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Tumor cells have long been recognized as a relative contraindication to hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer growth. However, in an oxygen deficit condition, tumor cells are more progressive and can be metastatic. HBOT increasing in oxygen partial pressure may benefit tumor suppression. In this study, we investigated the effects of HBOT on solid tumors, such as lung cancer. Non-small cell human lung carcinoma A549-cell-transferred severe combined immunodeficiency mice (SCID) mice were selected as an in vivo model to detect the potential mechanism of HBOT in lung tumors. HBOT not only improved tumor hypoxia but also suppressed tumor growth in murine xenograft tumor models. Platelet endothelial cell adhesion molecule (PECAM-1/CD31) was significantly increased after HBOT. Immunostaining of cleaved caspase-3 was demonstrated and apoptotic tumor cells with nuclear debris were aggregated starting on the 14th-day after HBOT. In vitro , HBOT suppressed the growth of A549 cells in a time-dependent manner and immediately downregulated the expression of p53 protein after HBOT in A549 cells. Furthermore, HBOT-reduced p53 protein could be rescued by a proteasome degradation inhibitor, but not an autophagy inhibitor in A549 cells. Our results demonstrated that HBOT improved tissue angiogenesis, tumor hypoxia and increased tumor apoptosis to lung cancer cells in murine xenograft tumor models, through modifying the tumor hypoxic microenvironment. HBOT will merit further cancer therapy as an adjuvant treatment for solid tumors, such as lung cancer.

Early neurologic improvement (ENI) after intravenous thrombolysis is associated with favorable outcome, but associated serum biomarkers were not fully determined. We aimed to investigate the issue based on a prospective cohort. In INTRECIS study, five centers were designed to consecutively collect blood sample from enrolled patients. The patients with ENI and without ENI were matched by propensity score matching with a ratio of 1:1. Preset 49 biomarkers were measured through microarray analysis. Enrichment of gene ontology and pathway, and protein-protein interaction network were analyzed in the identified biomarkers. Of 358 patients, 19 patients with ENI were assigned to ENI group, while 19 matched patients without ENI were assigned to Non ENI group. A total of nine biomarkers were found different between two groups, in which serum levels of chemokine (C-C motif) ligand (CCL)-23, chemokine (C-X-C motif) ligand (CXCL)-12, insulin-like growth factor binding protein (IGFBP)-6, interleukin (IL)-5, lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, plasminogen activator inhibitor (PAI)-1, platelet-derived growth factor (PDGF)-AA, suppression of tumorigenicity (ST)-2, and tumor necrosis factor (TNF)-α were higher in the ENI group, compared with those in the Non ENI group. We found that serum levels of CCL-23, CXCL-12, IGFBP-6, IL-5, LYVE-1, PAI-1, PDGF-AA, ST-2, and TNF-α at admission were associated with post-thrombolytic ENI in stroke. The role of biomarkers warrants further investigation. Clinical Trial Registration: https://www.clinicaltrials.gov; identifier: NCT02854592.

Introduction Hallux valgus (HV) is a common foot deformity, with metatarsus adductus (MA) identified as a potential predisposing factor. MA has been shown to negatively affect surgical outcomes for HV, particularly in severe cases. This study aims to clarify the prevalence of MA in the HV population using different metatarsus adductus angle (MAA) measurement methods and assess whether MAAs are influenced by HV severity. Materials and Methods This retrospective study included 294 feet from 147 participants. Patients were classified into non‐HV (normal) and HV subgroups, with HV severity graded as mild, moderate, or severe based on the hallux valgus angle (HVA) measured on dorsoplantar weight‐bearing radiographs. The prevalence of MA was assessed using four radiographic measurements: Sgarlato's MAA (MAA4), modified Sgarlato's MAA (MAA5), modified Engel's angle, and the calcaneo‐second metatarsal angle (rearfoot‐MT2). The interclass correlation coefficient was used to evaluate the reliability of the measurements. The correlation between HVA and MAA was analyzed using Spearman's Rho coefficient, and the prevalence of MA was compared using various measures. Results After excluding 87 feet, 207 feet (146 HV and 61 non‐HV) from 147 participants were analyzed. All four MAA measurements showed excellent reliability, with the modified Engel's angle demonstrating the highest interobserver reliability and strongest correlation with HVA. HVA was significantly higher in the MA (+) group compared to the MA (−) group (32.21 vs. 24.78° and p = 0.001). The overall prevalence of MA in the cohort was 19.3% (MAA4), 24.2% (MAA5), 18.4% (modified Engel's angle), and 8.2% (rearfoot‐MT2). MA was significantly more prevalent in the HV group compared to the normal group (24.0% vs. 4.9%) when using the modified Engel's angle, with MA prevalence increasing as HV severity worsened. Conclusions MA is common among patients with HV, with its prevalence increasing in parallel with HV severity. The modified Engel's angle is a reliable and sensitive method for detecting MA associated with HV, particularly in severe cases, and its use can help tailor surgical plans to improve outcomes. Surgeons should be mindful of the presence of concomitant MA when planning HV surgery, as it may negatively affect surgical outcomes and increase the risk of recurrence.

Objective evaluations of transverse tarsometatarsal (TMT) hypermobility/instability are lacking. This study aims to radiographically explore the relationship between transverse TMT instability and metatarsus adductus (MA) in hallux valgus (HV). This study retrospectively analyzed 207 feet with varying degrees of HV, employing the distance between the first and second metatarsals (M1-2 distance) to assess transverse TMT instability of the first ray. Participants were categorized into MA and non-MA groups. It was found that the M1-2 distance significantly increased with the hallux valgus angle (HVA) and metatarsus adductus angle (MAA), demonstrating significant differences between the MA and non-MA groups. The measurement of M1-2 distance showed high reliability, and its cutoff value was determined to be 4.05 mm. Additionally, the results suggest that the widening of the M1-2 distance may be a predisposing factor for MA in HV patients, highlighting its role in the pathogenesis of this foot condition. These findings highlight the need for a comprehensive assessment of TMT instability on both the axial and sagittal planes for the surgical planning of HV, particularly when complicated by a large MAA. Based on these insights, reoriented first-TMT arthrodesis might be recommended for HV with significant MA to address potential multiplanar instability.

This is a single-center retrospective analysis of the clinical data of 516 patients with acute ischemic stroke who underwent intravenous thrombolysis. This study was conducted to compare the therapeutic efficacy of smokers and non-smokers. Univariate analysis was used to analyze and compare the clinical data of smokers and non-smokers. Multivariate analysis was used to assess risk factors affecting the 90-day modified Rankin Scale (mRS) score. Among the 516 patients, 235 (45.5 %) were smokers. Univariate analysis showed that smokers have a better 90-day prognosis and a lower 90-day mRS score than non-smokers. Multivariate logistic regression analysis showed that smoking is not a protective factor affecting prognosis, while baseline National Institutes of Health Stroke Scale (NIHSS) score was an independent risk factor affecting the 90-day functional outcome. Subgroup analysis did not determine a relationship between the 90-day mRS score and the smoking intensity and duration. Smoking was not associated with a good 90-day prognosis after intravenous thrombolysis (IVT) treatment. The good clinical outcome of smokers in univariate analysis was bound up with their baseline characteristics. Baseline NIHSS score was the independent risk factor that affected the 90-day outcome of AIS patients undergoing IVT. •the smoker's paradox was observed in the treatment of intravenous thrombolysis.•smoking was not an independent factor affecting intravenous thrombolysis outcome.•good outcome in smokers is correlated with differences in baseline characteristics.

Interferon-beta (IFN-β) treatment may not be effective in neuromyelitis optica (NMO). Whether the poor response to IFN-β is related to long spinal cord lesions (LSCL) or the NMO disease entity itself is unclear. We evaluated the spinal cord involvement of patients with multiple sclerosis (MS) and NMO, as well as the response after receiving IFN-β. Forty-nine MS and 21 NMO patients treated with IFN-β for at least 2 years from 2002-2008 were enrolled in this study and the treatment response was analyzed 2 years post-treatment. In the study, spinal cord lesions were present in 57.1% (28/49) of the MS patients, of which 16.3% (8/49) presented spinal cord lesions longer than 3 vertebral segments (LSCL). Responses to IFN-β treatment were seen in 69.3% (34/49) of all the MS cases, of which the appropriate response rates were 76.1% (16/21) in MS patients without spinal cord lesions and 37.5% (3/8) in patients with LSCL. Only 14.2% (3/21) of NMO patients responded to IFN-β treatment. In conclusion, spinal cord lesion is common in MS patients in Taiwan. Both NMO and MS patients with LSCL had a poor response to IFN-β treatment. NMO patients had a worse response to IFN-β treatment than MS patients with LSCL, which shows that the crucial structural defect is something other than LSCL such as the elevated serum IL17 level in NMO compared to MS.

Multiple sclerosis (MS) is the most common prototypic inflammatory demyelinating disease. Neuromyelitis optica (NMO) is another inflammatory demyelinating disease of the central nervous system that exhibits clinical symptoms mainly associated with optic neuritis and myelopathy. The inflammatory reaction in MS is associated with an upregulation of a variety of T helper 1 (Th1)- or Th17-mediated cytokines. However, NMO and MS are intertwined both clinically and pathologically, which complicates their diagnosis and treatment. The aim of this study was to evaluate the differences in serum cytokine levels in patients with NMO and MS. We collected peripheral serum from patients with these central nervous system demyelinating diseases for the study. A cytometric bead array was used to assess the cytokine levels using flow cytometry. We found more inflammatory [interleukin (IL)-2 and interferon-γ) and anti-inflammatory (IL-4 and IL-10) cytokines in NMO than in MS. The differences in the optimal cutoff points of serum cytokines, including IL-2 ≥5 pg/mL, can differentiate NMO from MS. In conclusion, patients with NMO had an increased Th1-mediated inflammatory response, but similar Th17-mediated inflammation changes compared to patients with MS. Serum cytokine studies can differentiate NMO cases from MS.

Purpose. Nonalcoholic fatty liver disease (NAFLD) is a progressive and intractable disease associated with metabolic syndrome. Red yeast rice (RYR) contains monacolin K, a potent inhibitor of HMG-CoA reductase, and its consumption decreases cholesterol and triglyceride levels. We examined the efficacy of RYR constituents using a novel metabolic syndrome-NAFLD mouse model (MSG mice). Methods. Two types of RYR grown under different culture conditions were used. 1P-DU contained only 0.002 g/100 g of monacolin K, whereas 3P-D1 contained 0.131 g/100 g. MSG mice were divided into three groups: control (C) group fed standard food, RYR-C group fed standard food with 1% 1P-DU, and RYR-M group fed standard food with 1% 3P-D1. Mice were examined from 12 to 24 weeks of age. Results. Serum insulin, leptin, and liver damage as well as macrophage aggregation in visceral fat in RYR-C and RYR-M groups were lower than those in C group. The serum adiponectin levels in RYR-C group were significantly higher than those in RYR-M and C groups. Conclusions. RYR was effective against obesity-related inflammation, insulin resistance, and NAFLD in MSG mice irrespective of monacolin K levels. GABA and various peptides produced during fermentation were determined as the active constituents of RYR.

Objectives Migraine and restless legs syndrome (RLS) are often comorbid and share elements of pathology; however, their neuroanatomical underpinnings are poorly understood. This study aimed to identify patterns of gray matter volume (GMV) alteration specific to and common among patients with RLS, migraine, and comorbid migraine and RLS. Methods High‐resolution T1‐weighted images were acquired from 116 subjects: 27 RLS patients, 22 migraine patients, 22 patients with comorbid migraine and RLS, and 45 healthy controls. Direct group comparisons and conjunction analysis were first used to localize the distinct and shared neural signatures of migraine and RLS. We also investigated whether the shared neural signature could be replicated in an additional comorbid migraine/RLS group. Results Compared with healthy controls, migraine patients showed GMV changes in the lateral occipital cortex, cerebellum, frontal pole, and middle frontal gyrus (MFG), and RLS patients showed GMV changes in the thalamus, middle temporal gyrus, anterior cingulate cortex, insular cortex, and MFG. In migraine, compared with RLS, GMV differences were found in the precuneus, lateral occipital and occipital fusiform cortex, superior frontal and precentral gyri, and cerebellum. Conjunction analyses for these disorders showed altered GMV in the MFG, also found in patients with comorbid migraine and RLS. The GMV of the MFG also correlated with sleep quality in patients with comorbid migraine and RLS. Interpretation Migraine and RLS are characterized by shared and distinctive neuroanatomical characteristics, with a specific role of the MFG. These findings may be related to shared pathophysiology of these two distinct disorders.

BackgroundPrimary headache disorders (PHDs) are associated with sleep problems. It is suggested that headache and sleep disorder share anatomical and physiological characteristics. We hypothesised that patients with PHDs were exposed to a great risk for developing sleep apnoea (SA).MethodsIn this retrospective longitudinal study, the data obtained from the Longitudinal Health Insurance Database in Taiwan were analysed. The study included 1346 patients with PHDs who were initially diagnosed and 5348 patients who were randomly selected and age/sex matched with the study group as controls. PHDs, SA, comorbidities and other confounding factors were defined based on International Classification of Diseases, Ninth Revision, Clinical Modification. Cox proportional hazards regressions were employed to examine adjusted HRs after adjusting with confounding factors.ResultsOur data revealed that patients with PHDs had a higher risk (HR 2.17, 95% CI 1.259 to 3.739, p<0.05) to develop SA compared with matched cohorts, whereas patients with migraine exhibited a high risk (HR 2.553, 95% CI 1.460 to 4.395, p<0.01). The results showed that patients with PHDs aged 18–44 exhibited highest risk of developing SA. In addition, males with PHDs exhibited an HR 3.159 (95% CI 1.479 to 6.749, p<0.01) for developing SA, respectively. The impact of PHDs on SA risk was progressively increased by various follow-up time intervals.ConclusionOur results suggest that PHDs are linked to an increased risk for SA with sex-dependent and time-dependent characteristics.