Objective: Evidence supports the efficacy of coronary computed tomography angiography (CCTA)-based risk scores in cardiovascular risk stratification of patients with suspected coronary artery disease (CAD). We aimed to compare two CCTAbased risk score algorithms, Leiden and Confirm scores, in patients with diabetes mellitus (DM) and suspected CAD. Materials and Methods: This single-center prospective cohort study consecutively included 1241 DM patients (54.1% male, 60.2 ± 10.4 years) referred for CCTA for suspected CAD in 2015–2017. Leiden and Confirm scores were calculated and stratified as < 5 (reference), 5–20, and > 20 for Leiden and < 14.3 (reference), 14.3–19.5, and > 19.5 for Confirm. Major adverse cardiovascular events (MACE) were defined as the composite outcomes of cardiovascular death, nonfatal myocardial infarction (MI), stroke, and unstable angina requiring hospitalization. The Cox model and Kaplan–Meier method were used to evaluate the effect size of the risk scores on MACE. The area under the curve (AUC) at the median follow-up time was also compared between score algorithms. Results: During a median follow-up of 31 months (interquartile range, 27.6–37.3 months), 131 of MACE were recorded, including 17 cardiovascular deaths, 28 nonfatal MIs, 64 unstable anginas requiring hospitalization, and 22 strokes. An incremental incidence of MACE was observed in both Leiden and Confirm scores, with an increase in the scores (log-rank p < 0.001). In the multivariable analysis, compared with Leiden score < 5, the hazard ratios for Leiden scores of 5–20 and > 20 were 2.37 (95% confidence interval [CI]: 1.53–3.69; p < 0.001) and 4.39 (95% CI: 2.40–8.01; p < 0.001), respectively, while the Confirm score did not demonstrate a statistically significant association with the risk of MACE. The Leiden score showed a greater AUC of 0.840 compared to 0.777 for the Confirm score (p < 0.001). Conclusion CCTA-based risk score algorithms could be used as reliable cardiovascular risk predictors in patients with DM and suspected CAD, among which the Leiden score outperformed the Confirm score in predicting MACE.

Objective:To investigate the changes in adaptive phenotypes of Yersinia pestis ( Yp) during successive passages in macrophages. Methods:A Yp strain of 201-MI was induced by 50 successive passages of Yp 201 strain in Raw264.7 cells. Phenotypic characteristics of 201 and 201-MI strains were compared by analyzing their survival rates in macrophages, growth curves, biofilm formation abilities, acid and hydrogen peroxide-stress tolerance, and virulence to mammal cells (Raw264.7 and HeLa cells) and mice. Results:Comparing with 201 strain, 201-MI strain showed various phenotypic changes, including higher survival rate in Raw264.7 cells, faster growth in iron-deficient medium, higher tolerance to acid and hydrogen peroxide, decreased biofilm formation ability, and less damages to Raw264.7 and HeLa cells. More-over, 201-MI strain showed decreased virulence to mice in both subcutaneous and intraperitoneal challenges. Preliminary comparative genomics analysis revealed some indel and nonsense mutations in 201-MI strain, which might account for its phenotype changes.Conclusions:After successive passages in macrophages, Yp showed some phenotypic changes, which might reflect its adaptive evolution under the pressure of macrophages. Detailed multi-omics analysis would be of great help to understand the underlying genetic mechanisms of these changes, and the related Yp-macrophage interaction processes as well.

Objective To evaluate the diagnostic value of pathological features of atypical membranous nephropathy (AMN). Methods Ninety - one patients with AMN diagnosed by renal biopsy during 2011 and 2017 were enrolled in this study. On the basis of M - type phospholipase A2 receptor (PLA2R) and thrombospondin type - 1 domain - containing 7A protein (THSD7A) by immunohistochemistry, patients were divided into AMN group (25 cases without PLA2R and THSD7A) and idiopathic membranous nephropathy (IMN) group (66 cases with positive PLA2R or THSD7A). The results of immunofluorescence (IF), light microscopy (LM) and electron microscopy (EM) of these two groups were compared, and the parameters with statistical difference were screened out in order to assess their value in the diagnosis of AMN in fourfold table. Results IF results showed that in AMN group the proportions of IgG deposition on capillary wall and mesangial area as well as positive otherIgG subclasses and complement C1q but negative IgG4 were significantly higher than those in IMN group (respectively, 56.0％ vs 12.1％ , 44.0％ vs 0, both P＜0.05). Their diagnostic specificities for AMN were 87.9％ and 100.0％, respectively. However, the positive rates of IgG accompanied with IgA and/or IgM, predominant IgG4 with other IgG subclasses and complement C1q in two groups were not significantly different (all P＞0.05). LM results showed that the proportions of false double track sign on basement membrane and fuchsinophilic proteins under epithelium, endothelium, basement membrane and mesangial region in AMN group were significantly higher than those in IMN group (respectively, 36.0％ vs 0, 44.0％ vs 1.5％, both P＜0.05). Their diagnostic specificities for AMN were 100.0％ and 98.5％ , respectively. However, the scores of mesangial cell proliferation of these two groups showed no significantly difference (P＞0.05). EM results showed that the rate of endothelial electron dense deposits in AMN group was significantly higher than that in IMN group (36.0％ vs 1.5％, P＜0.05), and its diagnostic specificity for AMN was 98.5％. Conclusions IgG deposition on both capillary wall and mesangial area, positive other IgG subclasses and C1q with negative IgG4, false -double contour sign, multi - site fuchsinophilic deposits and endothelial electron dense deposits may help for the AMN diagnosis in the absence of PLA2R and THSD7A related data.

Objective To evaluate the efficacy and safety of tolvaptan therapy for edema in patients with nephrotic syndrome(NS).Methods Twelve patients with NS who had normal serum sodium and blood volume were enrolled.All of them were treated with oral tolvaptan of 15-30 mg per day for 7 days.The diuretic effects were observed and the adverse reactions including electrolyte disorders(especially hypernatremia),low blood volume,thromboembolic complications,and acute kidney injury were closely monitored.Results The average urine volume was significantly increased(F=5.792,P ＜ 0.001)and the body weight was significantly decreased(F=24.086,P ＜ 0.001)from the first day of tolvaptan therapy until the end of the treatment.The average serum sodium levels were significantly increased from the second day of tolvaptan therapy until the end of the treatment(F=2.790,P=0.012),but only 3 case-times(3.6％)among the total 84 case-times of serum sodium tests showed mild hypernatremia(the highest level 146.5 mmol/L)and all the hypernatremia returned back to normal after suspending tolvaptan for one day.There were no significant changes in the serum potassium levels(F=0.477,P=0.849)within the whole treatment course.There was also no significant difference of the blood volume between the level at the end of treatment and the baseline level[(74.3± 3.0)ml/kg vs(74.9±3.0)ml/kg,P=0.855].The thromboembolic complications and acute kidney injury both also did not take place.Conclusions As long as a rational and prudent treatment regimen is applied,tolvaptan has good diuretic effects and safety for treatment of edema in the NS patients with normal serum sodium and blood volume.

Objective To investigate whether the clinical and pathological injury of kidney in IgA nephropathy (IgAN) patients with hypertension is associated with circadian blood pressure rhythm change, particularly with elevated nocturnal blood pressure (BP). Methods This study was a retrospective cross-sectional study. Clinic and renal histopathological injury data were obtained from 83 IgAN patients with hypertension. First, 24 h ambulatory BP monitoring (ABPM) data were analyzed. Second, all these IgAN patients were divided into two groups, elevated nocturnal BP group and nocturnal normotensive BP group, and the clinical and pathological differences between this two groups were analyzed. Third, logistic regression analysis was used to analyze the influencing factors of renal tubulointerstitial injury in IgAN patients with hypertension. At last, all these IgAN patients were divided into two groups according to the level of estimated glomerular filtration rate (eGFR), group of patients with eGFR≥60 ml·min-1·(1.73 m2)-1 and the other group with eGFR<60 ml·min-1·(1.73 m2)-1, and the 24 h ABPM data were compared. Results (1) The proportion of non-dipper circadian rhythm of BP in IgAN patients with hypertension was 79.5％. (2) Compared with nocturnal normotensive BP group, patients in elevated nocturnal BP group had significantly higher levels of 24-hour urinary protein quantity and blood uric acid (both P<0.05), and lower eGFR and urine osmotic pressure clinically (both P<0.05). Index of interstitial fibrosis and tubular atrophy was significantly higher in nocturnal normotensive BP group (P<0.05), while the proportion of glomerular ischemia lesion was not significantly different between two groups. (3) Multivariate logistic regression analysis showed that elevated nocturnal BP was an independent risk factor for severe tubulointerstitial injury of IgAN (OR=1.113, 95％CI 1.038-1.192, P=0.002). (4) Compared with the group of eGFR≥60 ml·min-1·(1.73 m2)-1, 24-hour systolic blood pressure (SBP) and diastolic blood pressure (DBP), daytime SBP and DBP, nocturnal SBP and DBP were significantly higher in group of eGFR<60 ml·min-1·(1.73 m2)-1 (all P<0.05). Conclusion The proportion of non-dipper circadian rhythm of BP in IgAN patients with hypertension is as high as 79.5％. Elevated nocturnal BP is associated with the severity of renal damage, and elevated nocturnal BP is an independent risk factor for severe tubulointerstitial injury in IgAN patients with hypertension. Therefore, 24 h ABPM should be emphasized, and elevated nocturnal BP should be well controlled to slow the progression of IgAN.

Objective To evaluate the diagnostic value of clinical laboratory indexes on judgment of hypovolemia in the patients with nephrotic syndrome (NS).Methods The blood volume of each 50 cases of healthy adult men and women was assessed with indocyanine green-pulse dye densitometry (ICG-PDD).The normal range of blood volume and the cut-off value of hypovolemia were determined.The blood volume of 81 patients with NS was also measured with ICG-PDD and then these patients were divided into the hypovolemic group (21 cases) and the non-hypovolemic group (60 cases) according to the cut-off value of hypovolemia.The test data of clinical laboratory indexes of the patients in the two groups were compared,and the indexes with statistic difference were screened out.Their diagnostic values on judgment of hypovolemia were evaluated by receiver operating characteristic (ROC) curve analysis,and finally the indexes with high judgment accuracy were selected.Results ①The cut-off values of hypovolemia are ＜ 52.9 ml/kg for the male and ＜ 52.5 ml/kg for the women,which were determined with ICG-PDD.②The five clinical laboratory indexes,including orthostatic heart rate (OHR) increase ＞ 10 bit per minute,fractional excretion of sodium (FENa) ＜ 1,transtubular potassium gradient (TTKG) ＞ 60％,blood urea nitrogen/serum creatinine ratio (BUN/Scr) ＞ 20,and urine specific gravity (SG) ＞ 1.020,were used to judge the hypovolemia in NS patients in this study.ROC curve analysis showed that the diagnostic accuracy in judgment of hypovolemia by one index or two indexes combination only belonged to medium level.However,the diagnostic accuracy in judgment of hypovolemia by the following three indexes combination,i.e.OHR increase+FeNa+BUN/Scr,FeNa+ BUN/Scr+SG,OHR increase+TFKG+BUN/Scr,or ORG increase+FeNa+TTTKG,reached high level.Conclusion This study obtained the cutoff value of Chinese adults hypovolemia are ＜ 52.9 ml/kg for the male and ＜ 52.5 ml/kg for the women,which are determined with ICG-PDD,through evaluation we recommend applying the above four specific combinations of three indexes for diagnosis of hypovolemia in NS patients.

Objective To detect the level of serum α-klotho in different obese people and to investigate the correlation between serum α-klotho and obesity-related glomerulopathy (ORG).Methods A total of 48 cases of ORG diagnosed by renal biopsy were enrolled in the study.Fortyeight gender-,age-and BMI-matched obese participants,and 48 obese chronic kidney disease (CKD) patients without ORG were included as controls.The clinical manifestations,laboratory examinations of all three groups were collected,and the level of serum α-klotho protein was measured by ELISA.Results The patients with ORG were characterized by decreased serum α-klotho concentration compared with obese patients group and obese CKD patients group [572.66(439.92,690.58) pg/ml vs 635.85(559.52,769.20) pg/ml and 690.30(516.15,828.20) pg/ml,P＜ 0.01].Multinomial multiple logistic regression analysis revealed that serum α-klotho (per 100 pg/ml increased) was independently associated with the prevalence of ORG,and the risk of ORG decreased by 35％ in the obese participants (OR=0.652,95％ CI:0.487-0.872) and 38％ in CKD patients (OR=0.617,95％ CI:0.453-0.832) respectively.Conclusions The level of serum α-klotho is significantly decreased in ORG and associated with the prevalence of ORG independently.Serum α-klotho may be a protective factor for ORG.

Objective This study was to observe the effects of different test conditions on the qualitative and quantitative detection of cryoglobulin .Methods We prepared 5 blood samples of different types of cryoglobulinemia . We detect the cryoglobulin qualitatively and quantitatively at different temperatures (37 ℃and room temperature of 20-25 ℃), and with different observation time (3 days and 7 days) and with different amount of blood (5 ml and 20 ml) .Further we will categorize the type of cryoglobulin and detect the components of cryoglobulin by immunofixation electrophoresis ( IFE) and other laboratory tests.Results (1) Blood samples from two groups were clotting and the serums were separated at 37 ℃ and room temperature respectively , and cryoglobulins of two groups were all qualitatively positive . Quantitative detection of cryoglobulins showed that the concentrations of cryoglobulins of room temperature group are lower than that of 37℃group;(2) Compared with 7 days, observing for only 3 days may lead to false-negative results in qualitative detection of cryoglobulin , and concentrations of cryoglobulin are also decreased;(3) Compared with 20 ml blood sample,5 ml blood sample is not enough for qualitative and quantitative detection of cryoglobulins .It may lead to false-negative results;(4) After purification, IFE and other laboratory tests can be used to categorize the types and find the components of cryoglobulins .Such examinations are helpful for finding the potential causes of cryoglobulinemia .Conclusions The positive of serum cryoglobulin is a key indicator of cryoglobulinemia .Detection of cryoglobulin can be affected by temperature, observed time and the blood volume for measurement .In addition, IFE and other laboratory tests are helpful for finding the type and the components of cryoglobulin .

Over the past decade , with the rapid increase of the incidence of idiopathic membranous nephropathy (IMN) in our country, the diagnosis and treatment of IMN has been paid more and more attention.IMN is an autoimmune disease.Two important podocyte autoantigens , PLA2R and THSD7A, have been indentified sine 2009.Subsequently , serum anti-PLA2R antibody test and anti-THSD7A antibody test have also been used in clinical .Preliminary applications show that these two tests can not only help IMN diagnosis and differential diagnosis , but also help IMN prognosis.

Objective To investigate the relationship of α-klotho protein and obesity related glomerulonephritis.Methods The chronic kidney disease (CKD) patients with or without ORG were diagnosed by renal biopsy.The normal and abdominal obesity control people were enrolled from the physical examination center.Propensity scoring analysis was done to balance the four groups of people in important clinical characteristics.The α-klotho levels in blood and urine were detected by ELISA.ORG mouse model was established and the mRNA and protein expression of klotho protein were detected by real-time quantitative PCR and Western blotting.Results (1) The plasma α-klotho levels decreased in ORG patients,CKD patients and abdominal obesity control people compared with normal control people [(251.7 ± 124.1) ng/L,(336.3 ± 126.1) ng/L,(377.1 ± 120.4) ng/L vs (472.3 ± 204.2)ng/L,all P ＜ 0.05].The ORG patients had the lowest plasma α-klotho levels (P ＜ 0.05).(2) ORG patients also had the lowest urine α-klotho levels compared with CKD patients,abdominal obesity and normal control people [(24.7±11.4) mg/mol vs (82.5±33.8) mg/mol,(74.5±32.5) mg/mol,(100.8±51.1)mg/mol,all P ＜ 0.05].There was no difference in urine α-klotho levels of CKD patients,abdominal obesity and normal control people.(3) Compared with the normal control mouse,ORG model mouse showed decreased mRNA and protein expression of α-klotho protein in renal tissue.Conclusion The lower plasma and urine α-klotho levels in ORG patients may be due to the reduced expression of α -klotho protein in kidney.