Coupling of nanostraws with diverse physicochemical perforation strategies for intracellular DNA delivery.

Effective intracellular DNA transfection is imperative for cell-based therapy and gene therapy. Conventional gene transfection methods, including biochemical carriers, physical electroporation and microinjection, face challenges such as cell type dependency, low efficiency, safety concerns, and technical complexity. Nanoneedle arrays have emerged as a promising avenue for improving cellular nucleic acid delivery through direct penetration of the cell membrane, bypassing endocytosis and endosome escape processes. Nanostraws (NS), characterized by their hollow tubular structure, offer the advantage of flexible solution delivery compared to solid nanoneedles. However, NS struggle to stably self-penetrate the cell membrane, resulting in limited delivery efficiency. Coupling with extra physiochemical perforation strategies is a viable approach to improve their performance. This study systematically compared the efficiency of NS coupled with polyethylenimine (PEI) chemical modification, mechanical force, photothermal effect, and electric field on cell membrane perforation and DNA transfection. The results indicate that coupling NS with PEI modification, mechanical force, photothermal effects provide limited enhancement effects. In contrast, NS-electric field coupling significantly improves intracellular DNA transfection efficiency. This work demonstrates that NS serve as a versatile platform capable of integrating various physicochemical strategies, while electric field coupling stands out as a form worthy of primary consideration for efficient DNA transfection.

TRIP 13-dependent pathways promote the development of gastric cancer.

TRIP13 is highly expressed in various human tumors and promotes tumorigenesis. We aimed to explore the biological effect of TRIP13 on gastric cancer. The RNA sequence data were retrieved from TCGA to evaluate TRIP13 mRNA expression in gastric cancer. Paired formalin-fixed paraffin-embedded blocks were further analyzed to verify the relationship between TRIP13 expression and carcinogenic status. The functions of TRIP13 on the proliferation of gastric malignancy were investigated by MTT, flow cytometry, colony formation experiment, and nude mouse tumor formation experiment. Finally, microarray analysis of TRIP13-related pathways was performed to identify the potential underlying mechanism of TRIP13 in gastric cancer. TRIP13 was found to have high expression in tumor samples. TRIP13 expression status was significantly subjective to tumor-node-metastasis (TNM) staging and poor survival. The downregulation of TRIP13 promoted apoptosis and inhibited tumor growth. TRIP13-dependent JAK/STAT and NF-κB signaling cascade were found as two key pathways in the carcinogenesis of GC. In conclusion, TRIP13 participates in the carcinogenesis of stomach cancer, and its overexpression in the cancerous tissues dovetail with advanced stage and survival. Moreover, TRIP13 functions as an upstream regulator of the JAK/STAT and p53 signaling pathways, which play critical roles in developing various malignancies.

Changes in sex hormones and their interactions are related to pain perception between different menstrual subphases.

Whether sex hormones are related to pain perception across the menstrual cycle is unclear. We examined changes in experimental pain perception in healthy young females between the early to midfollicular subphase (emF) and the midluteal subphase (mL) and explored the role of sex hormones. Sixty-six participants were involved in the study. We tested pressure pain, cold pain, ischemic pain, and needle pain, while at the same time we measured sex hormones levels in two menstrual subphases. Only the right ulna pressure test showed a significant reduction in pain threshold (PPTh3) during the mL. The absolute change of PPTh3 (PPTh3mL - PPTh3emF) was related to the absolute change of prolactin. The relative change of the range of pain tolerance for pressure pain of the right ulna (RPT3rc) was related to the relative change of progesterone (Prc) and estradiol (E2rc) levels, and the interaction effects showed that at Prc ≤ 30, E2rc was positively correlated with RPT3rc. The same, the relative change of pressure pain tolerance of the pulp of the middle finger on the right hand (PPTo4rc) was related to E2rc and Prc, and the results of the interaction between E2rc and Prc suggest that when E2rc is ≤0.8, Prc is positively correlated with PPTo4rc. Two different formulas were applied in this study and showed inconsistent results. Most pain tests showed no difference between the two subphases of the menstrual cycle. Only the relative changes of the PPTo4 and RPT3 are related to the E2rc and Prc, respectively, between menstrual subphases in an interactive way in healthy young women.

Predictive values of procalcitonin for coinfections in patients with COVID-19: a systematic review and meta-analysis.

OBJECTIVES: To assess the ability of procalcitonin (PCT)-a promising marker for coinfections-to predict coinfections in patients with COVID-19. METHODS: In this systematic review and meta-analysis, PubMed, Embase, Web of Science, Cochrane, the China National Knowledge Infrastructure (CNKI), and Wanfang were searched to identify eligible studies (up to August 30, 2021). Articles that reported the predictive value of PCT for coinfections in patients with COVID-19 were included. Individual and pooled sensitivities and specificities were reported, and I2 was used to test heterogeneity. This study was prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO) database (registration number: CRD42021283344). RESULTS: Five studies involving a total of 2775 patients reported the predictive value of PCT for coinfections in patients with COVID-19. The sensitivity, specificity, and area under the curve of PCT in predicting coinfections in the pooled studies were 0.60 (95% CI 0.35-0.81, I2 = 88.85), 0.71 (95% CI 0.58-0.81, I2 = 87.82), and 0.72(95% CI 0.68-0.76) respectively. CONCLUSIONS: Although PCT has limited predictive value for coinfections in patients with COVID-19, lower PCT levels seem to indicate a decreased probability of having a coinfection.

Neuroprotective Effects of Dammarane Sapogenins Against lipopolysaccharide-induced Cognitive Impairment, Neuroinflammation and Synaptic Dysfunction.

Neuroinflammation is a critical driver in the pathogenesis and progression of neurodegenerative disorders. Dammarane sapogenins (DS), a deglycosylated product of ginsenoside, possess a variety of potent biological activities. The present study aimed to explore the neuroprotective effects of DS in a rat model of neuroinflammation induced by intracerebroventricular injection of lipopolysaccharide (LPS). Our study revealed that DS pretreatment effectively improved LPS-induced associative learning and memory impairments in the active avoidance response test and spatial learning and memory in Morris water maze test. DS also remarkably inhibited LPS-induced neuroinflammation by suppressing microglia overactivation, pro-inflammatory cytok ine release (TNF-α and IL-1ß) and reducing neuronal loss in the CA1 and DG regions of the hippocampus. Importantly, pretreatment with DS reversed LPS-induced upregulation of HMGB1 and TLR4 and inhibited their downstream NF-κB signaling activation, as evidenced by increased IκBα and decreased p-NF-κB p65 levels. Furthermore, DS ameliorated LPS-induced synaptic dysfunction by decreasing MMP-9 and increasing NMDAR1 expression in the hippocampus. Taken together, this study suggests that DS could be a promising treatment for preventing cognitive impairments caused by neuroinflammation.

Prognostic Value of Stress Hyperglycaemia Ratio in Young Patients with Ischaemic Stroke or Transient Ischaemic Attack.

INTRODUCTION: Stress hyperglycaemia is common in stroke. Recently, the stress hyperglycaemia ratio (SHR) has been proposed as a novel marker for stress hyperglycaemia and found to be associated with adverse outcomes in many diseases. However, data regarding the impact of the SHR on ischaemic stroke, especially in young adults, are limited. Therefore, the aim of this study was to investigate whether the SHR is associated with stroke severity and adverse outcomes in young adults with ischaemic stroke or transient ischaemic attack (TIA). METHODS: We retrospectively recruited patients aged 18-45 years with acute ischaemic stroke or TIA. The SHR was calculated as fasting blood glucose (FBG) divided by glycated haemoglobin. The primary and secondary outcomes were 90-day poor functional outcomes and stroke severity on admission, respectively. Multivariable logistic regression, restricted cubic spline models, and subgroup analysis were performed to validate the relationship between the SHR and ischaemic stroke or TIA in young adults. RESULTS: A total of 687 young adults (mean age 36.9 years) were recruited. Among them, 119 (17.3%) patients had prior diabetes, and 568 (82.7%) did not. The SHR was significantly associated with stroke severity and poor functional outcome. Compared with patients with lower SHR values, patients with higher SHR values were more likely to have moderate-to-severe stroke. The multivariable-adjusted OR (95% CI) was 1.70 (1.21-2.39) after adjusting for all potential confounders excluding FBG and 1.50 (1.03-2.17) after FBG adjustment. The restricted cubic spline showed a J-shaped association between the SHR and moderate-to-severe stroke. Compared with patients with lower SHR values, patients with higher SHR values were more likely to have poor functional outcome at 90-day follow-up. The multivariable-adjusted OR (95% CI) was 1.95 (1.12-3.41) after adjusting for all potential confounders excluding FBG and 1.84 (1.01-3.36) after FBG adjustment. A J-shaped association was found between the SHR and poor functional outcomes at the 90-day follow-up. In the subgroup analysis, SHR was independently associated with more severe stroke (OR, 1.79, 95% CI, 1.18-2.72) and poor functional outcomes (OR, 2.11, 95% CI, 1.32-3.35) in nondiabetic patients but not in diabetic patients in multivariate logistic analysis. Despite this, the interaction effects of prior diabetes on the association between the SHR and stroke severity and poor functional outcomes did not reach statistical significance. CONCLUSION: The SHR is independently related to more severe stroke and an increased risk of poor functional outcomes among young adults with ischaemic stroke or TIA.

Association Between Dysmenorrhea and Risk of Epilepsy in East Asian Populations: A Bidirectional Two-Sample Mendelian Randomization Study.

Dysmenorrhea is associated with epilepsy. Existing evidence is mostly limited to observational studies, which are liable to confounding and bias. This study investigated the causal relevance of dysmenorrhea on epilepsy using Mendelian randomization (MR). We extracted instrumental variants for dysmenorrhea and epilepsy from published genomewide association study data, focusing on individuals of East Asian descent. A comprehensive suite of MR estimations and sensitivity analyses was performed to ensure the robustness of the findings. Each outcome database was analyzed separately in both directions. For dysmenorrhea and epilepsy, 7 and 3 genetic variants respectively were selectively extracted as instrumental variants. The results suggest that dysmenorrhea is causally associated with an elevated risk of epilepsy (inverse variance weighted [IVW]: OR = 1.26; 95% CI [1.07, 1.47]; p = 4.42 × 10-3); conversely, no strong evidence was found to corroborate that epilepsy exerts a causal effect on the incidence of dysmenorrhea (IVW: OR = 1.04; 95% CI [0.82, 1.33]; p = .72). These findings provide novel insights into the causal relationship between dysmenorrhea and epilepsy, which may have implications for clinical decision-making in patients with epilepsy and dysmenorrhea.

Prevalence and clinical impact of frailty in COPD: a systematic review and meta-analysis.

BACKGROUND: Frailty has been increasingly identified as a risk factor of adverse outcomes in chronic obstructive pulmonary disease (COPD). The prevalence and impact of frailty on health outcomes in people with COPD require clarification. METHODS: PubMed, Embase, The Cochrane Library and Web of Science (January 1, 2002, to July 1, 2022) were comprehensively searched to identify studies related to frailty and COPD. Comparisons were made between people who did and did not have frailty for pulmonary function, dyspnea severity, 6-minute walking distance, activities of daily life, and mortality. RESULTS: Twenty studies (9 cross-sectional, 10 cohort studies,1 clinical trial) from Europe (9), Asia (6), and North and South America (4), Oceania (1) involving 11, 620 participants were included. The prevalence of frailty was 32.07% (95% confidence interval (CI) 26.64-37.49) with a range of 6.43-71.70% based on the frailty tool used. People with frailty had lower predicted forced expiratory volume in the first second (mean difference - 5.06%; 95%CI -6.70 to -3.42%), shorter 6-minute walking distance (mean difference - 90.23 m; 95%CI -124.70 to -55.76), poorer activities of daily life (standardized mean difference - 0.99; 95%CI -1.35 to -0.62), higher CAT(COPD Assessment Test) score(mean difference 6.2; 95%CI 4.43 to 7.96) and mMRC (modified Medical Research Council) grade (mean difference 0.93; 95%CI 0.85 to 1.02) compared with those who did not (P < 0.001 for all). Meta-analysis showed that frailty was associated with an increased risk of long-term all-cause mortality (HR 1.68; 95% CI 1.37-2.05; I2 = 0%, P < 0.001). CONCLUSION: Frailty is prevalent in people with COPD and linked with negative clinical outcomes including pulmonary function, dyspnea severity, exercise capacity, quality of life and mortality.

SiO2 dust induces inflammation and pulmonary fibrosis in rat lungs through activation of ASMase/ceramide pathway.

The role of ASMase/ceramide signaling pathway in the development of silicosis needs to be verified by in vivo experiments. We investigated the role of the ASMase/ceramide signaling pathway in the progression of silicosis and the effect of desipramine (DMI) (1 mg/mL) on the development of silicosis, by establishing a silica (1 mL, 50 mg/mL) dust-contaminated rat silicosis model and administering the ASMase inhibitor, DMI, to the dust-contaminated rats. The results showed that the levels of interleukin (IL)-1ß and IL-6 were increased in the lung tissues of the rats in the dust-contaminated group at the initial stage after dusting; the inflammatory cell aggregation in the lung tissue was increased. With time progression, the hydroxyproline content in the lung tissue increased, and alpha-smooth muscle actin (α-SMA), collagen I, and vimentin substantially increased, suggesting that silicosis was formed in the lung tissue of the rats 28 days after SiO2 dust treatment. Moreover, the levels of ASMase, ceramide, and sphingosine-1-phosphate (S1P) were increased in the lung tissue of rats. The expression of ß-catenin, fibronectin, and caspase-3 protein was increased, and E-cadherin protein expression was decreased in the lung tissue of the rats in the late stage of dust contamination. The ASMase and ceramide in the lung tissues of the rats in the DMI intervention group were reduced, as were the lung tissue inflammation levels, collagen expression, and lung fibrosis. These results suggest that SiO2 dust may activate the ASMase/ceramide signaling pathway in rat lung tissue, promoting pulmonary fibrosis. DMI inhibited this activation, attenuated apoptosis, blocked epithelial-mesenchymal transition, and halted silica dust-induced silicofibrosis.

Cytotoxic Edema and Adverse Clinical Outcomes in Patients with Intracerebral Hemorrhage.

BACKGROUND: Cytotoxic edema (CE) is an important form of perihematomal edema (PHE), which is a surrogate marker of secondary injury after intracerebral hemorrhage (ICH). However, knowledge about CE after ICH is insufficient. Whether CE has adverse effects on clinical outcomes of patients with ICH remains unknown. Therefore, we aimed to investigate the temporal pattern of CE and its association with clinical outcomes in patients with ICH. METHODS: Data were derived from a randomized controlled study (comparing the deproteinized calf blood extract with placebo in patients with ICH). Intervention in this original study did not show any impact on hematoma and PHE volume, presence of CE, or clinical outcomes. We conducted our analysis in 20 patients who underwent magnetic resonance imaging with diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) images at day 3 and within 7-12 days after symptom onset. CE was defined as an elevated DWI b1000 signal and an ADC value reduced by > 10% compared with the mirror area of interest in the perihematomal region. The modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), and Barthel Index (BI) were performed face to face at 30-day and 90-day follow-ups after ICH onset to assess the clinical outcomes of the patients. RESULTS: CE was detected in nearly two thirds of patients with ICH in our study and seemed to be reversible. CE within 7-12 days, rather than at day 3 after symptom onset, was associated with poor clinical outcome (mRS 3-6) at the 30-day follow-up (P = 0.020). In addition, compared with those without CE, patients with CE within 7-12 days had more severe neurological impairment measured by NIHSS score (P = 0.024) and worse daily life quality measured by BI (P = 0.004) at both the 30- and 90-day follow-ups. CONCLUSIONS: CE appears in the acute phase of ICH and might be reversible. CE within 7-12 days post ICH was related to poor outcomes, which provides a novel therapeutic target for ICH intervention.

Tenuifolin ameliorates the sleep deprivation-induced cognitive deficits.

Tenuifolin (TEN), a natural neuroprotective compound obtained from the Polygala tenuifolia Willd plant, has improved cognitive symptoms. However, the impact of TEN on memory impairments caused by sleep deprivation (SD) is unclear. Accordingly, the objective of this study was to investigate the mechanisms behind the preventative benefits of TEN on cognitive impairment caused by SD. TEN (10 and 20 mg/kg) and Huperzine A (0.1 mg/kg) were given to mice through oral gavage for 28 days during the SD process. The results indicate that TEN administrations improve short- and long-term memory impairments caused by SD in the Y-maze, object identification, and step-through tests. Moreover, TEN stimulated the generation of anti-inflammatory cytokines (interleukin-10), lowered the production of pro-inflammatory cytokines (interleukin-1ß, interleukin-6, and interleukin-18), and activated microglia, improving antioxidant status in the hippocampus. TEN treatments significantly boosted the expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 while considerably decreasing the expression of NOD-like receptor thermal protein domain associated protein 3 and caspase-1 p20. Additionally, TEN restored the downregulation of the brain-derived neurotrophic factor signaling cascade and the impaired hippocampal neurogenesis induced by SD. When considered collectively, our data suggest that TEN is a potentially effective neuroprotective agent for cognition dysfunction.

Polygonum sibiricum polysaccharides exert the antidepressant-like effects in chronic unpredictable mild stress-induced depressive mice by modulating microbiota-gut-brain axis.

Polygonum sibiricum polysaccharides (PSP) are one of the main active components of Polygonatum sibiricum, which is a traditional Chinese medicine with food and drug homologies. Recent studies have revealed the antidepressant-like effects of PSP. However, the precise mechanisms have not been clarified. Therefore, the present study was conducted to explore that whether PSP could exert the antidepressant-like effects via microbiota-gut-brain (MGB) axis in chronic unpredictable mild stress (CUMS)-induced depressive mice by transplantation of fecal microbiota (FMT) from PSP administration mice. FMT markedly reversed the depressive-like behaviors of CUMS-induced mice in the open field, the sucrose preference, the tail suspension, the forced swimming, and the novelty-suppressed feeding tests. FMT significantly increased the levels of 5-hydroxytryptamine and norepinephrine, decreased the levels of the pro-inflammatory cytokines in the hippocampus and reduced the levels of corticosterone, an adrenocorticotropic-hormone, in the serum of CUMS-induced mice. In addition, administration of PSP and FMT significantly increased the expressions of ZO-1 and occludin in the colon and decreased the levels of lipopolysaccharide and interferon-γ in the serum of CUMS-induced mice. Moreover, administration of PSP and FMT regulated the signaling pathways of PI3K/AKT/TLR4/NF-κB and ERK/CREB/BDNF. Taken together, these findings indicated that PSP exerted antidepressant-like effects via the MGB axis.

Treatment of phenolic wastewater by anaerobic fluidized bed microbial fuel cell using carbon brush as anode: microbial community analysis and m-cresol degradation mechanism.

Anaerobic fluidized bed microbial fuel cell (AFB-MFC) is a technology that combines fluidized bed reactor and microbial fuel cell to treat organic wastewater and generate electricity. The performance and the mechanism of treating m-cresol wastewater in AFB-MFC using carbon brush as biofilm anode were studied. After 48 h of operation, the m-cresol removal efficiency of AFB-MFC, MAR-AFB (fluidized bed bioreactor with acclimated anaerobic sludge), MAR-FB (ordinary fluidized bed reactor with only macroporous adsorptive resin) and AST (traditional anaerobic sludge treatment) were 95.29 ± 0.67%, 85.78 ± 1.81%, 71.24 ± 1.86% and 70.41 ± 0.32% respectively. The maximum output voltage and the maximum power density of AFB-MFC using carbon brush as biofilm anode were 679.7 mV and 166.6 mW/m2 respectively. The results of high-throughput sequencing analysis indicated the relative abundance of dominant electroactive bacteria, such as Trichococcus, Geobacter, and Pseudomonas, on the anode carbon brushes was higher than that of AST, and also identified such superior m-cresol-degrading bacteria as Bdellovibrio, Thermomonas, Hydrogenophaga, etc. Based on the determination of m-cresol metabolites detected by Gas Chromatography-Mass Spectrometry (GC-MS), the possible biodegradation pathway of m-cresol under anaerobic and aerobic conditions in AFB-MFC was speculated. The results showed that m-cresol was decomposed into formic acid-acetic anhydride and 3-methylpropionic acid under the action of electrochemistry, which is a simple degradation pathway without peripheral metabolism in AFB-MFC.

Perioperative renal function change after transcatheter aortic valve replacement: A single-center retrospective study in China.

BACKGROUND: In recent years, the kidney function after Transcatheter Aortic Valve Replacement (TAVR) has gradually become a hot spot that arouse extensive attention.Our study is aimed to evaluate the incidence and predictors of acute kidney recovery (AKR) after TAVR. METHODS: A total of 102 patients undergoing TAVR in Beijing Anzhen Hospital from June 2021 to March 2022 were enrolled in our study. Patients were divided into AKR group (n = 54), unchanged group (n = 40) and acute kidney injury (AKI) group (n = 8) based on the percent change of estimated glomerular filtration rate (eGFR). Univariate analysis was used to compare the differences in general clinical characteristics and other related indicators between the three groups to analyze the risk factors of AKR. RESULTS: The incidence of AKR was 53% (54/102) after TAVR. Multivariate analysis showed that the incidence of age and proportion of severe NYHA class (III or IV) was significantly higher in the AKR group while renal dysfunction (eGFR <60 mL/min/1.73 m2) was lower. Besides, fluid management/volume therapy was significantly different among the three groups. CONCLUSIONS: AKR is a generalizable phenomenon occurring frequently after TAVR. The age, proportion of severe NYHA class and the baseline renal function are independent predictors of AKR events in patients with severe aortic stenosis undergoing TAVR.

Overexpression of KLF4 Suppresses Pulmonary Fibrosis through the HIF-1α/Endoplasmic Reticulum Stress Signaling Pathway.

The hypoxia-inducible factor-1α/endoplasmic reticulum stress signaling pathway (HIF-1α/ERS) has a crucial role in the pathogenetic mechanism of pulmonary fibrosis (PF). However, the upstream regulatory mediators of this pathway remain unclear. In the present study, by conducting bioinformatics analysis, we found that Krüppel-like factor 4 (KLF4) expression was decreased in the lung tissues of patients with idiopathic pulmonary fibrosis (IPF) as compared to that in patients with non-IPF. Furthermore, KLF4 expression was significantly reduced (p = 0.0331) in bleomycin-induced fibrotic HFL-1 cells. Moreover, in mice with bleomycin-induced PF, the degree of fibrosis was significantly reduced in mice overexpressing KLF4 as compared to that in wild-type mice. In mice and HFL-1 cells, KLF4 overexpression significantly reduced bleomycin-induced protein expression of HIF-1α (p = 0.0027) and ERS markers, particularly p-IRE1α (p = 0.0255) and ATF6 (p = 0.0002). By using the JASPAR database, we predicted that KLF4 has five binding sites for the HIF-1α promoter. The results of in vitro and in vivo studies suggest that KLF4 may inhibit PF through the HIF-1α/ERS pathway. This finding could guide the development of future therapies for PF and facilitate the identification of appropriate biomarkers for routine clinical diagnosis of PF.

Icaritin Promotes Myelination by Simultaneously Enhancing the Proliferation and Differentiation of Oligodendrocyte Precursor Cells.

Myelin repair, which is known as remyelination, is critical to the treatment of neurodegenerative diseases, and myelination depends on not only the differentiation of oligodendrocyte precursor cells toward oligodendrocytes but also the renewal of oligodendrocyte precursor cells under pathological conditions. However, simultaneously promoting the differentiation and proliferation of oligodendrocyte precursor cells in lesions remains an unmet challenge and might affect demyelinating diseases. Kidney-tonifying herbs of traditional Chinese medicine (TCM) are effective in improving the symptoms of degenerative patients. However, herbs or compounds with dual functions are unverified. The purpose of this study was to find a kidney-tonifying TCM that synchronously improved the differentiation and proliferation of oligodendrocyte precursor cells under pathological conditions. Compounds with dual functions were screened from highly frequently used kidney-tonifying TCM, and the effects of the obtained compound on remyelination were investigated in an in vitro oligodendrocyte precursor cell differentiation model under pathological conditions and in demyelinating mice in vivo. The compound icaritin, which is an active component of Yin-Yang-Huo (the leaves of Epimedium brevicornu Maxim), demonstrated multiple effects on the remyelination process, including enhancing oligodendrocyte precursor cell proliferation, facilitating the differentiation of neural progenitor cells toward oligodendrocyte precursor cells and further toward oligodendrocytes, and maturation of oligodendrocytes under corticosterone- or glutamate-induced pathological conditions. Importantly, icaritin effectively rescued behavioral functions and increased the formation of myelin in a cuprizone-induced demyelination mouse model. The multiple effects of icaritin make it a promising lead compound for remyelination therapy.

Clinical significance of neutrophil to lymphocyte ratio in ischemic stroke and transient ischemic attack in young adults.

OBJECTIVE: Few studies evaluated the association between neutrophil to lymphocyte ratio (NLR) and clinical outcomes in ischemic stroke or transient ischemia attack (TIA) in young adults. We aimed to investigate the relationship of NLR with 90-day functional independence in ischemic stroke or TIA in young adults. METHODS: We retrospectively included patients aged 18-45 and diagnosed with ischemic stroke or TIA. Information including demographics, clinical and imaging characteristics, and the 90-day clinical outcome was collected. The primary outcome was excellent clinical outcome at 90 days, defined as mRS 0-1. Logistic regression analyses and a receiver operator characteristic (ROC) curve were used to investigate the association between NLR and 90-day clinical outcome. RESULTS: A total of 691 young patients with ischemic stroke or TIA were included in the final study. A higher level of NLR indicated poorer clinical outcome at 90 days (p for trend <0.001). The multivariable logistics regression suggested that NLR was an independent predictor of mRS 0-1 at 90 days (crude OR: 0.88, 95% CI 0.83-0.94, p < 0.001; adjusted OR of model 2: 0.87, 95% CI 0.84-0.94, p < 0.001; adjusted OR of model 3: 0.92, 95% CI 0.84-0.99, p = 0.04). CONCLUSION: In our study, a higher level of NLR was correlated with poorer functional outcomes at 90 days in ischemic stroke or TIA in young adults.

Impact of serum phosphate on severity and functional outcomes after ischemic stroke in young adults.

BACKGROUND AND AIMS: Serum phosphate is an essential nutrient that plays multiple physiological roles in cardiovascular function. The aim of this study was to investigate the association between serum phosphate and stroke severity and prognosis in ischemic stroke and transient ischemic attack (TIA) among young adults. METHODS AND RESULTS: We retrospectively recruited patients with acute ischemic stroke and TIA aged 18-45 years. The primary outcome was 90-day poor functional outcome (modified Rankin Scale score of 2-6). The secondary outcomes included stroke severity (NIHSS ≥5 was defined as moderate to severe stroke) and poor functional outcome at hospital discharge. A total of 687 patients with a mean age of 36.8 years were enrolled. Lower serum phosphate levels were significantly associated with more severe stoke (P for trend = 0.017). Compared with the fourth quartile, the odds ratio (95% CI) of the first quartile was 1.85 (1.19-3.22) for moderate to severe stroke. After adjusting for confounders other than stroke severity, the odds ratio (95% CI) of the first quartile was 1.74 (1.06-2.86) for poor functional outcome at hospital discharge and 1.90 (1.09-3.31) at 90-day follow-up compared with the fourth quartile. However, the significant association between serum phosphate and poor functional outcomes disappeared after stroke severity was further adjusted. CONCLUSIONS: Serum phosphate is more likely a marker of stroke severity than a contributor to poor functional outcomes after ischemic stroke and TIA in young adults. Lower serum phosphate levels were associated with more severe stroke.

Surgery versus radiotherapy in octogenarians with stage Ia non­small cell lung cancer: propensity score matching analysis of the SEER database.

OBJECTIVES: To compare overall survival (OS) and cancer-specific survival (CSS) outcomes of surgery with radiotherapy in octogenarians with stage Ia non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients aged ≥ 80 years with clinical stage Ia (T1N0M0) NSCLC between 2012 and 2017 were identified from the population-based Surveillance, Epidemiology, and End Results (SEER) database. Patients were assigned into surgery and radiotherapy groups. Multivariate Cox regression analysis was used to identify survival-associated factors. Treatment groups were adjusted by propensity score matching (PSM) analysis while OS and CSS outcomes were compared among groups by Kaplan-Meier analysis. RESULTS: A total of 1641 patients were identified, with 46.0% in the surgical group and 54.0% in the radiotherapy group. Compared to surgery, radiotherapy-treated patients were older, later diagnosed, had more often unmarried, more squamous cell carcinoma, more unknown grade and increased tumor sizes. Radiotherapy was associated with a significantly worse OS, compared to surgery (hazard ratio 2.426; 95% CI 2.003-2.939; P < .001). After PSM, OS (P < 0.001) and CSS (P < 0.001) were higher in the surgery group. The 1-, 3-, and 5-year OS rates of surgical and radiotherapy group were 90.0%, 76.9%, 59.9%, and 86.0%, 54.3%, 28.0%, respectively. The 1-, 3-, and 5-year CSS rates of surgical and radiotherapy group were 94.5%, 86.1%, 78.0% and 90.7%, 74.5%, 61.0%, respectively. There were no survival differences between the matched surgery without lymph node examination (LNE) and radiotherapy group, as well as between the matched surgery and radiotherapy who were recommended but refused surgery group. CONCLUSIONS: In octogenarians with stage Ia NSCLC, surgery with lymph node dissection offers better OS and CSS outcomes than radiotherapy.

The interplay between ASMase signaling pathway and NLRP3 in the epithelial to mesenchymal transition of HBE cells induced by silica.

Epithelial-mesenchymal transition (EMT) is an important part of pulmonary fibrosis. Our earlier study illustrated that the acid sphingomyelinase (ASMase) pathway plays significant role in silica (SiO2 )-induced transformation of lung fibroblasts into myofibroblasts. The metabolite of ASMase, ceramide (Cer), activates the inflammatory response by activating Nod-like receptor protein 3 (NLRP3) in macrophages, and NLRP3 is also involved in the EMT process. However, whether ASMase and NLRP3 are involved in regulating SiO2 -induced EMT has not been confirmed. In this study, an in vitro model of EMT in human bronchial epithelial (HBE) cells was established by SiO2 dust staining to investigate the role of ASMase and NLRP3 in EMT and to provide new clues for the molecular mechanism of silicosis. HBE cells were stained with 100 µg/ml SiO2 dust for 72 h to establish the EMT model. The ASMase inhibitor desipramine decreased the level of S1P and the expression of α-smooth muscle actin (α-SMA) and NLRP3 in SiO2 dust-stained HBE cells, whereas the expression of E-cadherin (E-cad) increased. The NLRP3 inhibitor MCC950 inhibited the secretion of interleukin-1ß (IL-1ß) and decreased the expression of NLRP3, Caspase-1, and α-SMA in SiO2 dust-stained HBE cells, whereas E-cad expression increased and ASMase activity and S1P levels decreased. It was concluded that SiO2 dust increases the release of the inflammatory factor and induces EMT in HBE cells. Inhibition of ASMase activity or NLRP3 expression reduced the SiO2 dust-induced cell inflammatory response and slowed the occurrence of EMT in HBE cells. Therefore, NLRP3 and ASMase may interact in SiO2 dust-induced EMT in HBE cells.