MicroRNA-375-3p Alleviates Salicylate-Induced Neuronal Injury by Targeting ELAVL4 in Tinnitus.

Purpose Tinnitus is a phantom perception of sound in the absence of acoustic source. Previous evidence has indicated that miR-375-3p is downregulated in rats with tinnitus in comparison to the controls. Nevertheless, its molecular mechanism underlying tinnitus pathogenesis is unclarified. Methods SH-SY5Y cells were differentiated into neuronlike cells and stimulated with salicylate to mimic tinnitus in vitro. Immunofluorescence staining was utilized for measuring expression of NR2B (glutamate ionotropic receptor NMDA type subunit 2B). Intracellular reactive oxygen species (ROS) level was determined using DCFH-DA assay kit. Real-time quantitative polymerase chain reaction as well as western blotting was utilized for examining RNA and protein levels. Luciferase reporter assay was implemented for verifying the interaction between miR-375-3p and ELAVL4 (ELAV-like RNA-binding protein 4). Results Salicylate treatment enhanced levels of NR2B and the early immediate gene ARC as well as ROS production. miR-375-3p was downregulated in salicylate-treated group. Overexpressing miR-375-3p attenuated the effects induced by salicylate in SH-SY5Y cells. miR-375-3p targeted ELAVL4 and upregulating ELAVL4 reversed miR-375-3p upregulation-triggered effects on SH-SY5Y cells under salicylate treatment. Conclusion miR-375-3p mitigates salicylate-triggered neuronal injury in SH-SY5Y cells by regulating ELAVL4 expression.

Berberine inhibits the malignant cell phenotype by inactivating PI3K/AKT/mTOR signaling in laryngeal squamous cell carcinoma.

BACKGROUND: Berberine is an active compound found in different herbs used in Chinese medicine and is well-known for its potential anticancer properties. The study aimed to figure out the role of berberine in regulating the malignant behavior of laryngeal squamous cell carcinoma (LSCC) cells. METHODS: LSCC cell lines (SNU-899 and AMC-HN-8) were treated with different concentrations of berberine (0-200 µM) to determine its cytotoxicity. The migration, invasion, and apoptosis of LSCC cells were measured by wound healing assays, Transwell assays, and flow cytometry. Western blot was performed for the quantification of proteins involved in PI3K/AKT/mTOR signaling. RESULTS: The viability of LSCC cells was dose-dependently reduced by berberine. Berberine dampened LSCC cell migration and invasion while augmenting cell apoptosis, as evidenced by a reduced wound closure rate, a decrease in invaded cell number, and a surge in cell apoptosis in the context of berberine stimulation. Importantly, the effects of berberine on the cancer cell process were enhanced by LY294002 (an inhibitor for PI3K) treatment. Moreover, the protein levels of phosphorylated PI3K, AKT, and mTOR were markedly reduced in response to berberine treatment. CONCLUSION: Berberine inhibits cell viability, migration, and invasion but augments cell apoptosis by inactivating PI3K/AKT/mTOR signaling in LSCC.

AQP4 regulates ferroptosis and oxidative stress of Muller cells in diabetic retinopathy by regulating TRPV4.

Diabetic retinopathy (DR) is a common microvascular complication that causes visual impairment or loss. Aquaporin 4 (AQP4) is a regulatory protein involved in water transport and metabolism. In previous studies, we found that AQP4 is related to hypoxia injury in Muller cells. Transient receptor potential cation channel subfamily V member 4 (TRPV4) is a non-selective cation channel protein involved in the regulation of a variety of ophthalmic diseases. However, the effects of AQP4 and TRPV4 on ferroptosis and oxidative stress in high glucose (HG)-treated Muller cells are unclear. In this study, we investigated the functions of AQP4 and TRPV4 in DR. HG was used to treat mouse Muller cells. Reverse transcription quantitative polymerase chain reaction was used to measure AQP4 mRNA expression. Western blotting was used to detect the protein levels of AQP4, PTGS2, GPX4, and TRPV4. Cell count kit-8, flow cytometry, 5,5',6,6'-tetrachloro-1,1,3,3'-tetraethylbenzimidazolyl carbocyanine iodide staining, and glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) kits were used to evaluate the function of the Muller cells. Streptozotocin was used to induce DR in rats. Haematoxylin and eosin staining was performed to stain the retina of rats. GSH, SOD, and MDA detection kits, immunofluorescence, and flow cytometry assays were performed to study the function of AQP4 and TRPV4 in DR rats. Results found that AQP4 and TRPV4 were overexpressed in HG-induced Muller cells and streptozotocin-induced DR rats. AQP4 inhibition promoted proliferation and cell cycle progression, repressed cell apoptosis, ferroptosis, and oxidative stress, and alleviated retinal injury in DR rats. Mechanistically, AQP4 positively regulated TRPV4 expression. Overexpression of TRPV4 enhanced ferroptosis and oxidative stress in HG-treated Muller cells, and inhibition of TRPV4 had a protective effect on DR-induced retinal injury in rats. In conclusion, inhibition of AQP4 inhibits the ferroptosis and oxidative stress in Muller cells by downregulating TRPV4, which may be a potential target for DR therapy.

NSUN2 mediates distinct pathways to regulate enterovirus 71 replication.

Increasing evidences suggest that the methyltransferase NSUN2 catalyzes 5-methylcytosine (m5C) modifications on viral RNAs, which are essential for the replication of various viruses. Despite the function of m5C deposition is well characterized, other potential roles of NSUN2 in regulating viral replication remain largely unknown. In this study, the m5C modified residues catalyzed by NSUN2 on enterovirus 71 (EV71) RNAs were mapped. NSUN2, along with m5C modifications, played multiple roles during the EV71 life cycle. Functional m5C modified nucleotides increased the translational efficiency and stability of EV71 RNAs. Additionally, NSUN2 was found to target the viral protein VP1 for binding and promote its stability by inhibiting the ubiquitination. Furthermore, both viral replication and pathogenicity in mice were largely attenuated when functional m5C residues were mutated. Taken together, this study characterizes distinct pathways mediated by NSUN2 in regulating EV71 replication, and highlights the importance of its catalyzed m5C modifications on EV71 RNAs for the viral replication and pathogenicity.

Accelerating the Development of LLZO in Solid-State Batteries Toward Commercialization: A Comprehensive Review.

Solid-state batteries (SSBs) are under development as high-priority technologies for safe and energy-dense next-generation electrochemical energy storage systems operating over a wide temperature range. Solid-state electrolytes (SSEs) exhibit high thermal stability and, in some cases, the ability to prevent dendrite growth through a physical barrier, and compatibility with the "holy grail" metallic lithium. These unique advantages of SSEs have spurred significant research interests during the last decade. Garnet-type SSEs, that is, Li7La3Zr2O12 (LLZO), are intensively investigated due to their high Li-ion conductivity and exceptional chemical and electrochemical stability against lithium metal anodes. However, poor interfacial contact with cathode materials, undesirable lithium plating along grain boundaries, and moisture-induced chemical degradation greatly hinder the practical implementation of LLZO-based SSEs for SSBs. In this review, the recent advances in synthesis methods, modification strategies, corresponding mechanisms, and applications of garnet-based SSEs in SSBs are critically summarized. Furthermore, a comprehensive evaluation of the challenges and development trends of LLZO-based electrolytes in practical applications is presented to accelerate their development for high-performance SSBs.

PITPNA-AS1 Inhibits Cell Proliferation and Migration in Ovarian Cancer by Regulating the MIR-223-3p/RHOB Axis.

Background: Ovarian cancer is a fatal gynecologic malignancy. Long non-coding RNA (lncRNA) has been verified to serve as key regulator in ovarian cancer tumorigenesis. Objective: The aim of the study was to study the functions and mechanism of lncRNA PITPNA-AS1 in ovarian cancer cellular process. Methods: Clinical ovarian cancer samples were collected and stored at an academic medical center. Cellular fractionation assays and fluorescence in situ hybridization were conducted to locate PITPNA-AS1 in OC cells. TUNEL staining, colony-forming assays, and Transwell assays were performed for evaluating cell apoptosis as well as proliferative and migratory abilities. Western blot was conducted for quantifying protein levels of epithelialmesenchymal transition markers. The binding relation between genes was verified by RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays. Gene expression levels in ovarian cancer tissues and cells were subjected to RT-qPCR. Results: PITPNA-AS1 level was downregulated in ovarian cancer samples and cells. PITPNA-AS1 overexpression contributed to the accelerated ovarian cancer cell apoptosis and inhibited cell migration, proliferation, and epithelial-mesenchymal transition process. In addition, PITPNA-AS1 interacted with miR-223-3p to regulate RHOB. RHOB knockdown partially counteracted the repressive impact of PITPNA-AS1 on ovarian cancer cell activities. Conclusion: PITPNA-AS1 inhibited ovarian cancer cellular behaviors by targeting miR-223-3p and regulating RHOB.

FERREG: ferroptosis-based regulation of disease occurrence, progression and therapeutic response.

Ferroptosis is a non-apoptotic, iron-dependent regulatory form of cell death characterized by the accumulation of intracellular reactive oxygen species. In recent years, a large and growing body of literature has investigated ferroptosis. Since ferroptosis is associated with various physiological activities and regulated by a variety of cellular metabolism and mitochondrial activity, ferroptosis has been closely related to the occurrence and development of many diseases, including cancer, aging, neurodegenerative diseases, ischemia-reperfusion injury and other pathological cell death. The regulation of ferroptosis mainly focuses on three pathways: system Xc-/GPX4 axis, lipid peroxidation and iron metabolism. The genes involved in these processes were divided into driver, suppressor and marker. Importantly, small molecules or drugs that mediate the expression of these genes are often good treatments in the clinic. Herein, a newly developed database, named 'FERREG', is documented to (i) providing the data of ferroptosis-related regulation of diseases occurrence, progression and drug response; (ii) explicitly describing the molecular mechanisms underlying each regulation; and (iii) fully referencing the collected data by cross-linking them to available databases. Collectively, FERREG contains 51 targets, 718 regulators, 445 ferroptosis-related drugs and 158 ferroptosis-related disease responses. FERREG can be accessed at https://idrblab.org/ferreg/.

Dual targeting total saponins of Pulsatilla of natural polymer crosslinked gel beads with multiple therapeutic effects for ulcerative colitis.

Oral colon targeted drug delivery system (OCTDDS) is desirable for the treatment of ulcerative colitis (UC). In this study, we designed a partially oxidized sodium alginate-chitosan crosslinked microsphere for UC treatment. Dissipative particle dynamics (DPD) was used to study the formation and enzyme response of gel beads from a molecular perspective. The formed gel beads have a narrow particle size distribution, a compact structure, low cytotoxicity and great colon targeting in vitro and in vivo. Animal experiments demonstrated that gel beads promoted colonic epithelial barrier integrity, decreased the level of pro-inflammatory factors, accelerated the recovery of intestinal microbial homeostasis in UC rats and restored the intestinal metabolic disorders. In conclusion, our gel bead is a promising approach for the treatment of UC and significant for the researches on the pathogenesis and treatment mechanism of UC.

Uvaol alleviates oxidative stress induced human umbilical vein endothelial cell injury by suppressing mitogen-activated protein kinase signaling pathway.

Deep venous thrombosis (DVT) is a potentially life-threatening disorder with high morbidity. Uvaol is a natural pentacyclic triterpene possessing multiple pharmacological activities. Nevertheless, the role of uvaol in DVT is unclarified. Human umbilical vein endothelial cells (HUVECs) were treated with hydrogen peroxide (H 2 O 2 ) to mimic DVT in vitro . CCK-8 assay and flow cytometry were utilized for measuring cell viability and apoptosis, respectively. Levels of the cell injury marker, thrombosis-associated factors, inflammatory cytokines, and oxidative stress-related markers were examined by commercial assay kits. Western blotting was used for evaluating the expression of mitogen-activated protein kinase (MAPK) signaling-associated proteins. Uvaol treatment attenuated H 2 O 2 -induced HUVEC apoptosis and injury. Uvaol reduced the expression of pro-thrombotic factors and inflammatory cytokines and attenuated oxidative stress in H 2 O 2 -stimulated HUVECs. Uvaol inhibited MAPK signaling pathway in H 2 O 2 -stimulated HUVECs. Activating MAPK signaling reversed uvaol-mediated protective effects on H 2 O 2 -treated HUVECs. Uvaol treatment alleviates H 2 O 2 -induced HUVEC injury, apoptosis, and oxidative stress by inactivating MAPK signaling.

ß-Carotene production from sugarcane molasses by a newly isolated Rhodotorula toruloides L/24-26-1.

Production of carotenoids by yeast fermentation is an advantaged technology due to its easy scaling and safety. Nevertheless, carotenoid production needs an economic culture medium and other efficient yeast stains. The study aims to isolate and identify a yeast strain capable of producing carotenoids using a cost-effective substrate. A new strain was identified as Rhodotorula toruloides L/24-26-1, which can produce carotenoids at different pretreated and unpretreated sugarcane molasses concentrations (40 and 80 g/L). The highest biomass concentration (18.6 ± 0.6 g/L) was reached in the culture using 80 g/L of hydrolyzed molasses. On the other hand, the carotenoid accumulation reached the maximum value using pretreated molasses at 40 g/L (715.4 ± 15.1 µg/g d.w). In this case, the ß-carotene was 1.5 times higher than that on the control medium. The yeast growth in molasses was not correlated with carotenoid production. The most outstanding production of The DPPH, ABTS, and FRAP tests demonstrated the antioxidant activity of the obtained carotenogenic extracts. This research demonstrated the R. toruloides L/24-26-1 strain biotechnological potential for carotenoid compounds. The yeast produces carotenoids with antioxidant activity in an inexpensive medium, such as sulfuric acid pretreated and unpretreated molasses.

Impact of Charlson Comorbidity Index on in-hospital mortality of patients with hyperglycemic crises: A propensity score matching analysis.

AIM: This study was designed to investigate the association between Charlson Comorbidity Index (CCI) and in-hospital mortality and other clinical outcomes among patients with hyperglycemic crises. METHOD: This retrospective cohort study was conducted using data from electric medical records. A total of 1668 diabetic patients with hyperglycemic crises from six tertiary hospitals met the inclusion criteria. CCI < 4 was defined as low CCI and CCI ≥ 4 was defined as high CCI. Propensity score matching (PSM) with the 1:1 nearest neighbour matching method and the caliper value of 0.02 was used to match the baseline characteristics of patients with high CCI and low CCI to reduce the confounding bias. In-hospital mortality, ICU admission, hypoglycemia, hypokalemia, acute kidney injury, length of stay (LOS), and hospitalisation expense between low CCI and high CCI were compared and assessed. Univariate and multivariate regression were applied to estimate the impact of CCI on in-hospital and other clinical outcomes. OUTCOME: One hundred twenty-one hyperglycemic crisis (HC) patients died with a mortality rate of 7.3%. After PSM, compared with low CCI, patients with high CCI suffered higher in-hospital mortality, ICU admission, LOS, and hospitalisation expenses. After multivariate regression, age (aOR: 1.12, 95% confidence interval [CI]: 1.06-1.18, p < 0.001), CCI(aOR: 4.42, 95% CI: 1.56-12.53, p = 0.005), uninsured (aOR: 22.32, 95% CI: 4.26-116.94, p < 0.001), shock (aOR: 10.57, 95% CI: 1.41-79.09, p = 0.022), mechanical ventilation (aOR: 75.29, 95% CI: 12.37-458.28, p < 0.001), and hypertension (aOR: 4.34, 95% CI: 1.37-13.82, p = 0.013) were independent risk factors of in-hospital mortality of HC patients. Besides, high CCI was an independent risk factor for higher ICU Admission (aOR: 5.91, 95% CI: 2.31-15.08, p < 0.001), hypoglycemia (aOR: 2.19, 95% CI:1.01-4.08, p = 0.049), longer LOS (aOR: 1.23, 95% CI: 1.19-2.27, p = 0.021), and higher hospitalisation expense (aOR: 2089.97, 95% CI: 193.33-3988.61, p = 0.031) of HC patients. CONCLUSION: CCI is associated with in-hospital mortality, ICU admission, hypoglycemia, LOS, and hospitalisation expense of HC patients. CCI could be an ideal indicator to identify, monitor, and manage chronic comorbidities among HC patients.

Sinomenine attenuates bleomycin-induced pulmonary fibrosis, inflammation, and oxidative stress by inhibiting TLR4/NLRP3/TGFß signaling.

OBJECTIVE: The present work concentrated on validating whether sinomenine alleviates bleomycin (BLM)-induced pulmonary fibrosis, inflammation, and oxidative stress. METHODS: A rat model of pulmonary fibrosis was constructed through intratracheal injection with 5 mg/kg BLM, and the effects of 30 mg/kg sinomenine on pulmonary inflammation, fibrosis, apoptosis, and 4-hydroxynonenal density were evaluated by hematoxylin and eosin staining, Masson's trichrome staining, TUNEL staining, and immunohistochemistry. Hydroxyproline content and concentrations of inflammatory cytokines and oxidative stress markers were detected using corresponding kits. MRC-5 cells were treated with 10 ng/ml PDGF, and the effects of 1 mM sinomenine on cell proliferation were assessed by EdU assays. The mRNA expression of inflammatory cytokines and the protein levels of collagens, fibrosis markers, and key markers involved in the TLR4/NLRP3/TGFß signaling were tested with RT-qPCR and immunoblotting analysis. RESULTS: Sinomenine attenuated pulmonary fibrosis and inflammation while reducing hydroxyproline content and the protein expression of collagens and fibrosis markers in BLM-induced pulmonary fibrosis rats. Sinomenine reduced apoptosis in lung samples of BLM-challenged rats by increasing Bcl-2 and reducing Bax and cleaved caspase-3 protein expression. In addition, sinomenine alleviated inflammatory response and oxidative stress in rats with pulmonary fibrosis induced by BLM. Moreover, sinomenine inhibited the TLR4/NLRP3/TGFß signaling pathway in lung tissues of BLM-stimulated rats. Furthermore, TLR4 inhibitor, TAK-242, attenuated PDGF-induced fibroblast proliferation and collagen synthesis in MRC-5 cells. CONCLUSION: Sinomenine attenuates BLM-caused pulmonary fibrosis, inflammation, and oxidative stress by inhibiting the TLR4/NLRP3/TGFß signaling, indicating that sinomenine might become a therapeutic candidate to treat pulmonary fibrosis.

Molecular weight control of poly-γ-glutamic acid reveals novel insights into extracellular polymeric substance synthesis in Bacillus licheniformis.

BACKGROUND: The structural diversity of extracellular polymeric substances produced by microorganisms is attracting particular attention. Poly-gamma-glutamic acid (γ-PGA) is a widely studied extracellular polymeric substance from Bacillus species. The function of γ-PGA varies with its molecular weight (Mw). RESULTS: Herein, different endogenous promoters in Bacillus licheniformis were selected to regulate the expression levels of pgdS, resulting in the formation of γ-PGA with Mw values ranging from 1.61 × 103 to 2.03 × 104 kDa. The yields of γ-PGA and exopolysaccharides (EPS) both increased in the pgdS engineered strain with the lowest Mw and viscosity, in which the EPS content was almost tenfold higher than that of the wild-type strain. Subsequently, the compositions of EPS from the pgdS engineered strain also changed. Metabolomics and RT-qPCR further revealed that improving the transportation efficiency of EPS and the regulation of carbon flow of monosaccharide synthesis could affect the EPS yield. CONCLUSIONS: Here, we present a novel insight that increased pgdS expression led to the degradation of γ-PGA Mw and changes in EPS composition, thereby stimulating EPS and γ-PGA production. The results indicated a close relationship between γ-PGA and EPS in B. licheniformis and provided an effective strategy for the controlled synthesis of extracellular polymeric substances.

Optimization of 3D printing supply chain in the era of live streaming e-commerce.

This study examines the effects of the rising live streaming e-commerce on the 3DP supply chain, employing system dynamics to develop separate models for pure polymer and polymer-metal mixed printing. The analysis focuses on optimizing the 3DP supply chain configuration. Results indicate that, based solely on printing time, cost, and quality metrics, Corporate-live-3DP services are optimal for live commerce scenarios. However, despite this, Private-live-3DP maintains a substantial consumer base in practice, as evidenced by literature data and case studies. Both models pose significant challenges to conventional supply chains, necessitating adaptation. For Corporate-live-3DP, optimization strategies may include technology advancements, digital transformation, agile manufacturing, global network optimization, innovative management, collaborative R&D, fine-tuned inventory control, quality system upgrades, talent development, and organizational restructuring. Conversely, Private-live-3DP can be optimized through consolidation of private 3D printing resources, demand prediction and order optimization, supply chain collaboration platforms, quality management extensions, inventory strategy adjustments, increased transparency, regulatory compliance, and risk mitigation measures.

Supplementation with NAD+ and its precursors: A rescue of female reproductive diseases.

Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme involved in many pathophysiological processes. Supplementation with NAD+ and its precursors has been demonstrated as an emerging therapeutic strategy for the diseases. NAD+ also plays an important role in the reproductive system. Here, we summarize the function of NAD+ in various reproductive diseases and review the application of NAD+ and its precursors in the preservation of reproductive capacity and the prevention of embryonic malformations. It is shown that NAD+ shows good promise as a therapeutic approach for saving reproductive capacity.

Circular RNA KIAA0564 Serves as a Competitive Endogenous RNA for MicroRNA-424-5p, Mediating the Expression of Lysine Demethylase 4a, Thereby Facilitating Intervertebral Disc Degeneration.

A growing body of research has confirmed the involvement of circular RNAs (circRNAs) in the regulation of intervertebral disc degeneration (IDD) progression. However, the underlying molecular networks remain largely elusive. This study aimed to explore whether a novel circRNA, named circKIAA0564, affects nucleus pulposus (NP) cell injury and to elucidate its molecular mechanism. Both in vivo and in vitro IDD models were established, and the expression patterns of circKIAA0564/miR-424-5p/lysine demethylase 4a (KDM4A) were evaluated through quantitative reverse transcription PCR and Western blot analysis. Actinomycin D, RNase R, and Northern blotting were utilized to assess the circular structure of circKIAA0564. The Cell Counting Kit-8, flow cytometry, enzyme-linked immunosorbent assay, commercial assay kits, Western blotting, and reactive oxygen species (ROS) probes were employed to assess the inflammatory and oxidative stress status in NP cells and tissues. Hematoxylin and eosin and TUNEL staining were used to evaluate pathological damage in mouse NP tissues. RNA immunoprecipitation and dual-luciferase reporter assays were conducted to assess the direct targeting relationships among circKIAA0564, miR-424-5p, and KDM4A. CircKIAA0564 was found to be abnormally overexpressed in IDD, functioning as a novel circRNA. Knockdown of circKIAA0564 ameliorated interleukin-1 beta (IL-1ß)-induced inflammation and oxidative stress in NP cells. The therapeutic effect of circKIAA0564 knockdown on NP cells was reversed by the silencing of miR-424-5p. Overexpression of circKIAA0564 exacerbated IL-1ß-induced NP cell injury, a process that was reversed by knockdown of KDM4A. CircKIAA0564 activated the toll-like receptor 4 (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) signaling pathway by regulating the miR-424-5p/KDM4A axis. CircKIAA0564 exacerbates IL-1ß-induced inflammation and oxidative stress in NP cells by competitively binding miR-424-5p, thereby mediating KDM4A and activating the TLR4/NF-κB/NLRP3 signaling pathway. These findings provide robust data support for targeted therapy of IDD and the development of future pharmaceuticals.

A potent Henipavirus cross-neutralizing antibody reveals a dynamic fusion-triggering pattern of the G-tetramer.

The Hendra and Nipah viruses (HNVs) are highly pathogenic pathogens without approved interventions for human use. In addition, the interaction pattern between the attachment (G) and fusion (F) glycoproteins required for virus entry remains unclear. Here, we isolate a panel of Macaca-derived G-specific antibodies that cross-neutralize HNVs via multiple mechanisms. The most potent antibody, 1E5, confers adequate protection against the Nipah virus challenge in female hamsters. Crystallography demonstrates that 1E5 has a highly similar binding pattern to the receptor. In cryo-electron microscopy studies, the tendency of 1E5 to bind to the upper or lower heads results in two distinct quaternary structures of G. Furthermore, we identify the extended outer loop ß1S2-ß1S3 of G and two pockets on the apical region of fusion (F) glycoprotein as the essential sites for G-F interactions. This work highlights promising drug candidates against HNVs and contributes deeper insights into the viruses.

Genetic Association of TIE2 with Diabetic Retinopathy and Diabetic Macular Edema.

PURPOSE: To evaluate the associations of the TIE2 gene with diabetic retinopathy (DR) and diabetic macular edema (DME). METHODS: This study included a Chinese cohort of 285 non-proliferative DR patients and 433 healthy controls. The DR patients were classified further into those with or without DME. Thirty haplotype-tagging single-nucleotide polymorphisms (SNPs) in TIE2 were genotyped using TaqMan technology. Associations of DR and subtypes were analyzed by logistic regression adjusted for age and sex. Stratification association analysis by sex was performed. RESULTS: TIE2 rs625767 showed a nominal but consistent association with DR [odds ratio (OR) = 0.71, P = 0.005] and subtypes (DR without DME: OR = 0.69, P = 0.016; DME: OR = 0.73, P = 0.045). SNP rs652010 was consistently associated with overall DR (OR = 0.74, P = 0.011) and DR without DME (OR = 0.70, P = 0.016), but not with DME. Moreover, SNPs rs669441, rs10967760, rs549099 and rs639225 showed associations with overall DR, whilst rs17761403, rs664461 and rs1413825 with DR without DME. In stratification analysis, three SNPs, rs625767 (OR = 0.62, P = 0.005), rs669441 (OR = 0.63, P = 0.006) and rs652010 (OR = 0.64, P = 0.007), were associated with DR in females, but not in males. Moreover, one haplotype T-T defined by rs625767 and rs669441 was significantly associated with DR in females only. CONCLUSIONS: This study revealed TIE2 as a susceptibility gene for DR and DME in Chinese, with a sex-specific association in females. Further validation should be warranted.

Unified Multi-modal Diagnostic Framework with Reconstruction Pre-training and Heterogeneity-combat Tuning.

Medical multi-modal pre-training has revealed promise in computer-aided diagnosis by leveraging large-scale unlabeled datasets. However, existing methods based on masked autoencoders mainly rely on data-level reconstruction tasks, but lack high-level semantic information. Furthermore, two significant heterogeneity challenges hinder the transfer of pre-trained knowledge to downstream tasks, i.e., the distribution heterogeneity between pre-training data and downstream data, and the modality heterogeneity within downstream data. To address these challenges, we propose a Unified Medical Multi-modal Diagnostic (UMD) framework with tailored pre-training and downstream tuning strategies. Specifically, to enhance the representation abilities of vision and language encoders, we propose the Multi-level Reconstruction Pre-training (MR-Pretrain) strategy, including a feature-level and data-level reconstruction, which guides models to capture the semantic information from masked inputs of different modalities. Moreover, to tackle two kinds of heterogeneities during the downstream tuning, we present the heterogeneity-combat downstream tuning strategy, which consists of a Task-oriented Distribution Calibration (TD-Calib) and a Gradient-guided Modality Coordination (GM-Coord). In particular, TD-Calib fine-tunes the pre-trained model regarding the distribution of downstream datasets, and GM-Coord adjusts the gradient weights according to the dynamic optimization status of different modalities. Extensive experiments on five public medical datasets demonstrate the effectiveness of our UMD framework, which remarkably outperforms existing approaches on three kinds of downstream tasks.

The value of SINO robot combined with Angio Render technology-assisted stereo-electroencephalography electrode implantation for the treatment of drug-resistant epilepsy.

BACKGROUND AND OBJECTIVE: Stereo-electroencephalography (SEEG) electrodes are implanted using a variety of stereotactic technologies to treat refractory epilepsy. The value of SINO-robot for SEEG electrode implantation is rarely reported. The aim of the current study was to assess the value of SINO-robot in conjunction with Angio Render technology, in SEEG electrode implantation. We also assess its efficacy by examining factors such as localization error, operation time, and complications. METHODS: Between June 2018 and October 2020, we retrospectively reviewed 58 patients who underwent SEEG implantation to resect or ablate their epileptogenic zone (EZ) while minimizing the risk of hemorrhage. SINO-robot combined with Angio Render technology-assisted SEEG electrode implantation was used to visualize each patient' blood vessel in a 3D plane. The 3D view functionality was used to increase the safety and accuracy of the implantation, and reducing the risk of hemorrhage by avoiding said blood vessel. RESULTS: In this study, 634 SEEG electrodes were implanted in 58 patients. The mean 10.92(range 5- 18) leads per patient. The mean entry point localization error (EPLE) was 0.94 ± 0.23 mm (range: 0.39- 1.63 mm), and the mean target point localization error (TPLE) was 1.49 ± 0.37 mm (range: 0.80-2.78 mm). The mean operating time per lead (MOTPL) was 6. 18 ± 1.80 min (range: 3.02- 14.61 min). And the mean depth of electrodes was 56.96± 3.62 mm (range:27.23-124.85 mm). At a follow-up of at least one year, totally 81.57% (47/58) of patients achieved an Engel class I of seizure freedom. There were 2 patients with asymptomatic brain hematomas following SEEG placement, and no late complications or mortality in this cohort. CONCLUSIONS: SINO-robot in conjunction with Angio Render technology assist, in SEEG electrode implantation is safe and accurate in mitigating the risk of intracranial hemorrhage in patients suffering from drug-resistant epilepsy.