3D-Slicer Software-Assisted Neuroendoscopic Surgery in the Treatment of Hypertensive Cerebral Hemorrhage.

OBJECTIVE: To explore the 3D-slicer software-assisted endoscopic treatment for patients with hypertensive cerebral hemorrhage. METHODS: A total of 120 patients with hypertensive cerebral hemorrhage were selected and randomly divided into control group and 3D-slicer group with 60 cases each. Patients in the control group underwent traditional imaging positioning craniotomy, and patients in the 3D-slicer group underwent 3D-slicer followed by precision puncture treatment. In this paper, we evaluate the hematoma clearance rate, nerve function, ability of daily living, complication rate, and prognosis. RESULTS: The 3D-slicer group is better than the control group in various indicators. Compared with the control group, the 3D-slicer group has lower complications, slightly higher hematoma clearance rate, and better recovery of nerve function and daily living ability before and after surgery. The incidence of poor prognosis is low. CONCLUSION: The 3D-slicer software-assisted endoscopic treatment for patients with hypertensive intracerebral hemorrhage has a better hematoma clearance effect, which is beneficial to the patient's early recovery and reduces the damage to the brain nerve of the patient.

Correction: High-resolution DNA size enrichment using a magnetic nano-platform and application in non-invasive prenatal testing.

Correction for 'High-resolution DNA size enrichment using a magnetic nano-platform and application in non-invasive prenatal testing' by Bo Zhang et al., Analyst, 2020, 145, 5733-5739, DOI: 10.1039/D0AN00813C.

Metabolic profile of heart tissue in cyanotic congenital heart disease.

BACKGROUND: Cyanotic congenital heart disease (CCHD) is one of the most common birth anomalies, in which chronic hypoxia is the basic pathophysiological process. METHODS: To investigate the heart's metabolic remodeling to hypoxia, we performed an untargeted metabolomic analysis of cardiac tissue from 20 CCHD patients and 15 patients with acyanotic congenital heart disease (ACHD). RESULTS: A total of 71 (63%) metabolites from 113 detected substances in cardiac tissue differed between the CCHD and ACHD groups. A partial least squares discriminant analysis showed separation between the CCHD and ACHD groups. A pathway enrichment analysis revealed that the most enriched metabolic pathways were amino acid metabolism and energy metabolism. Eleven amino acids were increased in CCHD patients, indicating that protein synthesis was down-regulated. Most of the metabolites in Krebs circle were increased in CCHD patients, suggesting down regulation of aerobic energy metabolism. Hierarchical cluster analysis showed that nicotinamide adenine dinucleotide (NAD) was clustered with Krebs cycle related substrates and its level was significantly higher in CCHD than that in ACHD patients. These analyses suggest that NAD might play an important role in response to hypoxia in CCHD patients. CONCLUSION: Our data showed a significantly different metabolic profile in CCHD patients compared to ACHD patients, including reduced protein synthesis and aerobic energy production, and the increased level of NAD in the myocardium may be a response mechanism to hypoxia.

High-resolution DNA size enrichment using a magnetic nano-platform and application in non-invasive prenatal testing.

Precise DNA sizing can boost sequencing efficiency, reduce cost, improve data quality, and even allow sequencing of low-input samples, while current pervasive DNA sizing approaches are incapable of differentiating DNA fragments under 200 bp with high resolution (<20 bp). In non-invasive prenatal testing (NIPT), the size distribution of cell-free fetal DNA in maternal plasma (main peak at 143 bp) is significantly different from that of maternal cell-free DNA (main peak at 166 bp). The current pervasive workflow of NIPT and DNA sizing is unable to take advantage of this 20 bp difference, resulting in sample rejection, test inaccuracy, and restricted clinical utility. Here we report a simple, automatable, high-resolution DNA size enrichment workflow, named MiniEnrich, on a magnetic nano-platform to exploit this 20 bp size difference and to enrich fetal DNA fragments from maternal blood. Two types of magnetic nanoparticles were developed, with one able to filter high-molecular-weight DNA with high resolution and the other able to recover the remaining DNA fragments under the size threshold of interest with >95% yield. Using this method, the average fetal fraction was increased from 13% to 20% after the enrichment, as measured by plasma DNA sequencing. This approach provides a new tool for high-resolution DNA size enrichment under 200 bp, which may improve NIPT accuracy by rescuing rejected non-reportable clinical samples, and enable NIPT earlier in pregnancy. It also has the potential to improve non-invasive screening for fetal monogenic disorders, differentiate tumor-related DNA in liquid biopsy and find more applications in autoimmune disease diagnosis.

MiR-106a-5p modulates apoptosis and metabonomics changes by TGF-ß/Smad signaling pathway in cleft palate.

BACKGROUND: The molecular mechanisms of abnormal palatogenesis were investigated in this study. A key regulator, miR-106a-5p, and its target pathway were analyzed. OBJECTIVES: This research is trying to clarify the underlying mechanism of the modulation of miRNA transcription during the formation of cleft palate by 7T and 9.4T NMR metabolomic platforms. METHOD: Differentially expressed miRNAs and mRNAs were analyzed by microarray analysis and verified by qRT-PCR. The protein expression in TGFß signaling pathways were analyzed by Western Blotting. The relationship between miR-106a-5p and TGFß were analyzed by luciferase reporter assay. Cell apoptosis were analyzed by flow cytometer. And finally, the metabonomics were analyzed by NMR and multivariate data analysis models (MVDA). RESULTS: The expression of miR-106a-5p increased in cleft palatal tissue and negatively correlated with the protein level of Tgfbr2. The luciferase assay further proved that the tgfbr2 was a direct target of miR-106a-5p. In another aspect, miR-106a-5p increased apoptosis level in palatal mesenchymal cells, possibly because its inhibition of TGFß signaling pathway. Moreover, low cholesterol and choline levels with high citric acid and lipid levels were observed by 7T and 9.4T NMR metabonomic analysis, which inferred the disorder of cell membrane synthesis in cleft palate formation. Furthermore, transformation from choline to phosphatidylcholine regulated by miR-106a-5p was also disrupted, resulting in phosphatidic choline synthesis disorder and reduced cell membrane synthesis. CONCLUSIONS: The regulatory mechanism of cleft palate was studied at transcriptional and metabolomics levels, which may provide important information in understanding the primary cause of this abnormality.

miRTarBase 2020: updates to the experimentally validated microRNA-target interaction database.

MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18-25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA-target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA-target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/.

Up-regulated ADP-Ribosylation factor 3 promotes breast cancer cell proliferation through the participation of FOXO1.

ADP-ribosylation factor 3 (ARF3) is a member of the KRAS proto-oncogene, GTPase(Ras) super-family of guanine nucleotide-binding proteins that mediates Golgi-related mitosis, but its role in malignant cells is unclear. In the present study, we found that mRNA and protein expression of ARF3 is up-regulated in breast cancer cells. Immunohistochemical analysis of 167 paraffin-embedded archived breast cancer tissues showed that ARF3 expression was localized primarily in the cytoplasm and was significantly up-regulated in malignant specimens compared to benign specimens. There were strong associations between ARF3 expression and clinicopathological characteristics in breast cancer. We also found that overexpressing ARF3 promoted, while silencing endogenous ARF3 inhibited, the proliferation of breast cancer cells by regulating cell cycle G1-S transition. Moreover, the pro-proliferative effect of ARF3 on breast cancer cells was associated with inactivation of the forkhead box O1 (FOXO1) transcription factor. ARF3 promotes breast cancer cell proliferation through the participation of FOXO1 and represents as a novel prognostic marker and therapeutic target for breast cancer.

Association Between an Interferon Regulatory Factor 6 Gene Polymorphism and Nonsyndromic Cleft Palate Risk.

Background: Involvement of interferon regulatory factor 6 (IRF6) gene polymorphisms in nonsyndromic cleft palate (NSCP) risk remains controversial. This investigation was performed to evaluate the relationship between IRF6 gene polymorphisms and NSCP risk. Materials and Methods: Two hundred forty-one patients with NSCP (including 103 complete trio families) were recruited, and 242 unaffected individuals were included as controls. Polymorphisms for the IRF6 rs2235371, rs801619, rs642961, rs44844880, and rs8049367 loci were characterized in both groups. Furthermore, eligible studies were identified from the databases through June 1, 2017, and were included in a meta-analysis to enhance the robustness of our conclusions. Results: The IRF6 rs2235371 A allele and AA genotype in the case group were found at higher frequencies than in the control group (A allele: p < 0.0016; AA genotype: p < 0.0049). The IRF6 rs801619 AA genotype and G allele were associated with NSCP risk (G allele: p < 0.0061; AA genotype: p < 0.0195). At the IRF6 rs642961, rs44844880, and rs8049367 loci genotype and allele frequencies were not statistically different between the NSCP group and normal controls. In the meta-analysis, the IRF6 A/G gene polymorphism (rs2235371) and IRF6 A/G gene polymorphism (rs642961) were associated with NSCP risk in the general population, whereas the IRF6 A/C gene polymorphism (rs2013162) was not. Conclusion: The IRF6 A/G gene polymorphisms at rs2235371 and rs642961, but not the IRF6 A/C gene polymorphism rs2013162, were associated with NSCP risk.

Kinesin Family Member 11 Enhances the Self-Renewal Ability of Breast Cancer Cells by Participating in the Wnt/ß-Catenin Pathway.

PURPOSE: Our previous studies have shown that kinesin family member 11 (KIF11) is markedly overexpressed in human breast cancer cells or tissues and positively correlated with distant metastasis and prognosis in patients with breast cancer, suggesting an important role in the regulation of cancer stem cells. Herein, we examined the role of KIF11 in breast cancer stem cells. METHODS: In the current study, we validated our previous findings through analysis of data collected in The Cancer Genome Atlas. Endogenous KIF11 was stably silenced in MCF-7 and SKBR-3 cells. Flow cytometry was used to measure the proportion of side-population (SP) cells. Mammosphere culture and tumor implantation experiments in immunodeficient mice were used to assess the self-renewal ability of breast cancer cells. Real-time polymerase chain reaction, western blot, immunofluorescence staining, luciferase reporter assays and Wnt agonist treatment were conducted to investigate the signaling pathways regulated by KIF11. RESULTS: We found that the expression level of KIF11 was positively correlated with stem cell-enrichment genes. The proportion of SP cells was significantly reduced in KIF11-silenced cells. Silencing endogenous KIF11 not only reduced the size and number of mammospheres in vitro, but also reduced the ability of breast cancer cells to form tumors in mice. Simultaneously, we found that KIF11 was involved in regulating the activation of the Wnt/ß-catenin signaling pathway. CONCLUSION: Endogenous KIF11 enhances the self-renewal of breast cancer cells by activating the Wnt/ß-catenin signaling pathway, thereby enhancing the characteristics of breast cancer stem cells.

Construction of a set of novel and robust gene expression signatures predicting prostate cancer recurrence.

We report here numerous novel genes and multiple new signatures which robustly predict prostate cancer (PC) recurrence. We extracted 696 differentially expressed genes relative to a reported PC signature from the TCGA dataset (n = 492) and built a 15-gene signature (SigMuc1NW) using Elastic-net with 10-fold cross-validation through analyzing their expressions at 1.5 standard deviation/SD below and 2 SD above a population mean. SigMuc1NW predicts biochemical recurrence (BCR) following surgery with 56.4% sensitivity, 72.6% specificity, and 63.24 median months disease free (MMDF) (P = 1.12e-12). The prediction accuracy is improved with the use of SigMuc1NW's cutpoint (P = 3e-15) and is further enhanced (sensitivity 67%, specificity 75.7%, MMDF 45.2, P = 0) when all 15 genes were analyzed through their cutpoints instead of their SDs. These genes individually associate with BCR using either SD or cutpoint as the cutoff points. Eight of 15 genes are individual risk factors after adjusting for age at diagnosis, Gleason score, surgical margin, and tumor stage. Eleven of 15 genes are novel to PC. SigMuc1NW discriminates BCR with time-dependent AUC (tAUC) values of 76.6% at 11.5 months (76.6%-11.5 m), 73.8%-22.3 m, 78.5%-32.1 m, and 76.4%-48.4 m. SigMuc1NW is correlated with adverse features of PC, high Gleason scores (odds ratio/OR 1.48, P < 2e-16), and advanced tumor stages (OR 1.33, P = 4.37e-13). SigMuc1NW remains an independent risk factor of BCR (HR 2.44, 95% CI 1.53-3.87, P = 1.62e-4) after adjusting for age at diagnosis, Gleason score, surgical margin, and tumor stage. In an independent PC (MSKCC) cohort (n = 140), these 15 genes were altered in PC vs normal tissue, metastatic PCs vs primary PCs, and recurrent PCs vs nonrecurrent PCs. Importantly, a 10-gene subsignature SigMuc1NW1 predicts BCR in MSKCC (P = 3.11e-15) and TCGA (P = 3.13e-12); SigMuc1NW1 discriminates BCR at 18.4 m with tAUC as 82.5%. Collectively, our analyses support SigMuc1NW as a novel and robust signature in predicting BCR of PC.

Biogenesis of MiRNA-195 and its role in biogenesis, the cell cycle, and apoptosis.

microRNA-195(miR-195) is an important member of the micro-15/16/195/424/497 family, and which is activated in multiple diseases, such as cancers, heart failure, and schizophrenia. Mir-195 regulates a plethora of target proteins, which are involved in the cell cycle, apoptosis, proliferation. WEE1, CDK6, and Bcl-2 are confirmed target genes of miR-195 that are involved in miR-195-mediated cell-cycle and apoptosis effects. However, the mechanism of miR-195 action is not completely understood. This review summarizes recent the research progress regarding the roles of miR-195 in the cell cycle and in apoptosis.

NINJ2 polymorphism is associated with ischemic stroke in Chinese Han population.

Recently, a genome-wide association study reported an association between two single nucleotide polymorphisms (SNPs) rs11833579 and rs12425791 near NINJ2 gene and ischemic stroke in Caucasians. Therefore, NINJ2 gene is an important candidate locus in the prevalence of ischemic stroke. We performed a hospital based genetic association study in Chinese Han subjects to investigate the relationship between NINJ2 gene and ischemic stroke. We genotyped 14 tagging single nucleotide polymorphisms (tSNP) in 749 ischemic stroke subjects and 924 control subjects and conducted the association between these tSNPs and ischemic stroke. We detected a tSNP rs10849373 in the first intron of the NINJ2 gene significantly associated with ischemic stroke (both genotype and allelic p=0.0001). The minor A allele increased the risk of ischemic stroke with a per-allele OR of 1.37 for the additive genetic model in univariate analysis (p=0.0001). The significance remained after adjustment for the covariates of age, gender, BMI, cigarette smoking, alcohol drinking, hypertension, and diabetes. Therefore, we report a new genetic variant, rs10849373, located in the first intron of the NINJ2 gene, conferring risk of ischemic stroke in Chinese Han subjects. Further genetic association and functional studies are required to search the causal functional variant in linkage disequilibrium with this polymorphism.

The effect of early and intensive statin therapy on ventricular premature beat or nonsustained ventricular tachycardia in patients with acute coronary syndrome.

BACKGROUND: To evaluate the prognostic value of early and intensive lipid-lowering treatment on ventricular premature beat or nonsustained ventricular tachycardia (NSVT) after acute coronary syndrome (ACS) (ST-elevation myocardial infarction [STEMI], non-STEMI, and unstable angina pectoris). HYPOTHESIS: Provided that early and intensive lipid-lowering treatment can reduce ventricular premature beat or non-sustained ventricular tachycardia after ACS. METHODS: A total of 586 patients with ACS were randomly divided into 2 groups: group A (with conventional statin therapy, to receive 10 mg/day atorvastatin, n = 289) and group B (early and intensive statin therapy, 60 mg immediately and 40 mg/day atorvastatin, n = 297). The frequency of ventricular premature beat and NSVT was recorded with Holter monitoring after hospitalization (24 hours and 72 hours). RESULTS: Seventy-seven (11.8%) patients had NSVT. When compared to patients with no documented NSVT, patients with NSVT were older and more often had myocardial infarction, diabetes mellitus, atrial fibrillation, and an ejection fraction < 40% in their history. Ventricular premature beats decreased significantly in the early and aggressive treatment group (24 hours, P < 0.01; 72 hours, P < 0.001). A significant reduction in NSVT was seen in the early and aggressive (24 hours, P < 0.01; 72 hours, P < 0.001) group. No side effects were observed in either group. CONCLUSIONS: Early and intensive lipid-lowering treatment can obviously decrease ventricular premature beats and NSVT.

Non-ST-segment elevation myocardial infarction in a patient with essential thrombocythemia treated with glycoprotein IIb/IIIa inhibitor: a case report.

Essential thrombocythemia (ET) can cause systemic vascular thrombosis but rarely cause obstruction of coronary arteries or acute myocardial infarction (MI). Treatment of acute MI in patients with ET may be a problem due to the important role of platelets in the pathogenesis of infarction. In this report, a 63-year-old man presented with acute chest pain and a greatly increased platelet count. The patient was successfully treated with intravenous tirofiban, a glycoprotein IIb/IIIa receptor blocker. Essential thrombocythemia was diagnosed based on bone marrow findings, clinical presentation, and laboratory analysis. Thrombocythemia had been controlled with hydroxyurea.

The effect of early and intensive statin therapy on ventricular premature beat or non-sustained ventricular tachycardia in patients with acute coronary syndrome.

BACKGROUND: Our study's aim was to evaluate the prognostic value of early and intensive lipid-lowering treatment on ventricular premature beat or non-sustained ventricular tachycardia (NSVT) after acute coronary syndrome (STEMI, non-STEMI, and unstable angina pectoris). METHODS: Some 586 patients with acute coronary syndrome were randomly divided into two groups: Group A (with conventional statin therapy, to receive 10 mg/day atorvastatin, n = 289) and Group B (given early and intensive statin therapy, 60 mg immediately and 40 mg/day atorvastatin, n = 297). The frequency of ventricular premature beat and NSVT was recorded via Holter monitoring after hospitalization (24 h and 72 h). RESULTS: Seventy seven (11.8%) patients had NSVT. When compared to patients with no documented NSVT, patients with NSVT were older and more frequently had myocardial infarction in their history, diabetes mellitus, atrial fibrillation and an ejection fraction < 40%. Ventricular premature beats decreased significantly in the early and aggressive treatment group (24 h, p < 0.01; 72 h, p < 0.001). A significant reduction in NSVT was seen in the early and aggressive treatment group (24 h, p < 0.01; 72 h, p < 0.001). There were no side effects observed in either group. CONCLUSIONS: Early and intensive lipid-lowering treatment can clearly decrease ventricular premature beats and NSVT.

[Effects of PPAR-gamma agonist rosiglitazone on MMP-9 and TIMP-1 expression of monocyte-derived macrophages isolated from patients with acute coronary syndrome].

OBJECTIVE: Coronary arterial plaque rupture and secondary thrombosis are the major pathogenesis of acute coronary syndrome (ACS). Metalloprotease (MMPs) secreted by monocyte/macrophage was the main predisposing factor of the plaque rupture and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is involved in a variety of inflammatory cytokine gene transcriptional regulations. We explored the possible role of PPAR-gamma in the regulation of MMP-9 and TIMP-1 expressed by peripheral monocyte-derived macrophages (MDMs) from patients with ACS. METHODS: Peripheral blood mononuclear cells were isolated from 48 patients with ACS and 28 healthy controls and stimulated by macrophage colony-stimulating factor (0.1 microg/ml for 24 hours) to form MDMs. MDMs were then incubated under various concentrations of rosiglitazone (0, 1, 10, 20 micromol/L) for 48 hours. The concentrations of MMP-9 and TIMP-1 in the supernatant were measured by enzyme linked immunosorbent assay, and the mRNA expression of PPAR-gamma, MMP-9 by RT-PCR and nuclear factor-kappaB P65 (NF-kappaB P65) expression by immunohistochemistry. RESULTS: PPAR-gamma mRNA expression was significantly lower while NF-kappaB P65 and MMP-9 expression as well as MMP-9 and TIMP-1 concentrations in supernatant were significantly higher in ACS group than those in control group (all P < 0.05). After rosiglitazone intervention, PPAR-gamma mRNA expression was significantly upregulated in both ACS and control groups in a dose-dependent manner. Both the MMP-9 concentration in the supernatant and MMP-9 mRNA expression were reduced post intervention with rosiglitazone in both groups. The TIMP-1 mRNA expression and concentration in supernatant were not affected by rosiglitazone in both groups. Rosiglitazone induced significant downregulation of NF-kappaB P65 expression in both groups. CONCLUSION: Rosiglitazone intervention may downregulate MMP-9 expression by upregulating PPAR-gamma expression, and by downregulating NF-kappaB expression in MDMs isolated from patients with ACS.