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Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) is characterized by clinical evidence of myocardial infarction with nonobstructive coronary stenosis on angiography (stenosis 50%). Studies on the effect that exercise-based cardiac rehabilitation (CR) has on outcomes in MINOCA patients are lacking. Therefore, the purpose of this study was to determine the effect of exercise-based CR on clinical outcomes in patients with MINOCA.A total of 524 participants with MINOCA were recruited in this prospective cohort study from August 2014 to October 2016 and followed for three years. We randomly divided 524 patients into an exercise-based cardiac rehabilitation group (CR+) and a control group (CR-). The CR+ group followed a home-based exercise-training program three times a week during the three years of moderate continuous training (MCT; 65%-75% of peak heart rate) on a bicycle or treadmill.After one year of follow-up, the Short Form 36 (SF-36) survey showed apparent improvement in the mean physical health score in the CR+ group compared with the CR- group (P 0.01). During the three-year follow-up, all-cause mortality occurred in 60 individuals, and major adverse cardiovascular events (MACE) happened in 136 individuals. Kaplan-Meier curves indicated a significant reduction in all-cause mortality (log-rank P 0.05) and MACE (log-rank P 0.01) in the CR+ group. A multivariate Cox regression analysis indicated that exercise-based CR was associated with a significant reduction in all-cause mortality (hazard ratio [HR] = 0.483; 95% confidence interval [CI], 0.279-0.818; P 0.01) and MACE (HR = 0.574; 95% CI, 0.403-0.827; P 0.001).A long-term exercise-based CR program was associated with superior physical health and a significant reduction in all-cause mortality and MACE in patients with MINOCA.

Background Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) accounts for approximately 5% ‐ 6% of acute myocardial infarction (AMI) patients. Anxiety symptoms are common in patients with coronary artery disease (CAD), and are associated with a poor prognosis. However, the association between anxiety and MINOCA outcomes is less clear. Hypothesis Anxiety will be associated with clinical outcomes in patients with MINOCA. Methods and Results Between November 2014 and December 2016, 620 hospitalized patients with MINOCA were recruited from a single center. Within 7 days of coronary angiography, anxiety was assessed using the Zung Self‐Rating Anxiety Scale. The primary endpoint was all‐cause mortality; secondary endpoint was any major adverse cardiovascular event (MACE). After 3 years, 87 deaths and 151 MACE had occurred. Kaplan‐Meier curves indicated the unadjusted rates of all‐cause mortality (log‐rank P = .045) and MACE (log‐rank P = .023) were significantly higher in the anxiety group compared with the control group of patients without anxiety. Multivariate Cox regression analysis showed that clinically significant anxiety was an independent prognostic factor for all‐cause mortality as well as MACE (hazard ratio [HR] = 1.547; 95% confidence interval [CI], 1.006‐2.380; P = .047; HR = 1.460; 95% CI, 1.049‐2.031; P = .025; respectively). Conclusions Anxiety is significantly and independently associated with an increased risk of all‐cause mortality and MACE in patients with MINOCA.

Background and Aims: Weight-loss diets reduce body weight and improve blood pressure control in hypertensive patients. Intermittent energy restriction (IER) is an alternative to continuous energy restriction (CER) for weight reduction. We aimed to compare the effects of IER with those of CER on blood pressure control and weight loss in overweight and obese patients with hypertension during a 6-month period.Methods: Two hundred and five overweight or obese participants (BMI 28.7 kg/m2) with hypertension were randomized to IER (5:2 diet, a very-low-calorie diet for 2 days per week, 500 kcal/day for women and 600 kcal/day for men, along with 5 days of a habitual diet) compared to a moderate CER diet (1,000 kcal/day for women and 1,200 kcal/day for men) for 6 months. The primary outcomes of this study were changes in blood pressure and weight, and the secondary outcomes were changes in body composition, glycosylated hemoglobin A1c (HbA1c), and blood lipids.Results: Of the 205 randomized participants (118 women and 87 men; mean [SD] age, 50.2 [8.9] years; mean [SD] body mass index, 28.7 [2.6]; mean [SD] systolic blood pressure, 143 [10] mmHg; and mean [SD] diastolic blood pressure, 91 [9] mmHg), 173 completed the study. The intention-to-treat analysis demonstrated that IER and CER are equally effective for weight loss and blood pressure control: the mean (SEM) weight change with IER was −7.0 [0.6] kg vs. −6.8 [0.6] kg with CER, the mean (SEM) systolic blood pressure with IER was −7 [0.7] mmHg vs. −7 [0.6] mmHg with CER, and the mean (SEM) diastolic blood pressure with IER was −6 [0.5] mmHg vs. −5 [0.5] mmHg with CER, (diet by time P = 0.62, 0.39, and 0.41, respectively). There were favorable improvements in body composition, HbA1c, and blood lipid levels, with no differences between groups. Effects did not differ according to completer analysis. No severe hypoglycemia occurred in either group during the trial.Conclusions: Intermittent energy restriction is an effective alternative diet strategy for weight loss and blood pressure control and is comparable to CER in overweight and obese patients with hypertension.Clinical Trial Registration:http://www.chictr.org.cn, identifier: ChiCTR2000040468.

The effects of maternal infection during pregnancy on the risk of attention-deficit/hyperactivity disorder (ADHD) in the offspring are unclear, and no overview is available.We searched the PubMed and EMBASE databases for relevant studies and performed a systematic review and meta-analysis of the literature.We found that that maternal infection during pregnancy was associated with a small increase in the risk of ADHD (OR 1.25, 95% CI 1.09, 1.44, P 0.0001; IThe statistically significant association between maternal infection during pregnancy and ADHD in the offspring can be partially explained by unmeasured confounding.

Characterization of the rheological properties of Chinese quince seed gum (CQSG) is fundamental when using it in food production. In the present paper, the chemical compositions and the rheological properties of CQSG at different concentrations, types of salts, temperatures and pH values were characterized by using shear or dynamic rheological experiments. The results demonstrated that uronic acid content of CQSG (31.7%) was high and different concentration CQSG solutions presented Newtonian plateaus followed by shear thinning regions. The viscosities of the gum solutions decreased with the addition of any salt, with increase in temperature and at extreme pH values (3 and 11). The stress and frequency sweep tests demonstrated a unique result in that the crossover frequency shifted to a higher value when the CQSG solution concentration increased. It is the basis for CQSG product development and quality control for its potential applications.

Background Hypertrophic cardiomyopathy (HCM) is considered to be the most common cause of sudden death in young people and is associated with an elevated risk of mood disorders. Depression has emerged as a critical risk factor for development and progression of coronary artery disease; however, the association between depression and HCM outcomes is less clear. We sought to examine the impact of depression on clinical outcomes in patients with HCM. Methods and Results Between January 2014 and December 2017, 820 patients with HCM were recruited and followed for an average of 4.2 years. End points were defined as sudden cardiac death (SCD) events and HCM‐related heart failure events. A Chinese version of the Structured Clinical Interview followed the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and was used to diagnose depression. During the follow‐up period, SCD events occurred in 75 individuals (21.8 per 1000 person‐years), and HCM‐related heart failure events developed in 149 individuals (43.3 per 1000 person‐years). Kaplan–Meier cumulative incidence curves showed a significant association of depression disorders with SCD events (log‐rank P =0.001) and HCM‐related heart failure events (log‐rank P =0.005). A multivariate Cox regression analysis indicated that depression was an independent predictor of SCD events and HCM‐related heart failure events (41.9 versus 21.7 per 1000 person‐years; adjusted hazard ratio [HR], 1.9; 95% CI, 1.6–2.3; P P Conclusions Depression is common among patients with HCM. The diagnosis of depression is significantly and independently associated with an increased risk of SCD events and heart failure events in patients with HCM.

The fast pace of work life has resulted in increased attention toward the rural landscape. Most research on rural landscapes has focused on visual preferences based on public consensus, but in-depth studies assessing a broad range of individual factors influencing visual and auditory preferences are still lacking. This study assessed the influence of 6 social/demographic/health factors and 7 visit-related factors on the preference for 11 visual and auditory elements of rural environments. Visit-related factors had a more significant impact on landscape preference than social/demographical/health factors. Length of stay was the most important factor, associated with 5 visual elements and 4 sounds. Females and older people showed greater preference for biological sounds. Thus, it is necessary to pay attention to the influence of individual factors on landscape preference and strengthen the support of rural internal and external environment to people���s needs to provide more rich and satisfying experiences in rural areas.

Background and Aims: Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) occurs in 5–10% of all patients with acute myocardial infarction. Obstructive sleep apnea-hypopnea syndrome (OSAHS) is linked to increased cardiovascular morbidity and mortality, but the relationship of OSAHS and outcomes in patients with MINOCA remains unknown. We aimed to evaluate the association between OSAHS and clinical outcomes in patients with MINOCA.Methods: Between January 2015 and December 2016, we carried out a consecutive cohort study of 583 patients with MINOCA and followed them up for 3 years. An apnea-hypopnea index of ≥ 15 events per hour recorded by polysomnography was defined as the diagnostic criterion for OSAHS. The primary end point was all-cause mortality, and the second end point was major adverse cardiovascular or cerebrovascular events (MACCE), a composite of cardiac death, non-fatal myocardial infarction, heart failure, cardiovascular-related rehospitalization, and stroke.Results: All-cause mortality happened in 69 patients and MACCE occurred in 113 patients during the 3-year follow-up. Kaplan–Meier survival curves indicated the significant relationship of OSAHS with all-cause mortality (log-rank P = 0.012) and MACCE (log-rank P = 0.002). Multivariate Cox regression analysis indicated OSAHS as an independent predictor of all-cause mortality and MACCE [adjusted hazard ratio: 1.706; 95% confidence interval (CI): 1.286–2.423; P = 0.008; and adjusted hazard ratio: 1.733; 95% CI: 1.201–2.389; P < 0.001; respectively], independent of age, sex, cardiovascular risk factors and discharge medications.Conclusions: OSAHS is independently associated with increased risk of all-cause mortality and MACCE in patients with MINOCA. Intervention and treatment should be considered to alleviate OSAHS-associated risk.

Thermomyces lanuginosus and Scytalidium thermophilum are among the most ubiquitous thermophilic fungi in compost and soil. Chemical study on these two prevalent strains collected from Yunnan led to isolation of 23 metabolites, including one new metabolite, therlanubutanolide, and 15 known compounds, isolated from the YGP culture broth of Thermomyces lanuginosus and 7 known compounds isolated from Scytalidium thermophilum, respectively. Therlanubutanolide shared the quite similar features of the same carbon skeleton and saturation as natural hexadecanoic acids. This was the first reported discovery of such a lactone as natural occurring metabolite. All the compounds were reported for the first time from thermophilic fungi. Among them, N-[(2S,3R,4E,8E)-1,3-dihydroxy-9-methyloctadeca-4,8-dien-2-yl]acetamide was for the first time reported to be a naturally occurring metabolite and its NMR data was first provided in this study. A type of PKS-derived metabolites, three 3,4-dihydronaphthalen-1(2H)-ones, which were widely found in plant pathogenic fungi as phytotoxins and reported to have antimicrobial activity, were obtained from both dominant thermophilic fungi. The frequent occurrence of such PKS phytotoxins in these two thermophilic fungi might suggest particular ecological interest.

The aim was to observe the analgesic effect of Fengshi Qutong Capsules(FSQTC) on chronic inflammatory pain in mice, and investigate its effect on p-ERK/COX-2 signal molecular activity. A model of chronic inflammatory pain was induced in mice by complete Freund's adjuvant(CFA). The mice were divided into normal control group, model group, model+FSQTC 0.3, 0.6 and 1.2 g·kg~(-1 )groups, model+positive control drug ibuprofen(IBP, 0.34 mg·kg~(-1)·d~(-1)) group, and normal control+ FSQTC 1.2 g·kg~(-1)group. FSQTC or IBP was given once a day by oral administration. Standard Von Frey fiber was used to evaluate the mechanical pain threshold, and the acetone stimulation was used to induce inflammatory plantar and observe the cold pain reaction scores. The mechanical pain threshold and cold pain reaction scores were observed before administration and 1, 2, 3, 4, 6 h after administration on the first day, as well as 3 h after administration on the 3 rd to 7 th day. The protein levels of PGE_2, COXs-1,2 and p-ERK in the spinal cord of the inflammatory foot and lumbar 4-5 were detected by enzyme-linked immunosorbent assay, Western blot, immunohistochemistry and immunofluorescence. The results showed that the mechanical pain threshold of the model group decreased and the cold pain reaction score increased as compared with the normal group. FSQTC application could dose-dependently increase the mechanical pain threshold and decrease the cold pain reaction score. The effect lasted for 6 h, most significant at 3 h. The effect of ibuprofen was similar to that of the 0.6 g·kg~(-1) dose group. In addition, FSQTC could reduce the abnormally increased protein content of PGE_2, COX-2 and p-ERK in the inflammatory foot and/or spinal cord of the model group, and the effect was most significant in middle and high dose groups. However, it had no effect on COX-1 in the inflammatory foot and spinal cord of mice. The results suggest that FSQTC has ob-vious analgesic effect on chronic inflammatory pain in mice, which may be related to inhibition of p-ERK/COX-2 signaling pathway.

To systematically evaluate the effects of Tripterygium Glycosides Tablets alone or in combination with methotrexate(MTX) and leflunomide(LEF) on the levels of pro-inflammatory cytokines in patients or animal models with rheumatoid arthritis(RA), and to provide reference for clinical application and related basic research, this study systematically searched databases of CNKI, VIP, WanFang, PubMed, Embase and Cochrane Library, collected relevant clinical or animal experimental studies, used risk assessment tools to evaluate the quality of research, and used Revman 5.3 software to conduct Meta-analysis or descriptive analysis of the outcome indicators included in the literatures. Of the 1 709 papers retrieved, 3 clinical studies and 12 animal experiments were included. The results showed that compared with MTX alone, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of peripheral blood TNF-α(SMD=-8.88,95%CI[-10.77,-6.99],Plt;0.000 01),IL-1β(Plt;0.000 01) and IL-6(SMD=-8.63, 95%CI[-10.57,-6.69], Plt;0.000 01) in RA patients. Compared with LEF alone, the combination of Tripterygium Glycosides Tablets and LEF could not further reduce the expression levels of TNF-α(P=0.20), IL-1β(P=0.17), IL-6(P=0.31). In RA animal model, compared with model group, Tripterygium Glycosides Tablets could reduce the expression levels of peripheral blood IL-1β(SMD=-6.29,95%CI[-9.64,-2.93],Plt;0.000 2)in peripheral blood(SMD=-1.39,95%CI[-1.77,-1.02],Plt;0.000 01), joint fluid(Plt;0.000 01) and paw plasma(P=0.02), and also reduce the expression levels of TNF-α in RA animal model group. Compared with MTX alone, Tripterygium Glycosides Tablets alone reduced the same levels of TNF-α(P=0.42) and IL-6(P=0.08) in joint fluid, while Tripterygium Glycosides Tablets combined with MTX could further reduce the levels of IL-6(P=0.000 1) in joint fluid; compared with LEF alone, Tripterygium Glycosides Tablets have the similar effects on reducing the expression levels of peripheral blood TNF-α(P=0.16), IL-1β(P=0.32), IL-6(P=0.12), while Tripterygium Glycosides Tablets combined with LEF could further reduce the expression levels of TNF-α(P=0.008), IL-1β(P=0.02), IL-6(Plt;0.000 1) in peripheral blood. Therefore, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of pro-inflammatory cytokines in peripheral blood of RA patients. Tripterygium Glycosides Tablets alone could reduce the expression levels of pro-inflammatory cytokines in peripheral blood and local joint of RA animal models. Tripterygium Glycosides Tablets combined with MTX or LEF could further reduce the express levels of pro-inflammatory cytokines in peripheral blood of RA animal models. Due to the limitation of literature, this conclusion needs to be further validated.

For dynamic reliability design of complex structures with multiple components, an improved weighted regression distributed collaborative surrogate model method (IWRDCSMM) is developed from the extremum response surface method (ERSM), decomposed-coordinated thought, and improved weighted regression principle. The ERSM is used to address the dynamic reliability and sensitivity analyses of multicomponent structures and enhance the computing efficiency. The decomposed-coordinated thought is applied to handle the relationship among multiple components. The improved weighted regression method is used to find the efficient samples with smaller errors to improve the modeling accuracy. The proposed method is first introduced for dynamic probabilistic analysis (including reliability analysis and sensitivity analysis) of multicomponent structures. The method is then mathematically modeled by adopting the efficient samples selected based on the improved weighted regression method. Finally, the radial deformation dynamic probabilistic analysis of an aeroengine turbine blisk assembled by blade and disk is accomplished, in respect of the IWRDCSMM, fluid-thermal-structure interaction, and the randomness of input parameters within the time domain [0, T]. The results illustrate that the reliability degree of turbine blisk radial deformation is 0.9951 when the allowable value uallow is 2.30 × 10−3 m, and all the input parameters affecting the turbine blisk radial deformation are gas temperature, angular speed, inlet velocity, outlet pressure, material density, and inlet pressure, successively. As revealed by the comparison of different methods, the IWRDCSMM has high fitting speed and simulation efficiency with the guarantee of accuracy. The efforts of this study provide a promising dynamic probabilistic analysis technique for complex structures with multiple components and enrich mechanical reliability theory.

Corn hulls were abundant and inexpensive byproducts of the corn dry or wet milling processes, but most of them were discarded as agro-wastes. The aim of this study was to extract the dietary fiber by hot-compressed water (HCW) from defatted corn hull and to determine the chemical properties. Results showed that temperature and time played critical roles in extraction efficiency; the maximal yield of dietary fiber A (DFA) extracted by HCW reached 33.0% at 150°C for 60 min. The yield of dietary fiber B (DFB) increased from 2.0% to 56.9% as the temperature increased from 110 to 180°C, while the yield of solid residue (SR) decreased from 88.7% to 27.7%. Fourier transform infrared spectroscopy (FT-IR) results demonstrated that C-H, O-H, C=O, COO- occurred in the DFA, SR and DFB. The dietary fiber polysaccharides consisted of arabinose, galactose, glucose, xylose and uronic acid.

In this investigation, a variety of innovative pH-sensitive polymers consisting of Chinese quince seed gum (CQSG) and poly (N,N-diethylacryl amide-co-methacrylic acid) were synthesized via free radical polymerization for controlled drug delivery. The resultant hydrogel polymers were characterized by scanning electron microscopy and X-ray diffraction, analyzed by Fourier-transform infrared spectroscopy, and confirmed with thermogravimetry. Results suggested the hydrogel polymers were composed of CQSG chains physically entangled in poly (N,N-diethylacryl amide-co-methacrylic acid) networks. Swelling properties of these hydrogels were strongly affected by the contents of CQSG and crosslinkers. The drug delivery applications of the hydrogels were evaluated using bovine serum albumin (BSA) as a model drug in vitro release. It was determined that BSA release from the hydrogels was pH-sensitive under simulated gastrointestinal conditions. All of these attributes imply that the new proposed CQSG/poly (N,N-diethylacryl amide-co-methacrylic acid) hydrogel polymers can be used as a good medium for oral delivery of proteinaceous drugs.

Chinese quince seed gum (CQSG) is a novel potential viscosifier or stabilizer with good storage stability. In this work, CQSG was extracted from the surface of Chaenomeles sinensis (Chinese quince) seeds, and purified by DEAE-Sepharose Fast-Flow and Sephacryl S-400 HR chromatography; three fractions were obtained (CQSG-1, -2, -3). The main fraction (CQSG-2) was investigated by monosaccharide analysis, methylation and one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) experiments to determine its structure. Results showed that CQSG-2 is composed of arabinose (Ara), glucose (Glu), xylose (Xly), galacturonic acid (Gala) and glucuronic acid (Glua) in a molar ratio of 4.0:0.3:15.2:4.2:3.8. →4-β- d -Xylp-1→ and →2, 4-β- d -Xylp-1→ constitute the backbone in a ratio of 5.9:4.5, and the Arap-1→, α- d -GalpA-1→, →2-α- d -GlcpA-1→, →4-β- d -Glcp-1→, and →2, 3, 5- l -Araf-1→ form the branched chain. The molecular aggregation of CQSG-2 with high molecular weight (Mw) (1.4 × 106 Da) was strong compared with CQSG-1 and CQSG-3. This is the first systematic elucidation of the structure of Chinese quince seed gum, and it provides the basis for developing applications for this gum in the food and pharmaceutical industries.

Background The evidence for a relationship between general anaesthesia induced in childhood and the risk of attention-deficit hyperactivity disorder (ADHD) in later life is inconsistent. We systematically assessed whether such an association existed. Methods We searched the PubMed and EMBASE databases for relevant cohort studies. Relative risks (RRs) and 95 % confidence intervals (CIs) were calculated to determine the relationship between induction of childhood general anaesthesia and the risk of ADHD in later life. Results Seven studies (eight publications) on developmental outcomes after the induction of childhood general anaesthesia met our inclusion criteria but not our exclusion criteria. Repeat childhood general anaesthesia (RR = 1.84, 95 CI% 1.14–2.97; P Conclusions Our meta-analysis indicated that the effect of general anaesthesia on the risk of ADHD is dose- or duration-dependent.

The present study was designed to prepare and compare bio-adhesive pellets of panax notoginseng saponins (PNS) with hydroxy propyl methyl cellulose (HPMC), chitosan, and chitosan : carbomer, explore the influence of different bio-adhesive materials on pharmacokinetics behaviors of PNSbio-adhesive pellets, and evaluate the correlation between in vivo absorption and in vitro release (IVIVC). In order to predict the in vivo concentration-time profile by the in vitro release data of bio-adhesive pellets, the release experiment was performed using the rotating basket method in pH 6.8 phosphate buffer. The PNS concentrations in rat plasma were analyzed by HPLC-MS-MS method and the relative bioavailability and other pharmacokinetic parameters were estimated using Kinetica4.4 pharmacokinetic software. Numerical deconvolution method was used to evaluate IVIVC. Our results indicated that, compared with ordinary pellets, PNS bio-adhesive pellets showed increased oral bioavailability by 1.45 to 3.20 times, increased Cmax, and extended MRT. What's more, the release behavior of drug in HPMC pellets was shown to follow a Fickian diffusion mechanism, a synergetic function of diffusion and skeleton corrosion. The in vitro release and the in vivo biological activity had a good correlation, demonstrating that the PNS bio-adhesive pellets had a better sustained release. Numerical deconvolution technique showed the advantage in evaluation of IVIVC for self-designed bio-adhesive pellets with HPMC. In conclusion, the in vitro release data of bio-adhesive pellets with HPMC can predict its concentration-time profile in vivo.

Visual landscapes and auditory soundscapes are considered to be integral elements of a sustainable habitat. Although numerous studies have indicated that natural imagery and sounds have positive impacts on human health and wellbeing, few have examined the specific effects of combined landscapes and soundscapes, or their health-promoting mechanisms. In this study, we conducted two comparative experiments in which we exposed 200 adult volunteers to a set of visual stimuli and auditory-visual stimuli. We created the Short-version Revised Restoration and Preference Scale to gather personal restorative potential and aesthetic preference data about the effects of adding auditory factors to images. We found that: (1) restorative value was positively associated with botanical and ecological educational backgrounds; (2) natural visual factors (natural water, shrubs and flowers) and auditory factors (flowing water sounds, wind-induced vegetation sounds, birdsong) were positive predictors of restorative value and preference, while human activities and voices were negative predictors; (3) nature-related auditory-visual stimuli were typically rated as having better health benefits than single visual stimuli; (4) the diversity and complexity of nature-related stimuli were significant restorative attributes; and (5) a generalized restorative environment comprised a mountain forest with biodiverse vegetation and natural sounds. This study proposes that restorative environments in urban green spaces can be achieved by taking full account of visual stimuli, auditory stimuli, and human activities. Our findings highlight the importance of multi-disciplinary cooperation and a multi-sensory approach in health-oriented environmental design.

To study the bioavailability of pueraria flavonoids bio-adhesive and floating pellets, the absorption of puerarin was studied using Caco-2 cell monolayer by liquid chromatography (HPLC) method, comparing the P(app) of pueraria flavonoids bio-adhesive and floating pellets with different bio-adhesive materials. Drugs were administered at a dose of 100 mg·kg(-1) via ig. The plasma concentration of puerarin was determined by HPLC, the pharmacokinetics were calculated with the WinNonlin 6.0 software. The results showed that the P(app) of bio-adhesive and floating pellets with hydroxypropyl methylcellulose (HPMC)-cabomer was largest, which had a significant difference (P0.05). The AUC(0-t) of pueraria flavonoids bio-adhesive and floating pellets was 1.79 times of pueraria flavonoids, the C(max) of pueraria flavonoids bio-adhesive and floating pellets and pueraria flavonoids had a significant difference (P0.05). What’s more the MRT had prolonged. In conclusion, pueraria flavonoids bio-adhesive and floating pellets with HPMC-cabomer could significantly facilitate the transport of puerarin on Caco-2 cellular monolayers. The bioavailability of pueraria flavonoids bio-adhesive and floating pellets with HPMC-cabomer was increased more than pueraria flavonoids with a sustained release effect.

In this study, on aspects of the nociceptive, anxiety and depressive syndromes in neuropathic pain (NP), the effects of dihydroartemisinine (DHA), artesunate (ART) and artemether (ARTN) (40 mg·kg⁻¹) were analyzed in the spinal cord ligation (SNL) mice. Clinical equivalent dose of the first-line drug for NP, pregabalin (PGB, 25 mg·kg⁻¹) and amitriptyline (ARP, 20 mg·kg⁻¹), were used as positive controls. General, from day 7 to 14, significant remissions of the nociceptive, anxiety and depressive behaviors were achieved by DHA, ART and ARTN separately. Moreover, on day 14, on aspects of the nociceptive behaviors, analyzed 1.5 h after the gavage administration, no significant difference between the shamed mice and mice administrated with DHA, ART and ARTN was detected; analyzed 3 h after the gavage, significant decreases of pain thresholds in ARTN, but not in DHA nor ART group, were detected as compared with thresholds measured 1.5 h; analyzed 24 h after gavage, pain thresholds in DHA, ART and ARTN were still higher than PGB, in spite of the significant decreases as compared to Sham group. On aspects of the anxiety and depressive behaviors, no significant difference was detected between the shamed mice and mice administrated with DHA nor ART. However, differences still remained between the shamed ones and ones administrated with ARTN. Preliminarily, the effects of DHA, ART and ARTN were consolidated in SNL mice. On aspects of the duration of analgesic effects and the control of negative emotion, ART and ARTN were proven more favorable than ARTN.

Cardiac disease has emerged as the leading cause of death worldwide, and food rich in phenolic acids has drawn much attention as sources of active substances of hypolipidemic drug. Ananas comosus L. (pineapple) is one of the most popular tropical and subtropical fruits. Isolated from pineapple leaves, EAL(Extract of Ananas Comosus L. Leaves) is rich in phenolic acids, such as p-coumaric acid, caffeic acid, and other phenolics, highly relevant to the putative cardiovascular-protective effects, which suggests its potential to be a new plant medicine for treatment of cardiac disease, but little is known about absorption, distribution, metabolism, and excretion of EAL in animals or human beings. In this study, we employed cDNA microarray, Caco-2 cell lines, and rat intestinal model to explore the absorption behavior of p-coumaric acid and caffeic acid in EAL. The permeation of 2 substances was concentration and time dependent. Results also indicated that monocarboxylic acid transporter was involved in the transepithelial transport of p-coumaric acid and caffeic acid.

Ying Li, Chunyan Zhu Department of Drug Delivery Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China Abstract: In oral administration, gastrointestinal physiological environment, gastrointestinal epithelial cell membranes, and blood circulation are typical biological barriers to hepatic delivery of ligand-modified nanoparticle drug delivery systems. To elucidate the mechanism of oral hepatic targeting of cholic acid receptor-mediated nanoliposomes (LPs) (distearoyl phosphatidylethanolamine–polyethylene glycol–cholic acid-modified LPs, CA-LPs), evaluations were performed on colon cancer Caco-2 cell monolayers, liver cancer HepG2 cells, and a rat intestinal perfusion model. CA-LPs, ~100nm in diameter, exhibited sustained-release behavior and had the greatest stability in rat gastrointestinal fluid and serum for both size and entrapment efficiency. CA-LPs demonstrated highest transport across Caco-2 cells and highest cellular uptake by HepG2 cells. The enhanced endocytosis of CA-LPs was found to be mediated by Na+/taurocholate cotransporting polypeptide and involved the caveolin-mediated endocytosis pathway. Further, we used fluorescence resonance energy transfer (FRET) technology to show that the CA-LPs maintained their structural integrity in part during the transport across the Caco-2 cell monolayer and uptake by HepG2 cells. Keywords: DSPE–PEG–cholic acid, nanoliposomes, hepatic targeting via oral administration, mechanism, FRET

To confirm the anticancer effect of total annonaceous acetogenins (TAAs) abstracted from Annona squamosa Linn. on human hepatocarcinoma.The inhibitory effect of TAAs was demonstrated in H22-bearing mice. The potency of TAAs was confirmed as its 50% inhibiting concentration (IC50) on Bel-7402 cell under Sulfur Rhodamine B staining. Both underlying mechanisms were explored as cellular apoptosis and cell cycle under flow cytometry. Mitochondrial and recipient apoptotic pathways were differentiated as mitochondrial membrane potential under flow cytometry and caspases activities under fluorescence analysis.The inhibitory rate of TAAs in mice was 50.98% at 4 mg/kg dose. The IC50 of TAAs on Bel-7402 was 20.06 µg/mL (15.13-26.61µg/mL). Effective mechanisms of TAAs were confirmed as both of arresting cell cycle at G1 phase and inducing apoptosis dose- and time-dependently. Mitochondrial and recipient pathways involved in apoptotic actions of TAAs.TAAs is effective for hepatocarcinoma, via inhibiting proliferation and inducing apoptosis.

Model parameters modification and numerical simulation based on the Knudsen–viscous transition model to predict the vacuum membrane distillation (VMD) performance of ethanol–water mixture and experiments were studied in a polytetrafluoroethylene flat-sheet membrane module. A novel approach to determine the model parameters K and B (modified Knudsen diffusion and viscous flow membrane characteristics, respectively) consisted of membrane morphological parameters was especially developed by fitting the water VMD experimental results. Furthermore, linear relations between the modified model parameter K or B and feed temperature were first established, and then successfully employed to predict by simulation the separation performances of 5 wt% ethanol–water mixture. The experiments of ethanol–water VMD demonstrated that the fluxes of ethanol and water both increased with temperature or vacuum degree, but the separation factor decreased. The simulation values agree quite well with experimental ones, finding the minimum and maximum discrepancies are 0.5% and 9.6% for flux and separation factor, respectively.

Background To evaluate the effects of Tadalafil, a phosphodiesterase 5 enzyme inhibitor, on Escherichia coli –induced renal damage in an acute pyelonephritis (PN) rat model. Methods Experimental PN was induced in 32 Wistar rats, and four groups were formed: group 1 (no treatment), group 2 (antibiotic), group 3 (Tadalafil), and group 4 (antibiotic + Tadalafil). Antibiotic was given on days 3 to 8, and Tadalafil was administered between days 0 and 28 of bacterial inoculation. Half of the rats were killed on the ninth day (early period) and histopathological parameters, immunohistochemical renal fibrosis markers, and oxidant/antioxidant system activities were evaluated. The rest of the rats were killed at the sixth week of the study and evaluated for histopathological parameters and renal fibrosis markers. Results Inflammatory activity was significantly milder in rats treated with antibiotic + Tadalafil versus no treatment group both in the early and late periods. In the late period, interstitial fibrosis or tubular atrophy was lower in the antibiotic + Tadalafil group versus the no treatment and antibiotic groups, and in Tadalafil versus antibiotic group. Tadalafil administration significantly reduced renal malondialdehyde and nitric oxide levels and enhanced superoxide dismutase and catalase activities. In addition, circulating tumor necrosis factor α, interleukin 1β was greatly reduced in Tadalafil group versus the no treatment group. Conclusions We have provided the first evidence that phosphodiesterase 5 enzyme inhibitor Tadalafil ameliorates circulating inflammatory cytokines, reverses oxidant/antioxidant dysfunction and eventually possesses an overall protective effect on renal tissue from Escherichia coli –induced PN-related kidney injury. Phophodieterase 5 inhibitor might be a novel therapeutic target for PN.

In this paper, we analyze a class of new generalized Emden-Fowler equations. By using the generalized Riccati transformation and specific analytical skills, new oscillation criteria are obtained which generalize and improve some known results.

Recently, cardiovascular disease has become the first cause of death for human health. Because of the complex etiology and long duration, the readmission rate for patients is extremely high during therapy, consuming a large amount of medical resources as well as producing expensive hospitalization costs. In order to solve this problem, this paper summarizes the current situation and problems of risk prediction relevant to the readmission for patients. Combined with data mining technology, a risk assessment model for patients was designed, followed by the design and development of readmission risk assessment system for patients with cardiovascular disease. The risk assessment model includes three parts: risk prediction, clustering analysis and regression analysis of risk factors, which can automatically predicate the risk level and risk factors for the discharged patients in thirty days. The model was accurate 90.62% of the time. Combined the model assessment results with risk control knowledge base, a personalized health management and health guidance given by care workers can be put forward intelligently, which can not only help medical personnel in the rational allocation but also guide patients to carry out self-management better, resulting in the decrease of readmission rate.

Recently, P2P networks play an important role in network. However, there exist a large amount of malicious actions in P2P networks resulting from the lack of reputation system. For example, nodes are willing to share resources each other and may withdraw from networks at any time. Thus, the system is difficult to guarantee effectiveness and availability. According to the behavior of fish school, A novel optimizing, Fish-swam Algorithm, was proposed in this paper, which can decide the next step when nodes have no interactive experience with others. The algorithm based on the model of autonoms animals and was presented to be a kind of efficient incentive mechanism, through a series of experimental study.

Background: Stroke volume variation (SVV) has been shown to be a reliable predictor of fluid responsiveness. However, the predictive role of SVV measured by FloTrac/Vigileo system in prediction of fluid responsiveness was unproven in patients undergoing ventilation with low tidal volume. Methods: Fifty patients undergoing elective gastrointestinal surgery were randomly divided into two groups: Group C [n1=20, tidal volume (Vt) = 8 ml/kg, frequency (F) = 12/min] and Group L [n2=30, Vt= 6 ml/kg, F=16/min]. After anesthesia induction, 6% hydroxyethyl starch130/0.4 solution (7 ml/kg) was intravenously transfused. Besides standard haemodynamic monitoring, SVV, cardiac output, cardiac index (CI), stroke volume (SV), stroke volume index (SVI), systemic vascular resistance (SVR) and systemic vascular resistance index (SVRI) were determined with the FloTrac/Vigileo system before and after fluid loading. Results: After fluid loading, the MAP, CVP, SVI and CI increased significantly, whereas the SVV and SVR decreased markedly in both groups. SVI was significantly correlated to the SVV, CVP but not the HR, MAP and SVR. SVI was significantly correlated to the SVV before fluid loading (Group C: r = 0.909; Group L: r = 0.758) but not the HR, MAP, CVP and SVR before fluid loading. The largest area under the ROC curve (AUC) was found for SVV (Group C, 0.852; Group L, 0.814), and the AUC for other preloading indices in two groups ranged from 0.324 to 0.460. Conclusion: SVV measured by FloTrac/Vigileo system can predict fluid responsiveness in patients undergoing ventilation with low tidal volumes during gastrointestinal surgery.