Barbed arrow-like structure membrane with ultra-high rectification coefficient enables ultra-fast, highly-sensitive lateral-flow assay of cTnI.

Acute myocardial infarction (AMI) has become a public health disease threatening public life safety due to its high mortality. The lateral-flow assay (LFA) of a typical cardiac biomarker, troponin I (cTnI), is essential for the timely warnings of AMI. However, it is a challenge to achieve an ultra-fast and highly-sensitive assay for cTnI (hs-cTnI) using current LFA, due to the limited performance of chromatographic membranes. Here, we propose a barbed arrow-like structure membrane (BAS Mem), which enables the unidirectional, fast flow and low-residual of liquid. The liquid is rectified through the forces generated by the sidewalls of the barbed arrow-like grooves. The rectification coefficient of liquid flow on BAS Mem is 14.5 (highest to date). Using BAS Mem to replace the conventional chromatographic membrane, we prepare batches of lateral-flow strips and achieve LFA of cTnI within 240 s, with a limit of detection of 1.97 ng mL-1. The lateral-flow strips exhibit a specificity of 100%, a sensitivity of 93.3% in detecting 25 samples of suspected AMI patients. The lateral-flow strips show great performance in providing reliable results for clinical diagnosis, with the potential to provide early warnings for AMI.

Deferoxamine-Loaded Injectable Chitosan-Grafted Chlorogenic Acid/Oxidized Hyaluronic Acid Hybrid Hydrogel with Antibacterial, Anti-inflammatory, and Angiogenesis-Promoting Properties for Diabetic Wound Repair.

Diabetic chronic wounds are notoriously difficult to heal as a result of their susceptibility to infection. To address this issue, we constructed an innovated and adaptable solution in the form of injectable chitosan (CS) hydrogel, denoted as CCOD, with enhanced antibacterial and anti-inflammatory properties. This hydrogel is created through a Schiff base reaction that combines chitosan-grafted chlorogenic acid (CS-CGA) and oxidized hyaluronic acid (OHA) with deferoxamine (DFO) as a model drug. The combination of CS and CGA has demonstrated excellent antibacterial and anti-inflammatory properties, while grafting played a pivotal role in making these positive effects stable. These unique features make it possible to customize injectable hydrogel and fit any wound shape, allowing for more effective and personalized treatment of complex bacterial infections. Furthermore, the hydrogel system is not only effective against inflammation and bacterial infections but also possesses antioxidant and angiogenic abilities, making it an ideal solution for the repair of chronic wounds that have been previously thought of as unmanageable.

Enhanced external counterpulsation treatment improves multi-organ hemodynamics for postoperative liver transplantation patient. A case report.

INTRODUCTION: Post liver transplantation (LT) patients endure high morbidity rate of multi-organ ischemic symptoms following reperfusion. We hypothesize that enhanced external counterpulsation (EECP) as a typical non-invasive assisted circulation procedure, which can efficiently inhibit the relative ischemic symptoms via the systemic improvement of hemodynamics. CASE PRESENTATION: A 51-year-old male patient, 76 kg, 172 cm, received orthotopic LT surgery for viral hepatitis B induced acute-on-chronic liver failure hepatic failure. His medical records revealed ischemic symptoms in multi-organ at the time of hospital discharge, including headache, refractory insomnia, abdominal paralysis, and lower limb pain. The EECP treatment was introduced for assisted rehabilitation and to improve the postoperative quality of life. Doppler Ultrasound examination showed significant augmentation of blood flow volume in the carotid arteries, the hepatic artery, the portal vein and the femoral artery during EECP intervention. A standard 35-hour EECP treatment led to significant improvement in quality of life, e.g. sleep quality and walking ability. CONCLUSION: We report a case of multi-organ ischemic symptoms in a post LT patient. EECP treatment can significantly improve the quality of life via the systematic promotion of hemodynamics.

TMEM135 maintains the equilibrium of osteogenesis and adipogenesis by regulating mitochondrial dynamics.

BACKGROUND: Disturbance in the differentiation process of bone marrow mesenchymal stem cells (BMSCs) leads to osteoporosis. Mitochondrial dynamics plays a pivotal role in the metabolism and differentiation of BMSCs. However, the mechanisms underlying mitochondrial dynamics and their impact on the differentiation equilibrium of BMSCs remain unclear. METHODS: We investigated the mitochondrial morphology and markers related to mitochondrial dynamics during BMSCs osteogenic and adipogenic differentiation. Bioinformatics was used to screen potential genes regulating BMSCs differentiation through mitochondrial dynamics. Subsequently, we evaluated the impact of Transmembrane protein 135 (TMEM135) deficiency on bone homeostasis by comparing Tmem135 knockout mice with their littermates. The mechanism of TMEM135 in mitochondrial dynamics and BMSCs differentiation was also investigated in vivo and in vitro. RESULTS: Distinct changes in mitochondrial morphology were observed between osteogenic and adipogenic differentiation of BMSCs, manifesting as fission in the late stage of osteogenesis and fusion in adipogenesis. Additionally, we revealed that TMEM135, a modulator of mitochondrial dynamics, played a functional role in regulating the equilibrium between adipogenesis and osteogenesis. The TMEM135 deficiency impaired mitochondrial fission and disrupted crucial mitochondrial energy metabolism during osteogenesis. Tmem135 knockout mice showed osteoporotic phenotype, characterized by reduced osteogenesis and increased adipogenesis. Mechanistically, TMEM135 maintained intracellular calcium ion homeostasis and facilitated the dephosphorylation of dynamic-related protein 1 at Serine 637 in BMSCs. CONCLUSIONS: Our findings underscore the significant role of TMEM135 as a modulator in orchestrating the differentiation trajectory of BMSCs and promoting a shift in mitochondrial dynamics toward fission. This ultimately contributes to the osteogenesis process. This work has provided promising biological targets for the treatment of osteoporosis.

Enhanced external counterpulsation treatment regulates blood flow and wall shear stress metrics in femoral artery: An in vivo study in healthy subjects.

As a non-invasive assisted circulation therapy, enhanced external counterpulsation (EECP) has demonstrated potential in treatment of lower-extremity arterial disease (LEAD). However, the underlying hemodynamic mechanism remains unclear. This study aimed to conduct the first prospective investigation of the EECP-induced responses of blood flow behavior and wall shear stress (WSS) metrics in the femoral artery. Twelve healthy male volunteers were enrolled. A Doppler ultrasound-basedapproach was introduced for the in vivo determination of blood flow in the common femoral artery (CFA) and superficial femoral artery (SFA) during EECP intervention, with incremental treatment pressures ranging from 10 to 40 kPa. Three-dimensional subject-specific numerical models were developed in 6 subjects to quantitatively assess variations in WSS-derived hemodynamic metrics in the femoral bifurcation. A mesh-independence analysis was performed. Our results indicated that, compared to the pre-EECP condition, both the antegrade and retrograde blood flow volumes in the CFA and SFA were significantly augmented during EECP intervention, while the heart rate remained constant. The time average shear stress (TAWSS) over the entire femoral bifurcation increased by 32.41%, 121.30%, 178.24%, and 214.81% during EECP with treatment pressures of 10 kPa, 20 kPa, 30 kPa, and 40 kPa, respectively. The mean relative resident time (RRT) decreased by 24.53%, 61.01%, 69.81%, and 77.99%, respectively. The percentage of area with low TAWSS in the femoral artery dropped to nearly zero during EECP with a treatment pressure greater than or equal to 30 kPa. We suggest that EECP is an effective and non-invasive approach for regulating blood flow and WSS in lower extremity arteries.

Can regional joint prevention and control of atmospheric reduce border pollution? Evidence from China's 12th Five-Year Plan on air pollution.

Border pollution is usually a difficult problem in environmental governance. Based on the data at the county level in China from 2005 to 2019, this study takes the 12th Five-Year Plan (FYP) for atmospheric pollution as a policy shock, and uses the difference-in-differences (DID) method to explore the impact of regional joint prevention and control (JPC) of atmospheric pollution policy on air pollution of the border regions. Empirical results show that: (1) After implementing the JPC of atmospheric pollution policy, the PM2.5 concentration in the border regions is reduced by 3.5%. (2) The mechanism analysis shows that there is a spillover effect in the governing behaviors of local governments. In the border areas under low economic growth pressure and high environmental protection pressure, the reduction effect of the JPC of atmospheric pollution policy is more significant on the PM2.5 concentration of the border regions. The research conclusions have new insights into the role and effect of macro-regional environmental JPC policy and border pollution control, and provide practical guidance for social green governance.

3D-printed gradient scaffolds for osteochondral defects: Current status and perspectives.

Articular osteochondral defects are quite common in clinical practice, and tissue engineering techniques can offer a promising therapeutic option to address this issue.The articular osteochondral unit comprises hyaline cartilage, calcified cartilage zone (CCZ), and subchondral bone.As the interface layer of articular cartilage and bone, the CCZ plays an essentialpart in stress transmission and microenvironmental regulation.Osteochondral scaffolds with the interface structure for defect repair are the future direction of tissue engineering. Three-dimensional (3D) printing has the advantages of speed, precision, and personalized customization, which can satisfy the requirements of irregular geometry, differentiated composition, and multilayered structure of articular osteochondral scaffolds with boundary layer structure. This paper summarizes the anatomy, physiology, pathology, and restoration mechanisms of the articular osteochondral unit, and reviews the necessity for a boundary layer structure in osteochondral tissue engineering scaffolds and the strategy for constructing the scaffolds using 3D printing. In the future, we should not only strengthen the basic research on osteochondral structural units, but also actively explore the application of 3D printing technology in osteochondral tissue engineering. This will enable better functional and structural bionics of the scaffold, which ultimately improve the repair of osteochondral defects caused by various diseases.

Genetic Diversity and Pathogenic Variation of the Rice False Smut Pathogen Ustilaginoidea virens from Different Rice Cultivars.

Rice false smut, caused by Ustilaginoidea virens, has become one of the most devastating grain diseases of rice worldwide. Understanding the genetic diversity of U. virens is essential for efficient disease control and breeding for disease resistance. However, little is known about the genetic variation of U. virens from different rice cultivars. We investigated the genetic diversity and pathogenic variation of U. virens isolates from 10 rice cultivars in Zhejiang, China. A total of 260 polymorphic loci and 27 haplotypes were identified based on the 2,137-bp combined DNA fragments of all individuals; hap_4 was the most common haplotype, represented by 41 isolates. Phylogeny indicated that all isolates were divided into four genetic groups. Group I was the largest, with 98 isolates, distributed mainly in eight cultivar populations, whereas 90% of the isolates collected from a Changxiang cultivar were clustered in Group IV. Furthermore, the pairwise FST values exhibited significant genetic differentiation in 27 of the pairwise comparisons between populations, accounting for 23.21% of the total genetic variation. The genetic composition of the isolates of the CX population was distinguishable from that of the other nine populations, and genetic recombination was found in a few isolates. Finally, 27 haplotype representative isolates showed high variation in pathogenicity, and the isolates from the genetic subpopulation I were likely to be more virulent than those from genetic subpopulations II and III. Collectively, these findings suggest that differences in rice cultivars play an important role in the genetic variation of U. virens.

Surface polydopamine modification of bone defect repair materials: Characteristics and applications.

Bone defects are a common challenge for clinical orthopedic surgeons. The existing bone defect repair materials are difficult to achieve satisfactory osseointegration between the material and the bone. Therefore, it is increasingly important to find effective methods to improve the integration of the materials with the bone and thus facilitate bone defect repair. Researchers have found that polydopamine (PDA) has a structure and properties similar to the adhesive proteins secreted by mussels in nature, with good biocompatibility, bioactivity, hydrophilicity, bio-adhesion and thermal stability. PDA is therefore expected to be used as a surface modification material for bone repair materials to improve the bonding of bone repair materials to the bone surface. This paper reviews research related to PDA-modified bone repair materials and looks at their future applications.

Can vertical environmental regulation induce enterprise green innovation? A new perspective from automatic air quality monitoring station in China.

Based on panel data of listed companies in China from 2006 to 2020, this study takes the establishment of automatic air quality monitoring stations as a quasi-natural experiment and uses the staggered difference-in-differences method to explore whether the establishment of monitoring stations promotes green innovation of listed companies. The empirical results show that: (1) The green innovation of companies achieves an increase of 3.5% with monitoring stations in their locations, and an increase of 2.3% with the establishment of each additional monitoring station. This conclusion is valid after a series of robustness tests and exclusive tests. (2) The heterogeneity analyses show that monitoring stations have a greater role in promoting green innovation for non-state-owned enterprises, enterprises in heavy polluting industries and enterprises in key cities for environmental protection. (3) The transmission mechanism test results show that the establishment of automatic air monitoring station has crowding-out effect rather than leverage effect on green innovation, substantial innovation rather than strategic innovation. (4) The further analyses manifest the promotion of end-to-end green innovation, independent invention and quality of green patents.

Characterization of Genetic Diversity and Variation in Pathogenicity of the Rice False Smut Pathogen Ustilaginoidea virens from a Single Source.

Rice false smut, caused by Ustilaginoidea virens, is one of the most destructive fungal diseases in rice-growing countries. Studies of the genetic diversity, evolution, and pathogenicity of U. virens can provide more information for disease control and cultivar breeding. Contrary to previous studies on the genetic diversity of different geographical populations of U. virens, this study analyzed the genetic variation of U. virens from different panicles of the same rice cultivar in a field in Yunnan Province using single nucleotide polymorphism molecular markers. A total of 183 polymorphic loci and five haplotypes, hap_1 to hap_5, were identified based on the 1,350-bp combined DNA fragment of 127 isolates, showing some genetic diversity. Hap_1 and hap_3 had the highest occurrence, indicating they were the dominant haplotypes in the field. Further analysis showed that most rice panicles could be coinfected by different haplotypes, and even a few spikelets could be coinfected by multiple haplotypes. The phylogeny indicated that all isolates were divided into five genetic groups. Groups I, II, and III clustered together and were distinguished from Groups IV and V. Significant genetic variations in five pairwise comparisons of panicle populations, accounting for 72.45% of the total variation, were found according to FST values. This variation might be caused by different field microenvironments and the uneven distribution of inoculum sources. An unweighted pair-group method with arithmetic means dendrogram and the population structure revealed that the genetic composition of the isolates collected from YN1, YN2, and YN4, which were dominated by the same genetic subgroup, was different from that collected from YN3. Finally, genetic recombination was found in 11 isolates; hap_2 and hap_5, probably as genetic recombination progenies produced by sexual hybridization between hap_1 and hap_3, acquired a greater virulence than their ancestors according to population structure and pathogenicity analyses. These results will help us understand the genetic diversity, evolution, and infection process of U. virens and aid in the development of more effective management strategies for rice false smut, including new cultivars with improved resistance.

Transcriptomic and metabolic responses of earthworms to contaminated soil with polypropylene and polyethylene microplastics at environmentally relevant concentrations.

Examining transcriptomic and metabolic responses of earthworms to microplastic-contaminated soil is critical for understanding molecular-level toxicity of microplastics; yet very little research on this topic exists. We investigated influences of environmentally relevant concentrations (ERC) of polypropylene (PP) and polyethylene (PE) microplastic-contaminated soil on earthworms at the transcriptomic, metabolic, tissue and whole-body levels to study their molecular toxicity. The addition of PP and PE at ERC induced oxidative stress on earthworms, as indicated by the high enrichment of glutathione metabolism and increased glutamine at the transcriptomic and metabolic levels. Digestive and immune systems of earthworms were damaged according to the injuries of the intestinal epithelium, partial shedding of chloragogenous tissues and unclear structure of coelom tissues, which were confirmed by pathway analysis at the transcriptomic level. Significant enrichment of arachidonic acid and glycerolipid metabolisms indicated that PP and PE disturbed the lipid metabolism in earthworms. Significantly increased betaine and myo-inositol, and decreased 2-hexyl-5-ethyl-3-furansulfonate suggested that PP and PE caused differences in osmoregulation extent. In conclusion, most similar responses of earthworm might result from special size rather than type effects of PP and PE microplastics. Contamination of soils with microplastics even at ERC has health risks to earthworms; therefore, proper management of microplastics to reduce their input to the environment is key to reducing the health risks to soil fauna.

Protective effects of Hirudin against compartment syndrome in rabbits through the activation of Nrf2/HO-1.

Compartment syndrome generates an oxidative condition causing the death of skeletal muscle cells. Hirudin has antioxidant and anti-inflammatory properties. However, its correlation with the pathway of Nrf2/HO-1 for the protection of the skeletal muscle is unknown. We aimed to evaluate the protective efficacy of double-doses of hirudin in compartment syndrome and its association with Nrf2/HO-1 expression. Compartment syndrome was induced in rabbits and double-doses of hirudin (0-8 ATU/kg) were locally administered to select an optimal Hirudin concentration that protects skeletal muscle from damage. The tissue structural changes, W/D ratio, lipid peroxidation level by MDA assay and inflammatory factors were determined in the skeletal muscle. To determine the musculoprotective efficacy of H8 at 72 h timepoint after compartment syndrome, and its association with the Nrf2/HO-1 pathway, the following assays were performed by TUNEL assay and immunofluorescence: necrosis (high-mobility group box-1; HMGB1), Nrf2, and HO-1. In addition, the HO-1 mRNA was evaluated by qPCR. Hirudin in a dose of 8 ATU/kg (H8) presented the lowest levels of histological damage, fibrosis, W/D ratio and oxidative stress in the studied groups. Moreover, treatment with H8 markedly downregulated the level of inflammatory factors including TNF-a, IL-1ß and IL-6. H8 showed a protective effect at 72 h timepoint after compartment syndrome, as revealed by a decrease in the levels of all damage markers. Nuclear translocation Nrf2 and HO-1 staining in cytoplasm were increased, and the levels of HO-1 mRNA were also increased. In conclusion, double-doses of H8 alleviate the death of muscle cells induced by oxidative stress 72 h after compartment syndrome in rabbits. This protective effect is associated with the nuclear translocation of Nrf2 and an elevated expression of HO-1.

Bismuth-coated 80S15C bioactive glass scaffolds for photothermal antitumor therapy and bone regeneration.

Background: Malignant bone tumors usually occur in young people and have a high mortality and disability rate. Surgical excision commonly results in residual bone tumor cells and large bone defects, and conventional radiotherapy and chemotherapy may cause significant side effects. In this study, a bifunctional Bi-BG scaffold for near-infrared (NIR)-activated photothermal ablation of bone tumors and enhanced bone defect regeneration is fabricated. Methods: In this study, we prepared the Bi-BG scaffold by in-situ generation of NIR-absorbing Bi coating on the surface of a 3D-printing bioactive glass (BG) scaffold. SEM was used to analyze the morphological changes of the scaffolds. In addition, the temperature variation was imaged and recorded under 808 nm NIR laser irradiation in real time by an infrared thermal imaging system. Then, the proliferation of rat bone mesenchymal stem cells (rBMSCs) and Saos-2 on the scaffolds was examined by CCK-8 assay. ALP activity assay and RT-PCR were performed to test the osteogenic capacity. For in vivo experiments, the nude rat tumor-forming and rat calvarial defect models were established. At 8 weeks after surgery, micro-CT, and histological staining were performed on harvested calvarial samples. Results: The Bi-BG scaffolds have outstanding photothermal performance under the irradiation of 808 nm NIR at different power densities, while no photothermal effects are observed for pure BG scaffolds. The photothermal temperature of the Bi-BG scaffold can be effectively regulated in the range 26-100°C by controlling the NIR power density and irradiation duration. Bi-BG scaffolds not only significantly induces more than 95% of osteosarcoma cell death (Saos-2) in vitro, but also effectively inhibit the growth of bone tumors in vivo. Furthermore, they exhibit excellent capability in promoting osteogenic differentiation of rBMSCs and finally enhance new bone formation in the calvarial defects of rats. Conclusion: The Bi-BG scaffolds have bifunctional properties of photothermal antitumor therapy and bone regeneration, which offers an effective method to ablate malignant bone tumors based on photothermal effect.

Identification of an unfolded protein response-related signature for predicting the prognosis of pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal malignancy. An effective prognosis prediction model is urgently needed for treatment optimization. Methods: The differentially expressed unfolded protein response (UPR)‒related genes between pancreatic tumor and normal tissue were analyzed using the TCGA-PDAC dataset, and these genes that overlapped with UPR‒related prognostic genes from the E-MTAB-6134 dataset were further analyzed. Univariate, LASSO and multivariate Cox regression analyses were applied to establish a prognostic gene signature, which was evaluated by Kaplan‒Meier curve and receiver operating characteristic (ROC) analyses. E‒MTAB‒6134 was set as the training dataset, while TCGA-PDAC, GSE21501 and ICGC-PACA-AU were used for external validation. Subsequently, a nomogram integrating risk scores and clinical parameters was established, and gene set enrichment analysis (GSEA), tumor immunity analysis and drug sensitivity analysis were conducted. Results: A UPR-related signature comprising twelve genes was constructed and divided PDAC patients into high- and low-risk groups based on the median risk score. The UPR-related signature accurately predicted the prognosis and acted as an independent prognostic factor of PDAC patients, and the AUCs of the UPR-related signature in predicting PDAC prognosis at 1, 2 and 3 years were all more than 0.7 in the training and validation datasets. The UPR-related signature showed excellent performance in outcome prediction even in different clinicopathological subgroups, including the female (p<0.0001), male (p<0.0001), grade 1/2 (p<0.0001), grade 3 (p=0.028), N0 (p=0.043), N1 (p<0.001), and R0 (p<0.0001) groups. Furthermore, multiple immune-related pathways were enriched in the low-risk group, and risk scores in the low-risk group were also associated with significantly higher levels of tumor-infiltrating lymphocytes (TILs). In addition, DepMap drug sensitivity analysis and our validation experiment showed that PDAC cell lines with high UPR-related risk scores or UPR activation are more sensitive to floxuridine, which is used as an antineoplastic agent. Conclusion: Herein, we identified a novel UPR-related prognostic signature that showed high value in predicting survival in patients with PDAC. Targeting these UPR-related genes might be an alternative for PDAC therapy. Further experimental studies are required to reveal how these genes mediate ER stress and PDAC progression.

Polydopamine Coating-Mediated Immobilization of BMP-2 on Polyethylene Terephthalate-Based Artificial Ligaments for Enhanced Bioactivity.

Background/objectives: Polyethylene terephthalate (PET)-based artificial ligaments are one of the most commonly used grafts in anterior cruciate ligament (ACL) reconstruction surgery. However, the lack of favorable hydrophilicity and cell attachment for PET highly impeded its widespread application in clinical practice. Studies found that surface modification on PET materials could enhance the biocompatibility and bioactivity of PET ligaments. In this study, we immobilized bone morphogenetic protein-2 (BMP-2) on the surface of PET ligaments mediated by polydopamine (PDA) coating and investigated the bioactivation and graft-to-bone healing effect of the modified grafts in vivo and in vitro. Methods: In this study, we prepared the PDA coating and subsequent BMP-2-immobilized PET artificial ligaments. Scanning electron microscopy (SEM) was used to analyze the morphological changes of the modified grafts. In addition, the surface wettability properties of the modified ligaments, amount of immobilized BMP 2, and the release of BMP-2 during a dynamic period up to 28 days were tested. Then, the attachment and proliferation of rat bone mesenchymal stem cells (rBMSCs) on grafts were examined by SEM and Cell Counting Kit-8 (CCK-8) assay, respectively. Alkaline phosphatase (ALP) assay, RT-PCR, and Alizarin Red S staining were performed to test the osteoinduction property. For in vivo experiments, an extra-articular graft-to-bone healing model in rabbits was established. At 8 weeks after surgery, biomechanical tests, micro-CT, and histological staining were performed on harvested samples. Results: A surface morphological analysis verified the success of the PDA coating. The wettability of the PET artificial ligaments was improved, and more than 80% of BMP-2 stably remained on the graft surface for 28 days. The modified grafts could significantly enhance the proliferation, attachment, as well as expression of ALP and osteogenic-related genes, which demonstrated the favorable bioactivity of the grafts immobilized with BMP-2 in vitro. Moreover, the grafts immobilized with BMP-2 at a concentration of 138.4 ± 10.6 ng/cm2 could highly improve the biomechanical properties, bone regeneration, and healing between grafts and host bone after the implantation into the rabbits compared with the PDA-PET group or the PET group. Conclusion: The immobilization of BMP-2 mediated by polydopamine coating on PET artificial ligament surface could enhance the compatibility and bioactivity of the scaffolds and the graft-to-bone healing in vivo.

Acute Hemodynamic Responses to Enhanced External Counterpulsation in Patients With Coronary Artery Disease.

Purpose: Enhanced external counterpulsation is a non-invasive treatment that increases coronary flow in patients with coronary artery disease (CAD). However, the acute responses of vascular and blood flow characteristics in the conduit arteries during and immediately after enhanced external counterpulsation (EECP) need to be verified. Methods: Forty-two patients with CAD and 21 healthy controls were recruited into this study to receive 45 min-EECP. Both common carotid arteries (CCAs), namely, the left carotid (LC) and right carotid (RC), the right brachial (RB), and right femoral (RF) artery were imaged using a Color Doppler ultrasound. The peak systolic velocity (PSV), end-diastolic velocity (EDV), mean inner diameter (ID), resistance index (RI), and mean flow rate (FR) were measured and calculated before, during, and after the 45 min-EECP treatment. Results: During EECP, in the CCAs, the EDV was significantly decreased, while the RI was markedly increased in the two groups (both P < 0.01). However, immediately after EECP, the RI in the RC was significantly lower than that at the baseline in the patients with CAD (P = 0.039). The FR of the LC was markedly increased during EECP only in the CAD patients (P = 0.004). The PSV of the patients with CAD was also significantly reduced during EECP (P = 0.015) and immediately after EECP (P = 0.005) compared with the baseline. Moreover, the ID of the LC, RB, and RF was significantly higher immediately after EECP than that at the baseline (all P < 0.05) in the patients with CAD. In addition, they were also higher than that in the control groups (all P < 0.05). Furthermore, by the subgroup analysis, there were significant differences in the FR, PSV, and RI between females and males during and immediately after EECP (all P < 0.05). Conclusions: Enhanced external counterpulsation creates different responses of vascular and blood flow characteristics in carotid and peripheral arteries, with more significant effects in both the carotid arteries. Additionally, the beneficial effects in ID, blood flow velocity, RI, and FR after 45 min-EECP were shown only in the patients with CAD. More importantly, acute improvement of EECP in the FR of the brachial artery was showed in males, while the FR and RI of the carotid arteries changed in females.

Hemodynamic Responses in Carotid Bifurcation Induced by Enhanced External Counterpulsation Stimulation in Healthy Controls and Patients With Neurological Disorders.

Enhanced external counterpulsation is a Food and Drug Administration-approved, non-invasive, assisted circulation therapy for ischemic cardiovascular and cerebrovascular diseases. Previous studies have confirmed that EECP stimulation induces largely different cerebral hemodynamic responses in patients with ischemic stroke and healthy controls. However, the underlying mechanisms remain uncertain. We hypothesize that different blood redistributions at the carotid bifurcation may play a key role. Ten subjects were enrolled in this study, namely, five patients with neurological disorders and five young healthy volunteers as controls. Magnetic resonance angiography (MRA) was performed on the carotid artery. All the subjects received a single session of EECP treatment, with external cuff pressures ranging from 20 to 40 kPa. Vascular ultrasound measurements were taken in the common carotid artery (CCA), external carotid artery (ECA) and internal carotid artery (ICA). Three-dimensional patient-specific numerical models were developed to calculate the WSS-derived hemodynamic factors. The results indicated that EECP increased CCA and ECA blood flow in both groups. The ICA blood flow in the patient group exhibited a mean increase of 6.67% during EECP treatment compared with the pre-EECP condition; a mean decrease of 9.2% was observed in the healthy control group. EECP increased the averaged wall shear stress (AWSS) throughout the carotid bifurcation in the patient group; the ICA AWSS of the healthy group decreased during EECP. In both groups, the oscillatory shear index (OSI) in the ICA increased proportionally with external cuff pressure. In addition, the relative resident time (RRT) was constant or slightly decreased in the CCA and ECA in both groups but increased in the ICA. We suggest that the benefits of EECP to patients with neurological disorders may partly result from blood flow promotion in the ICA and increase in WSS at the carotid bifurcation. In the healthy subjects, the ICA blood flow remained constant during EECP, although the CCA blood flow increased significantly. A relatively low external cuff pressure (20 kPa) is recommended as the optimal treatment pressure for better hemodynamic effects. This study may play an important role in the translation of physiological benefits of EECP treatment in populations with or without neurological disorders.

Acute Effect of Enhanced External Counterpulsation on the Carotid Hemodynamic Parameters in Patients With High Cardiovascular Risk Factors.

PURPOSE: Enhanced external counterpulsation (EECP) can improve carotid circulation in patients with coronary artery disease. However, the response of carotid hemodynamic parameters induced by EECP in patients with high cardiovascular risk factors remains to be clarified. This study aimed to investigate the acute effect of EECP on the hemodynamic parameters in the carotid arteries before, during, and immediately after EECP in patients with hypertension, hyperlipidemia, and type 2 diabetes. METHODS: Eighty-three subjects were recruited into this study to receive 45-min EECP, including patients with simple hypertension (n = 21), hyperlipidemia (n = 23), type 2 diabetes (n = 18), and healthy subjects (n = 21). Hemodynamic parameters in both common carotid arteries (CCAs) were measured and calculated from Doppler ultrasound images. Peak systolic velocity (PSV), end-diastolic velocity (EDV), mean inner diameter (ID), systolic/diastolic flow velocity ratio (VS/VD), flow rate (FR), and resistance index (RI) were monitored before, during, and immediately after 45-min EECP. RESULTS: EDV and VS/VD were significantly reduced, while RI of CCAs was significantly increased among four groups during EECP (all P < 0.01). Additionally, the ID of CCAs and the FR of left CCA increased in patients with hyperlipidemia during EECP (P < 0.05). PSV of left CCA was reduced in patients with type 2 diabetes (P < 0.05). Moreover, immediately after EECP, ID was significantly higher in patients with hyperlipidemia. The RI of patients with hypertension and PSV and VS/VD of patients with type 2 diabetes were significantly lower compared with baseline (all P < 0.05). CONCLUSION: EECP created an acute reduction in EDV, PSV, and VS/VD, and an immediate increase in the RI, FR, and ID of CCAs among the four groups. Additionally, a single 45-min session of EECP produced immediate improvement in the ID of patients with hyperlipidemia, the RI of patients with hypertension, and the PSV and VS/VD of patients with type 2 diabetes. The different hemodynamic responses induced by EECP may provide theoretical guidance for making personalized plans in patients with different cardiovascular risk factors.

A Numerical Model for Simulating the Hemodynamic Effects of Enhanced External Counterpulsation on Coronary Arteries.

Traditional enhanced external counterpulsation (EECP) used for the clinical treatment of patients with coronary heart disease only assesses diastolic/systolic blood pressure (Q = D/S > 1.2). However, improvement of the hemodynamic environment surrounding vascular endothelial cells of coronary arteries after long-term application of EECP is the basis of the treatment. Currently, the quantitative hemodynamic mechanism is not well understood. In this study, a standard 0D/3D geometric multi-scale model of the coronary artery was established to simulate the hemodynamic effects of different counterpulsation modes on the vascular endothelium. In this model, the neural regulation caused by counterpulsation was thoroughly considered. Two clinical trials were carried out to verify the numerical calculation model. The results demonstrated that the increase in counterpulsation pressure amplitude and pressurization duration increased coronary blood perfusion and wall shear stress (WSS) and reduced the oscillatory shear index (OSI) of the vascular wall. However, the impact of pressurization duration was the predominant factor. The results of the standard model and the two real individual models indicated that a long pressurization duration would cause more hemodynamic risk areas by resulting in excessive WSS, which could not be reflected by the change in the Q value. Therefore, long-term pressurization during each cardiac cycle therapy is not recommended for patients with coronary heart disease and clinical treatment should not just pay attention to the change in the Q value. Additional physiological indicators can be used to evaluate the effects of counterpulsation treatment.