AIM:To investigate the protection mechanisms of rosiglitazone on diabetic nephropathy.METHODS:Rat mesangial cells(MC) were incubated in media containing 5.5 mmol/L normal control glucose,25 mmol/L high concentration glucose,25 mmol/L glucose +20 ?mol/L rosiglitazone maleate.Cells proliferation were assessed by CCK-8.Synthesis of fibronectin(FN),type Ⅳ collagen(Col-Ⅳ),transforming growth factor-?1(TGF-?1) and matrix metalloproteinase inhibitor-1(TIMP-1) in supernatant were determined by ELISA method,the activities of matrix metalloproteinase-2,9(MMP-2,9) in supernatant were determined by gelatinase zymography.RESULTS:Compared with control group,MC cultured with high concentration glucose showed a high growth rate and increased synthesis of Col-Ⅳand FN,decreased the activities of MMP-2 and MMP-9,and increased secretion of TGF-?1 and TIMP-1.Compared with high glucose group,these changes could be reversed by rosiglitazone intervention.CONCLUSION:Rosiglitazone could inhibit high concentration glucose-induced proliferation of mesangial cells,decrease synthesis of extracellular matrix,and increase degradation of extracellular matrix.

AIM: To investigate the effects of fenofibrate(FB) and rosiglitazone(RG) on the signal passway of p38 mitogen-activated protein kinases(p38 MAPK) in glomerular mesangial cells cultivated in high concentration of glucose.METHODS: Rat mesangial cells(MC) were incubated in 5.5 mmol/L normal control glucose,25 mmol/L high glucose(HG),HG+100 ?mol/L fenofibrate(FB+HG),HG+20 ?mol/L rosiglitazone maleate(RG+HG),respectively.The fibronectin(FN) and type Ⅳ collagen(Col-Ⅳ) in supernatant were determined by ELISA.The expressions of p38MAPK and phospho-p38MAPK proteins in cytoplasm and nuclei were detected by Phospho-ELISA.The mRNA expression of p38MAPK was detected by semi-quantitative reverse transcription polymerase chain reaction(RT-PCR).RESULTS: Compared with normal control,the Col-Ⅳand FN in supernatant in HG group were much higher,the expression of p-p38MAPK was increased in cytoplasms and nuclei.Col-Ⅳ and FN were obviously decreased with the treatment of FB or RG,and the expression of p-p38MAPK in nuclei was down-regulated,but the expression of p-p38MAPK in intracytoplasm had no changes.There were no significant differences of the expressions of total protein and mRNA of p38MAPK among four groups.CONCLUSION: FB,RG could inhibit the activation of p38MAPK in nuceli of MC cultivated in high concentration of glucose,and then reduce the synthesis of extracellular matrix.

Objective To evaluate the changes of IL-1β and IL-lra in hippocampus of rats with frequent febrile seizures(FS).Methods 21-day-old male Sprague-Dawley(SD)rats were randomly divided into 3 groups:normal control group(NC group),hyperthermic control group(HC group)and febrile seizures group(FS group).IL-1β and IL-1ra levels in hippocampus of these rats were determined by ELISA methods,IL-1β mRNA and IL-1ra mRNA levels in hippocampus were measured by RT-PCR.Results IL-1β mRNA and protein levels in hippocampus of rats in FS group were significantly higher than those in NC group and HC group(P＜0.01,P＜0.05).IL-1ra mRNA and protein levels in hippocampus of rats in FS group were significantly higher than those in NC group and HC group(P＜0.01,P＜0.05),too.IL-1ra/IL-1β protein ratio showed no significant difference among 3 groups.Conclusion Frequent FS can cause the increase of IL-1β and IL-lra mRNA and protein levels in hippocampus,suggesting that IL-1β and IL-1ra may be involved in the pathogenesis of hippocampal neuron damage in FS rat.

Objective To investigate the kidney function changes and the risk factors in elderly patients aged 80 years and over.Methods A total of 1054 hospitalized patients aged ≥80 years in our hospital were selected.Serum levels of creatinine,urea,uric acid and urinate were tested.Cockcroft-Gault equation was used to estimate glomerular filtrate rate (GFR).Results The renal function in 87.1 ％ of the patients was reduced.The percentage of patients with 30≤eGFR ＜60 ml · min-1 · 1.73 m-2 was 66.2％.The percentage of patients with 15≤eGFR ＜30 ml · min-1 · 1.73 · m-2had a gender difference (P＜0.05).Serum creatinine level was not an ideal indicator for early renal dysfunction in the elderly,especially in emaciated elderly people.Multivariate logistic regression analysis showed that gender,hypertension,coronary heart disease and hyperuricemia were independent risk factors for the decline of renal function (OR=1.937,1.602,1.842,7.020,respectively,all P＜0.05).Conclusions The rate of renal dysfunction is high in very old people.Many risk factors affect renal dysfunction.

AIM: To investigate the molecular mechanism of amylin in inducing apoptosis of human pancreatic islet ?-cells. METHODS: Human pancreatic islet cells were isolated and cultured. The cells were treated with amylin or amylin and aminoguanidine (AG group) for 24 h, respectively. Apoptosis of pancreatic islet ?-cells was studied by in situ TUNEL method combined with double staining for insulin and ELISA. The levels of insulin, NO 2 -/NO 3 - and glutathione (GSH), p53 mRNA and bcl-2 mRNA were also detected. RESULTS: (1) The enrichment factor and the apoptosis rate of pancreatic islet ?-cells in amylin group were markedly higher than that in control group and AG group ( P

AIM: To investigate the effect of losartan on the mRNA expression of type 2 angiotensin II receptor and cytokines in diabetic rat kidney.METHODS: SD rats were randomly divided by following groups: control rats(group C),diabetic rats(group D) and diabetic rats treated with losartan (30(mg?kg~(-1)?d~(-1)),by gavage,group DT).At the end of 8-weeks study,mRNA expressions of the type 2 angiotensin II receptor(AT_2),transforming growth factor-?_1(TGF-?_1),platelet-derived growth factor-B(PDGF-B),tumor necrosis factor-?(TNF-?) and collagen Ⅳ in rats renal cortex were measured by RT-PCR,respectively.In addition,angiotensin Ⅱ level in renal cortex was determined by the radioimmunoassay.RESULTS: In group D,urine protein excretion(P

Urinary excretions of transforming grow th factor-? 1 (TGF-? 1), laminin (LN) and type Ⅳ collagen were determined i n 182 type 2 diabetic patients. Urinary excretions of TGF-? 1, LN and type Ⅳ collagen were increased in type 2 diabetic patients, and these findings were fa irly well correlated with severity of diabetic nephropathy (DN). Urinary TGF-? 1 seems to be the early index of DN, urinary LN and type Ⅳ collagen appear to be the indices of DN severity.

Objective:To correlate serum homocysteine (Hcy) level with psychiatric symptoms and social ability in patients with schizophrenia.Methods:A total of 143 patients with schizophrenia who received treatment in the Third Hospital of Quzhou from January 2018 to January 2020 were included in this study. They were randomly divided into abnormal Hcy group (Hcy ≥ 10) μmol/L, n = 46) and normal Hcy group (Hcy < 10 μmol/L, n = 97) according to different serum Hcy levels. Baseline data, the scores of the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), and the Substance Dependence Severity Scale (SDSS) were compared between the two groups. The correlation between serum Hcy level and psychiatric symptoms and social ability was analyzed using the Pearson correlation analysis. Results:PANSS total score and BPRS total score were (77.86 ± 8.37) points and (94.47 ± 9.36) points, respectively in the abnormal Hcy group, and (74.37 ± 7.94) points and (90.35 ± 9.26) points, respectively in the normal Hcy group. There were significant differences in PANSS total score and BPRS total score between the two groups ( t = 2.41, 2.47, both P < 0.05). SDSS total score was significantly higher in the abnormal Hcy group than in the normal Hcy group [(11.75 ± 2.38) points vs. (10.53 ± 2.28) points, t = 2.88, P < 0.05]. Pearson correlation analysis showed that serum Hcy level was positively correlated with PANSS positive subscale score ( r = 0.73, P < 0.001), general mental symptom score ( r = 0.43, P = 0.032) and PANSS total score ( r = 0.53, P = 0.027), but it was not correlated with PANSS negative symptom score ( P > 0.05). Serum Hcy level was positively correlated with BPRS excitement subscale score ( r = 0.42, P = 0.037) and hostility subscale score ( r = 0.37, P = 0.047), but it was not correlated with anxiety, blunted affect, unusual thought content subscale scores and BPRS total score (all P > 0.05). Conclusion:Serum Hcy level is correlated with psychiatric symptoms and social ability in patients with schizophrenia. The higher the level of Hcy, the more severe the psychiatric symptoms, and the higher the degree of social disability.

Objective: To explore the value of bioelectrical impedance analysis in evaluating hemodialysis patients′ nutritional status. Methods: Cross-sectional design was employed to evaluate 193 hemodialysis patients′ nutritional status in a Level 3 hospital in Zhuhai, with bioelectrical impedance analysis, modified quantitative subjective global assessment, physical and biochemical measurement. The correlation between each index and the predictive effect of bioelectrical impedance analysis on malnutrition of patients were analyzed. Results: According to bioelectrical impedance analysis, hemodialysis patients′ average muscle mass was (44.06±8.84) kg, body fat rate was (19.81±8.89)%, fat free mass index was (17.70±2.45) kg/m², presumed bone mass was (2.49±0.46) kg, and extracellular water rate was (40.54±3.75)%. The bioelectrical impedance analysis indexes were significantly correlated with most other nutritional evaluation indexes (P<0.05). The muscle mass and bone mass of the malnourished group were lower than that of the well-nourished group (P<0.01). Multivariable logistic regression analysis found that body fat rate (OR=0.94, 95%CI 0.89-0.99), fat free body mass index (OR=0.79, 95%CI 0.66-0.93) were associated with lower risk of malnutrition, age (OR=1.08, 95% CI 1.04-1.12), dialysis age (OR=1.02, 95%CI 1.01-1.04), high sensitive C reactive protein (OR=1.11, 95%CI 1.03-1.23) were associated with higher risk of malnutrition. Conclusion Bioelectrical impedance analysis is a valid measurement on evaluating maintenance hemodialysis patients′ nutritional status. There has a high prevalence of malnutrition in hemodialysis patients. The lower risk of malnutrition is associated with higher body fat rate and higher fat free mass index, and the higher risk of malnutrition is associated with older age, longer dialysis age and higher level of high sensitive C reactive protein.

Senescence of activated hepatic stellate cells (aHSCs) is a stable growth arrest that is implicated in liver fibrosis regression. Senescent cells often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). But little is known about how alanine-serine-cysteine transporter type-2 (ASCT2), a high affinity glutamine transporter, affects HSC senescence and SASP during liver fibrosis. Here, we identified ASCT2 is mainly elevated in aHSCs and positively correlated with liver fibrosis in human and mouse fibrotic livers. We first discovered ASCT2 inhibition induced HSCs to senescence in vitro and in vivo. The proinflammatory SASP were restricted by ASCT2 inhibition at senescence initiation to prevent paracrine migration. Mechanically, ASCT2 was a direct target of glutaminolysis-dependent proinflammatory SASP, interfering IL-1α/NF-κB feedback loop via interacting with precursor IL-1α at Lys82. From a translational perspective, atractylenolide III is identified as ASCT2 inhibitor through directly bound to Asn230 of ASCT2. The presence of -OH group in atractylenolide III is suggested to be favorable for the inhibition of ASCT2. Importantly, atractylenolide III could be utilized to treat liver fibrosis mice. Taken together, ASCT2 controlled HSC senescence while modifying the proinflammatory SASP. Targeting ASCT2 by atractylenolide III could be a therapeutic candidate for liver fibrosis.