Objective To investigate the association between podocytes and proteinuria in children with Alport syndrome. Methods Twenty-one children including 13 boys and 8 girls with Alport syndrome were divided into 3 groups according to 24-hour urinary protein, ＜30 mg/kgas the mild proteinuria group (10 patients), 30 to 50 mg/kg as the moderate proteinuria group (4 patients) and ＞50 wg/kg as the heavy proteinuria group (7 patients). The correlation between foot process width and the degree of proteinuria was analyzed. By immunoperoxidase staining on renal tissue, the key slit diaphragm molecules nephrin, podocin and podocyte cytoskeleton-associated molecule synaptopodin were studied. Results The foot process width (420-2270 nm) in patients with Alport syndrome was positively correlated with proteinuria significantly (r=0.765, P＜0.01).Foot process width was significantly lower in patients with mild proteinuria [475 (420-900) nm)compared with that in patients with heavy proteinuria [1520 (480-2270) nm] (P＜0.05). In Alport syndrome children with heavy proteinuria, the distribution of nephrin and podocin changed dramatically. In two children with shorter proteinuria period (1 year), dramatic distribution change of nephrin and podocin occurred, however, the foot process along with synaptopodin preserved.Conclusions Podocyte foot process effacement and injury of slit diaphragm participate in the mechanism of proteinuria in Alport syndrome. The injury of slit diaphragm seems to be an early event in the development of foot process effacement in Alport syndrome, which may guarantee early treatment.

To investigate the effects and the mechanism of visfatin on MIN6 cell signaling pathway and apoptosis induced by palmitate.Human recombinant visfatin promotes protein kinase B (Akt) and extracellularsignal regulating kinase (ERK)1/2 phosphorylation in dose-and time-dependent manner,and prevents MIN6 cell from apoptosis induced by palmitate (P<0.05 or P<0.01).The activation of Akt and ERK1/2 signaling pathway may be one of the molecular mechanisms of visfatin.

OBJECTIVE: To investigate the efficacy and safety of Mizolastine in the treatment of perennial allergic rhinitis. METHOD: Multicentric random Double-blind parallel-controlled study was adopted, and compared with placebo and Cetirizine. Patients (n = 177) were grouped, seventy-two in Mizolastine group, sixty-nine in Cetirizine and thirty-six in placebo group. RESULT: In the seventh curative day symptomatic and sign marks in Mizolastine group and Cetirizine group were lower, but the mark in Mizolastine group reduced more than in Cetirizine group and placebo group. Mizolastine group is better than Cetirizine group in improvement of nasal obstruction and itching with Visual analogue scale. In the twenty first curative day reduction of symptomatic and sign marks in Mizolastine group was lower than Cetirizine group, but no statistic difference. There were 27 adverse events, no serious adverse events in 177 patients during experimental period. Most adverse events were headache and dryness in mouth and eyes. There were 10 cases adverse events in Mizolastine group, one case was related with experiment and four cases might be related with experiment. There were 14 cases adverse events in Cetirizine group, one case was related with experiment and four cases might be related with experiment. There were three cases adverse events in placebo group. CONCLUSION Generally speaking the efficacy of Mizolastine in treatment of perennial allergic rhinitis is better than Cetirizine, Bad events are less. It is safe.
Adolescent ; Adult ; Aged ; Benzimidazoles ; adverse effects ; therapeutic use ; Cetirizine ; therapeutic use ; Child ; Double-Blind Method ; Female ; Histamine H1 Antagonists, Non-Sedating ; adverse effects ; therapeutic use ; Humans ; Male ; Middle Aged ; Rhinitis, Allergic, Perennial ; drug therapy ; Treatment Outcome ; Young Adult

Objective:To investigate the effect of dapagliflozin on cognitive function in middle-aged and elderly type 2 diabetes mellitus patients and related factors.Methods:This was a retrospective study. A total of 200 patients who were hospitalized in the Department of Endocrinology, the Second Affiliated Hospital of Anhui Medical University from August 2021 to August 2022 were recruited randomly. They were divided into the dapagliflozin group and control group. Clinical data were collected; plasma levels of β-amyloid protein(Aβ) 40 and Aβ42 were measured. The Montreal cognitive assessment(MoCA) and the mini-mental state examination(MMSE) were employed to assess cognitive function in both groups. Based on MoCA scores, patients in the dapagliflozin group were further categorized into mild cognitive impairment(MCI) and non-MCI subgroups. Differences among groups were analyzed and compared using t-test, χ2 test, and Mann-Whitney U test, and multivariable logistic regression was used to identify relevant factors associated with cognitive impairment in diabetes patients. Results:Compared to the control group, the dapagliflozin group exhibited significant increases in MMSE and MoCA scores, estimated glomerular filtration rate, and plasma concentration Aβ40(all P<0.05); And the incidence of MCI, homeostasis model assessment for insulin resistance(HOMA-IR), total cholesterol, triglycerides, urine albumin creatine ratio, plasma Aβ42, and Aβ42/Aβ40 ratio were significantly decreased(all P<0.05). Compared with the MCI subgroup, duration of dapagliflozin treatment in the non-MCI subgroup were significantly increased( P<0.05); There were statistically significant decreased in the non-MCI subgroup in age, systolic blood pressure, fasting plasma C-peptide, and HOMA-IR(all P<0.05). Multivariable logistic regression analysis showed that duration of dapagliflozin treatment was a protective factor for cognitive dysfunction( OR=0.322, 95% CI 0.150-0.692, P=0.004) and the age and HOMA-IR were risk factors( OR=1.109, 95% CI 1.014-1.212, P=0.023; OR=3.376, 95% CI 1.276-8.931, P=0.014). Conclusion:Dapagliflozin may improve cognitive function and significantly reduce the incidence of MCI in middle-aged and elderly patients with type 2 diabetes mellitus, possibly associated with the improvement of insulin resistance.

OBJECTIVETo analyze the clinical and genetic features of X-linked Alport syndrome (XLAS) in men positive for the collagen α5(Ⅳ) chain in epidermal basement membrane.

METHODThis was a retrospective study. Totally 725 families were diagnosed as Alport syndrome in Department of Pediatrics of Peking University First Hospital during January 1998 to December 2014, among them 450 patients were males with XLAS. Patients who met both of the following two criteria were included in this study. (1)Patients underwent α5(Ⅳ) chain staining in the epidermal basement membrane. (2)Mutations in COL4A5 gene were detected.Mann-Whitney test and χ(2) test were used.

RESULTTotally 140 males with XLAS were included in this study, 18 cases were α5 (Ⅳ)-positive and 122 cases were α5 (Ⅳ)-negative. The two groups of patients were compared, the median age at analysis was 11.0 vs. 7.2 years (Z = -1.839, P = 0.066), the 24-hour urine protein was 1.50 vs. 0.57 g/d (Z = -1.212, P = 0.226), the rate of hearing loss was 28% vs. 53% (χ(2) = 3.619, P = 0.067), the number of patients progressed to end stage renal disease (ESRD) was 4 vs. 12 (χ(2) =2.377, P = 0.128), the median age of ESRD was 31.0 vs. 16.6 years (Z = -2.554, P = 0.011), the rate of missense mutations in COL4A5 gene was 67% vs. 52% (χ(2) = 1.424, P = 0.313).

CONCLUSIONCompared the two groups of patients with positive and negative staining for the collagen Ⅳ α5 chain in epidermal basement membrane, there was no significant difference in the proteinuria level, the rate of hearing loss and genotype of COL4A5 gene. But the patients with positive staining progressed to ESRD significantly later than the patients with negative staining.

Basement Membrane ; pathology ; Child ; Collagen Type IV ; genetics ; DNA Mutational Analysis ; Deafness ; Humans ; Kidney Failure, Chronic ; Male ; Mutation, Missense ; Nephritis, Hereditary ; genetics ; pathology ; Proteinuria ; Retrospective Studies