Exploring the potential mechanism of Taohong Siwu decoction in the treatment of avascular necrosis of the femoral head based on network pharmacology and molecular docking.

Based on network pharmacology and molecular docking, this study seeks to investigate the mechanism of Taohong Siwu decoction (THSWD) in the treatment of avascular necrosis of the femoral head (AVNFH). The Traditional Chinese Medicine Systems Pharmacology database was used in this investigation to obtain the active ingredients and related targets for each pharmaceutical constituent in THSWD. To find disease-related targets, the terms "avascular necrosis of the femoral head," "necrosis of the femoral head," "steroid-induced necrosis of the femoral head," "osteonecrosis," and "avascular necrosis of the bone" were searched in the databases DisGeNET, GeneCards, Comparative Toxicogenomics Database, and MalaCards. Following the identification of the overlap targets of THSWD and AVNFH, enrichment analysis using gene ontology, Kyoto Encyclopedia of Genes and Genomes, Reactome, and WikiPathways was conducted. The "THSWD-drug-active compound-intersection gene-hub gene-AVNFH" network and protein-protein interaction network were built using Cytoscape 3.9.1 and string, and CytoHubba was used to screen hub genes. The binding activities of hub gene targets and key components were confirmed by molecular docking. 152 prospective therapeutic gene targets were found in the bioinformatics study of ONFH treated with THSWD, including 38 major gene targets and 10 hub gene targets. The enrichment analysis of 38 key therapeutic targets showed that the biological process of gene ontology analysis mainly involved cytokine-mediated signaling pathway, angiogenesis, cellular response to reactive oxygen species, death-inducing signaling complex. The Kyoto Encyclopedia of Genes and Genomes signaling pathway mainly involves TNF signaling pathway, IL-17 signaling pathway, and the Recactome pathway mainly involves Signaling by Interleukins, Apoptosis, and Intrinsic Pathway for Apoptosis. WikiPathways signaling pathway mainly involves TNF-related weak inducer of apoptosis signaling pathway, IL-18 signaling pathway. According to the findings of enrichment analysis, THSWD cured AVNFH by regulating angiogenesis, cellular hypoxia, inflammation, senescence, apoptosis, cytokines, and cellular proliferation through the aforementioned targets and signaling pathways. The primary component of THSWD exhibits a strong binding force with the key protein of AVNFH. This study sheds new light on the biological mechanism of THSWD in treating AVNFH by revealing the multi-component, multi-target, and multi-pathway features and molecular docking mechanism of THSWD.

A review of Duhuo Jisheng decoction mechanisms in intervertebral disc degeneration in vitro and animal studies.

Intervertebral disc degeneration (IVDD) has become a serious public health problem, placing a heavy burden on society and the healthcare system. Its pathogenesis is not completely clear and may be closely related to mechanical damage, inflammatory factors, oxidative stress and death of nucleus pulposus cells (NPCs). The treatment of IVDD mainly includes conservative treatment and surgery. Conservative treatment is based on hormonal and anti-inflammatory drugs and massage techniques, which can relieve the pain symptoms to a certain extent, but cannot solve the problem from the root cause. Surgical treatment is mainly by removing the herniated nucleus pulposus, but it is more traumatic for IVDD patients, expensive and not suitable for all patients. Therefore, it is extremely important to clarify the pathogenesis of IVDD, to find an effective and convenient treatment and to further elaborate its mechanism of action. The effectiveness of traditional Chinese medicine in the treatment of IVDD has been well demonstrated in clinical medical research. We have been working on the Chinese herbal formula Duhuo Jisheng Decoction, which is a common formula for the treatment of degenerative disc disease. Not only does it have significant clinical effects, but it also has few adverse effects. At present, we found that its mechanism of action mainly involves regulation of inflammatory factors, reduction of apoptosis and pyroptosis of NPCs, inhibition of extracellular matrix degradation, improvement of intestinal flora, etc. However, a few relevant articles have yet comprehensively and systematically summarized the mechanisms by which they exert their effect. Therefore, this paper will comprehensively and systematically explain on it. This is of great clinical significance and social value for elucidating the pathogenesis of IVDD and improving the symptoms of patients, and will provide a theoretical basis and scientific basis for the treatment of IVDD with traditional Chinese medicine.

Exploring the pharmacological mechanism of Duhuo Jisheng Decoction in treating intervertebral disc degeneration based on network pharmacology.

BACKGROUND: The purpose of this study was to examine the mechanism of Duhuo Jisheng Decoction (DHJSD) in the treatment of intervertebral disc degeneration (IVDD). METHODS: The active compounds of DHJSD and their corresponding targets were obtained from the TCMSP database. "Intervertebral disc degeneration" was used as a search term in the DisGeNET, GeneCards, Comparative Toxicogenomics Database, and MalaCards database to obtain disease-related targets. Following the discovery of overlapping DHJSD and IVDD targets, enrichment analyses for Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Reactome, and WikiPathways were performed. Cytoscape 3.9.1 was used to build the "DHJSD-Active Ingredients-Target Genes-IVDD" network and protein-protein interaction network, and CytoHubba was used to screen the pivotal genes. Molecular docking confirmed the binding activity of hub genes and key components. RESULTS: The bioinformatic analysis of DHJSD in the treatment of IVDD revealed 209 potential therapeutic gene targets, including 36 important gene targets and 10 of these crucial gene targets. Enrichment analysis of 36 key therapeutic targets showed that the biological processes involved in the Gene Ontology analysis of DHJSD in treating IVDD were mainly cytokine-mediated signaling pathway, inflammatory response, negative regulation of apoptotic process, and vascular endothelial growth factor production. The Kyoto Encyclopedia of Genes and Genomes signaling pathway is mainly involved in TNF signaling pathway, Th17 cell differentiation, IL-17 signaling pathway, and HIF-1 signaling pathway. The Recactome signaling pathway is mainly involved in cytokine signaling in immune system, cellular responses to stress, immune system, cytokines, and inflammatory response. HIF1A and PPARG regulation of glycolysis are mostly involved in the WikiPathways signaling system. The findings demonstrated that to cure IVDD, DHJSD affects the pathogenic processes of inflammation, extracellular matrix, cellular senescence, autophagy, apoptosis, focal death, and proliferation through the aforementioned targets and signaling pathways. The results of molecular docking demonstrated that the protein can be effectively bound by the DHJSD active component. Further evidence was provided for the molecular mechanism through which DHJSD works to treat IVDD. CONCLUSION: This study uncovers the multi-component, multi-target, and multi-pathway characteristics of DHJSD for the treatment of IVDD, offering fresh perspectives to further investigate the mechanism of DHJSD for the treatment of IVDD.

Evaluating Antioxidant Performance, Biosafety, and Antimicrobial Efficacy of Houttuynia cordata Extract and Microwave-Assisted Synthesis of Biogenic Silver Nano-Antibiotics.

From the traditional Chinese medicine point of view, although Houttuynia cordata extract (HCE) possesses an incredible amount of phytonutrients and exhibits antioxidant activities, excessive doses of HCE can cause danger to organisms and lead to death. In this study, we first examine HCE's overall phenolic and flavonoid content, antioxidant efficacy, and antibacterial activity. Results show that HCE is suitable as a bio-reducing agent for the microwave-assisted synthesis of silver nanoparticles (HCE-AgNPs) with enhanced antioxidant and antimicrobial performance. Under an optimized microwave condition (i.e., 100 °C for 10 min), the HCE-stabilized AgNPs were confirmed with a UV-visible peak at 430 nm and 19.7 ± 4.2 nm in size. Physicochemical properties of HCE-AgNPs were extensively characterized by zeta-potential, FT-IR, XRD, and XPS measurements. Compared to the HC extract counterpart, HCE-AgNPs display superior antioxidant activity, higher DPPH scavenging efficiency, and enhanced broad-spectrum bactericidal activity to inhibit the growth of all tested bacterial strains at doses of 2 µg/mL. Biosafety evaluation indicated that HCE-AgNPs are noncytotoxic on human red blood cells. These data show that the microwave synthesis of AgNPs exhibits a great antioxidant ability, superior antibacterial activity, and a trivial hemolytic effect, providing another bactericidal therapy strategy to address the increasing healthcare-associated infections.

Efficacy and safety of radiofrequency ablation for primary and secondary hyperparathyroidism with or without previous parathyroidectomy: a retrospective study.

INTRODUCTION: This study aimed to investigate and compare the therapeutic efficacy and safety of ultrasound-guided radiofrequency ablation (RFA), between primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism (SHPT) patients, with or without previous parathyroidectomy (PTX). SUBJECTS AND METHODS: A total of 21 patients (7 PHPT, 14 SHPT) underwent RFA for hyperparathyroidism (HPT) at Kaohsiung Chang Gung Memorial Hospital, Taiwan. Five of the 14 SHPT patients had previously received PTX. The laboratory data, volume change of each parathyroid nodule, symptomatic scores, and complications were analyzed and compared between all groups at 1 and 7 days, and at 1, 3, 6, and 12 months after RFA. RESULTS: After RFA, the volume reduction ratio (VRR) for all patients at the last follow-up was 93.76%, and clinical symptoms significantly improved. At 12 months, all PHPT patients achieved successful treatment of intact PTH (iPTH). In SHPT patients, the mean iPTH value significantly decreased 1-day post-RFA, subsequently exhibiting a transient rebound which proceeded to decrease, with 57.1% reaching successful treatment standards. SHPT patients with PTX showed a lower complication score, shorter ablation time, higher iPTH baseline and outcomes, and lower VRR, compared to patients without PTX. The serum calcium level significantly decreased to normal range in 85.7% of all patients at 12 months. Severe hypocalcemia occurred in 23.8% at 1 week, and all were corrected with calcium supplements. CONCLUSIONS: RFA demonstrates a therapeutic efficacy similar to PTX. It can thus be considered an effective alternative treatment for PHPT, SHPT, or post-PTX patients who are unsuitable for another PTX.

Nrf2-Dependent Protective Effect of Paeoniflorin on α-Naphthalene Isothiocyanate-Induced Hepatic Injury.

The pathological mechanism of cholestatic hepatic injury is associated with oxidative stress, hepatocyte inflammation, and dysregulation of hepatocyte transporters. Paeonia lactiflora Pall. and its compound can improve hepatic microcirculation, dilate bile duct, and promote bile flow, which is advantageous to ameliorate liver damage. Paeoniflorin (PEA), as the main efficacy component of Paeonia lactiflora Pall., has multiple pharmacological effects. PEA improves liver injury, but it remains obscure whether the protective action on [Formula: see text]-naphthalene isothiocyanate (ANIT)-induced cholestatic liver injury is dependent on the NF-E2 p45-related Factor 2 (Nrf2) signaling pathway. In this study, C57BL/6 mice were administrated with 80 mg⋅kg[Formula: see text]⋅d[Formula: see text] ANIT followed by PEA (75, 150, and 300 mg⋅kg[Formula: see text]⋅d[Formula: see text]) orally for 10 days, respectively. Tissue histology and liver function were detected, including serum enzymes, gallbladder (GB) weight, phenobarbital-induced sleeping time (PEN-induced ST), hepatic uridine di-phosphoglucuronosyltransferase (UDPG-T), malondialdehyde (MDA), and glutathione (GSH). The expressions of protein Nrf2, sodium taurocholate cotransporting polypeptide (Ntcp), and NADPH oxidase 4 (Nox4) were evaluated. Nrf2 plasmid or siRNA-Nrf2 transfection on LO2 cells and Nrf2-/- mice were used to explore the liver protective mechanism of PEA. Compared to ANIT-treated mice, PEA decreased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA), and phenobarbital-induced sleeping time. The bile secretion, hepatic UDPG-T, MDA, GSH, and liver histology were improved. The expressions of protein Nrf2 and Ntcp in liver tissues increased, but Nox4 decreased. After Nrf2 plasmid or small interfering RNA (siRNA)-Nrf2 transfection, the protective effects of PEA on LO2 cells were, respectively, strengthened or weakened. Moreover, PEA had no significant effects on ANIT-treated Nrf2-/- mice. Our results suggest that Nrf2 is essential for PEA protective effects on ANIT-induced liver injury.

Effects of bamboo leaf extract intervention on the growth performance, antioxidant capacity, and hepatic apoptosis in suckling piglets.

This study investigated whether bamboo leaf extract (BLE) could improve the growth performance, antioxidant capacity, and inhibit hepatic apoptosis in suckling piglets. Sixty-four suckling piglets were orally gavaged with vehicle (CON group) or 100, 200, or 300 mg BLE/kg body weight (BL, BM, and BH groups) at 3 d of age for 21 d (n = 8). The results showed that BLE treatment had no effects on the growth performance (P > 0.05). Compared with the CON group, the BM and BH groups decreased (P < 0.05) the jejunal and hepatic malondialdehyde (MDA) contents. Supplementation with BLE increased antioxidant enzymes activities and the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and several targeted genes in the jejunum and liver of suckling piglets. The hepatic apoptosis rate was lower (P < 0.05) in BLE treatment than in the CON group. Compared with the CON group, the BLE groups showed increased (P < 0.05) mRNA levels of B-cell-lymphoma protein 2 (BCL-2), whereas decreased (P < 0.05) BCL-2-associated X (BAX) and cysteine aspartate specific protease-3 (caspase-3) mRNA levels. The results of protein expressions of BCL-2 and caspase-3 were consistent with those of mRNA levels. Altogether, our results indicated that BLE intervention can improve the antioxidant capacity and inhibit hepatic apoptosis in suckling piglets.

Neonatal piglets suffer from severe birth oxidative stress due to the immaturity of their antioxidant system. In vitro and in vivo studies have now shown that the function of the antioxidant system can be modulated by bamboo leaf extract (BLE). However, the effects of BLE on the growth performance, antioxidant capacity, and hepatic apoptosis have not been explored in suckling piglets. The study's objective was to assess the effects of BLE on the growth performance, antioxidant capacity, and hepatic apoptosis in suckling piglets. Suckling piglets were orally gavaged with vehicle (CON group) or 100, 200, or 300 mg BLE/kg body weight at 3 d of age for 21 d. Compared to the CON group, BLE treatment had no effects on the growth performance; BLE treatment increased antioxidant enzymes activities and antioxidant-related genes at both the gene and protein expressions in the jejunum and liver of suckling piglets; BLE treatment also inhibited hepatic apoptosis, including hepatic apoptosis rate and the expressions of apoptosis-related genes. These results indicate the efficacy of BLE to improve antioxidant capacity and inhibit hepatic apoptosis in suckling piglets, demonstrating that BLE has a certain protective effect on suckling piglets at the postnatal stage.

Effects of yeast hydrolysate on growth performance, serum parameters, carcass traits, meat quality and antioxidant status of broiler chickens.

BACKGROUND: Yeast hydrolysate (YH) has multiple salutary biological activities. Nevertheless, the application of YH in broiler production is limited. This study was conducted to evaluate the protective effects of YH derived from Saccharomyces cerevisiae by exploring growth performance, serum parameters, organs relative weight, carcass traits, meat quality and antioxidant status of broilers. RESULTS: Supplementing YH linearly and quadratically improved (P < 0.05) body weight gain and gain-to-feed ratio compared to that in the control group. Triglycerides, low-density lipoprotein cholesterol and total cholesterol in serum, the decline in pH and cooking loss of breast muscle, and malonaldehyde concentration in serum and liver were decreased linearly and/or quadratically by YH (P < 0.05), whereas high-density lipoprotein cholesterol in serum, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in serum, GSH-Px activity in liver, glutathione content in serum and liver, eviscerated yield rate and chest muscle yield, and the relative weight of spleen and liver were linearly and/or quadratically increased (P < 0.05). Moreover, YH enhanced the mRNA levels of nuclear factor erythroid 2-related factor 2, heme oxygennase-1 (HO-1), GSH-Px1 and SOD1 (linear and/or quadratic, P < 0.05). CONCLUSION: Dietary YH beneficially affected growth performance, serum parameters, organ relative weight, carcass traits, meat quality and antioxidant status in broilers, indicating its potential application as a promising feed additive in broiler production. © 2021 Society of Chemical Industry.

Real-time monitoring of deformed wing virus-infected bee foraging behavior following histone deacetylase inhibitor treatment.

Impairment in the learning/memory behavior of bees is responsible for the massive disappearance of bee populations and its consequent agricultural economic losses. Such impairment might be because of o both pesticide exposure and pathogen infection, with a key contributor deformed wing virus (DWV). The present study found that sodium butyrate (NaB) significantly increased survival and reversed the learning/memory impairment of DWV-infected bees. A next-generation sequencing analysis showed that NaB affected the expression of genes involved in glycolytic processes and memory formation, which were suppressed by DWV infection. In addition, we performed a large-scale movement tracking experiment by using a wireless sensor network-based automatic real-time monitoring system and confirmed that NaB could improve the homing ability of DWV-infected bees. In short, we demonstrated the mechanism of how epigenetic regulation can resume the memory function of honeybees and suggest strategies for applying NaB to reduce the incidence of colony losses.

Effects of a yeast-derived product on growth performance, antioxidant capacity, and immune function of broilers.

Yeast culture plus enzymatically hydrolyzed yeast cell wall (YC-EHY) contains crude protein, mannan-oligosaccharide, ß-glucan and yeast culture. This study was carried out to explore the effects of dietary YC-EHY at different levels on growth performance, antioxidant capacity, and immune function of broiler chickens. A total of 320 one-day-age male broiler chicks were allocated into 4 groups and were fed with a basal diet supplemented with 0 mg/kg (the control group), 50 mg/kg, 100 mg/kg, 150 mg/kg YC-EHY for 42 d. Dietary YC-EHY improved average daily gain and feed efficiency during the starter, grower, and overall periods as well as average body weight of broiler chickens on 42 d (linear and quadratic, P < 0.05). Broiler chickens fed with YC-EHY quadratically increased jejunal sucrase activity on 21 d (quadratic, P < 0.05), and linearly and quadratically enhanced maltase activity on 21 and 42 d (linear and quadratic, P < 0.05). Supplementing YC-EHY linearly and quadratically enhanced jejunal superoxide dismutase (SOD) activity on 21 and 42 d and glutathione peroxidase (GPX) activity on 42 d whereas decreased malonaldehyde (MDA) concentration on 42 d (linear and quadratic, P < 0.05). Consistently, the jejunal genes expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and SOD1 on 21 and 42 d, heme oxygenase-1 (HO-1) and GPX1 on 42 d were enhanced by YC-EHY supplementation (linear and quadratic, P < 0.05). The concentrations of jejunal immunoglobulin G (IgG) on 21 and 42 d and secreted immunoglobulin A (SIgA) on 42 d were linearly and quadratically elevated by supplementing YC-EHY (linear and quadratic, P < 0.05). Dietary YC-EHY quadratically increased jejunal IgG and IgM genes expression on 21 d (quadratic, P < 0.05), and linearly and quadratically enhanced the genes expression of IgG and IgM on 42 d (linear and quadratic, P < 0.05). Overall, this study indicated that supplementing YC-EHY could exert beneficial effects on growth performance, intestinal antioxidant capacity and immune function in broiler chickens.

Identification of Immune Regulatory Genes in Apis mellifera through Caffeine Treatment.

Plants and pollinators are mutually beneficial: plants provide nectar as a food source and in return their pollen is disseminated by pollinators such as honeybees. Some plants secrete chemicals to deter herbivores as a protective measure, among which is caffeine, a naturally occurring, bitter tasting, and pharmacologically active secondary compound. It can be found in low concentrations in the nectars of some plants and as such, when pollinators consume nectar, they also take in small amounts of caffeine. Whilst caffeine has been indicated as an antioxidant in both mammals and insects, the effect on insect immunity is unclear. In the present study, honeybees were treated with caffeine and the expression profiles of genes involved in immune responses were measured to evaluate the influence of caffeine on immunity. In addition, honeybees were infected with deformed wing virus (DWV) to study how caffeine affects their response against pathogens. Our results showed that caffeine can increase the expression of genes involved in immunity and reduce virus copy numbers, indicating that it has the potential to help honeybees fight against viral infection. The present study provides a valuable insight into the mechanism by which honeybees react to biotic stress and how caffeine can serve as a positive contributor, thus having a potential application in beekeeping.

Effect of Self-Acupoint Massage on Blood Glucose Level and Quality of Life in Older Adults With Type 2 Diabetes Mellitus: A Randomized Controlled Trial.

The current study aimed to explore the effect of self-acupoint massage (SEAM) on blood glucose level and quality of life in community-dwelling older adults with type 2 diabetes mellitus (T2DM). Sixty-six older adults with T2DM were enrolled and randomly divided into observation and control groups. Participants in the control group received routine nursing interventions, whereas participants in the observation group received a SEAM intervention in addition to routine nursing interventions. After 12 weeks of SEAM, glycosylated hemoglobin (HbA1c) levels in the observation group decreased from 8.35% (SD = 1.84%) at baseline to 7.29% (SD = 1.38%) (p < 0.01). Total score of the Diabetes-Specific Quality of Life Scale (DSQLS) in the observation group improved from 45.96 (SD = 4.29) at baseline to 41.3 (SD = 3.89) (p < 0.01). The physiological dimension of the DSQLS in the observation group improved from 49.65 (SD = 7.33) at baseline to 38.54 (SD = 4.68) (p < 0.01). As SEAM effectively decreased older adults' HbA1c level and improved their quality of life, it can be used as a complementary approach to routine nursing interventions for community-dwelling older adults with T2DM. [Journal of Gerontological Nursing, 45(8), 43-48.].

Tom20 senses iron-activated ROS signaling to promote melanoma cell pyroptosis.

Iron has been shown to trigger oxidative stress by elevating reactive oxygen species (ROS) and to participate in different modes of cell death, such as ferroptosis, apoptosis and necroptosis. However, whether iron-elevated ROS is also linked to pyroptosis has not been reported. Here, we demonstrate that iron-activated ROS can induce pyroptosis via a Tom20-Bax-caspase-GSDME pathway. In melanoma cells, iron enhanced ROS signaling initiated by CCCP, causing the oxidation and oligomerization of the mitochondrial outer membrane protein Tom20. Bax is recruited to mitochondria by oxidized Tom20, which facilitates cytochrome c release to cytosol to activate caspase-3, eventually triggering pyroptotic death by inducing GSDME cleavage. Therefore, ROS acts as a causative factor and Tom20 senses ROS signaling for iron-driven pyroptotic death of melanoma cells. Since iron activates ROS for GSDME-dependent pyroptosis induction and melanoma cells specifically express a high level of GSDME, iron may be a potential candidate for melanoma therapy. Based on the functional mechanism of iron shown above, we further demonstrate that iron supplementation at a dosage used in iron-deficient patients is sufficient to maximize the anti-tumor effect of clinical ROS-inducing drugs to inhibit xenograft tumor growth and metastasis of melanoma cells through GSDME-dependent pyroptosis. Moreover, no obvious side effects are observed in the normal tissues and organs of mice during the combined treatment of clinical drugs and iron. This study not only identifies iron as a sensitizer amplifying ROS signaling to drive pyroptosis, but also implicates a novel iron-based intervention strategy for melanoma therapy.

Distribution and predictors of hospital charges for haemorrhagic stroke patients in Beijing, China, March 2012 to February 2015: a retrospective study.

OBJECTIVES: The purpose of this study is to analyse hospital charges for patients with haemorrhagic stroke in China and investigate potential factors associated with inpatient charges. METHODS: The study participants were in-hospital patients with a primary diagnosis of haemorrhagic stroke from all the secondary and tertiary hospitals in Beijing during the period from 1 March 2012 to 28 February 2015. Distribution characteristics of detailed hospital charges were analysed. The influence of potential factors on hospital charges was researched using a stepwise multiple regression model. RESULTS: A total of 34 890 patients with haemorrhagic stroke of mean age 61.19±14.37 years were included in the study, of which 37.2% were female. Median length of hospital stay (LOHS) was 15 days (IQR 9-23) and median hospital cost was 18 577 Chinese yuan (CNY) (IQR 10 442-39 784). The hospital costs for patients in Western medicine hospitals (median 19 651 CNY) were significantly higher (P<0.01) than those in traditional Chinese medicine hospitals (median 14 560 CNY), and were significantly higher (P<0.01) for Level 3 hospitals (median 20 029 CNY) than for Level 2 hospitals (median 16 095 CNY). The proportion of medicine fees and bed fees within total hospital charges showed a decreasing trend during the study period. With stepwise multiple regression, the major factors associated with hospital charges were LOHS, surgery, pulmonary infection, ventilator usage, hospital level, occupation, hyperlipidaemia, hospital type, in-hospital death, sex and age. CONCLUSION: We conclude that medicines form the largest part of hospital charges but are showing a decreasing trend, and LOHS is strongly associated with patient charges for haemorrhagic stroke in China. This implies that the cost structure is very unreasonable in China and medical technology costs fail to be fully manifested. A reasonable decrease in medicine charges and shortening LOHS may be effective ways to reduce hospital charges.

Pt-MWCNT modified carbon electrode strip for rapid and quantitative detection of H2O2 in food.

A single-use screen-printed carbon electrode strip was designed and fabricated. Nanohybrids, prepared by deposition of platinum (Pt) nanoparticles on multi-wall carbon nanotube (MWCNT), was modified on the surface of screen-printed carbon electrode for the development of a fast, sensitive and cost-effective hydrogen peroxide (H2O2) detection amperometric sensor strip. With Pt-MWCNT nanohybrids surface modification, current generated in response to H2O2 by the screen-printed carbon electrode strip was enhanced 100 fold with an applied potential of 300 mV. Quality of as-prepared electrode strip was assured by the low coefficient of variation (CV) (<5%) of currents measured at 5 s. Three linear detection ranges with sensitivity of 75.2, 120.7, and 142.8 µA mM-1 cm-2 were observed for H2O2 concentration in the range of 1-15 mM, 0.1-1 mM, and 10-100 µM, respectively. The lowest H2O2 concentration could be measured by the as-prepared strip was 10 µM. H2O2 levels in green tea infusion and pressed Tofu could be rapidly detected with results comparable to that measured by ferrous oxidation xylenol orange (FOX) assay and peroxidase colorimetric method.

Dietary supplementation of enzymatically treated Artemisia annua could alleviate the intestinal inflammatory response in heat-stressed broilers.

The study was undertaken to evaluate the effects of enzymatically treated Artemisia annua (EA) on the intestinal inflammatory response of heat-stressed broilers. A total of 144 male Arbor Acres broilers aged 21 days were randomly divided into 3 groups with 6 replicates per group and 8 broilers in each replicate. The 3 treatment groups were as follows: the control group, in which broiler chickens were raised at 22 ± 1°C and fed basal diets, the heat stress (HS) and HS-EA groups, in which broiler chickens were raised at 34 ± 1°C for 8h (0900-1700h) and 22 ± 1°C for 16h, and fed basal diets supplemented with 0 or 1g/kg EA, respectively. From 22 to 41 days, the heat treatment lasted for 20 consecutive days. Compared with the control group, HS increased the activity of plasma diamine oxidase (P < 0.05) and the concentration of intestinal interleukin-1ß, and up-regulated (P < 0.05) the mRNA expression of intestinal interleukin-1ß, interleukin-6, interferon-γ, toll-like receptor 4 and heat shock protein 70, down-regulated (P < 0.05) jejunal zonula occludens-1 and ileal occluding mRNA abundances and intestinal interleukin-10 at both protein and transcriptional levels. However, EA treatment significantly decreased (P < 0.05) plasma diamine oxidase activity, the mRNA expression of heat shock protein 70, toll-like receptor 4, interleukin-6, interleukin-1ß and interferon-γ in intestine of heat-stressed broilers, whereas upregulated (P < 0.05) the mRNA expression of ileal occluding, jejunal zonula occludens-1 and occluding. In addition, both protein and transcriptional levels of interleukin-10 in jejunum and ileum were increased (P < 0.05) by EA treatment in the HS group. In conclusion, dietary EA supplementation could alleviate the intestinal inflammatory response, and improve the intestinal barrier function in broilers during the heat stress period.

Fibroblast Activation Protein α Activated Tripeptide Bufadienolide Antitumor Prodrug with Reduced Cardiotoxicity.

Bufadienolides are the major pharmacologic constituents of traditional Chinese medicine Chan'su, which is frequently used clinically for cancer treatment in China. Motivated by reducing or avoiding the cardiac toxicity of bufadienolides, we have designed, synthesized, and evaluated the fibroblast activation protein α (FAPα) activated tripeptide arenobufagin prodrugs with the purpose of improving the safety of arenobufagin (a representative bufadienolide). Among these FAPα-activated prodrugs, 3f exhibited the best hydrolytic efficiency by recombinant human FAPα (rhFAPα) and was activated in tumors. The LD50 of 3f was 6.5-fold higher than that of arenobufagin. We also observed that there are nonapparent changes in echocardiography, pathological section of cardiac muscle, and the lactate dehydrogenase activities (LDH) in 3f-treatment tumor-bearing mice, even when the dose reached 3 times the amount of parent drug arenobufagin that was used. Compound 3f also exhibits significant antitumor activity in vitro and in vivo. The improved safety profile and favorable anticancer properties of 3f warrant further studies of the potential clinical implications. Our study suggests that FAPα prodrug strategy is an effective approach for successful increasing the therapeutic window of bufadienolides.

Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience.

Traditionally, the use of genomic information for personalized medical decisions relies on prior discovery and validation of genotype-phenotype associations. This approach constrains care for patients presenting with undescribed problems. The National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) hypothesized that defining disease as maladaptation to an ecological niche allows delineation of a logical framework to diagnose and evaluate such patients. Herein, we present the philosophical bases, methodologies, and processes implemented by the NIH UDP. The NIH UDP incorporated use of the Human Phenotype Ontology, developed a genomic alignment strategy cognizant of parental genotypes, pursued agnostic biochemical analyses, implemented functional validation, and established virtual villages of global experts. This systematic approach provided a foundation for the diagnostic or non-diagnostic answers provided to patients and serves as a paradigm for scalable translational research.

Application of diverse natural polymers in the design of oral gels for the treatment of periodontal diseases.

The objective of this study was to prepare periodontal gels using natural polymers such as badam gum, karaya gum and chitosan. These gels were tested for their physical and biochemical properties and assessed for their antibacterial activity against Aggregatibacter actinomycetemcomitans and Streptococcus mutans, two pathogens associated with periodontal disease. Badam gum, karaya gum and chitosan were used to prepare gels of varying concentrations. Moxifloxacin hydrochloride, a known antimicrobial drug was choosen in the present study and it was added to the above gels. The gels were then run through a battery of tests in order to determine their physical properties such as pH and viscosity. Diffusion studies were carried out on the gels containing the drug. Antimicrobial testing of the gels against various bacteria was then carried out to determine the effectiveness of the gels against these pathogens. The results showed that natural polymers can be used to produce gels. These gels do not have inherent antimicrobial properties against A. actinomycetemcomitans and S. mutans. However, they can be used as a transport vehicle to carry and release antimicrobial drugs.

Central blockade of salusin ß attenuates hypertension and hypothalamic inflammation in spontaneously hypertensive rats.

Salusin ß is a multifunctional bioactive peptide and is considered as a promising candidate biomarker for predicting atherosclerotic cardiovascular diseases. The present study was designed to investigate the roles and mechanisms of salusin ß in the paraventricular nucleus (PVN) in attenuating hypertension and hypothalamic inflammation and whether central salusin ß blockade has protective effects in essential hypertension. Normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were used in this study. The rats were chronic PVN infusion either specific salusin ß blocker, antisalusin ß IgG (SIgG), or control IgG (CIgG) for 2 weeks. Hypertensive rats had significantly increased salusin ß expression compared with normotensive rats. Central blockade of salusin ß attenuated hypertension, reduced circulating norepinephrine (NE) levels, and improved cardiac hypertrophy and function in hypertensive rats. Salusin ß blockade significantly reduced proinflammatory cytokines (PICs), nuclear factor-kappa B (NF-κB) activity, reactive oxygen species (ROS) levels, and altered renin-angiotensin system (RAS) components in the PVN of hypertensive rats. These findings suggest that the beneficial effects of salusin ß blockade in essential hypertension are possibly due to down-regulate of inflammatory molecules and ROS in the PVN.