Objective To prepare the immunoconjugate composed of Adriamycin nanoparticles and VEGFR 2 monoclonal antibody(conjugate of ADM-NP and VEGFR 2-MAb) and study its pharmacokinetics property. Methods Adriamycin nanoparticles were prepared by using double emulsion method, with PLA and O-CMC as materials. Conjugate of ADM-NP and VEGFR 2-MAb was prepared by using molecule conjugate technology. Immunoreactivity of the conjugate with type IV collagenase and H 22 cell were analyzed by using ELISA. Pharmacokinetics parameters of the immunoconjugate were obtained by using SD rats as study objects. Results The prepared ADM-NP was sphere particles under SEM, which diameters were (160±34) nm. The drug loading rate and entrapment rate were (30.15±3.5)% and (80.56±4.24)% respectively. Conjugate of ADM-NP and VEGFR 2-MAb was successfully prepared, which had immunoreactivity with type IV collagenase and H 22 cell. The immunoconjugate showed good ADM control-release ability and could prolong the retention time of ADM in vivo. Conclusion Conjugate of ADM-NP and VEGFR 2-MAb keeps the immunoreactivity of VEGFR 2-MAb and shows good ADM control-release ability.

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.

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.

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.

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.

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.

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.