CircPRMT5 promotes progression of osteosarcoma by recruiting CNBP to regulate the translation and stability of CDK6 mRNA.

Research has demonstrated that circular RNAs (circRNAs) exert critical functions in the occurrence and progression of numerous malignant tumors. CircPRMT5 was recently reported to be involved in the pathogenesis of cancers. However, the potential role of circPRMT5 in osteosarcoma needs further investigation. In present study, our results suggested that circPRMT5 was highly upregulated in osteosarcoma cells and mainly localizes in the cytoplasm. CircPRMT5 promoted the proliferation, migration and invasion capacities of osteosarcoma cells, and suppressed cell apoptosis. Knockdown of circPRMT5 exerted the opposite effects. Mechanically, circPRMT5 promoted the binding of CNBP to CDK6 mRNA, which enhanced the stability of CDK6 mRNA and facilitated its translation, thereby promoting the progression of osteosarcoma. Knockdown of CDK6 reversed the promoting effect of circPRMT5 on osteosarcoma cells. These findings suggest that circPRMT5 promotes osteosarcoma cell malignant activity by recruiting CNBP to regulate the translation and stability of CDK6 mRNA. Thus, circPRMT5 may represent a promising therapeutic target for osteosarcoma.

Blood urea nitrogen and clinical prognosis in patients with COVID-19: A retrospective study.

The aim of this study was to estimate the association between blood urea nitrogen (BUN) and clinical prognosis in patients with COVID-19. A multicenter, retrospective study was conducted in adult patients with COVID-19 in 3 hospitals in Zhenjiang from January 2023 to May 2023. Patients were divided into survival and death group based on whether they survived at day 28. The demographic, comorbidities, and laboratory data were independently collected and analyzed, as well as clinical outcomes. Total 141 patients were enrolled and 23 (16.3%) died within 28 days. Patients who died within 28 days had a higher level of BUN compared with survivors. Bivariate logistic regression analysis showed that BUN was a risk factor for 28-day mortality in patients with COVID-19. ROC curve showed that BUN could predict 28-day mortality of COVID-19 patients (AUC = 0.796, 95%CI: 0.654-0.938, P < .001). When the cutoff value of BUN was 7.37 mmol/L, the sensitivity and specificity were 84.62% and 70.31%. Subgroup analysis demonstrated that hyper-BUN (≥7.37 mmol/L) was associated with increased 28-day mortality among COVID-19 patients. Patients with COVID-19 who died within 28 days had a higher level of BUN, and hyper-BUN (≥7.37 mmol/L) was associated with increased 28-day mortality.

Mn2+/CpG Oligodeoxynucleotides Codecorated Black Phosphorus Nanosheet Platform for Enhanced Antitumor Potency in Multimodal Therapy.

Manganese ions (Mn2+)-coordinated nanoparticles have emerged as a promising class of antitumor nanotherapeutics, capable of simultaneously disrupting the immunosuppressive tumor microenvironment (TME) and triggering the stimulator of interferon genes (STING) pathway-dependent antitumor immunity. However, the activation of STING signaling by Mn2+-based monotherapies is suboptimal for comprehensive stimulation of antigen presenting cells and reversal of immunosuppression in the TME. Here, we report the design of a Mn2+/CpG oligodeoxynucleotides (ODNs) codecorated black phosphorus nanosheet (BPNS@Mn2+/CpG) platform based on the Mn2+ modification of BPNS and subsequent adsorption of synthetic CpG ODNs. The coordination of Mn2+ significantly improved the stability of BPNS and the adsorption of CpG ODNs. The acidic TME and endosomal compartments can disrupt the Mn2+ coordination, triggering pH-responsive release of CpG ODNs and Mn2+ to effectively activate the Toll-like receptor 9 and STING pathways. As a result, M2-type macrophages and immature dendritic cells were strongly stimulated in the TME, thereby increasing T lymphocyte infiltration and reversing the immunosuppression within the TME. Phototherapy and chemodynamic therapy, utilizing the BPNS@Mn2+/CpG platform, have demonstrated efficacy in inducing immunogenic cell death upon 808 nm laser irradiation. Importantly, the treatment of BPNS@Mn2+/CpG with laser irradiation exhibited significant therapeutic efficacy against the irradiated primary tumor and effectively suppressed the growth of nonirradiated distant tumor. Moreover, it induced a robust immune memory, providing long-lasting protection against tumor recurrence. This study demonstrated the enhanced antitumor potency of BPNS@Mn2+/CpG in multimodal therapy, and its proof-of-concept application as a metal ion-modified BPNS material for effective DNA/drug delivery and immunotherapy.

Hybrid interpenetrating network of polyester coronary stent with tunable biodegradation and mechanical properties.

Poly(l-lactide) (PLLA) is an important candidate raw material of the next-generation biodegradable stent for percutaneous coronary intervention, yet how to make a polyester stent with sufficient mechanical strength and relatively fast biodegradation gets to be a dilemma. Herein, we put forward a hybrid interpenetrating network (H-IPN) strategy to resolve this dilemma. As such, we synthesize a multi-functional biodegradable macromer of star-like poly(d,l-lactide-co-ɛ-caprolactone) with six acrylate end groups, and photoinitiate it, after mixing with linear PLLA homopolymer, to trigger the free radical polymerization. The resultant crosslinked polymer blend is different from the classic semi-interpenetrating network, and partial chemical crosslinking occurs between the linear polymer and the macromer network. Combined with the tube blow molding and the postprocessing laser cutting, we fabricate a semi-crosslinked-polyester biodegradable coronary stent composed of H-IPN, which includes a physical network of polyester spherulites and a chemical crosslinking network of copolyester macromers and a part of homopolymers. Compared with the currently main-stream PLLA stent in research, this H-IPN stent realizes a higher and more appropriate biodegradation rate while maintaining sufficient radial strength. A series of polymer chemistry, polymer physics, polymer processing, and in vitro and in vivo biological assessments of medical devices have been made to examine the H-IPN material. The interventional implanting of the H-IPN stent into aorta abdominalis of rabbits and the follow-ups to 12 months have confirmed the safety and effectiveness.

Mapping enhancer and chromatin accessibility landscapes charts the regulatory network of Alzheimer's disease.

BACKGROUND: Enhancers are regulatory elements that target and modulate gene expression and play a role in human health and disease. However, the roles of enhancer regulatory circuit abnormalities driven by epigenetic alterations in Alzheimer's disease (AD) are unclear. METHODS: In this study, a multiomic integrative analysis was performed to map enhancer and chromatin accessibility landscapes and identify regulatory network abnormalities in AD. We identified differentially methylated enhancers and constructed regulatory networks across brain regions using AD brain tissue samples. Through the integration of snATAC-seq and snRNA-seq datasets, we mapped enhancers with DNA methylation alterations (DMA) and chromatin accessibility landscapes. Core regulatory triplets that contributed to AD neuropathology in specific cell types were further prioritized. RESULTS: We revealed widespread DNA methylation alterations (DMA) in the enhancers of AD patients across different brain regions. In addition, the genome-wide transcription factor (TF) binding profiles showed that enhancers with DMA are pervasively regulated by TFs. The TF-enhancer-gene regulatory network analysis identified core regulatory triplets that are associated with brain and immune cell proportions and play important roles in AD pathogenesis. Enhancer regulatory circuits with DMA exhibited distinct chromatin accessibility patterns, which were further characterized at single-cell resolutions. CONCLUSIONS: Our study comprehensively investigated DNA methylation-mediated regulatory circuit abnormalities and provided novel insights into the potential pathogenesis of AD.

A rare presentation of primary cardiac diffuse large B­cell lymphoma: A case report.

Primary cardiac lymphomas display a low frequency, sudden onset, swift progression of illness and elevated mortality rates. The current study presents a unique instance of primary cardiac diffuse large B-cell lymphoma and examines its clinical manifestations, pathological characteristics and differential diagnosis. A 64-year-old male patient sought medical attention due to cardiac debility and exertional dyspnea persisting for >10 days. Chest enhanced computed tomography revealed a moderately enhancing irregular mass in the ventricular area, exhibiting limited demarcation from the pericardium and left atrium, accompanied by irregular thickening of the interventricular septum. The postoperative specimen showed the presence of yellow fish-like tumor tissue. Immunohistochemical analysis revealed the presence of lymphocytes positive for CD20, BCL-2, BCL-6, c-Myc-binding protein, mutated melanoma-associated antigen 1 and CD79a, along with a high Ki-67 proliferation index of 80%. Conversely, CD10, CD30, CD3, pan cytokeratin, cyclin D1, desmin and vimentin marker results were found to be negative. Additionally, in situ hybridization demonstrated a lack of Epstein-Barr virus-encoded small RNA expression. The present case report emphasizes the significance of conducting a thorough analysis of the clinical manifestations of diffuse large B-cell lymphoma to assist clinicians in establishing a diagnosis and determining an effective treatment approach, thereby enhancing the patient's prognosis.

Dual blockade of EGFR and PI3K signaling pathways offers a therapeutic strategy for glioblastoma.

BACKGROUND: Glioblastoma multiforme (GBM) is a devastating disease that lacks effective drugs for targeted therapy. Previously, we found that the third-generation epidermal growth factor receptor (EGFR) inhibitor AZD-9291 persistently blocked the activation of the ERK pathway but had no inhibitory effect on the phosphoinositide 3-kinase (PI3K)/Akt pathway. Given that the PI3K inhibitor GDC-0084 is being evaluated in phase I/II clinical trials of GBM treatment, we hypothesized that combined inhibition of the EGFR/ERK and PI3K/Akt pathways may have a synergistic effect in the treatment of GBM. METHODS: The synergistic effects of cotreatment with AZD-9291 and GDC-0084 were validated using cell viability assays in GBM and primary GBM cell lines. Moreover, the underlying inhibitory mechanisms were assessed through colony formation, EdU proliferation, and cell cycle assays, as well as RNA-seq analyses and western blot. The therapeutic effects of the drug combination on tumor growth and survival were investigated in mice bearing tumors using subcutaneously or intracranially injected LN229 xenografts. RESULTS: Combined treatment with AZD-9291 and GDC-0084 synergistically inhibited the proliferation and clonogenic survival, as well as induced cell cycle arrest of GBM cells and primary GBM cells, compared to monotherapy. Moreover, AZD-9291 plus GDC-0084 combination therapy significantly inhibited the growth of subcutaneous tumors and orthotopic brain tumor xenografts, thus prolonging the survival of tumor-bearing mice. More importantly, the combination of AZD-9291 and GDC-0084 simultaneously blocked the activation of the EGFR/MEK/ERK and PI3K/AKT/mTOR signaling pathways, thereby exerting significant antitumor activity. CONCLUSION: Our findings demonstrate that the combined blockade of the EGFR/MEK/ERK and PI3K/AKT/mTOR pathways is more effective against GBM than inhibition of each pathway alone, both in vitro and in vivo. Our results suggest that AZD-9291 combined with GDC-0084 may be considered as a potential treatment strategy in future clinical trials. Video Abstract.

Inhibition of GPR30 sensitized gefitinib to NSCLC cells via regulation of epithelial-mesenchymal transition.

Introduction: G-protein coupled receptor 30 (GPR30) is associated with cell metastasis and drug resistance in many different cancer cells. The present study aimed to reveal the sensitivity of GPR30 to gefitinib in non-small cell lung cancer (NSCLC) cells.Methods: Cell viability and proliferation were detected using cell counting kit 8 and 5-ethynyl-2'-deoxyuridine assays, respectively. Western blotting and quantitative real-time reverse transcription PCR were used to detect GPR30 or epithelial-mesenchyme transition (EMT)-related mRNA and protein expression.Results: The results showed that GPR30 expression is associated with gefitinib sensitivity. G15, as a GPR30 antagonist, reduced GPR30 expression. We chose the maximum concentration of G15 with minimal cytotoxicity to detect cell viability after combined treatment with gefitinib in NSCLC cells, which indicated that G15 could increase sensitivity to gefitinib. However, the effect of G15 on gefitinib sensitivity disappeared after treatment with a small interfering RNA targeting GPR30. Further research showed that G15 or GPR30 siRNA treatment could upregulate E-cadherin and downregulate vimentin levels.Conclusion: Taken together, these data suggested that G15 could enhance NSCLC sensitivity to gefitinib by inhibition of GPR30 and EMT.

Sex-dependent association of DNA methylation in the coding region of the corticotropin-releasing hormone gene and schizophrenia spectrum disorder.

BACKGROUND: Schizophrenia spectrum disorder (SSD) is a common mental disorder causing severe and chronic disability. Epigenetic changes in genes related to the hypothalamic-pituitary-adrenal (HPA) axis are believed to play an important role in SSD pathogenesis. The methylation status of the corticotropin-releasing hormone (CRH) gene, which is central to the HPA axis, has not been investigated in patients with SSD. AIM: We investigated the methylation status of the coding region of the CRH gene (hereafter, CRH methylation) using peripheral blood samples from patients with SSD. SUBJECTS AND METHODS: We used sodium bisulphite and MethylTarget to determine CRH methylation after collecting peripheral blood samples from 70 patients with SSD who had positive symptoms and 68 healthy controls. RESULTS: CRH methylation was significantly increased in patients with SSD, especially in male patients. CONCLUSIONS: Differences in CRH methylation were detectable in the peripheral blood of patients with SSD. Epigenetic abnormalities in the CRH gene were closely related to positive symptoms of SSD, suggesting that epigenetic processes may mediate the pathophysiology of SSD.

Mn2+-modified black phosphorus nanosensor for detection of exosomal microRNAs and exosomes.

The development and performance of a DNA probe adsorbing Mn2+-modified black phosphorus (BP@Mn2+/DNA) hybrid nanosensor is reported that enables rapid detection of cancer-derived exosomal microRNAs (miRNAs) and exosomes. This two-dimensional (2D) nanosensor can spontaneously penetrate the lipid bilayer of exosome membranes owing to its ultra-thin geometry. Subsequently, the adsorbed probe specifically hybridizes with the target miRNA and then dissociates from the nanosensor surface, generating fluorescent signals. Therefore, the BP@Mn2+/DNA nanosensor can differentiate between colorectal cancer (CRC) cell-derived exosomes and those derived from intestinal epithelial cells through sensing of exosomal miRNAs. Furthermore, when the epithelial cell adhesion molecule (EpCAM) aptamer is adsorbed onto BP@Mn2+ instead of the miRNA probe, the nanosensor is able to distinguish exosomes derived from the plasma of CRC patients from those of healthy controls by the recognition ability of the EpCAM aptamer. By utilizing this nanosensor, we were able to effectively differentiate cancer-derived exosomes through the direct detection of miRNA-21 within the exosomes, as well as the identification of specific exosomal membrane proteins. This nanosensor design paves the way for the development of rapid and efficient cancer-derived exosomal miRNA and exosome biosensing nanoplatforms.

Development of Wide-Angle Depolarizing Reflector at 1064 nm.

Optical coherence tomography is a new promising chromatographic imaging technique with the advantages of noncontact and high resolution without damage, which is widely used in the field of biological tissue detection and imaging. As an important optical element in the system, the wide-angle depolarizing reflector plays a key role in the accurate acquisition of optical signals. Ta2O5 and SiO2 are selected as the coating materials for the technical parameter requirements of the reflector in the system. Based on the basic theory of optical thin film and combined with MATLAB and OptiLayer software, the design of 0~60° incident 1064 ± 40 nm depolarizing reflective film is realized by establishing the evaluation function of the film system. To optimize the oxygen-charging distribution scheme during film deposition, the weak absorption properties of the film materials are characterized by optical thermal co-circuit interferometry. According to the sensitivity distribution of the film layer, the optical control monitoring scheme with a thickness error of less than 1% is designed rationally. "Crystal control + optical control" is used to precisely control the thickness of each film layer and complete the preparation of resonant cavity film. The measurement results show that the average reflectance is more than 99.5%, and the deviation of P-light and S-light is less than 1% in the 1064 ± 40 nm wavelength band range from 0° to 60°, which meets the requirements of optical coherence tomography system.

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration.

Salidroside (Sal) contains anti-carcinogenic, anti-hypoxic, and anti-inflammatory pharmacological activities. However, its underlying anti-breast cancer mechanisms have been only incompletely elucidated. Hence, this protocol intended to decode the potential of Sal in regulating the PI3K-AKT-HIF-1α-FoxO1 pathway in the malignant proliferation of human breast cancer MCF-7 cells. First, the pharmacological activity of Sal against MCF-7 was evaluated by CCK-8 and cell scratch assays. Moreover, the resistance of MCF-7 cells was measured by migration and Matrigel invasion assays. For cell apoptosis and cycle assays, MCF-7 cells were processed in steps with annexin V-FITC/PI and cell cycle-staining detection kits for flow cytometry analyses, respectively. The levels of reactive oxygen species (ROS) and Ca2+ were examined by DCFH-DA and Fluo-4 AM immunofluorescence staining. The activities of Na+-K+-ATPase and Ca2+-ATPase were determined using the corresponding commercial kits. The protein and gene expression levels in apoptosis and the PI3K-AKT-HIF-1α-FoxO1 pathway were further determined using western blot and qRT-PCR analyses, respectively. We found that Sal treatment significantly restricted the proliferation, migration, and invasion of MCF-7 cells with dose-dependent effects. Meanwhile, Sal administration also dramatically forced MCF-7 cells to undergo apoptosis and cell cycle arrest. The immunofluorescence tests showed that Sal observably stimulated ROS and Ca2+ production in MCF-7 cells. Further data confirmed that Sal promoted the expression levels of pro-apoptotic proteins, Bax, Bim, cleaved caspase-9/7/3, and their corresponding genes. Consistently, Sal intervention prominently reduced the expression of the Bcl-2, p-PI3K/PI3K, p-AKT/AKT, mTOR, HIF-1α, and FoxO1 proteins and their corresponding genes. In conclusion, Sal can be used as a potential herb-derived compound for treating breast cancer, as it may reduce the malignant proliferation, migration, and invasion of MCF-7 cells by inhibiting the PI3K-AKT-HIF-1α-FoxO1 pathway.

CircARF3 Mitigates Allergic Rhinitis through Targeting microRNA-205-5p/Sirtuin 5 Axis.

INTRODUCTION: Circular RNAs (circRNAs) are essential in the progression of allergic rhinitis (AR). The purpose of this research was to examine the role of circRNA ADP-ribosylation factor 3 (circARF3) in the pathogenesis of AR. METHODS: To generate an animal model of AR, mice were treated with house dust mite (HDM), and mice nasal epithelial cells (NEpCs) were treated with IL-4/IL-13 to imitate the inflammatory damage of AR in vitro. Sanger sequencing, qRT-PCR, and RNAse R digestion assays all validated the circularization structure of circARF3. The levels of circARF3, miR-205-5p, and sirtuin 5 (SIRT5) were determined by qRT-PCR or Western blotting. Luciferase reporter, RNA immunoprecipitation, and pull-down experiments were used to investigate the regulatory network. Flow cytometry was used to investigate the rate of cell apoptosis, and Western blotting was used to determine the levels of apoptotic-related proteins (cleaved caspase 3, cleaved polyadenosine-diphosphate-ribose polymerase) and HMGB1, TLR4, and MyD88. Enzyme-linked immunosorbent assay was used to assess the inflammatory response. Hematoxylin-eosin staining and TUNEL were used to detect the histology of injury and apoptosis of nasal mucosa tissues. RESULTS: CircARF3 and SIRT5 levels were reduced in HDM-treated animals and IL-4/IL-13-treated NEpCs, while miR-205-5p expression was increased. CircARF3 was generated by back-splicing exons 3-5 with a stable circular shape. CircARF3 overexpression mitigated IL-4/IL-13-induced apoptosis in NEpCs by inhibiting miR-205-5p. SIRT5 upregulation attenuated IL-4/IL-13-induced inflammatory injury in NEpCs, and SIRT5 knockdown induced opposite effects. miR-205-5p silencing reversed the effects of SIRT5 knockdown on IL-4/IL-13-induced inflammatory injury. Furthermore, circARF3 overexpression alleviated histological abnormalities, apoptosis, inflammatory response, and HMGB1/TLR4 signaling activation in HDM-treated animals. CONCLUSION: CircARF3 inhibited cell apoptosis and inflammation via the miR-205-5p/SIRT5 axis in IL-4/IL-13-treated NEpCs and HDM-treated mice.

A dominant variant in apoptosis-related gene XKR8 is relevant to hereditary auditory neuropathy.

BACKGROUND: Auditory neuropathy is an unusual type of hearing loss. At least 40% of patients with this disease have underlying genetic causes. However, in many hereditary auditory neuropathy cases, etiology remains undetermined. METHODS: We collected data and blood samples from a four-generation Chinese family. After excluding relevant variants in known deafness-related genes, exome sequencing was conducted. Candidate genes were verified by pedigree segregation, transcript/protein expression in the mouse cochlea, and plasmid expression studies in HEK 293T cells. Moreover, a mutant mouse model was generated and underwent hearing evaluations; protein localization in the inner ear was also assessed. RESULTS: The clinical features of the family were diagnosed as auditory neuropathy. A novel variant c.710G > A (p.W237X) in apoptosis-related gene XKR8 was identified. Genotyping of 16 family members confirmed the segregation of this variant with the deafness phenotype. Both XKR8 mRNA and XKR8 protein were expressed in the mouse inner ear, predominantly in regions of spiral ganglion neurons; Moreover, this nonsense variant impaired the surface localization of XKR8 in cells. Transgenic mutant mice exhibited late-onset auditory neuropathy, and their altered XKR8 protein localization in the inner ear confirmed the damaging effects of this variant. CONCLUSIONS: We identified a variant in the XKR8 gene that is relevant to auditory neuropathy. The essential role of XKR8 in inner ear development and neural homeostasis should be explored.

Epigenetically regulated lncRNAs dissect the intratumoural heterogeneity and facilitate immune evasion of glioblastomas.

Background: Glioblastomas are the most common and malignant central nervous system (CNS) tumors that occupied a highly heterogeneous tumor microenvironment (TIME). Long noncoding RNAs (lncRNAs), whose expression can be modified by DNA methylation, are emerging as critical regulators in the immune system. However, knowledge about the epigenetic changes in lncRNAs and their contribution to the immune heterogeneity of glioma is still lacking. Methods: In this study, we integrated paired methylome and transcriptome datasets of glioblastomas and identified 2 robust immune subtypes based on lncRNA methylation features. The immune characteristics of glioma subtypes were compared. Furthermore, immune-related lncRNAs were identified and their relationships with immune evasion were evaluated. Results: Glioma immunophenotypes exhibited distinct immune-related characteristics as well as clinical and epigenetic features. 149 epigenetically regulated (ER) lncRNAs were recognized that possessed inverse variation in epigenetic and transcriptional levels between glioma subtypes. Immune-related lncRNAs were further identified through the investigation of their correlation with immune cell infiltrations and immune-related pathways. In particular, the 'Hot' glioma subtype with higher immunoactivity while a worse survival outcome was found to character immune evasion features. We finally prioritized candidate ER lncRNAs associated with immune evasion markers and response to glioma immunotherapy. Among them, CD109-AS1 and LINC02447 were validated as novel immunoevasive biomarkers for glioma through in vitro experiments. Conclusion: In summary, our study systematically reveals the crosstalk among DNA methylation, lncRNA, and immune regulation in glioblastomas, and will facilitate the development of epigenetic immunotherapy approaches.

Clinical Profiles and Prognoses of Adult Patients with Full-Frequency Sudden Sensorineural Hearing Loss in Combination Therapy.

We aimed to characterize the clinical profiles and short-term outcomes of adult patients with full-frequency idiopathic sudden sensorineural hearing loss (ISSNHL) treated uniformly with combination therapy, and to determine the prognostic predictors for the combination therapy. A total of 131 eligible cases hospitalized in our department from January 2018 to June 2021 were retrospectively reviewed. All enrolled cases received a standardized combination therapy employing intravenous methylprednisolone, batroxobin, and Ginkgo biloba extract during the 12 days of hospitalization. The clinical and audiometric profiles were compared between recovered patients and their unrecovered counterparts. The overall recovery rate was 57.3% in the study. Accompanying vertigo (odds ratio = 0.360, p = 0.006) and body mass index (BMI, odds ratio = 1.158, p = 0.016) were two independent predictors of hearing outcomes of the therapy. The male gender and cigarette-smoking history were marginally associated with good hearing prognosis (p = 0.051 and 0.070, respectively). Patients with BMI ≥ 22.4 kg/m2 had a better chance of hearing recovery (p = 0.02). Conclusions: Accompanying vertigo and low BMI (<22.4 kg/m2) were independently associated with poor prognosis for full-frequency ISSNHL in combination therapy. Male gender and cigarette-smoking history might be considered positive effects on hearing prognosis.

The Efficacy of Defocus Incorporated Multiple Segments Lenses in Slowing Myopia Progression: Results from Diverse Clinical Circumstances.

PURPOSE: Defocus incorporated multiple segments (DIMS) spectacle lenses were reported to slow myopia progression significantly in a randomized controlled trial (RCT). The study evaluated their effectiveness in clinical settings. DESIGN: Retrospective study. PARTICIPANTS: Patient records involving use of DIMS and single-vision (SV) spectacle lenses were collected from subsidiary hospitals of Aier Eye Hospital Group. METHODS: The spherical equivalent (SE), determined by subjective refraction, was adopted to assess the myopia progression. The strategy of propensity score matching (PSM) was applied to match the confounding baseline characteristics between the 2 groups. The effectiveness was calculated based on the difference of myopia progression of these 2 approaches. MAIN OUTCOME MEASURES: Change in SE. RESULTS: Three thousand six hundred thirty-nine patients with DIMS and 6838 patients with SV spectacles were included. The age of the patients was 6 to 16 years (mean ± standard deviation: 11.02 ± 2.53 years). The baseline SE was between 0.00 and -10.00 diopters (D) (mean ± standard deviation: -2.78 ± 1.74 D). After the PSM, data on 2240 pairs with 1-year follow-up and on 735 pairs with 2-year follow-up were obtained. Significantly slower progression was seen in the DIMS group at both the 1-year (DIMS, -0.50 ± 0.43 D; SV, -0.77 ± 0.58 D; P < 0.001) and 2-year (DIMS, -0.88 ± 0.62 D; SV, -1.23 ± 0.76 D; P < 0.001) subdataset. In the 1-year subdataset, 40% and 19% showed myopia progression of no more than 0.25 D for the DIMS and SV groups, respectively (chi-square, 223.43; P < 0.001), whereas 9% and 22% showed myopia progression of more than 1.00 D for the DIMS and SV groups, respectively (chi-square, 163.38; P < 0.001). In the 2-year subdataset, 33% and 20% showed myopia progression of no more than 0.50 D for the DIMS and SV groups, respectively (chi-square, 31.15; P < 0.001), whereas 12% and 29% showed myopia progression of more than 1.50 D for the DIMS and SV groups (chi-square, 65.60; P < 0.001). CONCLUSIONS: Although the magnitude was lower than that reported in the previous RCT, this large-scale study with diversity of the data sources confirmed the effectiveness of DIMS spectacles to slow myopia progression in clinical practice. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Guanxin Danshen Dripping Pills Improve Quality of Life and Cardiovascular Prognoses of CHD Patients after PCI with Anxiety or Depression (GLAD Study): A Randomized Double-Blind Placebo-Controlled Study.

OBJECTIVE: To assess the efficacy and safety of Guanxin Danshen Dripping Pills (GXDS) in the treatment of depression or anxiety in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). METHODS: From September 2017 to June 2019, 200 CHD patients after PCI with depression and anxiety were included and randomly divided into GXDS (100 cases) and placebo control groups (100 cases) by block randomization and a random number table. Patients in the GXDS and control groups were given GXDS and placebo, respectively, 0.4 g each time, 3 times daily for 12 weeks. The primary outcomes were scores of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Scale (GAD-7) and the Seattle Angina Pectoris Scale (SAQ). The secondary outcomes included 12 Health Survey Summary Form (SF-12) scores and the first onset time and incidence of major adverse cardiovascular events (MACEs). Other indices including blood pressure, blood lipids, microcirculation and inflammatory-related indices, etc. were monitored at baseline, week 4, and week 12. RESULTS: In the full analysis set (200 cases), after treatment, the PHQ-9 and GAD-7 scores in the GXDS group were considerably lower than those in the control group (P<0.05). Compared with the baseline, the total PHQ-9 scores of the experimental and control groups decreased by 3.97 and 1.18, respectively. The corrected mean difference between the two groups was -2.78 (95% CI: -3.47, -2.10; P<0.001). The total GAD-7 score in the GXDS group decreased by 3.48% compared with the baseline level, while that of the placebo group decreased by 1.13%. The corrected mean difference between the two groups was -2.35 (95% CI: -2.95, -1.76; P<0.001). The degree of improvement in SAQ score, SF-12 score, endothelin and high-sensitive C-reactive protein levels in the GXDS group were substantially superior than those in the placebo group, and the differences between the two groups were statistically significant (P<0.05). Similar results were obtained in the per protocol population analysis of 177 patients. Three cases of MACES were reported in this study (1 in the GXDS group and 2 in the placebo group), and no serious adverse events occurred. CONCLUSIONS: GXDS can significantly alleviate depression and anxiety, relieve symptoms of angina, and improve quality of life in patients with CHD after PCI. (Registration No. ChiCTR1800014291).

[Correlation of temporal bone HRCT, SLC26A4 gene and hearing loss in enlarged vestibular aqueduct].

Objective:To explore the correlation between high-resolution computed tomography（HRCT） of temporal bones, SLC26A4 gene mutation and hearing loss in patients with enlarged vestibular aqueduct（EVA）. Methods:The medical records of 257 subjects hospitalized for moderate to severe sensorineural hearing loss in the Department of Otolaryngology Head and Neck Surgery, Hainan General Hospital between May 2018 to 2021 were retrospectively reviewed. All included cases received audiological examination, HRCT scanning of temporal bones and SLC26A4 gene sequencing. According to the Valvassori standard, cases with the diameter from the common peduncle of the semicircular canal to the midpoint of the outer orifice of the vestibular aqueduct（MP） over 1.5 mm, or the diameter of the outer orifice of the vestibular aqueduct（OP） more than 2.0 mm were diagnosed as EVA. There were 22 cases（44 ears） of EVA in the study, aged between 6 months to 17 years old. Based on the hearing changes at birth and during growth, 18 ears of which were classified into the stable hearing group, while the other 26 ears in the unstable group. Moreover, all involved cases were grouped by MP（1.5 to <3.0 mm and ≥3.0 mm） and OP（2.0 to <4.0 mm and ≥4.0 mm）. SPSS 25.0 software was applied in the study. The correlation between hearing loss and MP and OP was analyzed. The results of HRCT of temporal bones and SLC26A4 gene sequencing were compared as well. Results:Though the size of MP and OP was not statistically different between the stable and hearing groups in EVA ears（P>0.05）, it was significantly correlated with the severity of hearing loss（P<0.05）. Of the 22 EVA patients diagnosed by HRCT, 21 were positive for SLC26A4 gene mutation. The positive rate of EVA by SLC26A4 gene sequencing was highly consistent with HRCT（Kappa=0.975）. Conclusion:The size of MP and OP in EVA patients was related to the degree of hearing loss, but not to the stable nature of hearing loss. Temporal bone HRCT scanning and SLC26A4 gene sequencing are highly consistent in the diagnosis of EVA. The latter has no radiation and can be combined with hearing screening for early diagnosis of EVA.

The association of dietary spermidine with all-cause mortality and CVD mortality: The U.S. National Health and Nutrition Examination Survey, 2003 to 2014.

Background: Current studies on the protective effects of dietary spermidine (SPD) on cardiovascular disease (CVD) are mainly limited to animal studies, and the relationship between dietary SPD and CVD mortality remains inconclusive. Objective: This study aims to evaluate the association between dietary SPD intake and CVD and all-cause mortality. Methods: A total of 23,894 people enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2014 were recruited for this study. The dietary intake of SPD from 11 specific food origins and total SPD was categorized into tertiles or quartiles. Cox proportional hazard regression models were developed to evaluate the association of SPD intake with CVD and all-cause mortalities. Results: Among the 23,894 participants, 2,365 deaths, including 736 deaths due to CVD, were documented. After adjustment for potential confounders, compared with participants in the lowest quartile, participants in the highest quartile of total SPD had a significantly lower risk of CVD mortality (HR = 0.68, 95% CI: 0.51-0.91) and all-cause mortality (HR = 0.70, 95% CI: 0.60-0.82); participants in the highest tertiles or quartiles of vegetable-derived SPD, cereal-derived SPD, legume-derived SPD, nut-derived SPD, and cheese-derived SPD had a lower risk of CVD mortality (HR vegetable - derivedSPD = 0.68, 95% CI: 0.54-0.86; HR cereal - derivedSPD = 0.75, 95% CI: 0.57-0.97; HR legume - derivedSPD = 0.68, 95% CI: 0.52-0.88; HR nut - derivedSPD = 0.66, 95% CI: 0.53-0.80; HR cheese - derivedSPD = 0.68, 95% CI: 0.52-0.88) and all-cause mortality (HR vegetable - derivedSPD = 0.73, 95% CI: 0.64-0.84; HR cereal - derivedSPD = 0.80, 95% CI: 0.69-0.93; HR legume - derivedSPD = 0.70, 95% CI: 0.60-0.80;HR nut - derivedSPD = 0.72, 95% CI: 0.64-0.81; HR cheese - derivedSPD = 0.70, 95% CI: 0.61-0.81) than those in the lowest tertiles or quartiles. Moreover, subgroup analysis showed consistent associations among the people with hypertension and hyperlipidemia. Conclusion: Higher intake of dietary SPD is associated with decreased risk of CVD and all-cause mortality, and among specific food origin SPD, SPD derived from vegetables, cereals, legumes, nuts, and cheese was associated with reduced CVD and all-cause mortality.