MircoRNA-322-5p promotes lipopolysaccharide-induced acute kidney injury mouse models and mouse primary proximal renal tubular epithelial cell injury by regulating T-box transcription factor 21/mitogen-activated protein kinase/extracellular signal-related kinase axis.

INTRODUCTION AND OBJECTIVES: Acute kidney injury (AKI) is a common devastating complication characterized by an abrupt loss of renal function. It is of great significance to explore promising biomarkers for AKI treatment. MATERIALS AND METHODS: Here, we established LPS (lipopolysaccharide)-induced AKI mice models and LPS-induced AKI mouse renal tubular epithelial cell model. The severity of AKI was determined by the levels of BUN (blood urea nitrogen) and SCr (serum creatinine), the observation of pathological section as well as the renal tubular injury score. The apoptosis was determined by the measurement of Caspase-3 and Caspase-9 activities, and cell apoptosis assays. qRT-PCR (quantitative real-time PCR) and western blot revealed that miR-322-5p (microRNA-322-5p) was up-regulated in LPS -induced AKI models while Tbx21 (T-box transcription factor 21) was down-regulated in LPS-induced AKI models. Dual-luciferase reporter and RNA pulldown assays detected the interaction of Tbx21 with miR-322-5p. RESULTS: We found that miR-322-5p was overtly over-expressed in the in vitro LPS-induced AKI model and promoted the apoptosis of AKI mouse renal tubular epithelial cells via inhibiting Tbx21, which suppressed the mitochondrial fission and cell apoptosis through MAPK/ERK (mitogen-activated protein kinase/extracellular signal-related kinase) pathway. CONCLUSIONS: We demonstrated that miR-322-5p promotes LPS-induced mouse AKI by regulating Tbx21/MAPK/ERK axis, which might provide new sights for AKI research.

Correlation Between Tic Disorders and Serum 25-Hydroxyvitamin D Levels in Chinese Children.

Objective: To explore the correlation between serum 25-hydroxyvitamin D levels and tic disorders (TDs) in Chinese children. Methods: We selected 2960 children with TD and 2665 healthy controls, aged 5-14 years, from the Department of Neurology of the Shanghai Children's Hospital. Serum 25-hydroxyvitamin D levels and degrees of vitamin D deficiency were compared between patients with TD and healthy children. Results: The mean serum 25-hydroxyvitamin D level in the TD group was significantly lower than that in the control group (P < 0.001). The proportion of patients with 25-hydroxyvitamin D deficiency in the TD group was significantly higher than that in the control group. However, there was no correlation between 25-hydroxyvitamin D deficiency and the severity of TD. In addition, for age-wise comparison, mean levels of 25-hydroxyvitamin D and its deficiency in the TD group were the most significant in children over 9 years of age. Conclusion: There is a correlation between 25-hydroxyvitamin D deficiency and TD in Chinese children, but not between 25-hydroxyvitamin D deficiency and the severity of TD. There was a correlation between age and deficiency of 25-hydroxyvitamin D; this deficiency was most pronounced among those over the age of 9 years.

Clinical Study of 8 Cases of CHD2 Gene Mutation-Related Neurological Diseases and Their Mechanisms.

Background: The chromodomain helicase DNA-binding protein 2 (CHD2) gene, is an ATPase and part of the CHD family of chromatin remodelers. Mutations in the CHD2 gene are inherited in an autosomal-dominant manner and can lead to intellectual disability, epilepsy, and autism. We investigated the clinical characteristics of CHD2-related conditions and their possible pathogenesis. Methods: We collected and analysed the clinical data of patients that were identified as having CHD2 mutations. Genetic testing was performed using targeted sequencing or whole-exome sequencing. We analysed the expression of CHD2 and repressor element 1-silencing transcription factor (REST) in blood samples using quantitative PCR and the conservation of the mutations. The CHD2 mutations we identified were compared with the known mutations reported in the CHD2-related literature. Results: Eight patients with CHD2 gene mutations were analysed. Six mutations were identified; four were unreported previously (c.670C>T; c.4012A>C; c.2416dup; c.1727-1728insAT), and two were known mutations: c.5035C>T (two cases) and c.4173dup (two cases). Among these mutations, seven were de novo mutations, and one could not be determined because the parents refused genetic testing. The clinical manifestations included mild or severe intellectual disability, epilepsy, and behavioural abnormalities. Quantitative PCR showed that the CHD2 gene expression levels among the patients, parents, and the controls were not significantly different. The levels of REST gene expression in the patients were significantly higher than those of the controls; thus, mutation of the CHD2 gene led to an increase in the expression level of the REST gene. The mutations reported were all located in conserved positions in different species. Among the various medications administered for treatment, valproate showed the best results for the treatment of epilepsy caused by CHD2 gene mutation. Conclusion: Mutation in CHD2 did not lead to a significant decrease in its expression level, indicating that the clinical phenotype was unrelated to its expression level, and the mutant protein may retain some function. Most of the mutations relatively stable. In addition, the clinical manifestations from the same mutation in the CHD2 gene were different among the known cases; this may be related to the regulation of REST or other regulatory factors.

Serum albumin and albuminuria predict the progression of chronic kidney disease in patients with newly diagnosed type 2 diabetes: a retrospective study.

BACKGROUND: Diabetes-related kidney disease is associated with end-stage renal disease and a high mortality rate. However, data on risk factors associated with kidney disease in patients with newly diagnosed type 2 diabetes mellitus (DM) remains insufficient. The aim of the present study was to identify the risk factors significantly associated with chronic kidney disease progression in patients with newly diagnosed type 2 DM. METHODS: We reviewed a total of 254 consecutive patients who were newly diagnosed with type 2 diabetes at Nanjing First Hospital from January to December 2014. They were observed for two years, and baseline and biochemical variables were used to identify significant predictors of kidney failure progression. Kidney failure progression was defined as a ≥ 30% increase in serum creatine level. RESULTS: The mean age of patients was 58.96 years, 37.4% were women, and 57.1% had hypertension. Kidney function progressed in 40 patients (15.75%). Multivariable logistic regression analyses showed that serum albumin (p = 0.015) and microalbuminuria (p < 0.001) were associated with kidney failure progression in patients with newly diagnosed type 2 DM. Those with lower estimated glomerular filtration rate (eGFR; 30-60 ml/min/1.73 m2) at baseline had lower serum albumin levels compared to those of patients with higher eGFR. The albuminuria levels were higher in patients with lower eGFR than in those with eGFR ≥ 90 ml/min/1.73 m2. Receiver operating characteristic curve analysis showed that the area under the curve was 0.754 (95% CI [0.670-0. 0.837]). CONCLUSIONS: The overall rate of chronic kidney disease progression is relatively high, and low serum albumin and high albuminuria levels are associated with kidney failure progression in newly diagnosed diabetic patients.

The clinical characteristics and prognosis of ABPA are closely related to the mucus plugs in central bronchiectasis.

INTRODUCTION: The characteristics of Allergic Bronchopulmonary Aspergillosis (ABPA) based on its radiological classification is still unclear. OBJECTIVES: To investigate the clinical significances of ABPA patients with central bronchiectasis (ABPA-CB) by different radiological classifications of mucus plugs. METHODS: ABPA-CB patients from a pulmonary hospital between 2008 and 2015 were retrospectively included and analysed. According to the chest imaging in their first visit to physician, the ABPA-CB patients were divided into two groups based on the presence of high-attenuation mucus (HAM) or low-attenuation mucus (LAM). The primary endpoint was ABPA relapse within 1 year since the glucocorticoid withdrawal. The relationship between the imaging findings and the clinical prognosis was illuminated. RESULTS: A total of 125 ABPA patients were analysed in this study. Compared to the LAM group, the HAM group presented higher blood eosinophil cells counts, higher rates of Aspergillus detection isolated in sputum and expectoration of brownish-black mucus plugs, more affected lobes and segments, poorer pulmonary function and higher rate of relapse. CONCLUSIONS: The clinical characteristics and prognosis of ABPA-CB patients are closely related to its radiological phenotype of mucus plugs in the central bronchiectasis. Clinicians should promote a diversity of personalized treatments for different patients with different radiological characteristics.

Bioinformatics Analysis of Genes and Pathways of CD11b+/Ly6Cintermediate Macrophages after Renal Ischemia-Reperfusion Injury.

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), which could induce the poor prognosis. The purpose of this study was to characterize the molecular mechanism of the functional changes of CDllb+/Ly6Cintermediate macrophages after renal IRI. The gene expression profiles of CDllb+/Ly6Cintermcdiate macrophages of the sham surgery mice, and the mice 4 h, 24 h and 9 days after renal IRI were downloaded from the Gene Expression Omnibus database. Analysis of mRNA expression profiles was conducted to identify differentially expressed genes (DEGs), biological processes and pathways by the series test of cluster. Protein-protein interaction network was constructed and analysed to discover the key genes. A total of 6738 DEGs were identified and assigned to 20 model profiles. DEGs in profile 13 were one of the predominant expression profiles, which are involved in immune cell chemotaxis and proliferation. Signet analysis showed that Atp5al, Atp5o, Cox4i, Cdc42, Rac2 and Nhp2 were the key genes involved in oxidation-reduction, apoptosis, migration, M1-M2 differentiation, and proliferation of macrophages. RPS18 may be an appreciate reference gene as it was stable in macrophages. The identified DEGs and their enriched pathways investigate factors that may participate in the functional changes of CD 1lb+Ly6Cintermediate macrophages after renal IRI. Moreover, the vital gene Nhp2 may involve the polarization of macrophages, which may be a new target to affect the process of AKI.

Reassessment of Acute Kidney Injury after Cardiac Surgery: A Retrospective Study.

Objective To evaluate the incidence, risk, or protective factors of acute kidney injury (AKI) in patients after cardiac surgery based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Methods A retrospective analysis of 2,575 patients undergoing their first documented cardiac surgery with cardiopulmonary bypass (CPB) was conducted. Perioperative variables were collected and analyzed. Univariate and multiple logistic regression models were used for determining the association between the development of AKI and risk factors. Multiple Cox-proportional hazards modeling was performed to evaluate the impact of AKI on the mortality in the intensive care unit and hospital length of stay. Results Of 2,575 patients, 931 (36%) developed AKI. A total of 30 (1.2%) patients required renal replacement therapy. In the multivariate analysis, mechanical ventilation duration (OR1.446, 95% CI 1.195-1.749, p<0.001), CPB duration of ≥110 min (OR 1.314, 95% CI 1.072-1.611, p=0.009), erythrocytes transfusion (OR 1.078, 95% CI 1.050-1.106, p<0.001), and postoperative body temperature greater than 38°C within 3 days (OR 1.234, 95% CI 1.018-1.496, p=0.032) were independent risk factors for CSA-AKI, while ulinastatin use was associated with a reduced incidence of CSA-AKI (OR 0.694, 95% CI 0.557-0.881, p=0.006). CSA-AKI was significantly associated with in-hospital mortality (adjusted HR: 2.218, 95% CI 1.161-4.238, p=0.016), especially in patients needing renal replacement therapy (adjusted HR: 18.683, 95% CI 8.579-40.684, p<0.001). Conclusion Mechanical ventilation duration, erythrocytes transfusion, and postoperative body temperature above 38°C within 3 days were considered independent risk factors for CSA-AKI. The use of ulinastatin was associated with a reduced incidence of CSA-AKI.

Ulinastatin administration is associated with a lower incidence of acute kidney injury after cardiac surgery: a propensity score matched study.

BACKGROUND: Systemic inflammation is involved in the development of acute kidney injury (AKI) after cardiac surgery with cardiopulmonary bypass (CPB). Ulinastatin, a urinary trypsin inhibitor (UTI), possesses a variety of anti-inflammatory effects. Therefore, we hypothesized that the administration of ulinastatin would reduce the occurrence of AKI in patients undergoing cardiac surgery with CPB. METHODS: A retrospective propensity score matched analysis was used to evaluate the effect of ulinastatin on the development of AKI in patients undergoing first documented cardiac surgery with CPB between January 2008 and December 2012 in our hospital. Multiple logistic regression models were also employed to identify the association between UTI administration and development of AKI. RESULTS: A total of 2072 patients who underwent cardiac surgery with CPB met the inclusion criteria. Before propensity score matching, variables such as age, baseline creatinine, CPB duration, red blood cells transfused, and hematocrit were statistically different between the ulinastatin (UTI) group and the control group. On the basis of propensity scores, 409 UTI patients were successfully matched to the 409 patients from among those 1663 patients without UTI administration. After propensity score matching, no statistically significant differences in the baseline characteristics were found between the UTI group and the control group. The propensity score matched cohort analysis revealed that AKI and the need for renal replacement therapy occurred more frequently in the control group than in the UTI group (40.83% vs. 30.32%, P = 0.002; 2.44% vs. 0.49%, P = 0.02, respectively). However, there were no significant differences in mortality, length of intensive care unit stay, and length of hospital stay between the UTI group and the control group. Using multivariate logistic regression analysis, we found ulinastatin played a protective role in the development of AKI after cardiac surgery (odds ratio 0.71, 95% confidence interval 0.56-0.90, P = 0.005). CONCLUSIONS: This study shows that ulinastatin was associated with a lower incidence of AKI after cardiac surgery, suggesting that the administration of ulinastatin may be favorable for those patients undergoing cardiac surgery with CPB.

Clinical-psychological characteristics of refractory globus patients in China.

BACKGROUND: Refractory globus is not rare in clinical practice, but little research about it. AIMS: To investigate the clinical-psychological characteristics of patients with refractory globus. METHODS: Six hundred and nineteen globus patients were divided into the refractory globus group (n=149) and the non-refractory globus group (n=470). All subjects completed the following questionnaires: demographic characteristics, medical information, Hamilton Rating Scale of Anxiety/Depression, Pittsburgh Sleep Quality Index, Glasgow Edinburgh Throat Scale, and 36-item Short Form Health Survey. RESULTS: No significantly differences were found in demographic characteristics between the two groups, but the refractory globus group had longer disease duration and more serious symptoms. Sought healthcare more frequently but still had poorer quality of life than did the non-refractory globus group. Compared with the non-refractory globus group, the refractory globus group also had higher percentages of anxiety, depression, and sleep disorders. Positive correlations were observed between the severity of globus symptoms and HAMA, HAMD, and PSQI scores. CONCLUSIONS: Refractory globus is not rare in clinical practice and should receive more attention from patients and doctors because of its severe symptoms, long disease duration, poor quality of life, and accompanied by psychological disorders and sleep disorders.

Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice.

BACKGROUND: Uncoupling protein 2 (UCP2) is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy. METHODS: Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC), and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip) or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice. RESULTS: TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls). ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice. CONCLUSIONS: Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.

Clinical diagnostic performance of the simultaneous amplification and testing methods for detection of the Mycobacterium tuberculosis complex for smear-negative or sputum-scarce pulmonary tuberculosis in China.

BACKGROUND: Early detection of pulmonary tuberculosis (PTB) is a big challenge in smear negative and sputum scarce patients in China. Simultaneous amplification and testing methods for detection of the Mycobacterium tuberculosis (MTB) complex (SAT-TB assay) is a novel molecular technique established in our hospital. This method has a high sensitivity and specificity in the lab. In this study, the clinical diagnostic performance of this method in smear-negative or sputum-scarce PTB suspects was investigated and evaluated. METHODS: Two hundred smear negative and 80 sputum-scarce patients were recruited in this study. Samples that included sputum or bronchial washing fluid were collected and sent for both bacteria culture and SAT-TB assay. Diagnosis for these patients was based on the comprehensive evaluation of chestX- ray/CT study, histology examination, lab results, and treatment response. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each diagnostic test were investigated and calculated using confirmed tuberculosis (TB) and non-TB cases. The time required for detection of MTB was also measured for each method. RESULTS: Ninety-two patients (33%) were diagnosed as definitive TB, 112 patients (40%) were probable PTB, and 76 (27%) were non-TB. The sensitivity, specificity, PPV, and NPV of SAT-TB in smear-negative PTB suspects were 93% (95% CI, 84%-98%), 98% (95% CI, 90%-100%), 98% (95% CI, 91%-100%), and 93% (95% CI, 83%-98%). In sputum scarce PTB suspects, the sensitivity, specificity, PPV, and NPV of the SAT-TB assay on bronchial washing fluids were 90% (95% CI, 74%-98%), 100% (95% CI, 85%-100%), 100% (95% CI, 88%-100%), and 88% (95% CI, 69%-97%). The accuracy of the SAT-TB assay is consistent with the bacteria culture assay. The median time required for detecting MTB in the SAT-TB assay was 0.5 day, which was much faster than bacteria culture (28 days). CONCLUSIONS: The SAT-TB assay is a fast and accurate method for the detection of MTB. It can be widely applied in the clinic and be an asset in early detection and management of PTB suspects, especially in those patients who are smear negative or sputum scarce.