AIM:To investigate the effects of high concentration of glucose on the expressions of serum and glucocorticoid induced protein kinase 1 (SGK1) and fibronectin in human podocytes and detect the production of fibronectin in human podocytes transfected with active and mutant forms of SGK1.METHODS: The expressions of SGK1 and fibronectin in human podocytes exposed in high glucose for 24 h were detected by using Western blotting. Human podocytes were transfected with three kinds of plasmid: pIRES2-EGFP-SGK1SD (SGK1-active plasmid), pIRES2-EGFP-SGK1KN (SGK1-mutant plasmid) and pIRES2-EGFP (empty vector plasmide). The synthesis levels of fibronectin were detected by immunofluorescence.RESULTS: The expression of SGK1 in normal human podocytes was observed and the expression level was up-regulated in podocytes exposed to high glucose for 24 h (50?4 vs 35?3), parallelly with the high expression of fibronectin (19?4 vs 12?2). The secretion of fibronectin was increased obviously in SGK1-active plasmid (SGK1SD) transfected podocytes compared with the vector transfected podocytes. Whereas, the fibronectin level was decreased significantly but not completely abolished in SGK1-mutant plasmid (SGK1KN) transfected podocytes, compared with SGK1SD transfected podocytes. CONCLUSION: SGK1 may be involved in the synthesis of fibronectin in human podocytes induced by high glucose and play a critical role in the activation of human podocytes during early stage of diabetic nephropathy.

Objective:To investigate the expression and clinical significance of PD-L1 in colorectal cancer (CRC). Methods:A total of 210 CRC patients who accepted radical surgery in our hospital from January 2015 to January 2016 were divided into three groups, namely, high-frequency microsatellite instability (MSI-H), low-frequency microsatellite instability (MSI-L), and microsatellite stable (MSS). The expression of PD-L1 was detected by immunohistochemistry, and the expression characteristics of PD-L1 in different types of CRC were analyzed. Results:CRC cases with low differentiation had a higher expression of PD-L1 than CRC patients with high differ-entiation (P<0.05). PD-L1 had a positive rate of 75.8%in the MSI-H group and a rate of 9.3%in the MSI-L and MSS groups, wherein the difference between the two groups was statistically significant (P<0.05). Conclusion:PD-L1 was positively expressed in some CRC tu-mor tissues, and its positive rate was significantly higher in MSI-H than in MSI-L and MSS. The therapeutic effect of a PD-L1 blocker for patients with MSI-H CRC might be preferable.

Objective To evaluate the effectiveness of mouth gag which can inserted into lavage tube during gastric lavage. Methods The Sixty- six cases of acute poisoning patients with gastric lavage according to random number table method were randomly divided into two groups, 33 cases in each group. Observation group used the inserted mouth gag, and the control group used the metal ones. Results The observation group were lower than the control group at the time required to insert the lavage tube [(2.23±0.19)s to (3.26±0.30)s] and the incidence of complication rate [18.2%(6/33) to 45.5%(15/33)], the oral cavity bleeding [6.0%(2/33) to 30.3%(10/33)], lavage tube displacement [0(0/33)to 24.2%(8/33)], lavage tube twisting[0(0/33) to 24.2%(8/33)], the difference was statistically significant (P<0.01), while higher in the rate of successful intubation[100.0%(33/33)] to [54.5%(18/33)], the difference was statistically significant, χ2=19.4,P<0.01. Conclusions The application of the mouth gag which can insert into gastric lavage improved the successful intubation rate, saved the rescue time, reduced the complication and improved the nursing quality.

AIM: To investigate the effect of high glucose concentration on serum and glucocorticoid induced protein kinase (SGK) mRNA and protein expressions in human proximal tubular epithelial cells (HKC) and the possible role of SGK in the production of extracellular matrix (ECM) of HKC under the condition of high glucose. METHODS: HKC was divided into 3 groups: control glucose group (CG group, 5 5 mmol/L D-glucose); high glucose group (HG group, 25 mmol/L D-glucose) and osmotic control group (MG group, 19 5 mmol/L mannitol and 5 5 mmol/L D-glucose). The expressions of SGK mRNA and protein were assessed by semi-quantitative RT-PCR and Western blotting respectively. The level of secretary and cytoplasmic fibronectin (FN) were detected by enzyme-linked immunoabsordent assay (ELISA) and indirect-immunofluorescence. RESULTS: HKC expressed SGK1, SGK2 and SGK3 at mRNA and protein levels. Their mRNA level were up-regulated since 2 hours after cells exposed to D-glucose and this up-regulation persisted to the end of 8th hour, and SGK1 protein level elevated simultaneously. On the other hand, the increased FN secretion by high glucose was in a time-dependent manner and its improved secretion threshold was just followed by the high expression of SGK1. CONCLUSIONS: In response to high glucose, the expression of SGK1, SGK2 and SGK3 in human proximal tubular epithelial cells were up-regulated which was accompanied with FN accumulation. The high expression of SGK may mediate overproduction of ECM in proximal tubular epithelial cells and contribute to the diabetic nephropathy.

The role of serum and glucocorticoid-induced kinase 1 (SGK1) pathway in the connective tissue growth factor (CTGF) expression was investigated in cultured human mesangial cells (HMCs) under high glucose. By using RT-PCR and Western blot, the effect of SGK1 on the CTGF expression in HMCs under high glucose was examined. Overexpression of active SGK1 in HMCs transfected with pIRES2-EGFP-S422D hSGK1 (SD) could increase the expression of phosphorylated SGK1 and CTGF as compared with HMCs groups transfected with pIRES2-EGFP (FP) under high glucose or normal glucose. Overexpression of inactive SGK1 in HMCs transfected with pIRES2-EGFP-K127N hSGK1 (KN) could decrease phosphorylated SGK1 and CTGF expression as compared with HMCs groups transfected with FP under high glucose. In conclusion, these results suggest that high glucose-induced CTGF expression is mediated through the active SGK1 in HMCs.
Cells, Cultured ; Connective Tissue Growth Factor/genetics ; Connective Tissue Growth Factor/*metabolism ; Glucose/*pharmacology ; Immediate-Early Proteins/metabolism ; Immediate-Early Proteins/*physiology ; Mesangial Cells/cytology ; Mesangial Cells/*metabolism ; Protein-Serine-Threonine Kinases/metabolism ; Protein-Serine-Threonine Kinases/*physiology ; Signal Transduction/drug effects

To investigate the expression and the role of three isoforms of Serum and Glucocorticoid-inducible Kinase (SGK) in experimental diabetic nephropathy (DN), 12 male C57BL/6 mice of 8-weeks-old were divided into two groups. Streptozotocin (STZ)-induced diabetic nephropathy and normal controls were analyzed at the end of the 4th week after the induction of diabetes. Renal hemodynamics and histological studies were performed. The expression of SGK1 mRNA, SGK2 mRNA and SGK3 mRNA of kidney cortex were measured by RT-PCR, and the cortical SGK1 protein was detected with Western blotting. Our results showed that the blood glucose, blood HbA1c, 24h urinary protein, creatinine clearance and the renal index were all increased in DN group. More extracellular matrix (ECM) accumulation was observed. The level of cortical SGK1 mRNA and protein were up-regulated in DN group in comparison with control group. SGK2 and SGK3 mRNA were elevated in DN mice. In DN, mRNA level of three SGK isoforms and SGK1 protein were increased significantly. It is concluded that SGKs may contribute to the early renal injury of DN.

In recent years, tumor immunotherapy with immune checkpoint as the target has attracted much attention because of its remarkable efficacy. However, with the application of immune-checkpoint inhibitors (ICIs), more and more immune-related adverse events (irAEs) have been reported. IrAEs impose an additional risk of death on tumor patients treated with ICIs, limiting the widespread use of ICIs. To help patients actively prevent irAEs, biomarkers with the predictive value of irAEs are of great significance. This paper reviews the biomarkers with predictive value for irAEs from the aspects of serology, genetics and microbiology.

Objective:To study the clinical pathological features of patients with relapsed diffuse large B-celllymphoma (DLBCL) and to provide evidence for early clinical screening of recurrent cases.Methods:The clinical and pathological data of the 20 patients, who had relapsed DLBCL (relapsed group) and were admitted to the First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2019, were included. Meanwhile, other 34 patients with DLBCL who had achieved complete response (CR) for 36 months or more (CR group) were used as controls.Statistical methods were used to retrospectively analyze the differences in general conditions, clinical characteristics, lab resultsand pathological features between the two groups.Results:Clinically, there were 6 males and 14 females with a median age of 55.5 (33-85) years in the relapsed group and 14 males and 20 females with a median age of 53 (15-89) years in the CR group. The relapsed and CR groups had significant difference in Ann Arbor stage ( P=0.001), International Prognostic Index score ( P=0.006), primary lesions ( P=0.003), extranodal involvement ( P=0.002), and hepatitis B viral infection ( P=0.046), β2-MG level ( P=0.029), LDH level ( P=0.005) and CRP level ( P=0.006), while the age ( P=0.732), gender ( P=0.416), ECOG score ( P=0.248), B symptoms ( P=0.511), the presence of hypoalbuminemia ( P=0.279), anemia ( P=0.983) and A/G( P=0.416) showed no statistical difference.Pathologically, compared with the CR group, the relapsed group was mostly non-GCB type (85% vs. 59%, P=0.048), with a higher CD5 positive rate (25% vs.3%, P=0.014) and a lower bcl-6　positive rate (60% vs. 88%, P=0.017), while the expression of Ki-67, CD10, bcl-2, MUM1, CD20 and PAX5 was not different between the two groups. Conclusion:Most of the patients with relapsed DLBCL are non-GCB type. The patients with CD5 positivity, stage III-IV, International Prognostic Index score 3-5, nodal origin, often involving>1 extranodal organ, abnormally elevated LDH, CRP and β2-MG level, and HBV infection are more likely to relapse.

Objective:To assess the impact of timing of percutaneous catheter drainage (PCD) application (ANC and WON) on outcomes and complications in severe acute pancreatitis (SAP) treatment.Methods:The clinical data of 75 SAP patients treated with PCD from Jan. 1, 2018 to Dec.31, 2018 in Pancreatitis Treatment Center of Deyang People’s Hospital were retrospectively analyzed. The clinical manifestations, application period and curative effect of PCD were analyzed.Results:Among the 75 patients, 51 (68%) were ANC patients, (32%) were WON patients, 0 (0%) died, 70 (93.3%) were cured, and 5 (6.7%) underwent further surgical treatment. There was no significant difference between the average time of PCD application, or complications (such as pancreatic fistulae, catheter obstruction or falling and haemorrhage) ( P>0.05) . Conclusion:Percutaneous catheter drainage in different stages of acute necrotizing pancreatitis does not affect its safety and efficacy, and delayed use don’t have better curative effect.

To investigate the expression and the role of three isoforms of Serum and Glucocorticoidinducible Kinase (SGK) in experimental diabetic nephropathy (DN), 12 male C57BL/6 mice of 8-weeks-old were divided into two groups. Streptozotocin (STZ)-induced diabetic nephropathy and normal controls were analyzed at the end of the 4th week after the induction of diabetes. Renal hemodynamics and histological studies were performed. The expression of SGK1 mRNA, SGK2 mRNA and SGK3 mRNA of kidney cortex were measured by RT-PCR, and the cortical SGK1 protein was detected with Western blotting. Our results showed that the blood glucose, blood HbA1c, 24-h urinary protein, creatinine clearance and the renal index were all increased in DN group. More extracellular matrix (ECM) accumulation was observed. The level of cortical SGK1 mRNA and protein were up-regulated in DN group in comparison with control group. SGK2 and SGK3 mRNA were elevated in DN mice. In DN, mRNA level of three SGK isoforms and SGK1 protein were increased significantly. It is concluded that SGKs may contribute to the early renal injury of DN.