Marine reserves promote cycles in fish populations on ecological and evolutionary time scales.

Marine reserves are considered essential for sustainable fisheries, although their effectiveness compared to traditional fisheries management is debated. The effect of marine reserves is mostly studied on short ecological time scales, whereas fisheries-induced evolution is a well-established consequence of harvesting. Using a size-structured population model for an exploited fish population of which individuals spend their early life stages in a nursery habitat, we show that marine reserves will shift the mode of population regulation from low size-selective survival late in life to low, early-life survival due to strong resource competition. This shift promotes the occurrence of rapid ecological cycles driven by density-dependent recruitment as well as much slower evolutionary cycles driven by selection for the optimal body to leave the nursery grounds, especially with larger marine reserves. The evolutionary changes increase harvesting yields in terms of total biomass but cause disproportionately large decreases in yields of larger, adult fish. Our findings highlight the importance of carefully considering the size of marine reserves and the individual life history of fish when managing eco-evolutionary marine systems to ensure both population persistence as well as stable fisheries yields.

Comparison of the Clinical Outcomes of Vesselplasty vs. Percutaneous Vertebroplasty for the Treatment of Neurologically Intact Osteoporotic Kümmell's Disease: A Retrospective Study.

Kummell's disease (KD) is a rare clinical complication of osteoporotic vertebral compression fractures (OVCFs). Minimally invasive surgery is an important way to treat KD. In this paper, we used Percutaneous Vertebroplasty (PVP) and Vesselplasty (VP) to treat KD. 125 patients with KD were admitted to our hospital. Among them, 89 patients received PVP and 36 received VP. All patients underwent operations successfully. VAS scores and ODI of both groups at each postoperative time point were lower than preoperatively. Postoperative Cobb angle of both groups postoperatively was lower than preoperatively (p < 0.05). The anterior height and ratio of vertebra compression of both groups postoperatively was lower than preoperatively (p < 0.05). Cement leakage occurred in 16 vertebrae (16/89) in PVP group and one (1/36) in VP group. Two patients suffered from transient paraplegia in PVP group immediately after operation. Adjacent vertebral fractures occurred in one patient in PVP group and one in VP group. Re-fracture of affected vertebra occurred in one patient in PVP group. Besides, four patients suffered from bone cement loosening in PVP group while one in VP group. Both PVP and VP play an important effect in pain relief and functional recovery for the treatment of KD. And VP is more effective than PVP in preventing cement leakage.

A synthetic bacterial consortium improved the phytoremediation efficiency of ryegrass on polymetallic contaminated soil.

Polymetallic contamination of soils caused by mining activities seriously threatens soil fertility, biodiversity and human health. Bioremediation is thought to be of low cost and has minimal environmental risk but its effectiveness needs to be improved. This study aimed to identify the combined effect of plant growth and microbial strains with different functions on the enhancement of bioremediation of polymetallic contaminated soil. The microbiological mechanism of bioremediation was explored by amplicon sequencing and gene prediction. Soil was collected from polymetallic mine wastelands and a non-contaminated site for use in a pot experiment. Remediation efficiency of this method was evaluated by planting ryegrass and applying a mixed bacterial consortium comprising P-solubilizing, N-fixing and SO4-reducing bacteria. The plant-microbe joint remediation method significantly enhanced the above-ground biomass of ryegrass and soil nutrient contents, and at the same time reduced the content of heavy metals in the plant shoots and soil. The application of the composite bacterial inoculum significantly affected the structure of soil bacterial communities and increased the bacterial diversity and complexity, and the stability of co-occurrence networks. The relative abundance of the multifunctional genera to which the strains belonged showed a significant positive correlation with the soil nutrient content. Genera related to carbon (C), nitrogen (N), phosphorus (P), and sulphur (S) cycling and heavy metal resistance showed an up-regulation trend in heavy metal-contaminated soils after the application of the mixed bacterial consortium. Also, bacterial strains with specific functions in the mixed consortium regulated the expression of genes involved in soil nutrient cycling, and thus assisted in making the soil self-sustainable after remediation. These results suggested that the remediation of heavy metal-contaminated soil needs to give priority to the use of multifunctional bacterial agents.

GSK2795039 prevents RIP1-RIP3-MLKL-mediated cardiomyocyte necroptosis in doxorubicin-induced heart failure through inhibition of NADPH oxidase-derived oxidative stress.

Doxorubicin (DOX), which is widely used for the treatment of cancer, induces cardiomyopathy associated with NADPH oxidase-derived reactive oxygen species. GSK2795039 is a novel small molecular NADPH oxidase 2 (Nox2) inhibitor. In this study, we investigated whether GSK2795039 prevents receptor-interacting protein kinase 1 (RIP1)-RIP3-mixed lineage kinase domain-like protein (MLKL)-mediated cardiomyocyte necroptosis in DOX-induced heart failure through NADPH oxidase inhibition. Eight-week old mice were randomly divided into 4 groups: control, GSK2795039, DOX and DOX plus GSK2795039. H9C2 cardiomyocytes were treated with DOX and GSK2795039. In DOX-treated mice, the survival rate was reduced, left ventricular (LV) end-systolic dimension was increased and LV fractional shortening was decreased, and these alterations were attenuated by the GSK2795039 treatment. GSK2795039 inhibited not only myocardial NADPH oxidase subunit gp91phox (Nox2) protein, but also p22phox, p47phox and p67phox proteins and prevented oxidative stress 8-hydroxy-2'-deoxyguanosine levels in DOX-treated mice. RIP3 protein and phosphorylated RIP1 (p-RIP1), p-RIP3 and p-MLKL proteins, reflective of their respective kinase activities, markers of necroptosis, were markedly increased in DOX-treated mice, and the increases were prevented by GSK2795039. GSK2795039 prevented the increases in serum lactate dehydrogenase and myocardial fibrosis in DOX-treated mice. Similarly, in DOX-treated cardiomyocytes, GSK2795039 improved cell viability, attenuated apoptosis and necrosis and prevented the increases in p-RIP1, p-RIP3 and p-MLKL expression. In conclusion, GSK2795039 prevents RIP1-RIP3-MLKL-mediated cardiomyocyte necroptosis through inhibition of NADPH oxidase-derived oxidative stress, leading to the improvement of myocardial remodeling and function in DOX-induced heart failure. These findings suggest that GSK2795039 may have implications for the treatment of DOX-induced cardiomyopathy.

Functional Guilds, Community Assembly, and Co-occurrence Patterns of Fungi in Metalliferous Mine Tailings Ponds in Mainland China.

Metalliferous mine tailings ponds are generally characterized by low levels of nutrient elements, sustained acidic conditions, and high contents of toxic metals. They represent one kind of extreme environments that are believed to resemble the Earth's early environmental conditions. There is increasing evidence that the diversity of fungi inhabiting mine tailings ponds is much higher than previously thought. However, little is known about functional guilds, community assembly, and co-occurrence patterns of fungi in such habitats. As a first attempt to address this critical knowledge gap, we employed high-throughput sequencing to characterize fungal communities in 33 mine tailings ponds distributed across 18 provinces of mainland China. A total of 5842 fungal phylotypes were identified, with saprotrophic fungi being the major functional guild. The predictors of fungal diversity in whole community and sub-communities differed considerably. Community assembly of the whole fungal community and individual functional guilds were primarily governed by stochastic processes. Total soil nitrogen and total phosphorus mediated the balance between stochastic and deterministic processes of the fungal community assembly. Co-occurrence network analysis uncovered a high modularity of the whole fungal community. The observed main modules largely consisted of saprotrophic fungi as well as various phylotypes that could not be assigned to known functional guilds. The richness of core fungal phylotypes, occupying vital positions in co-occurrence network, was positively correlated with edaphic properties such as soil enzyme activity. This indicates the important roles of core fungal phylotypes in soil organic matter decomposition and nutrient cycling. These findings improve our understanding of fungal ecology of extreme environments.

Biomechanical characteristics of a novel interspinous distraction fusion device in the treatment of lumbar degenerative diseases: a finite element analysis.

BACKGROUND: A novel interspinous distraction fusion (ISDF) device has been used to treat lumbar degenerative diseases. As a minimally invasive technique, ISDF differs from the traditional interspinous process distraction devices. Currently, biomechanical studies on ISDF are rare. OBJECTIVE: To investigate the biomechanical properties of the ISDF device (BacFuse) which is used to treat lumbar degenerative diseases. METHODS: Three-dimensional L3-L5 models were created. The models were divided into four groups: intact (M1), local decompression alone (M2), internal fixation alone (M3) and local decompression combined with internal fixation (M4), based on different surgical procedures. Local laminectomy was performed to resect the lower part of the L4 lamina and the upper part of the L5 lamina at the right lamina of L4/5 in the M2 and M4 groups. After meshing the models elements, Abaqus were used to perform the finite element (FE) analysis. The intervertebral range of motion (ROM) was measured during flexion, extension, left lateral bending, right lateral bending, left rotation and right rotation under a follower load of 400 N with a 7.5Nm moment. The distributions of disc and facet joint stresses were observed and recorded. Spinal vertebral stress was compared, and internal fixation device stress was observed. RESULTS: The ROM of L4/5 in M2 increased in flexion, extension, left lateral bending, right lateral bending, left rotation and right rotation compared with that in M1. In all motion directions, the ROM at L4/5 decreased, and the ROM at L3/4 increased after implantation of the ISDF device in M3 and M4 groups. The disc stress and facet joint stresses in the instrumented segment decreased after implantation of the ISDF device. The spinous process loaded a certain amount of stress in M3 and M4 groups. The spikes of the internal fixation device were loaded with the maximum stress. CONCLUSION: BacFuse exhibited a reduction in intervertebral ROM, as well as decreased stress on the intervertebral disc and facet joint, while also demonstrating a discernible impact on the upper adjacent segment.

Research progress on metabolomics in the quality evaluation and clinical study of Panax ginseng.

Panax ginseng, an essential component of traditional medicine and often referred to as the king of herbs, has played a pivotal role in medicine globally for several millennia. Previously, traditional phytochemical methods were mainly used for quality evaluation and pharmacological mechanism studies of ginseng, resulting in the lack of systematicness and innovation and hindering the development and utilization of ginseng resources. Since the beginning of the new century, systems biology technology represented by metabolomics has shown unique advantages in the modernization and internationalization of herbal medicine, establishing a bridge for communication between traditional medicine and modern medicine. P. ginseng, a special herb used in medicine and food, is one of the main research objects for qualitative and quantitative analysis of metabolomics and has gradually become the focus of researchers globally. Here, we conducted a comprehensive summary and analysis of numerous studies published in ginseng metabolomics. This review aims to provide more novel ideas for the quality evaluation, development, and clinical application of ginseng in the future and offer more useful technical references for the modernization and internationalization of herbal medicine based on metabolomics.

Functional traits explain the consistent resistance of biodiversity to plant invasion under nitrogen enrichment.

Elton's biotic resistance hypothesis, which posits that diverse communities should be more resistant to biological invasions, has received considerable experimental support. However, it remains unclear whether such a negative diversity-invasibility relationship would persist under anthropogenic environmental change. By using the common ragweed (Ambrosia artemisiifolia) as a model invader, our 4-year grassland experiment demonstrated consistently negative relationships between resident species diversity and community invasibility, irrespective of nitrogen addition, a result further supported by a meta-analysis. Importantly, our experiment showed that plant diversity consistently resisted invasion simultaneously through increased resident biomass, increased trait dissimilarity among residents, and increased community-weighted means of resource-conservative traits that strongly resist invasion, pointing to the importance of both trait complementarity and sampling effects for invasion resistance even under resource enrichment. Our study provides unique evidence that considering species' functional traits can help further our understanding of biotic resistance to biological invasions in a changing environment.

Remarkable effects of microbial factors on soil phosphorus bioavailability: A country-scale study.

Low soil phosphorus (P) bioavailability causes the widespread occurrence of P-limited terrestrial ecosystems around the globe. Exploring the factors influencing soil P bioavailability at large spatial scales is critical for managing these ecosystems. However, previous studies have mostly focused on abiotic factors. In this study, we explored the effects of microbial factors on soil P bioavailability of terrestrial ecosystems using a country-scale sampling effort. Our results showed that soil microbial biomass carbon (MBC) and acid phosphatase were important predictors of soil P bioavailability of agro- and natural ecosystems across China although they appeared less important than total soil P. The two microbial factors had a positive effect on soil P bioavailability of both ecosystem types and were able to mediate the effects of several abiotic factors (e.g., mean annual temperature). Meanwhile, we revealed that soil phytase could affect soil P bioavailability at the country scale via ways similar to those of soil MBC and acid phosphatase, a pattern being more pronounced in agroecosystems than in natural ecosystems. Moreover, we obtained evidence for the positive effects of microbial genes encoding these enzymes on soil P bioavailability at the country scale although their effect sizes varied between the two ecosystem types. Taken together, this study demonstrated the remarkable effects of microbial factors on soil P bioavailability at a large spatial scale, highlighting the importance to consider microbial factors in managing the widespread P-limited terrestrial ecosystems.

Discovery and therapeutic implications of bioactive dihydroxylated phenolic acids in patients with severe heart disease and conditions associated with inflammation and hypoxia.

Our initial studies detected elevated levels of 3,4-dihydroxyphenyllactic acid (DHPLA) in urine samples of patients with severe heart disease when compared with healthy subjects. Given the reported anti-inflammatory properties of DHPLA and related dihydroxylated phenolic acids (DPAs), we embarked on an exploratory multi-centre investigation in patients with no urinary tract infections to establish the possible pathophysiological significance and therapeutic implications of these findings. Chinese and Caucasian patients being treated for severe heart disease or those conditions associated with inflammation (WBC ≥ 10 ×109/L or hsCRP ≥ 3.0 mg/L) and/or hypoxia (PaO2 ≤ 75 mmHg) were enrolled; their urine samples were analyzed by HPLC, HPLC-MS, GC-MS and biotransformation assays. DHPLA was detected in urine samples of patients, but undetectable in healthy volunteers. Dynamic monitoring of inpatients undergoing treatment showed their DHPLA levels declined in proportion to their clinical improvement. In DHPLA-positive patients' fecal samples, Proteus vulgaris and P. mirabilis were more abundant than healthy volunteers. In culture, these gut bacteria were capable of reversible interconversion between DOPA and DHPLA. Furthermore, porcine and rodent organs were able to metabolize DOPA to DHPLA and related phenolic acids. The elevated levels of DHPLA in these patients suggest bioactive DPAs are generated de novo as part of a human's defense mechanism against disease. Because DHPLA isolated from Radix Salvia miltiorrhizae has a multitude of pharmacological activities, these data underpin the scientific basis of this medicinal plant's ethnopharmacological applications as well as highlighting the therapeutic potential of endogenous, natural or synthetic DPAs and their derivatives in humans.

Ultra-Performance Liquid Chromatography-Q-Exactive Orbitrap-Mass Spectrometry Analysis for Metabolic Communication between Heart and Kidney in Adriamycin-Induced Nephropathy Rats.

BACKGROUND/AIMS: Although the adriamycin-induced nephropathy model is frequently employed in the study of nephrotic syndrome and focal segmental glomerulosclerosis, the accompanying myocardial damage has always been a cause for concern. Therefore, there is a great need to study cardiorenal communication in this model. METHODS: An adriamycin-induced nephropathy model was established via tail vein injection. The levels of the biochemical indicators serum albumin, serum globulin, serum total protein, serum cholesterol, serum creatinine (SCr), urinary protein, and urinary creatinine (UCr) were measured, and histopathological changes in the heart and kidneys were assessed using hematoxylin-eosin staining. Metabolomic changes in the heart, blood, and kidneys were analyzed using the metabolomics method based on ultra-performance liquid chromatography Q-Exactive Orbitrap mass spectrometry. RESULTS: Compared with the control group, the model group showed significant decreases in serum protein and total protein levels, albumin/globulin ratio, and creatinine clearance rate as well as significant increases in serum cholesterol, SCr, urinary protein, and UCr levels. Significant pathological changes were observed in the renal pathology sections in the model group, including diffusely merged glomerular epithelial cells, inflammatory infiltration, and vacuolated glomerular cells. Additionally, thickened myocardial fibers, swollen nuclei, inflammatory infiltration, and partial myocardial necrosis could be seen in the cardiac pathology sections in the model group. Based on multivariate statistical analysis, a total of 20 differential metabolites associated with 15 metabolic pathways were identified in the heart, 7 differential metabolites with 7 metabolic pathways were identified in the blood, and 16 differential metabolites with 21 metabolic pathways were identified in the kidney. Moreover, 6 common metabolic pathways shared by the heart and kidney were identified: arginine and proline metabolism; arginine biosynthesis; glutathione metabolism; alanine, aspartate, and glutamate metabolism; beta-alanine metabolism; and histidine metabolism. Among these metabolic pathways, alanine, aspartate, and glutamate metabolism was shared by the heart, blood, and kidney. Succinic acid was found to be the key regulatory metabolite in cardiorenal metabolic communication. CONCLUSION: Six metabolic pathways were found to be involved in cardiorenal metabolic communication in an adriamycin-induced nephropathy model, in which alanine, aspartate, and glutamate metabolism may be the metabolic link between the heart and kidney in the development and maintenance of oxidative stress and inflammation. Succinic acid may serve as a key regulatory metabolic switch or marker of cardiac and renal co-injury, as shown in an adriamycin-induced nephropathy model.

Insights into the development of pentylenetetrazole-induced epileptic seizures from dynamic metabolomic changes.

Epilepsy is often considered to be a progressive neurological disease, and the nature of this progression remains unclear. Understanding the overall and common metabolic changes of epileptic seizures can provide novel clues for their control and prevention. Herein, a chronic kindling animal model was established to obtain generalized tonic-clonic seizures via the repeated injections of pentylenetetrazole (PTZ) at subconvulsive dose. Dynamic metabolomic changes in plasma and urine from PTZ-kindled rats at the different kindling phases were explored using NMR-based metabolomics, in combination with behavioral assessment, brain neurotransmitter measurement, electroencephalography and histopathology. The increased levels of glucose, lactate, glutamate, creatine and creatinine, together with the decreased levels of pyruvate, citrate and succinate, ketone bodies, asparagine, alanine, leucine, valine and isoleucine in plasma and/or urine were involved in the development and progression of seizures. These altered metabolites reflected the pathophysiological processes including the compromised energy metabolism, the disturbed amino acid metabolism, the peripheral inflammation and changes in gut microbiota functions. NMR-based metabolomics could provide brain disease information by the dynamic plasma and urinary metabolic changes during chronic epileptic seizures, yielding classification of seizure stages and profound insights into controlling epilepsy via targeting deficient energy metabolism.

Host plant environmental filtering drives foliar fungal community assembly in symptomatic leaves.

Foliar fungi (defined as all fungal species in leaves after surface sterilization; hereafter, 'FF') are of great importance to host plant growth and health, and can also affect ecosystem functioning. Despite this importance, few studies have explicitly examined the role of host filtering in shaping local FF communities, and we know little about the differences of FF community assembly between symptomatic (caused by fungal pathogens) and asymptomatic leaves, and whether there is phylogenetic congruence between host plants and FF. We examined FF communities from 25 host plant species (for each species, symptomatic and asymptomatic leaves, respectively) in an alpine meadow of the Tibetan Plateau using MiSeq sequencing of ITS1 gene biomarkers. We evaluated the phylogenetic congruence of FF-plant interactions based on cophylogenetic analysis, and examined α- and ß-phylogenetic diversity indices of the FF communities. We found strong support for phylogenetic congruence between host plants and FF for both asymptomatic and symptomatic leaves, and a host-caused filter appears to play a major role in shaping FF communities. Most importantly, we provided independent lines of evidence that host environmental filtering (caused by fungal infections) outweighs competitive exclusion in driving FF community assembly in symptomatic leaves. Our results help strengthen the foundation of FF community assembly by demonstrating the importance of host environmental filtering in driving FF community assembly.

Apocynin prevents reduced myocardial nerve growth factor, contributing to amelioration of myocardial apoptosis and failure.

Reduced nerve growth factor (NGF) is associated with cardiac sympathetic nerve denervation in heart failure (HF) which is characterized by increased oxidative stress. Apocynin is considered an antioxidant agent which inhibits NADPH oxidase activity and improves reactive oxygen species scavenging. However, it is unclear whether apocynin prevents reduced myocardial NGF, leading to improvement of cardiac function in HF. In this study, we tested the hypothesis that apocynin prevents reduced myocardial NGF, contributing to amelioration of myocardial apoptosis and failure. Rabbits with myocardial infarction (MI) or sham operation were randomly assigned to receive apocynin or placebo for 4 weeks. MI rabbits exhibited left ventricular (LV) dysfunction, and elevation in oxidative stress, as evidenced by a decreased reduced-to-oxidized glutathione ratio and an increased 4-hydroxynonenal expression, and reduction in NGF and NGF receptor tyrosine kinase A (TrKA) expression in the remote non-infarcted myocardium. Apocynin treatment ameliorated LV dysfunction, reduced oxidative stress, prevented decreases in NGF and TrKA expression and reduced cardiomyocyte apoptosis after MI. In cultured H9C2 cardiomyocytes, hypoxia or hydrogen peroxide decreased NGF expression, and apocynin normalized hypoxia-induced reduction of NGF. Recombinant NGF attenuated hypoxia-induced apoptosis. Apocynin prevented hypoxia-induced apoptosis, and the suppressive effect of apocynin on apoptosis was abolished by NGF receptor TrKA inhibitor K252a. We concluded that apocynin prevented reduced myocardial NGF, leading to attenuation of cardiomyocyte apoptosis and LV remodelling and dysfunction in HF after MI. These findings suggest that strategies to prevent NGF reduction by inhibition of oxidative stress may be of value in amelioration of LV dysfunction in HF.

Effect of co-administration of Acori Tatarinowii Rhizoma volatile oil on pharmacokinetic fate of xanthotoxol, oxypeucedanin hydrate, and byakangelicin from Angelicae Dahuricae Radix in rat.

A combination of Angelicae Dahuricae Radix and Acori Tatarinowii Rhizoma has been widely used as the herb pair in traditional Chinese medicine to treat stroke, migraine, and epilepsy. However, the underlying synergistic mechanism of the herb pair remains unknown. This study was aimed at investigating the effects of Acori Tatarinowii Rhizoma volatile oil on the pharmacokinetic parameters of xanthotoxol, oxypeucedanin hydrate, and byakangelicin from Angelicae Dahuricae Radix in rat, and in vitro absorption behavior of the three compounds using rat everted gut sac, in situ single-pass intestinal perfusion, and Caco-2 cell monolayer models. The pharmacokinetic study exhibited clear changes in the key pharmacokinetic parameters of the three main coumarins through co-administering with Acori Tatarinowii Rhizoma volatile oil (50 mg/kg), the area under curve and the maximum plasma concentration of xanthotoxol increased 1.36 and 1.31 times; the area under curve, the maximum plasma concentration, mean residence time, half-life of elimination, and the time to reach peak concentration of oxypeucedanin hydrate increased by 1.35, 1.18, 1.24, 1.19 and 1.49 times, respectively; the area under curve, mean residence time, half-life of elimination, and time to reach peak concentration of byakangelicin climbed 1.29, 1.27, 1.37, and 1.28 times, respectively. The three coumarin components were absorbed well in the jejunum and ileum in the intestinal perfusion model, when co-administered with Acori Tatarinowii Rhizoma volatile oil (100 µg/mL). The in vivo and in vitro experiments showed good relevance and consistency. The results demonstrated that the three coumarin compounds from Angelicae Dahuricae Radix were absorbed through the active transportation, and Acori Tatarinowii Rhizoma volatile oil could promote the intestinal absorption and transport of these compounds by inhibiting P-glycoprotein (P-gp)-mediated efflux.

Pharmacokinetics of 13 active components in a rat model of middle cerebral artery occlusion after intravenous injection of Radix Salviae miltiorrhizae-Lignum dalbergiae odoriferae prescription.

As a representative formulation of Radix Salviae miltiorrhizae (Danshen)-Lignum Dalbergiae odoriferae (Jiangxiang), Xiangdan injection is widely prescribed for cardio- and cerebrovascular diseases in practice. This necessitates a pharmacokinetic investigation of this formulation to make it safer and more broadly applicable. We developed and validated a sensitive, selective, and reliable high-performance liquid chromatography with tandem mass spectrometry method for the simultaneous determination of 11 phenolic compounds including danshensu plus two diterpenoid quinones like cryptotanshinone and tanshinone IIA in rat. We applied this method for the pharmacokinetic studies of the 13 compounds in a rat model of middle cerebral artery occlusion after intravenous injection of Xiangdan injection or Danshen injection. In sham-operated rats, the animals taking Xiangdan injection exhibited significant growth of the area under the curve for danshensu, protocatechuic aldehyde, and tanshinone IIA compared with the changes seen in the data of those administrated with Danshen injection. Such a pattern was also observed in middle cerebral artery occlusion rats, whereas increased the area under the curve values were observed for danshensu, protocatechuic aldehyde, caffeic acid, rosmarinic acid, and tanshinone IIA. These results demonstrated that synergistic interactions occurred between the components of Danshen and the active compounds of Jiangxiang both in sham-operated and middle cerebral artery occlusion rats, increasing the bioavailability of Danshen. The results presented herein can be used to determine a reference dose for the clinical application of Xiangdan injection, and to elucidate the synergistic mechanism of Danshen and Jiangxiang.

U-shaped association between plasma sphingosine-1-phosphate levels and mortality in patients with chronic systolic heart failure: a prospective cohort study.

BACKGROUND: The endogenous lipid molecule sphingosine-1-phosphate (S1P) has received attention in the cardiovascular field due to its significant cardioprotective effects, as revealed in animal studies. The purpose of our study was to identify the distribution characteristics of S1P in systolic heart failure patients and the prognostic value of S1P for long-term prognosis. METHODS: We recruited 210 chronic systolic heart failure patients from June 2014 to December 2015. Meanwhile 54 healthy people in the same area were selected as controls. Plasma S1P was measured by liquid chromatography-tandem mass spectrometry. Patients were grouped according to the baseline S1P level quartiles, and restricted cubic spline plots described the association between S1P and all-cause death. Cox proportional hazard analysis was used to determine the relationship between category of S1P and all-cause death. RESULTS: Compared with the control group, the plasma S1P in chronic heart failure patients demonstrated a higher mean level (1.269 µmol/L vs 1.122 µmol/L, P = 0.006) and a larger standard deviation (0.441 vs 0.316, P = 0.022). Based on multivariable Cox regression with restricted cubic spline analysis, a non-linear and U-shaped association between S1P levels and the risk of all-cause death was observed. After a follow-up period of 31.7 ± 10.3 months, the second quartile (0.967-1.192 µml/L) with largely normal S1P levels had the lowest all-cause mortality and either an increase (adjusted HR = 2.368, 95%CI 1.006-5.572, P = 0.048) or a decrease (adjusted HR = 0.041, 95%CI 0.002-0.808, P = 0.036) predicted a worse prognosis. The survival curves showed that patients in the lowest quartile and highest quartile were at a higher risk of death. CONCLUSIONS: Plasma S1P levels in systolic heart failure patients are related to the long-term all-cause mortality with a U-shaped correlation. TRIAL REGISTRATION: CHiCTR, ChiCTR-ONC-14004463. Registered 20 March 2014.

Percutaneous vertebral augmentation using drill rotation for osteoporotic vertebral compression fractures with intravertebral vacuum cleft.

OBJECTIVE: To evaluate the efficacy of a new technique of percutaneous vertebral augmentation (PVA): drill rotation-cement injected under vacuum aspiration (DR-CIVAS) for vertebral compression fractures (OVCFs) with intravertebral vacuum cleft (IVC) sign. MATERIALS AND METHODS: A retrospective study was conducted in 46 consecutive patients with OVCFs and IVC signs, who underwent PVA using DR-CIVAS (n = 22, DR-CIVAS group) or traditional technique without DR-CIVAS (n = 24, control group). The pre- and postoperative vertebral height and wedge angle change and visual analog scale (VAS), the volume of cement injected, incidences of cement leakage, and subsequent new vertebral compression fractures were evaluated between the two groups. RESULTS: No significant difference was found in cement leakage incidences, pre- and postoperative VAS scores, vertebral height, and wedge angle change between the two groups. The mean cement volume was significantly higher (P < 0.001) in DR-CIVAS group (4.87 mL) than in the control group (3.58 mL). Of the 22 patients in DR-CIVAS group, the subsequent fractures occurred in 2 cases (9.1%) located in the nonadjacent levels. In the control group, the subsequent fractures occurred in 6 cases (25.0%) located in the adjacent level (n = 1) and the augmented levels (n = 5). Although DR-CIVAS group did not demonstrate a statistical reduction of the incidence of subsequent fractures (P = 0.25), the subgroup analysis revealed that subsequent fractures frequently involved the augmented level in the control group (P = 0.04). CONCLUSIONS: PVA with DR-CIVAS technique is effective for OVCFs with IVC sign, with lower incidences of subsequent new vertebral compression fractures in the augmented vertebra.

The NADPH oxidase inhibitor apocynin improves cardiac sympathetic nerve terminal innervation and function in heart failure.

NEW FINDINGS: What is the central question of this study? Does NADPH oxidase activation mediate cardiac sympathetic nerve denervation and dysfunction in heart failure. What is the main findings and its importance? Cardiac sympathetic nerve terminal density and function were reduced in heart failure after myocardial infarction in rabbits. The NADPH oxidase inhibitor apocynin prevented the reduction in cardiac sympathetic nerve terminal density and function in heart failure. This suggest that NADPH oxidase activation mediates cardiac sympathetic nerve terminal abnormalities in heart failure. NADPH oxidase may be a potential therapeutic target for cardiac sympathetic denervation and dysfunction in heart failure. ABSTRACT: Congestive heart failure (CHF) is characterized by cardiac sympathetic nerve terminal abnormalities, as evidenced by decreased noradrenaline transporter (NAT) density and cardiac catecholaminergic and tyrosine hydroxylase (TH) profiles. These alterations are associated with increased reactive oxygen species (ROS). NADPH oxidase is a major source of ROS in CHF. In this study, we tested the hypothesis that NADPH oxidase activation mediates cardiac sympathetic nerve terminal abnormalities in CHF. CHF was produced by myocardial infarction (MI) in rabbits. Rabbits with MI or a sham operation were randomized to orally receive an NADPH oxidase inhibitor, apocynin (6 mg kg-1  day-1 ), or placebo for 30 days. MI rabbits exhibited left ventricular dilatation, systolic dysfunction, and increases in NADPH oxidase activity and 4-hydroxynonenal expression in the remote non-infarcted myocardium, all of which were prevented by treatment with apocynin. Cardiac catecholaminergic histofluorescence profiles and immunostained TH and PGP9.5 expression were decreased, and the decreases were ameliorated by apocynin treatment. NAT, TH and PGP9.5 protein and mRNA expression were reduced and the reduction was mitigated by apocynin treatment. The effects of apocynin were confirmed by utilizing the NADPH oxidase inhibitor diphenyleneiodonium in a separate experiment. In conclusion, the NADPH oxidase inhibitor apocynin attenuated increased myocardial oxidative stress and decreased cardiac sympathetic nerve terminals in CHF after MI in rabbits. These findings suggest that the activation of NADPH oxidase mediates cardiac sympathetic nerve terminal abnormalities in CHF, and the inhibition of NADPH oxidase may be beneficial for the treatment of heart failure.

Vitamin D deficiency is associated with risk of developing peripheral arterial disease in type 2 diabetic patients.

BACKGROUND: The relationship between vitamin D levels and peripheral arterial disease (PAD) remains unclear. We assessed the association of serum 25-hydroxyvitamin D (25(OH)D) levels with the prevalence of PAD in patients with type 2 diabetes mellitus(T2DM). METHODS: A total of 1018 T2DM patients participated in this cross-sectional study. Serum 25(OH)D levels were measured and risk factors of PAD were recorded. PAD was diagnosed as an ankle-brachial index (ABI) < 0.9. RESULTS: The mean age of the diabetic patients was 58.59 ± 11.34 years. Of all the patients, only 20.1% had a 25(OH)D level ≥ 20 ng/mL. Compared to patients without PAD, serum 25(OH)D levels were significantly lower in those with PAD (14.81 ± 8.43 vs. 11.55 ± 5.65 ng/mL, P < 0.001). The overall prevalence of PAD was 7.7%. From the highest level (≥ 20 ng/mL) to the lowest level (< 10 ng/mL) of serum 25(OH)D, the prevalence of PAD was 2.8, 7.5 and 10.7% respectively. After adjustment for age, sex, body mass index (BMI), smoking status and season, compared to patients with serum 25(OH)D levels ≥20 ng/mL, the odds ratios of PAD in patients with a level of 10 to < 20 ng/mL and < 10 ng/mL was 3.587(95% CI: 1.314-9.790) and 5.540(95% CI: 2.004-15.320), respectively. When further considering the influence of coronary heart disease (CHD), hypertension and cerebral infarction, the ratios changed to 3.824(95% CI: 1.378-10.615) and 5.729(95% CI: 2.028-16.187), respectively. And after further adjustment for the duration of diabetes, glycated hemoglobin (HbA1c) and glomerular filtration rate (GFR), the ratios changed to 3.489(95% CI: 1.100-11.062) and 3.872(95% CI: 1.168-12.841), respectively. CONCLUSIONS: Reduced serum vitamin D levels were associated with an increased risk of PAD in T2DM patients. Randomized interventive clinical studies are required to verify the effects of vitamin D supplementation on PAD.