OBJECTIVETo determine the expression of kidney aquaporin-2 (AQP2) and urine AQP2 excretion in chronic heart failure (CHF) rats and investigate effects of perindopril on the expression and excretion of AQP2.

METHODSSixty rats were randomized into three groups: control group, CHF group, CHF + Perindopril group. According to left ventricular myocardial infarction size, CHF group and perindopril group were further divided into heart failure subgroup (LVMI ≥ 20%) and cardiac functional compensation subgroup (LVMI < 20%), respectively. Blood and urine samples were collected from the rats for measuring serum Na(+), urine volume and urine osmolality. The concentration of plasma arginine vasopressin (p-AVP) was detected by radioimmunoassay (RIA). Immunohistochemistry, semi-quantitative real time-polymerase chain reaction (RT-PCR) and Western blot were performed for measurement of kidney inner medullary AQP2. The concentration of Urine AQP2 was measured by indirect enzyme-linked immunosorbent assay (indirect ELISA).

RESULTSImmunohistochemistry, RT-PCR, Western blot examinations revealed increased quantity of the inner kidney medullary AQP2 expression (0.2013 ± 0.0417), AQP2 mRNA (0.98 ± 0.33) and AQP2 protein expression (0.94 ± 0.21) in heart failure subgroup (n = 13) compared to control group (n = 20, 0.1518 ± 0.0214, 0.58 ± 0.51, 0.51 ± 0.46), which could be significantly by perindopril (n = 13, 0.0712 ± 0.0218, 0.76 ± 0.45, 0.82 ± 0.49, all P < 0.05 vs. heart failure subgroup). The concentration of plasma arginine AVP [(19.72 ± 3.91) ng/ml] and Urine AQP2 [(82.52 ± 11.77) ng/L] were significantly higher in heart failure subgroup than in control group [n = 20, (51.67 ± 12.58) ng/L, (6.94 ± 3.10) ng/ml] (P < 0.05), which were significantly reduced by perindopril [n = 13, (15.65 ± 4.10) ng/L, (71.65 ± 9.21) ng/ml].

CONCLUSIONIncreased expression of the kidney inner medullary AQP2 and the excretion of urine AQP2 in chronic heart failure rats could be reduced by perindopril.

Animals ; Aquaporin 2 ; metabolism ; urine ; Disease Models, Animal ; Heart Failure ; metabolism ; Kidney ; drug effects ; metabolism ; Male ; Perindopril ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To explore the genetic basis of a Chinese pedigree affected with Dyggve-Melchior-Clausen syndrome. METHODS: Whole exome sequencing and Sanger sequencing were carried out to detect potential pathogenic variants associated with the syndrome. The function of candidate variant was verified by Western blotting. RESULTS: A novel homozygous variant, c.1222delG of the DYM gene was detected in the two affected siblings, for which both parents were heterozygous carriers. The variant has caused replacement of Asp by Met at amino acid 408 and generate a premature stop codon p.Asp408Metfs*10. Western blotting confirmed that the variant can result in degradation of the mutant DYM protein, suggesting that it is a loss of function variant. CONCLUSION The homozygous c.1222delG frameshift variant of the DYM probably underlay the Dyggve-Melchior-Clausen syndrome in the two affected siblings. Above findings has enabled clinical diagnosis and genetic counseling for the family.
China ; Dwarfism/genetics* ; Humans ; Intellectual Disability ; Osteochondrodysplasias/genetics* ; Pedigree

BACKGROUNDThe aim of this study was to assess the performance of apparent diffusion coefficient (ADC) measurement obtained with diffusion-weighted magnetic resonance imaging (DW-MRI) to distinguish renal cell carcinomas (RCCs) from small benign solid renal tumors (≤ 4 cm).

METHODSIn this cross-sectional study, 49 consecutive patients with histopathologically confirmed small solid renal tumors, and seven healthy volunteers were imaged using nonenhanced MRI and DW-MRI. The ADC map was calculated using the b values of 0, 50, 400, and 600 s/mm 2 and values compared via the Kruskal-Wallis and Mann-Whitney tests. The utility of ADC for differentiating RCCs and benign lesions was assessed using a receiver operating characteristic curve. Multiple nonenhanced MRI features were analyzed by Logistic regression.

RESULTSThe tumors consisted of 33 cases of clear-cell RCCs (ccRCCs) and 16 cases of benign tumors, including 14 cases of minimal fat angiomyolipomas and 2 cases of oncocytomas. The ADCs showed significant differences among benign tumors ([0.90 ± 0.52] × 10-3 mm 2 /s), ccRCCs ([1.53 ± 0.31] × 10-3 mm 2 /s) and the normal renal parenchyma ([2.22 ± 0.12] × 10-3 mm 2 /s) (P < 0.001). Moreover, there was statistically significant difference between high and low-grade ccRCCs (P = 0.004). Using a cut-off ADC of 1.36 × 10-3 mm 2 /s, DW-MRI resulted in an area under the curve (AUC), sensitivity, and specificity equal to 0.839, 75.8%, and 87.5%, respectively. Nonenhanced MRI alone and the combination of imaging methods led to an AUC, sensitivity and specificity equal to 0.919, 93.9%, and 81.2%, 0.998, 97%, and 100%, respectively. The Logistic regression showed that the location of the center of the tumor (inside the contour of the kidney) and appearance of stiff blood vessel were significantly helpful for diagnosing ccRCCs.

CONCLUSIONSDW-MRI has potential in distinguishing ccRCCs from benign lesions in human small solid renal tumors (≤ 4 cm), and in increasing the accuracy for diagnosing ccRCCs when combined with nonenhanced MRI.

Adult ; Aged ; Carcinoma, Renal Cell ; diagnosis ; Cross-Sectional Studies ; Diffusion Magnetic Resonance Imaging ; methods ; Female ; Humans ; Kidney Neoplasms ; diagnosis ; Male ; Middle Aged ; Young Adult

Objective: To investigate the accuracy of the Agatston score obtained with the ultra-high-pitch (UHP) acquisition mode using tin-filter spectral shaping (Sn150 kVp) and a kVp-independent reconstruction algorithm to reduce the radiation dose. Materials and Methods: This prospective study included 114 patients (mean ± standard deviation, 60.3 ± 9.8 years; 74 male) who underwent a standard 120 kVp scan and an additional UHP Sn150 kVp scan for coronary artery calcification scoring (CACS). These two datasets were reconstructed using a standard reconstruction algorithm (120 kVp + Qr36d, protocol A; Sn150 kVp + Qr36d, protocol B). In addition, the Sn150 kVp dataset was reconstructed using a kVp-independent reconstruction algorithm (Sn150 kVp + Sa36d, protocol C). The Agatston scores for protocols A and B, as well as protocols A and C, were compared.The agreement between the scores was assessed using the intraclass correlation coefficient (ICC) and the Bland–Altman plot. The radiation doses for the 120 kVp and UHP Sn150 kVp acquisition modes were also compared. Results: No significant difference was observed in the Agatston score for protocols A (median, 63.05; interquartile range [IQR], 0–232.28) and C (median, 60.25; IQR, 0–195.20) (p = 0.060). The mean difference in the Agatston score for protocols A and C was relatively small (-7.82) and with the limits of agreement from -65.20 to 49.56 (ICC = 0.997). The Agatston score for protocol B (median, 34.85; IQR, 0–120.73) was significantly underestimated compared with that for protocol A (p < 0.001). The UHP Sn150 kVp mode facilitated an effective radiation dose reduction by approximately 30% (0.58 vs. 0.82 mSv, p < 0.001) from that associated with the standard 120 kVp mode. Conclusion The Agatston scores for CACS with the UHP Sn150 kVp mode with a kVp-independent reconstruction algorithm and the standard 120 kVp demonstrated excellent agreement with a small mean difference and narrow agreement limits. The UHP Sn150 kVp mode allowed a significant reduction in the radiation dose.

Objective: To investigate the expression levels of serum miR-638 in the patients with breast cancer and its clinical value. Methods: One hundred and fifty-two patients with breast cancer were selected as the disease group, and 102 healthy persons as the control group. The expression levels of miR-638 in their serum samples were detected by the quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and the expression levels of serum miR-638 in the patients with different pathological stages, before and after operation, and before and after chemotherapy were compared. The diagnosis efficacy of serum miR-638 alone and in combination with CEA, CA125, CA15-3 for breast cancer was analyzed by the ROC curve and Z test. Results: The expression levels of serum miR-638 in the breast cancer group (3.6 [1.3～10.5]) were significantly lower than that in the control group (79.0 [52.5～120.8],P＜0.01). The linear regression analysis showed that chemotherapy and pathological staging were the main factors influencing the expression levels of serum miR-638. The area under the ROC curve (AUC ROC ) of serum miR-638 in the diagnosis of breast cancer was 0.954. When the cut-off value of serum miR-638 was 27.47, its sensitivity and specificity for the diagnosis of breast cancer were 94% and 86.2%, respectively. The area under the ROC curve (AUC ROC ) of serum miR-638 combined with CEA, CA125 and CA15-3 in the diagnosis of breast cancer was 0.978 8. When the combined cut-off value was 0.29, their sensitivity and specificity for the diagnosis of breast cancer were 95.4% and 89.5%, respectively. There was no significant difference in the AUC ROC between miR-638 alone and combined screening (Z=1.68,P=0.091). Conclusion Serum miR-638 may be a potential molecular marker for the screening of breast cancer.