Perioperative and long-term results of ultrasonography-guided single- and multiple-tract percutaneous nephrolithotomy for staghorn calculi.

BACKGROUND: It is possible that this condition will lead to urosepsis and progressive deterioration of renal function in the absence of surgical intervention. Several recent clinical studies have shown that multi-tract percutaneous nephrolithotomy (M-PCNL) has a similar stone free rate (SFR) as standard percutaneous nephrolithotomy (S-PCNL). As a result, M-PCNL was also recommended as a treatment option for staghorn calculi. AIM: To examine the perioperative and long-term results of ultrasonography-guided single- and M-PCNL. METHODS: This was a retrospective cohort study. Between March 2021 and January 2022, the urology department of our hospital selected patients for the treatment of staghorn calculi using percutaneous nephrolithotomy. The primary outcomes were complication rate and SFR, and the characteristics of patients, operative parameters, laboratory measurements were also collected. RESULTS: In total, 345 patients were enrolled in the study (186 in the S-PCNL group and 159 in the M-PCNL group). The SFR in the M-PCNL group was significantly higher than that in the S-PCNL group (P = 0.033). Moreover, the incidence rates of hydrothorax (P = 0.03) and postoperative infection (P = 0.012) were higher in the M-PCNL group than in the S-PCNL group. Logistic regression analysis demonstrated that post-operative white blood cell count (OR = 2.57, 95%CI: 1.90-3.47, P < 0.001) and stone size (OR = 1.59, 95%CI: 1.27-2.00, P < 0.001) were associated with a higher overall complication rate in the S-PCNL group. Body mass index (OR = 1.22, 95%CI: 1.06-1.40, P = 0.004) and stone size (OR = 1.70, 95%CI: 1.35-2.15, P < 0.001) were associated with increased overall complications in the M-PCNL group. CONCLUSION: Multiple access tracts can facilitate higher SFR while slightly increasing the incidence of acceptable complications.

Improving the second-tier classification of methylmalonic acidemia patients using a machine learning ensemble method.

INTRODUCTION: Methylmalonic acidemia (MMA) is a disorder of autosomal recessive inheritance, with an estimated prevalence of 1:50,000. First-tier clinical diagnostic tests often return many false positives [five false positive (FP): one true positive (TP)]. In this work, our goal was to refine a classification model that can minimize the number of false positives, currently an unmet need in the upstream diagnostics of MMA. METHODS: We developed machine learning multivariable screening models for MMA with utility as a secondary-tier tool for false positives reduction. We utilized mass spectrometry-based features consisting of 11 amino acids and 31 carnitines derived from dried blood samples of neonatal patients, followed by additional ratio feature construction. Feature selection strategies (selection by filter, recursive feature elimination, and learned vector quantization) were used to determine the input set for evaluating the performance of 14 classification models to identify a candidate model set for an ensemble model development. RESULTS: Our work identified computational models that explore metabolic analytes to reduce the number of false positives without compromising sensitivity. The best results [area under the receiver operating characteristic curve (AUROC) of 97%, sensitivity of 92%, and specificity of 95%] were obtained utilizing an ensemble of the algorithms random forest, C5.0, sparse linear discriminant analysis, and autoencoder deep neural network stacked with the algorithm stochastic gradient boosting as the supervisor. The model achieved a good performance trade-off for a screening application with 6% false-positive rate (FPR) at 95% sensitivity, 35% FPR at 99% sensitivity, and 39% FPR at 100% sensitivity. CONCLUSIONS: The classification results and approach of this research can be utilized by clinicians globally, to improve the overall discovery of MMA in pediatric patients. The improved method, when adjusted to 100% precision, can be used to further inform the diagnostic process journey of MMA and help reduce the burden for patients and their families.

Numerical and Field Investigations of Acoustic Emission Laws of Coal Fracture under Hydro-Mechanical Coupling Loading.

Taking coal under hydro-mechanical coupling as the research object, the discrete element software PFC3D (particle flow code) was used to analyze the relationships among the force, acoustic emission (AE), and energy during coal fracture. Based on the moment tensor (MT) inversion, we revealed the AE event distribution and source type during crack initiation and propagation until the final failure of coal. Meanwhile, we examined the relationships among the stress, number and type of cracks, magnitude, KE, and b value of AE under different water and confining pressures. The results show that the numerical simulation can effectively determine the microscopic damage mechanism of coal under different conditions. Moreover, the rupture type of the numerical simulation is consistent with the field investigations, which verifies the rationality of the simulation. These research results can provide reference for safety production evaluation of water inrush mines.

Poplar PsnICE1 enhances cold tolerance by binding to different cis-acting elements to improve reactive oxygen species-scavenging capability.

Low temperature is a major stress that severely affects plant growth and development. Inducer of CBF expression 1 (ICE1) plays a key role in plant cold tolerance by regulating the expression of cold stress-responsive genes. In the present study, we characterized the function and underlying regulatory mechanism of PsnICE1 from Xiaohei poplar (Populus simonii × Populus nigra). PsnICE1 was significantly induced in response to cold stress in the roots, stems and leaves. PsnICE1 proteins were found to localize to the nucleus and exert transactivation activity via their N-terminal transactivation domain. Compared with non-transgenic poplar, transgenic poplar overexpressing PsnICE1 showed substantially enhanced tolerance to cold stress, with higher survival rates and antioxidant enzyme activity levels and reduced reactive oxygen species (ROS) accumulation. In contrast, plants with RNA inhibition-mediated silencing of PsnICE1 showed the opposite phenotype. PsnICE1 can bind to H-box element and abscisic acid-responsive element (ABRE), and more importantly, it mainly binds to IBS1 (a newly discovered cis-acting element) and E-box elements to regulate stress-related genes involved in ROS scavenging. Overall, these results indicated that PsnICE1 functions as a positive regulator of cold tolerance and serves as a potential candidate gene for plant cold tolerance improvement via molecular breeding.

Exploring New Zintl Phases in the 9-4-9 Family via Al Substitution. Synthesis, Structure, and Physical Properties of Ae9Mn4-xAlxSb9 (Ae = Ca, Yb, Eu).

Three new quaternary Zintl phases with the "9-4-9" formula, Ae9Mn4-xAlxSb9 (Ae = Ca, Yb, Eu), have been synthesized using Pb as the metal flux, and their crystal structures have been established by single-crystal X-ray diffraction. Both Ca9Mn2.91(4)Al1.09Sb9 and Yb9Mn3.59(6)Al0.41Sb9 are isostructural with Ca9Mn4Bi9, and they crystallize in the orthorhombic space group Pbam with unit cell dimensions of a = 12.4571(8), 12.2884(16) Å, b = 22.1352(16), 22.024(3) Å, and c = 4.6012(3), 4.6187(6) Å, respectively. Their anionic structures can be viewed as infinite ribbons based on corner-shared tetrahedrons. Also, Eu9Mn2.87(4)Al1.13Sb9 has the space group Cmca and a = 9.4883(7) Å, b = 23.6895(18) Å, and c = 24.4845(19) Å. The structural relationships between Ca9Mn2.91(4)Al1.09Sb9 and Eu9Mn2.87(4)Al1.13Sb9 are compared and discussed as well. The successful Al3+ substitution provides additional electrons to the compounds to achieve structural stability. Magnetic susceptibility and electrical resistivity measurements, performed on single crystals of Eu9Mn2.87(4)Al1.13Sb9, indicate complex magnetic properties and semiconductor behavior. The physical properties of Yb9Mn3.59(6)Al0.41Sb9 are similar to those observed for Yb9Mn4.18(2)Sb9.

Evaluation of a panel of very long-chain lysophosphatidylcholines and acylcarnitines for screening of X-linked adrenoleukodystrophy in China.

BACKGROUND: Elevated blood C24:0- and C26:0-carnitines and lysophosphatidylcholines (LPCs) were reported as diagnostic biomarkers for X-linked adrenoleukodystrophy (X-ALD). Our aim was to establish the reference intervals of very long-chain (VLC) acylcarnitines (C20-C26) and LPCs in Chinese population, and evaluate valuable biomarkers and develop panel for screening X-ALD in China. METHODS: The method of FIA-MS/MS-based quantification of VLC acylcarnitines and LPCs was validated in order to determine their concentrations in dried blood spots from 7 X-ALD boys, 396 age-matched healthy controls, and 3078 putative normal newborns. Screening performance of these metabolites for X-ALD was clinically evaluated. RESULTS: The reference intervals of VLC acylcarnitines, LPCs and their ratios were established in Chinese population, and for some metabolites like C26 and C26:0-LPC, the reference intervals were found to be significantly different between children and newborns. C24 and C26, C26:0-LPC, C24/C22 and C26/C22 ratios were found to have better performance than other analytes to identify X-ALD boys from normal children. CONCLUSION: C26:0-LPC, C24 and C26 are three most valuable biomarkers for screening of X-ALD in children group. The information of age-related variations in concentration of some biomarkers is helpful for accurate screening of X-ALD.

Preoperative Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio are Associated with the Prognosis of Group 3 and Group 4 Medulloblastoma.

Inflammation and immunoreaction markers were correlated with the survival of patients in many tumors. However, there were no reports investigating the relationships between preoperative hematological markers and the prognosis of medulloblastoma (MB) patients based on the molecular subgroups (WNT, SHH, Group 3, and Group 4). A total 144 MB patients were enrolled in the study. The differences of preoperative hematological markers among molecular subgroups of MB were compared by One-way ANOVA method. Kaplan-Meier method was used to calculate the curves of progression free survival (PFS) and overall survival (OS). The comparison of survival rates in different groups were conducted by the Log-rank test. Multivariate analysis was used to evaluate independent prognostic factors. Increased preoperative NLR (neutrophil-to-lymphocyte ratio, PFS, P = 0.004, OS, P < 0.001) and PLR (platelet-to-lymphocyte ratio, PFS, P = 0.028, OS, P = 0.003) predicted poor prognosis in patients with MB, while preoperative MLR (monocyte-to-lymphocyte ratio), MPV (mean platelet volume), PDW (platelet distribution width), and AGR (albumin-to-globulin ratio) were revealed no predictive value on the prognosis of patients with MB. Furthermore, high preoperative NLR and PLR predicted unfavorable prognosis in childhood MB patients. However, preoperative NLR and PLR were not associated with the prognosis in adult MB patients. Multivariate analysis demonstrated preoperative NLR (PFS, P = 0.029, OS, P = 0.005) and PLR (PFS, P = 0.023, OS, P = 0.005) were the independent prognostic factors in MB patients. Emphatically, the levels of preoperative NLR and PLR in Group 3 MB were significantly higher than those in WNT MB. High preoperative NLR was associated with unfavorable OS in Group 3 (P = 0.032) and Group 4 (P = 0.027) tumors. Similarly, increased preoperative PLR predicted poor PFS (P = 0.012) and OS (P = 0.009) in Group 4 tumors. Preoperative NLR and PLR were the potential prognostic markers for MB patients. Preoperative NLR and PLR were significantly associated with the survival of Group 3 and Group 4 tumors.

Expression and function of lncRNA ANRIL in a mouse model of acute myocardial infarction combined with type 2 diabetes mellitus.

BACKGROUND: This study intends to explore whether lncRNA ANRIL has an influence on type 2 diabetes mellitus (T2DM) complicated with acute myocardial infarction (MI) and to further investigate the underlying mechanism. METHODS: The ANRIL level in peripheral blood from patients was detected by qRT-PCR. A T2DM mouse model was established by intraperitoneal injection of streptozocin (STZ). MI was induced by ligation of the left anterior descending coronary artery. Cardiac function parameters were measured using echocardiography. Triphenyltetrazolium chloride (TTC) staining was performed to determine the infarct size, and Masson staining was conducted to delineate the area of fibrosis in the myocardium. TUNEL staining was used to detect myocardial cell apoptosis. The expression of the myocardial fibrosis-related proteins TGF-ß1, collagen I and collagen III was analysed using Western blot. RESULTS: ANRIL was upregulated in peripheral venous blood from patients with T2DM-MI and in myocardial tissues from the established T2DM-MI model mice. Furthermore, ANRIL overexpression caused cardiac dysfunction and increased the heart/body weight rate and infarct size in the T2DM-MI mice. Moreover, ANRIL overexpression caused myocardial fibrosis and myocardial cell apoptosis, and it increased the expression of the myocardial fibrosis-related proteins TGF-ß1, collagen I and collagen III in the T2DM-MI mice. However, ANRIL knockdown exerted the opposite effects. CONCLUSION: ANRIL may be involved in the progression and development of T2DM-MI, which might provide novel ideas for the prevention and treatment of cardiovascular diseases.

Prognostic value of preoperative hematological markers combined with molecular pathology in patients with diffuse gliomas.

The prediction of clinical outcome for patients with infiltrative gliomas is challenging. Although preoperative hematological markers have been proposed as predictors of survival in glioma and other cancers, systematic investigations that combine these data with other relevant clinical variables are needed to improve prognostic accuracy and patient outcomes. We investigated the prognostic value of preoperative hematological markers, alone and in combination with molecular pathology, for the survival of 592 patients with Grade II-IV diffuse gliomas. On univariate analysis, increased neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), and decreased albumin-to-globulin ratio (AGR), all predicted poor prognosis in Grade II/III gliomas. Multivariate analysis incorporating tumor status based on the presence of IDH mutations, TERT promoter mutations, and 1p/19q codeletion showed that in lower-grade gliomas, high NLR predicted poorer survival for the triple-negative, IDH mutation only, TERT mutation only, and IDH and TERT mutation groups. NLR was an independent prognostic factor in Grade IV glioma. We therefore propose a prognostic model for diffuse gliomas based on the presence of IDH and TERT promoter mutations, 1p/19q codeletion, and NLR. This model classifies lower-grade gliomas into nine subgroups that can be combined into four main risk groups based on survival projections.

[Functional clear aligner treatment of class ⠡ malocclusion in teenagers].

Class Ⅱ malocclusion is a common orofacial deformity that could harm the facial esthetics and oral function. Two-stage treatment strategy always applies to functional and skeletal (mild and moderate) class Ⅱ malocclusion with man-dibular retrognathism in teenagers. Traditional functional orthopedic appliances are less comfortable and inconvenient to correct the dental arches, making the treatment duration long. With the rapid progress of digital technology and material science, functional clear aligners that offer comfort have emerged. Functional clear aligners can combine orthopedic and orthodontic treatments to correct the jaw relationship and align the dental arch, thereby shortening the treatment duration. This paper emphasizes the treatment key points, and clinical experience of using functional clear aligners.

Preliminary application of mxed reality in neurosurgery: Development and evaluation of a new intraoperative procedure.

During neurological surgery, neurosurgeons have to transform the two-dimensional (2D) sectional images into three-dimensional (3D) structures at the cognitive level. The complexity of the intracranial structures increases the difficulty and risk of neurosurgery. Mixed reality (MR) applications reduce the obstacles in the transformation from 2D images to 3D visualization of anatomical structures of central nervous system. In this study, the holographic image was established by MR using computed tomography (CT), computed tomography angiography (CTA) and magnetic resonance imaging (MRI) data of patients. The surgeon's field of vision was superimposed with the 3D model of the patient's intracranial structure displayed on the mixed reality head-mounted display (MR-HMD). The neurosurgeons practiced and evaluated the feasibility of this technique in neurosurgical cases. We developed the segmentation image masks and texture mapping including brain tissue, intracranial vessels, nerves, tumors, and their relative positions by MR technologies. The results showed that the three-dimensional imaging is in a stable state in the operating room with no significant flutter and blur. And the neurosurgeon's feedback on the comfort of the equipment and the practicality of the technology was satisfactory. In conclusion, MR technology can holographically construct a 3D digital model of patient's lesions and improve the anatomical perception of neurosurgeons during craniotomy. The feasibility of the MR-HMD application in neurosurgery is confirmed.

BplMYB46 from Betula platyphylla Can Form Homodimers and Heterodimers and Is Involved in Salt and Osmotic Stresses.

MYB proteins play important roles in the regulation of plant growth, development, and stress responses. Overexpression of BplMYB46 from Betula platyphylla improved plant salt and osmotic tolerances. In the present study, the interaction of eight avian myeloblastosis viral oncogene homolog (MYB) transcription factors with BplMYB46 was investigated using the yeast two-hybrid system, which showed that BplMYB46 could form homodimers and heterodimers with BplMYB6, BplMYB8, BplMYB11, BplMYB12, and BplMYB13. Relative beta-glucuronidase activity and chromatin immunoprecipitation assays showed that the interaction between BplMYB46 and the five MYBs increased the binding of BplMYB46 to the MYBCORE motif. A subcellular localization study showed that these MYBs were all located in the nucleus. Real-time fluorescence quantitative PCR results indicated that the expressions of BplMYB46 and the five MYB genes could be induced by salt and osmotic stress, and the BplMYB46 and BplMYB13 exhibited the most similar expression patterns. BplMYB46 and BplMYB13 co-overexpression in tobacco using transient transformation technology improved tobacco's tolerance to salt and osmotic stresses compared with overexpressing BplMYB13 or BplMYB46 alone. Taken together, these results demonstrated that BplMYB46 could interact with five other MYBs to form heterodimers that activate the transcription of target genes via an enhanced binding ability to the MYBCORE motif to mediate reactive oxygen species scavenging in response to salt and osmotic stresses.

IDH mutations but not TERTp mutations are associated with seizures in lower-grade gliomas.

Glioma is the most common malignant tumor in the central nervous system (CNS). Lower-grade gliomas (LGG) refer to Grade II and III gliomas. In LGG patients, seizure often appears as an initial symptom and play an important role in clinical performance and quality of life of the patients. To date, the relationship between the onset of seizures and the molecular pathology in gliomas is still poorly investigated. In this study, we investigate the potential relationship between isocitrate dehydrogenase (IDH)/telomerase reverse transcriptase promoter (TERTp) mutations and preoperative seizures in patients with LGG. 289 adult LGG patients were enrolled in this study. Data of clinical characteristics and molecular pathology were acquired. Sanger sequencing was used to detect IDH/TERTp mutations. Chi-square test was performed to determine if the IDH/TERTp mutations were associated with seizures and seizure types. In 289 LGG patients, preoperative seizures accounted for 25.3% (73/289), IDH mutations accounted for 34.3%(99/289), and TERTp mutations accounted for 44.3% (128/289). The correlation analysis demonstrated that IDH mutation is a significant factor influencing the occurrence of tumor-related epilepsy (P <.001, chi-square test). On the other hand, the statistical analysis revealed no significant correlation between TERTp mutations and seizure in LGG patients (P = .102, chi-square test). The tumor-related epilepsy rates vary among different subgroups according to IDH/TERTp mutations. However, there is no definite correlation between the IDH (P = 1.000, chi-square test)/TERTp (P = .613, chi-square test) mutations and the types of epileptic seizure. IDH mutations are more common in preoperative LGG patients with epileptic symptoms, suggesting that this mutation is positively correlated with seizures. However, there was no significant correlation between TERTp mutations and seizures. Different molecular pathologic types based on IDH/TERTp have different incidences of tumor-associated epilepsy in LGGs.

A Novel Tumor-Suppressor, CDH18, Inhibits Glioma Cell Invasiveness Via UQCRC2 and Correlates with the Prognosis of Glioma Patients.

BACKGROUND/AIMS: CDH18 (cadherin 18) is specifically expressed in the central nervous system and associated with various neuropsychiatric disorders. In this study, the role of CDH18 in glioma carcinogenesis and progression was investigated. METHODS: The expression of CDH18 and its prognostic value in patients with gliomas were analyzed in public database and validated by real-time PCR/immunohistochemical staining (IHC) in our cohort. CCK-8 assay, transwell migration assay, wound healing assay, clonogenic assay and tumorigenicity assay were used to compare the proliferation, invasion and migration ability of glioma cells with different expressions of CDH18. iTRAQ-based quantitative proteomic analysis were used to reveal the downstream target of CDH18. Rescue experiments were conducted to further validate the relationship between UQCRC2 and CDH18. RESULTS: The expression of CDH18 was depressed in a ladder-like pattern from normal tissues to WHO IV gliomas, and was an independent prognostic factor in TCGA (The Cancer Genome Atlas), CGGA (the Chinese glioma genome-atlas) and our glioma cohorts (n=453). Functional experiments in vitro and in vivo demonstrated that CDH18 inhibited invasion/migration, enhanced chemoresistance and suppressed tumorigenicity of glioma cells. UQCRC2 was identified as the downstream target of CDH18 by proteomic analysis. The expression of UQCRC2 was gradually absent as the WHO grades of gliomas escalated and was positively correlated with the expression of CDH18. Furthermore, in vitro assays demonstrated that down-regulation of UQCRC2 partly reversed the inhibition of invasion/migration ability and chemoresistance in CDH18 overexpressed glioma cell lines. Survival analysis demonstrated that combined CDH18/UQCRC2 biomarkers significantly influenced the prognosis of glioma patients. CONCLUSIONS: The present research demonstrated that CDH18 exerted its tumor-suppressor role via UQCRC2 in glioma cells and CDH18 might serve as a therapeutic target for treating gliomas.

Neuroprotective effects of genistein on SH-SY5Y cells overexpressing A53T mutant α-synuclein.

Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson's disease. However, the mechanism underlying this action remains unknown. This study investigated human SH-SY5Y cells overexpressing the A53T mutant of α-synuclein. Four groups of cells were assayed: a control group (without any treatment), a genistein group (incubated with 20 µM genistein), a rotenone group (treated with 50 µM rotenone), and a rotenone + genistein group (incubated with 20 µM genistein and then treated with 50 µM rotenone). A lactate dehydrogenase release test confirmed the protective effect of genistein, and genistein remarkably reversed mitochondrial oxidative injury caused by rotenone. Western blot assays showed that BCL-2 and Beclin 1 levels were markedly higher in the genistein group than in the rotenone group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed that genistein inhibited rotenone-induced apoptosis in SH-SY5Y cells. Compared with the control group, the expression of NFE2L2 and HMOX1 was significantly increased in the genistein + rotenone group. However, after treatment with estrogen receptor and NFE2L2 channel blockers (ICI-182780 and ML385, respectively), genistein could not elevate NFE2L2 and HMOX1 expression. ICI-182780 effectively prevented genistein-mediated phosphorylation of NFE2L2 and remarkably suppressed phosphorylation of AKT, a protein downstream of the estrogen receptor. These findings confirm that genistein has neuroprotective effects in a cell model of Parkinson's disease. Genistein can reduce oxidative stress damage and cell apoptosis by activating estrogen receptors and NFE2L2 channels.

Differences in airway remodeling and airway inflammation among moderate-severe asthma clinical phenotypes.

BACKGROUND: To identify asthma clinical phenotypes using cluster analysis and improve our understanding of heterogeneity in asthma. METHODS: Clustering approaches were applied to 203 patients who were diagnosed with asthma in XinHua Hospital (January 2012 to December 2015). One hundred and twenty patients underwent multi-slice spiral computed tomography (MSCT) examination and 30 underwent bronchial mucosal biopsy for evaluation of airway remodeling and airway inflammation among the phenotypes. RESULTS: Four groups were identified. Patients in cluster 1 (n=52) had early onset atopic asthma and patients in cluster 2 (n=65) had small airway obstruction and atopic asthma. Cluster 3 (n=52) was a unique group of patients with late-onset and non-atopic asthma. Patients in cluster 4 (n=34) had severe airflow obstruction and obvious airway remodeling as observed on MSCT (P<0.05). According to the immunohistochemistry of IL-5 and IL-17 (P<0.05), the results of clusters 1 and 2 may be attributable to the Th2 immune response, whereas those of clusters 3 and 4 to the Th17 immune response. CONCLUSIONS: Four distinct clinical phenotypes of asthma were identified by cluster analysis. The results of the MSCT and pathological examinations may suggest specific pathogeneses among the phenotypes.

Regulation of UHRF1 by microRNA-378 modulates medulloblastoma cell proliferation and apoptosis.

A previous study revealed that ubiquitin-like with PHD and RING finger domains 1 (UHRF1) promoted cell proliferation and was a potential biomarker in medulloblastoma (MB). In the present study, we reported that miR-378 inhibited the expression of UHRF1 to affect the proliferation of MB through competitive binding to the same region of its 3'-UTR. We found that the expression of miR-378 was significantly downregulated in MB tissues and inversely correlated with the expression of UHRF1. Western blot analysis revealed that overexpression of miR-378 led to the suppression of UHRF1. Moreover, a dual-luciferase assay demonstrated that miR-378 negatively regulated the activity of target gene UHRF1 by binding to its 3'-UTR. An in vitro assay revealed that overexpression of miR-378 suppressed MB cell proliferation and promoted cell apoptosis. Ectopic expression of UHRF1 rescued miR-378-suppressed cell proliferation and miR-378-promoted cell apoptosis. Collectively, the present study demonstrated that miR-378 could inhibit the proliferation of MB by downregulation of UHRF1 and act as a potential therapeutic target against MB.

Reduced glutathione and glutathione disulfide in the blood of glucose-6-phosphate dehydrogenase-deficient newborns.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is commonly detected during mass screening for neonatal disease. We developed a method to measure reduced glutathione (GSH) and glutathione disulfide (GSSG) using tandem mass spectrometry (MS/MS) for detecting G6PD deficiency. METHODS: The concentration of GSH and the GSH/GSSG ratio in newborn dry-blood-spot (DBS) screening and in blood plus sodium citrate for test confirmation were examined by MS/MS using labeled glycine as an internal standard. RESULTS: G6PD-deficient newborns had a lower GSH content (242.9 ± 15.9 µmol/L)and GSH/GSSG ratio (14.9 ± 7.2) than neonatal controls (370.0 ± 53.2 µmol/L and 46.7 ± 19.6, respectively). Although the results showed a significance of P < 0.001 for DBS samples plus sodium citrate that were examined the first day after preparation, there were no significant differences in the mean GSH concentration and GSH/GSSG ratio between the G6PD deficiency-positive and negative groups when examined three days after sample preparation. CONCLUSION: The concentration of GSH and the ratio of GSH/GSSG in blood measured using MS/MS on the first day of sample preparation are consistent with G6PD activity and are helpful for diagnosing G6PD deficiency.

Clinicopathological analysis of HOXD4 expression in diffuse gliomas and its correlation with IDH mutations and 1p/19q co-deletion.

BACKGROUNDS: HOX (homologous box) is known as the dominant gene of vertebrate growth and cell differentiation. Abnormal expression of HOX gene in various tumors has attracted the attention of scholars. As a component of HOX clusters, HOXD4 plays a controversial role in the tumorigenesis of central nervous system. RESULTS: The data demonstrated that and the results demonstrated that HOXD4 was overexpressed in glioma tissues compared to that of normal brain tissues. patients with high HOXD4 expression had a significant shorter survival than those with low HOXD4 expression in total glioma cohort (p<0.001), WHO Grade II cohort (p=0.003) and Grade III cohort (p<0.001), but not in Grade IV cohort when OS (overall survival) was analyzed (p=0.216). The findings were confirmed by the large-scale omics data analysis including lower-grade glioma (LGG) and glioblastoma multiforme (GBM) in TCGA (the cancer genome atlas) and CGGA (Chinese glioma genome atlas). Moreover, it was revealed that the expression of HOXD4 have a significant impact on the OS of Grade IV glioma with IDH wild-type and 1p/19q intact according to TCGA data. METHODS: Clinicopathological analysis of HOXD4 expression in 453 glioma patients was performed in the current study. Expression of HOXD4 was evaluated by qPCR and immunohistochemical (IHC) staining. Univariate and multivariate analysis were conducted to investigate the prognostic role of HOXD4 in glioma patients. CONCLUSIONS: Expression of HOXD4 was closely related to the clinical outcomes of patients with gliomas, and HOXD4 may be a potential prognostic biomarker of gliomas.

Reduced enhancement of high-frequency component in the cross spectrum of ECG and nostril airflow signals in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a chronic airway disease with increased airway resistance. This study investigated the common characteristics of electrocardiographic (ECG) and nostril airflow signals in COPD patients using cross-spectral analysis. Heart rate variability (HRV) measures and cross-spectral (cs) measures of ECG and nostril airflow were compared in COPD patients and normal subjects, and correlated with their clinical characteristics. We found that cross-spectral analysis can lead to a significant increase in normalized high-frequency power (nHFPcs) and a significant decrease in normalized very low-frequency power (nVLFPcs), normalized low-frequency power (nLFPcs), and low-/high-frequency power ratio (LHRcs) in both normal subjects and COPD patients, as compared with their corresponding HRV measures. Further analysis showed that the percentage increase in nHFP (%nHFP) and the percentage decrease in LHR (%LHR) due to cross-spectral analysis in COPD patients were significantly smaller than those of normal subjects. All cross-spectral measures of ECG and nostril airflow in COPD patients did not significantly correlate with their pulmonary function characteristics. However, the nHFPcs correlated significantly and negatively with body mass index (BMI) in both normal subjects and COPD patients, and the %nHFP correlated significantly and negatively with BMI in COPD patients. We conclude that cross-spectral analysis of ECG and nostril airflow signals could lead to reduced enhancement in the high-frequency component in the cross spectrum of COPD patients. The magnitude of reduced enhancement in the high-frequency component in the cross-spectrum was related to the BMI of the patients. Cross-spectral analysis of ECG and nostril airflow might be used to assess the cardiovascular-related functions of COPD patients.