CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia.

Resistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-of-function experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GCresistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GCs against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL.

Acromicric dysplasia caused by a mutation of fibrillin 1 in a family: A case report.

BACKGROUND: Acromicric dysplasia (AD) is a rare skeletal dysplasia. Its incidence is < 1/1000000, and only approximately 60 cases are reported worldwide. It is a disease characterized by severe short stature, short hands and feet, facial abnormalities, normal intelligence, and bone abnormalities. Unlike other skeletal dysplasia, AD has a mild clinical phenotype, mainly characterized by short stature. Extensive endocrine examination has not revealed a potential cause. The clinical effect of growth hormone therapy is still uncertain. CASE SUMMARY: We report a clinical phenotype of AD associated with mutations in the fibrillin 1 (FBN1) (OMIM 102370) gene c.5183C>T (p. Ala1728Val) in three people from a Chinese family. A 4-year-old member of the family first visited the hospital because of slow growth and short stature for 2 years, but no abnormalities were found after a series of laboratory tests, echocardiography, pituitary magnetic resonance imaging, and ophthalmological examination. Recombinant human growth hormone (rhGH) was used to treat the patient for > 5 years. The efficacy of rhGH was apparent in the first year of treatment; the height increased from -3.64 standard deviation score (SDS) to -2.88 SDS, while the efficacy weakened from the second year. However, long-term follow-up is required to clarify the efficacy of rhGH. CONCLUSION: FBN1-related AD has genetic heterogeneity and/or clinical variability, which brings challenges to the evaluation of clinical treatment. rhGH is effective for treatment of AD, but long-term follow-up is needed to clarify the effect.

Identification of a 3-Gene Prognostic Index for Papillary Thyroid Carcinoma.

The accurate determination of the risk of cancer recurrence is a critical unmet need in managing thyroid cancer (TC). Although numerous studies have successfully demonstrated the use of high throughput molecular diagnostics in TC prediction, it has not been successfully applied in routine clinical use, particularly in Chinese patients. In our study, we objective to screen for characteristic genes specific to PTC and establish an accurate model for diagnosis and prognostic evaluation of PTC. We screen the differentially expressed genes by Python 3.6 in The Cancer Genome Atlas (TCGA) database. We discovered a three-gene signature Gap junction protein beta 4 (GJB4), Ripply transcriptional repressor 3 (RIPPLY3), and Adrenoceptor alpha 1B (ADRA1B) that had a statistically significant difference. Then we used Gene Expression Omnibus (GEO) database to establish a diagnostic and prognostic model to verify the three-gene signature. For experimental validation, immunohistochemistry in tissue microarrays showed that thyroid samples' proteins expressed by this three-gene are differentially expressed. Our protocol discovered a robust three-gene signature that can distinguish prognosis, which will have daily clinical application.

Network Pharmacology to Explore the Molecular Mechanisms of Prunella vulgaris for Treating Hashimoto's Thyroiditis.

Purpose: Prunella vulgaris (PV), a traditional Chinese medicine, has been used to treat patients with thyroid disease for centuries in China. The purpose of the present study was to investigate its bioactive ingredients and mechanisms against Hashimoto's thyroiditis (HT) using network pharmacology and molecular docking technology to provide some basis for experimental research. Methods: Ingredients of the PV formula were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Additionally, HT-related genes were retrieved from the UniProt and GeneCards databases. Cytoscape constructed networks for visualization. A protein-protein interaction (PPI) network analysis was constructed, and a PPI network was built using the Search Tool for the Retrieval of Interacting Genes (STRING) database. These key targets of PV were enriched and analyzed by molecular docking verification, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Results: The compound-target network included 11 compounds and 66 target genes. Key targets contained Jun proto-oncogene (JUN), hsp90aa1.1 (AKI), mitogen-activated protein kinase 1 (MAPK1), and tumor protein p53 (TP53). The main pathways included the AGE-RAGE signaling pathway, the TNF signaling pathway, the PI3K-Akt signaling pathway, and the mitogen-activated protein kinase signaling pathway. The molecular docking results revealed that the main compound identified in the Prunella vulgaris was luteolin, followed by kaempferol, which had a strong affinity for HT. Conclusion: Molecular docking studies indicated that luteolin and kaempferol were bioactive compounds of PV and might play an essential role in treating HT by regulating multiple signaling pathways.

Prioritizing Susceptible Genes for Thyroid Cancer Based on Gene Interaction Network.

Thyroid cancer ranks second in the incidence rate of endocrine malignant cancer. Thyroid cancer is usually asymptomatic at the initial stage, which makes patients easily miss the early treatment time. Combining genetic testing with imaging can greatly improve the diagnostic efficiency of thyroid cancer. Researchers have discovered many genes related to thyroid cancer. However, the effects of these genes on thyroid cancer are different. We hypothesize that there is a stronger interaction between the core genes that cause thyroid cancer. Based on this hypothesis, we constructed an interaction network of thyroid cancer-related genes. We traversed the network through random walks, and sorted thyroid cancer-related genes through ADNN which is fusion of Adaboost and deep neural network (DNN). In addition, we discovered more thyroid cancer-related genes by ADNN. In order to verify the accuracy of ADNN, we conducted a fivefold cross-validation. ADNN achieved AUC of 0.85 and AUPR of 0.81, which are more accurate than other methods.

Significance of DMBT1 in Papillary Thyroid Carcinoma Concurrent With Hashimoto's Thyroiditis.

BACKGROUND: Papillary thyroid carcinoma (PTC) concurrent with Hashimoto's thyroiditis (HT) was associated with a better clinical prognosis. This study aimed to investigate a potential mRNA gene that affects the development of PTC, which helps PTC concurrent with HT patients have a better prognosis. MATERIAL/METHODS: PTC data were obtained from The Cancer Genome Atlas (TCGA) database. And the validation data of tissue specimens were collected from Guangzhou First People's Hospital. The thyroid tissue sections were hybridized with deleted in malignant brain tumor 1 (DMBT1) probes by situ hybridization. Survival rates were analyzed using Kaplan-Meier curves, and the log-rank test was used to compare group survival rates. Prognosis clinicopathological factors were analyzed by Cox regression. Gene Ontology (GO) and Kyoto Gene and Genomic Encyclopedia (KEGG) pathway enrichment analyses were performed using single-sample gene set enrichment analysis (ssGSEA). Finally, the correlation of deletion in DMBT1 expression with overall immune status, tumor purity, and human leukocyte antigen (HLA) gene expression profile was analyzed. RESULTS: HT was significantly associated with sex, tumor foci, extrathyroidal extension (ETE), residual tumor, and tumor stage (T stage). Moreover, PTC concurrent with HT had a lower risk of recurrence versus non-HT groups. A total of 136 differentially expressed mRNAs (DEMs) were identified between HT and non-HT groups. Among them, the expression level of DMBT1 in HT groups was statistically higher than that in non-HT groups. A significant association with ETE and recurrence was revealed in the high expression and the low expression of DMBT1. Furthermore, DMBT1 was an independent predictor of survival. The overall immune activity of high expression of DMBT1 was higher than that of the low-expression group. CONCLUSIONS: The PTC patients with HT had better behavior features and prognosis than those with simple PTC. DMBT1 in PTC-HT patients was a potential possible factor that inhibits tumors. High expression of DMBT1 may improve PTC prognosis by immune-related pathways.

Design and development of a new type of phimosis dilatation retractor for children.

BACKGROUND: Phimosis is one of the most common diseases in children. Early selection of appropriate treatment for phimosis in children is beneficial to the development of their reproductive organs and significantly improves the prognosis of phimosis in children. Although traditional circumcision is the most widely used, it has many disadvantages, including postoperative bleeding and incision infection, pain, obvious scars on the surgical incision, and unsatisfactory appearance. In addition, there is much controversy regarding treatment options and timing at home and abroad. Surgical procedures such as circumcision and cerclage for children with excessively long foreskin will greatly affect the normal life of children after the operation. Young children need general anesthesia, but this anesthesia carries a great risk. AIM: To design a new children phimosis dilatation retractor for children phimosis. METHODS: The children phimosis was dilated with an elastic dilation frame, in order to expand the foreskin mouth and expose the penis head, and after that, the phimosis was cured. RESULTS: A new type of phimosis dilatation retractor was designed, which can gently dilate the prepuce at multiple angles and in multiple directions at the same time. It has obtained the national patent for clinical application. CONCLUSION: The phimosis dilatation retractor based on the principle of elastically expanding the prepuce can achieve the purpose of expanding the phimosis. The clinical application shows that the effect of the children phimosis retractor is significant, which is worth promoting.

Interaction between CD9 and PI3K­p85 activates the PI3K/AKT signaling pathway in B­lineage acute lymphoblastic leukemia.

Our previous study has shown that CD9 knockdown could suppress cell proliferation, adhesion, migration and invasion, and promote apoptosis and the cytotoxicity of chemotherapeutic drugs in the B­lineage acute lymphoblastic leukemia (B­ALL) cell line SUP­B15. In this study, we further investigated the molecular mechanism underlying the effects of CD9 on leukemic cell progression and the efficacy of chemotherapeutic agents in B­ALL cells. Using the CD9­knockdown SUP­B15 cells, we demonstrated that the silencing of the CD9 gene significantly reduced the expression of phosphorylated­phosphatidylinositol­3 kinase (p­PI3K), phosphorylated­protein kinase B (p­AKT), P­glycoprotein (P­gp), multidrug resistance­associated protein 1 (MRP1), breast cancer resistance protein (BCRP), matrix metalloproteinase 2 (MMP2) and phosphorylated­focal adhesion kinase (p­FAK). In addition, glutathione S­transferase (GST) pull­down assay showed the binding between CD9 and both PI3K­p85α and PI3K­p85ß in vitro, while co­immunoprecipitation assay showed the binding between CD9 and both PI3K­p85α and PI3K­p85ß in vivo. Furthermore, the PI3K/AKT inhibitor LY294002 mirrored the effects of CD9 knockdown in SUP­B15 cells. Taken together, these findings demonstrated that CD9 activates the PI3K/AKT signaling pathway through direct interaction with PI3K­p85 in B­ALL cells. Our data provide evidence for the inhibition of the PI3K/AKT pathway as a novel therapeutic option in CD9 antigen­positive B­ALL.

Higher Red Blood Cell Distribution Width is a Poor Prognostic Factor for Patients with Chronic Myeloid Leukemia.

PURPOSE: Red blood cell distribution width (RDW) has been considered as a potential indicator of the effects of treatment or as a prognostic indicator for various malignancies. Most chronic myeloid leukemia (CML) patients are in the chronic phase, but some have transformed to accelerated phase or blast phase (blast crisis). However, the clinical significance of RDW in CML remains limited. PATIENTS AND METHODS: In the present study, detailed clinical information and the RDW of 168 healthy people and 153 CML patients (106 patients for the training cohort and 47 patients for the validation cohort) were retrospectively assessed. RESULTS: Multivariate analysis demonstrated that patient age (OR, 1.081; 95CI% 1.039~1.125; p < 0.001), platelet counts (OR, 0.997; 95CI% 0.994~0.999; p = 0.001) and RDW at admission (OR,1.469; 95CI% 1.121~1.925; p = 0.005) were significantly associated with the patients with advanced phase. Among CML patients in the chronic phase, higher RDW was significantly associated with overall survival (OS; p = 0.0008) and the event-free survival (EFS; p = 0.0221) among CML patients with chronic phase, but not with Transformation-free survival (TFS; p = 0.0821). Furthermore, higher RDW was associated with higher mortality compared to patients with low RDW (CML-associated deaths; p < 0.0001). In addition, a decline in RDW is associated with the treatment of CML patients with tyrosine kinase inhibitors, especially at 6 and 12 months after the start of treatment. CONCLUSION: Higher RDW is a potential prognostic biomarker for chronic CML patients.

ALDH5A1 acts as a tumour promoter and has a prognostic impact in papillary thyroid carcinoma.

Thyroid cancer is the most common endocrine carcinoma, with papillary thyroid carcinoma (PTC) accounting for 80%-90% of thyroid cancers. Accumulating studies reported that mitochondria plays an important role in the regulation of cell proliferation. ALDH5A1, may function as an oncogene or tumour suppressor in various human cancers, and the role of ALDH5A1 in PTC is still unclear. The aim of this study was to investigate the clinical significance of ALDH5A1 expression and its functions in PTC. In this present study, we studied ALDH5A1 expression on primary papillary thyroid carcinoma (PTC) in The Cancer Genome Atlas (TCGA) database. Results showed that the levels of ALDH5A1 were found positively correlated with tumour stage, metastasis, lymph node stage, and higher levels of ALDH5A1 demonstrated poor disease-free survival (DFS). Immunohistochemistry (IHC) revealed that significantly higher expression of ALDH5A1 was found in PTC tissues. On the other hand, knockdown of ALDH5A1 significantly inhibited PTC cell proliferation, migration and invasion detection found the migration and invasion of cells also were hindered when ALDH5A1 level was reduced. The knockdown of ALDH5A1 inhibited the expression of Vimentin and promoted the expression of E-cadherin. In brief, knockdown of ALDH5A1may act as a novel molecular target for the prevention and treatment of PTC. SIGNIFICANCE OF THE STUDY: The present study focused on the role and the potential mechanism of ALDH5A1 in papillary thyroid carcinoma. We demonstrated that reduced expression of ALDH5A1 might inhibit the progression of TC by inhibiting cell proliferation, migration and invasion and reversing epithelial-mesenchymal transition (EMT). The findings ensured the interaction relation between ALDH5A1 and EMT in PTC, providing a novel biological marker for PTC and enriching the potential strategies for TC treatment.

Proton pump inhibitors and the risk of hospital-acquired acute kidney injury in children.

BACKGROUND: To evaluate the association between use of proton pump inhibitor (PPI) and the risk of hospital-acquired acute kidney injury (HA-AKI) in hospitalized children. METHODS: We conducted a multicenter retrospective cohort study in hospitalized children aged 1 month to 18 years from 25 tertiary hospitals across China from 2013 to 2015. Patient-level data were obtained from the electronic hospitalization databases. AKI was defined and staged using the serum creatinine (SCr) data according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. RESULTS: Among 42,232 children analyzed, 11,496 (27.2%) used PPI, 1,760 (4.2%) used histamine 2 receptor antagonist (H2RA), and 3,514 (8.3%) had HA-AKI during hospitalization. Over 85% of PPIs were prescribed for prophylaxis of gastro-duodenal lesions in children. The use of PPI was associated with a significantly increased risk of HA-AKI compared with both non-users [odds ratio (OR), 1.37; 95% confidence interval (CI), 1.23-1.53)] and H2RA users (OR, 1.24; 95% CI, 1.01-1.52). The associations were consistent across children of different age range, gender, subtypes of PPIs and methods of administration. A larger effect was observed in children with chronic kidney disease (OR, 3.37; 95% CI, 2.46-4.62) and those needed intensive care (OR, 1.54; 95% CI, 1.33-1.78). The risk of HA-AKI was increased even within the recommended dosage range of PPI. CONCLUSIONS: PPIs were widely used and associated with an increased risk of HA-AKI in hospitalized children in China.

Association of Soluble Klotho Level with Adverse Outcomes in Patients on Maintenance Hemodialysis.

BACKGROUND: The predictive value of soluble Klotho (sKlotho) for adverse outcomes in patients on maintenance hemodialysis (MHD) is controversial. In this study, we aimed to clarify the potential association of sKlotho levels with adverse outcomes in this patient population. MATERIALS: A total of 211 patients on MHD were identified and stratified according to the median sKlotho level. Patients were followed up for adverse outcomes including cardiovascular (CV) morbidity and all-cause mortality. RESULTS: During the 36-month follow-up, 75 patients [51 CV events (including 16 CV deaths) and 40 deaths] experienced adverse outcomes. After stratification according to median sKlotho level, patients with a lower sKlotho level had a greater risk of CV events (38.2% vs. 19.5%, p = 0.006), all-cause mortality (28.4% vs. 11.6%, p = 0.003), and combined adverse outcomes (51.0% vs. 24.2%, p < 0.001). Similar observations were made from analyses using Kaplan-Meier survival curves. Cox regression analysis showed that a low sKlotho level was strongly correlated with CV morbidity [1.942 (1.030-3.661), p = 0.040)], all-cause mortality [2.073 (1.023-4.203), p = 0.043], and combined adverse outcomes [1.818 (1.092-3.026), p = 0.021] in fully adjusted models. CONCLUSIONS: The sKlotho level was an independent predictive factor of adverse outcomes including CV morbidity and mortality in patients on MHD.

MicroRNA-3690 promotes cell proliferation and cell cycle progression by altering DKK3 expression in human thyroid cancer.

An increasing amount of evidence has demonstrated the importance of microRNAs (miRNAs/miRs) in the tumorigenesis of malignant types of cancer, and data retrieved from The Cancer Genome Atlas database revealed that miR-3690 was upregulated in thyroid cancer (TC). The present study focused on the biological function and mechanism of miR-3690 in TC, demonstrating that miR-3690 expression was significantly elevated in TC cells and clinical tissues. Functional studies indicated that miR-3690 acted as an oncogene in TC by promoting cell proliferation, colony formation and cell cycle progression in association with the increased expression of cyclin E and c-myc. Mechanistically, prediction software indicated that Dickkopf-related protein 3 (DKK3) was a target of miR-3690, which was confirmed by the results of luciferase reporter assays and western blotting. DKK3 silencing abrogated the functions of miR-3690-in on TC cell proliferation. Collectively, the findings of the present study demonstrated that miR-3690 promoted TC cell proliferation and indicated miR-3690 as a potential biomarker and therapeutic target for TC.

Normal Absolute Monocyte Count at the Time of Relapse is Associated with Improved Survival After First Salvage Therapy in Adult Patients with Early Relapsed B-Lineage Acute Lymphoblastic Leukemia.

BACKGROUND: Peripheral monocytes, a key cell type for innate immunity, have been shown to be associated with survival in various types of hematological malignancies. However, no previous studies regarding the prognostic impact of peripheral absolute monocyte count (AMC) in early relapsed B-lineage acute lymphoblastic leukemia (B-ALL) have been reported. METHODS: Forty-nine cases of early relapsed adult B-ALL were reviewed. The upper (0.80 × 109/L) and lower limits (0.12 × 109/L) of the normal value for AMC were used as cut-off points. Kaplan-Meier curves and Log rank test were used for comparison of overall survival (OS). The univariate and multivariate Cox proportional hazards models were used for investigating the factors associated with OS. RESULTS: More than half (59.2%) of all patients showed a normal AMC (0.12-0.80 × 109/L). The median follow-up was 5.3 months from the start of first salvage therapy. Univariate analysis revealed that normal AMC (versus low/high AMC) at the time of relapse was a prognostic factor for improved OS (P = 0.021). On multivariate analysis, normal AMC (versus low/high AMC) at the time of relapse remained an independent prognostic factor for improved OS (hazard ratio = 0.43, P = 0.030). CONCLUSION: AMC at the time of relapse, which can be easily derived from routine clinical laboratory testing of complete blood count, might be used as a prognostic marker for survival outcomes in adult patients with early relapsed B-ALL.

Potential five-mRNA signature model for the prediction of prognosis in patients with papillary thyroid carcinoma.

Although the mortality rate of papillary thyroid carcinoma (PTC) is relatively low, the recurrence rates of PTC remain high. The high recurrence rates are related to the difficulties in treatment. Gene expression profiles has provided novel insights into potential therapeutic targets and molecular biomarkers of PTC. The aim of the present study was to identify mRNA signatures which may categorize PTCs into high-and low-risk subgroups and aid with the predictions for prognoses. The mRNA expression profiles of PTC and normal thyroid tissue samples were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNAs were identified using the 'EdgeR' software package. Gene signatures associated with the overall survival of PTC were selected, and enrichment analysis was performed to explore the biological pathways and functions of the prognostic mRNAs using the Database for Visualization, Annotation and Integration Discovery. A signature model was established to investigate a specific and robust risk stratification for PTC. A total of 1,085 differentially expressed mRNAs were identified between the PTC and normal thyroid tissue samples. Among them, 361 mRNAs were associated with overall survival (P<0.05). A 5-mRNA prognostic signature for PTC (ADRA1B, RIPPLY3, PCOLCE, TEKT1 and SALL3) was identified to classify the patients into high-and low-risk subgroups. These prognostic mRNAs were enriched in Gene Ontology terms such as 'calcium ion binding', 'enzyme inhibitor activity', 'carbohydrate binding', 'transcriptional activator activity', 'RNA polymerase II core promoter proximal region sequence-specific binding' and 'glutathione transferase activity', and Kyoto Encyclopedia of Genes and Genomes signaling pathways such as 'pertussis', 'ascorbate and aldarate metabolism', 'systemic lupus erythematosus', 'drug metabolism-cytochrome P450 and 'complement and coagulation cascades'. The 5-mRNA signature model may be useful during consultations with patients with PTC to improve the prediction of their prognosis. In addition, the prognostic signature identified in the present study may reveal novel therapeutic targets for patients with PTC.

New Criterion to Evaluate Acute-on-Chronic Kidney Injury Based on the Creatinine Reference Change.

BACKGROUND: The lack of consensus criteria of acute on chronic kidney injury (ACKI) affects the judgment for its clinical prognosis. METHODS: In this study, we analyzed the data from 711,615 hospitalized adults who had at least 2 serum creatinine (SCr) tests within 30 days. We estimated the reference change value (RCV) of SCr given initial SCr level in adults without known risks of acute kidney injury other than chronic kidney disease (CKD). We proposed a criterion for ACKI based on the RCV of SCr (cROCK), which defined ACKI as a ≥25% increase in SCr in 7 days. We validated cROCK by its association with the risks of in-hospital mortality, death after discharge, and CKD progression in a large cohort of patients with CKD stage 3. RESULTS: In 21,661 patients with CKD stage 3, a total of 3,145 (14.5%), 1,512 (7.0%), and 221 (1.0%) ACKI events were detected by both cROCK and Kidney Disease Improving Global Outcomes (KDIGO), cROCK only, and KDIGO only, respectively. cROCK detected 40% more ACKI events than KDIGO. Compared with patients without ACKI by both definitions, those with cROCK- but not KDIGO-defined ACKI had a significantly increased risk of in-hospital mortality (hazard ratio [HR] 5.53; 95% CI 3.75-8.16), death after discharge (HR 1.51; 95% CI 1.21-1.83), and CKD progression (OR 5.65; 95% CI 3.05-10.48). CONCLUSIONS: RCV-based criterion (cROCK) for ACKI is clinically valid in that it has a substantially improved sensitivity in identifying patients with high risk of adverse outcomes.

Targeting of TLE3 by miR-3677 in human breast cancer promotes cell proliferation, migration and invasion.

Numerous studies have indicated an important function of microRNAs (miRs) in breast cancer (BC) progression, oncogenesis and metastasis. However, the function of miR-3677, which has been revealed to be upregulated in BC [The Cancer Genome Atlas (TCGA) data], has not been investigated to date. In the present study, miR-3677 was revealed to be upregulated in BC as determined using TCGA. miR-3677 was significantly upregulated in BC tissues and cell lines compared with those noted in adjacent non-cancerous tissues and primary normal breast cells (P<0.05). The overexpression of miR-3677 promoted the cell proliferation, migration and invasion of BC cells. Using bioinformatics algorithms and luciferase assays, a novel target gene for miR-3677, namely transducin-like enhancer of Split3 (TLE3), was identified. Silencing of TLE3 in miR-3677-transfected BC cells suppressed their proliferation and migration. An inverse correlation was observed between miR-3677 and TLE3 expression levels in human BC tissues. In conclusion, the present study demonstrated that miR-3677 promoted BC cell proliferation, migration and invasion by inhibiting TLE3 expression, which provided a novel mechanism and a promising therapeutic target for patients with BC.

The prognostic value of soluble Klotho in patients with haemodialysis: a systematic review and meta-analysis.

AIM: The correlation between soluble Klotho (sKlotho) levels and clinical outcomes remains inconclusive for patients undergoing maintenance haemodialysis (MHD). We aimed to evaluate the potential predictive significance of sKlotho in this population by conducting a meta-analysis. METHODS: PubMed, Embase, Web of Science and Cochrane Library were comprehensively searched for studies concerning the association between sKlotho level and clinical outcomes including cardiovascular (CV) events and all-cause mortality. The pooled hazard ratios (HR) and 95% confidence intervals (CI) were generated using either random or fixed effects models. Sensitivity and subgroup analyses were used to explore heterogeneity sources. RESULTS: Eight prospective studies with 992 MHD participants were included and reduced sKlotho levels predicted more adverse outcomes in this meta-analysis. The pooled HRs and 95% CIs related to CV events, mortality, or composite outcomes were 1.73 (95% CI 1.08-2.76, p = 0.02), 2.34 (95% CI 1.34-2.07, p = 0.003) or 1.75 (95% CI 1.19-2.57, p = 0.005). Moderate heterogeneity was observed in the composite adverse outcomes (I 2 = 57%, p = 0.05). Age and sKlotho level were the main sources of heterogeneities in the subgroup analysis. CONCLUSION: Lower sKlotho levels were associated with more CV events and all-cause mortality, suggesting that sKlotho may have predictive value in CKD patients receiving haemodialysis.

Frequency-Specific Regional Homogeneity Alterations in Tourette Syndrome.

Tourette syndrome (TS) is a developmental neuropsychiatric disorder with onset during childhood. Because of its complex spectrum of phenotypes, the underlying pathophysiology of TS is still unclear. Resting-state functional magnetic resonance imaging demonstrated aberrant spontaneous neural synchronization in conventional frequency band (0.01-0.08 Hz) in TS. No published studies have reported abnormalities of local synchronization across different frequency bands. We estimated the alterations of local synchronization across five bands ranging from 0 to 0.25 Hz. Seventy-nine children with TS and 63 age-, sex-, and handedness-matched healthy children were recruited. Frequency-specific regional homogeneity (ReHo) and independent component analysis were used to identify functional alterations between TS and healthy children. TS patients showed significantly increased ReHo in the left precentral gyrus and decreased ReHo in the right operculum. Abnormal ReHo alterations of the superior frontal gyrus, superior parietal gyrus, anterior cingulate gyrus, putamen, superior temporal gyrus, and operculum were observed in different frequency bands. TS patients showed increased connectivity of the right superior frontal gyrus within the left executive control network. In addition, a significantly negative correlation was found between Yale Global Tic Severity Scale (YGTSS) vocal score and ReHo values of the right operculum in the highest frequency bands (0.198-0.25 Hz), while a significant positive correlation was found between YGTSS motor score and altered connectivity of the right superior frontal gyrus. The present study revealed frequency-specific abnormal alterations of ReHo in the whole brain and altered connectivity within the executive control network of TS children. Its neural importance and clinical practicability require further investigation.