ABSTRACT
Objective:To observe heart rate circadian rhythm in patients with chronic kidney disease (CKD) stage 5 and to analyze the effects of parathyroidectomy (PTX) on heart rate circadian rhythm in severe secondary hyperparathyroidism (SHPT) patients.Methods:A cross-sectional observation was performed in 213 patients with CKD stage 5 and 96 controls, and the patients were divided into those with severe SHPT (PTX group, n=70) and without severe SHPT (non-PTX group, n=143). Forty-six PTX patients were followed up prospectively. The baseline data were compared among these groups. Holter electrocardiogram was performed for each participant. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Multiple linear regression analysis was used to analyze the related factors of heart rate circadian rhythm in patients with CKD stage 5. Results:The 24-hour, daytime and nighttime mean heart rate in patients with CKD stage 5 were all higher than those in controls, especially in PTX group (all P<0.05). The night/day heart rate ratios of controls and CKD stage 5 patients were (0.81±0.08) and (0.91±0.08) respectively ( P<0.01). Correlation analysis showed 24-hour and daytime or nighttime mean heart rate in patients with CKD stage 5 were positively correlated with serum levels of phosphorus and ln(alkaline phosphatase), while nighttime mean heart rate and night/day heart rate ratio were positively related with serum intact parathyroid hormone level. After adjusting with postoperative follow-up period (median time: 10.9 months), 24-hour and nighttime mean heart rate, and night/day heart rate ratio in PTX patients all decreased significantly (all P<0.01). Conclusions:Heart rate is increased and circadian rhythm is abnormal in patients with CKD stage 5, which are related with mineral and bone disorder. PTX significantly decreases 24-hour and nighttime mean heart rate in severe SHPT patients, and improves the heart rate circadian rhythm.
ABSTRACT
Objective:To investigate the value of whole-lesion histogram parameters of apparent diffusion coefficient (ADC) in evaluating and predicting the pathological complete response(PCR) to neoadjuvant chemotherapy (NAC) in different subtypes of breast cancer.Methods:This retrospective study included 117 patients with breast cancer who underwent MRI examination before NAC prior to surgery from January 2016 to December 2017 in the First Affiliated Hospital of Nanjing University. All cases were divided into Luminal B, HER2 positive ( n=21) and triple negative ( n=26) groups. The surgical pathology after chemotherapy was evaluated by Miller-Payne (M-P) system and the patients were divided into PCR group and non-PCR (nPCR) group. Firevoxel software was used to generate the whole-lesion ADC histogram. The parameters included mean (ADC mean), skewness, kurtosis, the minimum (ADC min), the maximum (ADC max), 10th percentile(ADC 10%), 50th percentile (ADC 50%) and 90th percentile (ADC 90%). The two independent samples t test or Mann-Whitney U test was used to compare the differences between PCR and nPCR groups in each subtype. The diagnostic performance of statistically different ADC parameters for predicting PCR was evaluated by receiver operating characteristic (ROC) curve. Results:Kurtosis was significantly higher in PCR group than that in nPCR group in HER2 positive subtype ( P=0.039). It achieved an area under the curve (AUC) of 0.813 with sensitivity of 100% and specificity of 68.7% at the optimal cutoff value (1.861) for differentiating PCR from nPCR cases. In triple negative subtype, ADC mean and ADC 50% were smaller in PCR group than those in nPCR group ( P=0.028,0.013). They achieved AUCs of 0.800, 0.842, respectively. When ADC mean of 1.030×10 -3 mm 2/s and ADC 50% of 0.976×10 -3 mm 2/s were used as cutoff value to differentiate PCR from nPCR, the sensitivities were 75.0%, 80.0% and the specificities were 83.3%, 83.3%, respectively. Conclusion:Kurtosis can predict post-NAC PCR in patients with HER2 positive breast cancer, while ADC 50% has a high value in predicting post NAC PCR of triple negative breast cancer patients.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Objective To investigate the clinicopathologic characteristics and prognosis of triple negative breast cancer patients. Methods A retrospective analysis was performed for 1042 primary breast cancer patients admitted in the First Affiliated Hospital of Nanjing Medical University from January 2003 to December 2009.All breast cancer patients were categorized into three subgroups by immunohistochemistry:ERBB2 +,HR +/ERBB2 - and triple negative. Results Of 1042 breast cancer patients recruited,183 patients were in triple negative group.The rate of larger tumors ( greater than 2 cm in diameter) and grade Ⅲ in triple negative patients was higher than that in ERBB2 + and HR +/ERBB2 - patients (P ＜0.01 ).The positive rate of p53 status in ERBB2 + patients was higher than that in triple negative and HR +/ERBB2- patients (P ＜ 0.01 ).No significant differences were observed in other clinical variables.In survival analysis,more bone metastases were observed in HR +/ERBB2 - patients than in ERBB2 + and triple negative patients (P =0.006).However,no significant difference was observed in visceral metastases among the subgroups.There were significantly different recurrence-free survivals (RFS) among the three subgroups throughout the follow-up period ( P =0.029),the 5-year RFS of ERBB2 + was 80.3％,which was the worst in three groups. Conclusions Triple negative patients had higher rate of larger tumors (greater than 2 cm in diameter) and grade Ⅲ than that in ERBB2 + and HR +/ERBB2 - patients,while its 5-year RFS was higher than ERBB2 + patients.
ABSTRACT
ObjectiveTo study the scope of excison in breast-conserving surgery for breast carcinoma.MethodsClinical data of 275 breast cancer patients undergoing breast-conserving surgery in t he First Affiliated Hospital of Nanjing Medical University,the Affiliated Zhenjiang Hospital of Jiangsu University and Changzhou Traditional ChineseMedicine Hospital were retrospectively analyzed.The operation procedure and postoperative adjuvant therapy were carried out with the same protocol.Local and general conditions of patients were followed up regularly.Results271 out of 275 patients got follow-up.The follow-up rate was 98.5％.The follow-up time ranged from 1 month to 117 months,median follow-up time was 34 months.Six patients died of distant metastasis,2 with local recurrence.The 1-year,3-year,and 5-year overall survival rates were 99.5％,98.1％,and 95.7％,respectively.ConclusionsIt is safe to excise 1 cm normal breast tissue with clear margin confirmed by frozen section,followed by postoperative adjuvant therapy,endocrine therapy,and radiotherapy,this improves the life quality of patients with breast cancer.It is safe and effective to determine whether the disease is multicentric or multifocal by mammogram plus clinical breast examination.
ABSTRACT
Background: Epigenetic mechanisms of gene transcription, including inactivation of tumor suppressor genes by hypermethylation and activation of oncogenes by hypomethylation, have been shown to contribute to breast tumorigenesis. Phosphatase and tensin homolog deleted on chromosome ten (PTEN) and Spleen tyrosine kinase (SYK) are both tumor suppressor genes and survivin is a novel member of the inhibitor of apoptosis (IAP) family which may promote tumorigenesis.Objective: To investigate the methylation status of PTEN, SYK, and survivin genes in breast cancer derived from Chinese women.Materials and methods: We examined the methylation status of these three genes in 52 paraffin-embedded breast cancer tissues using methylation-specific PCR (MSP) assay in conjunction with sequencing analysis.Results: PTEN and SYK were both methylated in 15.4% (8/52) of breast tumor tissues, while the survivin gene was all demethylated in the examined samples. Random selection of MSP products sequence analyses to three genes all revealed a homogenous methylation status in the CpG sites.Conclusion: The present study showed a moderate methylation status of PTEN and SYK, and an unmethylation status of survivin in breast tumor tissues derived from Chinese women, which suggested methylation mechanisms might be involved in the aberrant expression of these three genes in breast cancer development.
ABSTRACT
Soladulcidine is a steroidal alkaloid abundant in Solanum dulcamara L. with antitumor and other biological activities. In this study, ten soladulcidine derivatives were synthesized through esterification at C-3-hydroxy group, modification at NH group of F ring of esterification of E ring-opening products. The in vitro antiproliferative activity of these synthesized derivatives against prostate cancer (PC-3) cell line was assessed. Within this series of compounds, compound 19 exhibited the most potent inhibitory effect against the proliferation of PC-3 cell line (IC50=4.80±.9μmol/L).