Prognostic value of serum cystatin C levels on kidney outcome in type 2 diabetes mellitus patients complicated with chronic kidney disease / 中华检验医学杂志

Objective:We aimed to explore the prognostic value of serum cystatin C (CysC) levels on kidney disease outcome in type 2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD).Methods:The clinical data and pathological examination results of 113 T2DM patients with CKD, who were hospitalized in the First Affiliated Hospital of Nanjing Medical University from January 2011 to July 2020, were retrospectively analyzed in this study. Clinicopathological features and renal outcomes were compared between patients with CysC>1.54 mg/L ( n=57) and CysC≤1.54 mg/L ( n=56) at the time of renal biopsy. Cox regression analysis was used to analyze the risk factors of poor renal prognosis. The relationship between serum CysC level and renal prognosis was analyzed by smoothing curve fitting and threshold effect. Kaplan-Meier survival curve was used to compare and analyze the difference of renal survival rate. Further, the receiver operator characteristic curve was used to evaluate the predictive value of serum CysC combined with renal tubular marker blood and urinary neutrophil gelatinase-associated lipocalin (NGAL) on renal prognosis in all enrolled patients and those with different kidney disease stages. Besides, the ability of serum CysC level to predict renal prognosis within 3 years was evaluated by time-dependent area under the curve (AUC). Results:Compared with patients with serum CysC levels≤1.54 mg/L, patients with CysC>1.54 mg/L had more deteriorated renal function, decreased levels of hemoglobin and serum 25(OH) vitamin D, but more severe interstitial inflammation, higher glomerular sclerosis ratio and severe vascular lesion (all P<0.05). During 36.77 (29.34, 44.20) months follow-up, the composite renal outcomes were noted in 37.2% patients. Kaplan-Meier survival curve showed that the cumulative survival rates of patients without renal end points was significantly lower in CysC level>1.54 mg/L group than in CysC≤1.54 mg/L group (χ 2=5.752, P=0.016). Adjusted multivariate Cox analysis showed that serum CysC level ( HR=7.850, 95% CI 1.248-49.382, P<0.05) was an independent risk factor for renal prognosis. Smoothing curve fitting analysis showed that there was a linear relationship between serum CysC level and relative risk of renal endpoint event (β=2.25, 95% CI 1.06-4.81, P=0.036). The time-dependent receiver operator characteristic curve showed that the AUC of serum CysC in predicting the poor renal prognosis of T2DM patients within 3 years after renal biopsy were 0.714, 0.625 and 0.631, respectively. The AUC of serum CysC combined with blood and urinary NGAL was 0.694 (sensitivity 55.56%, specificity 77.78%). In the population with eGFR less than 60 ml·min -1·1.73m -2 ( n=51), the AUC was 0.817 (sensitivity 66.67%, specificity 85.00%). Conclusions:Higher serum CysC level is associated with deteriorated renal function, more severe renal pathological lesions and increased risk of worse renal prognosis in T2DM patients. Serum CysC level presents better predictive value for the renal prognosis of T2DM patients within 1 year after renal biopsy. Combined with renal tubular marker blood and urinary NGAL, serum CysC level might serve as a potential tool for identifying cases with high-risk of unsatisfactory renal prognosis, especially in those with eGFR less than 60 ml·min -1·1.73m -2.

Research Progress on Animal Model for Cancer-related Fatigue / 肿瘤防治研究

Cancer-related fatigue (CRF) is a common symptom which associated with cancer itself or cancer treatments. CRF will not only interrupt the patient's treatment, but also affect the patient's quality of life seriously. To date, the pathogenesis of CRF is still unclear, and recognized effective treatment is lacking. It is the precondition of establishing standardized animal models for CRF to find effective treatments. This paper summarizes the animal model of CRF in order to find suitable methods, and distinguish the effects of different interventions.

Effect of preoperative serum D-dimer level on cardiac surgery-associated acute kidney injury / 中华肾脏病杂志

Objective:To evaluate the effect of preoperative plasma D-dimer level on the risk of cardiac surgery-associated acute kidney injury (CSA-AKI). Methods:The clinical data of patients who underwent cardiac surgery with cardiopulmonary bypass in the First Affiliated Hospital of Nanjing Medical University from January 2017 to December 2018 were collected retrospectively. All patients were distributed into two groups (normal D-dimer group with D-dimer level≤0.55 mg/L and elevated D-dimer group with D-dimer level>0.55 mg/L) according to the D-dimer threshold of 0.55 mg/L and the differences of clinical data between the two groups were compared. Kaplan-Meier survival analysis method was used to analyze the difference of the cumulative incidence of CSA-AKI between the two groups. Logistic regression analysis and restricted cubic splines analysis were used to analyze the association between serum D-dimer and the incidence of CSA-AKI. Results:There were 871 patients enrolled in the study with 427 females (49.0%) and age of (56.6±12.3) years, including 215 patients (24.7%) with high D-dimer and 259 patients (29.7%) with CSA-AKI. Compared with the normal D-dimer group, patients with elevated D-dimer had higher baseline serum creatinine, proportion of chronic kidney disease stage 3, international normalized ratio, fibrinogen, proportion of receiving renal replacement therapy and incidence of CSA-AKI (all P<0.05). The prothrombin time, operation time, extracorporeal circulation time, aortic occlusion time and hospital stay in the elevated D-dimer group were longer (all P<0.05), and the preoperative estimated glomerular filtration rate (eGFR) and hemoglobin levels were lower than those in the normal D-dimer group (both P<0.05). There was no statistical difference between the two groups in terms of age, gender, comorbid diseases, cardiac function classification, and hospital mortality (all P>0.05). Kaplan-Meier survival curve results showed that compared with the normal D-dimer group, the risk of CSA-AKI in the elevated D-dimer group was significantly increased (Log-rank χ2=14.227, P<0.001). The multivariate logistic regression showed that after adjusting variables including gender, age, diabetes mellitus, preoperative eGFR, cardiopulmonary bypass time and so on, the higher level of preoperative D-dimer (>0.55 mg/L) was still related to CSA-AKI ( OR=1.476, 95% CI 1.038-2.098, P=0.030). Restricted cubic splines analysis showed that the incidence of CSA-AKI raised when preoperative serum D-dimer concentration increased (non-linear P=0.262). Conclusion:Patients with high preoperative serum D-dimer have an increased risk of CSA-AKI.

Analysis of clinicopathological characteristics and renal prognosis of patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated glomerulonephritis / 中华肾脏病杂志

Objective:To determine the prognostic values of clinical and laboratory features at the time of presentation on renal survival of patients with myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody(ANCA)-associated glomerulonephritis (MPO-ANCA-GN).Methods:A total of 172 patients with MPO-ANCA-GN and hospitalized at the First Affiliated Hospital of Nanjing Medical University from January 2005 to December 2018 were enrolled. The baseline clinical characteristics and renal biopsy pathological data were analyzed, and the renal prognosis was followed up. The clinical and pathological characteristics of different renal prognosis in all patients and 112 patients who underwent renal biopsy were analyzed, and the related factors affecting renal survival were further discussed.Results:Among these 172 patients, 81 were males and 91 were females. The median serum creatinine at diagnosis was 343.7(174.2, 606.6) μmol/L and the median estimated glomerular filtration rate (eGFR) was 15.81(7.61, 38.04) ml·min -1·(1.73 m 2) -1. In total, 76 patients (44.2%) received initial renal replacement therapy (RRT). During a median follow-up duration of 20(3, 60) months, 73 patients (42.4%) progressed to end-stage renal disease (ESRD) and required dialysis, including 6 (8.2%) patients who entered RRT during follow-up and 67 (91.8%) patients who received RRT at the beginning. Among the 112 patients who underwent renal biopsy, the proportion of patients who progressed to ESRD in the sclerotic group was the highest (15/25, 60.0%). The baseline serum creatinine level ( P<0.001), urine red blood cell count ( P=0.012) and the proportion of glomerular sclerosis ( P=0.002) in the non-dialysis dependent group were significantly lower than those in the dialysis dependent group, while the levels of eGFR ( P<0.001), serum albumin ( P=0.002) and hemoglobin ( P<0.001) were higher than those of the dialysis-dependent group. Kaplan-Meier survival analysis showed that the renal survival rate of the focal group was the highest ( χ2=19.488, P<0.001, log-rank test), while the renal survival rate of the sclerotic group was significantly lower than that of the crescentic group ( χ2=5.655, P=0.017); higher levels of serum creatinine (>320 μmol/L, χ2=77.229, P<0.001) and urine red blood cell count (>300 cells/μl, χ2=8.511, P=0.004), lower levels of rheumatoid factor (<20 IU/ml, χ2=8.610, P=0.003), serum albumin (<30 g/L, χ2=11.060, P=0.001) and hemoglobin (<90 g/L, χ2=21.921, P<0.001) were associated with lower renal survival rate; in terms of treatment, the renal survival rate of the glucocorticoids plus mycophenolate mofetil group was significantly higher than that of the glucocorticoids plus cyclophosphamide ( χ2=5.056, P=0.025) or the glucocorticoids alone group ( χ2=16.459, P<0.001). Multivariate Cox regression showed that baseline serum creatinine >320 μmol/L ( HR=8.803, 95% CI 3.087-25.106, P<0.001) and serum albumin <30 g/L ( HR=2.566, 95% CI 1.246-5.281, P=0.011) were the related factors affecting renal survival. Conclusion:Serum creatinine and albumin levels of MPO-ANCA-GN patients at diagnosis may be the related factors that affect the patient's renal prognosis.

Value of combined measurement of urine insulin-like growth factor binding protein 7 and tissue inhibitor of metalloproteinase 2 in the early diagnosis and prognosis of cardiac surgery-associated acute kidney injury / 中华肾脏病杂志

Objective:To evaluate the value of combined measurement of urinary insulin-like growth factor-binding protein 7 (IGFBP7) and urinary metalloproteinase inhibitor-2 (TIMP-2) in the early diagnosis and prognosis of cardiac surgery-associated acute kidney injury (CSA-AKI).Methods:From March 2018 to June 2018, cardiac surgery patients admitted to the cardiac macrovascular surgery department of the First Affiliated Hospital of Nanjing Medical University were prospectively included, and the blood creatinine was monitored to observe the presence of acute kidney injury (AKI). The prognostic information of the patients was collected, including in-hospital dialysis, in-hospital death, complete recovery of kidney function at discharge, death in one year after surgery, and progression to chronic kidney disease. The levels of urine IGFBP7 and TIMP-2 at 6 h, 24 h and 48 h after cardiac surgery were detected by enzyme linked immunosorbent assay (ELISA), and the urine creatinine (Cr) was also measured. Moreover, receiver operating characteristic curves (ROC) were plotted and the areas under the curves ( AUC) were calculated to evaluate the predictive value and prognostic value of urinary [TIMP-2]·[IGFBP7] (T*I for short) and urine T*I/urine Cr 2 in CSA-AKI. Results:A total of 74 patients with age of (58.43±10.91) years old and 47 males, were enrolled in this study, of which 24 cases (32.4%) had AKI and 10 cases (13.5%) had stage 2-3 AKI. Compared with the non-AKI group, the AKI group had significantly higher levels of urine T*I levels at 6 h and 24 h (both P<0.05). The AUC of T*I at 24 h predicting for AKI was 0.71(95% CI 0.59-0.81, P=0.001, cutoff value 0.020, sensitivity 79.2%, specificity 56.0%), while the AUC for stage 2-3 AKI was 0.85 (95% CI 0.75-0.92, P<0.001, cutoff value 0.083, sensitivity 70.0%, specificity 90.6%). Urinary T*I normalized for urinary creatinine excretion did not show better predictive value. In addition, of T*I at 24 h predicting for poor hospitalization outcome, renal recovery, and one year postoperative death, the AUC was 0.82(95% CI 0.71-0.90, P=0.001), 0.80(95% CI 0.66-0.86, P<0.001), and 0.81(95% CI 0.70-0.89, P=0.047), respectively. Conclusion:The combined detection of TIMP-2 and IGFBP7 in urine is expected to be a biomarker for early diagnosis of CSA-AKI and has certain clinical value in predicting the prognosis of CSA-AKI.

Influencing factors of hungry bone syndrome in maintenance hemodialysis patients after parathyroidectomy / 中华肾脏病杂志

Objective To investigate the influencing factors of hungry bone syndrome (HBS) in maintenance hemodialysis patients with secondary hyperparathyroidism (SHPT) after parathyroidectomy (PTX). Methods A retrospective study was conducted on maintenance hemodialysis patients with SHPT undergoing successful parathyroidectomy with autotransplantation. Clinical data and perioperative indicators of the selected patients were collected. The enrolled patients were divided into HBS group and non-HBS group based on whether the lowest level of blood calcium less than 2.0 mmol/L after surgery. The difference of general clinical data and perioperative indicators between the two groups were compared. The risk factors of HBS were analyzed by logistic regression analysis. Multiple linear regression method was used to analyze the independent factors affecting the maintenance time of intravenous calcium supplementation, the total amount of calcium supplementation during intravenous calcium supplementation and the highest serum level of potassium within 24 h after surgery. Results A total of 306 patients were included in the study. All patients had low levels of serum calcium after operation. There were 230 patients (75.16% ) with the lowest blood calcium＜2.00 mmol/L after PTX (HBS group), and 76(24.84%) cases in the non-HBS group. Predialysis coefficient of serum calcium=(preoperative blood calcium-2.20) mmol/L÷0.01 mmol/L. Logistic regression analysis showed that higher predialysis coefficient of serum calcium (B=-0.063, OR=0.939, 95% CI 0.894-0.987, P=0.013) and lower level of preoperative serum alkaline phosphatase (ALP) (B=0.035, OR=1.033, 95%CI 1.019-1.050, P＜0.001) were independent risk factors for HBS. Multiple linear regression analysis revealed that preoperative blood intact parathyroid hormone (iPTH) (B=0.017, P＜0.001 and B=0.041, P＜0.001), preoperative serum ALP (B=0.052, P＜0.001 and B=0.107, P＜0.001) and preoperative hemoglobin (Hb) (B=-0.453, P=0.041 and B=-1.058, P=0.007) were independent factors affecting the maintenance time of intravenous calcium supplementation and the total amount of calcium supplementation in HBS patients. Preoperative predialysis level of serum potassium (B=0.859, P＜0.001) was the independent influencing factor of the maximum level of serum potassium within 24 hours after surgery. Conclusions Patients with lower levels of preoperative serum calcium and higher levels of serum ALP are prone to HBS after PTX. Postoperative calcium supplementation may need to be strengthened in HBS patients with higher preoperative iPTH and ALP levels and lower preoperative Hb levels. High preoperative basal potassium levels may increase the risk of hyperkalemia after PTX.

Assessment of fluid and nutritional status using bioelectrical impedance methods in acute kidney injury patients requiring continuous renal replacement therapy / 中华肾脏病杂志

Objective To investigate the predictive value of nutritional and fluid status measured by bioelectrical impedance methods for the prognosis of acute kidney injury (AKI) patients undergoing continuous renal replacement therapy (CRRT). Methods Patients with severe AKI received CRRT in the First Affiliated Hospital of Nanjing Medical University from September 2016 to September 2018 were enrolled, and divided into death group and survival group according to 28-day survival. Cox regression was used to analyze the association between 28-day survival and lean tissue index (LTI), fat tissue index (FTI), the ratio of extracellular water (ECW) and body cell mass (BCM) (ECW/BCM), and overhydration (OH), respectively. Results A total of 156 patients were included, including 101 males and 55 females. The age was (62.7 ± 15.4) years, with sequential organ failure assessment (SOFA) score of 9.9±3.9. The 28-day mortality rate was 46.2％. The pre-CRRT OH values in the 28-day survival group and death group were 2.95(1.80, 5.50) L and 4.20(2.95, 5.70) L(P=0.016), and ECW/BCM values were 1.00(0.76, 1.18) and 1.07(0.88, 1.25) (P=0.033), respectively. Univariate Cox regression analysis showed that pre-CRRT high OH values (HR=1.08, 95％CI 1.00-1.17, P=0.040) and high ECW/BCM values (HR=3.02, 95％CI 1.46-6.22, P=0.003) were associated with 28-day death. The changes of OH values (HR=0.83, 95％CI 0.72-0.95, P=0.008) and ECW/BCM values (HR=6.79, 95％CI 1.72-26.82, P=0.006) between pre - CRRT and the 7th day after CRRT initiation were significantly associated with 28-day mortality in patients who survived 7 days after CRRT initiation. After adjusting for age, gender, and SOFA scores, multivariate Cox regression analysis showed that the high OH value (HR=1.16, 95％CI 1.06-1.27, P=0.002) and the high ECW/BCM value (HR=2.80, 95％CI 1.30-6.06, P=0.003) before CRRT, the change of OH value (HR=0.82, 95％CI 0.72-0.95, P=0.008) and ECW/BCM value (HR=2.79, 95％CI 1.30-5.98, P=0.009) between the 7th day after CRRT initiation and pre-CRRT, were independently associated with 28-day death, while LTI (HR=0.93, 95％CI 0.86-1.02, P=0.113) and FTI (HR=0.98, 95％ CI 0.92-1.04, P=0.475) before CRRT were uncorrelated with 28-day death. Conclusions In bioelectrical impedance analysis, the high OH value and high ECW/BCM value before CRRT are associated with 28-day mortality in patients with AKI, while the nutritional indicators LTI and FTI before CRRT are not significantly related. The correction of fluid overload by CRRT within 7 days may reduce the risk of 28-day mortality.

The domestic hotspots research of formative assessment based on the knowledge map analysis / 中华医学教育探索杂志

Objective To summarize and analyze the present situation, hotspot and development trend of the research and practice about the formative assessment in Chinese medical teaching reform by bibliometrics, and provide a quantitative method for the study of formative assessment. Methods We took 567 journals about formative assessment from CNKI database as the research object, making co-word clus-tering and multidimensional scaling analysis as the main research method, and using Bicomb co-word anal-ysis software and SPSS to complete content data statistics and analysis. Result The knowledge map of formative assessment research can be divided into 7 fields: field 1 shows that most studies are mainly focused on practical research, the effectiveness evaluation on application are mainly focused on the improve-ment of students' independent learning ability. The proportion of research in traditional Chinese medicine colleges or universities is increasing, researches of clinical teaching take an important position, and nursing educations are paying more attention as well. Field 2 and field 4 show the synchronization between assess-ment reform and teaching content/strategy reform. Field 3 presents the general situation of teaching evaluation research in higher vocational colleges. Field 5 shows the theme of exploring the establishment of a formative assessment system . Field 6 shows the differences and similarities between examination and assessment . Field 7 shows the overview of medical English courses. Conclusion In the future, we should actively carry out the construction and exploration of the formative assessment system that conforms to China's national conditions, and attach importance to the construction of the sharing platform. We should avoid duplication of research , attach importance to the study and understanding of theoretical connotation and strengthen training, supervision and management.

Effects of parathyroidectomy on plasma iPTH, (1-84)PTH and (7-84)PTH levels in patients with stage 5 chronic kidney disease / 中华肾脏病杂志

Objective@#Currently, parathyroid hormone (PTH) is mainly measured by the second generation intact PTH (iPTH) assay which detects both full-length (1-84)PTH and (7-84)PTH fragments. The third generation whole PTH (wPTH) assay however has turned out to be specific for (1-84) PTH. The aim of this study is to investigate the features of plasma iPTH, (1-84)PTH, (7-84)PTH levels in patients with stage 5 chronic kidney disease (CKD), and evaluate the effects of parathyroidectomy (PTX) on above markers in severe secondary hyperparathyroidism (SHPT) patients.@*Methods@#A cross-sectional study including 90 controls and 233 stage 5 CKD patients, and a prospective follow-up study in 31 severe SHPT patients were conducted. Plasma iPTH and (1-84)PTH levels were measured by the second and third generation assay, respectively. Circulating (7-84)PTH level was calculated by subtracting the (1-84)PTH value from the iPTH value.@*Results@#Plasma levels of iPTH, (1-84)PTH, (7-84)PTH were higher (P<0.01), and (1-84)PTH/iPTH was lower (P<0.01) in stage 5 CKD patients than in controls. For severe SHPT patients with PTX (n=74), plasma iPTH, (1-84)PTH and (7-84)PTH concentrations were significantly increased compared to non-PTX group (n=159) (P<0.01), and the increase of (7-84)PTH level was more striking than (1-84)PTH. Meanwhile, the value of (1-84)PTH/iPTH was decreased (P<0.01). Plasma iPTH level was strongly correlated with (1-84)PTH level (r=0.980, P<0.01) in stage 5 CKD patients. Also, both iPTH and (1-84)PTH levels were positively correlated with serum alkaline phosphatase, dialysis vintage and serum phosphorus (P<0.01). After PTX (median interval of follow-up: 7.1 months), plasma iPTH, (1-84)PTH, (7-84)PTH concentrations were decreased (by 92.9%, 89.7%, 95.8%, P<0.01, respectively) greatly and (1-84)PTH/iPTH was increased (P<0.01).@*Conclusions@#In stage 5 CKD patients, plasma iPTH, (1-84)PTH, (7-84)PTH levels are greatly increased while (1-84)PTH/iPTH is decreased, and PTX can significantly improve abnormality of above markers in severe SHPT patients. The second generation PTH assay overestimates the severity of SHPT, and the accurate measurement of (1-84)PTH by the third assays is more conducive to diagnosis and treatment of CKD and SHPT patients.

Comparison of different equations for estimated glomerular filtration rate in patients with chronic kidney disease / 中华肾脏病杂志

Objective To compare different equations for estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease (CKD).Methods Hospitalized patients with CKD from the nephrology department of the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital) were recruited between December 2014 and May 2015.The calculations of eGFR and 24 h creatinine clearance rate (Ccr) were accomplished in three days after admission.The eGFRs were calculated separately using the 24 h creatinine clearance rate adjusted by the standard body surface area (Ccr_BSA),Cockcroft-Gault equation adjusted by the standard body surface area (eCcr_BSA),CKD-EPI creatinine equation (EPI_Cr),CKD-EPI cystatin C equation (EPI_CysC),CKDEPI creatinine-cystatin C equation (EPI_Cr_CysC),simplified MDRD (MDRD) and China MDRD equations.The EPI_Cr_CysC equation was used as the standard and the precision and accuracy of the other six equations were compared and analyzed.Results A total of 403 CKD participants were enrolled in the study,with 228 male patients and a mean age of (54.9± 18.4) years.The main primary diseases were chronic glomerulonephritis (43.7％) and diabetic nephropathy (13.2％).The median concentration of serum creatinine and cystatin C were 117.5 (69.7,242.4) μmol/L and 1.80 (1.13,3.31) mg/L,respectively.The median values of Ccr_BSA,eCcr_BSA,MDRD,China MDRD,EPI_Cr,EPI_CysC and EPI_Cr_CysC equations were 50.8 (21.1,96.2),51.9 (23.3,93.2),53.6 (23.0,97.4),52.2(22.4,94.1),53.2 (22.1,97.3),35.1 (15.4,67.0) and 49.1 (22.8,82.3) ml · min-1 · (1.73 m2)-1,respectively.There was well agreement among MDRD,China MDRD and EPI_Cr equations,while there were large differences between equations derived from CysC (EPI_Cr_CysC and EPI_CysC) and equations derived only from creatinine (EPI_Cr,MDRD,China MDRD,eCcr_BSA,Ccr_BSA equations).Compared with EPI_Cr_CysC equation (the reference equation),EPI_Cr equation showed the highest accuracy [percentage of other eGFR equation calculations that were ＞ 30％ of the reference equation calculations (1-P30),30.8％] while Ccr_BSA equation showed the lowest (1-P30,42.4％).EPI_CysC equation showed the highest precision [inter-quartile range (IQR) of the difference,11.7 ml·min-1 · (1.73 m2)-1] while Ccr_BSA equation showed the lowest [IQR of the difference,22.8 ml· min-1 ·(1.73 m2)-1].Conclusions The agreement among equations derived only from creatinine is better;while it exhibits some differences between equations with cystatin C and equations derived only from creatinine.The accuracy of EPI_Cr equation is second only to EPI_Cr_CysC equation and it is currently the most suitable eGFR equation for clinical popularization of renal glomerular function assessment.

Klotho alleviates toxic effect of indoxyl sulfate on vascular endothelial cells and its mechanism / 中华肾脏病杂志

Objective To investigate the effect of klotho on the human vein umbilical endothelial cells (HUVECs) injury induced by indoxyl sulfate (IS) and to explore its mechanism and the role of endoplasmic reticulum stress (ERS) in this process.Methods (1) The cell vitalities of HUVECs incubated with different concentration of IS (5,25,50 mg/L) for 48 h and with 50 mg/L IS fordifferent time points (12,24,48 h) were measured by CCK-8 assay.(2) HUVECs were incubated with 50 mg/L IS and different concentration of klotho (0,1,10,100 μg/L) for 48 h and their cell viabilities were measured by CCK-8 assay.(3) HUVECs were divided into four groups:control group,IS group (50mg/L IS),klotho group (50 mg/L IS+ 100 μg/L klotho) and Compound C group (50 mg/L IS+100 μg/L klotho+ 10 μmol/L Compound C).The cell vitality and the apoptosis of HUVECs were evaluated by CCK-8 assay and flow cytometry,respectively.The mRNA and protein expressions of GRP78 and CHOP were measured by real-time PCR and Western blotting.The phosphorylation level of AMPK was tested by Western blotting.Results IS inhibited cell vitality in the time-dependent and concentration-dependent manner.The cell viability of HUVECs with 50 mg/L IS was lower than normal control (P＜0.05).The inhibited cell vitality induced by IS was partly restored by klotho in concentration-dependent manner.The cell viability was higher in 100 μg/L klotho+50 mg/L IS group than 50 mg/L IS group (P ＜ 0.05).Compared with control group,the expressions of GRP78 and CHOP and cell apoptosis increased,however,the level of phosphorylated AMPK (p-AMPK) decreased in IS group (all P ＜ 0.05).Compared with IS group,the expressions of GRP78 and CHOP and cell apoptosis decreased and the level of p-AMPK increased in klotho group (all P ＜ 0.05).Furthermore,the above effects of klotho could be partly blocked by Compound C.The above indexes showed statistical differences between Compound C group and klotho group.Conclusions IS can inhibit the HUVECs cell vitality,and induce ERS and cell apoptosis.Klotho protein could antagonize the above effects,probably through activating AMPK pathway and reducing ERS-mediated cell apoptosis.

Klotho alleviates toxic effect of indoxyl sulfate on vascular endothelial cells and its mechanism / 中华肾脏病杂志

Objective To investigate the effect of klotho on the human vein umbilical endothelial cells (HUVECs) injury induced by indoxyl sulfate (IS) and to explore its mechanism and the role of endoplasmic reticulum stress (ERS) in this process.Methods (1) The cell vitalities of HUVECs incubated with different concentration of IS (5,25,50 mg/L) for 48 h and with 50 mg/L IS fordifferent time points (12,24,48 h) were measured by CCK-8 assay.(2) HUVECs were incubated with 50 mg/L IS and different concentration of klotho (0,1,10,100 μg/L) for 48 h and their cell viabilities were measured by CCK-8 assay.(3) HUVECs were divided into four groups:control group,IS group (50mg/L IS),klotho group (50 mg/L IS+ 100 μg/L klotho) and Compound C group (50 mg/L IS+100 μg/L klotho+ 10 μmol/L Compound C).The cell vitality and the apoptosis of HUVECs were evaluated by CCK-8 assay and flow cytometry,respectively.The mRNA and protein expressions of GRP78 and CHOP were measured by real-time PCR and Western blotting.The phosphorylation level of AMPK was tested by Western blotting.Results IS inhibited cell vitality in the time-dependent and concentration-dependent manner.The cell viability of HUVECs with 50 mg/L IS was lower than normal control (P＜0.05).The inhibited cell vitality induced by IS was partly restored by klotho in concentration-dependent manner.The cell viability was higher in 100 μg/L klotho+50 mg/L IS group than 50 mg/L IS group (P ＜ 0.05).Compared with control group,the expressions of GRP78 and CHOP and cell apoptosis increased,however,the level of phosphorylated AMPK (p-AMPK) decreased in IS group (all P ＜ 0.05).Compared with IS group,the expressions of GRP78 and CHOP and cell apoptosis decreased and the level of p-AMPK increased in klotho group (all P ＜ 0.05).Furthermore,the above effects of klotho could be partly blocked by Compound C.The above indexes showed statistical differences between Compound C group and klotho group.Conclusions IS can inhibit the HUVECs cell vitality,and induce ERS and cell apoptosis.Klotho protein could antagonize the above effects,probably through activating AMPK pathway and reducing ERS-mediated cell apoptosis.

Additional role of 99mTc-MIBI SPECT-CT imaging in preoperative localization of parathyroidectomy-clinical analysis of 359 patients with secondary hyperparathyroidism / 中华肾脏病杂志

Objective To evaluate the additional role of 99mTc-MIBI SPECT-CT imaging before parathyroidectomy (PTX) for secondary hyperparathyroidism (SHPT) patients.Methods A total of 359 SHPT patients from the First Affiliated Hospital of Nanjing Medical University were enrolled in the study from April 2011 to January 2016.Patients were divided into two groups according to the difference of 99mTc-MIBI imaging techniques preoperatively.Patients in group A had dual-phase 99mTc-sestamibi parathyroid scintigraphy performed only.Patients in group B had SPECT-CT parathyroid scintigraphy added in the early phase.With the parathyroid glands confirmed by pathology after operation being the referencc,scnsitivity,specificity,consistency and surgical success rates of the patients in two groups were compared.Results 359 patients (166 men and 193 women) were enrolled,among which 339 on hemodialysis and 20 on peritoneal dialysis.The average age of those patients was (45.90± 11.20) years and median dialysis age was 84 (60.0,120.0) months.Total detection sensitivity,specificity,consistency in group A (169 patients) were 65.54％,56.52％,65.24％ and in group B (190 patients) were 73.84％,84.62％,74.21％ respectively.Total sensitivity and consistency were higher in group B than those in group A (P ＜ 0.01),while no difference in total specificity was observed between two groups (P=0.055).In group A,detection sensitivity of parathyroid glands were 47.56％,77.44％,57.14％ and 79.88％ in right upper gland (RU),right lower gland (RL),left upper gland (LU) and left lower gland (LL) respectively.Consistency in group A were 48.52％,77.51％,56.21％ and 78.70％ respectively.In group B,sensitivity were 58.33％,83.78％,69.78％ and 82.89％ in RU,RL,LU and LL respectively.Consistency in group B were 59.47％,84.21％,70.53％ and 82.63％ respectively.Sensitivity and consistency of upper glands were lower than lower glands in both groups (P ＜ 0.01).When SPECT-CT was added,sensitivity and consistency of upper glands for both sides were higher in group B than those in group A,while no difference of surgical success rates was found between two groups (87.57％ vs 92.63％,P=0.107).Conclusion 99mTc-MIBI SPECT-CT can be combined with anatomic image effectively and increase the sensitivity and consistency of total and upper parathyroid glands.It can also make the accurate location of the lesions,which improves the efficiency of the operation.

Clinical analysis of operative treatment in 57 cases of secondary hyperparathyroidism / 重庆医学

Objective To investigate the clinical efficacy of total parathyroidectomy and autologous transplantation(PTX+ AT) for treating secondary hyperparathyroidism(SHPT) in the patients with uremic maintenance hemodialysis and postoperative calcium supplementation.Methods The clinical data in 57 patients with SHPT treated with PTX+ AT in the urology department of the First Affiliated Hospital of Nanjing Medical University from March 2015 to August 2015 were retrospectively analyzed.The changes of serum intact parathyroid hormone(iPTH),calcium and clinical symptoms were observed before and after operation.Results Serum iPTH levels at different time points of immediately after operation,postoperative 20 min,2 d,4 d were(288.57 ±194.71),(185.00±99.28),(83.83 ± 58.26),(17.91± 15.60) pg/mL respectively,which were significantly decreased compared with (2395.80 ± 829.04) pg/mL before operation (P＜ 0.05);blood calcium at postoperative 4,8,24,72 h was (2.34 ± 0.32),(2.16±0.37),(2.16±0.27),(2.25±0.25) mmol/L respectively,which were significantly decreased compared with(2.61±0.25)mmol/L before operation(P＜0.05);the symptoms such as bone pain,skin itching and so on were significantly improved.Conclusion PTX+AT can effectively treat uremic SHPT,and postoperative timely calcium supplementation can reduce the occurrence of hypocalcemia.

Delayed acute kidney injury recognition is not associated with poor short-term outcomes: a propensity score matched study / 中华肾脏病杂志

Objective Acute kidney injury (AKI) is common but usually under-diagnosed in hospitalized patients,of the impact of which on patients is still unclear.The paper was aimed to investigate the impact of delayed recognition of AKI on short-time prognosis of patients through a propensity score matched study.Methods From Oct 2013 to Sep 2014,1401 adult hospitalized patients with AKI in the First Affiliated Hospital of Nanjing Medical University were divided into delayed recognition group and timely-diagnosed group according to propensity score matching (1∶ 1) without replacement method.Primary endpoint was 30-day all-cause mortality,and secondary endpoints included recovery of kidney at discharge,length of hospitalization,length of intensive care unit stay and hospital costs.Results There were significant differences in age,department distribution,complications,stage of AKI,Charlson index,APACHE Ⅱ score,SOFA score between the two groups before matching.After matching,there were no significant difference in demographic data,department distribution,complications,stage of AKI,Charlson index,APACHE Ⅱ score,SOFA score between the two groups except in blood urea nitrogen (P=0.039) and use of diuretics (P=0.018).Delayed recognition of acute kidney injury was not associated with 30-day all-cause mortality in univariate (P=0.711) and multivariate Logistic regression analyses.The secondary endpoints did not differ in two groups.Conclusion Delayed acute kidney injury recognition did not associate with poor short-term outcomes in adult hospitalized patients.

Postoperative variations of bone turnover markers in uremic patients with secondary hyperparathyroidism after parathyroidectomy / 中华肾脏病杂志

Objective To study shortdated postoperative variation characteristics of bone turnover markers (BTMs) in uremic patients with secondary hyperparathyroidism (SHPT) underwent parathyroidectomy (PTX). Methods A total of 19 uremic patients with SHPT underwent successful PTX, hospitalized in the Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University from January 2017 to April 2017, were enrolled in the study. The operative model for all enrolled patients was total parathyroidectomy with forearm autotransplantation. The baseline epidemiological and clinical data before PTX and the levels of serum intact parathyroid hormone (iPTH) and serum BTMs after PTX (in the 1st, 3rd and 7th postoperative day) were collected. The correlations between serum iPTH and serum BTMs before PTX and the trend analysis of serum BTMs after PTX were studied. Results The levels of serum iPTH, serum alkaline phosphatase (ALP), serum typeⅠcollagen cross-linked C-telopeptides (CTX) and serum tartrate-resistant acid phosphatase 5b (TRACP-5b) before PTX were increased, in turn, (1512.4±612.0) ng/L, 267.4(153.1, 424.2) U/L, (5.78±1.15)μg/L and (8.79 ± 4.61) IU/L. Positive correlations between ALP and iPTH (r=0.577, P=0.010), TRACP-5b and iPTH (r=0.640, P=0.003), and ALP and TRACP-5b (r=0.698, P=0.001) were found. The serum levels of ALP increased, while the serum levels of CTX and TRACP-5b decreased within 7 days after PTX. Conclusions Renal osteodystrophy (ROD) with high bone turnover rate is common in uremic patients with severe SHPT. The activities of osteoblast and osteoclast are up-regulated in coupling with positive correlations to serum levels of iPTH. Increased activities of osteoblast and decreased activities of osteoclast were found shortdated postoperatively.

Determination of Nectandrin B in Uygur Medicine Arillus Myristicae by HPLC / 中国药师

Objective:To establish an HPLC method for determining nectandrin B in Uygur medicine Arillus Myristicae. Meth-ods:The analysis was performed on a SunFireTM C18 column (150 mm × 4. 6 mm, 5 μm) at 30°C using methanol /water (52 ∶48) as the mobile phase at a flow rate of 1. 0 ml·min-1 with the UV detection wavelength at 228. 4 nm. Results:The linear range of nectan-drin B was 3. 98 -79. 60 μg·ml-1(r=0. 999 2). The average recovery was 99. 89% with RSD of 1. 11%(n=6). Conclusion:The method is accurate, convenient and reproducible in the determination of nectandrin B in Uygur medicine Arillus Myristicae.

Bioartificial kidney alters cytokine response and survival time in acute uremic pigs with multiple organ dysfunction syndrome / 中华急诊医学杂志

Objective To study the effects of bioartificial kidney(BAK)treatment on cytokines interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α),biochemistry indexes,and survival time in acute uremic pigs with multiple organ dysfunction syndrome(MODS).Method Pigs with MODS and acute renal failure(ARF)were treated with BAK(group A,n = 6)or sham BAK containing no cells(group B,n = 6)or received no treatment(group C,n = 5).Data on blood pressure,hepatic and renal functions,serum IL-10 and TNF-α levels,arterial blood gas and survival time of all the pigs were recorded.Comparisons of values were done using Student's t-test or repeated-measures analysis of variance(ANOVA).ResultsMean arterial pressure(MAP,mmHg)responsed more rapidly and reached higher values in group A (91.82±5.73)compared with group B and C at 24 hours(P＜0.01).The peak level of serum EL-10(pg/mL)ingroupA(249.57±43.51)was significantly higher than that in group B and C(132.06± 17.53,104.25 ±13.42,P＜0.01).Serum TNF-a level(pg/mL)in group A dropped gradually to(402.91 ± 32.47)at 24 hours,and had significant discrepancy compared with that before the treatment(537.16 ± 38.45)and that in groupB(P＜0.05).The average survival time(hours)in group A(113.01 ± 14.32)was significantly longer than that in the group B and C(P＜0.01),which was prolonged by 35.93%and 63.90%,respectively.ConclusionsTreatment with BAK can prolong the survival time of uremic pigs with MODS,possibly through ameliorating the MAP,increasing the level of IL-10 and reducing the concentration of TNF-α.

Volt-Ampere Characteristics of Acupoint Neiguan (PC 6) on Patients with Hyperthyroidism / 针灸推拿医学（英文版）

Objective:To observe volt-ampere characteristic of Acupoint Neiguan (PC 6) on patients with hyper-thyroidism for probing into the actions of acupoints and change of qi and blood of human body as well as the relationship between the action of acupoint and the metabolism of energy. Methods:A self-made high-sensitive apparatus was applied to detect volt-ampere curves of Acupoint Neiguan(PC 6)and its control point on 33 patients with hyperthyroidism and 30 healthy people.Results:In patients,the volt-ampere areas (VAA)of both ampere.Increasing scan(AIS)and ampere—decreasing Scan(ADS)as well as the inertia areas (IS) of both side Neiguan(PC 6)were significantly smaller than the control points(P0.05).Conclusion:The volt-ampere characteristics of theright and left Neiguan(PC 61 on patients with hyperthyroidism are in imbalance.Hyperthyroidism exerts certaininfluenceontheheartfunction.

Relationship etween Electroacupuncture and Spleen Function on Leukocyte / 针灸推拿医学（英文版）

Objective: To explore the underlying mechanism by which acupuncture regulates the peripheral leukocyte count and observe the relationship between the effects of electroacupuncture (EA) and the spleen ultrastructure in leukopenia. Methods: Leukopenia models of rabbits were established by injecting cyclophosphamide (CY) into rabbits' ear vein,and then the rabbits were treated with acupuncture. The peripheral leukocyte count and classification were measured daily. At last, after the animals were anesthesized, the abdominal cavity was opened, and a piece of spleen tissue was cut. The diameter of splenic sinusoid basal lamina eyehole was measured under electric microscope. Results: The peripheral blood leukocyte count in the EA group increased significantly with shift to right of the granulocyte nuclei compared with model control group (P＜0.01). Moreover, the calibers of splenic sinusoid basal lamina eyehole in the EA group were larger than those in the model control group (P＜0.05). Conclusion: Acupuncture can enhance the peripheral leukocyte count by promoting spleen activity in the early phase of leukopenia.