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We aimed to investigate the association between polysocial risk score (PsRS), an estimator of individual-level exposure to cumulative social risks, and incident type 2 diabetes in the UK Biobank study.This study includes 319,832 participants who were free of diabetes, cardiovascular disease and cancer at baseline in the UK Biobank study. The PsRS was calculated by counting the 12 social determinants of health from three social risk domains (namely socioeconomic status, psychosocial factors, and neighbourhood and living environment) that had a statistically significant association with incident type 2 diabetes after Bonferroni correction. A healthy lifestyle score was calculated using information on smoking status, alcohol intake, physical activity, diet quality and sleep quality. A genetic risk score was calculated using 403 SNPs that showed significant genome-wide associations with type 2 diabetes in people of European descent. The Cox proportional hazards model was used to analyse the association between the PsRS and incident type 2 diabetes.During a median follow-up period of 8.7 years, 4427 participants were diagnosed with type 2 diabetes. After adjustment for major confounders, an intermediate PsRS (4-6) and high PsRS (≥7) was associated with higher risks of developing type 2 diabetes with the HRs being 1.38 (95% CI 1.26, 1.52) and 2.02 (95% CI 1.83, 2.22), respectively, compared with those with a low PsRS (≤3). In addition, an intermediate to high PsRS accounted for approximately 34% (95% CI 29, 39) of new-onset type 2 diabetes cases. A healthy lifestyle slightly, but significantly, mitigated PsRS-related risks of type 2 diabetes (pA higher PsRS was related to increased risks of type 2 diabetes. Adherence to a healthy lifestyle may attenuate elevated diabetes risks due to social vulnerability. Genetic susceptibility and disadvantaged social status may act synergistically, resulting in additional risks for type 2 diabetes.

The fat-to-muscle mass ratio (FMR), which integrates the antagonistic effects of fat and muscle mass, has been proposed as a useful indicator to assess disease risk independent of overall obesity. However, little is known about the association between FMR and dementia risk. We aimed to prospectively investigate the sex-specific associations between total and regional FMR and incident dementia.A total of 491 420 participants (223 581 men and 267 839 women; mean age 56.7 ± 8.2 and 56.3 ± 8.0 years old, respectively) free of dementia at baseline from the UK Biobank were included. Fat mass and muscle mass were measured using a bioelectrical impedance assessment device. Cox regression analyses were used to examine the associations of total and regional FMR with incident all-cause dementia, Alzheimer's disease (AD) and vascular dementia (VD). The shape of the associations of the continuous scale of FMR and incident dementia were examined using restricted cubic spline analysis.During a median 8.65 years of follow-up, we documented 2 225 incident all-cause dementia cases, including 836 AD and 468 VD cases. There was an L-shaped association between whole body FMR and all-cause dementia risk in both sexes after adjusting body mass index (BMI) and other covariates (P for non-linear0.001 in men and women), where all-cause dementia risk decreased steeply with increasing FMR and levelled off at around the medians (0.35 in men, 0.61 in women) with a hazard ratio (HR) of 0.78 (95% CI: 0.64, 0.96; P = 0.019) and 0.60 (0.47, 0.77;0.001) per 1 standard deviation (SD) increase in men and women, respectively. Compared with other body parts, FMR of the leg showed the strongest inverse associations [HR (95% CI; P) per 1 SD below the medians: 0.60 (0.48, 0.75;0.001); 0.61 (0.47, 0.79;0.001) in men and women, respectively]. Specifically, the inverse associations of whole body FMR on all-cause dementia risk were significant only among participants over the age of 60 (P for trend0.001). Multivariable adjusted Cox models showed inverse associations of whole body FMR with AD in men only (P for trend = 0.003), whereas no statistically significant decrease was detected in VD among men and women.Our analyses provide strong evidence for L-shaped associations of total and regional FMR with the development of dementia among participants aged 60 years or older independent of overall obesity.

The combined effect of global warming and the heat island effect keeps the temperature of cities rising in the summer, seriously threatening the physical and mental health of urban residents. Taking the area within the Sixth Ring Road of Beijing as an example, based on Landsat remote sensing images, meteorological stations, and questionnaires, this study established a relational model between temperature and hostility and then analyzed the changes in the emotional health risk (hostility) in the study area and the mechanism of how outdoor activity duration influences hostility. Results show that: (1) the area within the Sixth Ring Road of Beijing had a higher and higher temperature from 1991 to 2020. Low-temperature areas gradually shrank, and medium- and high-temperature areas extended outwards from the center. (2) The threat of high temperature to residents' hostility gradually intensified—the sphere of influence expanded, low-risk areas quickly turned into medium-high-risk areas, and the level of hostility risk increased. Level 1 risk areas of hostility had the most obvious reduction—a 74.33% reduction in area proportion; meanwhile, Level 3 risk areas had the most significant growth—a 50.41% increase in area proportion. (3) In the first 120 min of outdoor activities under high temperature, residents' hostility was negatively correlated with outdoor activity duration; after more than 120 min, hostility became positively correlated with duration. Therefore, figuring out how temperature changes influence human emotions is of great significance to improving the living environment and health level of residents. This study attempts to (1) explore the impact of temperature changes and outdoor activity duration on hostility, (2) evaluate residents' emotional health risk levels affected by high temperature, and (3) provide a theoretical basis for the early warning mechanism of emotional health risk and the planning of healthy cities.

Summary Background & aims Plasma ceramides have been identified as novel risk factors for metabolic and cardiovascular diseases. We aimed to evaluate the effects of dietary anthocyanins on plasma ceramides and to disentangle whether the alterations in ceramides could be related with those in other cardiometabolic risk factors in the dyslipidemia. Methods In a randomized double-blinded placebo-controlled trial, 176 eligible dyslipidemia subjects were randomly assigned into four groups receiving placebo, 40, 80, or 320 mg/day anthocyanins, respectively for 12 weeks. Results A total of 169 subjects completed the study. After 12-week intervention, dietary anthocyanins dose-dependently reduced plasma concentrations of all six ceramide species in the dyslipidemia subjects (all Ptrend values Conclusions Reductions in plasma Cer 16:0 and Cer 18:0 after 12-week anthocyanin intervention were dose-dependently associated with improvements in plasma lipids and cholesterol efflux capacity in the dyslipidemia. Clinical trial registration The study was registered at ClinicalTrials.gov with the identifier No. NCT03415503.

BACKGROUND Dyslipidemia induces platelet hyperactivation and hyper-aggregation, which are linked to thrombosis. Anthocyanins could inhibit platelet function in vitro and in mice fed high-fat diets with their effects on platelet function in subjects with dyslipidemia remained unknown. This study aimed to investigate the effects of different doses of anthocyanins on platelet function in individuals with dyslipidemia. METHODS A double-blind, randomized, controlled trial was conducted. Ninety-three individuals who were initially diagnosed with dyslipidemia were randomly assigned to placebo or 40, 80, 160 or 320 mg/day anthocyanin groups. The supplementations were anthocyanin capsules (Medox, Norway). Platelet aggregation by light aggregometry of platelet-rich plasma, P-selectin, activated GPⅡbⅢa, reactive oxygen species (ROS), and mitochondrial membrane potential were tested at baseline, 6 weeks and 12 weeks. FINDINGS Compared to placebo group, anthocyanins at 80 mg/day for 12 weeks reduced collagen-induced platelet aggregation (-3.39±2.36%) and activated GPⅡbⅢa (-8.25±2.45%) (P

Coenzyme Q10 (CoQ10) had shown promising effects in improving the lipid and glycemic profile in dyslipidemic individuals in our previous work, but little is known about how it affects high-density lipoprotein (HDL) function in patients with dyslipidemia. The aim of this study was to explore the effects of CoQ10 supplementation on HDL function in people with dyslipidemia.A 24-wk, randomized, double-blind, placebo-controlled trial was conducted in 101 people with dyslipidemia. All patients were randomized into the CoQ10 group (120 mg/d, n = 51) or the placebo group (n = 50). High-density lipoprotein-mediated cholesterol efflux capacity (CEC), HDL inflammatory index (HII), and HDL intrinsic oxidation were measured at baseline, 12 wk, and 24 wk.CoQ10 supplementation for 24 wk significantly improved HDL-mediated CEC (mean change, 1.21±2.44 versus -0.12±2.94; P = 0.014) and reduced HII (mean change, -0.32±0.58 versus -0.05±0.49, P = 0.014) compared with placebo. However, there was no significant difference in the effect of CoQ10 on HDL intrinsic oxidation between the two groups after 24 wk (P = 0.290). A positive correlation was found between the changes in CEC and HDL cholesterol in the CoQ10 group (r, 0.30; P = 0.032). Furthermore, we also found that the improved HDL functions were more obvious in elderly, female, or non-obese individuals, which indicated a specific population that benefits most from CoQ10 intervention.This study suggested that supplementation of CoQ10 for 24 wk can significantly improve HDL-mediated CEC and antiinflammatory function of HDL in patients with dyslipidemia.

Increased oxidative stress and platelet apoptotic in middle-aged and elderly adults are important risk factors for atherosclerotic cardiovascular disease (ASCVD). Therefore, it is of great significance to control the oxidative stress and platelet apoptosis in middle-aged and elderly adults. Previous acute clinical trials have shown that water-soluble tomato concentrate (WSTC) from fresh tomatoes could exert antiplatelet benefits after 3 h or 7 h, but its effects on platelet apoptosis and oxidative stress are still unknown, especially in healthy middle-aged and elderly adults. This current study aimed to examine the efficacies of WSTC on platelet apoptosis and oxidative stress in healthy middle-aged and elderly adults via a randomized double-blinded placebo-controlled crossover clinical trial (10 weeks in total). A total of 52 healthy middle-aged and elderly adults completed this trial. The results showed that WSTC could increase the serum total antioxidant capacity levels (p < 0.05) and decrease the serum malondialdehyde levels (p < 0.05) after a 4-week WSTC supplementation in healthy middle-aged and elderly adults. Platelet endogenous reactive oxygen species generation (p < 0.05), mitochondrial membrane potential dissipation (p < 0.05) and phosphatidylserine exposure (p < 0.05) were attenuated. In addition, our present study also found that WSTC could inhibit platelet aggregation and activation induced by collagen or ADP after intervention (p < 0.05), while having no effects on adverse events (p > 0.05). The results suggest that WSTC can inhibit oxidative stress and its related platelet apoptosis, which may provide a basis for the primary prevention of WSTC in ASCVD.

Saponins derived from Panax notoginseng root are widely used as herbal medicines and dietary supplements due to their wide range of health benefits. However, the effects of those from Panax notoginseng flowers (PNF) on platelet function and thrombus formation remain largely unknown. Using a series of platelet function assays, we found that G-Rb2 and G-Rd2, among the ten PNF saponin monomers, significantly inhibited human platelet aggregation and activation induced by adenosine diphosphate (ADP) in vitro. The 50% inhibitory concentration (IC50) of G-Rb2 and G-Rd2 against ADP-induced platelet aggregation was 85.5 ± 4.5 μg mL-1 and 51.4 ± 4.6 μg mL-1, respectively. Mechanistically, G-Rb2 and G-Rd2 could effectively modulate platelet P2Y12-mediated signaling by up-regulating cAMP/PKA signaling and down-regulating PI3K/Akt/Erk1/2 signaling pathways. Co-incubation of the P2Y12 antagonist cangrelor with either G-Rb2 or G-Rd2 did not show significant additive inhibitory effects. G-Rb2 and G-Rd2 also substantially suppressed thrombus growth in a FeCl3-induced murine arteriole thrombosis model in vivo. Interestingly, G-Rd2 generally exhibited more potent inhibitory effects on platelet function and thrombus formation than G-Rb2. Thus, our data suggest that PNF-derived G-Rb2 and G-Rd2 effectively attenuate platelet hyperactivity through modulating signaling pathways downstream of P2Y12, which indicates G-Rb2 and G-Rd2 may play important preventive roles in thrombotic diseases.

For a patient with a unilateral orbital defect, an esthetic orbital prosthesis plays an essential role in enhancing quality of life. This technique describes the combined use of a facial scanner and an intraoral scanner to acquire the digital scan for the design and fabrication of an orbital prosthesis. The method results in an esthetic prosthesis with accurate skin texture reproduction.

Sea buckthorn seed oil (SBSO) has been used as a functional food in the prevention of heart diseases. The present study investigates the effects of SBSO on blood cholesterol and the gut microbiota in hypercholesterolemia hamsters. Four groups of hamsters (n = 8 each) were given one of four diets, namely a non-cholesterol control diet (NCD), a high-cholesterol control diet (HCD) containing 0.1% cholesterol, and an HCD diet with sea buckthorn seed oil replacing 50% lard (SL) or replacing 100% lard (SH). Feeding SL and SH diets could reduce blood total cholesterol by 20-22%. This was accompanied by the down-regulation of the gene expression of acyl-CoA:cholesterol acyltransferase 2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP-binding cassette transporter8 (ABCG8). SBSO supplementation also increased the production of intestinal short-chain fatty acids and fecal outputs of neutral sterols. Metagenomic analysis demonstrated that feeding SL and SH diets could favorably modulate the relative abundance of Bacteroidales_S24-7_group, Ruminococcaceae, and Eubacteriaceae. It was therefore concluded that SBSO was effective in reducing blood cholesterol in hypercholesterolemic hamsters via increasing intestinal cholesterol excretion and promoting the growth of SCFA-producing bacteria.

Analyzing sleep quality and sleep structure in patients with patent foramen ovale (PFO) complicated with obstructive sleep apnea (OSA) and the interaction between OSA and PFO in sleep. We compared patients with PFO complicated with OSA, patients with simple PFO, and controls. Pittsburgh Sleep Quality Index was used to compare sleep quality and polysomnography was used to compare sleep structure of the three groups. Compared with the control group (n = 62), PFO with OSA (n = 48) and simple PFO (n = 61) groups had more frequent occurrence of poor sleep quality (χ2 = 89.901; p < 0.001). These two groups also showed decreased sleep efficiency (p < 0.010), lower percentages of REM sleep, and reduced N3 sleep (p < 0.050). The N2 sleep was prolonged (p < 0.010). The nocturnal lowest SpO2 was lower and the oxygen desaturation index was higher (p < 0.50). Compared with the simple PFO group, the poor sleep quality was more frequent in the PFO with OSA group; sleep latency (p < 0.001) was prolonged; wake after sleep onset (p < 0.001) and arousal times (p = 0.031) were increased; and sleep micro-arousal index (p = 0.037), periodic leg movement index (p = 0.024), and apnea hypopnea index (p < 0.001) were higher in the PFO with OSA group. Patients with PFO and OSA have poor sleep quality with changes in sleep stage and high occurrence rate of sleep disorders. OSA further deteriorates sleep quality and alters sleep structure in patients with PFO.

Trimethylamine

Hypercholesterolemia, as one of the major risk factors in development of cardiovascular diseases, is of mounting prevalence worldwide in recent years. Many nutraceuticals and phytochemical supplements serve as a promising complementary therapy in the management of hypercholesterolemia. Among them, spicy foods have attracted special attention. Plasma lipid-lowering activity of garlic, ginger, and turmeric have been well-studied in both humans and animals. Consumption of either 3 g/day of ginger or 2 g/day of curcumin for over 4 weeks effectively reduced blood cholesterol in hypercholesterolemia subjects. However, effects of chili and black peppers on blood cholesterol are studied little clinically. The present review is to summarize the findings of recent studies on the efficacy and mechanism of spicy foods and their primary bioactive components in management of hypercholesterolemia from preclinical studies to clinical trials.

This study investigated the effect of konjac glucomannan (KGM) of different molecular weight on fecal microflora against antibiotic disturbance. KGM (~1.8 × 107 Da) was partially hydrolysed with trifluoroacetic acid (TFA) for 10 and 60 min to KGM1 (~2.1 × 104 Da) and KGM2 (7413 Da), respectively. The acid treatment caused significant reduction of intrinsic viscosity, average molecular weight (MW) and particle size of KGM, but brought limited change to the molecular structure. Low-MW KGM2 showed the most significant effect on fecal microflora in the presence of two common antibiotics (ampicillin and clindamycin), by increasing the relative abundance of Bifidobacteriaceae while decreasing the proportion of Enterobacteriaceae. Additionally, both the native and acid-treated KGM counteracted the adverse influence of antibiotics on the production of short chain fatty acids. The results have demonstrated the effect of KGM on gut microbiota with antibiotic disturbance.

Previous studies have shown that short-chain fatty acids (SCFAs) are capable of decreasing plasma cholesterol. However, the relative plasma-cholesterol-lowering activity of individual SCFAs and the underlying mechanisms by which SCFAs decrease plasma cholesterol remain largely unknown. The present study was done to compare the plasma-cholesterol-lowering potencies of four common SCFAs with 2-5 carbons and to investigate their interactions with gene expressions of key regulatory factors involved in cholesterol metabolism. For 6 weeks, five groups of male Golden hamsters were fed either a control high-cholesterol diet (HCD) or one of the four experimental HCDs containing 0.5 mol of acetate (Ac), propionate (Pr), butyrate (Bu), or valerate (Va) per kilogram of the diet. The results showed that Ac, Pr, and Bu significantly reduced plasma total cholesterol (TC) by 24, 18, and 17% (P < 0.05), respectively. All four SCFAs could decrease non-HDL cholesterol (non-HDL-C) and the non-HDL-C/HDL-C ratio. The addition of Ac, Pr, or Bu into the diet significantly promoted fecal excretion of bile acids by 121, 113, or 120% (P < 0.05), respectively, and upregulated the gene expressions of sterol-regulatory-element-binding protein 2 (SREBP2), low-density-lipoprotein receptor (LDLR), and cholesterol 7α-hydroxylase (CYP7A1) in the liver. It was concluded that SCFAs with 2-4 carbons (Ac, Pr, and Bu) are more hypocholesterolemic than Va, which has 5 carbons, via enhancing fecal excretion of bile acids and promoting the hepatic uptake of cholesterol from the blood.

Little is known about which currently available a priori dietary indexes provide best guidance for reducing cardiometabolic risk factors (CMRF) among hyperlipidemic patients. This study was designed to compare the associations between four a priori dietary indexes, including Diet Balance Index (DBI-16), Chinese Healthy Eating Index (CHEI), Mediterranean Diet Score (MDS) and Dietary Approaches to Stop Hypertension (DASH) and CMRF among hyperlipidemic patients. A total of 269 participants were enrolled into the cross-sectional study. DBI-16, CHEI, MDS, and DASH scores were calculated using established methods. CMRF was measured using standard methods. DBI-total scores (DBI-TS) were inversely associated with triglyceride concentrations and TC:HDL-C ratio, and positively associated with HDL-C and ApoA1 concentrations (all p &lt, 0.05), while the results for DBI-low bound scores (DBI-LBS) were opposite. DBI-high bound scores (DBI-HBS) and DASH scores were positively and inversely associated with glucose concentrations, respectively (both p &lt, 0.05). Higher diet quality distance (DQD) was positively associated with higher TC, LDL-C and ApoB concentrations, and TC:HDL-C and LDL-C:HDL-C ratios, and lower HDL-C and ApoA1 concentrations and ApoA1:ApoB ratio (all p &lt, 0.05). CHEI scores were inversely associated with triglyceride concentrations (p = 0.036). None of the dietary indexes was associated with blood pressures. DBI-16 provided most comprehensive evaluations of the overall diet quality and balance for optimizing cardiometabolic health among hyperlipidemic individuals.

Scope Platelet integrin αIIbβ3 is the key mediator of atherothrombosis. Supplementation of coenzyme Q10 (CoQ10), a fat-soluble molecule that exists in various foods, exerts protective cardiovascular effects. This study aims to investigate whether and how CoQ10 acts on αIIbβ3 signaling and thrombosis, the major cause of cardiovascular diseases. Methods and results Using a series of platelet functional assays in vitro, it is demonstrated that CoQ10 reduces human platelet aggregation, granule secretion, platelet spreading, and clot retraction. It is further demonstrated that CoQ10 inhibits platelet integrin αIIbβ3 outside-in signaling. These inhibitory effects are mainly mediated by upregulating cAMP/PKA pathway, where CoQ10 stimulates the A2A adenosine receptor and decreases phosphodiesterase 3A phosphorylation. Moreover, CoQ10 attenuates murine thrombus growth and vessel occlusion in a ferric chloride (FeCl3 )-induced thrombosis model in vivo. Importantly, the randomized, double-blind, placebo-controlled clinical trial in dyslipidemic patients demonstrates that 24 weeks of CoQ10 supplementation increases platelet CoQ10 concentrations, enhances the cAMP/PKA pathway, and attenuates αIIbβ3 outside-in signaling, leading to decreased platelet aggregation and granule release. Conclusion Through upregulating the platelet cAMP/PKA pathway, and attenuating αIIbβ3 signaling and thrombus growth, CoQ10 supplementation may play an important protective role in patients with risks of cardiovascular diseases.

Dentin is a suitable scaffold for tooth tissue engineering and can provide the appropriate combinations and concentrations of bioactive proteins to accommodate odontogenic cells. Freeze drying is a possible strategy to treat dentin because it ensures long-term stability of biopharmaceutical products and can increase the stability of dentin for improved distribution and storage. We hypothesized that freeze-dried dentin matrix (FDDM) constitutes a novel bioinstructive scaffold for tooth tissue engineering.This study used a modified technique to prepare an FDDM that preserved the mechanical and biological properties of dentin. The compression resistance and microhardness of FDDM were determined. Similarly, various biological characteristics, including cell morphology, cell proliferation, collagen secretion, alkaline phosphatase activity, and gene and protein expression, were investigated. To assess the inductive capacity of FDDM in vivo, FDDM and human dental pulp stem cell (DPSC) sheets were subcutaneously implanted in the dorsal pockets of nude mice. At 8 weeks postimplantation, the transplants were removed and histologically studied.The results show that FDDM has mechanical and biological characteristics similar to those of dentin (P.05). DPSCs cultured on FDDM and dentin showed superior attachment, growth, viability, and collagen secretion capacity but decreased mineral capability compared with DPSCs cultured with alpha minimum essential medium or hydroxyapatite (P.05). The histologic results show that FDDM, which is similar to dentin, supported dentin/pulplike tissue regeneration in vivo as shown by the related expression levels of dentin markers, such as dentin sialoprotein and alkaline phosphatase.These results suggest that FDDM constitutes a novel superior scaffold for tooth tissue engineering.

Health benefits of soybean germ oil have not yet been fully explored. The present study examined the blood cholesterol-lowering activity of soybean germ oil and the underlying mechanisms in hypercholesterolemic hamsters. Forty hamsters were randomly assigned into five groups and fed a non-cholesterol diet, a high cholesterol diet and one of three high cholesterol diets containing 0.50% cholestyramine, 4.75% soybean germ oil, and 9.50% soybean germ oil, respectively, for 6 weeks. The result showed that soybean germ oil significantly decreased plasma cholesterol by 18.5-31.5%, which was accompanied by 28.3-62.7% increase in excretion of fecal neutral sterols and bile acids. The effect was mediated by down-regulation of intestinal Niemann-Pick C1-like 1 protein (NPC1L1) and up-regulation of liver cholesterol-7α-hydroxylase (CYP7A1). We concluded that soybean germ oil favorably modulated the blood cholesterol concentration by inhibiting cholesterol absorption through inhibiting gene expression of NPC1L1 and by enhancing bile acid excretion via promoting gene expression of CYP7A1.

Resveratrol (RSV) is a dietary polyphenol with well-documented cardio-protective activity, but its effects on blood cholesterol levels remain to be established. Due to its poor bioavailability, tissue accumulation of RSV is extremely low except for that in the small intestine. In the present study, we aimed to investigate the dose-dependent effects of RSV on blood cholesterol levels and the involvement of small intestine in the cholesterol-lowering impacts of RSV. Mice were administrated with RSV at various doses with high-fat diet (HFD) or high-fat and high-cholesterol diet (HCD) for 12 weeks. The fecal neutral sterol contents were analyzed, and intestinal perfusion test was performed. An enteric barrier model using Caco-2 cells was established. We observed that RSV reduced blood cholesterol levels in a dose-dependent manner in mice fed with HFD or HCD. Further investigation revealed that RSV administration increased the bile acid pool size but did not affect cholesterol consumption or de novo cholesterol synthesis. Interestingly, RSV promoted trans-intestinal cholesterol excretion (TICE) by 2-fold in the intestinal perfusion test. In addition, RSV upregulated the expressions of ATP-binding cassette sub-family G member 5 or 8 (Abcg5/8) and ATP-binding cassette sub-family B member 1a or 1b (Abcb1a/b) by up to 8 times in the duodenum mucosa but not in the liver. RSV also significantly downregulated the expression of intestinal Niemann-Pick C1-Like 1 (Npc1l1). Knock-down of liver X receptor alpha (LXRα) but not Sirt1 by siRNA significantly blocked RSV-induced cholesterol excretion in Caco-2 cells. In conclusion, RSV could decrease circulating cholesterol levels through enhancing TICE and limiting cholesterol absorption via selective activation of intestinal LXRα.

Craniofacial deformities caused by congenital defects or trauma remain challenges for clinicians, whereas current surgical interventions present limited therapeutic outcomes. Injection of bone marrow-derived mesenchymal stem cells (BMSCs) into the defect is highly desirable because such a procedure is microinvasive and grafts are more flexible to fill the lesions. However, preventing hypertrophic transition and morphological contraction remain significant challenges. We have developed an “all host derived” cell transplantation system composed of chondrocyte brick (CB)-enriched platelet-rich plasma (P) gel and BMSCs (B). Without exogenous biomaterials or growth factors, such grafts regenerate cartilage efficiently and present great clinical promise. In immunodeficient mice, we compared performance of BMSCs and BMSCs lacking angiogenic potential in CB-B-P constructs and followed the cartilage maturation process by histology, immunostaining, micro-computed tomography, and protein analysis. We determined that angiogenesis occurred quickly inside rudimentary cartilage derived from CB-B-P constructs after implantation, which improved tissue survival, tissue growth, and production of chondrogenic signals from chondrocytes. In contrast, silencing angiogenic potential of BMSCs led to poor chondrogenesis accompanied by necrosis. Chondrocyte bricks merged rapidly with angiogenesis, which constituted an enclosed chondrogenic niche and effectively inhibited runt-related transcription factor-2-dependent hypertrophic transition of BMSCs as well as endochondral ossification; progressive chondrogenic differentiation of BMSCs resulted in vascularization regression, thus favoring persistent chondrogenesis and effectively augmenting nasal cartilage. In conclusion, these findings provided a novel, efficient approach to regenerating cartilage tissues in vivo. Chondrocyte bricks mixed with P provide transient vascularization and a persistently chondrogenic microenvironment for BMSCs; this provides a mini-invasive approach for craniofacial cartilage reconstruction.

Xi Chen,1 Shizhu Bai,1 Bei Li,2 Huan Liu,1 Guofeng Wu,1 Sha Liu,3 Yimin Zhao1 1State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics, 2State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Oral Diseases, Center for Tissue Engineering, School of Stomatology, 3Department of Plastic and Reconstructive Surgery, Xijing Hospital, The Fourth Military Medical University, Shaanxi, People’s Republicof China Introduction: Periodontitis is a chronic infectious disease and is the major cause of tooth loss and other oral health issues around the world. Periodontal tissue regeneration has therefore always been the ultimate goal of dentists and researchers. Existing fabrication methods mainly focused on a top–down tissue engineering strategy in which several drawbacks remain, including low throughput and limited diffusion properties resulting from a large sample size. Gelatin methacrylate (GelMA) is a kind of photocrosslinkable and biocompatible hydrogel, with the capacities of enabling cell encapsulation and regeneration of functional tissues. Here, we developed a novel method to fabricate GelMA/nanohydroxylapatite (nHA) microgel arrays using a photocrosslinkable strategy. The viability, proliferation, and osteogenic differentiation and in vivo osteogenesis of human periodontal ligament stem cells (hPDLSCs) encapsulated in microgels were evaluated. The results suggested that such microgels provide great potential for periodontal tissue repair and regeneration. Methods: Microgel arrays were fabricated by blending different weight ratios of GelMA and nHA. hPDLSCs were encapsulated in GelMA/nHA microgels of various ratios for a systematic evaluation of cell viability, proliferation, and osteogenic differentiation. In vivo osteogenesis in nude mice was also studied. Results: The GelMA/nHA microgels exhibited appropriate microarchitecture, mechanical strength, and surface roughness, thus enabling cell adhesion and proliferation. Additionally, the GelMA/nHA microgels (10%/2% w/v) enhanced the osteogenic differentiation of hPDLSCs by elevating the expression levels of osteogenic biomarker genes, such as ALP, BSP, OCN, and RUNX2. In vivo ectopic transplantation results showed that GelMA/nHA microgels (10%/2% w/v) increased mineralized tissue formation with abundant vascularization, compared with the 1%, 3%, and the pure GelMA group. Conclusion: The GelMA/nHA microgels (10%/2% w/v) facilitated hPDLSCs viability, proliferation, and osteogenic differentiation in vitro and further promoted new bone formation in vivo, suggesting that the GelMA/nHA microgels (10%/2% w/v) provide great potential for periodontal tissue regeneration. Keywords: periodontal ligament stem cells, gelatin methacrylate, nanohydroxyapatite, microgel array, differentiation, periodontal tissue regeneration

Numerous preclinical and clinical studies have focused on the periodontal regenerative functions of enamel matrix derivative (EMD), a heat-treated preparation derived from enamel matrix proteins (EMPs) of developing porcine teeth. In this study, periodontal ligament (PDL) stem cells (PDLSCs) were isolated, and the effects of EMD on the extracorporeal induction process and the characteristics of PDLSC sheets were investigated for their potential as a more effective stem-cell therapy. EMD-enhanced cell sheets could be induced by complete medium supplemented with 50 μg/mL vitamin C and 100 μg/mL EMD. The EMD-enhanced cell sheets appeared thicker and more compact than the normal PDLSC sheets, demonstrated more layers of cells (3-7 layers), secreted richer extracellular matrix (ECM), showed varying degrees of increases in mRNA expression of periodontal tissue-specific genes (COL I, POSTN), calcification-related genes (RUNX2, OPN, OCN) and a cementum tissue-specific gene (CAP), and possessed a better mineralization ability in terms of osteogenic differentiation in vitro. These EMD-enhanced cell sheets may represent a potential option for stem-cell therapy for PDL regeneration.

This study investigated whether the anthocyanin cyanidin-3-O-β-glucoside (Cy-3-g) could affect platelet apoptosis and proplatelet formation in vitro. Thrombin-stimulated or resting human platelets and Meg-01 megakaryocytes were incubated with Cy-3-g (0, 0.5, 5, or 50 μM). We found that the percentage of the platelet mitochondrial membrane potential treated with 5 and 50 μM Cy-3-g was significantly higher than control (15.50% ± 3.24% and 29.77% ± 4.06% versus 2.76% ± 1.33%, respectively; P0.05). Treatment with 5 and 50 μM Cy-3-g significantly increased phosphatidylserine exposure compared with control (40.56% ± 10.53% and 76.62% ± 8.28% versus 15.43% ± 3.93%, respectively; P0.05). Moreover, Cy-3-g significantly increased the expression of Bax, Bak, and cytochrome c while markedly decreasing Bcl-xL and Bcl-2 expression as well as stimulating caspase-3, caspase-9, caspase-8, Bid, and gelsolin cleavage in thrombin-activated platelets in a dose-dependent manner ( P0.05). However, no significant differences were observed in the apoptosis of resting platelets when treated with Cy-3-g ( P0.05). Furthermore, Cy-3-g significantly ( P0.05) enhanced cell viability (50 μM versus control, 1.34 ± 0.01 versus 0.35 ± 0.02), the number of colony-forming unit-megakaryocytes (50 μM versus control, 38 ± 3 versus 8 ± 3), CD41 expression (50 μM versus control, 96.80% ± 2.55% versus 25.57% ± 2.86%), DNA ploidy (16N) (50 μM versus control, 19.73% ± 2.34% versus 4.42% ± 1.96%), and proplatelet formation (50 μM versus control, 27.5% ± 3.77% versus 7.67% ± 2.25%) in Meg-01 cells. In conclusion, Cy-3-g promotes activated platelet apoptosis and enhances megakaryocyte proliferation, differentiation, and proplatelet formation in vitro.

Summary Background & aims The results of randomized controlled trials in relation to the effect of regular black tea consumption on serum cholesterol concentration were inconsistent. We aimed to investigate and quantify the effect of black tea consumption on serum concentrations of total, LDL and HDL cholesterol. Methods We systematically searched and identified relevant literatures in PubMed, Scopus and the Cochrane Library. Inclusion and exclusion of studies, data extraction, quality assessment and meta-analysis were conducted according to the PRISMA statement. Results Ten eligible studies with 411 participants were identified in the present meta-analysis. No significant heterogeneity was found between studies. Consumption of black tea significantly reduced LDL cholesterol concentration (−4.64 mg/dL; 95% CI: −8.99, −0.30 mg/dL; P = 0.036). No remarkable change was detected in total cholesterol (−2.04 mg/dL; 95% CI: −6.43, 2.35 mg/dL; P = 0.363) or HDL cholesterol (−1.15 mg/dL; 95% CI: −3.04, 0.75 mg/dL; P = 0.236). Subgroup analysis showed that the lowering effect on LDL cholesterol was more effective in subjects with higher cardiovascular risk. Conclusions Black tea consumption significantly lowered serum concentration of LDL cholesterol, especially in subjects with higher cardiovascular risk. Black tea intake did not impose obvious effect on serum concentrations of total and HDL cholesterol.

Periodontal disease is considered as a widespread infectious disease and the most common cause of tooth loss in adults. Attempts for developing periodontal disease treatment strategies, including drug delivery and regeneration approaches, provide a useful experimental model for the evaluation of future periodontal therapies. Recently, emerging advanced biomaterials including hydrogels, films, micro/nanofibers and particles, hold great potential to be utilized as cell/drug carriers for local drug delivery and biomimetic scaffolds for future regeneration therapies. In this review, first, we describe the pathogenesis of periodontal disease, including plaque formation, immune response and inflammatory reactions caused by bacteria. Second, periodontal therapy and an overview of current biomaterials in periodontal regenerative medicine have been discussed. Third, the roles of state-of-the-art biomaterials, including hydrogels, films, micro/nanofibers and micro/nanoparticles, developed for periodontal disease treatment and periodontal tissue regeneration, and their fabrication methods, have been presented. Finally, biological properties, including biocompatibility, biodegradability and immunogenicity of the biomaterials, together with their current applications strategies are given. Conclusive remarks and future perspectives for such advanced biomaterials are discussed.

Previous research has shown that Tartary buckwheat flour is capable of reducing plasma cholesterol. The present study was to examine the effect of rutin and Tartary buckwheat protein on plasma total cholesterol (TC) in hypercholesterolemia hamsters. In the first animal experiment, 40 male hamsters were divided into four groups fed either the control diet or one of the three experimental diets containing 8.2 mmol rutin, 8.2 mmol quercetin, or 2.5 g kg–1 cholestyramine, respectively. Results showed that only cholestyramine but not rutin and its aglycone quercetin decreased plasma TC, which suggested that rutin was not the active ingredient responsible for plasma TC-lowering activity of Tartary buckwheat flour. In the second animal experiment, 45 male hamsters were divided into five groups fed either the control diet or one of the four experimental diets containing 24% Tartary buckwheat protein, 24% rice protein, 24% wheat protein, or 5 g kg–1 cholestyramine, respectively. Tartary buckwheat protein reduced p...

The association between breastfeeding status and childhood overweight is inconclusive. The aim of the present study was to investigate the relation between exclusive breastfeeding and childhood overweight risk in children 4-5 y of age in Southeast China. Among 97,424 children enrolled between 1999 and 2009 in the Jiaxing Birth Cohort, 42,550 of them were included in the final analysis with complete records on breastfeeding status and anthropometric measurements at 4-5 y of age (48-60 mo). Overweight and being at risk of overweight were identified as a body mass index (BMI)-for-age Z-score ≥ 2 and between 1 and 2, respectively. After 4-5 y of follow-up, 4845 (11.4%) children were identified as being at risk of overweight, and 1343 (3.16%) children were overweight. Adjusting for important child and maternal characteristics, longer duration of breastfeeding was associated with lower risk of childhood overweight (P-trend = 0.009) and being at risk of overweight (P-trend < 0.001). Children exclusively breastfed for 3-5 mo and ≥6 mo had 13% (RR = 0.87; 95% CI: 0.77, 0.99) and 27% (RR = 0.73; 95% CI: 0.56, 0.95) lower risk of becoming overweight compared with children exclusively breastfed for

Fibroblasts, which play an important role in biological seal formation and maintenance, determine the long-term success of percutaneous implants. In this study, well-defined microporous structures with micropore diameters of 10–60 µm were fabricated by microelectromechanical systems and their influence on the fibroblast functionalities was observed. The results show that the microporous structures with micropore diameters of 10–60 µm did not influence the initial adherent fibroblast number, however, those with diameters of 40 and 50 µm improved the spread, actin stress fiber organization, proliferation and fibronectin secretion of the fibroblasts. The microporous structures with micropore diameters of 40–50 µm may be promising for application in the percutaneous part of an implant.

BACKGROUND The aim of this study was to investigate the association between T950C (rs2073617) and G1181C (rs2073618) polymorphisms of the osteoprotegerin gene (OPG) and the susceptibility of peri-implantitis in the Chinese Han population. MATERIAL AND METHODS 110 patients with peri-implantitis and 116 healthy persons from the Chinese Han population were included in this study using a case-control design; rs2073617 and rs2073618 in OPG were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The linkage disequilibrium (LD) and haplotype analysis were performed with Haploview software. Hardy-Weinberg equilibrium (HWE) was assessed in the control group based on the genotype distributions of OPG polymorphisms. The genotype, allele, and haplotype distribution differences between the case and control groups were analyzed by chi-square test, and the relative risk of PD was expressed by odds ratio (OR) and 95% confidence interval (CI). RESULTS The study results showed that people carrying the CC genotype of rs2073618 were more likely to have peri-implantitis than GG genotype carriers (OR=2.18, 95% CI=1.03-4.62, p=0.04). In addition, patients with the C allele had 1.47 times the risk of suffering from peri-implantitis (OR=1.47, 95% CI=1.01-2.13, p=0.04), but not rs2073617 polymorphism. The G-C haplotype frequency of rs2073618-rs2073617 in OPG was significantly correlated to the increased susceptibility of peri-implantitis (OR=2.27, 95% CI=1.20-4.30). CONCLUSIONS OPG rs2073618 polymorphism may be related to the risk of peri-implantitis, but not rs2073617. Moreover, haplotype is also a non-ignorable risk factor.

Rationale: Although intrathecal opioid infusion has been used for decades for the treatment of severe pain, myoclonus as one of the complications of this therapeutic modality is now beginning to be recognized more. Patients concerns: Here, we report three patients who developed myoclonus after dose adjustment in intrathecal drug delivery system for the treatment of refractory cancer pain. Diagnosis: Spinal myoclonus is a sudden, brief, shock-like muscle contractions originating from the central nervous system.[1] In our cases, it occurred after opioid administration via intrathecal delivery system with no abnormality found in laboratory or imaging examinations. Interventions: Spinal myoclonus can be treated effectively by reducing the dose or infusion rate as described in case 1, or changing from an intrathecal to systemic administration in case 2, or correcting infusion and bolus parameters mistakes in case 3. Outcomes: All patients recovered quickly after stopping or decreasing the intrathecal drug infusion. Lessons: Prevention is more important than treatment as for spinal myoclonus. Pain management teams should be aware of this distressing complication. Dose of intrathecal drugs should not exceed the recommended maximal daily doses by guidelines and patient education is important for successful intrathecal analgesic therapy.

Periodontal regeneration involves the restoration of at least three unique tissues: cementum, periodontal ligament tissue (PDL) and alveolar bone tissue. Here, we first isolated human PDL stem cells (PDLSCs) and jaw bone mesenchymal stem cells (JBMSCs). These cells were then induced to form cell sheets using an ascorbic acid-rich approach, and the cell sheet properties, including morphology, thickness and gene expression profile, were compared. Platelet-rich fibrin (PRF) derived from human venous blood was then fabricated into bioabsorbable fibrin scaffolds containing various growth factors. Finally, the in vivo potential of a cell-material construct based on PDLSC sheets, PRF scaffolds and JBMSC sheets to form periodontal tissue was assessed in a nude mouse model. In this model, PDLSC sheet/PRF/JBMSC sheet composites were placed in a simulated periodontal space comprising human treated dentin matrix (TDM) and hydroxyapatite (HA)/tricalcium phosphate (TCP) frameworks. Eight weeks after implantation, the PDLSC sheets tended to develop into PDL-like tissues, while the JBMSC sheets tended to produce predominantly bone-like tissues. In addition, the PDLSC sheet/PRF/JBMSC sheet composites generated periodontal tissue-like structures containing PDL- and bone-like tissues. Further improvements in this cell transplantation design may have the potential to provide an effective approach for future periodontal tissue regeneration.

Associations of folic acid supplementation with risk of preterm birth (PTB) and small-for-gestational-age (SGA) birth were unclear for the Chinese populations. The aim of the present study was to investigate the associations in a large Chinese prospective cohort study: the Jiaxing Birth Cohort. In the Jiaxing Birth Cohort, 240 954 pregnant women visited local clinics or hospitals within their first trimester in Southeast China during 1999–2012. Information on anthropometric parameters, folic acid supplementation and other maternal characteristics were collected by in-person interviews during their first visit. Pregnancy outcomes were recorded during the follow-up of these participants. Multinomial logistic regression was used to examine the association of folic acid supplementation with pregnancy outcomes. The prevalence of folic acid supplementation was 24·9 % in the cohort. The prevalence of PTB and SGA birth was 3·48 and 9·2 %, respectively. Pre-conceptional folic acid supplementation was associated with 8 % lower risk of PTB (relative risk (RR) 0·92; 95 % CI 0·85, 1·00; P=0·04) and 19 % lower risk of SGA birth (RR 0·81; 95 % CI 0·70, 0·95; P=0·008), compared with non-users. Higher frequency of pre-conceptional folic acid use was associated with lower risk of PTB (Ptrend=0·032) and SGA birth (Ptrend=0·046). No significant association between post-conceptional initiation of folic acid supplementation and either outcome was observed. In conclusion, the present study suggests an association between pre-conceptional, but not post-conceptional, folic acid supplementation and lower risk of PTB and SGA birth in the Jiaxing Birth Cohort. Further research in other cohorts of large sample size is needed to replicate these findings.

Purpose The aims of this study are to introduce a novel method of 3-dimensional (3D) analysis of the face and to provide normative data of the Chinese face for surgeons. Materials and Methods Fifty men and 50 women were recruited, and a 3D stereophotogrammetry system was used to acquire their facial image data. For each subject, the image was aligned to a unified coordinate system, and coordinate values of 31 facial landmarks were collected. Mean values for each landmark were calculated within genders, and 3D models of both genders were constructed based on the mean values. Subsequently, to evaluate the sexual dimorphism, the models were superimposed. Then, to delineate the shape differences independent of size, the models were normalized and superimposed again. The application of the 3D models was also exemplified by analysis of a subject's facial deformity. Results Linear and polyhedron 3D models representing the facial shape were built for both genders. The superimposed models and the absolute differences between each landmark in both genders illustrated the sexual dimorphism of the Chinese face, and the normalized models and relative difference for each landmark also delineated the shape differences independent of size. In addition, a subject's facial deformity was evaluated by referring to the normative 3D facial models. Conclusions This study describes a new 3D analysis method for facial morphology. Three-dimensional models representing the facial shape of Chinese subjects were built, and sexual dimorphism was investigated. These would provide useful guidance for facial anthropometry and plastic surgeons in clinical practice.

We describe a technique for the design and fabrication of realistic facial prostheses using three-dimensional optical imaging and computer-aided design and manufacturing (CAD/CAM). A three-dimensional dataset of the facial surface of a patient who needed a facial prosthesis was obtained using a sensing system, and the three-dimensional image of the face was reconstructed. A decreased and thinned virtual prosthesis was designed based on the facial image and converted into a rapid prototyping wax prosthesis using a selective laser sintering technique. The rapid prototyping wax prosthesis was then dipped into melted base-plate wax which generated a layer of wax on the internal and external surfaces to record its size and thickness. The modified prosthesis was evaluated and refined, and processed to generate a realistic silicone prosthesis. Three-dimensional data acquisition using the sensing system and computer-assisted design and manufacture of the prosthesis allows us to see a whole face without damaging the soft tissues or causing discomfort to the patient or exposure to radiation. The final prosthesis was of satisfactory size, shape, and cosmetic appearance, matched the malformed area, and suited the patient's requirements.

We have developed a new way of three-dimensional and functional reconstruction of unilateral large maxillary defects by multiplanar and combined distraction osteogenesis of the zygoma, maxillary alveolar process, and hard palate. In the first procedure we started the internal curvilinear distraction osteogenesis of the left zygoma in one patient who had had a left maxillectomy to rebuild midfacial bony support. In the second procedure, the internal curvilinear distraction osteogenesis of the maxillary anterior alveolar process and straight distraction osteogenesis of the right hard palate were used to restore the posterior alveolar process and left palate. In the third procedure, the distracted zygoma and alveolar process were connected by a small local bone graft. The important lost maxillary bony architecture was re-established three-dimensionally and resulted in a natural facial appearance, normal speech and swallowing, and good foundation for chewing. This may be the first example of three-dimensional and functional reconstruction of unilateral large maxillary defects that did not require bone grafts from other anatomical areas.

Traditionally, wax or clay sculpted patterns have been used in the development of facial prostheses. New advances in rapid prototyping technologies have demonstrated significant advantages compared to more conventional techniques for fabricating facial prostheses. The use of selective laser sintering technology described in this report is an alternative approach for fabricating a wax pattern for a partial nasal prosthesis. This new approach can generate the wax nasal pattern directly and reduce labor-intensive laboratory procedures. (J Prosthet Dent 2008;100:56-60)

The objective of this study was to evaluate the biological activity enhancement of a novel glycidyl methacrylated dextran (Dex-GMA)/gelatin hybrid hydrogel containing microspheres loaded with bone morphogenetic proteins (BMP) as periodontal cell/tissue scaffold. Larger number of human periodontal ligament cells (PDLCs) attached was observed in scaffolds containing microspheres loaded with BMP when compared to those without microspheres. When osteogenic differentiation of PDLCs in such scaffolds was evaluated, the alkaline phosphatase (ALP) activity, osteocalcin content, and calcium deposition became maximum for the scaffold containing microspheres loaded with BMP, as compared with those without microspheres but adsorbed with the same amount of BMP aqueous solution, although both values were significantly higher than those in BMP-free scaffold. In addition, the osteoinduction activity was also studied following the implantation of these scaffolds into the periodontal defects of dogs in terms of histological examinations, significantly more new bone formation and periodontal ligaments regeneration were observed throughout scaffold containing microspheres. We conclude that the attachment, proliferation, and osteogenic differentiation of PDLCs can be enhanced by Dex-GMA/gelatin hydrogel scaffold containing microspheres loaded with BMP, and such scaffold is promising to enhance periodontal tissue regeneration in periodontal therapy.

Novel thermomechanical hydrogel scaffolds containing our previously prepared microspheres loaded with bone morphogenetic proteins (BMP) were successfully generated by radical crosslinking and low dose γ-irradiation from combination of two kind of biomaterials: glycidyl methacrylated dextran (Dex-GMA) and gelatin. The structure of those resulting smart hybrid hydrogels was evaluated by mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM) analyses, and as a function of the degree of Dex-GMA's substitution (DS), the proportion between Dex-GMA and gelatin, and the initial polyethyleneglycol (PEG) concentration used in the preparation of the hydrogels. The swelling and degradation properties and the temperature-sensitive drug release manner were determined by dynamic evaluation methods in vitro , and the gel content was also calculated. MIP analysis showed that by systematically altering the preparation parameters, the overall networks were clearly macroporous with pore sizes ranging from 5.6 ± 4.2 to 37.7 ± 13.7 μm. As expected, the pore size decreased as DS and initial PEG concentration increased, whereas the opposite was found for the gel content. Moreover, the porosity values ranged from 73.7 ± 12.4% up to 89.6 ±6.3%. The SEM results also showed the inter-connective pores as well as microspheres encased into their porous structure of those hydrogels. The swelling and degradation properties of the resultant hydrogels varied according to the DS of Dex-GMA and initial PEG concentration, while the proportion between Dex-GMA and gelatin had no significant influence on those characterizations. By changing the composition ratio of the two precursors, the phase transition temperature (lower critical solution temperature, LSCT) of the hydrogel scaffolds could also be adjusted to be or near the body temperature, so BMP release from microsphere–hydrogel compounds could be accordingly controlled and the release period could be varied from 18 to more than 28 days. These results demonstrated that a novel temperature-sensitive and biodegradable Dex-GMA/gelatin scaffold containing microspheres loaded with BMP could be successfully developed from both dextran- and gelatin-based biomaterials, which could promisingly satisfy the need, desire, and expectation of both self-regulated drug delivery and tissue-engineering applications.

The present case-control study explored the interaction between marine-derived n-3 long chain polyunsaturated fatty acids (n-3 LC PUFAs) and uric acid (UA) on glucose metabolism and risk of type 2 diabetes mellitus (T2DM). Two hundred and eleven healthy subjects in control group and 268 T2DM subjects in case group were included. Plasma phospholipid (PL) fatty acids and biochemical parameters were detected by standard methods. Plasma PL C22:6n-3 was significantly lower in case group than in control group, and was negatively correlated with fasting glucose (r = −0.177, p &lt, 0.001). Higher plasma PL C22:6n-3 was associated with lower risk of T2DM, and the OR was 0.32 (95% confidence interval (CI), 0.12 to 0.80, p = 0.016) for per unit increase of C22:6n-3. UA was significantly lower in case group than in control group. UA was positively correlated with fasting glucose in healthy subjects, but this correlation became negative in T2DM subjects. A significant interaction was observed between C22:6n-3 and UA on fasting glucose (p for interaction = 0.005): the lowering effect of C22:6n-3 was only significant in subjects with a lower level of UA. In conclusion, C22:6n-3 interacts with UA to modulate glucose metabolism.

The present work focused on the design of novel hydrogel microspheres based on both dextran- and gelatin-derived biomaterials, and discussed whether locally controlled delivery of IGF-I from dextran-co-gelatin hydrogel microspheres (DG-MP) was useful for periodontal regeneration enhancement. Microspheres were synthesized when gelatin was cooperating with glycidyl methacrylate (GMA) derivatized dextrans (Dex-GMA) and the resultant DG-MP with a hydrogel character of which the cross-linking density could be controlled by the degree of substitution (DS, the number of methacrylates per 100 glucopyranose residues) of Dex-GMA. In this study, three types of DG-MP (DG-MP4.7, DG-MP6.3 and DG-MP7.8) obtained from gelatin and Dex-GMA (differing in DS: 4.7, 6.3 and 7.8 respectively) were prepared and characterized by swelling and degradation properties, drug release kinetics and biological capability in promoting tissue regeneration. By swelling in aqueous positively charged IGF-I solutions, the protein could be encapsulated in DG-MP by polyionic complexation with negatively charged acidic gelatin. No obvious influence of Dex-GMA's DS on DG-MP's configuration and size was observed, and the release and degraded properties showed no significant difference between three types of DG-MP in PBS buffer either. However, high DS of Dex-GMA could lower microsphere's swelling, prolong its degraded time and minimize IGF-I burst release markedly in dextranase-containing PBS, where IGF-I release from a slow release type of microspheres (DG-MP7.8) could be maintained more than 28 days, and an effective protein release kinetics without a significant burst but a relevantly constant release after the initial burst was achieved. IGF-I in DG-MP resulted in more new bone formation in the periodontal defects within 4 or 8 weeks than IGF-I in blood clot directly did (P < 0.01). The observed newly formation of periodontal tissues including the height and percentage of new bone and new cementum on the denuded root surfaces of the furcation area in DG-MP7.8 group were more than that in other groups (P < 0.05). The adequate width of regenerative periodontal ligament (PDL), regular Sharpey's fibers and alveolar bone reconstruction could be observed only in DG-MP7.8 group. These combined results demonstrate that effective release kinetics can be realized by adjusting the DS of Dex-GMA and followed cross-linking density of DG-MP, and that locally controlled delivery of IGF-I from slow release type of DG-MP may serve as a novel therapeutic strategy for periodontal tissue regeneration.

Purpose: This study evaluated the retrospective outcomes of implant-borne dental rehabilitation in patients with mandibular defects reconstructed with a fibula free flap. Materials and Methods: Patients with segmental mandibular defects were enrolled in this cohort study. Defects in these patients were caused by oral neoplasm, trauma, and osteoradionecrosis. The patients were treated with a fibula free flap procedure and dental implant-borne prostheses between 1988 and 2010. Clinical and radiographic data were evaluated; Kaplan-Meier survival analysis and Poisson regression analysis were used to evaluate implant survival parameters. The statistical significance (α = .05) of the results was determined. Results: Seventy-four patients were selected in this study. All patients were available for continuous follow-up. Nine patients (12.1%) developed fibular graft complications postoperatively: 3 in donor sites and 6 in recipient sites. One hundred ninety-two implants were inserted, and 18 implants failed (9.3%). Overall implant survival in patients was 90.1%, 83.1%, and 69.3% after 5, 10, and 20 years, respectively. In 152 implants, probing depth (PD) ranged from 2 to 3 mm. In 31 implants, PD was greater than 5 mm. In 9 implants, PD was greater than 7 mm. The highest implant failure rates were expected for men (odds ratio [OR] = 2.948; 95% confidence interval [CI], 1.10 to 7.85; P = .031), patients receiving primary fibula free flap reconstruction (OR = 3.696; 95% CI,1.16 to 11.73; P = .027), and patients receiving radiotherapy (OR = 5.269; 95% CI, 1.40 to 19.7; P = .014). Conclusion: Fibula free flap procedures and implant-borne prostheses proved to be reliable approaches for rehabilitation of mandibular defects and oral function. The overall postoperative fibula free flap and peri-implant complication rates proved to be low. Regular follow-up visits and proper oral hygiene maintenance contributed to the long-term successful treatments.

Objective: To determine the inhibitory potency of budesonide on interleukin (IL)-4, 6 and 8, GM-CSF and TNF-α release from the human mast cell line (HMC-1) in comparison with the systemic glucocorticosteroid, dexamethasone, and H1 antagonist, desloratadine. Methods: HMC-1 was stimulated with 25 ng/ml phorbol 12- myristate 13-acetate (PMA) and 2.5 × 10−7 M ionomycin (A23187) for 6, 12 and 24 h in both the presence and absence of 10−6−10−10 M concentrations of the test drugs. Culture supernatants were collected and assayed by ELISAs. Results: HMC-1 produced substantial amounts of GM-CSF and IL-8 and smaller amounts of TNF-α, IL-4 and IL-6 after being stimulated with PMA together with A23187. Budesonide and dexamethasone had potent inhibitory effects and desloratadine had modest inhibitory effects on the release of these cytokines. Budesonide was more potent than dexamethasone at most concentrations and time points. IL-4 was the cytokine which was most susceptible to inhibition by the three tested drugs. The inhibitory effects, in some cases, were time- and concentration-dependent. Conclusion: Budesonide had a potent inhibitory effect on cytokine release from HMC-1. Its potency was greater than that of both dexamethasone and desloratadine.

Neurofibromatosis type 1, an autosomal dominant inherited disease, presents pathologic symptoms of multiple systems, including neurofibromatosis, skeletal dysplasia, café-au-lait spots in skins, and so on. A 45-year-old man with neurofibromatosis type 1 was reported in this article. The patient presented a giant neurofibroma in his head and neck, dysplasia of skull, facial bones and spinal columns, and multiple café-au-lait spots in systematic skins. Satisfactory curative effects were obtained in this case after tumor resection and prosthesis implantation.

OBJECTIVE: The aim of this study is to investigate the effects of irradiation on the proliferation and differentiation of MC3T3-E1 osteoblastic cells. METHODS: MC3T3-E1 cells were irradiated 24 h after initial seeding. Gamma-radiation was administered at 0, 4, and 8 Gy as single doses by using a (60)Co source. Cell proliferation was assessed at days 1, 3, 5, and 7 post-irradiation by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide assay. The collagen secretion of the cells was measured through sirius red staining at day 12 post-irradiation. The expressions of osteogenesis-related genes were assessed through real time fluorescence quantitative polymerase chain reaction at day 16 post-irradiation. The matrix mineralization caused by cells was evaluated through alizarin red staining at day 28 post-irradiation. RESULTS: The cells exposed to 4 Gy or 8 Gy demonstrated significantly lower proliferation rates compared with the non-irradiated group. Doses of 4 Gy or more significantly inhibited the expressions of osteogenesis-related genes (Osterix and osteocalcin). Collagen secretion and cell mineralization were significantly reduced by the 8 Gy dose. CONCLUSION: (60)Co γ-rays dose-dependently suppress the proliferation, collagen secretion, and mineralization of MC3T3-E1 cells. Furthermore, radiation seems to dose-dependently inhibit the expressions of osteogenesis-related genes of the cells.

ObjectiveWe aimed to use the meta-analysis method to assess the relationship between coffee drinking and all-cause mortality.DesignCategorical and dose–response meta-analyses were conducted using random-effects models.SettingWe systematically searched and identified eligible literature in the PubMed and Scopus databases.SubjectsSeventeen studies including 1 054 571 participants and 131 212 death events from all causes were included in the present study.ResultsSeventeen studies were included and evaluated in the meta-analysis. A U-shaped dose–response relationship was found between coffee consumption and all-cause mortality (Pfor non-linearity ConclusionsThe present meta-analysis of prospective cohort studies indicated that light to moderate coffee intake is associated with a reduced risk of death from all causes, particularly in women.

To examine the association between the timing and type of complementary feeding and childhood adiposity in Mainland China.During 1999-2009, 97 424 singletons were enrolled in the Jiaxing Birth Cohort, a population-based prospective cohort study in Southeast China. Of these children, 43 848 children provided complementary diet information and other anthropometric measurements at 1, 3, and 6 months of age and were followed up until 4-5 years of age. Obesity and overweight were identified as body mass index (BMI)-for-age z-score (SD) ≥2 and between 1 and 2, respectively.Among 40 510 children in the statistical analysis, 3.18% were overweight and 64.8% were fed complementary food before 3 months of age. Early introduction of complementary foods was associated with greater BMI z-score (P-trend.001) and higher risk of overweight (P-trend = .033). Compared with introduction of complementary foods between 4-6 months of age, before 3 months of age of introduction was associated with 11% greater risk of overweight (OR 1.11, 95% CI 1.03-1.19). No significant association between timing of complementary feeding and obesity was observed. Fish liver oil was the major type of complementary food associated with adiposity. Early introduction of fish liver oil was associated with greater BMI z-score (P.001) and greater risk of overweight (P-trend = .004).Early introduction of fish liver oil is associated with greater childhood BMI and risk of overweight in Chinese children at 4-5 years of age.