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Background: The COVID-19 pandemic is our generation's greatest global challenge to our public health system. Vaccines are considered one of the most effective tools available for preventing COVID-19 infection and its complications and sequelae. Understanding and addressing the psychological stress related to COVID-19 vaccination may promote acceptance of these vaccines.Methods: We conducted an online survey from January 29 to April 26, 2021 to explore stress levels related to COVID-19 vaccination among the general public in China. Participants were asked to evaluate their psychological stress of considering whether or not to get vaccinated at the beginning period of the COVID-19 mass vaccination, after getting access to the information about the vaccine, as well as after getting vaccinated, using visual analog stress scale. Multiple linear regression analysis was performed to explore factors potentially associated with COVID-19-related psychological stress levels before and after getting vaccinated.Results: A total of 34,041 participants were included in the final analysis. The mean stress score concerning COVID-19 vaccination was 3.90 ± 2.60 among all participants, and significantly decreased over time. In addition, the vaccine-related stress level significantly decreased after accessing information about the COVID-19 vaccine (N = 29,396), as well as after getting vaccinated (N = 5,103). Multivariable regression analysis showed higher stress levels related to COVID-19 vaccination in participants who were younger, having lower education level, having history of chronic diseases, mistrusting vaccine's efficacy, experience of vaccine allergy events, being affected by the COVID-19 epidemic, and having mental illness symptoms. Moreover, mistrust in vaccine efficacy and experience of vaccine allergy events had a long-term impact on psychological stress levels about COVID-19 vaccination even after getting vaccinated.Conclusions: The current findings profiled the COVID-19 vaccine-related psychological stress among the general public in China. Population-specific management and interventions targeting the stress related to COVID-19 vaccination are needed to help governments and policy makers promote individual's willingness to get vaccinations for public well-being during the COVID-19 pandemic.

Residual cancer after incomplete ablation remains a major problem for radiofrequency ablation (RFA). We aimed to investigate the synergetic treatment efficacy of RFA combined with ultrasonic cavitation for liver tumor. Sixty rabbits with VX2 liver tumor were randomly divided into three groups. Group A was control group without any treatment. Combined ultrasonic cavitation with RFA was performed for group B1. Group B2 underwent RFA alone. The histopathological results were compared at the 5th, 11th, and 18th day of experiment, and the survival time and metastasis were assessed. The tumor volume growth rate, percentage of necrosis area, microvessel density, and apoptosis index showed significant differences among these groups at the 5th day, 11th day, and 18th day of experiment (P < .05). In contrast, the difference of metastatic score was not significant at the 5th and 11th day (P > .05). At the 18th day, the metastatic score of group A was significant higher than that of group B1 (P < .05), whereas the differences between group A and group B2, or group B1 and group B2 were not significant (P > .05). The median/range interquartile of survival time in groups A, B1, and B2 were 25/8 days, 50/19 days, and 48/20 days, respectively, and there was significant difference between groups A and B1 or B2 (P < .05). The difference between groups B1 and B2 was not significant (P > .05). Ultrasonic cavitation after incomplete RFA for liver tumor improved the antitumor effect, which could be considered as a potentially useful combined therapeutic strategy for liver malignancy. Keywords: Radiofrequency ablation, Ultrasound, Liver neoplasms, Residual cancer, Microbubbles

Abstract Cyclic AMP receptor protein (Crp) is a major transcriptional regulator in bacteria. This study demonstrated that Crp affects numerous virulence-related phenotypes, including colonization of mice, motility, fimbria-mediated adhesion, and glucose stress tolerance in uropathogenic Proteus mirabilis. Diabetic mice were more susceptible to kidney colonization by wild-type strain than nondiabetic mice, in which the crp mutant exhibited increased kidney colonization. Loss of crp or addition of 10% glucose increased the P. mirabilis adhesion to kidney cells. Direct negative regulation of pmpA (which encodes the major subunit of P-like fimbriae) expression by Crp was demonstrated using a reporter assay and DNase I footprinting. Moreover, the pmpA/crp double mutant exhibited reduced kidney adhesion comparable to that of the pmpA mutant, and mouse kidney colonization by the pmpA mutant was significantly attenuated. Hence, the upregulation of P-like fimbriae in the crp mutant substantially enhanced kidney colonization. Moreover, increased survival in macrophages, increased stress tolerance, RpoS upregulation, and flagellum deficiency leading to immune evasion may promote kidney colonization by the crp mutant. This is the first study to elucidate the role of Crp in the virulence of uropathogenic P. mirabilis, underlying mechanisms, and related therapeutic potential.

Microvascular complications eventually affect nearly all patients with diabetes. Advanced glycation end-products (AGEs) resulting from hyperglycemia are a complex and heterogeneous group of compounds that accumulate in the plasma and tissues in diabetic patients. They are responsible for both endothelial dysfunction and diabetic vasculopathy. The aim of this study was to investigate the cytotoxicity of AGEs on pancreatic islet microvascular endothelial cells. The mechanism underlying the apoptotic effect of AGEs in pancreatic islet endothelial cell line MS1 was explored. The results showed that AGEs significantly decreased MS1 cell viability and induced MS1 cell apoptosis in a dose-dependent manner. AGEs dose-dependently increased the expressions of cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase in MS1 cells. Treatment of MS1 cells with AGEs also resulted in increased nuclear factor (NF)-κB-p65 phosphorylation and cyclooxygenase (COX)-2 expression. However, AGEs did not affect the expressions of endoplasmic reticulum (ER) stress-related molecules in MS1 cells. Pretreatment with NS398 (a COX-2 inhibitor) to inhibit prostaglandin E2 (PGE2) production reversed the induction of cleaved caspase-3, cleaved PARP, and MS1 cell viability. Moreover, AGEs significantly increased the receptor for AGEs (RAGE) protein expression in MS1 cells, which could be reversed by RAGE neutralizing antibody. RAGE Neutralizing antibody could also reverse the induction of cleaved caspase-3 and cleaved PARP and decreased cell viability induced by AGEs. These results implicate the involvement of NF-κB-activated COX-2/PGE2 up-regulation in AGEs/RAGE-induced islet endothelial cell apoptosis and cytotoxicity. These findings may provide insight into the pathological processes within the pancreatic islet microvasculature induced by AGEs accumulation.

Preparation of SiC-Si3N4 composite refractory materials without sintering entails only low energy consumption and incurs little cost compared with traditional preparation methods. This paper investigated the effect of Al2O3 addition on bulk density, apparent porosity, linear shrinkage and oxidation resistance of as-fabricated non-sintered SiC-Si3N4 composite refractory materials. Meanwhile, the compressive and flexural strengths both before and after heat treatment were analyzed. The mechanisms of oxidation resistance and cryolite resistance of the SiC-Si3N4 composite refractory materials are discussed. Increasing amounts of Al2O3 reduced linear shrinkage but increased oxidation resistance and cryolite resistance. Moreover, compressive and flexural strengths initially increased and then decreased, with maximum values achieved at an Al2O3 addition of 8% w/w. [ABSTRACT FROM AUTHOR]

Polypropylene/montmorillonite (PP/MMT) nanocomposites were prepared by in-situ polymerization using a MMT/MgCl[SUB2]-EB Ziegler-Natta catalyst activated by triethylaluminum (TEA). The enlarged layer spacing of MMT was confirmed by X-ray wide angle diffraction (WAXD), demonstrating that MMT were intercalated by the catalyst components, X-ray photoelectron spectrometry (XPS) analysis provided that TiCl[SUB4] was mainly supported on MgCl[SUB2] instead of on the surface of MMT. The exfoliated structure of MMT layers in the PP matrix of PP/MMT composites was demonstrated by WAXD patterns and transmission electron microscopy (TEM) observation. The higher class transition temperature and higher storage patterns and transmission electron microscopy (TEM) observation. The higher class transition temperature and higher storage modulus of the PP/MMT composites in comparison with pure PP were revealed by dynamic mechanical analysis (DMA). [ABSTRACT FROM AUTHOR]

Studies have reported that the hemostatic effect of Sanguisorbae Radix(SR) is significantly enhanced after processing with charcoal. However, the standard components(tannins and gallic acid) specified in the Chinese Pharmacopeia decrease in charcoal-fried Sanguisorbae Radix(CSR), which is contrast to the enhancement of the hemostatic effect. Therefore, this study aimed to optimize the charcoal-frying process of SR based on its hemostatic efficacy and comprehensively analyze the components of SR and its processed products, thus exploring the material basis for the hemostatic effect. The results indicated that SR processed at 250 ℃ for 14 min(14-min CSR) not only complied with the description in the Chinese Pharmacopeia but also demonstrated improved blood-coagulating and blood-adsorbing effects compared with raw SR(P&lt;0.05). Moroever, 14-min CSR reduced the bleeding time in the rat models of tail snipping, liver bleeding, and muscle injury, surpassing both raw and excessively fried SR(16 min processed) as well as tranexamic acid(P&lt;0.05). Ellagitannin, ellagic acid, methyl gallate, pyrogallic acid, protocatechuic acid, Mg, Ca, Mn, Cu, and Zn contributed to the hemostatic effect of CSR over SR. Among these substances, ellagitannin, ellagic acid, Mg, and Ca had high content in the 14 min CSR, reaching(106.73±14.87),(34.86±4.43),(2.81±0.23), and(1.21±0.23) mg·g~(-1), respectively. Additionally, the color difference value(ΔE~*ab) of SR processed to different extents was correlated with the content of the aforementioned hemostatic substances. In summary, this study optimized the charcoal-frying process as 250 ℃ for 14 min for SR based on its hemostatic effect. Furthermore, ellagic acid and/or the powder chromaticity are proposed as indicators for the processing and quality control of CSR.

Coronary heart disease(CHD) is a common cardiovascular disease in clinical practice. Curcumae Rhizoma(CR), an important herbal medicine for breaking blood stasis and resolving mass, is often used for the treatment of CHD caused by blood stasis syndrome. However, the anti-CHD components, targets, and mechanism are still unclear. Therefore, in this study, the chemical components of CR were separated and identified by ultra high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS). Based on the identified components, network pharmacology analysis, including target prediction and functional enrichment, was applied to screen out the main active components against CHD, and the potential mechanism was discussed. Finally, molecular docking was performed to verify the binding between the active components and the targets. The results showed that among the 52 chemical components identified in CR, 28 were related to CHD, involving 75 core targets. The core components included(4S)-4-hydroxy-gweicurculactone, curcumadione, and curcumenone, and the core targets included phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha(PIK3 CA), mitogen-activated protein kinase 1(MAPK1), and mitogen-activated protein kinase 3(MAPK3). In summary, through the active components, such as(4S)-4-hydroxy-gweicurculactone, curcumadione, and curcumenone, CR regulates the nerve repair, vasoconstriction, lipid metabolism, and inflammatory response, thereby exerts therapeutic effect on CHD.

This study aims to study the effective substance and mechanism of Ziziphi Spinosae Semen extract in the treatment of insomnia based on serum metabolomics and network pharmacology. The rat insomnia model induced by p-chlorophenylalanine(PCPA) was established. After oral administration of Ziziphi Spinosae Semen extract, the general morphological observation, pentobarbital sodium-induced sleep test, and histopathological evaluation were carried out. The potential biomarkers of the extract in the treatment of insomnia were screened by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS) combined with multivariate analysis, and the related metabolic pathways were further analyzed. The &quot;component-target-pathway&quot; network was constructed by ultra-high performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry(UHPLC-Q-Exactive-MS/MS) combined with network pharmacology to explore the effective substances and mechanism of Ziziphi Spinosae Semen in the treatment of insomnia. The results of pentobarbital sodium-induced sleep test and histopathological evaluation(hematoxylin and eosin staining) showed that Ziziphi Spinosae Semen extract had good theraputic effect on insomnia. A total of 21 endogenous biomarkers of Ziziphi Spinosae Semen extract in the treatment of insomnia were screened out by serum metabolomics, and the metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and nicotinate and nicotinamide metabolism were obtained. A total of 34 chemical constituents were identified by UHPLC-Q-Exactive-MS/MS, including 24 flavonoids, 2 triterpenoid saponins, 4 alkaloids, 2 triterpenoid acids, and 2 fatty acids. The network pharmacological analysis showed that Ziziphi Spinosae Semen mainly acted on target proteins such as dopamine D2 receptor(DRD2), 5-hydroxytryptamine receptor 1 A(HTR1 A), and alpha-2 A adrenergic receptor(ADRA2 A) in the treatment of insomnia. It was closely related to neuroactive ligand-receptor interaction, serotonergic synapse, and calcium signaling pathway. Magnoflorine, N-nornuciferine, caaverine, oleic acid, palmitic acid, coclaurine, betulinic acid, and ceanothic acid in Ziziphi Spinosae Semen may be potential effective compounds in the treatment of insomnia. This study revealed that Ziziphi Spinosae Semen extract treated insomnia through multiple metabolic pathways and the overall correction of metabolic disorder profile in a multi-component, multi-target, and multi-channel manner. Briefly, this study lays a foundation for further research on the mechanism of Ziziphi Spinosae Semen in treating insomnia and provides support for the development of innovative Chinese drugs for the treatment of insomnia.

L~*, a~* and b~* values of prepared slices of Curcumae Rhizoma were measured by spectrophotometer. SPSS 21.0 was used for discriminant analysis to establish the color range and mathematical prediction model of prepared slices of Curcumae Rhizoma. The values of L~*, a~* and b~* of kwangsiensis ranged from 58.09-62.40, 4.53-5.66 and 23.61-24.29, while the values of L~*, a~* and b~* of phaeocaulis were between 64.02-70.71,-0.89-4.13 and 44.59-54.52, respectively. The values of L~*, a~* and b~* of wenyujin were 68.55-70.99,-0.11-1.47 and 28.26-32.19, respectively. The mathematical prediction model was proved to be able to realize 100% identification of Curcumae Rhizome of different origins through original and cross validation and external samples validation. A dual wavelength HPLC was established; the contents of 9 sesquiterpenoids and 3 Curcumae Rhizomes were determined simultaneously; and the contents of Curcumae Rhizome of different origins were determined. The results showed that kwangsiensis had higher contents of neocurdione, β-elemene and isocurcumaenol, phaeocaulis curcumin, furadienone, demethoxycurcumin and curcumin; and wenyujin mainly contained curdione, furadienes and guimarone. Pearson correlation analysis on L~*, a~*, b~* value and content of 12 components showed that curcumin, furadienone, demethoxycurcumin and curcumin had a significant positive correlation with b~* value(P&lt;0.01). There was a significant negative correlation between neocurdione, β-elemene and isocurcumaenol and L~* value(P&lt;0.01). Curdione, furadienes and guimarone were significantly correlated with L~* value(P&lt;0.01),indicating that the appearance co-lor of Curcumae Rhizoma could reflect the change of the content of the internal components. This study provided reference for the rapid recognition of Curcumae Rhizoma and the establishment of quality evaluation system.

There are many chemical components in the volatile oil of Dictamni Cortex. The complex network relationship of &quot;component-target-disease&quot; can be revealed by using the network pharmacology method, and the mechanism of the efficacy of Dictamni Cortex can be revealed. In this study, we used Swiss Target Prediction database to predict the target of action, STRING database to build protein interaction network, and Cytoscape software to build &quot;component-target-disease&quot; network. The results showed that the antibacterial, anti-inflammatory and antiallergic effects of Dictamni Cortex were closely related to the components of thymol methyl ether, elemenol, anethole, and the related targets of each component were cross-linked to play a multi-target pharmacodynamic role. This study laid a foundation for the study of the effective substance basis and quality control evaluation of the Dictamni Cortex, and provided a scientific basis for further revealing its mechanism.

Aim: To assess neovascularization within human carotid atherosclerotic soft plaques in patients with ischemic stroke., Methods: Eighty-one patients with ischemic stroke and 95 patients without stroke who had soft atherosclerotic plaques in the internal carotid artery were studied. The thickest soft plaque in each patient was examined using contrast-enhanced ultrasound. Time-intensity curves were collected from 5 s to 3 min after contrast injection. The neovascularization within the plaques in the internal carotid artery was evaluated using the ACQ software built into the scanner by 2 of the experienced investigators who were blinded to the clinical history of the patients., Results: Ischemic stroke was present in 7 of 33 patients (21%) with grade I plaque, in 14 of 51 patients (28%) with grade II plaque, in 26 of 43 patients (61%) with grade III plaque, and in 34 of 49 patients (69%) with grade IV plaque (P < 0.001 comparing grade IV plaque with grade I plaque and with grade II plaque and P = 0.001 comparing grade III plaque with grade I plaque and with grade II plaque). Analysis of the time intensity curves revealed that patients with ischemic stroke had a significantly higher intensity of enhancement (IE) than those without ischemic stroke (P < 0.01). The wash-in time (WT) of plaque was significantly shorter in stroke patients (P < 0.05). The sensitivity and specificity for IE in the plaque were 82% and 80%, respectively, and for WT were 68% and 74%, respectively. There was no significant difference in the peak intensity or time to peak between the 2 groups., Conclusion: This study shows that the higher the grade of plaque enhancement, the higher the risk of ischemic stroke. The data suggest that the presence of neovascularization is a marker for unstable plaque.

Objective: To evaluate the effects of San'ao decoction (SAD) and its analogous prescriptions (APs), compounds of traditional Chinese herbal medicine for asthma, on airway inflammation in mice with respiratory syncytial virus (RSV)- and ovalbumin (OVA)-induced asthma., Methods: A total of 110 mice were randomly divided into control group, untreated group, dexamethasone (DM) group, small-dose SAD (SAD-S) group, large-dose SAD (SAD-L) group, AP I-S group, AP I-L group, AP II-S group, AP II-L group, AP III-S group, and AP III-L group. The asthma model was reproduced by sensitization with multipoint intraperitoneal injection of OVA, followed by repeated inhalation of OVA combined with intranasal instillation of RSV. Cells in bronchoalveolar lavage fluid (BALF) were counted and classified. The supernatant of the BALF was used for detecting the contents of interleukin-4 (IL-4), interleukin-5 (IL-5) and interferon-gamma (IFN-gamma) by enzyme-linked immunosorbent assay. Pathological changes in lung tissue were observed by hematoxylin and eosin staining and the scores of pathological changes were also calculated to determine the degree of inflammation., Results: Compared with the control group, the amounts of lymphocytes, eosinophils, neutrophils in BALF in the untreated group were increased significantly (P<0.01); the changes of lung histopathology in the untreated group were much more serious, and the content of IFN-gamma was sharply decreased, while the contents of IL-4 and IL-5 were significantly increased (P<0.05). The counts of eosinophils in BALF of the treated groups all decreased obviously (P<0.01) as compared with the untreated group. The count of the neutrophils in BALF of the AP II-L group was obviously lower than that in the untreated group (P<0.01). Most of Chinese herbal formulas and DM could increase the level of IFN-gamma, and decrease the level of IL-4. All concentrations of the APs and SAD could decrease the level of IL-5 as compared with the untreated group, especially of the AP II-L and AP I-L (P<0.05, P<0.01)., Conclusion: SAD and its APs had some therapeutic effects on RSV-induced asthma in mice. Among the formulas, AP II has a better therapeutic efficacy in treatment of asthma by decreasing the amount of neutrophils.