Basilar artery curvature increases the risk of posterior circulation infarction occurrence in patients without vertebrobasilar stenosis.

INTRODUCTION: Limited cross-sectional or case-control studies have identified the relationship between basilar artery (BA) curvature and posterior circulation infarction (PCI). This study aimed to identify the influence of BA curvature severity on the risk of PCI occurrence in patients without vertebrobasilar stenosis through a prospective cohort study. METHODS: In this study, we enrolled 171 patients with BA dolichosis but without vertebrobasilar stenosis. The BA geometric parameters were evaluated on MRA. The primary outcome was the occurrence of PCI, mainly referring to cerebellar and/or brainstem infarction. Cox proportional hazard models were used to detect possible predictors of PCI. RESULTS: Among them, 134 (78.4%) patients were diagnosed with BA curvature, including 124 with moderate curvature and 10 with prominent curvature. The defined PCI occurrence was observed in 32 (18.7%) patients with a median follow-up time of 45.6 months. Cox proportional hazard analysis showed that BA prominent curvature (HR = 6.09; 95% CI: 1.36-27.28; P = 0.018) significantly increased the risk of PCI occurrence, and bending length (BL) was also significantly associated with PCI occurrence, with the adjusted HR per 1-mm increase of BL of 1.09 (95% CI: 1.01-1.18; P = 0.040). In the subgroup analysis stratified by age, BA prominent curvature was highly associated with PCI occurrence in patients aged > 61 years (HR = 11.76; 95% CI: 1.21-113.90; P = 0.033). Additionally, good antiplatelet therapy adherence could significantly reduce the risk of PCI occurrence. CONCLUSION: BA curvature may increase the risk of PCI occurrence, especially in elderly patients with prominent curvature. Improving adherence to antiplatelet therapy can help reduce the risk of PCI occurrence.

Moving silicone oil particles in the ventricle: a case report and updated review.

BACKGROUND: The movement of intraventricular silicone oil observed in the supine position is extremely rare. Herein, we describe a patient who presented with dynamically moving silicone oil particles in the ventricle when changing position and provide an updated review of this phenomenon. CASE PRESENTATION: We report a case of a 70-year-old woman who presented with intraventricular hyperdensities that were occasionally found on brain computed tomography (CT). Initial nonenhanced brain CT demonstrated nondependent hyperdensities in the bilateral anterior horns of the lateral ventricles, the third ventricle, and the right suprasellar cistern, mimicking an intraventricular hemorrhage. Further brain magnetic resonance imaging (MRI) in the supine position revealed abnormal signals in the bilateral anterior horns of the lateral ventricles, the posterior horn of the right lateral ventricle, the third ventricle, the right suprasellar cistern, and the bilateral eyeballs, with isosignal intensities surrounded by low-signal chemical shift artifacts on T1-weighted imaging and variable signals (hypo- or hyperintensity) on T2-weighted imaging. The lesion in the anterior horn of the right ventricle largely moved to the posterior horn of the ipsilateral ventricle. The final craniocervical CT angiography showed that the lesion in the posterior horn had moved back to the anterior horn of the right lateral ventricle. These features were consistent with intraventricular silicone oil migration. The final spinal MRI did not demonstrate a migration of silicone oil into the spinal subarachnoid space. DISCUSSION AND CONCLUSIONS: This case report describes a dynamic process of silicone oil displacement in the supine position and provides a comprehensive imaging presentation. The moving pattern and a characteristic chemical shift artifact on MRI are key to the diagnosis and may help prevent unnecessary examinations or intervention.

A novel, complex RUNX2 gene mutation causes cleidocranial dysplasia.

BACKGROUND: Haploinsufficiency of the runt-related transcription factor 2 (RUNX2) gene is known to cause cleidocranial dysplasia (CCD). Here, we investigated a complex, heterozygous RUNX2 gene mutation in a Chinese family with CCD and the pathogenesis associated with the variations. METHODS: Genomic DNA extracted from peripheral venous blood was taken from the proband, her parents and 3 siblings, and 150 normal controls. Analysis of their respective RUNX2 gene sequences was performed by PCR amplification and Sanger sequencing. Pathogenesis associated with RUNX2 mutations was investigated by performing bioinformatics, real-time PCR, western blot analysis, and subcellular localization studies. RESULTS: We identified 2 complex heterozygous mutations involving a c.398-399 insACAGCAGCAGCAGCA insertion and a c.411-412 insG frameshift mutation in exon 3 of the RUNX2 gene. The frameshift mutation changed the structure of the RUNX2 protein while did not affect its expression at the mRNA level. Transfection of HEK293T cells with a plasmid expressing the RUNX2 variant decreased the molecular weight of the variant RUNX2 protein, compared with that of the wild-type protein. Subcellular localization assays showed both nuclear and cytoplasmic localization for the mutant protein, while the wild-type protein localized to the nucleus. CONCLUSIONS: Our findings demonstrated that the novel c.398-399insACAGCAGCAGCAGCA mutation occurred alongside the c.411-412insG frameshift mutation, which resulted in RUNX2 truncation. RUNX2 haploinsufficiency was associated with CCD pathogenesis. These results extend the known mutational spectrum of the RUNX2 gene and suggest a functional role of the novel mutation in CCD pathogenesis.

980 nm Photobiomodulation Promotes Osteo/Odontogenic Differentiation of the Stem Cells from Human Exfoliated Deciduous Teeth Via the Cross talk Between BMP/Smad and Wnt/ß-Catenin Signaling Pathways.

Increasing evidence suggests stem cells from human exfoliated deciduous teeth (SHEDs) serve as desirable sources of dentin regeneration. Photobiomodulation (PBM) has shown great potential in enhancing the proliferation and osteogenesis of human bone marrow mesenchymal stem cells (hBMMSCs). However, the specific role of PBM in odontogenic differentiation of SHEDs is little know, and we further investigated potential mechanism of PBM osteo/odontogenisis. A 980 nm diode laser with different energy densities of (0.5, 5, 10 J cm-2 ) in a 100-mW continuous wave was used for irradiation every 24 h. Osteo/odontogenic differentiation of SHEDs was achieved by performing alkaline phosphatase (ALP) and alizarin red staining (ARS) and osteo/odontogenic markers were also evaluated by qRT-PCR and western blotting. Additionally, western blot and immunohistochemical staining were performed to evaluate the levels of BMP/Smad and Wnt/ß-catenin signaling-related proteins. We found that PBM at 5 J cm-1 increased mineral deposition and upregulated the expression of related osteo/odontogenic markers along with the elevated expression of ß-catenin and phosphorylation level of Smad1/5/9. Furthermore, Wnt signaling inhibition using DKK1 and BMP signaling inhibition using noggin inhibited PBM-induced osteo/odontogenic marker expression when used individually or jointly. In conclusion, PBM induces the osteo/odontogenic differentiation of SHEDs through cross talk between BMP/Smad and Wnt/ß-catenin signaling pathways.

Prevalence and associated factors of basilar artery dolichosis in patients with acute cerebral infarction.

Introduction: Little attention has been given to the factors associated with basilar artery (BA) dolichosis. This study aims to elucidate the prevalence and associated factors of BA dolichosis in patients with acute cerebral infarction (ACI). Methods: We collected the clinical and laboratory data of 719 patients with ACI admitted to our department. Magnetic resonance angiography was used to evaluate the geometric parameters of the BA and intracranial vertebral arteries (VAs). A BA curve length > 29.5 mm or bending length (BL) > 10 mm was identified as BA dolichosis. Univariate and multivariate logistic regression were performed to determine the factors associated with BA dolichosis. Results: Among 719 patients with ACI, 238 (33.1%) demonstrated BA dolichosis, including 226 (31.4%) with simple BA dolichosis and 12 (1.7%) with basilar artery dolichoectasia (BADE). Pearson correlation analyses showed that BA curve length was positively correlated with BL (r = 0.605). Multivariate logistic regression analysis demonstrated that current smoking (OR = 1.50, 95% CI: 1.02-2.21, p = 0.039), diabetes mellitus (OR = 1.66, 95% CI: 1.14-2.41, p = 0.008), BA diameter (OR = 3.04, 95% CI: 2.23-4.13, p < 0.001), BA bending (OR = 4.24, 95% CI: 2.91-6.17, p < 0.001) and BL (OR = 1.45, 95% CI: 1.36-1.55, p < 0.001) were significantly associated with BA dolichosis. Conclusion: This study suggests that BA dolichosis was common in patients with ACI, and the morphological parameters of the vertebrobasilar artery and acquired risk factors (including smoking and diabetes) were risk factors for BA dolichosis.

Basilar Artery Dolichosis Increases the Risk of Long-Term Recurrence in Patients With Pontine Infarction: A Prospective Cohort Study.

Background and Purpose: Patients with basilar artery (BA) dolichosis are at high risk of acute pontine infarction (API), but the association between BA dolichosis and long-term stroke recurrence has received little attention. We aimed to identify the effect of BA dolichosis on the risk of long-term brainstem infarction recurrence in patients with API. Methods: In this prospective cohort study, we enrolled 113 patients with API admitted to our department. BA dolichosis was diagnosed by a BA curve length >29.5 mm or bending length (BL) >10 mm on magnetic resonance angiography. The primary outcome was the occurrence of diffusion-weighted imaging (DWI)-confirmed brainstem infarction. The Cox proportional hazard model was used to detect possible predictors of brainstem infarction recurrence. Results: Among 113 patients with API, 39 (34.5%) patients had BA dolichosis, and DWI-confirmed brainstem infarction recurred in 15 (13.3%) patients with a mean follow-up time of 31.2 months; the estimated 5-year incidence of brainstem infarction recurrence was 23.1% in patients with BA dolichosis, which was significantly higher than the incidence of 8.1% in patients without BA dolichosis. Cox proportional hazard analysis showed that age ≥65 years (hazard ratio (HR) = 3.341, 95% confidence interval (CI): 1.079-10.348, P = 0.036) and BA dolichosis (HR = 3.048, 95% CI: 1.069-8.693, P = 0.037) were significantly associated with a higher risk of brainstem infarction recurrence. In a subgroup analysis stratified by age, the patients aged ≥65 years with BA dolichosis had a higher risk of brainstem infarction recurrence (HR = 7.319, 95% CI: 1.525-35.123, P = 0.013). Conclusions: This study indicates that BA dolichosis may increase the risk of long-term brainstem infarction recurrence in patients with API, especially in elderly patients, and therefore warrants more attention in clinical practice.

Establishment of an Immortalized Mouse Bmp2 Knockout Dental Papilla Mesenchymal Cell Line.

Bone morphogenetic protein 2 (Bmp2) is essential for dentin formation. Bmp2 cKO mice exhibited similar phenotype to dentinogenesis imperfecta (DGI), showing dental pulp exposure, hypomineralized dentin, and delayed odontoblast differentiation. As it is relatively difficult to obtain primary Bmp2 cKO dental papilla mesenchymal cells and to maintain a long-term culture of these primary cells, availability of immortalized deleted Bmp2 dental papilla mesenchymal cells is critical for studying the underlying mechanism of Bmp2 signal in odontogenesis. Here we describe the generation of an immortalized deleted Bmp2 dental papilla mesenchymal (iBmp2ko/ko-dp) cell line by introducing Cre fluorescent protein (GFP) into the immortalized mouse floxed Bmp2 dental papilla mesenchymal (iBmp2flox/flox-dp) cells.

Atypical "nine" syndrome in bilateral pontine infarction: A case report.

RATIONALE: "Nine" syndrome, that is "eight-and-a-half" syndrome associated with hemiplegia and hemidysesthesia, is a rare disorder. This study aimed to report a Chinese patient with acute bilateral pontine infarction manifesting as eight-and-a-half syndrome plus hemiplegia (atypical nine syndrome), and also the clinical and neuroimaging findings were explained and discussed with review of the literature. PATIENT CONCERNS: A 79-year-old woman experienced sudden vertigo, nausea, vomiting, and weakness at her left arm and leg. The neurological examination disclosed her right horizontal gaze palsy, internuclear ophtalmoplegia (INO), and right-sided peripheral facial paralysis combined with slight left-sided hemiplegia, which were consistent with atypical nine syndrome. DIAGNOSES: Cranial magnetic resonance imaging (MRI) displayed acute multiple ischemic infarction, involving bilateral pontine tegmentum, basilar part of right paramedian pontine, and left cerebellar hemisphere. Intracranial MR angiography (MRA) revealed right middle cerebral artery occlusion, no clear visualization of bilateral vertebral arteries, and basilar artery hypoplasia with stenotic segments. INTERVENTIONS: Thrombolysis could not be performed due to the time window. The patient was given low molecular weight heparin for anticoagulation because of posterior circulation and progressive stroke. OUTCOMES: The vertigo disappeared, and a notable improvement with minimal restriction in the right horizontal gaze and partial relief of her facial paralysis were found at discharge, while her left hemiparesis was fully resolved. No recurrence of cerebral infarction was observed during follow-up as well. LESSONS: This case report with atypical nine syndrome is fairly rare. Nine syndrome may refer to the lesion located in unilateral tegmentum of the caudal pontine plus paramedian pontine, with an important localization value.

Therapeutic effects of caspase-1 inhibitors on acute lung injury in experimental severe acute pancreatitis.

AIM: To assess the therapeutic effect of Caspase-1 inhibitors (ICE-I) on acute lung injury (ALI) in experimental severe acute pancreatitis (SAP). METHODS: Forty-two SD rats were randomly divided into 3 groups: healthy controls (HC, n = 6); SAP-S group (n = 18); SAP-ICE-I group (n = 18). SAP was induced by retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. HC rats underwent the same surgical procedures and duct cannulation without sodium taurocholate infusion. In SAP-S group, rats received the first intraperitoneal injection of isotonic saline 2 h after induction of acute pancreatitis and a repeated injection after 12 h. In SAP-ICE-I group, the rats were firstly given ICE inhibitors intraperitoneally 2 h after induction of pancreatitis. As in SAP-S group, the injection was repeated at 12 h. Serum IL-1beta was measured by ELISA. Intrapulmonary expression of Caspase-1, IL-1beta and IL-18 mRNA were detected by semi-quantitative RT-PCR. The wet/dry weight ratios and histopathological changes of the lungs were also evaluated. RESULTS: Serum IL-1beta levels in SAP-S group were 276.77 +/- 44.92 pg/mL at 6 h, 308.99 +/- 34.95 pg/mL at 12 h, and 311.60 +/- 46.51 pg/mL at 18 h, which were increased significantly (P < 0.01, vs HC). In SAP-ICE-I group, those values were decreased significantly (P < 0.01, vs SAP-S). Intrapulmonary expression of Caspase-1, IL-1beta and IL-18 mRNA were observed in the HC group, while they were increased significantly in the SAP-S group (P < 0.01, vs HC). The expression of IL-1beta and IL-18 mRNA were decreased significantly in the SAP-ICE-I group (P < 0.01, vs SAP-S), whereas Caspase-1 mRNA expression had no significant difference (P > 0.05). The wet/dry weight ratios of the lungs in the SAP-S group were increased significantly (P < 0.05 at 6 h, P < 0.01 at 12 h and 18 h, vs HC) and they were decreased significantly in the SAP-ICE-I group (P < 0.05, vs SAP-S). Caspase-1 inhibitors ameliorated the severity of ALI in SAP. CONCLUSION: Caspase-1 activation, and overproduction of IL-1beta and IL-18 play an important role in the course of ALI, and Caspase-1 inhibition is effective for the treatment of ALI in experimental SAP.

Emodin enhances alveolar epithelial barrier function in rats with experimental acute pancreatitis.

AIM: To investigate the effect of emodin on expression of claudin-4, claudin-5 and occludin, as well as the alveolar epithelial barrier in rats with pancreatitis induced by sodium taurocholate. METHODS: Experimental pancreatitis was induced by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. Emodin was injected via the external jugular vein 3 h after induction of acute pancreatitis. Rats from sham operation group and acute pancreatitis group were injected with normal saline (an equivalent volume as emodin) at the same time point. Samples of lung and serum were obtained 6 h after drug administration. Pulmonary morphology was examined with HE staining. Pulmonary edema was estimated by measuring water content in lung tissue samples. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) level were measured by enzyme-linked immunospecific assay. Serum amylase and pulmonary myeloperoxidase (MPO) activity were detected by spectrophotometry. Alveolar epithelial barrier was assessed by pulmonary dye extravasation. Expression of claudin-4, claudin-5 and occludin in lung tissue samples was examined by immunohistology, quantitative real-time reverse transcription polymerase chain reaction and Western blotting analysis, respectively. RESULTS: Pancreatitis-associated lung injury was characterized by pulmonary edema, leukocyte infiltration, alveolar collapse, and elevated serum amylase level. The pulmonary damage, pulmonary pathological scores, serum amylase and MPO activity, TNF-alpha and IL-6 levels, and wet/dry ratio were decreased in rats after treatment with emodin. Immunostaining of claudin-4, claudin-5 and occludin was detected in lung tissue samples from rats in sham operation group, which was distributed in alveolar epithelium, vascular endothelium, and bronchial epithelium, respectively. The mRNA and protein expression levels of claudin-4, claudin-5 and occludin in lung tissue samples were markedly decreased, the expression level of claudin-4, claudin-5 and occluding was increased, and the pulmonary dye extravasation was reduced in lung tissue samples from rats with acute pancreatitis after treatment with emodin. CONCLUSION: Emodin attenuates pulmonary edema and inflammation, enhances alveolar epithelial barrier function, and promotes expression of claudin-4, claudin-5 and occludin in lung tissue samples from rats with acute pancreatitis.

CXCR4 antagonist AMD3100 attenuates colonic damage in mice with experimental colitis.

AIM: To investigate the effects of the chemokine stromal cell-derived factor-1 (CXCL12) receptor (CXCR4) antagonist AMD3100 on colonic inflammation and epithelial barrier in dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: Experimental colitis was induced by administration of 5% DSS for 7 d, and assays performed on intestinal segments from the ileocecal valve to the anus. Colonic morphology was examined by hematoxylin and eosin staining. Colonic cytokines were determined by enzyme-linked immunosorbent assay. Myeloperoxidase (MPO) activity (indicator of inflammatory infiltration) was observed spectrophotometrically. Gut permeability was assessed by mucosal-to-serosal clearance of fluorescein isothiocyanate-conjugated dextran 4000 (FD4) in everted gut sacs. The apoptosis of colonic epithelium was assessed by Hoechst-33342 staining. To further elucidate the role of CXCR4 in colonic inflammation, we also investigated the effect of AMD3100 on migration and cytokine production of isolated peripheral blood mononuclear cells (PBMCs). RESULTS: DSS-induced colitis was characterized by morphologic changes, as well as increased colonic cytokines, inflammatory infiltration, epithelial apoptosis, and intestinal permeability in mice. In AMD3100-treated mice, epithelial destruction, inflammatory infiltration, and submucosal edema were markedly reduced; colonic tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) levels, as well as MPO activity were significantly decreased. Increased intestinal permeability in DSS-treated mice was significantly reduced by AMD3100. The number of apoptotic cells in colitis mice was markedly increased after DSS administration, and decreased when treated with the CXCR4 antagonist AMD3100. In pre-activated PBMCs, CXCL12 stimulation significantly increased the migration of PBMCs, and was inhibited by AMD3100. Moderately increased TNF-alpha, IL-6, and IFN-gamma from CXCL12-treated PBMCs were also reduced by AMD3100. CONCLUSION: The CXCR4 antagonist AMD3100 exerts therapeutic effects on experimental colitis by inhibiting colonic inflammation and enhancing epithelial barrier integrity.