Acute kidney injury(AKI) has emerged as a major public health problem that leads to decreased survival.In AKI,cell hyperplasia,hypertrophy and apoptosis are related to the cell cycle control.Two supervisory restriction points,G1/S and G2/M checkpoints,are responsible for cell-cycle control.Furthermore,cell cycle regulatory proteins are also involved in the regulation of the cell cycle in AKI.This review focuses on the cell cycle regulation mechanism of AKI.

Acute kidney injury (AKI) has emerged as a major public health problem that leads to decreased survival. Renal tubular epithelial cells are mainly damaged cells in AKI. Renal tubular epithelial cell remodeling plays a vital role in AKI. The regulatory mechanism of renal tubule remodeling is not yet clear. This review is written to address the renal tubule remodeling regulation mechanism of AKI.

BACKGROUND: Angiotensinogen (AGT) gene is the firstly discovered candidate gene for essential hypertension, both the T174M and M235T polymorphisms locate at the second exons of AGT gene, and there is existence of linkage disequilibrium. The polymorphism at A-6G and G-217A sites in promotor region plays an important role in regulating the gene expression, and the products of keep close correlation with the level of blood pressure. OBJECTIVE: To investigate the association between the polymorphism of AGT gene at A-6G, T174M and G-217A sites and the risk for the attack of essential hypertension in Chinese Han population, DESIGN: A cluster sampling and case-control analysis. SETTINGS: Department of Geriatrics and Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University; Southern Research Center of National Human genome; Department of Cardiology, Dongtai People's Hospital of Jiangsu Province. PARTICIPANTS: The experiment was carried out in the countryside of Dongtai county, Yancheng city, Jiangsu province. All the subjects were selected from the countryside of Dongtai county, Yancheng city, Jiangsu province. Totally 177 patients with essential hypertension who had never accepted any drug treatment, were taken as the essential hypertension group, and hypertension was diagnosed according to the diagnostic standard of hypertension set by WHO/ISH in 1999 (systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg); Another 86 normal person were taken as the normal control group. ② Inclusive criteria: The enrolled subjects should be Han nationality; long-term local residents but not from other places; able to answer questions clearly; diagnosed by disease history, clinical symptoms, physical signs and assistant examinations; have complete data of investigation of uniform questionnaires by face-to-face interview (including demographic information, profession history, family history and life styles of smoking, drinking, drinking tea, etc.). ③ Exclusive criteria: The patients with secondary hypertension in the essential hypertension group, subjects having family hisory of hypertension in the normal control group, and those with chronic diseases of liver and kidney, and diabetes mellitus in both groups were excluded. METHODS: Peripheral venous blood samples (3 mL) were collected, and DNA was extracted from human peripheral blood with FlexiGene DNA Kit (250). The Primer3 software was applied to design primers, and the polymorphism sites in the primer sequence were excluded. After multiplex polymerase chain reaction (PCR), 3 μL products were selected to detected the amplified results by agarose gel electrophoresis. The successfully amplified PCR products were purified with the QIAquick PCR Purification Kit, and the purified products were fragmentized with Dnase Ⅰ . The fragmentized products of enzyme digestion were labeled with fluorescein by deoxynucleotide terminal transferase. Two allele specific probes and one mismatched probe were designed respectively for each single nucleotide polymorphism. The chips were prepared with the OmniGridTM 100 TLC samler, each probe was repeated for three times to form three matrix. The hyridization solution was degenerated at 95 ℃ for 10 minutes, and then immediately cut on ice. 10 μL hybridization solution was added onto the chip matrix, hybridized at 50 ℃ for 2 hours, then washed and dried. The chips were scanned with the GenePix 4000B laser confocal scanner (Figure 2),and the intensity of the fluorescent signal for each probe was extracted with GenePix Pro, and the allele score of each single nucleotide polymorphism was calculated to judge the genotype. MAIN OUTCOME MEASURES: ① Comparison of the frequencies of genotype distribution at each polymorphism site of AGT gene in both groups; ② Correlation analysis of the polymorphism of AGT gene at A-6G and T-174M sites with the risk for the attack of essential hypertension; ③ Effects of the polymorphism of AGT gene at A-6G, T-174M and G-217A sites on blood pressure.RESULTS: According to the intention-to-treat analysis,all the 263 subjects were involved in the analysis of results. ① At the A-6G site of AGT gene, the frequencies of AA, AG and GG genotypes (P=0.014) and A and G alleles (P=0.004, OR=0.44) had significant differences between the essential hypertension group and normal control group; At the T174M site, the frequencies of CC, CT and TT genotypes (P=0.031) and A and G alleles (P=0.014, OR=0.55) were significantly different; At the G-217A site, no obvious differences were found in the GG, AG and AA genotypes (P=0.722) and G and A alleles (P=0.403, OR=0.80). ② The risk of essential hypertension in the individuals carrying AA genotype of A-6G polymorphism and CC genotype of T174M polymorphism was reduced by 57% (95%CI= 0.23-0.82, P= 0.010) and 56% (95%CI= 0.25-0.79, P= 0.006) respectively. ③ There were no significant differences in the systolic blood pressure, diastolic blood pressure and mean arterial pressure among different genotypes at the A-6G, T174M sites and G-217A sites (F=0.100- 2.911, P ＞ 0.05). CONCLUSION: The AA genope at A-6G and the CC genotype at T174M site of AGT gene may reduce the risk for the attack of essential hypertension in Chinese Hun population, and no significant correlation was found between the genotype of G-217A polymorphism and the attack of essential hypertension.

Objective To investigate the impact factors of real-time shear wave elastography ( SWE) by using the ultrasound phantoms . Methods The noduled phantoms with different densities and viscosities and background phantoms with three textures ( soft ,medium ,and hard) were prepared by using gelatin as the main ingredient . Nodule phantoms were embedded in background phantom in different depths . The elasticity ( Emax ) was measured by SWE . Factorial designed was used to evaluate the effects of various factors ,including density ,viscosity and depth of nodule phantom and texture of background phantom on Emax of nodule phantom . Binary Logistic regression was used to analysis the effects of various factors , including density ,viscosity ,diameter ,depth of nodule phantom and texture of background phantom on the window phenomenon . Results The density ,viscosity and the Emax of nodule phantoms increased as the gelatin ratio increased . The Emax of nodule phantoms in shallow position ( depth < 3 .0 cm ) were higher than those in deep position ( depth ≥ 3 .0 cm) . In hard-background phantoms ,the Emax of nodule phantoms was maximal ,soft-background phantoms was minimal . Main effects of the density ,viscosity ,depth of nodule phantoms and texture of background phantoms on Emax of nodule phantoms were different ,and all of the factors had interactive effects ( P < 0 .05 ) . The density ,viscosity ,diameter and depth of nodule phantoms were independent risk factors of the windowphenomenon ( P < 0 .05 ) . According to OR ( 23 .846 ,0 .093 ,and 0 .003 ,respectively) ,reduced density and viscosity ,or increased diameter and depth of nodule phantoms ,could increase the incidence of the window phenomenon . Conclusions The density and viscosity of self-making ultrasound phantoms can be easily and flexibly controlled .Density ,viscosity , diameter ,depth of nodule and texture of background are the impact factors of shear wave elastography .

Objective To analyze the changes of benign and malignant thyroid nodules during followup and to increase the diagnostic accuracy.Methods The ultrasonographic changes of 161 thyroid nodules confirmed by pathology were retrospectively analyzed,including size,internal components,echogenicity,margin,microcalcification,anteroposterior to transverse dimension ratio(A/T) and the relationships with thyroid capsule,and the change of cervical lymph nodes.Results Ninety-three benign thyroid nodules and 68 malignant thyroid nodules were enrolled in this study,the changes in size,internal components,microcalcification,the relationships with glandular capsule,and cervical lymph nodes were significantly different (P ＜ 0.05),while the echogenicity,margin,and A/T were not significantly different,benign nodules changed more easily in size and internal components,while malignant nodules changed more easily in microcalcification.Both the nodules broken the thyroid capsule or cervical lymph nodes exhibited malignant signs suggest probable malignancy.Conclusions Analyzing the ultrasonographic changes during follow-up contributes to identify benign and malignant thyroid nodules.

Objective To investigate the values of urine neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecular-1 (KIM-1) and interleukin-18 (IL-18) in the diagnosis of acute kidney injury (AKI) in children after cardiopulmonary by-pass (CPB). Methods Sixty-seven patients who had undergone CPB were recruited from March to June 2013 and assigned to acute kidney injury group (AKI group) or non-acute kidney injury group (non-AKI group) according to the pediatric RIFLE (pRIFLE) cri-teria. Serum and urine samples were collected from each patient at 30 min, 2 h, 4 h, 24 h, 48 h and 72 h after CPB for serum and urine creatinine, urine NGAL, KIM-1 and IL-18. All the data were evaluated by receiver operator characteristic curve (ROC) analysis and area under curve (AUC) analysis. Results Twenty-three cases (34.3%) had AKI in 67 children after CPB. Among them 15 cases were risk-stage AKI, 4 cases injury-stage AKI, 3 cases failure-stage AKI and 1 cases loss-stage AKI. The levels of urine NGAL/Ucr were higher in AKI group than those in non-AKI group at 4h, 48h and 72h after CPB (P<0.05). The cut-off value of NGAL/Ucr was 1.200 at 4 h after CPB, the sensitivity and specificity for prediction of AKI were 0.864 and 0.561, and the AUC was 0.671 (95%CI:0.537-0.804). The levels of urine KIM-1/Ucr were higher in AKI group than those in non-AKI group at 48h and 72 h after CPB (P<0.05). The cut-off value of KIM-1/Ucr was 1.162 at 24h after CPB, the sensitivity and specificity for prediction of AKI were 0.773 and 0.512, and the AUC was 0.698 (95%CI:0.563-0.834). The levels of IL-18/Ucr were higher in AKI group than those in non-AKI group at 4 h after CPB (P<0.05). The cut-off value of IL-18/Ucr was 0.04 at 4 h after CPB, the sensitivity and specificity for predici-ton of AKI were 0.773 and 0.561, and the AUC was 0.655 (95%CI:0.510-0.800). Conclusions It is indicated that urine NGAL, KIM-1 and IL-18 may have important clinical values for early prediction of AKI.

Objective To explore the value of high frequency ultrasound in differential diagnosis in dorsal thyroid (including gland dorsal or posterior) nodules.Methods Ultrasonographic features of 101 patients with ultrasonography suspected or misdiagnosed nodules in the dorsal area of the thyroid gland,which were then confirmed by pathology or hyaluronography/gastroscopy,were retrospectively analyzed.Ultrasonographic homogeneity (other nodules with similar ultrasonographic features were found in the ipsilateral gland),parenchyma homology (nodule parenchyma was continuous with glandular parenchyma) and blood homology (blood flow signals in nodules were continuous with those in glandular parenchyma) were applied as indicators for determinng thyroid nodules.Double-line sign or vascular arch sign at the edge of nodules served as an indicator for determining parathyroid nodules.Results Of the 101 cases,there were 46 thyroid nodules,35 parathyroid nodules,7 enlarged lymph nodes;6 esophageal diverticulum,6 esophageal cancer,1 cleft cyst.The determination of thyroid nodules by at least one of ultrasonographic homogeneity,parenchyma homology and blood homology showed sensitivity of 73.5 ％,specificity of 96.5 ％ and accuracy of 85.8％.In the determination of parathyroid nodules by double-line sign or vascular arch sign at the edge of nodules,sensitivity,specificity and accuracy was 54.1％,85.5 ％ and 74.5 ％,respectively.Conclusions Nodules in the dorsal area of the thyroid gland have different sources,and the understanding of corresponding characteristic ultrasonographic appearances is helpful for improving the differential diagnosis of these nodules.

Objective To observe the expression levels of kidney injury molecule-1(KIM-1) in renal tissues of ischemia-reperfusion rats,and to explore the value in the diagnosis of acute kidney injury.Methods Rats were randomly divided into two groups,control(CON) group (n=64) and acute kidney ischemia reperfusion injury (AIKI) group (n=64).Rats were sacrificed following reperfusion 2h,6h,24h,48h,72h,1 week (w),2 w,and 4 w.The changes of morphology were checked on HE staining sections under light microscope.The extent of tubulointerstitial injury was determined by Sayhan classification.The distribution and expression of KIM-1 in renal tissue were observed by immunohistochemistry and Western blotting.Serum samples were collected and serum creatinine measurement was performed at different reperfusion time points.Results (1) Compared with the CON group,the renal tubulointerstitial injury scores of AIKI group were significantly higher at all times after reperfusion (P<0.01).(2) The expression of KIM-1 was consistent with the tubulointerstitial injury.The positive correlation between KIM-1 and the tubulointerstitial injury scores was significant(r=0.887,P=0.003).(3) Compared with the CON group,serum creatinine in AIKI group was significant higher at 2h,6h,24h,48h,72h after reperfusion (P<0.05).Serum creatinine had no correlation with the damage of renal tubulointerstitial.Conclusion The expression of KIM-1 increases significantly in renal ischemia reperfusion injury,and it is consistent with the tubulointerstitial injury.Compared with serum creatinine,KIM-1 may be a more accurate biomarker of renal damage.

Objective To observe the meshed capillary pattern(CP)on the surface of colorectal lesions by narrow-band imaging system with magnifying endoscopy(NBI-ME),and to distinguish neoplasm from non-neoplasm by the change of capillary patterns.Methods A total of 144 colorectal lesions in 102 patients detected by conventional colonoscopy were evaluated by NBI-ME to observe the CP on surface,and by staining magnifying colonoscopy to observe the pit pattern.Results All lesions were resected endoscopically (129/144)or by surgery(15/144),and the pathological evaluation diagnosed 30 cases of non-neoplasm (including 20 cases of hyperproliferative polyps and 10 of inflammatory polyps)and 1 14 cases of neoplasm (including 95 cases of adenoma and 19 cases of adenocarcinoma).The diagnostic accuracy rate,sensitivity and specificity of conventional colonoscopy were 75.7%,85.1%and 40.O%,respectively,which were significantly lower than those of NBI-ME and staining magnifying colonoscopy(P＜0.005),while there was no significant difference between NBI-ME and staining magnifying colonoscopy.The CP of type Ⅰ,Ⅱ,Ⅳ and Ⅵa were totally correspondent with pit pattern of type Ⅰ,Ⅱ,Ⅳ and ⅤI. Conclusion NBI-ME findings of colorectal lesions correlated with those of staining magnifying colonoscopy.These two techniques are both helpful in differentiating colorectal neoplasms from non-neoplasms.

Objective To determine the effect of mitochondria on the protection of heat-shock proteins B1(HSPB1) from oxidative damage in rat cardiac cell.Methods HSPB1 gene-transfected rat cardiomyocytes cell line H9c2 (HSPB1 H9c2) and empty vector transfected H9c2 (control) were established,and treated by 0-1000?mol/L H_2O_2 for 2h.And then the cell morphology, mitochondrial membrane potential and endogenous reactive oxygen species (ROS) were detected. Results (1)HSPB1 inhibited the morphological changes induced by H_2O_2 markedly.(2)HSPB1 inhibited the loss of mitochondrial membrane potential induced by H_2O_2.Following the stimulation of 0,75,150,300,500,1000?mol/L H_2O_2,mitochondrial membrane potential in HSPB1 and control H9c2 cells were (10.0?0.11)vs (7.01?0.26),(9.11?0.17)vs (6.05?0.19),(7.69?0.28)vs (5.14?0.28),(6.95?0.13)vs (4.66?0.11),(6.61?0.20)vs (1.85?0.35),(6.60?0.05)vs (1.19?0.01),respectively (all P0.05).Conclusions HSPB1 protects rat cardiomyocytes cell line(H9c2) from oxidative damage,which suggests that stabilization of mitochondrial membrane potential and the decreased endogenous reactive oxygen species after oxidative stress may be involved in the protection of HSPB1 against oxidative stress in H9c2.