ABSTRACT
BACKGROUND: The molecular mechanisms of osteosarcoma (OS) are complex. In this study, we focused on the functions of melanoma cell adhesion molecule (MCAM), methyltransferase 3 (METTL3) and insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) in OS development. METHODS: qRT-PCR assay and western blot assay were performed to determine mRNA and protein expression of MCAM, METTL3, IGF2BP1 and YY1. MTT assay and colony formation assay were conducted to assess cell proliferation. Cell apoptosis, invasion and migration were evaluated by flow cytometry analysis, transwell assay and wound-healing assay, respectively. Methylated RNA Immunoprecipitation (MeRIP), dual-luciferase reporter, Co-IP, RIP and ChIP assays were performed to analyze the relationships of MCAM, METTL3, IGF2BP1 and YY1. The functions of METTL3 and MCAM in tumor growth were explored through in vivo experiments. RESULTS: MCAM was upregulated in OS, and MCAM overexpression promoted OS cell growth, invasion and migration and inhibited apoptosis. METTL3 and IGF2BP1 were demonstrated to mediate the m6A methylation of MCAM. Functionally, METTL3 or IGF2BP1 silencing inhibited OS cell progression, while MCAM overexpression ameliorated the effects. Transcription factor YY1 promoted the transcription level of METTL3 and regulated METTL3 expression in OS cells. Additionally, METTL3 deficiency suppressed tumor growth in vivo, while MCAM overexpression abated the effect. CONCLUSION: YY1/METTL3/IGF2BP1/MCAM axis aggravated OS development, which might provide novel therapy targets for OS.
Subject(s)
Adenosine , Methyltransferases , Osteosarcoma , RNA-Binding Proteins , Osteosarcoma/genetics , Osteosarcoma/metabolism , Methyltransferases/metabolism , Methyltransferases/genetics , Humans , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Adenosine/analogs & derivatives , Adenosine/metabolism , Adenosine/genetics , Cell Line, Tumor , Animals , Mice , Cell Proliferation , Bone Neoplasms/genetics , Bone Neoplasms/metabolism , Disease Progression , Mice, Nude , Apoptosis , Cell Movement , Gene Expression Regulation, NeoplasticABSTRACT
Objective: The aim of this study was to identify the risk factors for postoperative adverse events in children with duplex kidney undergoing upper pole heminephrectomy. Methods: We collected clinical data from pediatric patients with duplex kidney who underwent upper pole heminephrectomy. Based on the presence or absence of postoperative adverse events, the patients were divided into two groups: an adverse events group (n = 16) and a non- adverse events group (n = 37), using multivariate logistic regression analysis to screen for independent risk factors for postoperative adverse events. Results: Through univariate and multivariate analysis, we found that the presence of upper renal ureterocele (P = 0.042, OR = 7.116, 95% CI 1.073-47.172), as well as the presence of accessory renal artery type (P = 0.016, OR = 10.639, 95% CI 1.551-72.978) and other types (P = 0.039, OR = 3.644, 95% CI 0.351-37.836) as the upper kidney's blood supply artery increase the risk of postoperative adverse events, with these differences being statistically significant. Conclusions: In pediatric patients with duplex kidney undergoing upper pole heminephrectomy, the presence of upper renal ureterocele and the presence of accessory renal artery type and other types as the upper kidney's blood supply artery are independent risk factors for postoperative adverse events.
ABSTRACT
Many studies have shown that ingestion of the T-2 toxin is harmful to articular cartilage. However, the mechanisms underlying damaged articular cartilage induced by T-2 toxin have not been elucidated. Twenty-four SD rats were randomly divided into T-2 toxin and control groups. In the control group, the 12 rats were administered 4% absolute ethanol by gavage, and in the T-2 toxin group, the 12 rats were administered T-2 toxin (100 ng/g, BW/day) by gavage. After the rats were sacrificed, the knee joints were collected, and RNA was extracted using TRIzol reagent for RNA sequencing (RNA-seq). Differentially expressed mRNA was identified based on p < 0.05 and | log2 (fold change) | > 1. The T-2 toxin-related genes were obtained from the GeneCards database. An online tool (https://www.bioinformatics.com.cn) was used for enrichment analysis. Hematoxylin and eosin (H&E) staining was used to observe damaged articular cartilage, and immunohistochemical (IHC) staining was used to validate differentially expressed proteins. The H&E staining shows the number of cells decreased significantly, and the arrangement of chondrocytes became disordered in the T-2 toxin group. RNA-seq analysis identified 195 upregulated and 89 downregulated mRNAs in the T-2 toxin group. The top immune-related biological processes (Gene Ontology) were regulation of hormone secretion, regulation of peptide hormone secretion, and regulation of transcription involved in cell fate commitment. KEGG pathway enrichment analysis revealed that the IL-17 and tumor necrosis factor signaling pathways were significantly expressed, and the IL-17 signaling pathway was also identified in the enrichment analysis of T-2 toxin-related genes. Also, Mmp3, Tnf, Mapk10, Ccl11, Creb5, Cxcl2, and Cebpb were significantly enriched in the two pathways. The immunohistochemical staining showed that the levels of Mmp3 and Tnf proteins were significantly increased in the T-2 toxin group, which was consistent with the RNA-seq results. This study revealed the critical roles of IL-17 and TNF signaling pathways in damaged cartilage induced by T-2 toxin.
ABSTRACT
OBJECTIVE: Based on the eighth TNM staging system, T3a renal cell carcinoma (RCC) is identified as an anatomical extrarenal invasion and does not consider the size of the tumor; however, it may not fully predict the prognosis of the patient. The objective of this study was to evaluate the prognostic value of tumor size effects on prognosis in T3a RCC and propose an alternative tumor stage system combined with T1-2. METHODS: Data relating to T1-3aN0M0 RCC (n = 49586) were obtained from the Surveillance, Epidemiology, and End Results database (2004-2015). Survival analyses were conducted by Cox regression and Fine and Gray regression. Harrell's concordance index (c-index) was used to assess the discriminatory ability of the prognostic factors. RESULTS: A 1-cm increase in T3a RCC resulted in an 8% increase in all-cause mortality (hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 1.06-1.10, p < 0.001) and 14% increase in the risk of RCC-specific mortality (sub-distribution HR [sHR]: 1.14; 95% CI: 1.11-1.16, p < 0.001). T3a tumor size stratified by the cutoff of 4 cm and 7 cm showed a better prediction of RCC-special survival (c-index: 0.644), compared with a cutoff just by 4 cm (c-index: 0.571) or by 7 cm (c-index: 0.602). Compared with T1b tumors, T3a RCC ≤4 cm showed no differences in terms of all-cause mortality (HR: 0.93; 95% CI: 0.79-1.09; p = 0.37) and mortality caused by RCC (sHR: 0.91; 95% CI: 0.70-1.19; p = 0.50). Last, the alternative T-staging system (T1a, a combination of T1b and T3a [≤4 cm], T2a, T2b, T3a [4-7 cm], and T3a [>7] cm) demonstrated good RCC-special survival predictive accuracy (c-index: 0.729), which was higher than that shown by the current eighth edition T-staging system (c-index: 0.720). CONCLUSION: Tumor size should be taken into consideration for T3aN0M0 RCC rather than based on anatomical features alone.
Subject(s)
Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Databases, Factual , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Neoplasm Staging/standards , Nephrectomy/mortality , Aged , Aged, 80 and over , Carcinoma, Renal Cell/surgery , Female , Follow-Up Studies , Humans , Kidney Neoplasms/surgery , Male , Middle Aged , Retrospective Studies , Survival RateABSTRACT
OBJECTIVES: N6-methyladenosine (m6A) is a ubiquitous epigenetic RNA modification that plays a pivotal role in tumour development and metastasis. In this study, we aimed to investigate the expression profiling, clinical significance, biological function and the regulation of m6A-related genes in hepatoblastoma (HB). MATERIALS AND METHODS: The mRNA and protein expression levels of m6A-related genes were analysed using Gene Expression Omnibus (GEO) and tissue microarray (TMA) cohort. Kaplan-Meier analysis was performed to evaluate the prognostic value of m6A-related genes in HB. Knockdown of m6A-related genes was conducted to analyse its function on cell proliferation, migration and invasion. Furthermore, bioinformatics analysis and experimental verification were used to explore the potential molecular mechanism and signalling pathway. RESULTS: We found that most m6A-related genes were significantly upregulated in HB tumour tissues. High levels of methyltransferase-like 3 (METTL3, P = .013), YTHDF2 (P = .037) and FTO (P = .032) indicated poor clinical outcomes, and the upregulation of METTL3 was an independent prognostic factor in HB patients. Functional assays showed that knockdown of METTL3 could dramatically suppress the proliferation, migration and invasion of HB cells. In addition, METTL3 was identified to be a direct target of microRNA-186 (miR-186). Consistently, miR-186 was low expressed in HB tumour tissues. Moreover, overexpression of miR-186 significantly inhibited cell aggressive phenotype both in vitro and in vivo, while the inhibitory effect could be reversed by METTL3 overexpression. Mechanism study indicated that miR-186/METTL3 axis contributed to the progression of HB via the Wnt/ß-catenin signalling pathway. CONCLUSIONS: M6A-related genes were frequently dysregulated in HB. miR-186/METTL3/Wnt/ß-catenin axis might serve as novel therapeutic targets and prognostic biomarkers in HB.
Subject(s)
Hepatoblastoma/genetics , Liver Neoplasms/genetics , Methyltransferases/genetics , MicroRNAs/genetics , Adenosine/analogs & derivatives , Adenosine/genetics , Animals , Disease Progression , Gene Expression Regulation, Neoplastic , Hep G2 Cells , Hepatoblastoma/diagnosis , Hepatoblastoma/metabolism , Hepatoblastoma/pathology , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Male , Mice, Inbred C57BL , Mice, Nude , Prognosis , Wnt Signaling PathwayABSTRACT
Hepatoblastoma (HB) is the most common hepatic neoplasm in childhood and the therapeutic outcomes remain undesirable due to its recurrence and metastasis. Increasing evidence shows that dipeptidase 1 (DPEP1) has pivotal function in tumorigenesis in multiple tumors. However, the expression pattern, biological function, and underlying mechanism of DPEP1 in HB have not been reported. Here we showed that DPEP1 was significantly upregulated and was associated with poor prognosis in HB patients. In vitro and in vivo assays indicated that silencing DPEP1 significantly suppressed HB cell proliferation, migration, and invasion, while DPEP1 overexpression exhibited the opposite effect. In addition, we identified that DPEP1 was a direct target of microRNA-193a-5p (miR-193a-5p). Functional experiments demonstrated that overexpression of miR-193a-5p significantly inhibited cell proliferation and invasion of HB cells, while the inhibitory effect could be reversed by DPEP1 overexpression. Moreover, miR-193a-5p was decreased in HB tumor tissues and associated with a poor clinical prognosis. Mechanistically, our results indicated that the miR-193a-5p/DPEP1 axis participated to the progression of HB via regulating the PI3K/Akt/mTOR (phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin) signaling. In conclusion, our findings suggest that the miR-193a-5p /DPEP1 axis might be a good prognostic predictor and therapeutic target in HB.
Subject(s)
Dipeptidases/metabolism , Hepatoblastoma/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Disease Progression , GPI-Linked Proteins/metabolism , Hepatoblastoma/pathology , Humans , Middle AgedABSTRACT
We used blood serum samples collected from 31 lung cancer (LC) patients and 29 healthy volunteers in this study. Levels of serum metabolites were qualitative quantified with gas chromatography-mass spectrometry (GC-MS), and the data were analyzed by partial least-squares discrimination analysis (PLS-DA). Based on the Kyoto Encyclopedia of Genes and Genomes database, we performed pathway-based analysis utilizing metabolites presented at differential abundance between the LC serum samples and the normal healthy serum samples for systematical investigation on the metabolic alterations associated with LC pathogenesis. Finally, we analyzed the significantly enriched pathways as well as their relevant differentially expressed messenger RNAs, and drawn a correlation network plot to identify the serum metabolic biomarkers and the significantly altered metabolic pathways for LC. GC-MS analysis showed that 23 of the 169 metabolites identified were significantly different. PLS-DA model revealed that 13 of these metabolites were with variable importance > 1, and particularly five were with area under curve > 0.9. Pathway-based analysis demonstrated that five of eight enriched metabolic pathways were statistically significant with false discovery rate < 0.05. Lastly, the correlation networks between these pathways and their related genes suggested that 29 genes had correlation degree > 10, which were mainly engaged in the purine metabolism. In conclusion, we identified indole-3-lactate, erythritol, adenosine-5-phosphate, paracetamol and threitol as serum metabolic biomarkers for LC through metabolomics analysis. Besides, we identified the purine metabolism as the significantly altered metabolic pathway in LC with the help of transcriptomics analysis.
ABSTRACT
OBJECTIVE: Our study aimed to explore the relationship between CD36 methylation and the development of lung cancer and investigate the effect of combine treatment of Decitabine and Chidamide in lung cancer. METHODS: The differentially expression genes in tumor samples and normal samples were determined by microarray analysis. Weighted gene co-expression network analysis (WGCNA) was utilized to analyze gene expression data of lung cancer and the hub genes were screened in the modules. Methylation-specific PCR (MSP) was conducted to detect the methylation level of CD36 in lung cancer cells. QRT-PCR analysis and western blotting were performed to explore the relative mRNA expression and protein level. MTT assays, wound healing assay, Transwell assays and flow cytometry were conducted to clarify the cell proliferation, migration, invasion and cell cycle of lung carcinoma cell lines in vitro respectively. By xenograft and immunohistochemistry, the effect of co-treatment of Decitabine and Chidamide was further verified in vivo. RESULTS: The heatmap displayed that the top 20 differential mRNA-expression gene in lung cancer tissues and normal tissues in which CD36 was low expressed in the tumor samples and high expressed in the normal samples. By WGCNA, CD36 was selected to be the hub gene in the brown module. And then CD36 was confirmed to be differential expressed and hypermethylated in lung cancer through qRT-PCR and western blotting. CD36 inhibited the lung cancer cell proliferation, promoted cell apoptosis, blocked cell cycle at G0/G1 phase, and inhibited cell migration. What's more, we found that Decitabine (DCTB) and Chidamide (CDM) co-treatment induced de-methylation and re-expression of silenced CD36 by conducting the vivo experiments. DCTBâ¯+â¯CDM co-treatment synergistically suppressed tumor growth. CONCLUSION: Our results showed that the high methylation of CD36 in lung cancer played an important role in the procession of lung cancer and Decitabine joint Chidamide had obvious effect of inhibiting the growth of lung tumor.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , CD36 Antigens/genetics , CD36 Antigens/metabolism , DNA Methylation , Down-Regulation , Lung Neoplasms/genetics , Aminopyridines/therapeutic use , Animals , Azacitidine/analogs & derivatives , Azacitidine/therapeutic use , Benzamides/therapeutic use , Cell Line, Tumor , Cell Movement , Cell Proliferation , Decitabine , Disease Progression , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Mice , Neoplasm Invasiveness , Xenograft Model Antitumor AssaysABSTRACT
Breast cancer (BC) is the second-leading cause of cancer mortality after lung cancer in women owing partly to a lack of specific and sensitive tests for early screening and monitoring. The detection of novel specific BC serum indicators for screening purposes is an essential clinical need. A total of 437 serum specimens from 310 BC patients that were divided into mining and testing sets were collected in this study. In contrast with the conventional BC indicators through receiver operating characteristic, survival and hazard function curves, and multivariate Cox regression analyses, we intended to hunt for stable protein indicators from serum specimens and identify their diagnostic and prognostic potential for BC. We identified a unique serum peptide located at 6648 Da originated from apoC-III with a validated correlation with BC tumorigenesis with confirmation in a substantive testing set and minimization of systematic bias by pre-analytical parameters. We found that the diagnostic efficacy of this peptide is better than the present conventional BC diagnostic indicators either alone or in combination with conventional indicators in distinguishing BC patients from control volunteers. Moreover, this peptide denotes a stronger prognostic factor for BC patients than conventional indicators. In light of these findings, we speculate that this peptide is a potential diagnostic and prognostic indicator and a supplement to conventional indicators in monitoring BC. The detection of this peptide located at 6648 Da in sera could enhance early screening and assessment of the postoperative survival opportunity for BC patients.
Subject(s)
Biomarkers, Tumor/blood , Blood Proteins/analysis , Breast Neoplasms/blood , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Amino Acid Sequence , Blood Proteins/chemistry , Blotting, Western , Breast Neoplasms/diagnosis , Demography , Enzyme-Linked Immunosorbent Assay , Female , Humans , Middle Aged , Peptides/chemistry , Prognosis , Reproducibility of ResultsABSTRACT
OBJECTIVE: We investigated the expression of microRNA-124a and its methylation status in the spinal cords of rats with congenital spina bifida versus rats with normal fetuses. METHODS: Real-time quantitative reverse transcription-polymerase chain reaction was used to compare the expression of microRNA-124a in the spinal cords of 42 rats with all-trans retinoic acid induced congenital spina bifida and 42 rats with normal fetuses. The DNA methylation status in the promoter region of miRNA-124a was detected using methylation specific-PCR. RESULTS: Compared with rats with normal fetuses, expression of microRNA-124a was significantly decreased in rats with congenital spina bifida fetuses. The percentages of spinal cords with DNA hypermethylation in the microRNA-124a promoter were 81% and 14% in the congenital spina bifida and normal control groups, respectively. The difference was statistically significant. Further apoptosis testing revealed increased apoptosis cell numbers in the congenital spina bifida samples. Meanwhile, the phosphorylated mitogen-activated protein kinase protein expression level dramatically decreased in the congenital spina bifida samples. CONCLUSION: Aberrant DNA methylation was responsible for down-regulation of microRNA-124a by regulating the mitogen-activated protein kinase pathway, suggesting that microRNA-124a is a potential diagnostic biomarker in congenital spina bifida.
Subject(s)
Gene Expression Regulation, Developmental , MicroRNAs/metabolism , Spinal Cord/embryology , Spinal Dysraphism/embryology , Spinal Dysraphism/genetics , Animals , Biomarkers/metabolism , Blotting, Western , Case-Control Studies , Down-Regulation , Female , Immunohistochemistry , Male , Methylation , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Spinal Cord/metabolism , Spinal Dysraphism/metabolismABSTRACT
OBJECTIVE: To screen and identify serum biomarkers for childhood hepatoblastoma (HB). METHODS: The serum samples from 30 children with hepatoblastoma (HB), 20 children with systemic inflammatory response syndrome, and 20 normal children were treated with magnetic bead-based weak cation exchange chromatography. The platform of surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) was used to eliminate the interference of inflammatory factors and to screen out the differentially expressed proteins in serum between tumor group and normal group. After the purification and separation of target proteins were performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight-mass spectrometry was used to determine their amino acid sequences. The SwissProt database was searched for matched proteins. Finally, real-time PCR and ELISA were used to verify and measure the expression of target proteins. RESULTS: After SELDI-TOF-MS was used for screening and elimination of the interference of inflammatory factors, a differentially expression protein with a mass-to-charge ratio of 9 348 Da was found in serum between HB group and normal group, and the HB group had significantly lower expression of this protein than the normal group (p<0.05). This protein was identified as apolipoprotein A-1 (Apo A-I). Real-time PCR and ELISA verified the low mRNA and protein expression of Apo A-I in serum in the HB group and high expression in serum in the normal group. CONCLUSIONS: Apo A-I can be used as a non-inflammatory protein marker for HB and has a certain value in the early diagnosis of HB.
Subject(s)
Apolipoprotein A-I/blood , Biomarkers/blood , Early Detection of Cancer , Hepatoblastoma/diagnosis , Liver Neoplasms/diagnosis , Apolipoprotein A-I/genetics , Child, Preschool , Female , Hepatoblastoma/blood , Humans , Infant , Liver Neoplasms/blood , Male , Real-Time Polymerase Chain Reaction , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
Women with triple-negative breast cancer (TNBC) have poor prognosis because of the aggressive nature of the tumor, delayed diagnosis and non-specific symptoms in the early stages. Identification of novel specific TNBC serum biomarkers for screening and therapeutic purposes therefore remains an urgent clinical requirement.We obtained serum samples from a total of 380 recruited individuals split into mining and testing sets, with the aim of screening for reliable protein biomarkers from TNBC and non-TNBC (NTNBC) sera. Samples were assessed using mass spectrometry, followed by receiver operating characteristic (ROC), survival and hazard function curve as well as multivariate Cox regression analyses to ascertain the potential of the protein constituents as diagnostic and prognostic biomarkers for TNBC.We identified upregulated apolipoprotein C-I (apoC-I) with a validated positive effect on TNBC tumorigenesis, with confirmation in an independent test set and minimization of systematic bias by pre-analytical parameters. The apoC-I protein had superior diagnostic ability in distinguishing between TNBC and NTNBC cases. Moreover, the protein presented a more robust potential prognostic factor for TNBC than NTNBC. The apoC-I protein identified in this study presents an effective novel diagnostic and prognostic biomarker for TNBC, indicating that measurement of the peak intensity at 7785 Da in serum samples could facilitate improved early detection and estimation of postoperative survival prognosis for TNBC.
Subject(s)
Apolipoprotein C-I/blood , Biomarkers/blood , Mass Spectrometry/methods , Triple Negative Breast Neoplasms/diagnosis , Adult , Female , Humans , Prognosis , Triple Negative Breast Neoplasms/pathologyABSTRACT
OBJECTIVE: To investigate the effectiveness of ileal mucosal seromuscular patch for bladder expansion combined with rehabilitation training for treating neurogenic bladder dysfunction (NBD) with hyperreflexia. METHODS: A retrospective study was performed on the clinical data of 61 patients with NBD and hyperreflexia who were treated and followed up between July 2008 and June 2013. There were 36 males and 25 females, aged 6-23 years (mean, 10 years). The reasons included meningomyelocele operation (43 patients),surgery for lipoma in lumbar vertebra (4 patients), operation of thoracolubar teratoma (2 patients), and lumbosacral spina B3ifida (12 patients). The results of urodynamics indicated that bladder volume decreased obviously and the residual urine increased. The voiding cystourethrography (VCUG) showed the vesicoureteral reflux (VUR), including 6 cases (10 sides) of grade V, 7 cases (12 sides) of grade IV, and 6 cases (8 sides) of grade III. The color doppler ultrosound showed mild hydronephrosis in 23 cases (41 sides), moderate hydronephrosis in 25 cases (42 sides), and severe hydronephrosis in 13 cases (22 sides). The blood biochemical examination suggested chronic renal failure (CRF) in 13 cases. The treatment included augmentation for bladder and rehabilitation training after operation. RESULTS: The operation time was (157+/- 26) minutes; the intraoperative blood loss was (43 +/- 15) mL, and no patient was given blood transfusion. The patients were followed up 1.5-6.0 years (mean, 4.5 years). Vesical fistula occurred in 4 cases, urinary infection in 5 cases, dysuresia in 2 cases, and cystolith in 1 case after operation. At 1 year after operation, the International Consultation on Incontinence Questionnaire-Urinary Incontience Short Form (IQ-F) score was significantly better than peoperative score (H=9.813, P=0.000). The aurdynmic data showed that the difference value between observed and theoretical bladder volumes, bladder compliance, residual urine volume, maximum flow rate, and maximum storage detrusor pressure were significantly better than preoperative ones (P<0.05). And the color doppler ultrasound showed mild hydronephrosis in 34 cases (56 sides), moderate hydronephrosis in 18 cases (33 sides), and severe hydronephrosis in 9 cases (16 sides). VCUG showed that bladder volume obviously increased, no contracture was observed; and VUR was improved. And renal function was improved in 13 patients with CRF. CONCLUSION: Heal mucosal seromuscular patch for bladder expansion combined with postoperative rehabilitation training has good effectiveness in treating NBD with hyperreflexia.
Subject(s)
Reflex, Abnormal , Urinary Bladder, Neurogenic/rehabilitation , Vesico-Ureteral Reflux/diagnosis , Adolescent , Child , Female , Humans , Hydronephrosis , Male , Retrospective Studies , Ultrasonography, Doppler, Color , Urination , Urodynamics , Vesico-Ureteral Reflux/surgery , Young AdultABSTRACT
MicroRNAs (miRNAs) are dynamically regulated during neurodevelopment, yet few reports have examined their role in spina bifida. In this study, we used an established fetal rat model of spina bifida induced by intragastrically administering olive oil-containing all-trans retinoic acid to dams on day 10 of pregnancy. Dams that received intragastric administration of all-trans retinoic acid-free olive oil served as controls. The miRNA expression profile in the amniotic fluid of rats at 20 days of pregnancy was analyzed using an miRNA microarray assay. Compared with that in control fetuses, the expression of miRNA-9, miRNA-124a, and miRNA-138 was significantly decreased (> 2-fold), whereas the expression of miRNA-134 was significantly increased (> 4-fold) in the amniotic fluid of rats with fetuses modeling spina bifida. These results were validated using real-time quantitative reverse-transcription polymerase chain reaction. Hierarchical clustering analysis of the microarray data showed that these differentially expressed miRNAs could distinguish fetuses modeling spina bifida from control fetuses. Our bioinformatics analysis suggested that these differentially expressed miRNAs were associated with many cytological pathways, including a nervous system development signaling pathway. These findings indicate that further studies are warranted examining the role of miRNAs through their regulation of a variety of cell functional pathways in the pathogenesis of spina bifida. Such studies may provide novel targets for the early diagnosis and treatment of spina bifida.
ABSTRACT
BACKGROUND: Gastric cancer (GC) is a highly aggressive cancer type associated with significant mortality owing to delayed diagnosis and non-specific symptoms observed in the early stages. Therefore, identification of novel specific GC serum biomarkers for screening purposes is an urgent clinical requirement. METHODS: This study recruited a total of 432 serum samples from 296 GC patients split into the mining and testing sets. We aimed to screen for reliable protein biomarkers from matched serum samples based on mass spectrometry, followed by comparison with three representative conventional markers using receiver operating characteristic and survival curve analyses to ascertain their potential values as diagnostic and prognostic biomarkers for GC. RESULTS: We identified an apoC-III fragment with confirmation in an independent test set from a second hospital. We found that the diagnostic ability of this fragment performed better than current standard GC diagnostic biomarkers both individually and in combination in distinguishing patients with GC from healthy individuals. Moreover, we found that this apoC-III protein fragment represents a more robust potential prognostic factor for GC than the three conventional markers. CONCLUSIONS: In view of these findings, we suggest that apoC-III protein fragment is a novel diagnostic and prognostic biomarker, a complement to conventional biomarkers in detecting GC.
Subject(s)
Adenocarcinoma/blood , Adenocarcinoma/diagnosis , Blood Proteins/analysis , Stomach Neoplasms/blood , Stomach Neoplasms/diagnosis , Adenocarcinoma/pathology , Biomarkers, Tumor/blood , Case-Control Studies , Female , Humans , Male , Mass Spectrometry/methods , Middle Aged , Prognosis , Stomach Neoplasms/pathologyABSTRACT
AIM: Combination treatment consisting of surgery and pre-or post-operative corticosteroids for chronic subdural hematoma (CSH) tend to have better outcomes than surgery only. However, there are many complications after long-term use of corticosteroids. In this study, we evaluated the clinical outcomes of local application of corticosteroids combined with surgery for CSH. MATERIAL AND METHODS: We retrospectively analysed the data of the patients undergoing surgery and local application of Methylprednisolone Sodium Succinate for Injection (MPSS) into the hematoma cavity. Neurological status was assessed by Markwalder's Grading Scale (MGS). Recurrence was defined as deteriorating neurological status with radiological evidence of reaccumulation. RESULTS: A total of 26 patients were enrolled in this study. During the follow-up period, all patients made excellent neurological recovery. 24 (92.3%) patients' MGS was grade 0 at 12 months after the surgery. There was no mortality or recurrence. 5 patients (19.2%) suffered postoperative complications, of which 2 developed some subdural air collection, 2 had a partial seizure attack and 1 developed an acute epidural hemorrhage. CONCLUSION: The results suggest that local application of MPSS combined with surgery is a safe and effective method in the management of CSH. It may reduce hematoma recurrence.
Subject(s)
Adrenal Cortex Hormones/pharmacology , Hematoma, Subdural, Chronic/drug therapy , Hematoma, Subdural, Chronic/surgery , Methylprednisolone Hemisuccinate/pharmacology , Adolescent , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , Adult , Aged , Aged, 80 and over , Child , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Methylprednisolone Hemisuccinate/administration & dosage , Methylprednisolone Hemisuccinate/adverse effects , Middle Aged , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: To summarize retrospectively developmental dysplasia of the hip (DDH) screening of children within 36 months. METHODS: Newborn infants underwent initial DDH screening at First Affiliated Hospital, Zhengzhou University from September 2011 to May 2013. The examinations included double hip function, abduction test and Ortolani/Barlow test. After initial DDH screening, suspected and abnormal infants were transferred to our department for re-screening. And clinical physical examinations, type B ultrasound or radiological imaging were performed for confirmation or elimination. RESULTS: A total of 10 428 children were DDH screened. And 1 260 children were examined with ultrasound and 346 suspected and abnormal children (445 hips) were transferred for further assessments. Among them, 33 children (49 hips) were positive with Ortolani or Barlow test, 61 children (88 hips) had dysplasia of hip and 48 children (14 boys, 34 girls) (69 hips) received a final diagnosis of DDH. Left (n = 52) and right hip (n = 17) were involved with a disease incidence of DDH at 0.46%. CONCLUSIONS: Ultrasonic examination is both simple and cost-effective for DDH screening of children within 6 months. And meticulous medical examinations and imaging studies are effective DDH screening for children from 6 to 36 months.
Subject(s)
Hip Dislocation, Congenital/diagnosis , Child, Hospitalized , Child, Preschool , Early Diagnosis , Female , Hip Dislocation, Congenital/diagnostic imaging , Humans , Infant , Infant, Newborn , Male , Mass Screening , UltrasonographyABSTRACT
OBJECTIVE: To analyze the treatment of acute renal failure caused by irrational drug use. METHOD: Data of 41 cases of acute renal failure seen from July 2008 to June 2012 in our hospital were reviewed. Bilateral renal parenchymas diffuse echo was found enhanced by ultrasound in all cases. Calculus image was not found by X-ray. All children had medical history of using cephalosporins or others. Alkalinization of urine and antispasmodic treatment were given to all children immediately, 17 children were treated with hemodialysis and 4 children accepted intraureteral cannula placement. RESULT: In 24 children who accepted alkalinization of urine and antispasmodic treatment micturition could be restored within 24 hours, in 11 children micturition recovered after only one hemodialysis treatment and 2 children gradually restored micturition after hemodialysis twice, 4 children who accepted intraureteral cannula immediately restored micturition. In all children micturition recovered gradually after a week of treatment. Ultrasound examination showed that 39 children's calculus disappeared totally and renal parenchymas echo recovered to normal. The residual calculi with diameter less than 5 mm were found in 2 children, but they had no symptoms. The children received potassium sodium hydrogen citrate granules per os and were discharged from hospital. Ultrasound showed calculus disappeared totally one month later. CONCLUSION: Irrational drug use can cause children urolithiasis combined with acute renal failure, while renal dysfunction can reverse by drug withdrawal and early alkalinization of urine, antispasmodic treatment, intraureteral cannula or hemodialysis when necessary, most calculus can be expelled after micturition recovered to normal.
Subject(s)
Acute Kidney Injury/therapy , Ceftriaxone/adverse effects , Kidney/physiopathology , Urinary Calculi/therapy , Acute Kidney Injury/chemically induced , Acute Kidney Injury/diagnosis , Ceftriaxone/administration & dosage , Child , Child, Preschool , Diuretics/therapeutic use , Female , Fluid Therapy , Humans , Infant , Kidney/pathology , Male , Potassium Citrate/therapeutic use , Renal Dialysis , Retrospective Studies , Treatment Outcome , Urinary Calculi/chemically induced , Urinary Calculi/diagnosisABSTRACT
PURPOSE: Noninvasive and convenient biomarkers for early diagnosis of breast cancer remain an urgent need. The aim of this study was to discover and identify potential protein biomarkers specific for breast cancer. METHODS: Two hundred and eighty-two (282) serum samples with 124 breast cancer and 158 controls were randomly divided into a training set and a blind-testing set. Serum proteomic profiles were analyzed using SELDI-TOF-MS. Candidate biomarkers were purified by HPLC, identified by LC-MS/MS and validated using ProteinChip immunoassays and western blot technique. RESULTS: A total of 3 peaks (m/z with 6,630, 8,139 and 8,942 Da) were screened out by support vector machine to construct the classification model with high discriminatory power in the training set. The sensitivity and specificity of the model were 96.45 and 94.87%, respectively, in the blind-testing set. The candidate biomarker with m/z of 6,630 Da was found to be down-regulated in breast cancer patients, and was identified as apolipoprotein C-I. Another two candidate biomarkers (8,139, 8,942 Da) were found up-regulated in breast cancer and identified as C-terminal-truncated form of C3a and complement component C3a, respectively. In addition, the level of apolipoprotein C-I progressively decreased with the clinical stages I, II, III and IV, and the expression of C-terminal-truncated form of C3a and complement component C3a gradually increased in higher stages. CONCLUSIONS: We have identified a set of biomarkers that could discriminate breast cancer from non-cancer controls. An efficient strategy, including SELDI-TOF-MS analysis, HPLC purification, MALDI-TOF-MS trace and LC-MS/MS identification, has been proved very successful.