LncRNA H19 deficiency protects against the structural damage of glomerular endothelium in diabetic nephropathy via Akt/eNOS pathway.

Objective: This study aimed to investigate the functions of lncRNA H19 on glomerular endothelial structural damage of diabetic nephropathy (DN).Materials and Methods: Rats were fed a high sugar and fat high feed die, and intraperitoneally administrated with streptozotocin (30 mg/kg) to induce DN model. Meanwile, rat glomerular endothelial cells (rGEnCs) were treated with high a level of glucose （HG, 30 mM glucose）to induce structural damage.Results: Our results showed that H19 level was drastically increased in diabetic glomeruli and high-glucose (HG)-stimulated rat glomerular endothelial cells (rGEnCs). Deficiency of H19 ameliorated microalbumin, creatinine, BUN, and histopathological alterations in diabetic rats. In addition, H19 deficiency significantly attenuated the damage of endothelial structure by upregulating the expression of junction proteins ZO-1 and Occludin, glycolcalyx protein Syndecan-1, and endothelial activation marker sVCAM-1 and sICAM-1 in diabetic rats. The in vitro results also showed that H19-siRNA alleviated glycocalyx shedding, tight junctions damage, and endothelial activation in HG-stimulated rGEnCs. Moreover, H19 deficiency significantly enhanced the expression of p-Akt and p-eNOS and NO concentration in vitro and in vivo. Pre-treatment with Akt inhibitor LY294002 abrogated these favourable effects mediated by H19 deficiency.Discussion and Conclusion: These results indicate that H19 deficiency could mitigate the structural damage of glomerular endothelium in DN via activating Akt/eNOS pathway.

Current situation and cost-effectiveness of 18F-FDG PET/CT for the diagnosis of fever of unknown origin and inflammation of unknown origin: A single-center, large-sample study from China.

PURPOSE: 18F-FDG PET/CT has an important role in the evaluation of fever of unknown origin (FUO) and inflammation of unknown origin (IUO). Our study was to investigate the current status of the inclusion of 18F-FDG PET/CT within FUO/ IUO diagnostic work-up and evaluate the cost-effectiveness of it in China. METHODS: A total of 741 FUO/IUO patients admitted to our hospital from January 2012 to December 2019 were retrospectively reviewed. The clinical characteristic, medical expenses to reach diagnosis and the proportion of definite etiological diagnosis achieved upon hospital discharge were compared between patients examined by 18F-FDG PET/CT (18F-FDG PET/CT group) and patients not examined by 18F-FDG PET/CT (non-18F-FDG PET/CT group). RESULTS: The mean age, proportion of critically-ill patients, proportion of rheumatologic diseases, the number of examinations and hospitalisation days to reach diagnosis in the 18F-FDG PET/CT group were significantly higher than those in the non-18F-FDG PET/CT group. The mean medical costs of 18F-FDG PET/CT group were significantly higher than those of non-18F-FDG PET/CT group, whereas the proportion of definite etiological diagnosis achieved upon hospital discharge of 18F-FDG PET/CT group was significantly higher than that of non-18F-FDG PET/CT group. The mean hospitalisation days and mean medical costs before diagnosis were significantly lower in patients who undertook 18F-FDG PET/CT ≤ 7 days after hospital admission than those in patients who undertook 18F-FDG PET/CT > 7 days after hospital admission. CONCLUSIONS: 18F-FDG PET/CT is mostly used in critically-ill and hard-to-diagnose FUO/IUO patients currently in China, which may conceal its cost-effective advantage. While the early use of 18F-FDG PET/CT according to patient characteristics and etiological clues could help to reduce hospitalization stay, limit medical costs, thus producing its diagnostic effect to the great extent.

Skimmin protects diabetic cardiomyopathy in streptozotocin-induced diabetic rats.

Skimmin, a natural coumarin derivate, has been showed to be protective against experimental diabetic nephropathy; however, its protective effect on diabetic cardiomyopathy (DCM) is not clarified. By using in vitro and in vivo models, we investigated skimmin's protective effect on impaired heart tissues in DCM. DCM was induced by streptozotocin (STZ, 60 mg/kg) using Sprague Dawley rats, and diabetic rats were treated with either skimmin (15 or 30 mg/kg) or the vehicle for 16 weeks, and normal rats were used as a control. Hematoxylin and eosin and Masson's trichrome staining were performed to evaluate the cardiac histopathology, and the oxidative stress and proinflammation cytokines in heart tissues were measured. The protein levels of key mediators in fibrosis, pyroptosis, and autophagy in heart tissues were investigated using western blotting. In vitro, primary neonatal cardiomyocytes were treated with skimmin (2 and 10 µM) under stimulation by high glucose (30 mM) and low glucose (5 mM) respectively, and the molecular mechanisms on pyroptosis and autophagy were studied. Compared to the vehicle-treated DCM group, skimmin treatment significantly improved the ejection fraction and fractional shortening of the left ventricle and reduced the oxidative stress by increasing the glutathione level and activity of superoxide dismutase and catalase. Skimmin also reduced cardiac fibrosis, and decreased proinflammation cytokines in cardiac tissues. Mechanism studies showed skimmin may enhance the autophagy and ameliorate NLRP3 inflammasome activation to play a protective role in DCM. This study, for the first time, indicates that skimmin might be a promising lead compound for DCM.

[Pelvic retroperitoneal tumors: clinical analysis of 16 cases].

OBJECTIVE: To explore the diagnostic rationales for pelvic retroperitoneal tumors and summarize their therapeutic regimens. METHODS: A total of 16 retroperitoneal tumor patients were recruited. And their general information, previous medical history, physical examinations, auxiliary tests, surgical findings and postoperative pathological results were analyzed. RESULTS: Two cases were diagnosed through preoperative magnetic resonance imaging (MRI) while others found intraoperatively. Complete tumor resection was performed in all except for one case. Postoperative pathological examinations revealed 10 benign cases. And there was one case of pelvic endometriosis (mild cytologic atypia). Five cases were malignant. The operation duration was 1.45-8.5 hours and peri-operative bleeding volume 50-5000 ml. Among them, 12 patients had heavy adhesion in pelvic cavity, 7 cases underwent operations collaboratively with related departments because of surgical difficulties and vascular injury and bladder rupture occurred in 1 case. During the follow-ups, one case was lost, two patients died from disease recurrence and another one had a postoperative relapse at Month 4. The other 12 cases recovered well and had no recurrence. CONCLUSION: Surgery remains a key for retroperitoneal tumors. With a low diagnostic rate, they are often found surprisingly intraoperatively. Because of surgical difficulties and frequent complications, multi-departmental collaboration is necessary. Preoperative correct diagnosis and adequate preoperative preparation are essential. And MRI is an effective auxiliary examination.