[ORY-1001 inhibits glioblastoma cell growth by downregulating the Notch/HES1 pathway via suppressing lysine-specific demethylase 1 expression].

OBJECTIVE: To explore the inhibitory effect ORY-1001, a lysine-specific histone demethylase 1 (LSD1) inhibitor, on growth of glioblastoma (GBM) and the underlying mechanism. METHODS: We analyzed LSD1 expressions in GBM and normal brain tissues based on data from TCGA and HPA databases. Female BALB/c mouse models bearing xenografts derived from U87 cells or cells with lentivirus-mediated LSD1 silencing or Notch overexpression were treated with saline or 400 µg/kg ORY-1001 by gavage every 7 days, and GBM formation and survival time of the mice were recorded. The effect of ORY-1001 on GBM cell viability was assessed, and its effect on LSD1 expression was analyzed with Western blotting. The genes and pathways associated with LSD1 were analyzed using bioinformatics methods. Western blotting and qRT-PCR were used to detect Notch/HES1 pathway expression after LSD1 silencing and ORY-1001 treatment. The impact of ORY-1001 on viability of U87 cells with Notch1 silencing or overexpression was assessed, and the regulatory effects of ORY-1001 on Notch/HES1 pathway were analyzed using chromatin immunoprecipitation assay. RESULTS: A high expression of LSD1 in GBM was negatively correlated with patient survival (P < 0.001). ORY-1001 and LSD1 silencing obviously reduced tumor burden and prolonged the survival time of GBM-bearing mice. ORY-1001 treatment significantly inhibited the viability and dose-dependently decreased LSD1 expression in GBM cells, and such inhibitory effect of ORY-1001 was attenuated by LSD1 silencing. The Notch pathway enriched the differential genes related to LSD1, and Notch/HES1 pathway expression was significantly down-regulated after LSD1 silencing and ORY-1001 treatment. Notch1 overexpression significantly attenuated the anti-tumor effect of ORY-1001 on GBM. Mechanistically, ORY-1001 disrupted the interaction between LSD1 and the Notch pathway target genes including Notch3, HES1 and CR2. CONCLUSION: ORY-1001 down-regulates the Notch/HES1 pathway by inhibiting LSD1 expression to suppress the growth of GBM in mice.

Risk factors for infection in patients undergoing shoulder arthroscopy: a systematic review and meta-analysis.

We conducted a meta-analysis to determine the risk of infection following shoulder arthroscopy and to identify risk factors for infection. We systematically searched the PubMed/Medline, Embase and Cochrane Library databases, as well as the reference lists of previous systematic reviews and meta-analyses; manual searches were also performed. A random-effects model was employed to estimate pooled odds ratios (ORs), based on sample size, the P-value of Egger's test and heterogeneity among studies. Of the 29,342 articles screened, 16 retrospective studies comprising 74,759 patients were included. High-quality evidence showed that patients with diabetes (OR, 1.30; 95% confidence interval (CI), 1.20-1.41) or hypertension (OR, 1.26; 95% CI, 1.10-1.44) had a higher risk of infection, while moderate quality evidence showed that patients with obesity (body mass index ≥30 kg/m2) (OR, 1.42; 95% CI, 1.28-1.57), those who were male (OR, 1.65; 95% CI, 1.12-2.44), those who had an American Society of Anesthesiologists (ASA) class ≥3 (OR, 2.02; 95% CI, 1.02-3.99) and those who had a history of smoking (OR, 2.44; 95% CI, 1.39-4.28) had a higher risk of infection. The meta-analysis revealed that there was no association between age, time of surgery, or alcohol consumption and infection. This meta-analysis identified six significant risk factors for infection following shoulder arthroscopy including diabetes, obesity, hypertension, male sex, ASA class, history of smoking. These patient-related risk factors may help identify postoperative patients at higher risk for infection following shoulder arthroscopy.

[Efficacy evaluation of short-term personalized vestibular rehabilitation in the treatment of acute unilateral vestibulopathy].

Objective: To explore the efficacy and effective node of short-term personalized vestibular rehabilitation (ST-PVR) in treating acute unilateral vestibulopathy (AUVP). Methods: A randomized controlled trial was carried out. The AUVP patients who were admitted to the First Affiliated Hospital of Zhengzhou University from July 2022 to March 2023 were selected and randomized to the vestibular rehabilitation (VR) group and control group via computer-generated randomization. Standard care was the medical treatment with betahistine and prednisolone. Meanwhile, the VR group received ST-PVR. All the patients completed the baseline assessment and underwent follow-up assessments at 1 month and 3 months after the treatment. The assessments were consisted of spontaneous nystagmus (NYS), Romberg test (ROM), head thrust test (HTT), visual analogue scale (VAS) for vertigo, dizziness handicap inventory scale (DHI), activities-specific balance confidence scale (ABC), caloric test using video-electronystagmograph (VNG), and video-head impulse test (vHIT). The measurement data that did not conform to normal distribution were represented by M (Q1, Q3). Generalized estimating equation (GEE) was used to analyze the influence of the ST-PVR on the values of these clinical indicators and the VR grading score. The values of clinical indicators and the VR grading score were compared between the two groups at each follow-up point. Results: Seventy-one AUVP patients were included, with 35 cases in the VR group [14 males and 21 females, aged 51 (33, 55) years] and 36 cases in control group [17 males and 19 females, aged 46 (34, 59) years]. There were statistically significant differences in the impact of ST-PVR on the values of clinical indicators between the two groups (ABC: ß=10.89, P<0.001; VAS: ß=-1.64, P<0.001; DHI: ß=-8.70, P<0.001; NYS: ß=26.73, P<0.001; vHIT: ß=1.41, P=0.047; the VR grading score: ß=1.03, P=0.045). The assessments of the VR group in the positive rate of NYS [14.3% (5/35) vs 50.0% (18/36), P<0.001], ROM [48.6% (17/35) vs 55.6% (20/36), P<0.001], directional preponderance (DP) [34.3% (12/35) vs 75.0% (27/36), P<0.001] and DHI [26 (22, 32) vs 36 (30, 60), P=0.001] were significantly lower than that of the control group at 1 month after the treatment. The results showed a statistically significant difference in ABC [88 (80, 90) vs 76 (61, 88), P<0.001], VAS [2 (1, 3) vs 3 (2, 5), P<0.001] at 3-months after the treatment. The VR grading score of the VR group was improved significantly than those of the control group at 1 month after treatment [21 (17, 21) vs 16 (13, 20), P=0.001]. Conclusion: ST-PVR could improve the results of clinical indicators and VR grading score of the AUVP patients effectively after 1 month of the systematical treatment, and alleviate the symptoms and signs of dizziness in the acute phase as early as possible.

Stable color-tunable Ca3Y(GaO)3(BO3)4:Bi3+/Tb3+/Eu3+ phosphors for application in n-UV-pumped wLEDs.

For further development of light sources, white light-emitting diodes (wLEDs) have attracted widespread attention as promising next-generation light sources fabricated via the combination of phosphors and LED chips. However, latent defects, such as chemical/thermal instability, low color rendering index (CRI) and high correlated color temperature (CCT), of current mainstream wLEDs seriously hinder their further large-scale implementation. Herein, in order to overcome these limitations, single-phase color-tunable gaudefroyite (Ca3Y(GaO)3(BO3)4 (CYGB)) tridoped with Bi3+/Tb3+/Eu3+ ions was synthesized for the first time and detailed characterisation was performed via high-temperature solid-state reaction and structural/spectral analyses, respectively. Radius difference percentage calculations and Rietveld refinements indicate that dopants occupy both Y3+ and Ca2+ sites but preferably the Y3+ site over the Ca2+ site due to the same valence state. Through subtly regulating the (co)doping contents and skillfully utilizing the energy transfer (ET) strategy from the allowed transition of blue light-emitting Bi to the forbidden transition of green/red light-emitting Tb/Eu, the color hue (including white light) of highly efficient PL can be easily tuned according to the need. Meanwhile, composition/content-optimized white light-emitting CYGB:2%Bi/10%Tb/12%Eu also shows splendid chemical/thermal stability. Finally, as a proof-of-concept experiment, the CYGB:2%Bi/10%Tb/12%Eu phosphor-converted wLED (pc-wLED) was fabricated and encapsulated via the up-to-date remote 'capping' method, which imparted attractive performances. Altogether, the stable CYGB:Bi/Tb/Eu phosphor is a promising candidate for application in lighting/display fields.

Sub-region based radiomics analysis for prediction of isocitrate dehydrogenase and telomerase reverse transcriptase promoter mutations in diffuse gliomas.

AIM: To enhance the prediction of mutation status of isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase (TERT) promoter, which are crucial for glioma prognostication and therapeutic decision-making, via sub-regional radiomics analysis based on multiparametric magnetic resonance imaging (MRI). MATERIALS AND METHODS: A retrospective study was conducted on 401 participants with adult-type diffuse gliomas. Employing the K-means algorithm, tumours were clustered into two to four subregions. Sub-regional radiomics features were extracted and selected using the Mann-Whitney U-test, Pearson correlation analysis, and least absolute shrinkage and selection operator, forming the basis for predictive models. The performance of model combinations of different sub-regional features and classifiers (including logistic regression, support vector machines, K-nearest neighbour, light gradient boosting machine, and multilayer perceptron) was evaluated using an external test set. RESULTS: The models demonstrated high predictive performance, with area under the receiver operating characteristic curve (AUC) values ranging from 0.918 to 0.994 in the training set for IDH mutation prediction and from 0.758 to 0.939 for TERT promoter mutation prediction. In the external test sets, the two-cluster radiomics features and the logistic regression model yielded the highest prediction for IDH mutation, resulting in an AUC of 0.905. Additionally, the most effective predictive performance with an AUC of 0.803 was achieved using the four-cluster radiomics features and the support vector machine model, specifically for TERT promoter mutation prediction. CONCLUSION: The present study underscores the potential of sub-regional radiomics analysis in predicting IDH and TERT promoter mutations in glioma patients. These models have the capacity to refine preoperative glioma diagnosis and contribute to personalised therapeutic interventions for patients.

Three-dimensional analysis of mandibular morphology asymmetry and temporomandibular joint position in patients with unilateral Brodie bite.

OBJECTIVE: Previous studies have shown unilateral posterior crossbite is associated with mandibular asymmetry in morphology and position. However, it remains unclear whether unilateral Brodie bite plays a similar role in mandibular development. Therefore, this study aims to investigate the morphological and positional symmetry of mandibles in patients with unilateral Brodie bite by three-dimensional anaylsis. METHODS: Fourteen patients with unilateral Brodie bite (mean age 18.43 ± 4.24 years) and fourteen sex- and age-matched patients with normal occlusion (mean age 18.07 ± 5.48 years) underwent cone-beam computed tomography (CBCT) scans. 3D surface mesh models of their mandibles were established using Mimics Research 19.0. The surface matching percentage was compared between the original and mirrored mandible by Geomagic Control X software. Furthermore, the dimension and position of the temporomandibular joint (TMJ) were determined for both groups using InVivoDental 5.0. RESULTS: For surface-to-surface deviation analysis, the percentage of mismatch in patients with unilateral Brodie bite was significantly higher than the control group at ±0.50 mm, ±0.75 mm, and ±1.00 mm tolerance (P < .001). In patients with unilateral Brodie syndrome, the condyles on the scissors-bite side showed a significantly more anterior position (P = .03), greater medial inclination (P < .01), and larger posterior TMJ space (P = .01) than the non-scissors-bite side. CONCLUSION: Patients with unilateral Brodie bite exhibit a more asymmetrical mandibular morphology, with a greater anterior condylar position and posterior joint space on the scissors-bite side, indicating that early diagnosis and treatment may be necessary for patients with unilateral Brodie bite.

DACH1 attenuated PA-induced renal tubular injury through TLR4/MyD88/NF-κB and TGF-ß/Smad signalling pathway.

BACKGROUND: Palmitic acid (PA), the major saturated fatty acid in the blood, often induces the initiation and progression of diabetic kidney disease (DKD). However, the underlying mechanism remains unclear. DACH1 is an important regulator of kidney functions. Herein, we investigated the roles of DACH1 in PA-induced kidney injury. METHODS: Clinical data from the NHANES database were subjected to analyse the association between serum PA (sPA), blood glucose and kidney function. Molecular docking of PA was performed with DACH1. Immunohistochemistry, cell viability, annexin V/7-AAD double staining, TUNEL assay, immunofluorescent staining, autophagic flux analysis, qRT-PCR and western blot were performed. RESULTS: Clinical data confirmed that sPA was increased significantly in the pathoglycemia individuals compared with controls and correlated negatively with renal function. Our findings suggested that PA could dock with DACH1. DACH1 enhances cell viability by inhibiting apoptosis and attenuating autophagy blockage induced by PA. Furthermore, the results demonstrated that DACH1 ameliorated inflammation and fibrosis through TLR4/MyD88/NF-κB and TGF-ß/Smad signalling pathway in PA-treated renal tubular epithelial cell line (HK-2). CONCLUSIONS: This study proved that sPA presents a risk factor for kidney injuries and DACH1 might serve as a protective target against renal function deterioration in diabetic patients.