Does low-intensity pulsed ultrasound accelerate phasic calcium phosphate ceramic-induced bone formation?

PURPOSE: Low-intensity pulsed ultrasound (LIPUS) has been used to stimulate the healing of the fresh fracture, delayed union, and non-union in both animal and clinical studies. Besides, biphasic calcium phosphate ceramic (BCP) is a promising biomaterial for bone repair as it shows favorable biocompatibility, osteoinduction, and osteoconduction. However, scarcity is known about the combined effect of LIPUS and BCP on bone formation. METHODS: The combined effect of LIPUS and BCP was studied in a beagle model. Twelve dogs were used. BCP granules without any additions were implanted into bilateral erector spinae muscles. One side is the BCP group, while the counterlateral side is LIPUS + BCP group. Histological and histomorphometric analyses, and quantitative real-time polymerase chain reaction were evaluated. RESULTS: Compared with BCP alone, the LIPUS + BCP showed no advantages in early bone formation. Furthermore, the Notch signaling pathway-related mRNA has no significant difference between the two groups. CONCLUSIONS: The preliminary results showed that the BCP, which has intrinsic osteoinduction nature, was an effective and promising material. However, LIPUS has no enhanced effect in BCP induced ectopic bone formation. Furthermore, LIPUS has no effect on the Notch signaling pathway. Whether costly LIPUS could be used in combination with BCP should be a rethink.

Does low-intensity pulsed ultrasound accelerate phasic calcium phosphate ceramic-induced bone formation?

Purpose: Low-intensity pulsed ultrasound (LIPUS) has been used to stimulate the healing of the fresh fracture, delayed union, and non-union in both animal and clinical studies. Besides, biphasic calcium phosphate ceramic (BCP) is a promising biomaterial for bone repair as it shows favorable biocompatibility, osteoinduction, and osteoconduction. However, scarcity is known about the combined effect of LIPUS and BCP on bone formation. Methods: The combined effect of LIPUS and BCP was studied in a beagle model. Twelve dogs were used. BCP granules without any additions were implanted into bilateral erector spinae muscles. One side is the BCP group, while the counterlateral side is LIPUS + BCP group. Histological and histomorphometric analyses, and quantitative real-time polymerase chain reaction were evaluated. Results: Compared with BCP alone, the LIPUS + BCP showed no advantages in early bone formation. Furthermore, the Notch signaling pathway-related mRNA has no significant difference between the two groups. Conclusions: The preliminary results showed that the BCP, which has intrinsic osteoinduction nature, was an effective and promising material. However, LIPUS has no enhanced effect in BCP induced ectopic bone formation. Furthermore, LIPUS has no effect on the Notch signaling pathway. Whether costly LIPUS could be used in combination with BCP should be a rethink.

Investigation and influencing factors about well-being level of elderly chronic patients during COVID-19 postpandemic period in Beijing.

ABSTRACT: The Corona Virus Disease 2019 (COVID-19) pandemic has huge impacts on the world, including human health and economic decline. The COVID-19 has severe infectivity, especially the elderly with chronic diseases will cause various complications after infection and accelerate the disease process. In addition, COVID-19 will also affect their mental health. Therefore, the mental health of elderly patients with chronic diseases cannot be ignored. The aim of this study was to investigate the well-being level of elderly people with chronic disease during COVID-19 postpandemic period in Beijing and analysis related influencing factors, so as to provide a basis for improving the well-being level of elderly chronic patients during the postpandemic period.Elderly patients with chronic diseases who met the inclusion criteria in 5 different administrative regions in Beijing were selected to carry out a questionnaire survey. The contents of the questionnaire included general data, the Memorial University of Newfoundland Happiness scale and the awareness situation of the COVID-19 pandemic. A total of 500 questionnaires were distributed by WeChat and 486 valid questionnaires were collected. The t test and one-way analysis of variance were used to compare Memorial University of Newfoundland Happiness scores between 2 or more groups, multiple linear regression analysis was used to conduct multiple factor analysis to explore the related factors about well-being level of elderly chronic patients.A total of 109 cases (22.43%) were evaluated high well-being level, 319 cases (65.64%) were evaluated moderate well-being level and 58 cases (11.93%) were evaluated low well-being according to the Memorial University of Newfoundland Happiness (MUNSH) scores rating. The multiple linear regression indicated that the education level, number of chronic diseases, medical expenses, frequency of children's visits, taking care of grandchildren or not, and group activity frequency significantly affected the well-being of patients with chronic diseases during COVID-19 postpandemic period in Beijing (P < .05).Most elderly patients with chronic diseases had moderate or above sense of well-being during postpandemic period, but we should still pay attention to the mental health of those elderly chronic patients with low education level, much comorbidity, more medical expenses, less visits by children, not take care of grandchildren and never participate in group activities.

Zinc-Doping Induces Evolution of Biocompatible Strontium-Calcium-Phosphate Conversion Coating on Titanium to Improve Antibacterial Property.

Implant-associated infections (IAI) remains a common and devastating complication in orthopedic surgery. To reduce the incidence of IAI, implants with intrinsic antibacterial activity have been proposed. The surface functionalization and structure optimization of metallic implants can be achieved by surface modification using the phosphate chemical conversion (PCC) technique. Zinc (Zn) has strong antibacterial behavior toward a broad-spectrum of bacteria. Herein, Zn was incorporated into strontium-calcium-phosphate (SrCaP) coatings on titanium (Ti) via PCC method, and the influence of its doping amount on the phase, microstructure, antibacterial activity, and biocompatibility of the composite coating was researched. The results indicated that traces of Zn doping produced grain refinement of SrCaP coating with no significant effect on its phase and surface properties, while a higher Zn content induced its phase and microstructure transformed into zinc-strontium-phosphate (SrZn2(PO4)2). SrCaP-Zn1 and SrCaP-Zn4 represented trace and high content Zn-doped coatings, respectively, which exhibited a similar bacterial attachment for a short time but showed inhibition of biofilm formation after continuous incubation up to 24 h. The killing rates of SrCaP-Zn1 coating for Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) reached 61.25% and 55.38%, respectively. While that data increased to 83.01% and 71.28% on SrCaP-Zn4 coating due to the more-releasing Zn2+. Furthermore, in vitro culture of MC3T3-E1 cells proved that the Zn-doped coatings also possessed excellent biocompatibility. This study provides a new perception for the phase and microstructural optimization of phosphate coatings on implant surfaces, as well as fabricating promising coatings with excellent biocompatibility and antimicrobial properties against IAI.

Comprehensive Evaluation of 24 Red Raspberry Varieties in Northeast China Based on Nutrition and Taste.

Red raspberry is a kind of fruit with high nutritional values. To evaluate the comprehensive quality of 24 red raspberry varieties in Northeast China, physicochemical properties, bioactive compounds and sensory characteristics were measured, followed by principal component analysis (PCA) and cluster analysis (CA). Altogether, eight important property indexes for processing attributes were selected out using PCA, including titratable acidity (TAC), sugar-acid ratio (SAR), pH, length, diameter, weight, sucrose and citric acid. Six individual sugars, including l-rhamnose monohydrate, fructose, glucose, sucrose, maltose and d-trehalose anhydrous, as well as eight organic acids, including oxalic acid, tartaric acid, malic acid, α-ketoglutaric acid, lactic acid, citric acid, fumaric acid and succinic acid, were identified in red raspberry. The two main clusters according to individual sugar, organic acids and SAR indicated that varieties including 'European red', 'DNS9', 'Bulgaskc', 'Canby' and 'Samodiva' were suitable for fresh-eating or processing to juice or other products directly because they had suitable SAR; other varieties with relatively low SAR were unsuitable for fresh-eating and need to adjust their excessive sour taste during processing.

Optimization of the Administration Strategy for the Armed Oncolytic Adenovirus ZD55-IL-24 in Both Immunocompromised and Immunocompetent Mouse Models.

ZD55-IL-24 is an armed oncolytic adenovirus similar but superior to ONYX-015. Virotherapeutic strategies using ZD55-IL-24 have been demonstrated to be effective against several cancer types. However, it is unclear whether the traditional administration strategy is able to exert the maximal antitumor efficacy of ZD55-IL-24. In this study, we sought to optimize the administration strategy of ZD55-IL-24 in both A375-bearing immunocompromised mouse model and B16-bearing immunocompetent mouse model. Although the underlying antitumor mechanisms are quite different, the obtained results are similar in these two mouse tumor models. We find that the antitumor efficacy of ZD55-IL-24 increases as injection times increase in both of these two models. However, no obvious increase of efficacy is observed as the dose of each injection increases. Our further investigation reveals that the administration strategy of sustained ZD55-IL-24 therapy can achieve a better therapeutic effect than the traditional administration strategy of short-term ZD55-IL-24 therapy. Furthermore, there is no need to inject every day; every 2 or 3 days of injection achieves an equivalent therapeutic efficacy. Finally, we find that the sustained rather than the traditional short-term ZD55-IL-24 therapy can synergize with anti-PD-1 therapy to reject tumors in B16-bearing immunocompetent mouse model. These findings suggest that the past administration strategy of ZD55-IL-24 is in fact suboptimal and the antitumor efficacy can be further enhanced through administration strategy optimization. This study might shed some light on the development of clinically applicable administration regimens for ZD55-IL-24 therapy.

Enhanced anti-melanoma efficacy through a combination of the armed oncolytic adenovirus ZD55-IL-24 and immune checkpoint blockade in B16-bearing immunocompetent mouse model.

Although the recent treatment in melanoma through the use of anti-PD-1 immunotherapy is successful, the efficacy of this approach remains to be improved. Here, we explore the feasibility of combination strategy with the armed oncolytic adenovirus ZD55-IL-24 and PD-1 blockade. We find that combination therapy with localized ZD55-IL-24 and systemic PD-1 blockade leads to synergistic inhibition of both local and distant established tumors in B16-bearing immunocompetent mouse model. Our further mechanism investigation reveals that synergistic therapeutic effect is associated with marked promotion of tumor immune infiltration and recognition in both local and distant tumors as well as spleens. PD-1 blockade has no obvious effect on promotion of tumor immune infiltration and recognition. Localized therapy with ZD55-IL-24, however, can help PD-1 blockade to overcome the limitation of relatively low tumor immune infiltration and recognition. This study provides a rationale for investigation of such combination therapy in the clinic.

The armed oncolytic adenovirus ZD55-IL-24 eradicates melanoma by turning the tumor cells from the self-state into the nonself-state besides direct killing.

ZD55-IL-24 is similar but superior to the oncolytic adenovirus ONYX-015, yet the exact mechanism underlying the observed therapeutic effect is still not well understood. Here we sought to elucidate the underlying antitumor mechanism of ZD55-IL-24 in both immunocompetent and immunocompromised mouse model. We find that ZD55-IL-24 eradicates established melanoma in B16-bearing immunocompetent mouse model not through the classic direct killing pathway, but mainly through the indirect pathway of inducing systemic antitumor immunity. Inconsistent with the current prevailing view, our further results suggest that ZD55-IL-24 can induce antitumor immunity in B16-bearing immunocompetent mouse model in fact not due to its ability to lyse tumor cells and release the essential elements, such as tumor-associated antigens (TAAs), but due to its ability to put a "nonself" label in tumor cells and then turn the tumor cells from the "self" state into the "nonself" state without tumor cell death. The observed anti-melanoma efficacy of ZD55-IL-24 in B16-bearing immunocompetent mouse model was practically caused only by the viral vector. In addition, we also notice that ZD55-IL-24 can inhibit tumor growth in B16-bearing immunocompetent mouse model through inhibiting angiogenesis, despite it plays only a minor role. In contrast to B16-bearing immunocompetent mouse model, ZD55-IL-24 eliminates established melanoma in A375-bearing immunocompromised mouse model mainly through the classic direct killing pathway, but not through the antitumor immunity pathway and anti-angiogenesis pathway. These findings let us know ZD55-IL-24 more comprehensive and profound, and provide a sounder theoretical foundation for its future modification and drug development.

Improving Cycling Behaviors of Dockless Bike-Sharing Users Based on an Extended Theory of Planned Behavior and Credit-Based Supervision Policies in China.

Motivating users' civilized cycling plays a significant role in alleviating the troubles of dockless bike-sharing programs (DBSPs) and promoting the sustainable development of bike-sharing organizations. Based on the theory of planned behavior (TPB) and observed practices in China, this study develops a theoretical framework to examine how attitudes (ATT), subjective norms (SN), perceived behavioral control (PBC), and personal norms (PN) motivate users' civilized cycling behavior through civilized cycling intentions. Furthermore, the moderating effect of perceived policy effectiveness (PPE) between users' civilized cycling intention and their actual behavior is tested. Using structural equation model-multiple group analysis (SEM-MGA) for a sample of 874 valid questionnaire responses in Beijing and Shanghai, China, our results reveal that (1) ATT, PBC, and PN are positively related to both users' civilized cycling intentions and their actual behavior, while SN positively affect users' civilized cycling intention only; (2) users' civilized cycling intentions mediate the relationship between the four influencing factors and their actual behavior; and (3) PPE plays a moderating role for the effect of users' civilized cycling intentions on their actual civilized cycling behavior. Our results indicate that the four influencing factors can encourage users' civilized cycling behavior, especially when civilized cycling intention exists. Policies like credit-based supervision mechanisms could promote users' civilized-cycling intentions, which could then be transformed into actual behavior.

MicroRNA-802 plays a tumour suppressive role in tongue squamous cell carcinoma through directly targeting MAP2K4.

OBJECTIVES: Tongue squamous cell carcinoma (TSCC) is the most common oral tumours. MicroRNAs play crucial roles in many cell processes including cell viability, development, apoptosis, migration and invasion. The role of miR-802 in the TSCC is still unknown. MATERIALS AND METHODS: The miR-802 expression in TSCC tissues and cell lines was determined by quantitative real-time polymerase chain reaction. CCK-8 assay was performed to measure the cell viability, while the cell invasion assay was used to determine the cell invasion. Dual-luciferase reporter and western blot were used to confirm the potential target gene of miR-802. RESULTS: In our study, we demonstrated that miR-802 expression was downregulated in TSCC tissues and cell lines. Elevated expression of miR-802 suppressed the TSCC cell viability and invasion. Moreover, enforced expression of miR-802 increased the expression of E-cadherin, while suppressed the expression of N-cadherin, Snail and Vimentin in the TSCC cell. In addition, we identified the mitogen-activated protein kinase 4 (MAP2K4) as a direct target gene of miR-802 in the TSCC cell. We also demonstrated that the expression of MAP2K4 was higher in the TSCC tissues than that in the adjacent normal tissues. Furthermore, the expression level of MAP2K4 was inversely associated with the expression of miR-802 in TSCC tissues. We also demonstrated that the MAP2K4 expression was upregulated in TSCC cell lines. Elevated expression of miR-802 inhibited TSCC cell viability and invasion through inhibiting MAP2K4 expression. CONCLUSIONS: Our data revealed that miR-802 played as a tumour suppressor gene and might act as a therapeutic target in TSCC patients.

Cells responding to surface structure of calcium phosphate ceramics for bone regeneration.

Surface structure largely affects the inductive bone-forming potential of calcium phosphate (CaP) ceramics in ectopic sites and bone regeneration in critical-sized bone defects. Surface-dependent osteogenic differentiation of bone marrow stromal cells (BMSCs) partially explained the improved bone-forming ability of submicron surface structured CaP ceramics. In this study, we investigated the possible influence of surface structure on different bone-related cells, which may potentially participate in the process of improved bone formation in CaP ceramics. Besides BMSCs, the response of human brain vascular pericytes (HBVP), C2C12 (osteogenic inducible cells), MC3T3-E1 (osteogenic precursors), SV-HFO (pre-osteoblasts), MG63 (osteoblasts) and SAOS-2 (mature osteoblasts) to the surface structure was evaluated in terms of cell proliferation, osteogenic differentiation and gene expression. The cells were cultured on tricalcium phosphate (TCP) ceramics with either micron-scaled surface structure (TCP-B) or submicron-scaled surface structure (TCP-S) for up to 14 days, followed by DNA, alkaline phosphatase (ALP) and quantitative polymerase chain reaction gene assays. HBVP were not sensitive to surface structure with respect to cell proliferation and osteogenic differentiation, but had downregulated angiogenesis-related gene expression (i.e. vascular endothelial growth factor) on TCP-S. Without additional osteogenic inducing factors, submicron-scaled surface structure enhanced ALP activity and osteocalcin gene expression of human (h)BMSCs and C2C12 cells, favoured the proliferation of MC3T3-E1, MG63 and SAOS-2, and increased ALP activity of MC3T3-E1 and SV-HFO. The results herein indicate that cells with osteogenic potency (either osteogenic inducible cells or osteogenic cells) could be sensitive to surface structure and responded to osteoinductive submicron-structured CaP ceramics in cell proliferation, ALP production or osteogenic gene expression, which favour bone regeneration. Copyright © 2017 John Wiley & Sons, Ltd.

Controlling Growth and Osteogenic Differentiation of Osteoblasts on Microgrooved Polystyrene Surfaces.

Surface topography is increasingly being recognized as an important factor to control the response of cells and tissues to biomaterials. In the current study, the aim was to obtain deeper understanding of the effect of microgrooves on shape and orientation of osteoblast-like cells and to relate this effect to their proliferation and osteogenic differentiation. To this end, two microgrooved polystyrene (PS) substrates, differing in the width of the grooves (about 2 µm and 4 µm) and distance between individual grooves (about 6 µm and 11 µm, respectively) were fabricated using a combination of photolithography and hot embossing. MG-63 human osteosarcoma cells were cultured on these microgrooved surfaces, with unpatterned hot-embossed PS substrate as a control. Scanning electron- and fluorescence microscopy analyses showed that on patterned surfaces, the cells aligned along the microgrooves. The cells cultured on 4 µm-grooves / 11 µm-ridges surface showed a more pronounced alignment and a somewhat smaller cell area and cell perimeter as compared to cells cultured on surface with 2 µm-grooves / 6 µm-ridges or unpatterned PS. PrestoBlue analysis and quantification of DNA amounts suggested that microgrooves used in this experiment did not have a strong effect on cell metabolic activity or proliferation. However, cell differentiation towards the osteogenic lineage was significantly enhanced when MG-63 cells were cultured on the 2/6 substrate, as compared to the 4/11 substrate or unpatterned PS. This effect on osteogenic differentiation may be related to differences in cell spreading between the substrates.

MicroRNA-137 suppresses tongue squamous carcinoma cell proliferation, migration and invasion.

OBJECTIVES: Tongue squamous cell carcinoma (TSCC) is the most frequent type of oral malignancy. Increasing evidence has shown that miRNAs play key roles in many biological processes such as cell development, invasion, proliferation, differentiation, metabolism, apoptosis and migration. MATERIALS AND METHODS: qRT-PCR analysis was performed to measure miR-137 expression. CCK-8 analysis, cell colony formation, wound-healing analysis and invasion were performed to detect resultant cell functions. The direct target of miR-137 was labelled and measured by luciferase assay and Western blotting. RESULTS: We demonstrated that expression of miR-137 was downregulated in TSCC tissues compared to matched normal ones. miR-137 expression was downregulated in TSCC lines (SCC4, SCC1, UM1 and Cal27) compared to the immortalized NOK16B cell line and normal oral keratinocytes in culture (NHOK). In addition, we have shown that miR-137 expression was epigenetically regulated in TSCCs. Overexpression of miR-137 suppressed TSCC proliferation and colony formation. Ectopic expression of miR-137 promoted expression of the epithelial biomarker, E-cadherin, and inhibited the mesenchymal biomarker, N-cadherin, as well as vimentin and Snail expression, indicating that miR-137 suppressed TSCC epithelial-mesenchymal transition (EMT). We also showed that ectopic expression of miR-137 inhibited TSCC invasion and migration. In addition, we identified SP1 as a direct target gene of miR-137 in SCC1 cells. SP1 overexpression rescued inhibitory effects exerted by miR-137 on cell proliferation and EMT. CONCLUSIONS: These results indicate that miR-137 acted as a tumour suppressor in TSCC by targeting SP1.

Independent effects of the chemical and microstructural surface properties of polymer/ceramic composites on proliferation and osteogenic differentiation of human MSCs.

UNLABELLED: Within the general aim of finding affordable and sustainable regenerative solutions for damaged and diseased tissues and organs, significant efforts have been invested in developing synthetic alternatives to natural bone grafts, such as autografts. Calcium phosphate (CaP) ceramics are among widely used synthetic bone graft substitutes, but their mechanical properties and bone regenerative capacity are still outperformed by their natural counterparts. In order to improve the existing synthetic bone graft substitutes, it is imperative to understand the effects of their individual properties on a biological response, and to find a way to combine the desired properties into new, improved functional biomaterials. To this end, we studied the independent effects of the chemical composition and surface microstructure of a poly(lactic acid)/hydroxyapatite (PLA/HA) composite material on the proliferation and osteogenic differentiation of clinically relevant bone marrow-derived human mesenchymal stromal cells (hMSCs). While the molecular weight of the polymer and presence/absence of the ceramic phase were used as the chemical variables, a soft embossing technique was used to pattern the surfaces of all materials with either pits or pillars with identical microscale dimensions. The results indicated that, while cell morphology was affected by both the presence and availability of HA and by the surface microstructure, the effect of the latter parameter on cell proliferation was negligible. The osteogenic differentiation of hMSCs, and in particular the expression of bone morphogenetic protein 2 (BMP-2) and osteopontin (OP) were significantly enhanced when cells were cultured on the composite based on low-molecular-weight PLA, as compared to the high-molecular-weight PLA-based composite and the two pure polymers. The OP expression on the low-molecular-weight PLA-based composite was further enhanced when the surface was patterned with pits. Taken together, within this experimental set up, the individual effect of the chemistry, and in particular of the presence of CaP, was more pronounced than the individual effect of the surface microstructure, although their combined effects were, in some cases, synergistic. The approach presented here opens new routes to study the interactions of biomaterials with the biological environment in greater depths, which can serve as a starting point for developing biomaterials with improved bioactivity. STATEMENT OF SIGNIFICANCE: The aim of the this study was to obtain insight into independent effects of the chemical composition and surface microstructure of a poly(lactic acid)/hydroxyapatite (PLA/HA) composite material on the morphology, proliferation and osteogenic differentiation of clinically relevant bone marrow-derived human mesenchymal stromal cells (hMSCs). While the need for synthetic alternatives for natural bone in bone regenerative strategies is rapidly increasing, the clinical performance of synthetic biomaterials needs to be further improved. To do this successfully, we believe that a better understanding of the relationship between a property of a material and a biological response is imperative. This study is a step forward in this direction, and we are therefore convinced that it will be of interest to the readers of Acta Biomaterialia.

Characteristics of participants' and caregivers' influence on non-response in a cross-sectional study of dementia in an older population.

OBJECTIVE: The issue of non-response in dementia epidemiological studies, which may result in the underestimation of the prevalence of dementia, has attracted little attention. We aimed to explore the causes and related factors of non-response in a dementia survey among Chinese veterans. METHODS: A two-phase, cross-sectional study investigated the prevalence of dementia and mild cognitive impairment in Chinese veterans aged ≥ 60 years. We collected the socio-demographic data and prior medical history, evaluated the health status of veterans and their caregivers, assessed the cognitive status of veterans, and evaluated the care burden of caregivers by Caregiver Burden Inventory (CBI). RESULTS: Of 9676 eligible participants, 525 (5.4%) veterans in phase 1 and 1706 (35.0%) veterans among 4875 veterans in phase 2 did not respond. Illness, hospitalization and death accounted for 63.0% and 75.5% non-response in phases 1 and 2, respectively. Non-participation in social activities, self-perceived poor health status, worsened health changes, self-reported need for life care, and history of hearing loss or glaucoma independently predicted non-response in phase 1 or 2. The heavy care burden, suggested by the higher CBI scores and self-reported health deterioration of the primary caregivers, predicted non-response in phase 1 or 2. CONCLUSIONS: The negative factors from both the participants and their caregivers independently predicted the non-response in the dementia study in an older population. Preventative strategies from the perspectives of the participants and caregivers should be developed to improve the response rates in both phases in a cross-sectional study.

Veratric Acid Inhibits LPS-Induced IL-6 and IL-8 Production in Human Gingival Fibroblasts.

Veratric acid, one of the major benzoic acid isolated from vegetables and fruits, has been reported to have anti-inflammatory activity. The purpose of this study was to investigate the anti-inflammatory effects of veratric acid on lipopolysaccharide (LPS)-induced inflammatory response in human gingival fibroblasts (HGFs). HGFs were pretreated with veratric acid 1 h before LPS stimulation. The productions of IL-6 and IL-8 were detected by ELISA. The expression of iNOS, COX-2, PI3K, AKT, and NF-κB were detected by western blotting. The results showed that veratric acid inhibited LPS-induced IL-6 and IL-8 production, as well as iNOS and COX-2 expression. Veratric acid also inhibited LPS-induced NF-κB activation. In addition, veratric acid was found to suppress LPS-induced PI3K and AKT phosphorylation. In conclusion, the anti-inflammatory mechanism of veratric acid is due to its ability to inhibit PI3K/Akt/NF-κB signaling pathway.

Development of Highly Functional Biomaterials by Decoupling and Recombining Material Properties.

Development of functional biomaterials by a design-driven approach is described, whereby individual properties are first decoupled to investigate their sole effects on a biological process. Following this investigation, they are recombined in such a way that the overall performance and applicability of the biomaterial is improved. This is in contrast to classical, processing-driven biomaterials development where the properties of a material are mainly determined by the possibilities of the technique used to produce it.

[Effect of zero-balanced ultrafiltration and modified ultrafiltration on pulmonary function after cardiac surgery in infants].

OBJECTIVE: To determine the protective effect of zero-balanced ultrafiltration and modified ultrafiltration on infants' pulmonary function after cardiac surgery. METHODS: Sixty infants with congenital heart diseases were randomly divided into 3 groups: a zero-balanced ultrafiltration group (Z group), a modified ultrafiltration group (M group) and a zero-balanced ultrafiltration with modified ultrafiltration group (Z+M group). Oxygenation index (OI), difference of alveoli-arterial oxygen pressure (P(A-α)O2), static lung compliance (Cstat), and airway resistance (Raw) were measured before caridopulmonary bypass (CPB, T1), 20 minutes after the CPB (T2), 2 h after the operation (T3), 6 h after the operation (T4) and 12 h after the operation (T5). The time of mechanical ventilation was also monitored. RESULTS: After the CPB, OI and Cstat in all groups decreased significantly, while Raw and P(A-α)O2 increased significantly. At T3, T4 and T5, OI and Cstat in the Z+M group were significantly higher than those in the Z group and the M group (P<0.05), Raw and P(A-α)O2 in the Z+M group were significantly lower than those in the Z group and the M group (P<0.05). The ventilation time in the Z+M group was significantly shorter than that in the Z group and the M group (P<0.05). CONCLUSION: Zero-balanced ultrafiltration and modified ultrafiltration can effectively promote the pulmonary function after cardiac surgery in infants.

Construction of the Chinese Veteran Clinical Research (CVCR) platform for the assessment of non-communicable diseases.

BACKGROUND: Based on the excellent medical care and management system for Chinese veterans, as well as the detailed medical documentation available, we aim to construct a Chinese Veteran Clinical Research (CVCR) platform on non-communicable diseases (NCDs) and carry out studies of the primary disabling NCDs. METHODS: The Geriatric Neurology Department of Chinese People's Liberation Army General Hospital and veterans' hospitals serve as the leading and participating units in the platform construction. The fundamental constituents of the platform are veteran communities. Stratified typical cluster sampling is adopted to recruit veteran communities. A cross-sectional study of mental, neurological, and substance use (MNS) disorders are performed in two stages using screening scale such as the Mini-Mental State Examination and Montreal cognitive assessment, followed by systematic neuropsychological assessments to make clinical diagnoses, evaluated disease awareness and care situation. RESULTS: A total of 9 676 among 277 veteran communities from 18 cities are recruited into this platform, yielding a response rate of 83.86%. 8 812 subjects complete the MNS subproject screening and total response rate is 91.70%. The average participant age is (82.01±4.61) years, 69.47% of veterans are 80 years or older. Most participants are male (94.01%), 83.36% of subjects have at least a junior high school degree. The overall health status of veterans is good and stable. The most common NCD are cardiovascular disorders (86.44%), urinary and genital diseases (73.14%), eye and ear problems (66.25%), endocrine (56.56%) and neuro-psychiatric disturbances (50.78%). CONCLUSION: We first construct a veterans' comprehensive clinical research platform for the study of NCDs that is primarily composed of highly educated Chinese males of advanced age and utilize this platform to complete a cross-sectional national investigation of MNS disorders among veterans. The good and stable health condition of the veterans could facilitate the long-term follow-up studies of NCDs and provide prospective data to the prevention and management of NCDs.

Synthesis, in vitro antimycobacterial and antibacterial evaluation of IMB-070593 derivatives containing a substituted benzyloxime moiety.

A series of novel IMB-070593 derivatives containing a substituted benzyloxime moiety and displaying a remarkable improvement in lipophilicity were synthesized and evaluated for their in vitro antimycobacterial and antibacterial activity. Our results reveal that the target compounds 19a-m have considerable Gram-positive activity (MIC: <0.008-32 µg/mL), although they are generally less active than the reference drugs against the Gram-negative strains. In particular, compounds 19h, 19j, 19k and 19m show good activity (MICs: <0.008-4 µg/mL) against all of the tested Gram-positive strains, including ciprofloxacin (CPFX)- and/or levofloxacin (LVFX)-resistant MSSA, MRSA and MSSE. Moreover, compound 19l (MIC: 0.125 µg/mL) is found to be 2-4 fold more active than the parent IMB070593, CPFX and LVFX against M. tuberculosis H37Rv ATCC 27294.