Objective To investigate the clinicopathological relation between the TNF-? and IgA nephropathy. Methods TNF-? levels in serum, urine and renal tissues of 50 patients with IgA nephropathy were measured, and 10 patients with minimal change nephrotic syndrome(MCNS) and 10 healthy subjects served as negative control group. Results The serum and urine levels of TNF-? in the patients with IgA nephropathy were significantly higher than those in the patients with MCNS and healthy subjects, and had a significant positive correlation with the degree of proteinuria and renal demage. TNF-? expression was mainly localized in the cytoplasm of the proximal renal tubular epithelial cells, and the interstitium with more monocyte-macrophages infiltration. Conclusion TNF-? took part in the onset of hematuria and proteinuria, was correlated with the degree of renal damage, and played an important role in the aggravation of IgA nephropathy.

Objective To observe the expression of acid-sensing ion channel la (ASICla) and to investigate the effect of intracellular Ca2 + concentration on focal cerebral ischemia in diabetic rats.Methods 108 male Wistar rats were divided into three groups:group A [rats with middle cerebral artery occlusion (MCAO)],group B [rats with MCAO and diabetes (DM + MCAO)],group C [rats with MCAO and diabetes treated with fasudil intervention (DM+ MCAO+ fasudil)] (n=36 each).Samples were obtained at the time points of 1,3,6 and 24 h after ischemia respectively (n=9).Models of MCAO and DM+MCAO were prepared.Rats in DM+MCAO+Fasudil group were treated with fasudil 1 mg/Kg by caudal vein injection after half an hour when DM+MCAO model successfully prepared.ASICla expressions were detected at different time points of ischemia in the 3 groups respectively.Ca2+ concentration in ischemia cortex cells were determined at different time points of ischemia in group B and C.Results ASICla expressions were gradually increased along with the ischemia time in group A and B (group A:0.71±0.10,0.80±0.11,0.86±0.08,0.93±0.09;groupB:0.86±0.11,1.05±0.51,2.42±0.08,2.78±0.04; all P＜ 0.05),and ASICla expressions at different time points were higher in group B than in group A (all P＜ 0.05).Ca2-concentration were gradually increased along with the ischemia time in group B (106.32± 18.6,137.84±14.32,151.94± 18.38,183.61±7.96,all P＜0.05).Compared with group B,the levels of ASICla expression and calcium current were reduced in group C.Conclusions The activation of ASICla increases calcium ion flow internal pathway leading to intracellular calcium overload,which may be one of the reasons for the aggravation of focal cerebral ischemia in diabetes.

Objective To investigate the expressions of CXCR4,MMP-2 and VEGF in pancreatic carcinoma and the relationship with biological behavior of pancreatic carcinoma.Methods Immunohistochemical PV6000 technique was used to detect the expression of CXCR4,MMP-2 and VEGF in 47 cases of pancreatic carcinoma tissues,and the relationship between the expressions and pathologic parameters,and the relationship among the expressions of the 3 proteins were analysed.Results The expression rates of CXCR-4,MMP-2 and VEGF were 72.3%,66.O%and 61.7%in pancreatic carcinoma tissues,and all these proteins were correlated with metastasis,clinical staging and prognosis(X2=5.84～12.69;P＜0.05).The expression of CXCR-4,MMP-2 and VEGF was not correlated with sex,age,tumor size and differentiation(X2=0.03～4.27;P＞0.05).There was a positive relationship between the expression of CXCR-4 and MMP-2 or VEGF in pancreatic carcinoma(r=0.587,0.521;P＜0.01).Conclusions CXCR-4 could up-regulate the expression of MMP-2 and VEGF in pancreatic carcinoma,and they may contribute to metastasis and invasion of pancreatic carcinoma.

Objective To analyze the impac factors of serum N?terminal pro?brain natriuretic peptide (NT?proBNP) in patients with renal failure in non?dialysis phase, and to determine the cut?off point of as a diagnostic values in these patients with heart failure (HF). Methods Cross?sectional study was applied. Clinical data of 145 patients (37 cases of CKD4, 89 cases of CKD5, and 19 cases of acute renal injury (AKI) with renal failure in non?dialysis phase were collected. Comparison between groups and lineal regression analysis were utilized to investigate the impact factors of NT?proBNP, and the receiver operating characteristic curve (ROC curve) to select a better cut?off point of diagnosis in these patients with HF. Results (1) Compared with patients without HF, patients with HF had significantly higher edema, cardiac troponin I, serum phosphorus concentration, and left atrial diameter (LA), while ALB and left ventricular ejection fraction (LVEF) were decreased (P<0.05). (2) The NT?proBNP was divided into 4 groups with four points: First groups of 36 cases, NT?proBNP 1 ?862 ng/L, second groups 37 cases, 866?2670 ng/L, third groups 37 cases, 2790?20 000 ng/L, fourth groups 35 cases, 20 900?35 000 ng/L. With the increase of NT?proBNP levels, the occurrence of AKI and CKD4 decreased gradually while the occurrence of CKD and edema were significantly increased (P<0.01). Systolic blood pressure, troponin I, uric acid, serum phosphorus, parathyroid hormone, 24 hours urine protein, LA, interventricular septum thickness (IVS), left ventricular posterior wall thickness (LVPW) level gradually increased. Hb, ALB, calcium, CO2, eGFR, LVEF significantly decreased (P<0.01). The serum NT?proBNP of patients with HF was significantly higher than that of patients without HF (19 150 ng/L vs 1530 ng/L, P<0.01). The serum NT?proBNP of patients with edema was significantly higher than that in patients without edema (5460 ng/L vs 1630 ng/L, P<0.01). (3) Single factor linear regression analysis indicated that higher NT?proBNP was positive correlated with HF, edema, cardiac troponin I, uric acid, serum phosphorus, LA, IVS and LVPW (P<0.05), while negative correlated with Hb, eGFR, ALB, serum calcium, CO2, LVEF (P<0.05), and not correlated with eGFR, uric acid, serum calcium (P>0.05). (4) The best cut?off point of NT?proBNP predicting HF in patients with renal failure in non?dialysis phase was 3805 ng/L, AUC=0.848, 95%CI 0.786?0.910. Sensitivity was 82.4%, specificity 74.5%, positive predictive value 62.1%, negative predictive value 87.3%, positive likelihood ratio 3.2, negative likelihood ratio 0.24. Conclusions The level of NT?proBNP>20 000 ng/L is mainly found in end?stage renal disease patients with HF. HF is a main factor for the increase of NT?proBNP in patients with renal failure in non?dialysis phase. High phosphorus viremia, anemia, and hypoalbuminemia are closely related to NT?proBNP. Therefore NT?proBNP predicting HF should take into account the effects of these confounding factors in these patients.

Purpose To investigate the role of PTEN in podocyte injury in patients with diabetic nephropathy ( DN) . Methods Uri-nary samples from 30 patients with DN and 10 healthy volunteers were collected to detect the level of PCX by ELISA. Renal biopsies were reviewed to observe the morphological changes. All patients with DN were divided into three groups by glomerular lesion. The ex-pression of p-Akt and PTEN in glomeruli was detected by immunohistochemistry. Results The levels of PCX in the urine were signifi-cantly higher in patients with DN compared with those in healthy volunteers, and gradually increased along with glomerular lesion aggra-vating. The expression of p-Akt and PTEN increased in patients with DN compared with healthy volunteers. Although the expression of p-Akt and PTEN decreased with the aggravation of glomerular lesion, they were still higher than that in volunteers. There were obvious-ly positive correlation between the level of PCX and 24-h urinary protein and negative correlation between the level of PCX and the ex-pression level of p-Akt and PTEN. Conclusion PTEN down-regulation may be associated with podocyte injury in DN, which may be associated with the phosphorylation of Akt.

Objective To investigate the effects of TNF-?,IL-12,IL-15 and underglycosylation IgA_1 in mesangial deposition in the clinicopathological study of IgA nephropathy(IgAN).Methods Seventy-four patients with IgAN were enrolled in the study,with 10 patients randomly selected after remission,10 MCD and 10 healthy volunteers as control groups.The levels of TNF-? in serum and urine were examined by radioimmunoassay,and the levels of IL-12 and IL-15 were examined by ELISA.Immunohistochemistry was used to detect the expression of TNF-? in renal tissue,and the directed immunofluorescence was used to detect the underglycosylation of IgA_1(UGIgA_1)in mesangial deposition.Results The levels of TNF-?,IL-12 and IL-15 in serum of patients with IgAN were higher than those of MCD group,healthy control group and remission group.Compared with the negative group,33 patients with UGIgA_1 positive in renal tissues had lower levels of TNF-? in serum,longer course and less class of renal tissue injury.The positive areas of TNF-? in renal tissue and levels of TNF-? in serum were positively correlated with urinary protein(r=0.249,0.702,P=0.000).There was negative correlation between the levels of TNF-? in serum and Ccr(r=-0.231,P=0.048).The levels of IL-15 was positively correlated with the course of disease(r=0.266,P=0.022) and negatively with Scr(r=-0.320,P=0.005).Conclusions The TNF-?,IL-12 and IL-15 are all involved in the onset of proteinuria in IgAN patients,and IL-15 acts as a factor against renal injury.The patients with UGIgA_1 positive in mesangial have longer course and less pathological changes damaged than those of the UGIgA_1 negative patients.The TNF-? may serve as an important factor in the aggravation of IgAN.

The clinical features of 172 female and 1 067 male residents with gout in the coastal regions of Shandong province were analyzed.The results showed that as compared with male patients the onset of gout occurred at an older age in the female patients,and there were less obesity and tophi as well as less alcohol consumption and medication needed in the female patients.However,comorbidity with diabetes mellitus and coronary heart disease,as well as involvement of upper limb and other metatarsophalangeal joints were more prevalent in the female patients.

Purpose To investigate the role of SOCS3 on diabetic renal injury. Methods Male CD-1 mice were randomly divided into four groups:control group, diabetic group, empty plasmid vector transfection group and SOCS3 plasmid transfection group. The diabet-ic mice were induced by intraperitoneal injection of STZ at a dose of 150 mg/kg body weight. The mice of transfection group were re-ceived an injection of SOCS3 plasmid or empty vector at every 7 days thereafter. Specimens were collected at 12 week after STZ injec-tion. The morphological changes of tubular epithelial cells were observed by transmission electron microscope. RT-PCR and immuno-histochemistry were used to determine the mRNA and protein expression of CK18 and α-SMA. Western blotting analysis was used to determine the protein expression of SOCS3, p-STAT3, CK18 and α-SMA. Results SOCS3 overexpression in kidney down-regulated the levels of p-STAT3 andα-SMA but up-regulated the expression of CK18. Conclusion Overexpression of SOCS3 can ameliorate the tubular epithelial-mesenchymal transdifferentiation of diabetic mice via inhibiting the phosphorylation of STAT3.

Purpose To investigate the role of S3I-201 on tubular interstitial lesion in lupus nephritis.Methods MRt/MpJ mice were designated as the control group.MRL/lpr nice were randomly divided into LN group,S3I-201 group and DMSO group.The serum and 24 h-urine were collected to detect the serum creatinine,blood urea nitrogen and urine protein.Immunohistochemistry was used to detect the expression of FN.Western blotting analysis was used to determine the expression of E-cadherin,α-SMA,MCP-1,ICAM1,STAT3 and p-STAT3.Results Compared with the expression level in control group,the protein level of α-SMA,MCP-1,ICAM1 and FN were increased in renal tissue of MRL/lpr mice,while the expression of E-cadherin was markedly decreased.And the STAT3 was activated in renal tissue of MRL/lpr mice.The administration of S3I-201 could inhibite the activation of STAT3 and ameliorate the expression of E-cadherin,α-SMA,MCP-1,ICAM-1 and FN.Conclusion S3I-201 can relieve the tubular interstitial leison,which maybe concerned with the phosphorylation of STAT3.

Objective:To establish a 180-day mortality predictive score based on frailty syndrome in elderly sepsis patients [elderly sepsis score (ESS)].Methods:A prospective study for sepsis patients aged 60 years and above who were admitted to a medical intensive care unit of the General Hospital of Southern Theatre Command from January 1st, 2018 to December 31st, 2018 was conducted. Univariate analysis was performed on 19 independent variables including gender, age, body mass index (BMI), tumor, charlson comorbidity index (CCI), activity of daily living (ADL), instrumental activity of daily living (IADL), mini-mental state examination (MMSE), geriatric depression scale (GDS), clinical frail scale (CFS), sequential organ failure assessment (SOFA), Glasgow coma scale (GCS), acute physiology and chronic health evaluation (APACHEⅡ, APACHEⅣ), modified NUTRIC score (MNS), multiple drug resistance (MDR), mechanical ventilation (MV), continuous renal replacement therapy (CRRT) and palliative care. Continuous independent variables were converted into classified variables. Multivariate binary regression analysis of risk factors was conducted to screen independent risk factors which affecting 180-day mortality in elderly sepsis patients. Then a 180-day mortality predictive score was established, and the discrimination of the mortality of patients using CFS, SOFA, GCS, APACHEⅡ, APACHEⅣ, MNS scores were compared.Results:A total of 257 patients were enrolled, with a 180-day mortality of 60.7%. Univariate analysis showed that age, tumor, CCI, ADL, IADL, MMSE, CFS, SOFA, GCS, APACHEⅡ, APACHEⅣ, MNS, MDR, MV, CRRT, palliative care were risk factors of 180-day mortality in elderly sepsis patients [age: odds ratio ( OR) = 1.027, 95% confidence interval (95% CI) was 1.005-1.050, P = 0.018; tumor: OR =2.001, 95% CI was 1.022-3.920, P = 0.043; CCI: OR = 1.193, 95% CI was 1.064-1.339, P = 0.003; ADL: OR = 0.851, 95% CI was 0.772-0.940, P = 0.001; IADL: OR = 0.894, 95% CI was 0.826-0.967, P = 0.005; MMSE: OR = 0.962, 95% CI was 0.937-0.988, P = 0.004; CFS: OR = 1.303, 95% CI was 1.089-1.558, P = 0.004; SOFA: OR = 1.112, 95% CI was 1.038-1.191, P = 0.003; GCS: OR = 0.918, 95% CI was 0.863-0.977, P = 0.007; APACHEⅡ: OR = 1.098, 95% CI was 1.053-1.145, P < 0.001; APACHEⅣ: OR = 1.032, 95% CI was 1.020-1.044, P < 0.001; MNS: OR = 1.315, 95% CI was 1.159-1.493, P < 0.001; MDR: OR = 2.029, 95% CI was 1.197-3.437, P = 0.009; MV: OR = 6.408, 95% CI was 3.480-11.798, P < 0.001, CRRT: OR = 2.744, 95% CI was 1.529-4.923, P = 0.001, palliative care: OR = 5.760, 95% CI was 2.177-15.245, P < 0.001]. By binary regression analysis, CFS stratification ( OR = 1.934, 95% CI was 1.267-2.953, P = 0.002), MV ( OR = 4.531, 95% CI was 2.376-8.644, P < 0.001), CRRT ( OR = 2.471, 95% CI was 1.285-4.752, P = 0.007), palliative care ( OR = 6.169, 95% CI was 2.173-17.515, P = 0.001) were independent risk factors of 180-day mortality in elderly patients with sepsis. The model of "ESS = 0.660×CFS stratification+1.511×MV+0.905×CRRT+1.820×palliative care" was established. Receiver operating characteristic curve (ROC curve) analysis showed that the area under the ROC curve (AUC) for predicting 180-day mortality by ESS was 0.785 (95% CI was 0.730-0.834, P < 0.001). When the best cut-off value was 2.2 points, its sensitivity was 78.9%, specificity was 70.3%, the positive predictive value was 80.4%, and the negative predictive value was 68.3%. Simplified ESS was defined as "0.5×CFS stratification+1.5×MV+1×CRRT+2×palliative care". ROC curve analysis showed that AUC for predicting 180-day mortality by simplified ESS was 0.784 (95% CI was 0.729-0.833, P < 0.001). When the best cut-off value was 2.0 points, sensitivity was 76.9%, specificity was 70.3%, the positive predictive value was 80.0%, and the negative predictive value was 66.4%. Compared with CFS, SOFA, GCS, APACHEⅡ, APACHEⅣ and MNS, ESS had a significant difference in discriminating 180-day mortality in elderly patients with sepsis (AUC was 0.785 vs. 0.607, 0.607, 0.600, 0.664, 0.702, 0.657, 95% CI: 0.730-0.734 vs. 0.537-0.678, 0.537-0.677, 0.529-0.671, 0.598-0.730, 0.638-0.766, 0.590-0.725, all P < 0.05). Conclusions:CFS, MV, CRRT, and palliative care are independent risk factors of 180-day mortality in elderly patients with sepsis. We established ESS based on these risk factors. The ESS model has good discrimination and can be used as a reference and assessment tool for prediction and treatment guidance in elderly patients with sepsis.