Dental pulp mesenchymal stem cell-derived exosomes inhibit neuroinflammation and microglial pyroptosis in subarachnoid hemorrhage via the miRNA-197-3p/FOXO3 axis.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a severe stroke subtype that lacks effective treatment. Exosomes derived from human dental pulp stem cells (DPSCs) are a promising acellular therapeutic strategy for neurological diseases. However, the therapeutic effects of DPSC-derived exosomes (DPSC-Exos) on SAH remain unknown. In this study, we investigated the therapeutic effects and mechanisms of action of DPSC-Exos in SAH. MATERIALS AND METHODS: SAH was established using 120 male Sprague-Dawley rats. One hour after SAH induction, DPSC-Exos were administered via tail vein injection. To investigate the effect of DPSC-Exos, SAH grading, short-term and long-term neurobehavioral assessments, brain water content, western blot (WB), immunofluorescence staining, Nissl staining, and HE staining were performed. The role of miR-197-3p/FOXO3 in regulating pyroptosis was demonstrated through miRNA sequencing, bioinformatics analysis, and rescue experiments. The SAH model in vitro was established by stimulating BV2 cells with hemoglobin (Hb) and the underlying mechanism of DPSC-Exos was investigated through WB and Hoechst/PI staining. RESULTS: The expressions of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) were increased after SAH. DPSC-Exos alleviated brain edema and neuroinflammation by inhibiting the expression of FOXO3 and reducing NLRP3 inflammasome activation, leading to improved neurobehavioral functions at 24 h after SAH. In vitro, the expression of the NLRP3 inflammasome components (NLRP3 and caspase1-p20), GSDMD-N, and IL-18 was inhibited in BV2 cells pretreated with DPSC-Exos. Importantly, DPSC-Exos overexpressing miR-197-3p had a more obvious protective effect than those from NC-transfected DPSCs, while those from DPSCs transfected with the miR-197-3p inhibitor had a weaker protective effect. Functional studies indicated that miR-197-3p bound to the 3'-untranslated region of FOXO3, inhibiting its transcription. Furthermore, the overexpression of FOXO3 reversed the protective effects of miR-197-3p. CONCLUSIONS: DPSC-Exos inhibited activation of the NLRP3 inflammasome and related cytokine release via the miR-197-3p/FOXO3 pathway, alleviated neuroinflammation, and inhibited microglial pyroptosis. These findings suggest that using DPSC-Exos is a promising therapeutic strategy for SAH.

Transfer of miR-877-3p via extracellular vesicles derived from dental pulp stem cells attenuates neuronal apoptosis and facilitates early neurological functional recovery after cerebral ischemia-reperfusion injury through the Bclaf1/P53 signaling pathway.

Cerebral ischemia-reperfusion injury (I/RI) is one of the principal pathogenic factors in the poor prognosis of ischemic stroke, for which current therapeutic options to enhance neurological recovery are notably insufficient. Dental pulp stem cell-derived extracellular vesicles (DPSC-EVs) have promising prospects in stroke treatment and the specific underlying mechanisms have yet to be fully elucidated. The present study observed that DPSC-EVs ameliorated the degree of cerebral edema and infarct volume by reducing the apoptosis of neurons. Furthermore, the miRNA sequencing and functional enrichment analysis identified that miR-877-3p as a key component in DPSC-EVs, contributing to neuroprotection and anti-apoptotic effects. Following target prediction and dual-luciferase assay indicated that miR-877-3p interacted with Bcl-2-associated transcription factor (Bclaf1) to play a function. The miR-877-3p inhibitor or Bclaf1 overexpression reversed the neuroprotective effects of DPSC-EVs. The findings reveal a novel therapeutic pathway where miR-877-3p, transferred via DPSC-EVs, confers neuroprotection against cerebral I/RI, highlighting its potential in promoting neuronal survival and recovery post-ischemia.

Electrical injuries in children-a 6-year retrospective study.

BACKGROUND: This study aimed to assess the clinical epidemiological characteristics of children with electrical injuries and discuss the countermeasures for the prevention of electrical injuries in children. METHODS: The children with electrical injuries were grouped according to whether or not they were admitted to the hospital for treatment into inpatient and outpatient groups. Clinical data such as gender, causes of injury and injury-causing voltage distribution in different age groups were analyzed. The factors affecting hospitalization were subjected to χ2 test, Kruskal-Wallis H test, and logistic regression analysis. RESULTS: A total of 321 children were included with 37 divided into inpatient group and 284 divided into outpatient group. The incidence of electrical injuries was highest in children ≤6 years old and in the summer. There were significantly different in gender, place of occurrence, cause of injury and injury-causing voltage between the two groups (p < 0.05). Injury-causing voltage is an independent risk factor affecting hospitalization of children with electrical injuries (OR = 0.116, 95 %CI = 0.040-0.334, p = 0.000). In children ≤6 years old, boys suffered electrical injuries more frequently than girls; battery powered vehicle (47.53 %) was primarily the cause of injury; most of the patients (64.64 %) were exposed to low voltage below 100 Vs, mainly in the case of adolescent children. CONCLUSION: Male preschoolers accounted for the majority of electrical injury cases, and these accidents mostly happened in household electrical appliances and household battery cars. Overall, it is necessary to improve family electrical safety education and reinforce protective measures against electric injury to children.

The clinical characteristics and risk factors for necrotizing soft tissue infection in children.

Importance: Necrotizing soft tissue infection (NSTI) is a serious infectious disease. However, the early clinical manifestations and indicators of NSTI in children are still unclear. Objective: The purpose of this study was to analyze the clinical characteristics and risk factors of NSTI in pediatric patients. Methods: A total of 127 children with skin and soft tissue infection (SSTI) were treated at our hospital and divided into two groups: the NSTI group and the non-NSTI group, based on their discharge diagnosis from January 2011 to December 2022. Then, we collected and analyzed the clinical characteristics and risk factors of all patients, including sex and age, disease inducement, admission temperature, local skin manifestations, infection site, the presence of sepsis, bacterial culture, and laboratory indicators. Results: In our study, there was a statistical difference in the age distribution and disease inducement between NSTI and non-NSTI groups. The occurrence of local skin manifestations (blisters/bullae and ecchymosis) and the presence of sepsis significantly increased in the NSTI group compared to the non-NSTI group. Additionally, only the platelet count on laboratory tests was statistically different between the NSTI and non-NSTI groups. Finally, the logistic regression analysis suggested that local skin manifestations such as blisters/bullae, and ecchymosis, as well as the presence of sepsis, were identified as risk factors for NSTI. Interpretation: Children with SSTI and skin manifestations such as blisters/bullae, ecchymosis, and the presence of sepsis are at a higher risk of developing NSTI. These symptoms serve as useful indicators for early detection of NSTI.

Characteristics and risk factors for electrical burn injuries: a study based on World Health Organization Global Burn Registry.

OBJECTIVE: Electrical burn injuries (EBIs) represent an important subset of burn injuries, but the information on them from the global level is limited. We aimed to investigate the characteristics and risk factors for EBIs reported to the World Health Organization Global Burn Registry. METHODS: Patients with EBIs and non-EBIs were identified from the registry. Patient demographics, income of the country, setting of the injury occurred, and outcomes were described and compared. Multivariable analysis was performed to identify risk factors associated with the EBIs and their outcomes. RESULTS: Of the 9276 patients, 814 (8.8%) were grouped as EBIs. EBIs patients had a median age of 28 years, and they were predominantly males (89.2%). EBIs were more likely to occur in lower-middle- and low-income countries (60.9% versus 43.4%) and in an occupational setting (49.1% versus 6.7%) than the non-EBIs. Older age, male, lower-income, and occupational and public setting were risk factors for EBIs. For EBIs patients, adolescents and young adults, those from low-middle and low-income countries, and those injured by high-voltage electricity were more likely to have more than 15% of the total body surface area. In addition, those from low-middle and low-income countries and those injured by high-voltage electricity were more likely to die. CONCLUSION: The characteristics of EBIs are significantly different from that of non-EBIs. To prevent EBIs and avoid unpleasant outcomes, particular attention should be given to adolescent boys and young adult men who are employed in electrical jobs in lower-income countries.

Clinical study on the role of platelet-rich plasma in human acellular dermal matrix with razor autologous skin graft repair of giant congenital pigmented nevus in children.

BACKGROUND: NA OBJECTIVE: Evaluate the safety and feasibility of platelet-rich plasma (PRP) in the treatment of giant congenital melanocytic nevi (GCMN) in children with human acellular dermal matrix (HADM) transplantation. PATIENTS AND METHODS: A total of 22 children with GCMN were included in the study. They were divided into an experimental and a control group. The experimental group used the method of HADM with Razor Autologous Skin Graft combined with PRP to repair skin and soft tissue defects after giant nevus resection (Group A, n = 11). The control group was treated with HADM with Razor Autologous Skin Graft (Group B, n = 11) only. To compare the survival rate of skin grafts, we used the Vancouver Scar Scale (VSS) for the postoperative skin graft area and the Patient and Observer Scar Assessment Scale (POSAS) to compare the two groups of patients. RESULTS: There was no statistically significant difference in age, gender, location of giant nevi, and pathological classification between Group A and Group (P > 0.05). The survival rate of skin grafting and the VSS and POSAS scores of scar tissue in group A were superior to those of group B (P < 0.05). CONCLUSIONS: PRP has improved the survival rate of composite skin grafting in children with GCMN, and long-term satisfactory prognosis of scar healing. Therefore, we consider this treatment method a valuable contribution to clinical practice.

Hypoxic microenvironment promotes dermal fibroblast migration and proliferation via a BNIP3-autophagy pathway.

Upon injury, nearby cells, including fibroblasts at the wound edge, are often found in a hypoxic microenvironment. Nevertheless, the influence of hypoxia on skin fibroblasts is poorly understood. Using previously established mouse full-thickness wounds, we show that Bcl-2 and adenovirus E1B 19-kDa interacting protein 3 (BNIP3) expression was significantly elevated at the wound edge, and hypoxia treatment enhanced BNIP3 expression in fibroblasts. Interestingly, BNIP3 promoted the migration and proliferation, as well as the activation of autophagy, in fibroblasts under hypoxia. The hypoxia-induced autophagy was found to induce the migration and proliferation of fibroblasts, a process that could be reversed by knocking down the autophagy-related gene for autophagy protein 5, ATG5. Furthermore, hypoxia-inducible factor 1 subunit alpha (HIF-1α) was significantly upregulated in fibroblasts under hypoxia treatment, and HIF-1α knockdown attenuated the hypoxia-induced expression of BNIP3 and the migration and proliferation of fibroblasts. Altogether, our results establish the hypoxia-BNIP3-autophagy signaling axis as a newly identified regulatory mechanism of skin fibroblast migration and proliferation upon wounding. Autophagy intervening might thus represent a promising therapeutic strategy for patients with chronic refractory wounds.

Combined exposure to multiple metals on hypertension in NHANES under four statistical models.

Metals exposure has gained increasing attention in the hypertension prevention. However, previous studies have focused on the impacts of single or separated metals on hypertension, and the critical metals contributing to the prevalence of hypertension are still under discussion. We collected data from 5092 participants across three consecutive National Health and Nutrition Examination Survey (NHANES) circles (2011-2016). Weighted logistic regression, weighted quantile sum (WQS) regression, quantile-based g-computation (QGC), and Bayesian kernel machine regression (BKMR) analyses were conducted to evaluate the combined and individual effects of 15 urinary metals, as well as to identify the critical metals on the development of hypertension. In our study, the weighted prevalence of hypertension was 37.9%, and the average age was 47.42 years. Manganese, uranium and tin were found as the independent risk factors for hypertension, while barium, lead, and thallium were found to have protective effects against hypertension. Lead, barium, tungsten, uranium, and tin were determined as critical elements for the prediction of hypertension. No significant interaction relationship was detected between multiple metals. There might be potential positive combined effects of urinary metal mixture on hypertension. Tungsten, uranium, and tin were positively associated with hypertension while lead and barium were negatively associated with hypertension. The underlying mechanisms of urinary metal exposure on the risk of hypertension deserve further investigations.

Application of Autologous Hair Transplantation Technique in Children with Cicatricial Alopecia.

INTRODUCTION: Cicatricial alopecia not only affects the appearance of children's heads and faces but also their mental health in the long term. This study aims to explore the therapeutic characteristics and clinical effects of autologous hair transplantation technology in children with cicatricial alopecia. METHODS: Children in our department who received autologous hair transplantation technology for cicatricial baldness of the scalp from February 2019 to October 2022 were collected. Their basic information was analyzed, and postoperative follow-up was conducted, including calculation of hair follicle survival rate, hair growth, complications, and an efficacy satisfaction survey given to the children's family members. RESULTS: Thirteen children were included in this study (10 males and 3 females), aged from 4 years 1 month to 12 years 10 months, with an average age of 7 years 5 months. Two hundred to 2500 hair follicular units were extracted, with an average recipient area of 22.7 cm2, an average hair follicle unit density of 55.3 ± 9.1 per cm2, and an average hair/follicular unit (hair/FU) ratio of 1.75 ± 0.07. Thirteen children in this group were followed up for 6-12 months with the following treatment options: FUE (follicular unit extraction, 9 cases), FUT (follicular unit transplantation, 3 cases), and FUT combined with FUE (1 case). The average hair survival rate was 85.3%. Except for one child with temporary folliculitis, there were no complications. The GAIS score is divided into five levels: complete improvement (2 cases), obvious improvement (10 cases), partial improvement (1 case), no improvement (0 cases), and deterioration (0 cases). The patient satisfaction results included very satisfied (2 cases), mostly satisfied (10 cases), and dissatisfied (1 case). CONCLUSION: Autologous hair transplantation technology is a safe and effective method for children with cicatricial alopecia.

Coiling embolization strategy for medium-to-giant-sized intracranial aneurysms treated with pipeline embolization device: a propensity score-weighted study.

OBJECTIVES: We aim to investigate associations between different coil strategies and outcomes in the aneurysms treated by a pipeline embolization device (PED). METHODS: Patients with medium-to-giant-sized aneurysms treated by PED were included. The total cohort was divided into PED-alone and PED-coiling groups, and the PED-coiling group was further divided into loose and dense packing subgroups. Multivariate logistic analyses and stabilized inverse probability of treatment weighting (sIPTW) were performed to investigate the relationships between coiling strategies and outcomes. Restricted cubic spline (RCS) curves were used to describe the coiling degree and angiographic outcome relationship. RESULTS: A total of 398 patients with 410 aneurysms were included. Aneurysms treated with PED coiling had a lower incomplete occlusion rate (15.3% vs. 30.3%, p = 0.002), higher total perioperative complication rate (14.2% vs. 3.5%, p = 0.001), longer production time (142.14 min vs. 101.26 min, p < 0.001), and higher total cost ($45,158.63 vs. $34,680.91, p < 0.001) than those treated with PED alone. There were no differences in outcomes between the loose and dense packing subgroups. However, the total cost was higher in the dense packing group ($43,787.46 vs. $47,288.32, p = 0.001) than in the loose packing group. The result was still robust in the multivariate and sIPTW analyses. The RCS curves showed "L-shape" relationships between the coil degree and angiographic outcomes. CONCLUSION: Compared with PED alone, PED coiling could improve aneurysm occlusion. However, it could also increase the total complication risk, prolong procedure time, and increase the total cost. Compared with loose packing, dense packing did not enhance the treatment effectiveness but increased the treatment cost. CLINICAL RELEVANCE STATEMENT: The additional treatment effect from coiling embolization declines sharply after a certain point. Specifically, the aneurysm occlusion rate is roughly stable when the coil number is greater than 3 or the total coil length is longer than 150 cm. KEY POINTS: • Compared with pipeline embolization device (PED) alone, PED combined with coiling can improve aneurysm occlusion. • Compared with PED alone, PED combined with coiling increases the total complication risk, cost, and prolongs procedure time. • Compared with loose packing, dense packing did not increase the treatment effectiveness but increased the cost.

Association between smoking and intracranial artery dissection in patients aged less than 50 years: A propensity score-matched analysis.

INTRODUCTION: Smoking is a common risk factor for stroke in the young population. Intracranial artery dissection (ICAD) is a major cause of stroke in this population. However, the association between smoking and ICAD in young patients is not well characterized. We aimed to evaluate the association between smoking and ICAD in young individuals using propensity score-matched analysis. METHODS: We conducted a retrospective study of consecutive patients aged <50 years with ICAD who were admitted to Beijing Tiantan Hospital between January 2016 and December 2020. Patients with other non-atherosclerotic/non-aneurysmal cerebrovascular diseases were selected as controls. Propensity score matching was based on age and sex. Smoking and other vascular risk factors were compared between the two groups. RESULTS: The ICAD and control group included 120 and 197 patients, respectively. Propensity score matching resulted in 70 matched pairs. Smoking was the only significant factor association with ICAD in the matched cohort (p=0.031). CONCLUSIONS: In this propensity score-matched analysis, smoking showed a positive association with ICAD in young patients with common cerebrovascular diseases that were neither atherosclerotic nor aneurysmal. Further studies are required to investigate the predictive role of smoking for ICAD in the young population.

Application of vertical transposition flap in closure for large facial soft tissue defects in children.

Background: While transposition flap is widely used for the repairs of facial defects, few studies has reported its application among children with large defects. In this study, we aimed to investigate the surgical techniques and principles in different locations on face of vertical transposition flap in children. Methods: We retrospectively reviewed our hospital database and identified children who were treated with vertical transposition flap for large facial defects between January 2014 and December 2021. Information was collected including patients' demographics, location and dimension of the lesion, surgical procedure, additional surgeries, complications, and outcomes. Results: A total of 122 patients (77 boys, 63.1%) were included in this study. The average age for participants was 3.3 years (3 months to 9 years). One hundred and four (85.3%) patients had melanin nevus and 18 (14.8%) had sebaceous nevus. The average size of defects was 5.8 cm2 (ranging from 0.8-16.5 cm2). Ten patients (8.2%) suffered from dermal layer or full-thickness necrosis in the distal part of their flaps, They all recovered after conservative treatment and there were noticeable scars at discharge. Five patients (4.1%) had slight traction of the mouth and eyelid, all recovered about 2 week after surgery. An acceptable cosmetic outcome was achieved for all the patients at last time follow-up. Conclusions: Repairing large facial defects with vertical transposition flap is effective in Children, especially on forehead, cheek and mandible. However, this technique is far from perfect. Careful selection of appropriate patients and flap design might be needed.

Pathological changes in the brain after peripheral burns.

Brain injuries are common complications in patients with thermal burns and are associated with unpleasant outcomes. In clinical settings, it was once believed that brain injuries were not major pathological processes after burn, at least in part due to the unavailability of specific clinical manifestations. Burn-related brain injuries have been studied for more than a century, but the underlying pathophysiology has not been completely clarified. This article reviews the pathological changes in the brain following peripheral burns at the anatomical, histological, cytological, molecular and cognitive levels. Therapeutic indications based on brain injury as well as future directions for research have been summarized and proposed.

Systemic immune-inflammation index is associated with aneurysmal wall enhancement in unruptured intracranial fusiform aneurysms.

Introduction: Inflammation plays a key role in the progression of intracranial aneurysms. Aneurysmal wall enhancement (AWE) correlates well with inflammatory processes in the aneurysmal wall. Understanding the potential associations between blood inflammatory indices and AWE may aid in the further understanding of intracranial aneurysm pathophysiology. Methods: We retrospectively reviewed 122 patients with intracranial fusiform aneurysms (IFAs) who underwent both high-resolution magnetic resonance imaging and blood laboratory tests. AWE was defined as a contrast ratio of the signal intensity of the aneurysmal wall to that of the pituitary stalk ≥ 0.90. The systemic immune-inflammation (SII) index (neutrophils × platelets/lymphocytes) was calculated from laboratory data and dichotomized based on whether or not the IFA had AWE. Aneurysmal symptoms were defined as sentinel headache or oculomotor nerve palsy. Multivariable logistic regression and receiver operating characteristic curve analyses were performed to determine how well the SII index was able to predict AWE and aneurysmal symptoms. Spearman's correlation coefficients were used to explore the potential associations between variables. Results: This study included 95 patients, of whom 24 (25.3%) presented with AWE. After adjusting for baseline differences in neutrophil to lymphocyte ratios, leukocytes, and neutrophils in the multivariable logistic regression analysis, smoking history (P = 0.002), aneurysmal symptoms (P = 0.047), maximum diameter (P = 0.048), and SII index (P = 0.022) all predicted AWE. The SII index (P = 0.038) was the only independent predictor of aneurysmal symptoms. The receiver operating characteristic curve analysis revealed that the SII index was able to accurately distinguish IFAs with AWE (area under the curve = 0.746) and aneurysmal symptoms (area under the curve = 0.739). Discussion: An early elevation in the SII index can independently predict AWE in IFAs and is a potential new biomarker for predicting IFA instability.

Aneurysm wall enhancement, atherosclerotic proteins, and aneurysm size may be related in unruptured intracranial fusiform aneurysms.

OBJECTIVE: This cross-sectional study aimed to investigate the associations between aneurysm wall enhancement (AWE), atherosclerotic protein levels, and aneurysm size in unruptured intracranial fusiform aneurysms (IFAs). METHODS: Patients with IFAs underwent high-resolution magnetic resonance imaging (HR-MRI) and atherosclerotic protein examinations from May 2015 to December 2021 were collected. A CRstalk (signal intensity [SI] of IFA wall/SI of pituitary stalk) > 0.60 was considered to indicate AWE. Atherosclerotic protein data was obtained from the peripheral blood. Aneurysmal characteristics included the maximal diameter of the cross-section (Dmax), location, type of IFA, presence of mural thrombus, and mural clots. Statistical analyses were performed with univariate analysis, logistic regression analysis, and Spearman's correlation coefficient. RESULTS: Seventy-one IFAs from 71 patients were included in the study. Multivariate analysis revealed statin use (OR = 0.189, p = 0.026) and apolipoprotein B (Apo-B) level (OR = 6.019, p = 0.026) were the independent predictors of AWE in IFAs. In addition, statin use (OR = 0.813, p = 0.036) and Apo-B level (OR = 1.610, p = 0.003) were also the independent predictors of CRstalk. Additionally, we found that CRstalk and AWE were significantly positively associated with Dmax (rs = 0.409 and 0.349, respectively; p < 0.001 and p = 0.003, respectively). CONCLUSIONS: There may be correlations between AWE, atherosclerotic protein levels, and aneurysm size in patients with IFAs. Apo-B and statin use were independent predictors of AWE in IFAs, which have the potential to be new therapeutic targets for IFAs. KEY POINTS: • There may be correlations between aneurysm wall enhancement, atherosclerotic protein levels in the peripheral blood, and aneurysm size in patients with intracranial fusiform aneurysms. • Apolipoprotein B and statin use were independent predictors of aneurysm wall enhancement in intracranial fusiform aneurysms.

Predicting flow diverter sizing using the AneuGuideTM software: a validation study.

BACKGROUND: Stent sizing remains a challenging task for flow diverter implantation because of stent foreshortening. In this study, we aimed to quantify the change in length after implantation and assess the error in length prediction using AneuGuideTM software. METHODS: In a retrospective cohort of 101 patients with 102 aneurysms undergoing treatment with a pipeline embolization device (PED; Covidien, Irvine, California, USA), we used AneuGuideTM software to obtain measured lengths (ML) and calculated lengths (CL) after stent implantation. Stent elongation was defined as the ratio of ML-LL to the labeled length (LL). Simulation error was defined as the ratio of the absolute value of CL-ML to ML. The correlation and consistency between ML and LL and between ML and CL were analyzed using Pearson's correlation test and the Bland-Altman plot. Statistical significance was set at p<0.05. RESULTS: The mean elongation of ML was 32.6% (range 26.3-109.2%). Moderate consistency was observed between LL and ML (ρ=0.74, p<0.001). With the AneuGuideTM software, the mean simulation error was 6.6% (range 0.32-21.2%). Pearson's correlation test and the Bland-Altman plot showed a high correlation and consistency between ML and CL (ρ=0.96, p<0.001). CONCLUSION: Labeled length provides only a low reference value for predicting the actual length of the flow diverter after implantation. The high consistency between ML and CL obtained from AneuGuideTM software shows its great potential for the optimization of the flow diverter sizing process.

Morphological characteristics associated with ruptured intracranial vertebral artery dissecting aneurysms.

OBJECTIVE: Morphological risk factors for the rupture of intracranial vertebral artery dissecting aneurysms (IVADAs) have not been well characterized. In this study, we aim to identify morphological characteristics associated with IVADA rupture. METHODS: We conducted a retrospective study of 249 consecutive patients with single IVADAs (31 ruptured and 218 unruptured) admitted to Beijing Tiantan Hospital between January 2016 and December 2020. Various morphological parameters were measured using three-dimensional digital subtraction angiography images. Univariate and multivariate logistic regression analyses were performed to identify morphological characteristics associated with IVADA rupture. RESULTS: Univariate regression analysis revealed that the coexistence of significant proximal and distal stenosis and posterior inferior cerebellar artery (PICA) involvement were associated with IVADA rupture, while the origin from the dominant vertebral artery was inversely associated with the rupture. Multivariate regression analysis demonstrated that the coexistence of significant proximal and distal stenosis (OR 22.00, 95% CI 5.60 to 86.70, p<0.001) and PICA involvement (OR 4.55, 95% CI 1.36 to 15.20, p=0.014) were independently associated with IVADA rupture. CONCLUSION: The coexistence of significant proximal and distal stenosis and PICA involvement were independently associated with IVADA rupture. These morphological characteristics may facilitate the assessment of rupture risk in patients with IVADAs.

Economic evaluation of intravenous alteplase for stroke with the time of onset between 4.5 and 9 hours.

BACKGROUND: A clinical trial proved the clinical effectiveness of perfusion imaging-guided intravenous thrombolysis with alteplase for patients with acute ischemic stroke (AIS) with the time of onset between 4.5 and 9 hours. This study aimed to assess the lifetime cost-effectiveness of alteplase versus placebo from the perspective of Chinese and United States (US) healthcare payers. METHODS: A decision-analytic model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) associated with alteplase or placebo. Model inputs were extracted from published sources. Incremental costs, incremental QALYs, and incremental cost-effectiveness ratio (ICER) were calculated to evaluate the base-case scenario. One-way and probabilistic sensitivity analysis were performed to evaluate uncertainty in the results. RESULTS: In China, alteplase yielded an additional lifetime QALY of 0.126 with an additional cost of Chinese Yuan (¥) ¥9552 compared with placebo, and the ICER was ¥83 950 (US$12 157)/QALY. In the US, alteplase had a higher QALY (difference: 0.193) with a lower cost (difference: US$-2024) compared with placebo. In probabilistic sensitivity analyses, alteplase had a 42.54% to 78.3% probability of being cost-effective compared with placebo in China when the willingness-to-pay (WTP) threshold ranged from ¥72 447/QALY to ¥217 341/QALY. In the US, alteplase had a 93.47% to 93.57% probability of being cost-effective under the WTP threshold of US$100 000/QALY to US$150 000/QALY. These findings remained robust under one-way sensitivity analysis. CONCLUSION: For patients with AIS with a time of onset between 4.5 and 9 hours, perfusion imaging-guided intravenous alteplase was likely to be cost-effective in China and was cost-effective in the US when compared with placebo.

Internal flow field analysis of heterogeneous porous scaffold for bone tissue engineering.

The internal pore structure of the porous scaffold for bone tissue engineering and the pressure and velocity distributions of its flow field affect the attachment, proliferation and differentiation of osteoblasts. The permeability of the porous scaffold determines its ability to transport cellular nutrients and metabolites. Therefore, studying the fluid flow characteristics of the porous scaffold plays a vital role in its biological applications. Heterogeneous porous scaffolds (HPS) with irregular internal pore structure have more bionic characteristics of natural structure than uniform porous scaffolds with regular internal pore structure. In order to comprehensively grasp the biological properties of HPS, this article designed HPS with different porosities based on the Voronoi generation method and random theory, and then used computational fluid dynamics (CFD)software to conduct fluid flow simulations. The velocity and pressure distribution rules of the internal flow field of HPS with different porosities were obtained by CFD simulation analysis, and the relationship between the porosity and the distribution rules was studied. Furthermore, the permeabilities of HPS with different porosities were calculated based on Darcy's law, and the influence rule of porosity on the permeability was obtained.

Design and mechanical properties analysis of heterogeneous porous scaffolds based on bone slice images.

Bone tissue engineering plays an extremely important role in the clinical treatment of bone defects. Porous scaffold is one of the three essential factors of bone tissue engineering, and its structural design has attracted more and more attention . At present, most of the design methods of porous scaffolds focus on uniform porous scaffolds with periodic and regular pore structures. However, periodic and regular pore structure cannot comprehensively and accurately simulate the microstructures and mechanical properties of natural bone. To address this problem, based on bone slice images and VT (Voronoi-Tessellation) method, this article proposed a design method of HPS (Heterogeneous Porous Scaffolds) with bionic pore structure and controllable porosity. The FDM (fused deposition modeling) printing technology was applied to fabricate HPS with different porosities, and the mechanical properties of the HPS were analyzed by experiments. The research results illustrate that the HPS constructed by the design method proposed in this article have good controllability, and their internal pore structures are highly similar to those of natural bone, which have biomimetic characteristics. The mechanical property analysis illustrate that the stiffness and compressive strength of HPS decrease with the increase of porosity, in addition, the heterogeneous pore distribution makes HPS have the characteristics of non-concentrated and discontinuous damage distribution. This study provides a new idea for the design of porous scaffolds and a theoretical basis for the bionic design of HPS.