Increased expression of NLRP3 associated with elevated levels of HMGB1 in children with febrile seizures: a case-control study.

BACKGROUND: High mobility group box-1 (HMGB1) is an endogenous danger signal that mediates activation of the innate immune response including NLR pyrin domain containing 3 (NLRP3) inflammasome activation and proinflammatory cytokine release. Although HMGB1 and NLRP3 have been implicated in the pathophysiology of seizures, the correlation between HMGB1 and NLRP3 expression has not been determined in children with febrile seizures (FS). To explore the relationship between extra-cellular HMGB1 and NLRP3 in children with FS, we analyzed serum HMGB1, NLRP3, caspase-1, and proinflammatory cytokines in patients with FS. METHODS: Thirty children with FS and thirty age-matched febrile controls were included in this study. Blood was obtained from the children with FS within 1 h of the time of the seizure; subsequently, the serum contents of HMGB1, NLRP3, caspase-1, interleukin (IL)-1ß, interleukin (IL)-6, and tumour necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay. The Mann‒Whitney U test was used to compare serum cytokine levels between FS patients and controls. Spearman's rank correlation coefficient was calculated to detect significant correlations between cytokine levels. RESULTS: Serum levels of HMGB1, NLRP3, caspase-1, IL-1ß, IL-6, and TNF-α were significantly higher in FS patients than in febrile controls (p < 0.05). Serum levels of HMGB1 were significantly correlated with levels of NLRP3 and caspase-1 (both, p < 0.05). Serum levels of caspase-1 were significantly correlated with levels of IL-1ß (p < 0.05). Serum levels of IL-1ß were significantly correlated with levels of IL-6 and TNF-α (p < 0.05). CONCLUSIONS: HMGB1 is up-regulated in the peripheral serum of FS patients, which may be responsible, at least in part, for the increased expression of NLRP3 and Caspase-1. Increased expression of caspase-1 was significantly associated with elevated serum levels of IL-1ß. Given that activated Caspase-1 directly regulates the expression of mature IL-1ß and positively correlates with activation of the NLRP3 inflammasome, our data suggest that increased levels of peripheral HMGB1 possibly mediate IL-1ß secretion through the activation of the NLRP3 inflammasome in children with FS. Thus, both HMGB1 and NLRP3 might be potential targets for preventing or limiting FS.

Evaluation of efficacy and safety of DPP-4 inhibitors for Chinese elderly patients with type 2 diabetes mellitus.

BACKGROUND: The safety of hypoglycemic drugs should be paid more attention to in elderly patients with type 2 diabetes mellitus due to their concomitant diseases, physiological decline of liver and kidney function and cognitive decline. The aim of this study was to evaluate the efficacy and safety of DPP-4 inhibitors in elderly patients with type 2 diabetes mellitus. METHODS: From January 2010 to November 2018, 300 patients with type 2 diabetes mellitus who were over 60 years old were enrolled in the outpatient clinic of Geriatric Medical Center. Their medication records and follow-up medical records were used for retrospective analysis. The duration of treatment with DPP-4 inhibitors was more than 3 months. The changes of fasting blood glucose (GLU), glycosylated hemoglobin (HbA1C), body weight, body mass index (BMI) and liver and kidney function were compared before and after treatment. RESULTS: The average age of 300 patients (212 males and 88 females) was 73.7 ± 9.1 years old, BMI was 26.5 ± 2.8 kg/m2 and the duration of diabetes was 10.7 ± 8.2 years. The results of retrospective analysis showed that HbA1C decreased by 0.27% after treatment (P < 0.001). In the group of DPP-4 inhibitors used for less than 12 months, there was no difference in liver transaminase (ALT and AST) between before and after treatment, whereas in the group of DPP-4 inhibitors used formore than 12 months, liver transaminase decreased statistically compared with after treatment (P < 0.001). The incidence of fatty liver in elderly diabetic patients decreased after using DPP-4 inhibitors. There was no significant change in serum creatinine level and creatinine clearance rate in elderly patients with type 2 diabetes mellitus after treatment of DPP-4 inhibitor. In addition, the body weight and BMI of the patients decreased significantly (P < 0.001). No hypoglycemic reaction and gastrointestinal discomfort were found in the medical records. CONCLUSION: After DPP-4 inhibitors were used in elderly patients with type 2 diabetes mellitus, the elevated glycosylated hemoglobin could be controlled with improved safety of liver and kidney, and might have the effect of weight loss.

[Analyses on the relative factors regarding diabetic nephropathy among 1758 cases of type 2 diabetic patients].

OBJECTIVE: To analyze the prevalence rate of diabetic nephropathy (DN) and the related factors on DN among type 2 diabetic patients. METHODS: A total number of 1758 type 2 diabetic patients who were hospitalized in the Beijing Hospital from 2003 to 2010 were analyzed retrospectively. Three groups were divided according to the rate of urinary albumin excretion (UAER). Patients whose UAER < 20 µg/min belonged to normal albuminuria (NA) group. The ones whose UAER from 20 to 200 µg/min belonged to microalbuminuria (MA) group, and the others whose UAER ≥ 200 µg/min belonged to large albuminuia (LA) group. The clinical characteristics were then compared. The related factors of DN were analyzed. RESULTS: (1) There were 1246 patients in NA group, 408 patients in MA group, and 104 patients in LA group. The constituent ratio of nephropathy was 29.1%. (2) The ages of NA group, MA group and LA group were (59.87 ± 12.77, 62.52 ± 12.74, 64.44 ± 12.74) years old, respectively, with body mass index (BMI) as (24.90 ± 3.42, 25.53 ± 4.00, 25.53 ± 3.91) kg/m(2) respectively; duration of diabetes as (8.39 ± 7.12, 10.77 ± 8.02, 12.84 ± 7.97) years; systolic blood pressure (SBP) as (133.42 ± 18.19, 142.72 ± 20.21, 151.12 ± 21.91) mm Hg; diastolic blood pressure as (78.75 ± 10.66, 80.79 ± 12.21, 83.33 ± 13.61) mm Hg; fasting blood sugar (FBS) as (8.25 ± 3.43, 9.02 ± 3.72, 9.22 ± 4.62) mmol/L; glycated hemoglobin (HbA1c) as (8.88 ± 2.10, 9.34 ± 2.36, 9.10 ± 2.36)%; uric acid (UA) as (288.04 ± 90.41, 307.23 ± 96.96, 374.28 ± 105.47) mmol/L; triglyceride as (1.72 ± 1.51, 2.06 ± 1.88, 1.94 ± 1.42) mmol/L, high density lipoprotein cholesterol as (1.08 ± 0.30, 1.02 ± 0.29, 1.07 ± 0.28) mmol/L; fasting insulin as (9.24 ± 9.02, 11.24 ± 9.74, 11.06 ± 9.29) µU/ml; fasting C peptide as (462.31 ± 289.94, 510.02 ± 350.08, 595.93 ± 445.86) pmol/L. There were significant differences between NA, MA and LA groups in all above items (P < 0.01 or P < 0.05). (3) Logistic regression analysis showed that DN were related with duration of diabetes, BMI, SBP, HbA1c, FBS, UA (OR values were 1.041, 1.055, 1.028, 1.116, 1.100, 1.004 respectively, P < 0.05 or P < 0.01). CONCLUSION: It would be helpful to prevent and retard progression of DN that comprehensively controlling high blood glucose, hypertension, hyperuricemia and body weight of type 2 diabetic patients.