Objective:To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD.Methods:This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality.Results:A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC=0. 698,95% CI:0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC=0.596, 95% CI: 0.523-0.669) and DPG ( AUC=0.526, 95% CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P<0.05), while DPG did not showed significance ( P>0.05). Multivariate Cox regression analysis showed that age, PVR and log 2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion:Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

OBJECTIVES: To evaluate the value of thrombospond in Type I domain-containing 7A (THSD7A) and M-type phospholipase A2 receptor (PLA2R) in primary membranous nephropathy (PMN) and to explore the relationship between their antibody levels and prognosis. METHODS: Renal tissues in 128 patients with membranous nephropathy in the Second Xiangya Hospital of Central South University were collected from February 2015 to August 2017, including 108 patients with primary membranous nephropathy (PMN group) and 20 patients with secondary membranous nephropathy (SMN) (SMN group). Indirect immunofluorescence method was used to detect the expression of PLA2R antigen in kidney tissues,and the glomerular expression of THSD7A antigen was examined by immunohistochemistry and indirect immunofluorescence. The serum levels of anti-PLA2R antibodies and THSD7A antibodies were also detected by ELISA. According to the results of PMN examination,the patients were also divided into a PLA2R-related membranous nephropathy group and a THSD7A-related membranous nephropathy group. RESULTS: The positive rate of PLA2R in the renal tissues in the PMN group was higher than that in the SMN group (78% in the PMN group, 35% in the SMN group, <0.01),while the positive rate of anti-PLA2R antibody in the PMN group was also higher than that in the SMN group (50% in the PMN group, 25% in the SMN group, <0.05).The serum level of anti-PLA2R antibody was positively correlated with 24 h urine protein (=0.254, <0.05) and negatively correlated with serum albumin (=-0.236, <0.05). The expression of THSD7A was positive in glomeruli in 7 cases of the PMN group (6%) by immuno-histochemistry, and which was positive in 1case of the SMN group (5%).The serum levels of anti-THSD7A antibody in the PMN group were higher than those in the SMN group [(0.49±0.26) pg/mL in the PMN group,(0.34±0.27) pg/mL in the SMN group, <0.05]. There was no difference in the clinical characteristics between the PLA2R-related membranous nephropathy group and the THSD7A-related membranous nephropathy group. CONCLUSIONS PLA2R and THSD7A are the target antigen of PMN, and the associated autoantibodies are helpful for the differential diagnosis of PMN. The anti-PLA2R antibody levels can reflect the severity of the disease and evaluate the effect of treatment. The incidence of THSD7A membranous nephropathy is low, and monitoring the serum anti-THSD7A antibody levels can assess patients' condition and predict disease outcome.
Autoantibodies ; Glomerulonephritis, Membranous ; Humans ; Immunohistochemistry ; Receptors, Phospholipase A2 ; Thrombospondins

In this paper, 2 cases of collagen Type Ⅲ glomerulopathy were analyzed. The clinical manifestations mainly included nephrotic syndrome, proteinuria, hypertension and renal dysfunction. One patient showed that the complement factor H-related protein 5 (CFHR5) gene was likely a disease-causing mutation. The pathological examination of renal tissues showed hyperplasia of mesangial matrix, sub-endothelial insertion, and double-track formation. Immunohistochemistry of Type III collagen was positive. Electron microscopy revealed that massive collagen fibers (40-70 nm in diameter) deposited in the mesangial matrix and basement membrane. As for the follow-up results, the normal renal function had kept steady and the proteinuria was moderate in 1 case treated with angiotensin Ⅱ receptor blocker. Due to other system disease, another case developed into acute kidney injury and then received hemodialysis. The clinical manifestations of collagen Type Ⅲ glomerulopathy was atypical, the light microscope pathological features were various, and the disease was mainly diagnosed by electron microscopy and immunohistochemistry.
Collagen Type III ; genetics ; Glomerular Mesangium ; Humans ; Kidney Diseases ; Kidney Glomerulus ; Proteinuria

Objective:To examine the expression ofphospholipase A2 receptor (PLA2R) in renal tissues and the level of anti-PLA2R antibody in serum in patients with idiopathic membranous nephropathy (IMN) and secondary membranous nephropathy (SMN),and to evaluate their diagnostic value in IMN.Methods:A total of 73 patients,who were diagnosed between May,2014 and February,2015 in the Department of Nephrology of the Second Xiangya Hospital,Central South University,were divided into three groups:an IMN group (n=48),an SMN group (n=17) and a minimal change disease group (n=8) according to the renal biopsy.PLA2R expression in renal tissues and the level of antiPLA2R antibody in serum were detected by indirect immunofluorescence technique.Results:The positive rate and fluorescence intensity for PLA2R in the renal tissues in the IMN group were higher than those in the SMN group (91.7％ in the IMN group vs 29.4％ in the SMN group,P＜0.05),while the positive rate and serum level for anti-PLA2R antibody in the IMN group were higher than those in the SMN group (85.4％ in the IMN group vs 29.4％ in the SMN group,P＜0.05);the expression of PLA2R in renal tissues and the serum level for anti-PLA2R antibody were not detected in the minimal change disease group,The serum level of anti-PLA2R antibody was positively correlated with 24 h urine protein (r=0.432,P＜0.01) and negatively correlated with serum albumin (r=-0.307,P＜0.05).Conclusion:The expression of PLA2R in renal tissues and the serum level of anti-PLA2R antibody might be potential markers for diagnosis oflMN.

Objective: To evaluate the effect of transcatheter aortic valve replacement(TAVR) using Venus-A valve for treating patients with severe aortic stenosis. Methods: In this prospective study, 101 consecutive severe aortic stenosis patients with high surgical risk(Society of Thoracic Surgeon(STS) score ≥4%) or at prohibitive surgical risk were enrolled from 5 academic cardiovascular centers in China(Fuwai hospital, the second affiliated hospital of Zhejiang university school of medicine, West China hospital of Sichuan university, the first affiliated hospital of Nanjing medical university, Ruijin hospital of Shanghai Jiaotong university school of medicine) from September 2012 to January 2015, and Venus-A valves were used in TAVR for these patients. The primary endpoints were death from any cause and major stroke in 1 year. The secondary endpoints included efficacy and safety of TAVR in 1 year. Results: TAVR success rate was 97.9%(98/101), and 3 patients were transferred to receive surgical AVR. There were 85 patients using 1 Venus-A valve, and 13 patients underwent valve-in-valve implantation using 2 Venus-A valves. There were 1 case(1.0%) of stroke, 2 cases(2.0%)of acute myocardial infarction, 5 cases(5.0%) of pericardial effusion, 6 cases(5.9%) of severe vascular complication, and 2 cases(2.0%) of death after 7 days of TAVR. Meanwhile, aortic pressure gradient derived from echocardiography was significantly reduced when compared with pre-procedure level(11(8, 15) mmHg (1 mmHg=0.133 kPa) vs. 59(45, 71)mmHg, P<0.01), and there was no aortic root rupture or leaflets thrombosis. Rate of NYHA functional class ≤Ⅱ improvements were observed at 6 months follow-up when compared with pre-procedure(94.4%(84/89)vs. 21.3%(21/89), P<0.01). The primary endpoint was 7.9%(8/11), and the incidence of all cause death and stroke was 5.9%(6/101) and 2.0%(2/101) respectively at 1 year after the procedure. Kaplan-Meier survival analysis showed that cumulative survival rate was 94.1% at 1 year after the procedure. Conclusion TAVR using Venus-A valve for treating patients with severe aortic stenosis is effective and safe in the early and medium term post procedure.

Objective To explore the relationship between glycated albumin ( GA ) in 2 consecutive months and hemoglobin A1c ( HbA1c) in diabetes patients.Methods Totally 100 consecutive patients with main diagnosis of diabetes mellitus were enrolled retrospectively from April 2015 to January 2016 in outpatient clinic of endocrinology of Peking Union Medical College Hospital, who had undertaken GA tests every 4 weeks for 2 successive months and had HbA1c test in the second month.GA was measured with liquid enzymatic method. HbA1c was measured by ion-exchange high performance liquid chromatography.The relationship between HbA1c and GA for the 2 successive months was determined.Results A total of 85 patients were enrolled.The regres-sion equation between HbA1c (y) and average GA (j) for successive 2 months was y=3.187+0.218j (adjusted R2 =0.520, P=0.000), which showed a similar effect as the regression equation for HbA1c and the levels of GA tested for the 2 successive months (adjusted R2 =0.514, P=0.000), and both had more significant regressive effect than the regression equation for HbA1c and single measurement of GA (adjusted R2 =0.392, P=0.000). Conclusions The regressive effect between HbA1c and GA (or the average of GA) in successive 2 months is bet-ter than that with single measurement of GA, hence could better predict HbA1c in clinical practice.

To examine levels of M-type phospholipase A2 receptor (PLA2R) and its antibody in the patients with hepatitis B virus-associated membranous nephropathy (HBV-MN), and to explore the correlation of PLA2R with laboratory parameters and pathological characteristics.
 Methods: A total of 49 adult patients with biopsy-proved HBV-MN were enrolled in this study. Levels of anti-PLA2R antibody in serum and PLA2R in renal tissue were detected. Patients were assigned into two groups: a positive PLA2R group and a negative PLA2R group. Differences in laboratory parameters and pathological characteristics were compared between the two groups.
 Results: Of 49 patients with HBV-MN, 17 had positive PLA2R expression in renal tissues. In the positive PLA2R group, 10 patients were positive for serum anti-PLA2R antibody. Patients with positive PLA2R expression in renal tissues showed higher levels of 24 hour urinary protein [(4.6±3.9) g/d], serum HbsAg (70.5%) and renal HbsAg expression (71%), while lower level of serum albumin [(24.1±7.5) g/L] than those of the negative group.
 Conclusion: PLA2R is expressed in the renal tissues and serum anti-PLA2R antibody can be detected in some HBV-MN patients. Positive PLA2R expression in renal tissue might be related to HbsAg deposition in serum and renal tissues. Patients with positive PLA2R expression in renal tissue have more severe glomerular sclerosis.
Adult ; Antibodies ; Autoantibodies ; genetics ; physiology ; Biopsy ; Glomerulonephritis, Membranous ; complications ; etiology ; genetics ; Hepatitis B ; complications ; Hepatitis B Surface Antigens ; adverse effects ; Hepatitis B virus ; Humans ; Kidney ; blood supply ; chemistry ; physiopathology ; Kidney Diseases ; etiology ; genetics ; physiopathology ; Male ; Prognosis ; Proteinuria ; epidemiology ; genetics ; Receptors, Phospholipase A2 ; blood ; physiology ; Serum Albumin ; genetics

Atrioventricular Block ; complications ; Atrioventricular Node ; surgery ; Heart Neoplasms ; complications ; surgery ; Humans

Objective To evaluate the clinical and biochemical characteristics of pregnant women with different glucose tolerance status,and their secretion characteristics of insulin,glucagon and glucagon-like peptide-1 (GLP-1) after oral glucose challenge.Methods We analyzed 74 cases pregnant women with positive results of 50 g glucose challenge test in 24-28 gestational weeks,who received regular obstetrical follow-up in Peking Union Medical College Hospital from January 2009 to June 2012.A further 100 g oral glucose tolerance test (OGTT) was performed,based on which the included women were divided into three groups,namely gestational diabetes mellitus (GDM) group (n =25),impaired glucose tolerance (IGT) group (n =25) and normal glucose tolerance (NGT) group (n =24).The general clinical data and biochemical indexes of the three groups were compared,and the indexes about insulin resistance and the function of pancreatic islet beta cells were calculated.Glucose,insulin,glucagon and GLP-1 were measured in OGTT.The secretion characteristics of each of these hormones and their correlation with other indicators were evaluated.Results Compared with the NGT group,the GCT [(9.21 ±0.75) mmol/L vs.(8.52 ±0.50) mmol/L,P ＜0.05] and glycosylated hemoglobin A1c [(5.39±0.34)％ vs.(5.18 ±0.20)％,P＜0.05] were significantly higher in the GDM group.In OGTT,the area under curve (AUC) of glucose in the GDM group was significantly higher than that inthe IGT group and NGT group [(26.58 ±2.02) mmol/(L · h) vs.(23.20 ± 1.51) mmoL/(L · h),(26.58 ± 2.02) mmol/(L · h) vs.(19.84 ± 1.95) mmol/(L · h),both P ＜ 0.05].The peak values of insulin secretion in the GDM group and IGT group were delayed to 2 hours after OGTT.The 3-hour insulin level in the GDM group was significantly higher than that in the NGT group (P ＜ 0.05).Compared with the NGT group,the glucagon levels in each time point after OGTT and the AUC of glucagon levels were reduced in the GDM group and the IGT group,but with no significant differences.The peak glucagon levels in the 3 groups all appeared at 3 hours after OGTT.The GLP-1 levels in each time point of OGTT were gradually increased from the NGT group to the IGT group to the GDM group,but no significant differences were found.The peak value of GLP-1 level was presented at 1 hour after OGTT in the NGT group and the IGT group and at 2 hours after OGTT in the GDM group.The valley values of GLP-1 level in the 3 groups all appeared at 3 hours after OGTT.In comparison with the NGT group,the ratios of GLP-1 to blood glucose levels (GLP/BG) at 1-hour and 2-hour were significantly decreased in the GDM group (P ＜ 0.05).The AUC of glucagon levels in OGTT were negatively correlated with fasting blood glucose (r =-0.287,P =0.013) and 1-hour glucose levels (r =-0.266,P =0.022) in OGTT and positively correlated with insulin secretion sensitivity index (ISSI) (r =0.297,P =0.010) and HOMA-β (r =0.236,P =0.043).Moreover,the AUC of GLP-1 levels in OGTT was negatively correlated with the levels of C-reactive protein (r =-0.264,P =0.035).The AUC of GLP/BG in OGTT was positively correlated with ISSI (r=0.406,P＜0.001).Conclusions Pregnant women with GDM and IGT in the second trimester have insulin resistance and dysfunction of pancreatic islet β cells.Potential GLP-1 resistance and inadequate secretion may exist in GDM patients.GLP/BG may be a better parameter to evaluate the secretion function of L cells in pregnancy and an effective parameter to estimate the compensatory function of pancreatic β cells indirectly.Glucagon levels may not start to change obviously before 28 gestational weeks.

Objective To evaluate clinical features,insulin sensitivity,and serum adipocytokines levels in pregnant women with different glucose tolerance status and to investigate the possible serum predictive biomarkers of gestational diabetes mellitus (GDM).Methods We included 74 pregnant women with positive results of 50 g glucose challenge test (GCT),who received regular obstetrical follow-up in Peking Union Medical College Hospital from January 2009 to June 2012.A further 100 g oral glucose tolerance test was performed in 24-28 gestational weeks,based on which the 74 pregnant women were divided into GDM group (n =25),impaired glucose tolerance (IGT) group (n =25) and normal glucose tolerance (NGT) group (n =24).The clinical data were recorded in detail.Serum fibroblast growth factor (FGF)-19,FGF-21,visceral adiposespecific serine protease inhibitor (vaspin),leptin,insulin-like growth factor binding protein-1 (IGFBP-1),and adiponectin levels of the 3 groups were measured by enzyme-linked immunosorbent assay (ELISA) and compared.The associations of these adipocytokines with the patients' baseline data and metabolic indexes were analyzed.Results The blood glucose after GCT and glycosylated hemoglobin A1c in the GDM group were significantly higher than those in the NGT group [(9.21 ±0.75) mmol/L vs.(8.52 ±0.50) mmol/L,P ＜0.05;(5.39 ± 0.34) ％ vs.(5.18 ± 0.20) ％,P ＜ 0.05],but not significantly different from those in the IGT group [(9.14 ± 0.64) mmol/L,P ＞ 0.05;(5.28 ± 0.28) ％,P ＞ 0.05].Age,systolic blood pressure and diastolic blood pressure in the first trimester,pre-gestational body mass index (BMI),increment of BMI during pregnancy,serum total cholesterol,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,and C-reactive protein levels in the three groups showed no significant differences (all P ＞0.05).From the NGT group to the IGT group to the GDM group,the area under curve of blood glucose (AUCBG) [(19.84±1.95),(23.20±1.51),(26.58±2.02) mmol/(L · h)] and AUC of insulin (AUCINS) [(1.84± 0.91) ×103,(1.85 ±1.15) ×103,(2.49 ±1.36) ×103 pmol/(L · h)] both gradually increased.Compared with the NGT group,the GDM group had significantly higher HOMA-IR [3.0 (1.5,5.2) vs.2.5 (1.5,3.4),P ＜0.05] significantly lower HOMA-β [230.5 (144.6,311.6) vs.235.6 (168.1,350.0),P ＜ 0.05].Among the GDM,the IGT,and the NGT groups,there were no significant differences in serum FGF-19 [(284.42±78.16),(268.17 ±72.97),(283.86 ±79.74) ng/L],FGF-21 [(798.16±273.57),(882.43 ±322.17),(842.75 ±343.01) ng/L],vaspin [(22.36 ±7.27),(23.53 ±7.90),(22.63±9.11) μag/L],leptin [(5.51 ± 1.44),(5.58 ± 1.58),(5.48 ± 1.47) μg/L],adiponectin [(798.85 ± 255.14),(863.44 ± 252.18),(828.36 ± 249.32) μg/L] and IGFBP-1 [(40.44 ± 16.41),(49.57±12.60),(43.80±16.58) μg/L] levels (all P＞0.05).Conclusions There are no significant differences of a variety of adipocytokines in pregnant women with different glucose tolerance status,and no effective serum predictors of GDM are found.The effect of adipocytokines in the pathogenesis of GDM remains to be further investigated.