Objective To investigate the relationship between the steroid-sensitive nephrotic syndrome(SSNS) and interleukin-18(IL-18) and to approach the inhibitive role of dexamethasone(DEX) on expression of IL-18 of peripheral blood mononuclear cells(PBMC) in children with SSNS in vitro.Methods IL-18 levels of serum, urine and supernatants of PBMC cultured in vitro were measured by enzyme linked immunosorbent assay(ELISA) in 23 children with SSNS who were either before or after treatment. Fifteen age-matched healthy children served as normal control group, and another 18 children with respiratory infections as infectious control group.Results There were signi-ficant differences of IL-18 in serum and urine before and after treatment in children with SSNS (t=15.072,16.149 Pa

OBJECTIVENephrotic syndrome (NS) is characterized by marked urinary excretion of albumin and other intermediated-size plasma proteins such as transferrin. The aim of this study was to determine the changes of serum iron and transferrin and the relationship between the serum and urinary transferrin.

METHODSThe indexes related to iron metabolism, including serum iron, ferritin, transferrin, total iron-binding capacity, transferrin saturation and hematological parameters (Hb, MCV, MCH), and urinary transferrin were measured in 37 children with NS before treatment and at the remission stage. Thirty-five age-matched healthy children served as controls.

RESULTSSerum iron levels (18.8 +/- 3.8 micromol/L) in NS patients before treatment were significantly lower than in the healthy controls (22.2 +/-3.8 micromol/L) and those measured at the remission stage (21.0 +/- 3.5 micromol/L) (P < 0.01). Serum transferrin levels in NS patients before therapy (1.9 +/- 0.3 g/L) also decreased compared with those in the healthy controls (3.1 +/- 0.5 g/L) and those measured at the remission stage (2.9 +/- 0.6 g/L) (P < 0.01). In contrast, serum total iron-binding capacity and transferrin saturation were noticeably higher in NS patients before treatment than those in the healthy controls (total iron-binding capacity 56.4 +/- 9.2 micromol/L vs 50.7 +/- 6.8 micromol, P < 0.01; transferrin saturation 55.7 +/- 9.2 % vs 46.4 +/- 8.2%, P < 0.01) and were also higher than those measured at the remission stage (51.9 +/-7.7 micromol/L and 47.4 +/- 13.3%) (P < 0.01). Serum transferrin positively correlated to serum albumin (r = 0.609, P < 0.01) and negatively correlated to urinary transferrin (r = -0.550, P < 0.01) in NS patients before treatment.

CONCLUSIONSSerum iron and transferrin levels markedly decreased in NS patients, which may be partially related to the urinary loss of transferrin.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Iron ; blood ; Male ; Nephrotic Syndrome ; blood ; Transferrin ; analysis ; urine

OBJECTIVETo investigate the cell-killing effect of adenovirus-mediated TK-ganciclovir (GCV) gene therapy in combination with tumor necrosis factor-alpha (TNF-alpha) against murine bladder carcinoma cells in vitro.

METHODSMurine bladder carcinoma MB49 cells were transfected with the adenoviral vector containing TK gene and green fluorescent protein (GFP) gene. The transfection efficiency was observed and the TK gene expression in the transfected cells was detected by RT-PCR. The survival rate of MB49 cells in response to TNF-alpha treatment and that of the TK gene-transfected cells after treatment with GCV and GCV+TNF-alpha were determined by MTT assay. The apoptosis of the cells after the treatments was analyzed by flow cytometry.

RESULTSIn cells transfected with TK gene, the cell inhibition rate increased gradually with the increment of GCV and TNF-alpha concentration. GCV in combination with TNF-alpha resulted in significantly increased killing efficiency of the cells as compared with GCV or TNF-alpha treatment alone, and the effect of the combined treatment was enhanced as the TNF-alpha concentration increased. GCV treatment (50 microg/ml) alone produced a cell killing rate of (24.39-/+1.10)%, and when combined with 5 microg/ml TNF-alpha, the rate was increased to (40.05-/+0.97) %, and further to (65.47-/+0.67) % when TNF-alpha concentration increased to 20 microg/ml. Flow cytometry revealed obvious apoptosis of the cells 8 h after treatments with TK/GCV, TNF-alpha, or TK/GCV+TNF-alpha, and the combined treatment resulted in the highest cell apoptotic rate.

CONCLUSIONTK/GCV in combination with TNF-alpha can enhance the effect of suicide gene therapy against murine bladder carcinoma cells and effectively induce apoptosis of the cells.

Adenoviridae ; genetics ; Animals ; Antiviral Agents ; pharmacology ; Cell Line, Tumor ; Cell Survival ; drug effects ; Ganciclovir ; metabolism ; pharmacology ; Genetic Therapy ; methods ; Green Fluorescent Proteins ; genetics ; metabolism ; Mice ; Reverse Transcriptase Polymerase Chain Reaction ; Thymidine Kinase ; genetics ; metabolism ; Transfection ; Tumor Necrosis Factor-alpha ; pharmacology ; Urinary Bladder Neoplasms ; genetics ; metabolism ; pathology

Objective To ohserve the rat myocardial damage induced by citreoviridin(CIT)in the status of combined selenium and protein deficiency.Methods According to 2×2 factorial design,forty 4-week-old healthy Wistar rats were randomly divided into four groups.i.e.combined selenium and protein adequate with no CIT and with some CIT groups(Se+Pro+CIT-.Se+Pro+CiT+),combined selenium and protein deficiency with no CIT and with some CIT groups(Se-Pro-CIT-,Se-Pro-CIT+).The numbers of male and female were fifty-fifty.Theserats were fed with combined selenium and protein adequate and combined selenium and protein deficiency fodder until the 16th week. Cardiac toxicity of CIT was evaluated by general state of health, heart weight index, myocardial pathological change, the levels of selenium and the activities of glutathion peroxidase (GSH-Px) and creatine kinase (CK) in serum, and the activity of superoxide dismutase(SOD) of myocardium. Results The interaction effects of combined selenium and protein deficiency and adequate CIT on body weight, serum levels of selenium and albumin, heart weight index, the activities of CK and GSH-Px in serum and SOD of myocardium were statistically not significant(F= 0.000, 1.210, 0.625, 0.981, 2.785, 0.074, 0.001, all P> 0.05). The main effects of combined selenium and protein on the levels of serum selenium and albumin, heart weight index and the activity of GSH-Px in serum were statistically significant(F = 507.698, 87.734, 4.201, 109.389, all P < 0.05). The main effects of CIT on body weight, the levels of serum selenium and albumin, heart weight index and the activity of CK in serum were statistically significant(F = 10.929, 4.371, 26.108, 24.844, 4.439, all P < 0.05). The mean levels of serum selenium of Se-Pro- groups [(70.4 ± 40.0), (87.7 ± 59.6 )μg/L] were lower than those of Se+Pro+ groups [(446.1 ± 74.8),(502.1 ± 39.2)μg/L, all P < 0.05]. The mean levels of serum albumin of Se-Pro- groups [(34.36 ± 1.28 ), (33.38 ±2.48)g/L] were lower than those of Se+Pro+ groups[(40.69 ± 1.30), (38.71 ± 2.15)g/L, all P < 0.05]. The mean levels of heart weight index of CIT+ groups[(4.14 ± 0.36) × 10-3, (4.39 ± 0.53) x 10-3] were higher than those of CIT-groups[(3.56 ± 0.26) x 10-3, (3.80 ± 0.28) x 10-3, all P < 0.05] respectively at the same levels of selenium and protein. The mean levels of CK in serum of Se-Pro-CIT+ group[(2.54 ± 0.56)kU/L] was lower than that of Se-Pro-CIT- group [(3.37 ± 0.67 )kU/L, P < 0.05]. The mean levels of activity of GSH-Px in serum of Se-Progroups[(408.1 ± 412.6), (510.5 ± 392.0)U/L] were lower than those of Se+Pro+ groups[(1667.8 ± 102.2),(1731.5 ± 144.4)U/L, all P < 0.05]. In Se+Pro+CIT+ group, there was part of intercalary disc of cardiac myocytes fragmented;the conjunctions between myoeytes were broken;in some region, cardiac myocytes became edematous,even dissolved. In Se-Pro-CIT- group, the change of cardiac myocytes membrane structures was not obvious;filament structure was disappeared around nucleus;deposition of mass floccule could be seen. In Se-Pro-CIT+ group,the structure of sarcomeres was not obvious;mitochondrial cristae was loosened;cavities in myocytes could be seen occasionally;there were lots of disseminated sareoplasmic reticulum extending. Conclusions .CIT is the main risk factor in inducing myocardial damage. The deficiency of combined selenium and protein can aggravate the damage,but its independent pathogenic effect is weak.

Objective: To investigate the relationship between P27，P53 and PCNA expression in human gastric carcinoma tissues and clinicopathological parameters. Methods: The expression of P27，P53 and PCNA in 62 human gastric carcinoma tissues was examined with immunohistochemistry SP method. Results: Positive rates of P27，P53 and PCNA expression were 37.1％, 40.4%，83.9％. P27 expression was related with Bormann type, infiltrative depth, lymph node and distant metastasis and clinical stage. P53 expression was related with sex of patients, distant metastasis and clinical stage. PCNA expression was related with age of patients and infiltrative depth of tumor. P27 positive expression group was higher than negative group as to 5-year survival. P27 expression was in reverse relation with PCNA expression. Conclusion: The expression of P27, P53 and PCNA may be regarded as an important marker in judging malignant degree of gastric carcinoma,distant metastasis and prognosis.

Objective To explore the virulence of enterovirus 71 from infected children in neonatal mice. Methods Three strains of EV71 were isolated from the mild, severe and dead patients. Symptoms, weight and death of mice were recorded throughout 14 days. The mice were sacrificed on the first, third, fifth, seventh and ninth days post infection to gain the tissue virus load including the liver, spleen, lung, intestine, brain and muscle tissue which were used to detect the virus tilter by real-time RT-QPCR, and pathological lesions using HE staining. Results As to the severity of symptoms, no significant difference was found between the severe and mild groups (P＝0. 693), which were more serious than that of the fatal group. (P＝0. 000 ＜ 0. 05/6, P＝0. 000 ＜ 0. 05/6). The survival rate of the mice with mild, severe and fatal virus infection was 77. 2%, 81. 7% and 97. 8%, respectively, and there was a significant difference among the three groups (P＝0. 0010 ＜ 0. 05, P＝0. 001 ＜ 0. 05, P＝0. 0004 ＜ 0. 05). Lung hemorrhage of the mild group was the most serious, and there were no significant differences in pathological lesions of the brain, muscle, spleen and intestine. Virus titer in the liver and muscle was higher than the other tissues and that in mild group of different tissues tended to be higher than the other two groups. Conclusions Neonatal mice infected with the mild strain of enterovirus 71 presents heaviest symptoms, which are not consistent with the outcomes of humans. It is considered to be related to the virus gene, host and other factors.

Background: Lateral compartmental osteoarthritis (LCOA), a major complication after medial mobile?bearing unicompartmental knee arthroplasty (UKA), is highly associated with the increased stress of the lateral compartment. This study aimed to analyze the effects on the stress and load distribution of the lateral compartment induced by lower limb alignment and coronal inclination of the tibial component in UKA through a finite element analysis. Methods: Eight three?dimensional models were constructed based on a validated model for analyzing the biomechanical effects of implantation parameters on the lateral compartment after medial Oxford UKA: postoperative lower limb alignment of 3° valgus, neutral and 3° varus, and the inclination of tibial components placed in 4°, 2° valgus, square, and 2° and 4° varus. The contact stress of femoral and tibial cartilage and load distribution were calculated for all models. Results: In the 3° valgus lower limb alignment model, the contact stress of femoral (3.38 MPa) and tibial (3.50 MPa) cartilage as well as load percentage (45.78%) was highest compared to any other model, and was increased by 36.75%, 47.70%, and 27.63%, respectively when compared to 3° varus. In the condition of a neutral position, the outcome was comparable for the different tibial tray inclination models. The inclination did not greatly affect the lateral compartmental stress and load distribution. Conclusions: This study suggested that slightly varus (undercorrection) lower limb alignment might be a way to prevent LCOAin medial mobile?bearing UKA. However, the inclination (4° varus to 4° valgus) of the tibial component in the coronal plane would not be a risk factor for LCOA in neutral position.

Objective: To examine the association of hypertension onset age with diabetes, so as to provide insights into reducing the the risk of cardiovascular events. Methods: Permanent residents aged 35 to 75 years were selected through the program of early screening and comprehensive intervention for the high-risk cardiovascular disease population in Changning District and Baoshan District, Shanghai Municipality from 2016 to 2020. Demographic information, disease history, hypertension onset age, blood pressure and fasting blood glucose were collected through questionnaire surveys, physical examination and laboratory tests. The residents were divided into four groups based on the onset age of hypertension: <45, 45-<55, 55-<65 and ≥65 years old, and the residents with normal blood pressure were selected as control. The association of hypertension onset age with prediabetes and diabetes were identified using a multivariable logistic regression model. Results: A total of 25 228 residents were recruited, including 8 753 males (34.70%) and 16 475 females (65.30%). The prevalence of hypertension was 43.80%. There were 1 779, 3 274, 3 781 and 2 217 cases with hypertension onset age of <45, 45-<55, 55-<65 and ≥65 years old, respectively, and 14 177 residents with normal blood pressure. The prevalence of prediabetes and diabetes were 24.01% and 11.29%, respectively. Multivariable logistic regression analysis showed that after adjusting for confounding factors such as gender, marital status and educational level, compared with the normal blood pressure group, the risk of prediabetes was higher in the hypertension onset age groups of <45 (OR=1.345, 95%CI: 1.164-1.553), 45-<55 (OR=1.365, 95%CI: 1.212-1.536) and 55-<65 years old (OR=1.376, 95%CI: 1.239-1.527), and the risk of diabetes was higher in the hypertension onset age groups of <45 (OR=2.302, 95%CI: 1.906-2.775), 45-<55 (OR=2.349, 95%CI: 2.016-2.734), 55-<65 (OR=1.909, 95%CI: 1.667-2.184) and ≥65 years old (OR=1.315, 95%CI: 1.131-1.526). Conclusion There are statistically significant associations between hypertension onset age with prediabetes and diabetes.

Accurate identification of compound-protein interactions (CPIs) in silico may deepen our understanding of the underlying mechanisms of drug action and thus remarkably facilitate drug discovery and development. Conventional similarity-or docking-based computational methods for predicting CPIs rarely exploit latent features from currently available large-scale unlabeled com-pound and protein data and often limit their usage to relatively small-scale datasets. In the present study, we propose DeepCPI, a novel general and scalable computational framework that combines effective feature embedding (a technique of representation learning) with powerful deep learning methods to accurately predict CPIs at a large scale. DeepCPI automatically learns the implicit yet expressive low-dimensional features of compounds and proteins from a massive amount of unla-beled data. Evaluations of the measured CPIs in large-scale databases, such as ChEMBL and Bind-ingDB, as well as of the known drug-target interactions from DrugBank, demonstrated the superior predictive performance of DeepCPI. Furthermore, several interactions among small-molecule compounds and three G protein-coupled receptor targets (glucagon-like peptide-1 recep-tor, glucagon receptor, and vasoactive intestinal peptide receptor) predicted using DeepCPI were experimentally validated. The present study suggests that DeepCPI is a useful and powerful tool for drug discovery and repositioning. The source code of DeepCPI can be downloaded from https://github.com/FangpingWan/DeepCPI.

OBJECTIVETo study the expression of SUMO-modified CCAAT enhancer binding protein α (C/EBPα) in preterm rat model of bronchopulmonary dysplasisa (BPD) induced by hyperoxia exposure and its role.

METHODSEighteen preterm rats were randomly divided into an air group and a hyperoxia group (n=9 each). The model of BPD was prepared in preterm rats exposed to hyperoxia. The rats from the two groups were sacrificed on postnatal days 4, 7 and 14 respectively (3 rats at each time) and lung tissues were harvested. Periodic acid-Schiff (PAS) staining was used to observe the differentiation of rat lung tissues. Ki67 expression was detected by immunohistochemistry. Western blot was used to measure the protein expression of small ubiquitin-related modifier-1(SUMO1) and C/EBPα. A co-immunoprecipitation assay was performed to measure the protein expression of SUMO-modified C/EBPα.

RESULTSCompared with the air group, the hyperoxia group showed a decreased glycogen content in the lung tissue on postnatal day 4, and an increased content on postnatal days 7 and 14. Over the time of hyperoxia exposure, the hyperoxia group showed an increased expression of Ki67 in the lung tissue compared with the air group at all time points. Compared with the air group, the protein expression of C/EBPα increased on postnatal day 4 and decreased on postnatal days 7 and 14 in the hyperoxia group (P<0.05). The hyperoxia group had significantly upregulated expression of SUMO1 and SUMO-modified C/EBPα compared with the air group at all time points (P<0.05). In the hyperoxia group, the protein expression of SUMO-modified C/EBPα was positively correlated with the glycogen content (r=0.529, P<0.05) and the expression of Ki67 (r=0.671, P<0.05).

CONCLUSIONSHyperoxia may induce over-proliferation and differentiation disorders of alveolar epithelial cells in preterm rat model of BPD, possibly through an increased expression of SUMO-modified C/EBP&alpha.

Animals ; Animals, Newborn ; Bronchopulmonary Dysplasia ; etiology ; metabolism ; pathology ; CCAAT-Enhancer-Binding Protein-alpha ; metabolism ; Cell Proliferation ; Disease Models, Animal ; Hyperoxia ; complications ; pathology ; Ki-67 Antigen ; analysis ; Pulmonary Alveoli ; pathology ; Rats ; Rats, Sprague-Dawley ; Sumoylation