Abstract Our study investigated the causal relationship between immune cells, metabolites, and epilepsy using two-sample Mendelian Randomization (MR) and mediation MR analysis of 731 immune cell traits and 1,400 metabolites. Our core methodology centered on inverse-variance weighted MR, supplemented by other methods. This approach was crucial in clarifying the potential intermediary functions of metabolites in the genetic links between traits of immune cells and epilepsy. We found a causal relationship between immune cells and epilepsy. Specifically, the genetically predicted levels of CD64 on CD14-CD16 are positively correlated with the risk of epilepsy (p < 0.001, OR = 1.0826, 95% CI 1.0361–1.1312). Similarly, metabolites also exhibit a causal relationship with both immune cells (OR = 1.0438, 95% CI:1.0087–1.0801, p = 0.0140) and epilepsy (p = 0.0334, OR = 1.0897, 95% CI: 1.0068–1.1795), and sensitivity analysis was conducted to further validate these relationships. Importantly, our intermediate MR results suggest that the metabolite Paraxanthine to linoleate (18:2n6) ratio may mediate the causal relationship between immune cell CD64 on CD14-CD16 and epilepsy, with a mediation effect of 5.05%. The results suggest the importance of specific immune cell levels and metabolites in understanding epilepsy's pathogenesis. This is significant for understanding the pathogenesis of epilepsy and its prevention and treatment.

Evidence supports using antiplatelet therapy in patients with acute ischemic stroke. However, neurological deterioration remains common under the currently recommended antiplatelet regimen, leading to poor clinical outcomes. To determine whether intravenous tirofiban administered within 24 hours of stroke onset prevents early neurological deterioration in patients with acute noncardioembolic stroke compared with oral aspirin. This investigator-initiated, multicenter, open-label, randomized clinical trial with blinded end-point assessment was conducted at 10 comprehensive stroke centers in China between September 2020 and March 2023. Eligible patients were aged 18 to 80 years with acute noncardioembolic stroke within 24 hours of onset and had a National Institutes of Health Stroke Scale (NIHSS) score of 4 to 20. Patients were assigned randomly (1:1) to receive intravenous tirofiban or oral aspirin for 72 hours using a central, web-based, computer-generated randomization schedule; all patients then received oral aspirin. The primary efficacy outcome was early neurological deterioration (increase in NIHSS score ≥4 points) within 72 hours after randomization. The primary safety outcome was symptomatic intracerebral hemorrhage within 72 hours after randomization. A total of 425 patients were included in the intravenous tirofiban (n = 213) or oral aspirin (n = 212) groups. Median (IQR) age was 64.0 years (56.0-71.0); 124 patients (29.2%) were female, and 301 (70.8%) were male. Early neurological deterioration occurred in 9 patients (4.2%) in the tirofiban group and 28 patients (13.2%) in the aspirin group (adjusted relative risk, 0.32; 95% CI, 0.16-0.65; P = .002). No patients in the tirofiban group experienced intracerebral hemorrhage. At 90-day follow-up, 3 patients (1.3%) in the tirofiban group and 3 (1.5%) in the aspirin group died (adjusted RR, 1.15; 95% CI, 0.27-8.54; P = .63), and the median (IQR) modified Rankin scale scores were 1.0 (0-1.25) and 1.0 (0-2), respectively (adjusted odds ratio, 1.28; 95% CI, 0.90-1.83; P = .17). In patients with noncardioembolic stroke who were seen within 24 hours of symptom onset, tirofiban decreased the risk of early neurological deterioration but did not increase the risk of symptomatic intracerebral hemorrhage or systematic bleeding. ClinicalTrials.gov Identifier: NCT04491695.

Previously, we have screened 59 differentially expressed miRNAs and 419 mRNAs in the glioblastoma samples that have been compared to the peritumoral tissues using bioinformatics analyses, which included miRNA-383-5p and vascular endothelial growth factor A (VEGFA). miRNA-383-5p and VEGFA/Akt/mTOR pathway play important regulatory roles in the malignant biological behavior of glioma. Glioma cell lines, U87 and U251, were collected for in vitro experiments. miRNA-383-5p and VEGFA expression levels were detected with qRT-PCR and WB. The protein expressions of Akt, mTOR, and VEGFR in U87 and U251 were detected with WB. The effect of miRNA-383-5p on the VEGFA activity was verified by dual-luciferase reporter assay. CCK-8 was used to examine the U87 and U251 cells' inhibition. Flow cytometry and transwell assays were used to detect cell apoptosis and invasion, respectively. Our research data indicated overexpression of miRNA-383-5p to suppress malignant biological behavior, which was manifested as promoting the apoptosis of U87 and U251 cells and inhibiting invasion, proliferation, and metastasis. VEGFA is one of the downstream target genes of miRNA-383- 5p. miRNA-383-5p could inhibit the expression of VEGFA and Akt/mTOR signaling pathways. Overexpression of VEGFA can reverse the inhibitory effect of miRNA-383-5p and reactivate the Akt/mTOR signaling pathway. Our results indicate that miRNA-383-5p functions as an anti-oncogene by inhibiting the VEGFA/Akt/mTOR signaling pathway in glioma cells. These data provide potential therapeutic targets for glioblastoma.

As one of the interesting signaling mechanisms, the in situ growth reaction on a photoelectrode has proven its powerful potential in photoelectrochemical (PEC) bioanalysis. However, the specific interaction between the signaling species with the photoactive materials limits the general application of the signal mechanism. Herein, on the basis of an in situ growth reaction on a photoelectrode of single-atom-based photoactive material, a general PEC immunoassay was developed in a split-type mode consisting of the immunoreaction and PEC detection procedure. Specifically, a single-atom photoactive material that incorporates Fe atoms into layered Bi4O5I2 (Bi4O5I2-Fe SAs) was used as a photoelectrode for PEC detection. The sandwich immunoreaction was performed in a well of a 96-well plate using Ag nanoparticles (Ag NPs) as signal tracers. In the PEC detection procedure, the Ag+ converted from Ag NPs were transferred onto the surface of the Bi4O5I2-Fe SAs photoelectrode and thereafter AgI was generated on the Bi4O5I2-Fe SAs in situ to form a heterojunction through the reaction of Ag+ with Bi4O5I2-Fe SAs. The formation of heterojunction greatly promoted the electro-hole separation, boosting the photocurrent response. Exemplified by myoglobin (Myo) as the analyte, the immunosensor achieved a wide linear range from 1.0 × 10-11 to 5.0 × 10-8 g mL-1 with a detection limit of 3.5 × 10-12 g mL-1. This strategy provides a general PEC immunoassay for disease-related proteins, as well as extends the application scope of in situ growth reaction in PEC analysis.

Abstract Background: The rapid expansion of social media has given rise to a myriad of challenges among college students facing psychological distress. An abundance of fragmented and repetitive information, often referred to as information overload, inundates users on social media platforms. This inundation presents significant hurdles for college students experiencing psychological distress when acquiring and processing information. This study investigates the associative mechanisms between information overload in the context of social media and information avoidance behaviors among college students experiencing psychological distress. Methods: From May to November 2023, semi-structured interviews were conducted with 30 college students experiencing psychological distress in a prefecture-level city in Henan Province, China, to collect textual data. Grounded theory was employed to conduct three-level coding of the 30 sets of textual data. Special emphasis was placed on analyzing the process of perceiving social media information overload. Subsequently, this analysis served as the foundation for constructing a factor model influencing information avoidance behaviors among college students experiencing psychological distress. Results: The study findings indicate that, within the context of social media, college students experiencing psychological distress are prone to prolonged exposure to information overload, leading to the development of negative emotions such as anxiety and fatigue, subsequently resulting in dissatisfaction with social media. In order to alleviate these negative emotions, they employ information avoidance strategies. These strategies evolve from initially skipping or skimming information to eventually directly avoiding or even discontinuing the use of specific social media platforms. This process is not only closely linked to negative emotions but is also influenced by negative cognitive tendencies. Coupled with the role of virtual social satisfaction and social scarcity, it easily triggers social comparisons and the fear of missing out, resulting in a cyclic impact. Conclusions: Within the context of social media, information overload and information avoidance behaviors among college students experiencing psychological distress are subject to a cyclic influence stemming from negative emotions, negative cognitive tendencies, virtual social satisfaction and social scarcity, social comparisons, and the fear of missing out. This study explores the mechanisms underlying the impact of information overload and information avoidance behaviors among college students experiencing psychological distress within the context of social media. It offers valuable insights for the prevention and intervention of psychological crises among college students.

Abstract Percutaneous balloon compression (PBC) offers substantial immediate relief from the severe pain associated with trigeminal neuralgia (TN). To investigate the effect of compression Frequency during balloon compression on facial numbness in patients with primary trigeminal neuralgia, we conducted a nested case–control study. A retrospective analysis was performed on clinical data from 150 TN patients treated with PBC from October 2017 to May 2022. Of these, 60 patients underwent a single PBC compression, while the remaining 90 underwent two compressions. The Barrow Neurological Institute Pain Intensity (BNI-P) score was employed to measure the severity of pain. The Barrow Neurological Institute facial numbness score (BNI-N) was used to assess the degree of postoperative pain relief and facial numbness. At time point T1, the BNI-P scores for the “two compressions” group were significantly lower than those for the “single compression” group (P < 0.05). From T2 to T5, no significant differences in BNI-P scores were observed between the groups. For the BNI-N score, there was no notable difference between the groups at T0, while from T1 to T4, the “double compressions” group exhibited significantly lower BNI-N scores than the “single compression” group (P < 0.05). At T5, no significant difference in BNI-N scores was observed between the groups. The application of two compressions in PBC is a safe and effective surgical method that not only maintains the efficacy of the procedure but also significantly reduces the degree and duration of postoperative facial numbness.

ABSTRACT Objectives To investigate the clinical value of rigid bronchoscopy combined with fiberoptic bronchoscopy in patients with early bronchogenic lung cancer who underwent sleeve lobectomy. Methods A retrospective study was performed on 76 patients with early bronchogenic lung cancer admitted to our center from March 2016 to March 2017. Patients in the control group received conventional sleeve lobectomy (n = 38), while patients in the observation group underwent sleeve lobectomy by using rigid bronchoscopy combining fiberoptic bronchoscopy (n = 38). We compared perioperative period indicators and the recovery of pulmonary function indexes one month after the operation were compared in two groups. The prognosis of the patients were also analyzed. Results Compared with the control group, the intraoperative blood loss, operation duration and airway reconstruction duration in the observation group were significantly reduced. The total incidence of perioperative complications was markedly lower in the observation group than in the control group. The percentage of DLCO% was significantly improved in the observation group. The relapse-free survival (RFS) in the observation group was remarkably longer than in the control group. Conclusion Rigid bronchoscopy combined with fiberoptic bronchoscopy is beneficial to improve the clinical outcome and prognosis of patients with early bronchogenic lung cancer more effectively.

Inflammatory cytokines that are secreted into the spinal trigeminal nucleus caudalis (Sp5C) may augment inflammation and cause pain associated with temporomandibular joint disorders (TMD). In a two-step process, we attached triphenylphosphonium (TPP) to the surface of a cubic liposome metal-organic framework (MOF) loaded with ruthenium (Ru) nanozyme. The design targeted mitochondria and was designated Mito-Ru MOF. This structure scavenges free radicals and reactive oxygen species (ROS) and alleviates oxidative stress. The present study aimed to investigate the effects and mechanisms by which Mito-Ru MOF ameliorates TMD pain. Intra-temporomandibular joint (TMJ) injections of complete Freund's adjuvant (CFA) induced inflammatory pain for ≥10 d in the skin areas innervated by the trigeminal nerve. Tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), long non-coding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1), and ROS also have been proved to be significantly upregulated in the Sp5C of TMD mice. Moreover, a single Mito-Ru MOF treatment alleviated TMD pain for 3 d and downregulated TNF-α, NF-κB, lncRNA NEAT1, and ROS. NF-κB knockdown downregulated NEAT1 in the TMD mice. Hence, Mito-Ru MOF inhibited the production of ROS and alleviated CFA-induced TMD pain via the TNF-α/NF-κB/NEAT1 pathway. Therefore, Mito-Ru MOF could effectively treat the pain related to TMD and other conditions associated with severe acute inflammatory activation.

Correction for 'Mitochondria-targeting nanozyme alleviating temporomandibular joint pain by inhibiting the TNFα/NF-κB/NEAT1 pathway' by Qian Bai et al., J. Mater. Chem. B, 2023, https://doi.org/10.1039/d3tb00929g.

The acquired resistance of cancer to cisplatin (DDP) limits the efficacy of chemotherapy. The prognostic value of long noncoding RNA (lncRNA) LINC00460 has been reported in cervical cancer. However, its effect on DDP sensitivity in cervical cancer remains poorly understood. In present study, LINC00460 was screened out through bioinformatics analysis. The expression levels of mRNAs and proteins were measured by reverse transcription-quantitative PCR (RT-qPCR) or western blot analysis. The sensitivity to DDP was investigated using an CCK8 assay. Cell apoptosis was determined by flow cytometry. The differentially expressed genes that were associated with the poor prognosis of cervical cancer were screened, and their correlations with LINC00460 expression were explored using Pearson's correlation analysis. Tumor xenograft model was used to assess the effect of LINC00460 knockdown on DDP sensitivity invivo. The interaction between miR-338-3p and LINC00460 or transforming growth factor β-induced protein (TGFBI) was confirmed by RNA immunoprecipitation (RIP) and luciferase reporter assays. LINC00460 expression was increased in cervical cancer tissues and cells. High expression of LINC00460 was associated with dismal prognosis in cervical cancer patients. Silencing of LINC00460 increased drug sensitivity and induced apoptosis in DDP-resistant-cervical cancer cells. LINC00460 knockdown enhanced DDP sensitivity in cervical cancer cells largely by downregulating TGFBI expression. LINC00460 knockdown enhanced the sensitivity of cervical cancer to DDP invivo, and this effect was partly mediated by the downregulation of TGFBI. LINC00460 positively regulated TGFBI expression, possibly by acting as a sponge of miR-338-3p. LINC00460 knockdown contributed to DDP sensitivity of cervical cancer by downregulating TGFBI, providing a novel mechanism underlying the acquisition of DDP sensitivity.