 h, cell apoptosis rates in fluid A+powder B group were significantly higher than those at corresponding time points in blank control group , normal control group and fluid A+powder B+rottlerin group (P<0.05). Compared with normal control group, blank control group and fluid A+powder B+rottlerin group, the expression of PKCδ mRNA and protein of U937 cells in fluid A+powder B group were significantly increased (P<0.05). There was no significant difference in cell apoptosis rates and expression of PKCδ mRNA and protein between fluid A+fluid B group and blank control group, normal control group and fluid A+fluid B+rottlerin group (P＞0.05). Conclusion Fluid A+powder B can significantly increase apoptosis of U937 cell line, the mechanism of which may be associated with the up-regulation of expression of PKCδ. Compared with fluid A+powder B, fluid A+fluid B is superior in reducing apoptosis of peripheral blood monouclear cells.

Objectives To investigate the epidemiological and clinical characteristics of dyslipidemia as well as its treatment and influence on accompanying diseases in impaired glucose status among inpatients. Methods A cross-sectional survey was conducted among the inpatients registered in ten university hospitals of Guangdong, China during the week before the Diabetes Day in 2004. The fasting blood glucose (FBG), lipid profiles, BMI, waist to hip ratio (WHR) and concomitant disorders of the first screen during the hospitalization period were recorded. Those who had FBG level from 5.6 to 6. 9 mmol/L and not been previously diagnosed diabetes (PDM) underwent oral glucose tolerance test (OGTF). Results Of the 8753 inpatients investigated, 1067 eases had complete medical records(CMR case) including PDM cases and previously non-diagnosed diabetes ones with FBG ≥ 5. 6 mmol/L. Of the previously non-diagnosed diabetes cases with FBG levels from 5.6 to 6.9 mmmol/L, 65.8% accepted OGTT. Of the CMR cases, 41.9% had PDM, 21.7% was newly diagnosed diabetes mellitus (NDM), 29. 1% had impaired glucose regulation (IGR) and only 7.3% had normal glucose tolerance (NGT). The TG levels in NDM and PDM group were higher than those in IGR and NGT group (P < 0.05, respectively). The HDL-C levels in IGR, NDM and PDM group were lower than those in NGT group (P < 0.05, respectively). Sixty-nine point six percent of the diabetes mellitus (DM) inpatients was accompanied with dyslipidemia and the rate was higher than those in NGT (56.4%) and IGR inpatients (52.5%, P <0.05, respectively). Only 22. 8% of the PDM inpatients underwent treatment of dyslipidaemia and just 3.4% achieved the target suggested by the guideline of ATP-Ⅲ. BMI was higher and waistline longer in the PDM and NDM inpatients than those in the NGT cases (P <0.05, respectively). Seventy-two point eight percent of the PDM inpatients was complicated with more than one type of vascular diseases. Nine point seven percent and 0. 2% of the NDM inpatients were tormented by diabetic nephropathy and diabetic retinopathy respectively. Conclusions More inpatients with accompany DM or IGR had concomitant dyslipidemia than those with NGT, which included hypertriglyccridemia, hypo-high-density lipoproteinemia and metabolic syndrome. Concomitant vascular diseases were more frequently found in PDM inpatients than in the others. Some of the NDM and IGT inpatients were complicated with microvascular diseases.

Objective To compare the excursion of blood glucose (BG) in the type 2 diabetes mellitus treated with oral antidiabetic drugs (OADs) plus glargine or human isophane insulin (HII). Methods A 1 : 1 randomization schedule assigned 30 type 2 diabetics inadequately controlled on OADs (fasting BG>9.0 mmol/L and HbA1C > 8.5%) to 2 groups additionally treated with glargine or HII. The insulin dose was titrated to achieve fasting capillary BG<6.0 mmol/L. Montoring BG with continuous glucose monitoring system, then the standard deviation of BG (SDBG), maximal excursion of BG (LAGE) and coefficient of variation (CV) of fasting plasma glucose (FPG) were calculated. Results SDBG (1.49±0.35 vs 1.73±0.46), LAGE (3.23±0.76 vs 3.73± 1.00) and CV-FPG (17.26±2.24 vs 20.33±3.21) were lower in glargine group than those in HII group (P< 0.05). No difference could be found in hypoglycaemia between two groups. Conclusion OADs plus glargine could make blood glucose more stable than OADs plus HII without increasing the incidence of hypoglycaemia.

The human La protein is recently identified as a host factor potentially involved in the post-transcriptional regulation of hepatitis B virus (HBV) RNA. The La binding site is mapped to a predicted stem-loop structure within a region shared by all HBV RNAs, and it is known that human La protein protected HBV RNA against Rnase-mediated degradation. HLa mutants lost the ability of binding and protecting HBV RNA, which make it easy for HBV RNA to degrade and the virus replication to terminate. This review summarizes the latest investigation about the interaction of La protein,HBV RNA and Nuclear RNases, and discusses the possible mechanisms of HBV RNA degradation, the effect of La protein and its mutants on the translation initiation of HBV RNA, and the replication of the virus.

Objective:To prove whether La protein could effect the replications of the HBV in cultured cells.Methods:Three specific SiRNAs for human La protein was obtained by transcription in vitro. After transfection with the SiRNAs into HepG2.2.15 cell, the levels of La protein mRNA and HBV DNA were detected by real-time PCR.Results:The HBV DNA secreted by the cell transfected with the SiRNAs was reduced with reduction of the mRNA of the La protein.Conclusion:The La protein can protect the replications of the HBV in cultured cells.