Single-Cell Transcriptomics Reveals Crucial Cell Subsets and Functional Heterogeneity Associated With Carotid Atherosclerosis and Cerebrovascular Events.

BACKGROUND: Carotid atherosclerosis is a chronic inflammatory disorder and is responsible for the vast majority of ischemic strokes. Inappropriate innate and adaptive immune responses synergize with malfunctional vascular wall cells to cause atherosclerotic lesions. Yet, functional characteristics of specific immune and endothelial cell subsets associated with atherosclerosis and cerebrovascular events are poorly understood. METHODS: Here, using single-cell RNA sequencing, the unprecedentedly largest data set from 20 patients' carotid artery plaques and paired peripheral blood mononuclear cells was generated, with which an ultra-high-precision cellular landscape of the atherosclerotic microenvironment involving 372 070 cells was depicted. RESULTS: Compared with peripheral blood mononuclear cells, 3 plaque-specific T-cell subsets exhibiting proatherogenic features of both activation and exhaustion were identified. Strikingly, usually antiatherogenic, CD4+FOXP3+ regulatory T cells from plaques of patients with symptomatic disease acquired proinflammatory properties by probably converting to T helper 17 and T helper 9 cells, while CD4+NR4A1+/C0 and CD8+SLC4A10+ T cells related to cerebrovascular events possessed atherogenic attributes including proinflammation, polarization, and exhaustion. In addition, monocyte-macrophage dynamics dominated innate immune response. Two plaque-specific monocyte subsets performed diametrically opposed functions, EREG+ monocytes promoted cerebrovascular events while C3+ monocytes are anti-inflammatory. Similarly, IGF1+ and HS3ST2+ macrophages with classical proinflammatory M1 macrophage features were annotated and contributed to cerebrovascular events. Moreover, SULF1+ (sulfatase-1) endothelial cells were also found to participate in cerebrovascular events through affecting plaque vulnerability. CONCLUSIONS: This compendium of single-cell transcriptome data provides valuable insights into the cellular heterogeneity of the atherosclerotic microenvironment and the development of more precise cardiovascular immunotherapies.

Prevalence and risk factors for severe linezolid-associated thrombocytopenia in pediatric patients: An analysis of a public database.

Linezolid is widely used in various clinical settings. Studies have revealed that it may cause thrombocytopenia in adults. However, the correlation between the use of linezolid and thrombocytopenia in pediatric patients is still unclear. This study aimed to identify the impact of Linezolid on the occurrence of thrombocytopenia in children. A retrospective observational study was conducted using data on patients treated with linezolid from the Pediatric Intensive Care clinical database. Univariate and multiple logistic regression analyses were performed to identify the risk factors of linezolid-related severe thrombocytopenia. A total of 134 patients were included. The prevalence of severe thrombocytopenia was 8.96% (12/134). Univariate analysis indicated that the severe thrombocytopenia group showed significantly higher proportion of concomitant carbapenem (75% vs 44.3%; P < .05) and piperacillin/tazobactam (25% vs 6.6%; P < .05) than that of the non-severe thrombocytopenia group. Multivariate analysis also revealed that the occurrence of severe thrombocytopenia was significantly associated with concurrent use of carbapenem (odd ratio = 4.058; 95% confidence interval: 1.012-16.274; P = .048) and piperacillin/tazobactam (odd ratio = 5.335; 95% confidence interval: 1.117-25.478; P = .036). 75% of patients (9/12) developed severe thrombocytopenia within the first 7 days of linezolid use. The concomitant use of carbapenem and piperacillin/tazobactam was associated with an increased probability of severe thrombocytopenia in pediatric patients undergoing linezolid treatment. Further prospective clinical studies are required, and more detailed mechanisms of blood toxicity in pediatric patients must be investigated.

Research on cognitive evaluation of forest color based on visual behavior experiments and landscape preference.

Forest colors are important elements for public enjoying the scenery. So increasing attention has been acquired on forest color cognition. However researches on relationship between forest colors and public response are still insufficient, which cannot provide sufficient theoretical basis for the regulation of forest landscape in color. Therefore, We seek to examine the relationship between forest color and visual behavior based on eye tracking technology, and further interpret the visual indicators through the value of scenic beauty. This study researched Jiaozi Mountain in China by selecting 29 sampling points, counting up 116 photographs in 4 seasons by a mountainous region. On this basis, Matlab was performed to quantitatively extract color elements, while ArcGIS and Fragstats were applied to extract the spatial index of color patches. A total of 10 indicators were obtained to explain the color characteristics of each forest image. Through both visual behavior experiment and landscape preference evaluation, the results showed that people tend to have different visual behaviors and preference cognition when observing forest colors of different seasonal types. Based on the study of forest landscape color in all seasons, the subjects tend to judge the image in comparison to other seasonal forest landscape color photos to identify it more easily. For a single-season forest colors, diversified color information and abundant visual attention are important factors influencing the correlation between visual behavior, landscape preference, and forest color characteristics. This study aims to further reveal people's perceptions and psychological preference to forest colors, contribute to the establishment of a more quantitative and scientific scenery evaluation system, and provide a scientific basis for forest color planning and design.

Effects of Municipal Solid Waste on Planting Properties and Scouring Resistance of Vegetation Concrete (Wuhan, China).

Vegetation concrete (VC) laid as a reinforcement base and covered by a soil layer with vegetation has been increasingly used to beautify the landscape, reduce environmental pollution and control stormwater runoff. In this study, the effects of municipal solid waste (MSW) on vegetation characteristics of modified VC were tested under different mix compositions. We first explored the effects of the mixed concrete environment on Festuca elata and perennial Ryegrass for 60 days. Then, the influence of various MSW contents added to different percentages of cement on scouring resistance of VC was examined. The experimental results revealed that the germination rates and plant heights of both species decreased with the increase in concrete content. Considering the scouring resistances, the optimal mix proportion of MSW-modified VC was recommended as No. 25, with 5% KW fertilizer, 8% cement and 0.5% wheat straw in this study. Furthermore, adding a small amount of fallen leaves or silica fume to VC can promote the growth of both species to some extent, although these additions had an inverse effect on the scouring resistances. The results contribute to beneficial knowledge for future research on the feasibility of the use these species with VC technology for slope ecological restoration.

Different Grades of Collateral Circulation for Evaluating Cerebral Hemodynamic Status in Carotid Artery Stenosis.

Normally, ipsilateral hemodynamic compromise of patients with carotid stenosis (CS) is subjectively identified by collateral circulation through cerebral angiography in the clinical process. It is unclear whether collaterals would linearly determine cerebral perfusion in CS patients. This study aimed to investigate the independent role of collateral circulation on cerebral perfusion in CS patients and the underlying interrelations among them. From 2017 to 2020, 124 CS patients who underwent carotid endarterectomy (CEA) with both preoperative CTP and digital substruction angiography (DSA) images were enrolled. Division of subgroups was based on degree of CS (50-70%, 70-90%, and near-occlusion (NO)) and grades of collateral circulation by DSA. Differences in CTP parameters between CS patients with different collateral circulation were analyzed. Among 124 CS patients, grades 2 and 3 were highly associated with carotid NO (n = 22, 32.35% and n = 22, 32.35%) compared with others (P < 0.0001). The collateral circulation was found to have poor relation with cerebral perfusion parameters in all enrolled patients but significantly improved ipsilateral cerebral perfusion in patients with carotid NO (P < 0.05). Linear hemodynamic compromise was barely related to degree of CS in lobes supplied by middle cerebral artery (MCA) except the frontal lobe (P < 0.05). The grades of collateral circulation are positively associated with degree of CS while having nonsignificant effect on cerebral perfusion. Overall, severity of CS is poorly related to hemodynamic status while the perfectibility of compensation defined by grades of collateral circulation effectively alleviates ipsilateral cerebral perfusion deficit in carotid NO.

Independent role of circle of Willis for peri-procedural evaluation of carotid endarterectomy in patients with severe carotid stenosis.

OBJECTIVES: In patients with severe carotid stenosis (CS), collateral circulation via circle of Willis (CoW) is considered a compensatory response to maintain blood flow. The aim of this study was to evaluate the impact of CoW in patients with severe CS throughout carotid endarterectomy (CEA). METHODS: A database of patients (n = 124) undergoing CEA was sampled from 2013 to 2020. Severe CS was defined as 90-99% caliber stenosis and collateral circulation was identified by CoW opening. Baseline characteristics, Age-related white matter change (ARWMC) score, immediate neurologic events (INEs) and manifestations were recorded and compared. Correlation and regression analysis for CoW were further investigated. RESULTS: All patients enrolled were divided into two groups regarding to the visualized CoW opening and complete CoW was noticed in 57 patients. The prevalence of complete CoW was higher among asymptomatic patients (n = 39, 68.4%), while higher percentage of TIA or previous stroke were noticed in incomplete CoW (n = 45, 67.2%). Patients with incomplete CoW had a significantly higher median ARWMC score and remarkable cerebral perfusion deficit (P < 0.05*). Totally, 4 INEs (6.0%) were noted in patients with incomplete CoW after CEA. Cerebral hyperperfusion syndrome (CHS) was noticed in 10 patients and early-phase of postoperative hypertension (EPOH) in 15 ones with incomplete CoW versus patients with complete CoW (14.9% and 22.4% vs 3.5% and 7.0%, P < 0.05). Correlation analysis showed strong relationship between CoW opening and peri-operative factors like pre-operative symptoms, ARWMC, CHS and EPOH (P < 0.05*). Overall, CoW opening was an independent predictor of both CHS and EPOH (95% CI, 0.021-0.715 and 0.060-0.949, P < 0.05*) with logistic regression. CONCLUSIONS: Sufficient collateral circulation via CoW may promote ipsilateral cerebral perfusion and mitigate WMC in patients with severe CS. In addition, collaterals may improve the predictive power of the risk scale for post-procedural complications after CEA.

Implementation of the visual aesthetic quality of slope forest autumn color change into the configuration of tree species.

Urban expansion leads to changes in the visual aesthetic quality and ecological degradation of the surrounding slope forest landscapes. Color is a crucial visual element to examine when viewing this large-scale slope forest landscape from a long distance. This is particularly true for the autumn color of slope forest, which is very attractive to the public. An exploration of the relationship between the change in color of a natural slope forest and its visual aesthetic quality enables the implementation of the configuration of superior aesthetic tree species. Therefore, it can provide aesthetic rules and a reference to configure local tree species to support their visual aesthetic quality, ecological sustainability and native biodiversity restoration in a local urban slope forest. However, such research is critically lacking. This study investigated the visual aesthetic quality of the color dynamics of a natural slope forest in Jiaozi Mountain, China in the autumn. We analyzed both the composition of tree species and the changes in color for each species of tree in nine forest sites that exhibited superior visual aesthetic quality. The results showed that the forests with superior visual aesthetic quality were more green, red, and yellow, had moderately higher saturation and value, more obvious color contrast, and diverse colors with primary and secondary contrast. Diverse and balanced color patches or a dominant color patch contrasted by many small patches with interspersed color components also highlighted the superior visual aesthetic quality of slope forest features. Different combinations of color features can result in high visual aesthetic quality. The 84 tree species in the superior visual aesthetic quality forests primarily displayed 10 types of color changes that varied as green, yellow, blue, red, withered yellow, withered red and gray.

Curcumin inhibits pancreatic cancer cell proliferation by regulating Beclin1 expression and inhibiting the hypoxia-inducible factor-1α-mediated glycolytic pathway.

Background: Pancreatic cancer has a high degree of malignancy and high mortality. Understanding its biological status can provide more therapeutic targets for the future. The present study was to investigate whether curcumin can inhibit pancreatic cancer cell proliferation by regulating Beclin1 expression and inhibiting the hypoxia-inducible factor-1α (HIF-1α)-mediated glycolytic pathway. Methods: Two pancreatic cancer cell lines, PANC-1 and SW1990, were treated with different concentrations of curcumin (0, 20, 40, and 60 µM). Cell viability was detected using the Cell Counting Kit-8 (CCK-8) assay and flow cytometry was performed to determine the apoptosis rate and cell cycle arrest of the pancreatic cancer cells. PANC-1 and SW1990 cells were treated with different concentrations of curcumin under hypoxic conditions for 48 hours to detect the relative expression of the Beclin1 protein. The co-immunoprecipitation (co-IP) method was used to determine whether curcumin could inhibit the interaction between Beclin1 and HIF-1α. Results: The proliferation inhibition rates of PANC-1 cells after exposure to 0, 20, 40, and 60 µM curcumin were 0%, 31.6%, 47.2%, and 63.9%, respectively, and that of SW1990 cells were 0%, 18.8%, 46.3%, and 63.5% respectively. Western blot analyses showed decreased expression of Beclin1 in cells treated with curcumin. The expression of Beclin1 in the nucleus and cytoplasm decreased with increasing concentrations of curcumin. Co-IP results demonstrated that curcumin inhibited the interaction between Beclin1 and HIF-1α. Treatment with the higher doses of curcumin (40 and 60 µM) significantly decreased the protein expression levels of HIF-1α. In addition, the expression levels of Kidney-Specific Cadherin (HSP70, HSP90, and von Hippel-Lindau protein (pVHL) were significantly decreased in pancreatic cancer cells while the expression of prolyl hydroxylase (PHD) and receptor of activated protein kinase C (RACK1) increased significantly. Furthermore, curcumin reduced cellular adenosine triphosphate (ATP) production in a dose-dependent manner. Compared with control pancreatic cancer cells, the expression levels of GLUT1, HK2, LDHA, and PDK1 gradually decreased with increasing curcumin concentrations. Conclusions: Curcumin can inhibit the expression of Beclin1 and HIF-1α in pancreatic cancer cells under anoxic conditions, thereby affecting the glycolysis pathway and inhibiting cell proliferation.

Analysis of the anatomic eligibility for transcarotid artery revascularization in Chinese patients who underwent carotid endarterectomy and transfemoral carotid artery stenting.

Objective: Transcarotid artery revascularization (TCAR) is thought to be a promising technique and instrument for treating carotid stenosis with favorable outcomes. Since there remain several differences in anatomic characteristics among races, this study was conducted to investigate the anatomic eligibility of TCAR in Chinese patients who underwent carotid revascularization. Methods: A retrospective review of patients with carotid stenosis from 2019 to 2021 was conducted. The anatomic eligibility of TCAR was based on the instruction of the ENROUTE Transcarotid Neuroprotection System. The carotid artery characteristics and configuration of the circle of Willis (CoW) were evaluated by CT angiography. The demographic and clinical characteristics and procedure-related complications were recorded. Logistic regression was used to analyze the independent factors for TCAR eligibility. Results: Of 289 consecutive patients [222 for carotid endarterectomy (CEA) and 67 for transfemoral carotid artery stenting (TF-CAS)] identified, a total of 215 patients (74.4%) met TCAR anatomic eligibility. Specifically, 83.7% had mild common carotid artery (CCA) puncture site plaque, 95.2% had 4-9 mm internal carotid artery diameters, 95.8% had >6 mm CCA diameter, and 98.3% had >5 cm clavicle to carotid bifurcation distance. Those who were female (OR, 5.967; 95% CI: 2.545-13.987; P < 0.001), were of an older age (OR, 1.226; 95% CI: 1.157-1.299; P < 0.001), and higher body mass index (OR, 1.462; 95% CI: 1.260-1.697; P < 0.001) were prone to be associated with TCAR ineligibility. In addition, 71 patients with TCAR eligibility (33.0%) were found to combine with incomplete CoW. A high risk for CEA was found in 29 patients (17.3%) with TCAR eligibility, and a high risk for TF-CAS was noted in nine patients (19.1%) with TCAR eligibility. Overall, cranial nerve injury (CNI) was found in 22 patients after CEA, while 19 of them (11.3%) met TCAR eligibility. Conclusion: A significant proportion of Chinese patients meet the anatomic criteria of TCAR, making TCAR a feasible treatment option in China. Anatomic and some demographic factors play key roles in TCAR eligibility. Further analysis indicates a potential reduction of procedure-related complications in patients with high-risk carotid stenosis under the TCAR procedure.

Correlation between SHP-1 and carotid plaque vulnerability in humans.

BACKGROUND: Advanced atherosclerotic plaques tend to indicate an increased risk of cerebral ischemic events. SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1) is a class I classical nonreceptor protein tyrosine phosphatase associated with plaque stability, as shown by analysis of a Gene Expression Omnibus (GEO) dataset showing differences in mRNA levels. However, the correlation between SHP-1 and human carotid plaque stability at the protein level remains unclear. METHODS AND RESULTS: Thirty-nine carotid plaque tissue samples were acquired from 39 carotid artery stenosis patients after carotid endarterectomy. Hematoxylin and eosin, Masson trichrome, and CD68 staining was performed for pathological characterization, and immunohistochemical staining for SHP-1 was carried out. Within stable and unstable plaques, SHP-1 mainly accumulated in the necrotic area, plaque shoulder, and fibrous cap, similar to the distribution of CD68. A quantitative analysis of SHP-1 was carried out. The relative SHP-1-positive cell area was higher in the vulnerable group than in the stable group (P < .001). The number of symptomatic patients in the vulnerable group was no greater than that in the stable group (P = .098). Moreover, the integrated optical density (IOD)/area of SHP-1 was significantly higher in the vulnerable group than in the stable group (P < .001). Besides, SHP-1 colocalized with CD68 and vascular cell adhesion protein 1(VCAM-1). CONCLUSIONS: We demonstrate that SHP-1 expression increases during carotid atherosclerotic plaque progression. The protein expression of SHP-1 was related to an increase in plaque instability in not only symptomatic but also asymptomatic patients with carotid artery stenosis. SHP-1 may play a role in atherosclerosis progression by macrophage polarization-mediated efferocytosis. Furthermore, SHP-1 may become a promising biomarker for plaque vulnerability in the future.

Effect of nerve electrical stimulation for treating chemotherapy-induced nausea and vomiting in patients with advanced gastric cancer: A randomized controlled trial.

BACKGROUND: This randomized controlled trial evaluated the effectiveness of nerve electrical stimulation (NES) for the treatment of chemotherapy-induced nausea and vomiting (CINV) in patients with advanced gastric cancer (AGC). METHODS: One hundred twenty-four eligible patients with AGC were included in this randomized controlled trial. They were equally divided the NES group and the sham group. The patients in the NES group received NES intervention, while the subjects in the sham group underwent sham NES. The primary outcome included symptoms severity and appetite. The secondary outcomes included quality of life, as measured by the MD Anderson Symptom Inventory (MDASI) score, and functional impairment, as evaluated by the Karnofsky score. Additionally, adverse events were also documented during the period of the treatment. RESULTS: After treatment, NES showed greater effectiveness in reducing the severity of nausea (P = .02), and vomiting (P = .04), as well as the appetite improvement (P = .02), compared with the sham NES. Furthermore, no adverse events related to NES treatment were detected. CONCLUSION: The results of this study demonstrated that NES may help to relieve CINV in patients with AGC. Future studies are still needed to warrant these results.