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Digital in-line holographic microscopy (DIHM) is a widely used interference technique for real-time reconstruction of living cells’ morphological information with large space-bandwidth product and compact setup. However, the need for a larger pixel size of detector to improve imaging photosensitivity, field-of-view, and signal-to-noise ratio often leads to the loss of sub-pixel information and limited pixel resolution. Additionally, the twin-image appearing in the reconstruction severely degrades the quality of the reconstructed image. The deep learning (DL) approach has emerged as a powerful tool for phase retrieval in DIHM, effectively addressing these challenges. However, most DL-based strategies are data-driven or end-to-end net approaches, suffering from excessive data dependency and limited generalization ability. Herein, a novel multi-prior physics-enhanced neural network with pixel super-resolution (MPPN-PSR) for phase retrieval of DIHM is proposed. It encapsulates the physical model prior, sparsity prior and deep image prior in an untrained deep neural network. The effectiveness and feasibility of MPPN-PSR are demonstrated by comparing it with other traditional and learning-based phase retrieval methods. With the capabilities of pixel super-resolution, twin-image elimination and high-throughput jointly from a single-shot intensity measurement, the proposed DIHM approach is expected to be widely adopted in biomedical workflow and industrial measurement.

Objective In orthopedic trauma, identification of extremity trauma combined with vascular injury is challenging. Missed diagnosis may result in amputation or even death. The purpose of this study was to investigate whether physical examination combined with handheld vascular ultrasound Doppler examination could be an effective method of screening for peripheral vascular injury and to explore the characteristics of vascular injuries in orthopedic trauma patients. Methods Retrospective analysis of patients in the emergency department of orthopedic trauma in our hospital from January 2022 to October 2023. Physical examination combined with handheld vascular ultrasound Doppler examination was used as a screening method for suspected vascular injuries. Patients with suspected vascular injury would undergo further angiography and receive multidisciplinary treatment. Angiography was used as the gold standard for diagnosing vascular injuries. Patient demographics, mechanism of injury, location and type of injury, angiographic results, surgical notes, and early treatment outcome data were recorded. Results A total of 55 cases (58 limb injuries) with suspected vascular injury were ultimately included. Angiography revealed that 53 cases (55 limbs, positive rate 94.8%) were considered to have confirmed vascular injuries. Forty‐three were male (81.1%) and 10 were female (18.9%), with mean age 44.1 ± 16.6 years. The main mechanism of injury was traffic accident (30, 56.7%). Most common site of vascular injuries was knee joint (30/55, 54.5%), and popliteal artery (23, 47.9%) was the most commonly injured blood vessel. After multidisciplinary collaborative treatment, overall patient mortality was 3.8% (2/53), and limb survival rate among surviving patients was 81.1% (43/53) in our study. Conclusion In orthopedic trauma, “Hard signs” and “soft signs” combined with handheld vascular ultrasound Doppler examination were effective ways to screen for suspected vascular injuries. Most limbs had associated fractures or dislocations at the site of vascular injury. Collaboration of vascular surgery, microsurgery and orthopedic trauma may help improve patients' prognosis.

Abstract Background Traumatic proximal tibiofibular fracture and dislocation (PTFD) have been rarely studied and are easily missed in clinical practice. PTFD is considered a marker of severely traumatized knees. The purpose of this study was to retrospectively analyze the incidence and impact of PTFD in traumatized knees with vascular injury. Methods Patients with knee trauma and vascular injury were included from January 2022 to October 2023. X-rays and CT scans of included patients were retrospectively analyzed to determine the presence of PTFD. Patients were further divided into PTFD group and non-PTFD group for further comparative analysis. Results A total of 27 patients (28 limbs) were included. Incidence of PTFD was 39.3% (11/28) in traumatic knee with vascular injury, including 8 anterolateral dislocations and 3 posteromedial dislocations. PTFD group had significantly more limbs with open injuries compared with non-PTFD group (10/11 VS 7/17, p0.05). Conclusions PTFD was easily overlooked or missed. In traumatized knees with vascular injury, incidence of PTFD was high. The presence of PTFD might indicate severe knee trauma and the possibility of open injury. Although there was no significant difference compared with non-PTFD group, PTFD group had a relatively high amputation rate of 40%.

Abstract Cardiovascular function and adipose metabolism were markedly influenced under high altitudes. However, the interplay between adipokines and heart under hypoxia remains to be elucidated. We aim to explore alterations of adipokines and underlying mechanisms in regulating cardiac function under high altitudes. We investigated the cardiopulmonary function and five adipokines in Antarctic expeditioners at Kunlun Station (4,087 m) for 20 days and established rats exposed to hypobaric hypoxia (5,000 m), simulating Kunlun Station. Antarctic expeditioners exhibited elevated heart rate, blood pressure, systemic vascular resistance, and decreased cardiac pumping function. Plasma creatine phosphokinase-MB (CK-MB) and platelet-endothelial cell adhesion molecule-1 (sPecam-1) increased, and leptin, resistin, and lipocalin-2 decreased. Plasma leptin significantly correlated with altered cardiac function indicators. Additionally, hypoxic rats manifested impaired left ventricular systolic and diastolic function, elevated plasma CK-MB and sPecam-1, and decreased plasma leptin. Chronic hypoxia for 14 days led to increased myocyte hypertrophy, fibrosis, apoptosis, and mitochondrial dysfunction, coupled with reduced protein levels of leptin signaling pathways in myocardial tissues. Cardiac transcriptome analysis revealed leptin was associated with downregulated genes involved in rhythm, Na+/K+ transport, and cell skeleton. In conclusion, chronic hypoxia significantly reduced leptin signaling pathways in cardiac tissues along with significant pathological changes, thus highlighting the pivotal role of leptin in regulation of cardiac function under high altitudes.

We report the case of a 22-year-old male who underwent endoluminal surgery and was implanted an Option Elite filter in the superior vena cava (SVC) while the filter retraction hook was attached to the vessel wall. The patient requested to remove the filter after 155 days. Preoperative ultrasonography and CT examination revealed that the filter retraction hook was very likely to penetrate the SVC wall and its tip was very close to the right pulmonary artery. The SVC was not obstructed, and no thrombus was observed in either upper limb. After the filter retrieval device (ZYLOX, China) failed to capture the filter hook, we introduced a pigtail catheter with its tip partly removed and a loach guidewire, used a modified loop-snare technique to cut the proliferative tissues and free the hook, and finally removed the filter successfully by direct suspension of the guidewire. During this procedure, the patient experienced discomfort, such as chest pain and palpitations, but these symptoms disappeared when procedure completed. Repeated multiangle angiography revealed no contrast medium extravasation, no complications such as pericardial tamponade, pleural effusion, SVC haematoma formation, right pulmonary artery dissecting aneurysm, or intramural haematoma. We initially presented the modified loop-snare technique used to remove a conical superior vena cava filter (SVCF), so this method can be considered a practical and novel auxiliary technique for successful filter retrieval.

The exacerbation of wildfires caused by global warming poses a significant threat to human health and environmental integrity. This review examines the particulate matter (PM) and gaseous pollutants resulting from fire incidents and their impacts on individual health, with a specific focus on the occupational hazards faced by firefighters. Of particular concern is the release of carbon-containing gases and fine particulate matter (PM2.5) from forest fires and urban conflagrations, which exceed the recommended limits and pose severe health risks. Firefighters exposed to these pollutants demonstrate an elevated risk of developing pulmonary and cardiovascular diseases and cancer compared to the general population, indicating an urgent need for enhanced protective measures and health management strategies for firefighters. Through a meticulous analysis of the current research findings, this review delineates future research directions, focusing on the composition and properties of these pollutants, the impacts of fire-emitted pollutants on human health, and the development of novel protective technologies.

Limb ischemia is a refractory disease characterized by persistent inflammation, insufficient angiogenesis, and tissue necrosis. Although mesenchymal stem cells (MSCs) have shown potential for treating limb ischemia, their therapeutic effects are limited by low engraftment rates. Therefore, developing an optimal MSC delivery system that enhances cell viability is imperative. Selenium, known for its cytoprotective properties in various cell types, offers a potential strategy to enhance therapeutic effect of MSCs. In this study, we evaluated the cytoprotective effects of selenium on MSCs, and developed an injectable thermosensitive selenium-containing hydrogel based on PLGA-PEG-PLGA triblock copolymer, as a cell carrier to improve MSC viability after engraftment. The biocompatibility, biodegradability, and cytoprotective capabilities of selenium-containing hydrogels were assessed. Furthermore, the therapeutic potential of MSCs encapsulated within a thermosensitive selenium-containing hydrogel in limb ischemia was evaluated using cellular and animal experiments. Selenium protects MSCs from oxidative damage by upregulating GPX4 through a transcriptional mechanism. The injectable thermosensitive selenium-containing hydrogel exhibited favorable biocompatibility, biodegradability, and antioxidant properties. It can be easily injected into the target area in liquid form at room temperature and undergoes gelation at body temperature, thereby preventing the diffusion of selenium and promoting the cytoprotection of MSCs. Furthermore, MSCs encapsulated within the selenium-containing hydrogel effectively inhibited macrophage M1 polarization while promoting macrophage M2 polarization, thus accelerating angiogenesis and restoring blood perfusion in ischemic limbs. This study demonstrated the potential of an injectable thermosensitive selenium-containing hydrogel as a promising method for MSC delivery. By addressing the challenge of low retention rate, which is a major obstacle in MSC application, this strategy effectively improves limb ischemia.

In this study, an alkali solution and acid precipitation method were used to extract protein from peony seed meal. Solid-liquid ratio, pH, time, and temperature were selected to carry out a single-factor study and combined with the response surface method to optimize the optimal extraction process. The optimum process conditions were determined: The protein yield reached 23.81%±0.04% when the ratio of solid to liquid was 1:25 g/mL, pH10.6, the temperature was 55 ℃, and time was 130 min. The peony seed meal protein obtained under these conditions contained 18 kinds of amino acids. The water and oil retention of peony seed meal protein was 3.72 g/g and 3.67 g/g, respectively. Foamability and foam stability decreased significantly at pH2~4, and the lowest was at pH4. Between pH6 and 10, foamability continued to increase, while foam stability increased significantly and then decreased slightly. With the increase in pH, the emulsification and emulsification stability increased. The results were consistent with the variation trend of particle size and Zeta potential. This study provided a theoretical basis for the industrial production and comprehensive utilization of peony seed meal protein.

ObjectiveWinter-over expeditioners in Antarctica are challenged by various environmental and psycho-social stress factors, which may induce psychophysiological changes. The autonomic nervous system (ANS) plays a crucial role in the adaptation process under stress. However, the relationship between ANS activity and the mood states of expeditioners remains largely unexplored. This study aims to uncover the pattern of ANS adjustment under extreme Antarctic environments and provide new insights into the correlations between ANS activity and mood state changes, which may provide scientific data for medical interventions.MethodsFourteen expeditioners at Zhongshan Station participated in this study. The study was conducted during four representative periods: pre-Antarctica, Antarctica-1 (pre-winter), Antarctica-2 (winter), and Antarctica-3 (summer). The heart rate variability (HRV) of the expeditioners was continuously measured for 24 hours to evaluate ANS activity. Plasma levels of catecholamines were tested by ELISA. Mood states were assessed by the Profile of Mood States (POMS) scale.ResultsHRV analysis showed a disturbance of ANS during winter and summer periods. For frequency domain parameters, very low frequency (VLF), low frequency (LF), high frequency (HF), and total power (TP) significantly increased during the second half of the mission. Especially, LF/HF ratio decreased during summer, indicating the predominance of vagal tone. Results of the time domain analysis showed increased heart rate variability during the austral winter and summer. Plasma epinephrine (E) significantly increased during residence in Antarctica. Compared with pre-Antarctica, the vigor, depression, and anger scores of the expeditioners decreased significantly during the austral summer. Notably, the depression score showed a moderate positive correlation with LF/HF, while weak negative correlations with other HRV indicators, including TP, VLF, and LF. Anger score showed a moderate positive correlation with LF/HF and weak negative correlations with the average normal-to-normal (NN) interval, and the root mean square of differences between adjacent RR intervals (RMSSD). Plasma E level weakly correlated with the average NN interval.ConclusionProlonged residence in Antarctica increased the ANS activities and shifted the cardiac autonomic modulation towards vagal predominance. The alteration of HRV correlated with mood states and plasma epinephrine levels.

Abstract Background There is a paucity of data regarding the prevalence of preoperative deep vein thrombosis (DVT) in patients with long bone (including femur, tibia and fibula) fractures of the lower limbs. We performed a meta-analysis to address the issue. Methods Electronic databases, including PubMed, EMBASE, the Web of Science, the Cochrane Library, the VIP database, CNKI, and the Wanfang database, were systematic searched for original articles that reported the prevalence of preoperative DVT in long bone fractures of the lower limbs from January 2016 to September 2021. The prevalence of preoperative DVT was pooled using random-effects models, and subgroups were established according to study type, detection method, sample size and fracture site. Results Twenty-three articles reporting on 18,119 patients were eligible. The overall pooled preoperative DVT prevalence was 24.1% (95% CI 19.3–28.8%). In different subgroups, the preoperative DVT prevalences were 18.2–27.3%, 15.2–28.6%, 23.1–24.9%, 18.2–26.0% and 23.2–23.4% for different study designs, sample sizes, age groups, detection methods and fracture sites, respectively. Conclusions Despite the heterogeneity among studies, this systematic review suggests that the prevalence of preoperative DVT, which may seriously affect the prognosis of patients, is high. Therefore, greater efforts should be devoted to the improvement of screening and prevention strategies for preoperative DVT in lower-extremity long bone fractures. Level of Evidence: Level III. Trial Registration The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database with the registration number CRD42022324706.

In this research, an ammonium perchlorate/polydopamine (AP/PDA) core–shell composite was prepared in a non-aqueous solution to reduce the mechanical sensitivity of ammonium perchlorate (AP). The result showed that the AP/PDA core–shell composite could be successfully constructed in ethyl acetate solution with an AP recovery rate that reached 86%. The mechanical sensitivity of the obtained AP/PDA core–shell composite was significantly reduced with a PDA content of only 0.76%. The DSC and TG also indicated that the coating of PDA showed catalytic activity in the thermal decomposition of AP with a lower decomposition temperature and a decreased Ea value of AP. Thus, this study proposed a simple strategy for achieving a good balanced between harnessing the energy and ensuring the safety of ammonium perchlorate by significantly reducing its mechanical sensitivity by using a very low polydopamine coating layer content, and this shows great potential for the design and fabrication of insensitive energetic composites for use in propellants.

Electricity consumption forecasting (ECF) plays a crucial role in the new open electricity market nowadays, and in order to pass the ECF test, the ECF error is required to be less than 5%. However, for historical electricity consumption (EC) data and the error distribution of ECF is usually nonlinear and non-Gaussian distributed, and some random events and data collection errors have a great impact on the forecasting accuracy. Therefore, the traditional forecasting methods designed based on mean squared error (MSE) have the problem of unstable forecasting results and difficult to improve the accuracy. To solve this problem, this paper first uses the Generalized Maximum Correntropy Criterion to optimize the Kernel Extreme Learning Machine, and proposes a new forecasting model of KELM-GMCC. Finally, the historical EC and corresponding temperature data of a commercial customer in China in 2018 and 2019 are used to test and guide the electricity prediction in 2020 and 2021. The model proposed in this paper has a mean absolute percentage error of 1.46% in forecasting daily EC using annual data. The results show that the proposed model is robust and has high forecasting accuracy compared with existing models such as Back Propagation (BP), Support Vector Regression (SVR), and Extreme Learning Machine (ELM).

ATP-dependent SWI/SNF chromatin remodeling complexes (CRCs) are evolutionarily conserved multi-component machines that regulate transcription, replication, and genome stability in eukaryotes. SWI/SNF components play pivotal roles in development and various stress responses in plants. However, the compositions and biological functions of SWI/SNF complex subunits remain poorly understood in soybean. In this study, we used bioinformatics to identify 39 genes encoding SWI/SNF subunit distributed on the 19 chromosomes of soybean. The promoter regions of the genes were enriched with several cis-regulatory elements that are responsive to various hormones and stresses. Digital expression profiling and qRT-PCR revealed that most of the SWI/SNF subunit genes were expressed in multiple tissues of soybean and were sensitive to drought stress. Phenotypical, physiological, and molecular genetic analyses revealed that GmLFR1 (Leaf and Flower-Related1) plays a negative role in drought tolerance in soybean and Arabidopsis thaliana. Together, our findings characterize putative components of soybean SWI/SNF complex and indicate possible roles for GmLFR1 in plants under drought stress. This study offers a foundation for comprehensive analyses of soybean SWI/SNF subunit and provides mechanistic insight into the epigenetic regulation of drought tolerance in soybean.

BackgroundThe permanent placement of inferior vena cava (IVC) filters may lead to numerous complications and their removal is recommended once the risk of pulmonary embolism is reduced. Removal of IVC filters by endovenous means is preferred. But failure of endovenous removal happens when recycling hooks penetrate the vein wall and filters are left in place for too long time. In these scenarios, open surgery may be effective for removal of IVC filters. We aimed to describe the surgical approach, outcomes, and 6-month follow-up of the removal of IVC filter by open surgery, after the failure of removal via the endovenous method.MethodsA total of 1,285 patients with retrievable IVC filters were admitted from July 2019 to June 2021, including 1,176 (91.5%) endovenous filter removals, and 24 (1.9%) open surgical IVC filter removals after the failure by endovenous method, of whom 21 (1.6%) were followed-up and eligible for analysis of the study. Patient characteristics, filter type, filter removal rate, IVC patency rate, and complications were retrospectively analyzed.ResultsTwenty-one patients were left with IVC filters for 26 (10, 37) months, of which 17 (81.0%) patients had non-conical filters and 4 (19.0%) had conical filters; all 21 filters were successfully removed, with a 100% removal rate, no deaths, no serious complications, and no symptomatic pulmonary embolism. At the 3rd month follow-up after surgery and 3rd month follow-up after discontinuation of anticoagulation therapy, only 1 case (4.8%) had IVC occlusion, but without any occurrence of new lower limb deep venous thrombosis and silent pulmonary embolism.ConclusionOpen surgery can be used for the removal of IVC filters after failure of removal by endovenous method or when accompanied by complications without symptoms of pulmonary embolism. Open surgical approach can be used as an adjunctive clinical intervention for the removal of such filters.

Abstract Background Steatotic livers tolerate ischemia–reperfusion injury (IRI) poorly, increasing the risk of organ dysfunction. Ferroptosis is considered the initiating factor of organ IRI. Heme oxygenase oxygen-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) (HO-1/BMMSCs) can reduce hepatic IRI; however, the role of ferroptosis in IRI of steatotic grafts and the effect of HO-1/BMMSCs-derived exosomes (HM-exos) on ferroptosis remain unknown. Methods A model of rat liver transplantation (LT) with a severe steatotic donor liver and a model of hypoxia and reoxygenation (H/R) of steatotic hepatocytes were established. Exosomes were obtained by differential centrifugation, and the differentially expressed genes (DEGs) in liver after HM-exo treatment were detected using RNA sequencing. The expression of ferroptosis markers was analyzed. microRNA (miRNA) sequencing was used to analyze the miRNA profiles in HM-exos. Results We verified the effect of a candidate miRNA on ferroptosis of H/R treated hepatocytes, and observed the effect of exosomes knockout of the candidate miRNA on hepatocytes ferroptosis. In vitro, HM-exo treatment reduced the IRI in steatotic grafts, and enrichment analysis of DEGs suggested that HM-exos were involved in the regulation of the ferroptosis pathway. In vitro, inhibition of ferroptosis by HM-exos reduced hepatocyte injury. HM-exos contained more abundant miR-124-3p, which reduced ferroptosis of H/R-treated cells by inhibiting prostate six transmembrane epithelial antigen 3 (STEAP3), while overexpression of Steap3 reversed the effect of mir-124-3p. In addition, HM-exos from cell knocked out for miR-124-3p showed a weakened inhibitory effect on ferroptosis. Similarly, HM-exo treatment increased the content of miR-124-3p in grafts, while decreasing the level of STEAP3 and reducing the degree of hepatic ferroptosis. Conclusion Ferroptosis is involved in the IRI during LT with a severe steatotic donor liver. miR-124-3p in HM-exos downregulates Steap3 expression to inhibit ferroptosis, thereby attenuating graft IRI, which might be a promising strategy to treat IRI in steatotic grafts. Graphical Abstract

Abstract Background Liver transplantation (LT) is required in many end-stage liver diseases. Donation after cardiac death (DCD) livers are often used, and treatment of acute rejection (ACR) requires the use of immunosuppressive drugs that are associated with complications. Bone marrow mesenchymal stem cells (BMMSCs) are used in treatment following LT; however, they have limitations, including low colonization in the liver. An optimized BMMSC application method is required to suppress ACR. Methods BMMSCs were isolated and modified with the heme oxygenase 1 (HO-1) gene. HO-1/BMMSCs were perfused into donor liver in vitro using a normothermic machine perfusion (NMP) system, followed by LT into rats. The severity of ACR was evaluated based on liver histopathology. Gene chip technology was used to detect differential gene expression, and flow cytometry to analyze changes in natural killer (NK) T cells. Results NMP induced BMMSCs to colonize the donor liver during in vitro preservation. The survival of HO-1/BMMSCs in liver grafts was significantly longer than that of unmodified BMMSCs. When the donor liver contained HO-1/BMMSCs, the local immunosuppressive effect was improved and prolonged, ACR was controlled, and survival time was significantly prolonged. The application of HO-1/BMMSCs reduced the number of NKT cells in liver grafts, increased the expression of NKT cell co-inhibitory receptors, and reduced NKT cell expression of interferon-γ. Conclusions NK cell and CD8+ T cell activation was inhibited by application of HO-1/BMMSCs, which reduced ACR of transplanted liver. This approach could be developed to enhance the success rate of LT.

We report the case of a patient who underwent endovascular retrieval of a conical inferior vena cava (IVC) filter with a ruptured retraction hook that was attached to the IVC wall. A 21-year-old woman with a Celect (Cook) filter, implanted 1,522 days prior, requested retrieval. Preoperative ultrasound and CT examinations showed that the filter was inclined, the retraction hook was attached to the IVC wall, and one of the filter’s pedicles was broken. The inferior vena cava was patent, with no thrombus. Old superficial femoral vein thrombosis could be seen in the right lower extremity. The filter retrieval equipment (Gunther Tulip, Cook) failed to capture the retraction hook. By means of a pigtail catheter (with a partly removed catheter tip) and loach guidewire, we applied a modified loop-snare technique to successfully cut the proliferative tissue near the tip of the retraction hook, by which the hook re-entered the inferior vena cava. Although the snare successfully captured the retraction hook and retrieved the filter, the broken pedicle was retained in the inferior vena cava. We used forceps to capture and pull it to the distal end. In the end, the inferior vena cava became patent, with no contrast agent spillage or residual, and no symptomatic pulmonary embolization. A simultaneous occurrence of oblique adherence and fracture is rarely found in the same filter; however, by using the modified loop-snare technique and biopsy forceps technique, we successfully retrieved the filter and broken pedicle. Our case provides a practical auxiliary technique for regular clinical practice.

High-density planting is a major way to improve crop yields. However, shade-avoidance syndrome (SAS) is a major factor limiting increased planting density. First Green Revolution addressed grass lodging problem by using dwarf/semi-dwarf genes. However, it is not suitable for soybean, which bear seeds on stalk and whose seed yield depends on plant height. Hence, mining shade-tolerant germplasms and elucidating the underlying mechanism could provide meaningful resources and information for high-yield breeding. Here, we report a high-plant density-tolerant soybean cultivar, JiDou 17, which exhibited an inactive SAS (iSAS) phenotype under high-plant density or low-light conditions at the seedling stage. A quantitative trait locus (QTL) mapping analysis using a recombinant inbred line (RIL) population showed that this iSAS phenotype is related to a major QTL, named shade-avoidance response 1 (qSAR1), which was detected. The mapping region was narrowed by a haplotype analysis into a 554 kb interval harboring 44 genes, including 4 known to be key regulators of the SAS network and 4 with a variance response to low-light conditions between near isogenic line (NIL) stems. Via RNA-seq, we identified iSAS-specific genes based on one pair of near isogenic lines (NILs) and their parents. The iSAS-specific genes expressed in the stems were significantly enriched in the “proteasomal protein catabolic” process and the proteasome pathway, which were recently suggested to promote the shade-avoidance response by enhancing PIF7 stability. Most iSAS-specific proteasome-related genes were downregulated under low-light conditions. The expression of genes related to ABA, CK, and GA significantly varied between the low- and normal-light conditions. This finding is meaningful for the cloning of genes that harbor beneficial variation(s) conferring the iSAS phenotype fixed in domestication and breeding practice.

Exploring new composite explosives based on 1,1-diamino-2,2-dinitroethylene (FOX-7) is significant in the field of insensitive high explosives (IHE). Despite having good detonation performance compared to RDX, FOX-7 has not been successfully applied in the preparations of aluminized explosives due to the poor explosion heat values. In this paper, the explosion heat and detonation velocity of FOX-7-based aluminized explosives were studied systematically. The experiment results showed that the explosion heat of FOX-7-based aluminized explosives are significantly lower than that of RDX-based ones, especially when the content of aluminum powder exceeds 30%. To solve this problem, a simple but effective method of adding RDX to FOX-7-based aluminized explosives was developed, leading to a huge growth of explosion heat values. Finally, in order to compare the safety performance with RDX-based aluminized explosives, the low vulnerability of the FOX-7/RDX-based aluminized explosives formulation was investigated by fast cook-off, sympathetic detonation and 12.7 mm bullet impact tests. The results showed that the safety performance of FOX-7/RDX-based aluminized explosives is better than that of RDX-based aluminized explosives, proving that good low vulnerability is kept with the addition of RDX into FOX-7-based aluminized explosives.

Three-dimensional NAND flash memory is widely used in sensor systems as an advanced storage medium that ensures system stability through fast data access. However, in flash memory, as the number of cell bits increases and the process pitch keeps scaling, the data disturbance becomes more serious, especially for neighbor wordline interference (NWI), which leads to a deterioration of data storage reliability. Thus, a physical device model was constructed to investigate the NWI mechanism and evaluate critical device factors for this long-standing and intractable problem. As simulated by TCAD, the change in channel potential under read bias conditions presents good consistency with the actual NWI performance. Using this model, NWI generation can be accurately described through the combination of potential superposition and a local drain-induced barrier lowering (DIBL) effect. This suggests that a higher bitline voltage (Vbl) transmitted by the channel potential can restore the local DIBL effect, which is ever weakened by NWI. Furthermore, an adaptive Vbl countermeasure is proposed for 3D NAND memory arrays, which can significantly minimize the NWI of triple-level cells (TLC) in all state combinations. The device model and the adaptive Vbl scheme were successfully verified by TCAD and 3D NAND chip tests. This study introduces a new physical model for NWI-related problems in 3D NAND flash, while providing a feasible and promising voltage scheme as a countermeasure to optimize data reliability.

In recent years, recommendation systems based on collaborative filtering (CF) have achieved a high performance. Most of the existing recommendation systems use similarity measures to determine the suitability of items for users based on latent factor models (LFM). However, these recommendation systems reduce the explainability of recommendations and hide the reasons for recommending specific items. As a result, users tend to distrust the recommendation results. To address this problem, we propose the neural explicit factor model (NEFM). Based on the user–item rating matrix, we propose adding both user–feature attention matrix and an item–feature quality matrix to improve the explainability of user and item vectors. In addition, a feedforward neural network and a one-dimensional convolutional neural network extract features from user, item and the item–feature vector. Finally, a prediction layer performs the inner product of user data, item data, and item features. Experiments on the MovieLens and Yahoo Movies datasets validate the proposed model, and comparisons with similar recommendation models show the higher accuracy and explainability of our proposal.

Abstract Background Leiomyosarcoma (LMS) is an uncommon mesenchymal neoplasm, which infrequently metastasizes to pancreas and thigh. Clinical presentation and imaging findings of metastatic broad ligament LMS are often nonspecific. Complete excision plays an important role in treatment of patients with localized LMS. Case presentation Here, we report a case of a 33-year-old woman with recurrent broad ligament LMS metastasizing to pancreas and thigh. Previously, she was diagnosed with broad ligament LMS and underwent hysterectomy, bilateral salpingo-oophorectomy. The disease-free interval was 2.5 years until metastases were found. Computerized tomography (CT) of abdomen and thighs, magnetic resonance imaging (MRI) of thighs and whole-body 18-fluorodeoxyglucose positron emission tomography - computed tomography (PET-CT) performed, revealed pancreatic and thigh metastasis. Ultrasonography-guided biopsy and histological examinations confirmed LMS at both the sites. Pancreatic metastasis was completely resected first. Then the patient underwent surgical resection of thigh metastasis when both chemotherapy and radiotherapy failed. She recovered well and remained free of disease recurrence in the 2 years follow-up. Conclusions Though imaging lacks specificity, it is a valuable asset in assessing the burden of disease and characterizing lesions while histological examination with immunohistochemistry is helpful for the diagnosis of LMS. Complete surgical resection of all metastatic sites where-ever feasible should be strongly considered in a treated case of broad ligament LMS with a durable disease-free interval.

Traumatic peripheral vascular injury is a significant cause of disability and death either in civilian environments or on the battlefield. Penetrating trauma and blunt trauma are the most common forms of vascular injuries. Besides, iatrogenic arterial injury (IAI) is another pattern of vascular trauma. The management of peripheral vascular injuries has been improved in different environments and wars. There are different types of vascular injuries, such as vasospasm, contusion, intimal flaps, intimal disruption or hematoma, external compression, laceration, transection and focal wall defects, etc. The main clinical manifestations of vascular injuries are shock following massive hemorrhage and limb necrosis due to tissue and organ ischemia. Ultrasound, computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are most valuable for assessment of peripheral vascular injuries. Angiography remains the gold standard for diagnosing vascular trauma. Immediate hemorrhage control and rapid restoration of blood flow are the primary goals of vascular trauma treatment. There are many operative treatment methods for vascular injuries, such as vascular suture or ligation, vascular wall repair and vascular reconstruction with blood vessel prostheses or vascular grafts. Embolization, balloon dilation and covered stent implantation are the main endovascular techniques. Surgical operation is still the primary treatment for vascular injuries. Endovascular treatment is a promising alternative, proved to be safe and effective, and preferred selection for patients. In summary, rapid diagnosis and timely surgical intervention remain the mainstays of the treatment. However, many issues need to be resolved by further studies. Keywords: Endovascular procedures, Surgical procedures, Operative, Peripheral vascular trauma

Purpose: To explore the significance of traditional vascular reconstruction and covered stent for limb salvage after subclavian artery injury. Methods: Patients with subclavian artery injury admitted to Beijing Jishuitan Hospital from January 2010 to December 2018 were retrospectively analyzed. All the injuries have been confirmed by intraoperative exploration, computed tomography angiography or digital subtraction angiography. Complete or partial amputation injuries were excluded. Mild artery defect or partial intimal damage was treated by interventional implantation, while other patients received open surgeries, including direct suture of small defect less than 2 cm and transplantation with autologous vein or artificial blood when the defect was more than 2 cm. Patients were divided into open surgery group and stent implantation group based on the treatment they received. Patients were followed up at 2 weeks (first stage) and 6 months (second stage) after operation to investigate limb salvage. Student's t-test was used to compare the general data between two groups and Chi-square test to analyze the rate of limb salvage. Results: Altogether 50 cases of subclavian artery injury were treated, including 36 cases of open surgery and 14 cases of stent implantation. Combination of nerve injury was observed in 27 cases (75.0%) in open surgery group and 12 cases (85.7%) in stent implantation group. Amputation developed in 3 cases with open surgery and 1 case with stent implantation. Consequently the rate of successful limb salvage was respectively 91.7% (33/36) and 92.9% (13/14), revealing no significant difference (p > 0.05). Conclusion: Rapid reconstruction of blood circulation is crucial following subclavian artery injury, no matter what kinds of treatment strategies have been adopted. Interventional stent implantation can achieve a good effect for limb salvage. Keywords: Subclavian artery injury, Vascular transplantation, Covered stent

Purpose: To discuss and share the experience of treatment of traumatic innominate arterial injury. Methods: A retrospective analysis was performed on patients with innominate arterial injuries admitted from January 2016 to July 2018 at the department of vascular surgery, Beijing Jishuitan Hospital, China. All the arterial injuries were confirmed by arteriography. Clinical data including mechanism of injury, type of injury, demographics, concomitant injuries, time interval from trauma to blood flow reconstruction, and operation methods were collected. Follow-up program included outpatient visit and duplex-ultrasonography. SPSS version 23.0 was adopted for data analysis. Categorical variables are presented as number and/or frequency and continuous variables as mean ± standard deviation. Result: Altogether 7 patients were included and 6 (85.7%) were male. The mean age of patients was (29.43 ± 7.98) years, range 19-43 years. Six patients had isolated innominate arterial injuries and the rest 1 combined innominate arterial and vein injuries. The injury causes were road accidents in 3 patients, stab wound in 2, gunshot wound in 1, and crush injury in 1. All the 7 patients presented hemorrhagic shock at admission, which was timely and effectively corrected. No perioperative death or technical complications occurred. Intimal injury (n = 2) and partial transaction (n = 2) of the innominate artery were treated with covered stents. Two patients with complete transection of artery received vascular reconstruction by artificial grafts. One patient with partial transaction received balloon dilation and open surgical repair (hybrid operation). The mean time interval from trauma to blood flow reconstruction was (4.27 ± 0.18) h, range 4.0–4.5 h; while the operation time was (48.57 ± 19.94) min, range 25–75 min. Cerebral infarction occurred in one patient with brain injury due to anticoagulation contraindication. The average follow-up was (13.29 ± 5.65) months, range 6–24 months. No severe stenosis, occlusion, and thrombosis of covered stents or artificial vessels were found by color Doppler ultrasound. Conclusion: Urgent control of hemorrhage and restoration of blood supply are critical for the treatment of traumatic innominate arterial injury. Endovascular therapy is a feasible and effective method with short operation time and less trauma. Keywords: Endovascular procedures, Innominate artery, Surgical revascularization

To optimize the energy output and improve the energy utilization efficiency of an aluminized explosive, an explosion device was developed and used to investigate the detonation pressure and temperature of R1 (Al6) aluminum powder and the aluminum powder particle gradation of R2 (Al6+Al13), R3 (Al6+Al24) and R4 (Al6+Al flake) in a confined space. By using gas chromatography, quantitative analysis and calculations were carried out to analyze the gaseous detonation products. Finally, the reaction ratios of the aluminum powder and the explosion reaction equations were calculated. The results show that in a confined space, the quasi-static pressures and equilibrium temperature of the aluminum powder in air are higher than in vacuum. In vacuum, the quasi-static pressures and equilibrium temperatures of the samples in descending order are R1>R3>R4>R2 and R3>R4>R1>R2, respectively. In air, the quasi-static pressures and equilibrium temperatures of the samples in descending order are R1>R2>R4>R3 and R1>R4>R2>R3, respectively. R4 (Al6+Al flake) and R3 (Al6+Al24) have relatively higher temperatures after detonation, which shows that the particle gradation method can enhance the reaction energy output of aluminum during the initial reaction stage of the explosion and increase the reaction ratio by 10.6% and 8.0%, respectively. In air, the reaction ratio of Al6 aluminum powder can reach as high as 78.16%, and the reaction ratio is slightly reduced after particle gradation. Finally, the reaction equations of the explosives in vacuum and in air were calculated by quantitative analysis of the explosion products, which provides a powerful basis for the study of RDX-based explosive reactions. Keywords: Particle gradation, Quasi-static pressure, Equilibrium temperature, Reaction ratio

Objective: Adenomatous polyposis coli 2 (APC2) is a colorectal cancer (CRC) tumor-suppressor gene. The progression of several kinds of cancer is closely associated with Forkhead box O4 (FOXO4). However, the function of FOXO4 in CRC is unclear. This study focused on the role of FOXO4 and the relationship between FOXO4 and APC2 in CRC migration and metastasis.Methods: The expressions of FOXO4, APC2, and p(S37)-β-catenin were detected in CRC tissues by immunohistochemistry, and their correlation was analyzed using the Spearman coefficient. Chromatin immunoprecipitation was used to test whether FOXO4 binds and regulates APC2 as a transcription factor. Either FOXO4 overexpression or APC2 knockdown was performed in CRC cell lines. The roles of FOXO4 and APC2 were investigated in CRC migration and metastasis.Results: FOXO4 was downregulated in CRC tissues compared with normal tissues and positively correlated with APC2 and p(S37)-β-catenin. FOXO4 could combine the promoter region of APC2 to upregulate its expression and increase the phosphorylated degradation of β-catenin. Stemness genes (CD133, ABCG1, and SOX2) were inhibited by FOXO4 overexpression in SW620 and HCT116 cell lines. Overexpressed FOXO4 suppressed epithelial–mesenchymal transition and the migration of CRC cell lines and metastasis of HCT116 in both the spleen and liver of nude mice, which was reversed by APC2 knockdown.Conclusion: This research demonstrates that overexpressed FOXO4 inhibits the migration and metastasis of CRC cells by enhancing the APC2/β-catenin axis, suggesting that FOXO4 is a potential therapeutic target of CRC.

Background: The combined index of hemoglobin, albumin, lymphocyte, and platelet (HALP) is considered a novel score to reflect systemic inflammation and nutritional status. This study aimed to investigate the association between HALP score and poor outcome in patients with acute ischemic stroke (AIS).Methods: Consecutive AIS patients within 24 h after onset were prospectively enrolled. Poor outcome was a combination of a new stroke event (ischemic and hemorrhagic) and all-cause death within 90 days and 1 year. The association between HALP score and poor outcome was analyzed using Cox proportional hazards.Results: A total of 1,337 patients were included. Overall, 60 (4.5%) and 118 (8.8%) patients experienced poor outcome within 90 days and 1 year, respectively. Patients in the highest tertile of HALP score had a lower risk of poor outcome within 90 days and 1 year (hazard ratio: 0.25 and 0.42; 95% confidence intervals: 0.11–0.57 and 0.25–0.69, P for trend

Livers from donors after circulatory death (DCD) are inevitably exposed to a longer warm ischemic period, which might increase the incidence of postoperative bile duct complications. Bone marrow mesenchymal stem cells (BMMSCs) have tissue repair properties. The present study was aimed at exploring the repair effect of heme oxygenase-1- (HO-1-) modified BMMSCs (HO-1/BMMSCs) combined with normothermic machine perfusion (NMP) on bile duct injury after DCD liver transplantation and at revealing the underlying mechanisms. Rat livers were exposed to in situ warm ischemia for 30 min; then, NMP was performed through the portal vein for 4 h with BMMSCs, HO-1/BMMSCs, or neither before implantation. Obvious bile duct histological damage and liver functional damage were observed postoperatively. In the group treated with HO-1/BMMSCs combined with NMP (HBP group), liver functions and bile duct histology were improved; meanwhile, cell apoptosis was reduced and cell proliferation was active. A large number of regenerative cells appeared at the injured site, and the defective bile duct epithelium was restored. Dilatation of peribiliary glands (PBGs), proliferation of PBG cells, high expression of vascular endothelial growth factor (VEGF), and increased proportion of bile duct progenitor cells with stem/progenitor cells biomarkers were observed. Blocking Wnt signaling significantly inhibited the repair effect of HO-1/BMMSCs on bile duct injury. In conclusion, HO-1/BMMSCs combined with NMP were relevant to the activation of biliary progenitor cells in PBGs which repaired bile duct injury in DCD liver transplantation via the Wnt signaling pathway. Proliferation and differentiation of PBG cells were involved in the renewal of the injured biliary epithelium.

Background: Despite the acknowledged benefits of immune checkpoint inhibitor (ICI)-based combination therapy (either with other checkpoint inhibitors, chemotherapy, targeted therapy, or radiotherapy), little is known about the impact of age on the efficacy of ICI -based combination therapy in non-small-cell lung cancer (NSCLC) patients. We conducted a systematic review and meta-analysis to investigate the differences in the benefits of ICI-based combination therapy for NSCLC by age (cut-off age, 65 years).Methods: We systematically searched randomized controlled trials (RCTs) of ICI plus other therapies including other ICIs, chemotherapies, targeted therapies, or radiotherapies, in the PubMed, Embase, and Cochrane databases with available hazard ratios (HRs) and 95% confidence intervals (CIs) for death and disease progression according to patient age. The search deadline was May 25, 2020. First, we calculated the pooled HRs of younger and older patients based on the HRs from each trial. Second, we assessed the pooled ratio of HRs reported in older patients to the HRs reported in younger patients for progression or death by the random-effects model. An estimated pooled HR ratio was lower than 1 indicating a better effect in older patients and higher than 1 indicating a better effect in younger patients.Results: A total of 10 eligible RCTs were included in our meta-analysis. The pooled HR for overall survival (OS) comparing ICI combined with other therapies to non-ICI regimens was 0.67 (95%CI 0.58–0.78) for younger patients and 0.79 (95%CI 0.70–0.90) for older patients. The pooled HRs ratio for OS reported in older patients compared to younger patients was 1.16 (95%CI 0.99–1.34), indicating no statistically significant difference between younger and older patients. Consistent with the findings related to OS, the analysis also demonstrated that ICI-based immunotherapy could significantly prolong progression-free survival (PFS) in younger and older patients (HR = 0.55; 95% CI 0.47–0.66, and HR = 0.64; 95% CI 0.57–0.71). The same results could also be observed in the pooled HRs ratio for PFS (HR = 1.15, 95%CI 0.91–1.46) indicating comparable efficacy of ICI-based combination therapy in younger and older patients with NSCLC.Conclusion: ICI-based combination therapy vs. non-ICI treatment had comparable efficacy in younger and older NSCLC patients with a cut-off age of 65 years.

Most speakers' first language (L1) in Hong Kong and Guangdong China is Cantonese. Even though the L1 of both Guangdong Cantonese speakers and Hong Kong Cantonese speakers is the same, their second languages (L2) belong to different language families. Previous studies have pointed out that L2 status in third language (L3) acquisition is a salient factor. This study aimed to: (1) examine Guangdong Cantonese speakers' pronunciation error patterns in their L2 Mandarin and L3 English and explore the language interaction patterns among these three languages; (2) compare the findings with those of Hong Kong Cantonese speakers whose L2 is English and L3 Mandarin in Chen and Han (2019. L3 phonology: contributions of L1 and L2 to L3 pronunciation learning by Hong Kong speakers. International Journal of Multilingualism, 16(4), 492-512. https://doi.org/10.1080/14790718.2019.1573901) to identify the roles of L1 and L2 in L3 acquisition. Results of the reading aloud tasks, a questionnaire survey and interview data show that the language interaction patterns among L1, L2 and L3 are influenced by learners' language proficiency.

State of charge (SOC) estimation plays a crucial role in battery management systems. Among all the existing SOC estimation approaches, the model-driven extended Kalman filter (EKF) has been widely utilized to estimate SOC due to its simple implementation and nonlinear property. However, the traditional EKF derived from the mean square error (MSE) loss is sensitive to non-Gaussian noise which especially exists in practice, thus the SOC estimation based on the traditional EKF may result in undesirable performance. Hence, a novel robust EKF method with correntropy loss is employed to perform SOC estimation to improve the accuracy under non-Gaussian environments firstly. Secondly, a novel robust EKF, called C-WLS-EKF, is developed by combining the advantages of correntropy and weighted least squares (WLS) to improve the digital stability of the correntropy EKF (C-EKF). In addition, the convergence of the proposed algorithm is verified by the Cramér–Rao low bound. Finally, a C-WLS-EKF method based on an equivalent circuit model is designed to perform SOC estimation. The experiment results clarify that the SOC estimation error in terms of the MSE via the proposed C-WLS-EKF method can efficiently be reduced from 1.361% to 0.512% under non-Gaussian noise conditions.

PURPOSEWe aimed to examine the efficacy and safety of Tempofilter II (B. Braun, Melsungen, Germany) implantation to prevent pulmonary embolism in patients with lower-extremity fractures and proximal deep vein thrombosis (DVT).MATERIALS AND METHODSThe records of patients with lower limb fractures and proximal DVT who were implanted with Tempofilter II devices from May 2004 to August 2009 were reviewed. Data collected included success rate, occurrence of pulmonary embolism, retrieval rate, and complications.RESULTSA total of 176 eligible patients, including 129 males (73.3%) and 47 females (26.7%) with a median age of 42.0 years (interquartile range [IQR], 34.0–52.0 years) were included in the study. Filters were successfully implanted in 174 patients (98.9%). One patient experienced a pulmonary embolism after implantation and died. Filters were removed without complications in all other patients. Median filter implantation time was 27 days (IQR, 25.0–29.0 days). Visible organized thrombi were present on the surface of 144 (82.8%) of filters after removal, and the diameter of most thrombi (n=124) ranged from 0.5 to 1.0 cm. Filters migrated

The electricity consumption forecasting (ECF) technology plays a crucial role in the electricity market. The support vector regression (SVR) is a nonlinear prediction model that can be used for ECF. The electricity consumption (EC) data are usually nonlinear and non-Gaussian and present outliers. The traditional SVR with the mean-square error (MSE), however, is insensitive to outliers and cannot correctly represent the statistical information of errors in non-Gaussian situations. To address this problem, a novel robust forecasting method is developed in this work by using the mixture maximum correntropy criterion (MMCC). The MMCC, as a novel cost function of information theoretic, can be used to solve non-Gaussian signal processing; therefore, in the original SVR, the MSE is replaced by the MMCC to develop a novel robust SVR method (called MMCCSVR) for ECF. Besides, the factors influencing users’ EC are investigated by a data statistical analysis method. We find that the historical temperature and historical EC are the main factors affecting future EC, and thus these two factors are used as the input in the proposed model. Finally, real EC data from a shopping mall in Guangzhou, China, are utilized to test the proposed ECF method. The forecasting results show that the proposed ECF method can effectively improve the accuracy of ECF compared with the traditional SVR and other forecasting algorithms.

In recent years, with the deepening of China’s electricity sales side reform and electricity market opening up gradually, the forecasting of electricity consumption (FoEC) becomes an extremely important technique for the electricity market. At present, how to forecast the electricity accurately and make an evaluation of results scientifically are still key research topics. In this paper, we propose a novel prediction scheme based on the least-square support vector machine (LSSVM) model with a maximum correntropy criterion (MCC) to forecast the electricity consumption (EC). Firstly, the electricity characteristics of various industries are analyzed to determine the factors that mainly affect the changes in electricity, such as the gross domestic product (GDP), temperature, and so on. Secondly, according to the statistics of the status quo of the small sample data, the LSSVM model is employed as the prediction model. In order to optimize the parameters of the LSSVM model, we further use the local similarity function MCC as the evaluation criterion. Thirdly, we employ the K-fold cross-validation and grid searching methods to improve the learning ability. In the experiments, we have used the EC data of Shaanxi Province in China to evaluate the proposed prediction scheme, and the results show that the proposed prediction scheme outperforms the method based on the traditional LSSVM model.

A series of new 4β-5-Fu-substituted 4'-demethylepipodophyllotoxin derivatives were synthesized and evaluated, together with some previously prepared ones, for their cytotoxic activities against four tumor cell lines (HL60, P388, A549 and BEL7402). Three of these compounds exhibited superior in vitro anticancer activity against P388 and A549 than the reference compound etoposide. In addition, the partition coefficients (P) of all the new and previously synthesized derivatives were determined.

Background Recently, computational fluid dynamics (CFD) has been used to simulate blood flow of symptomatic intracranial atherosclerotic stenosis (sICAS) and investigate the clinical implications of its haemodynamic features, which were systematically reviewed in this study.Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology statements, we searched PubMed and Embase up to March 2024 and screened for articles reporting clinical implications of haemodynamic parameters in sICAS derived from CFD models.Results 19 articles met the inclusion criteria, all studies recruiting patients from China. Most studies used CT angiography (CTA) as the source image for vessel segmentation, and generic boundary conditions, rigid vessel wall and Newtonian fluid assumptions for CFD modelling, in patients with 50%-99% sICAS. Pressure and wall shear stress (WSS) were quantified in almost all studies, and the translesional changes in pressure and WSS were usually quantified with a poststenotic to prestenotic pressure ratio (PR) and stenotic-throat to prestenotic WSS ratio (WSSR). Lower PR was associated with more severe stenosis, better leptomeningeal collaterals, prolonged perfusion time and internal borderzone infarcts. Higher WSSR and other WSS measures were associated with positive vessel wall remodelling, regression of luminal stenosis and artery-to-artery embolism. Lower PR and higher WSSR were both associated with the presence and severity of cerebral small vessel disease. Moreover, translesional PR and WSSR were promising predictors for stroke recurrence in medically treated patients with sICAS and outcomes after acute reperfusion therapy, which also provided indicators to assess the effects of stenting treatment on focal haemodynamics.Conclusions CFD is a promising tool in investigating the pathophysiology of ICAS and in risk stratification of patients with sICAS. Future studies are warranted for standardisation of the modelling methods and validation of the simulation results in sICAS, for its wider applications in clinical research and practice.

Intracranial atherosclerotic disease (ICAD) is a common cause of ischaemic stroke and transient ischaemic attack (TIA) with a high recurrence rate. It is often referred to as intracranial atherosclerotic stenosis (ICAS), when the plaque has caused significant narrowing of the vessel lumen. The lesion is usually considered ‘symptomatic ICAD/ICAS’ (sICAD/sICAS) when it has caused an ischaemic stroke or TIA. The severity of luminal stenosis has long been established as a prognostic factor for stroke relapse in sICAS. Yet, accumulating studies have also reported the important roles of plaque vulnerability, cerebral haemodynamics, collateral circulation, cerebral autoregulation and other factors in altering the stroke risks across patients with sICAS. In this review article, we focus on cerebral haemodynamics in sICAS. We reviewed imaging modalities/methods in assessing cerebral haemodynamics, the haemodynamic metrics provided by these methods and application of these methods in research and clinical practice. More importantly, we reviewed the significance of these haemodynamic features in governing the risk of stroke recurrence in sICAS. We also discussed other clinical implications of these haemodynamic features in sICAS, such as the associations with collateral recruitment and evolution of the lesion under medical treatment, and indications for more individualised blood pressure management for secondary stroke prevention. We then put forward some knowledge gaps and future directions on these topics.

Background and purpose Symptomatic intracranial atherosclerotic stenosis (sICAS) is associated with a considerable risk of recurrent stroke despite contemporarily optimal medical treatment. Severity of luminal stenosis in sICAS and its haemodynamic significance quantified with computational fluid dynamics (CFD) models were associated with the risk of stroke recurrence. We aimed to develop and compare stroke risk prediction nomograms in sICAS, based on vascular risk factors and these metrics.Methods Patients with 50%–99% sICAS confirmed in CT angiography (CTA) were enrolled. Conventional vascular risk factors were collected. Severity of luminal stenosis in sICAS was dichotomised as moderate (50%–69%) and severe (70%–99%). Translesional pressure ratio (PR) and wall shear stress ratio (WSSR) were quantified via CTA-based CFD modelling; the haemodynamic status of sICAS was classified as normal (normal PR&WSSR), intermediate (otherwise) and abnormal (abnormal PR&WSSR). All patients received guideline-recommended medical treatment. We developed and compared performance of nomograms composed of these variables and independent predictors identified in multivariate logistic regression, in predicting the primary outcome, recurrent ischaemic stroke in the same territory (SIT) within 1 year.Results Among 245 sICAS patients, 20 (8.2%) had SIT. The D2H2A nomogram, incorporating diabetes, dyslipidaemia, haemodynamic status of sICAS, hypertension and age ≥50 years, showed good calibration (P for Hosmer-Lemeshow test=0.560) and discrimination (C-statistic 0.73, 95% CI 0.60 to 0.85). It also had better performance in risk reclassification and provided larger net benefits in decision curve analysis, compared with nomograms composed of conventional vascular risk factors only, and plus the severity of luminal stenosis in sICAS. Sensitivity analysis in patients with anterior-circulation sICAS showed similar results.Conclusions The D2H2A nomogram, incorporating conventional vascular risk factors and the haemodynamic significance of sICAS as assessed in CFD models, could be a useful tool to stratify sICAS patients for the risk of recurrent stroke under contemporarily optimal medical treatment.