Cerebral venous thrombosis at high altitude: more severe symptoms and specific predisposing factors than plain areas.

BACKGROUND: Exposure to a high-altitude environment is a risk factor for cerebral venous thrombosis (CVT) probably due to hypercoagulability. The study aims to explore the unique characteristics of CVT patients in high-altitude areas of China by comparing them with those in plain areas. METHODS: We retrospectively included consecutive patients with CVT admitted to Tibet Autonomous Region People's Hospital (altitude 3650 m) and Peking Union Medical College Hospital (altitude 43.5 m) between January 2015 and December 2023. Patients from the plateau and the plain were considered two independent groups in this study. The risk factors, clinical and radiological presentations, treatment, and outcomes were analyzed and compared between the two groups. RESULTS: A total of 169 patients with CVT were included in the study, 48 patients from plateau and 121 patients from plain. The median age was 27 and 34 years old, and women accounted for 66.7% and 54.5% respectively. Headache (91.7% vs. 71.1%, P = 0.004), altered consciousness (31.3% vs. 16.5%, P = 0.033), hemorrhage (41.7% vs. 19.0%, P = 0.002), and venous infarction (50.0% vs. 25.6%, P = 0.002) on imaging were more common in patients from plateau than those from plain. Pregnancy or puerperium was significantly more common in highland patients (25% vs. 5.8%, P < 0.001). The levels of D-Dimer (1.7 vs. 0.8 mg/L FEU, P = 0.01), fibrinogen (3.7 vs. 3.0 g/L, P < 0.001), hemoglobin (157 vs. 129 g/L, P = 0.01), white blood cells (9.6 vs. 7.5*1012/L, P < 0.001) and highly sensitive C-reactive protein (20.2 vs. 3.2 mg/L, P = 0.005) were remarkably higher in highland patients. The percentage of receiving anticoagulant therapy was lower in high-altitude patients (70.8% vs. 93.4%, P < 0.001). Favorable outcome at follow-up was observed in 81.4% of highland patients and 90.7% of lowland patients, with a median follow-up time of 330 days and 703 days respectively. CONCLUSIONS: The more severe clinical and imaging manifestations along with prominent inflammatory and hypercoagulable states were observed in plateau CVT patients, probably due to exposure to the hypoxic environment at high altitude. Pregnancy or puerperium were more common in highland patients. The overall prognosis of CVT patients from both groups were favorable.

Current status and value of testing antiphospholipid antibody in patients with acute ischemic stroke: a retrospective single-center study in China.

BACKGROUND AND PURPOSE: Testing for antiphospholipid antibodies (aPL) is useful to determine the cause of ischemic stroke in young and female patients. However, the clinical relevance of aPL in older patients with ischemic stroke remains unclear. We aimed to explore the status and diagnostic value of initial aPL testing in all patients with acute ischemic stroke. METHODS: We retrospectively analyzed patients with acute ischemic stroke who were consecutively hospitalized in our hospital between June 2012 and January 2022 and investigated the factors associated with performing aPL screening in real-world clinical practice. Furthermore, factors associated with initial aPL positivity were evaluated by comparing the demographic, etiological, and therapeutic characteristics. RESULTS: Of 1209 patients, 287 (23.7%) were tested for aPL and 58 (20.2%) tested positive. Physicians tended to conduct aPL testing on female patients (P<0.001), younger patients (P<0.001), patients with fewer vascular risk factors (P<0.001), and multiple infarctions in the multivascular blood supply area (P<0.001). Multivariate logistic regression analysis showed that only stroke of other determined etiology type was a significant influencing factor for positive aPL results (OR 2.97, 95% CI 1.137, 7.774, P=0.026), adjusting for sex, age, and causes of stroke, etc. CONCLUSION: Approximately one-quarter of the patients with acute ischemic stroke were tested for aPL. Age, sex, number of vascular risk factors, and neuroimaging features affected the discretion in performing aPL testing. aPL testing may be appropriate in older patients with no identified cause of ischemic stroke and may provide additional diagnostic opportunities for acute ischemic stroke.

Mechanisms of in-hospital acute ischemic stroke and their relevance to prognosis: A retrospective analysis.

OBJECTIVES: In-hospital stroke (IHS) is common and has a poor prognosis. Limited data were about the mechanisms of IHS, posing a challenge in taking measures to prevent stroke during hospitalization. This study aims to investigate the mechanisms of IHS and their relevance to prognosis. MATERIALS AND METHODS: Patients with in-hospital acute ischemic stroke at Peking Union Medical College Hospital from June 2012 to April 2022 were consecutively enrolled. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification of stroke and detailed mechanisms were evaluated by two experienced neurologists. Functional outcome at discharge was evaluated. RESULTS: A total of 204 IHS patients were included, with a median age of 64 (IQR 52-72) and 61.8% male. The most common mechanism was embolism (57.8%), followed by hypoperfusion (42.2%), hypercoagulation (36.3%), small vessel mechanism (19.1%), discontinuation of antithrombotic drugs (13.2%), and iatrogenic injury (9.8%). Iatrogenic injury (P = 0.001), hypoperfusion (P = 0.006), embolism (P = 0.03), and discontinuation of antithrombotic drugs (P = 0.004) were more common in perioperative stroke compared to non-perioperative stroke. Median NIHSS improvement (2 vs 1, P = 0.002) and median mRS improvement (1 vs 0.5, P = 0.02) at discharge were higher in perioperative patients. Advanced age and higher NIHSS at onset were significantly associated with a poorer prognosis, whereas embolism mechanism was associated with a better prognosis. CONCLUSIONS: The etiologies and mechanisms of IHS are complex. Perioperative and non-perioperative IHS have different mechanisms and prognostic features. Determining the causes and mechanisms of IHS will help to identify the population at risk and prevent stroke appropriately during hospitalization.

Draft genome of the wheat A-genome progenitor Triticum urartu.

Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat.

The genome of the pear (Pyrus bretschneideri Rehd.).

The draft genome of the pear (Pyrus bretschneideri) using a combination of BAC-by-BAC and next-generation sequencing is reported. A 512.0-Mb sequence corresponding to 97.1% of the estimated genome size of this highly heterozygous species is assembled with 194× coverage. High-density genetic maps comprising 2005 SNP markers anchored 75.5% of the sequence to all 17 chromosomes. The pear genome encodes 42,812 protein-coding genes, and of these, ~28.5% encode multiple isoforms. Repetitive sequences of 271.9 Mb in length, accounting for 53.1% of the pear genome, are identified. Simulation of eudicots to the ancestor of Rosaceae has reconstructed nine ancestral chromosomes. Pear and apple diverged from each other ~5.4-21.5 million years ago, and a recent whole-genome duplication (WGD) event must have occurred 30-45 MYA prior to their divergence, but following divergence from strawberry. When compared with the apple genome sequence, size differences between the apple and pear genomes are confirmed mainly due to the presence of repetitive sequences predominantly contributed by transposable elements (TEs), while genic regions are similar in both species. Genes critical for self-incompatibility, lignified stone cells (a unique feature of pear fruit), sorbitol metabolism, and volatile compounds of fruit have also been identified. Multiple candidate SFB genes appear as tandem repeats in the S-locus region of pear; while lignin synthesis-related gene family expansion and highly expressed gene families of HCT, C3'H, and CCOMT contribute to high accumulation of both G-lignin and S-lignin. Moreover, alpha-linolenic acid metabolism is a key pathway for aroma in pear fruit.

Texture-Differentiated Grain Growth in Silicon Steel: Experiments and Modeling.

Grain growth for various texture components in silicon steel was investigated via experiments and modeling. It was found that the clustered spatial arrangement of grains with specific orientations significantly altered the local environment for grain growth and consequently resulted in texture-differentiated grain size distribution (GSD) evolution. A novel local-field model was proposed to describe grain growth driven by continuous changing orientation and size distribution of adjacent grains. The modelling results show that the texture-differentiated grain growth in microstructure with grain clusters can produce a GSD with increased proportion in small-sized range and large-sized range by more than two-times, accompanied with an evident change in area fractions of various texture components. The effect of clustered spatial arrangement on grain growth can be precisely predicted, which is valuable to design and control the texture-differentiated GSD as well as the global GSD.

Efficacy and safety of tirofiban in patients with acute branch atheromatous disease-related stroke (BRANT): a protocol for a randomised controlled trial.

INTRODUCTION: Branch atheromatous disease (BAD)-related stroke is increasingly becoming a clinical entity and prone to early neurological deterioration (END) and poor prognosis. There are no effective regimens to reduce the disability caused by BAD-related stroke in acute phase. Recent studies have indicated the efficacy of tirofiban in acute ischaemic stroke; however, its efficacy has not been validated in patients with BAD-related stroke. Thus, we aim to test whether intravenous tirofiban initiated within 48 hours after the onset would improve the functional outcome in patients with acute BAD-related stroke, in comparison with the standard antiplatelet therapy based on the current guideline. METHODS AND ANALYSIS: BRANT is a multicentre, randomised, open-label, blinded endpoint, parallel-controlled, phase III trial conducted in 21 hospitals in China. Participants aged 18-75 years with acute BAD-related stroke within 48 hours after the stroke onset are randomised in a 1:1 ratio to the tirofiban or control group. The treatment period is 48 hours in both groups. The primary outcome is the excellent functional outcome (modified Rankin Scale Score: 0-1) at 90 days. The secondary outcomes include END, major bleeding, stroke, death, functional status, serious adverse events and change in bleeding-related markers. Assuming the rates of the primary outcome to be 74% in the tirofiban group and 62% in the control group, a total of 516 participants are needed for 0.8 power (two-sided 0.05 alpha). ETHICS AND DISSEMINATION: BRANT study has been approved by the Ethics Committee of the Peking Union Medical College Hospital (I-23PJ1242). Written informed consent is required for all the patients before enrolment. The results of the study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT06037889).

Clinical and prognostic characteristics of cerebral venous thrombosis at high altitude: a single-center retrospective study of Tibet.

OBJECTIVE: Data regarding diagnosis, management, and prognosis of patients with cerebral venous thrombosis (CVT) from high altitude are limited. The aim of the present study is to identify the clinical features, risk factors, and outcomes of cerebral venous thrombosis (CVT) in Tibet. METHODS: We retrospectively included patients with a diagnosis of CVT consecutively admitted to Tibet Autonomous Region People's Hospital between July 2015, and September 2022. The risk factors, clinical and radiological presentations, treatment and outcomes were analyzed. RESULTS: A total of 38 patients with CVT were included in this study. The median age was 31 years, and females accounted for 63.2%. Patients of Tibetan nationality accounted for 71.1% (n = 27) and the median altitude of residence in Tibet was 3800 m (3657, 4054). Headache was the most common symptom (92.1%). The most common risk factors of CVT were infection in the past 4 weeks (34.2%) and pregnancy or puerperium (23.7%). Lateral sinus (transverse and/or sigmoid sinus) (68.4%) and superior sagittal sinus (55.3%) were the most commonly involved. The D-dimer increased in 31 patients (81.6%). All three patients who died in hospital and during follow-up had risk factor of recent infection. Favorable outcome at follow-up with a median length of 454 days (189, 1059) was observed in 85.3% of patients. CONCLUSIONS: CVT at high altitude is more common in young patients and women, with various clinical manifestations and risk factors. Recent infection is the most common risk factor and may increase the mortality of CVT at high altitude. The long-term prognosis of CVT at high altitude is favorable.

Neighbor-Affected Orientation Rotation in the Grain Boundary Region.

Orientation rotation at grain boundary regions associated with neighboring orientations in Fe-3.0 wt.% Si non-oriented silicon steel has been investigated by crystal plastic simulation. Rotation tendency relative to a certain target orientation is evaluated by deviation angle variation. Taking ideal λ (<001>//ND, normal direction) as the target orientation, the deviation angle of scattered {001} orientations at grain boundary regions affected by neighboring orientations during rolling is calculated and verified by experimental measurements. The rotation tendency and rotation velocity field at grain boundary regions are significantly changed by neighboring orientations. According to the neighbor affected orientation rotation, the initial texture can be precisely designed to control the deformation texture at grain boundary regions.

Characterization and Calculation of the Dynamic Recrystallization Texture in Fe-3.0 Wt.% Si Alloy.

High-temperature plane-strain compression tests were performed on Fe-3.0 wt.% Si alloy from 900 °C to 1150 °C at strain rates of 5 s-1 to 1 s-1, and the texture development from different initial textures was investigated by means of electron backscattered diffraction. Dynamic recrystallization occurs by strain-induced boundary migration, and the evolutions of the microstructure and different texture components vary with the initial texture. The critical orientation boundary separating the weakened and enhanced texture components moves with the initial texture, and a quantitative relationship is established to represent the dependence of the critical Taylor factor on the instantaneous texture. A model is proposed to describe the dynamic recrystallization texture by incorporating the oriented nucleation probability with a variable critical Taylor factor. The present work could improve the accuracy of hot deformation texture prediction based on strain-induced boundary migration.

Distinct lesion features and underlying mechanisms in patients with acute multiple infarcts in multiple cerebral territories.

Objective: To determine the etiology spectrum and lesion distribution patterns of patients with acute multiple infarcts in multiple cerebral territories (AMIMCT) and provide guidance for treatment and prevention strategies in these patients. Methods: Patients with acute ischemic stroke diagnosed using diffusion-weighted imaging (DWI) were consecutively included in this study between June 2012 and Apr 2022. AMIMCT was defined as non-contiguous focal lesions located in more than one cerebral territory with acute neurological deficits. We retrospectively analyzed the clinical and imaging characteristics, etiology spectra and underlying mechanisms in patients with and without AMIMCT. Infarct lesion patterns on DWI and their relevance to etiology were further discussed. Results: A total of 1,213 patients were enrolled, of whom 145 (12%) were diagnosed with AMIMCT. Patients with AMIMCT tended to be younger (P = 0.016), more often female (P = 0.001), and exhibited less common conventional vascular risk factors (P < 0.05) compared to those without AMIMCT. The constitution of the Trial of Org 10,172 in Acute Stroke Treatment classification was significantly different between patients with and without AMIMCT (P = 0.000), with a higher proportion of stroke of other determined causes (67.6% vs. 12.4%). For detailed etiologies, autoimmune or hematologic diseases were the most common (26.2%) etiologies of AMIMCT, followed by periprocedural infarcts (15.2%), cardioembolism (12.4%), tumor (12.4%), large artery atherosclerosis (10.3%), and sudden drop in blood pressure (8.3%). Hypercoagulability and systemic hypoperfusion are common underlying mechanisms of AMIMCT. Distinctive lesion distribution patterns were found associated with stroke etiologies and mechanisms in AMIMCT. Most of patients with large artery atherosclerosis (73.3%), autoimmune/hematologic diseases (57.9%) manifested the disease as multiple infarct lesions located in bilateral supratentorial regions. However, 66.7% of cardioembolism and 83.8% of cardiovascular surgery related stroke presented with both supratentorial and infratentorial infarct lesions. Conclusion: The etiologies and mechanisms of patients with AMIMCT were more complex than those without AMIMCT. The distribution characteristics of infarct lesions might have important implications for the identification of etiology and mechanism in the future, which could further guide and optimize clinical diagnostic strategies.

Comparing characteristics and outcomes of in-hospital stroke and community-onset stroke.

BACKGROUND: In-hospital strokes account for 4-17% of all strokes and usually lead to urgent and severe conditions. However, features of in-hospital strokes have been scarcely reported in China, and the management systems of in-hospital strokes are unestablished. The study aims to analyze the characteristics of in-hospital strokes in comparison to community-onset strokes and provides evidence for the development of national in-patient stroke care systems. METHODS: We retrospectively analyzed consecutive patients with in-hospital strokes (IHS group) and community-onset strokes (COS group) hospitalized in our hospital between June 2012, and January 2022. Clinical characteristics, care measures, and outcomes were compared between the two groups. RESULTS: A total of 1162 patients (age 61 ± 16 and 65% male) were included, of whom 193 (16.6%) had an in-hospital stroke and 969 (83.4%) had community-onset stroke. Compared with COS group, patients in IHS group had higher NIHSS at onset (7.25 vs 5.96, P = 0.054), higher use of endovascular therapy (10.4% vs 2.0%, P < 0.001), and lower use of intravascular thrombolysis (1.6% vs 7.2%, P = 0.003). Also, in-hospital strokes were associated with lower rate of mRS0-2 at discharge (OR[95%CI] = 0.674[0.49, 0.926], P = 0.015) and increased in-hospital mobility (OR[95%CI] = 3.621[1.640, 7.996], P = 0.001), after adjusting for age, sex, and cardiovascular risk factors. CONCLUSION: Compared with community-onset strokes, the patients with in-hospital stroke had insufficient urgent treatment and poorer outcomes, reflecting the need for increased awareness of in-patient stroke, and strategies to streamline in-hospital acute stroke care.

Rapid Secondary Recrystallization of the Goss Texture in Fe81Ga19 Sheets Using Nanosized NbC Particles.

Herein, a simple and efficient method is proposed for fabricating Fe81Ga19 alloy thin sheets with a high magnetostriction coefficient. Sharp Goss texture ({110}<001>) was successfully produced in the sheets by rapid secondary recrystallization induced by nanosized NbC particles at low temperatures. Numerous NbC precipitates (size ~90 nm) were obtained after hot rolling, intermediate annealing, and primary recrystallization annealing. The relatively higher quantity of nanosized NbC precipitates with 0.22 mol% resulted in finer and uniform grains (~10 µm) through thickness after primary recrystallization annealing. There was a slow coarsening of the NbC precipitates, from 104 nm to 130 nm, as the temperature rose from 850 °C to 900 °C in a pure nitrogen atmosphere, as well as a primary recrystallization textured by strong γ fibers with a peak at {111} <112> favoring the development of secondary recrystallization of Goss texture at a temperature of 850 °C. Matching of the appropriate inhibitor characteristics and primary recrystallization texture guaranteed rapid secondary recrystallization at temperatures lower than 950 °C. A high magnetostriction coefficient of 304 ppm was achieved for the Fe81Ga19 sheet after rapid secondary recrystallization.

Complete Goss Secondary Recrystallization by Control of the Grain Size and Texture of Primary Recrystallization in Grain-Oriented Silicon Steel.

Matrix microstructure and texture controlling is an important way to optimize Goss ({110}<001>) abnormal grain growth (AGG) in high magnetic induction grain-oriented silicon (Hi-B) steel during primary recrystallization. In the present work, a matrix with homogeneous grain size and favorable texture components was obtained through two-stage normalized annealing followed by primary recrystallization. Furthermore, secondary recrystallization was performed for sharp Goss orientation by slow heating and purified annealing. It was found that plenty of island grains, which occurred and disappeared gradually, accompanied the process of AGG. Through analyzing the evolution of microstructure and texture, we realized that the formation of island grains was related to the large-size grains in matrix, and the elimination of that was attributed to the special grain boundaries which satisfied both coincident site lattice (CSL) and high-energy (HE) models. It was essential to control grain size and favorable orientations in matrix comprehensively for the high-efficient abnormal growing of sharp Goss orientation, through which excellent magnetic properties could be obtained simultaneously.

3-Bromopyruvate alleviates the development of monocrotaline-induced rat pulmonary arterial hypertension by decreasing aerobic glycolysis, inducing apoptosis, and suppressing inflammation.

BACKGROUND: Pulmonary arterial hypertension (PH) is a progressive disease with limited therapeutic options, ultimately leading to right heart failure and death. Recent findings indicate the role of the Warburg effect (aerobic glycolysis) in the development of PH. However, the effect of the glycolysis inhibitor 3-bromopyruvate (3-BrPA) on the pathogenesis of PH has not been well investigated. This study aimed to determine whether 3-BrPA inhibits PH and its possible mechanism. METHODS: PH was induced in adult Sprague-Dawley rats by a single intraperitoneal injection of monocrotaline (MCT). 3-BrPA, or phosphate-buffered saline (PBS) was administered via intraperitoneal injection every other day from the first day of MCT-injection to 4 weeks of follow-up, and indices such as right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), pulmonary arteriolar remodeling indicated by percent media thickness (% MT), lactate levels and glucose consumption, were evaluated. Pulmonary arteriolar remodeling and right ventricular hypertrophy were observed in hematoxylin-eosin-stained lung sections. Western blotting, immunohistochemistry, and/or immunofluorescence analyses were used to measure the expression of relevant proteins. A cytochrome C release apoptosis assay and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining were used to measure cell apoptosis. RESULTS: MCT-induced PH showed a significant increase in glucose consumption (0 vs. 4 weeks: 0.87 ±â€Š0.23 vs. 2.94 ±â€Š0.47, P = 0.0042) and lactate production (0 vs. 4 weeks: 4.19 ±â€Š0.34 vs. 8.06 ±â€Š0.67, P = 0.0004). Treatment with 3-BrPA resulted in a concomitant reduction in glucose consumption (1.10 ±â€Š0.35 vs. 3.25 ±â€Š0.47, P = 0.0063), lactate production (5.09 ±â€Š0.55 vs. 8.06 ±â€Š0.67, P = 0.0065), MCT-induced increase in RVSP (39.70 ±â€Š2.94 vs. 58.85 ±â€Š2.32, P = 0.0004), pulmonary vascular remodeling (% MT, 43.45% ±â€Š1.41% vs. 63.66% ±â€Š1.78%, P < 0.0001), and right ventricular hypertrophy (RVHI, 38.57% ±â€Š2.69% vs. 62.61% ±â€Š1.57%, P < 0.0001) when compared with those of the PBS-treated group. 3-BrPA, a hexokinase 2 inhibitor, exerted its beneficial effect on PH by decreasing aerobic glycolysis and was also associated with inhibiting the expression of glucose transporter protein-1, inducing apoptosis, and suppressing inflammation. CONCLUSIONS: 3-BrPA might have a potential beneficial effect on the PH treatment.

A Novel Computational Method of Processing Map for Ti-6Al-4V Alloy and Corresponding Microstructure Study.

The Arrhenius-type constitutive equation is mostly used to describe flow behaviors of material. However, no processing map has been constructed directly according to it. In this study, a novel computational method was applied for establishing the processing map for Ti-6Al-4V alloy in the temperature and strain rate range of 800⁻1050 °C and 0.001⁻10 s-1, respectively. The processing map can be divided into four domains according to its graphic features. Among the four domains, the optimal domain is in the temperature and strain rate range of 850⁻925 °C and 0.001⁻0.1 s-1, where peak efficiency η is 0.54 and the main microstructural evolution is DRX (dynamic recrystallization). When the alloy is processed in the α + ß phase field, the temperature and strain rate range of 800⁻850 °C and 3⁻10 s-1 should be avoided, where instability parameter ξ is negative and the microstructural feature is flow localization. When the alloy is processed in the ß phase field, DRV (dynamic recovery) and slight DRX of ß phase is the main microstructural characteristics in the range of 1000⁻1050 °C and 0.001⁻0.02 s-1. However, flow localization of ß phase is the main microstructural feature in the range of 1000⁻1050 °C and 1⁻10 s-1, which should be avoided.