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Objective:To investigate the value of nasal provocation testï¼NPTï¼ in evaluating the efficacy of allergen immunotherapyï¼AITï¼ in patients with dust mite induced allergic rhinitisï¼ARï¼. Methods:A total of 83 patients with dust mite induced AR with/without asthma were included. Symptom scoreï¼SSï¼, daily medication scoreï¼DMSï¼, combined symptom and medication scoreï¼CSMSï¼, rhinoconjunctivitis quality of life questionnaireï¼RQLQï¼, NPT and skin prick testï¼SPTï¼ were assessed before and after 1 year AIT. Results:There were statistical differences in SSï¼P<0.000 1ï¼, DMSï¼P<0.000 1ï¼, CSMSï¼P<0.000 1ï¼, and RQLQï¼P<0.000 1ï¼ after 1 year of AIT compared with pre-treatment. The effective rate of CSMS was 73.49%, and the effective rate of NPT was 42.17%. CSMS was consistent with NPT in efficacy assessmentï¼Kappa=0.437, P<0.001ï¼; while in 54 patients with pre-treatment NPT concentrations other than the original concentration, CMSM and NPT showed better consistenceï¼Kappa=0.895, P<0.001ï¼. Among the 48 patients with ineffective NPT assessment in the first year, 25 patients completed the second-year follow-up, and 12 patientsï¼48.00%ï¼ showed effective in NPT. However, 10 out of 12 patientsï¼83.33%ï¼ with NPT concentration other than original solution pre-treatment showed effective NPT at the second year. Conclusion:NPT can be used as one of the indicators for efficacy evaluation for dust mite induced AR patients, especially for patients with positive NPT induced at lower concentrations before treatment.
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Pyroglyphidae , Rinitis Alérgica , Animales , Humanos , Alérgenos , Pruebas de Provocación Nasal , Calidad de Vida , Rinitis Alérgica/diagnóstico , Rinitis Alérgica/terapia , Desensibilización Inmunológica , Pruebas Cutáneas , PolvoRESUMEN
The phenotypic plasticity hypothesis suggests that exotic plants may have greater phenotypic plasticity than native plants. However, whether phenotypic changes vary according to different environmental factors has not been well studied. We conducted a multi-species greenhouse experiment to study the responses of six different phenotypic traits, namely height, leaf number, specific leaf area, total biomass, root mass fraction, and leaf mass fraction, of native and invasive species to nutrients, water, and light. Each treatment was divided into two levels: high and low. In the nutrient addition experiment, only the leaf mass fraction and root mass fraction of the plants supported the phenotypic plasticity hypothesis. Then, none of the six traits supported the phenotypic plasticity hypothesis in the water or light treatment experiments. The results show that, for different environmental factors and phenotypes, the phenotypic plasticity hypothesis of plant invasion is inconsistent. When using the phenotypic plasticity hypothesis to explain plant invasion, variations in environmental factors and phenotypes should be considered.
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Background and Objective: Hyperuricemia is closely related to chronic kidney disease (CKD). The effects of urate-lowering therapy (ULT) on renal outcomes are uncertain, and whether it is warranted in CKD patients is currently unclear. The aim of our meta-analysis of randomized clinical trials (RCTs) was to assess the effectiveness and safety of ULT for improving kidney function in patients with CKD. Methods: RCTs were retrieved from the PubMed, Embase, MEDLINE and Cochrane Central Register of Controlled Trials databases. The meta-analysis was performed using Review Manager and Stata/SE software. The outcomes were changes in renal function and serum uric acid (SUA), serum creatinine, and adverse events. Results: Twelve RCTs with 1,469 participants were included in the meta-analysis. ULT was found to effectively lower SUA (standard mean difference (SMD): -2.70; 95% confidence interval (CI): -3.71, -1.69) but the renoprotective effects were not superior to those of control therapy (placebo or usual therapy), which were stable in the subgroup analyses and sensitivity analyses. Regarding adverse events, their risks did not increase in the ULT group compared with the control group and were stable in the sensitivity analyses. Conclusion: The findings of our meta-analysis suggested that ULT can effectively lower SUA, but there is insufficient evidence to support the renoprotective effects of ULT in CKD patients. In addition, ULT is safe for patients with CKD. Systematic Review Registration: https://clinicaltrials.gov/, identifier PROSPERO (CRD42020200550).
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The construction of large earth/rock fill dams, albeit its remarkable progress, still relies largely on past experiences. Therefore, a comprehensive yet dependable monitoring program is particularly beneficial for guiding the practice. However, conventional measurements can only produce limited discrete data. This paper exploits the potential of the terrestrial laser scanning (TLS) for an accurate inventory of as-built states of a concrete-faced rockfill dam under construction and for a full-field analysis of the 3D deformation pattern over its upstream face. For the former, a well-designed 3D geodetic system, with a particular consideration of the topography, promises a regulated acquisition of high-quality and blind-zone-free point cloud at field and also eases the cumbersome data registration process while maintaining its precision in house. For the latter, a problem-tailored processing pipeline is proposed for deformation extraction. Its core idea is to achieve a highly precise alignment of the point clouds with Iterative Closed Point algorithms from different epochs in datum areas that displays a featured, undeformed geometry at stable positions across epochs. Then, the alignment transformation matrix is applied to the point clouds of respective upstream face for each epoch, followed by pairwise comparisons of multiple adjusted point clouds for deformation evaluation. A processing pipeline is used to exploit the peal scene data redundancy of the GLQ dam acquired at six different epochs. Statistical analysis shows that satisfactory accuracy for deformation detection can be repeatably achieved, regardless of the scanner's positioning uncertainties. The obtained 3D deformation patterns are characterised by three different zones: practically undeformed, outward and inward deformed zones. Their evolutions comply well with real construction stages and unique 3D valley topography. Abundant deformation results highlight the potential of TLS combined with the proposed data processing pipeline for cost-efficient monitoring of huge infrastructures compared to conventional labor-intense measurements.
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Background: Hyperuricemia is very common in patients with chronic kidney disease (CKD); the role of hyperuricemia in the occurrence and progression of kidney disease remains an interesting and unresolved issue for nephrologists, and whether urate-lowering therapy (ULT) is warranted in CKD patients is still in controversy. To summarize and compare the clinical outcomes and adverse events (AEs) of three common ULT drugs, we performed a systematic review and network meta-analysis of randomized clinical trials (RCTs). Method: PubMed, MEDLINE, Clinical Trials.gov, EMBASE, and the Cochrane Central Register of Controlled Trials electronic databases were searched. The network meta-analysis was performed using the "gemtc 0.8-7" and its dependent packages in R software. The primary outcome was the change of renal function and uric acid; creatinine, proteinuria, blood pressure, and adverse events were assessed as the secondary outcomes. Results: 16 RCTs involving 1,943 patients were included in the final network analysis. Febuxostat, allopurinol, and benzbromarone were not found to exert superior effects over placebo upon renoprotective effect. With respect to lowering urate, the three drugs showed to be statistically superior to placebo, while febuxostat could better lower urate than allopurinol (MD: -1.547; 95% CrI: -2.473 to -0.626). It is also indicated that febuxostat was superior to placebo at controlling blood pressure, while no differences were observed when allopurinol and benzbromarone were compared to placebo. These results are stable in subgroup analysis. Conclusion: There is insufficient evidence to support the renoprotective effects of the three urate-lowering agents in CKD patients with hyperuricemia; febuxostat shows a tendency to be superior to allopurinol on lowering the decline of eGFR and increment of proteinturia, but the difference does not reach a statistical significance. Regarding its urate-lowering effect, febuxostat appears to be a satisfactory alternative to allopurinol and benzbromarone, and can control blood pressure better.
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Prolonged type 2 diabetes mellitus (T2DM) produces a common complication, peripheral neuropathy, which is accompanied by nerve fiber disorder, axon atrophy, and demyelination. Growing evidence has characterized the beneficial effects of acidic fibroblast growth factor (aFGF) and shown that it relieves hyperglycemia, increases insulin sensitivity, and ameliorates neuropathic impairment. However, there is scarce evidence on the role of aFGF on remodeling of aberrant myelin under hyperglycemia condition. Presently, we observed that the expression of aFGF was rapidly decreased in a db/db T2DM mouse model. Administration of exogenous aFGF was sufficient to block acute demyelination and nerve fiber disorganization. Furthermore, this strong anti-demyelinating effect was most likely dominated by an aFGF-mediated increase of Schwann cell (SC) proliferation and migration as well as suppression of its apoptosis. Mechanistically, the beneficial biological effects of aFGF on SC behavior and abnormal myelin morphology were likely due to the inhibition of hyperglycemia-induced oxidative stress activation, which was most likely activated by kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid-derived-like 2 (Nrf2) signaling. Thus, this evidence indicates that aFGF is a promising protective agent for relieving myelin pathology through countering oxidative stress signaling cascades under diabetic conditions.
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Diabetes Mellitus Tipo 2/terapia , Factor 1 de Crecimiento de Fibroblastos/uso terapéutico , Animales , Modelos Animales de Enfermedad , Factor 1 de Crecimiento de Fibroblastos/farmacología , Masculino , Ratones , Estrés Oxidativo , Ratas , Especies Reactivas de OxígenoRESUMEN
The blood-spinal cord barrier plays a vital role in recovery after spinal cord injury. The neurovascular unit concept emphasizes the relationship between nerves and vessels in the brain, while the effect of the blood-spinal cord barrier on the neurovascular unit is rarely reported in spinal cord injury studies. Mouse models of spinal cord injury were established by heavy object impact and then immediately injected with platelet-derived growth factor (80 µg/kg) at the injury site. Our results showed that after platelet-derived growth factor administration, spinal cord injury, neuronal apoptosis, and blood-spinal cord barrier permeability were reduced, excessive astrocyte proliferation and the autophagy-related apoptosis signaling pathway were inhibited, collagen synthesis was increased, and mouse locomotor function was improved. In vitro, human umbilical vein endothelial cells were established by exposure to 200 µM H2O2. At 2 hours prior to injury, in vitro cell models were treated with 5 ng/mL platelet-derived growth factor. Our results showed that expression of blood-spinal cord barrier-related proteins, including Occludin, Claudin 5, and ß-catenin, was significantly decreased and autophagy was significantly reduced. Additionally, the protective effects of platelet-derived growth factor could be reversed by intraperitoneal injection of 80 mg/kg chloroquine, an autophagy inhibitor, for 3 successive days prior to spinal cord injury. Our findings suggest that platelet-derived growth factor can promote endothelial cell repair by regulating autophagy, improve the function of the blood-spinal cord barrier, and promote the recovery of locomotor function post-spinal cord injury. Approval for animal experiments was obtained from the Animal Ethics Committee, Wenzhou Medical University, China (approval No. wydw2018-0043) in July 2018.
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Marine mammals are an important part of ocean ecosystems, of which, whales play a vital role in the marine food chain. In this study, the mucosa and contents from different intestinal tract segments (ITSs) of a stranded dwarf minke whale (Balaenoptera acutorostrata) were analyzed. The gut microbiota were sequenced using high-throughput sequencing technology, based on a 16S rRNA approach. The microbial composition of the intestinal mucosa and its contents were similar in every single ITS. Large intestine microbiota richness and diversity were significantly higher when compared to the duodenum and jejunum. The dominant bacteria in the gut were Firmicutes and Actinobacteria; the former was enriched in the large intestine, whereas the latter was more abundant in the duodenum and jejunum. Our findings provide novel insights for microbiota in B. acutorostrata.
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Microbioma Gastrointestinal , Intestinos/microbiología , Ballena Minke/microbiología , Animales , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , ADN Bacteriano/genética , ARN Ribosómico 16S/genéticaRESUMEN
Peripheral nerve injury (PNI), one of the most common concerns following trauma, can result in a significant loss of sensory or motor function. Restoration of the injured nerves requires a complex cellular and molecular response to rebuild the functional axons so that they can accurately connect with their original targets. However, there is no optimized therapy for complete recovery after PNI. Supplementation with exogenous growth factors (GFs) is an emerging and versatile therapeutic strategy for promoting nerve regeneration and functional recovery. GFs activate the downstream targets of various signaling cascades through binding with their corresponding receptors to exert their multiple effects on neurorestoration and tissue regeneration. However, the simple administration of GFs is insufficient for reconstructing PNI due to their short halflife and rapid deactivation in body fluids. To overcome these shortcomings, several nerve conduits derived from biological tissue or synthetic materials have been developed. Their good biocompatibility and biofunctionality made them a suitable vehicle for the delivery of multiple GFs to support peripheral nerve regeneration. After repairing nerve defects, the controlled release of GFs from the conduit structures is able to continuously improve axonal regeneration and functional outcome. Thus, therapies with growth factor (GF) delivery systems have received increasing attention in recent years. Here, we mainly review the therapeutic capacity of GFs and their incorporation into nerve guides for repairing PNI. In addition, the possible receptors and signaling mechanisms of the GF family exerting their biological effects are also emphasized.
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Factores de Crecimiento Nervioso/uso terapéutico , Regeneración Nerviosa/efectos de los fármacos , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Nervios Periféricos/efectos de los fármacos , Transducción de Señal/fisiología , Animales , Axones/metabolismo , Ensayos Clínicos como Asunto , Humanos , Traumatismos de los Nervios Periféricos/fisiopatología , Nervios Periféricos/fisiología , Células de Schwann/metabolismoRESUMEN
Rationale: Autophagy in Schwann cells (SCs) is crucial for myelin debris degradation and clearance following peripheral nerve injury (PNI). Nerve growth factor (NGF) plays an important role in reconstructing peripheral nerve fibers and promoting axonal regeneration. However, it remains unclear if NGF effect in enhancing nerve regeneration is mediated through autophagic clearance of myelin debris in SCs. Methods: In vivo, free NGF solution plus with/without pharmacological inhibitors were administered to a rat sciatic nerve crush injury model. In vitro, the primary Schwann cells (SCs) and its cell line were cultured in normal medium containing NGF, their capable of swallowing or clearing degenerated myelin was evaluated through supplement of homogenized myelin fractions. Results: Administration of exogenous NGF could activate autophagy in dedifferentiated SCs, accelerate myelin debris clearance and phagocytosis, as well as promote axon and myelin regeneration at early stage of PNI. These NGF effects were effectively blocked by autophagy inhibitors. In addition, inhibition of the p75 kD neurotrophin receptor (p75NTR) signal or inactivation of the AMP-activated protein kinase (AMPK) also inhibited the NGF effect as well. Conclusions: NGF effect on promoting early nerve regeneration is closely associated with its accelerating autophagic clearance of myelin debris in SCs, which probably regulated by the p75NTR/AMPK/mTOR axis. Our studies thus provide strong support that NGF may serve as a powerful pharmacological therapy for peripheral nerve injuries.
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Autofagia/efectos de los fármacos , Vaina de Mielina/metabolismo , Factor de Crecimiento Nervioso/farmacología , Regeneración Nerviosa/efectos de los fármacos , Células de Schwann/metabolismo , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Proteínas Quinasas Activadas por AMP/farmacología , Animales , Autofagia/fisiología , Línea Celular , Humanos , Masculino , Ratones , Ratones Noqueados , Vaina de Mielina/fisiología , Factor de Crecimiento Nervioso/administración & dosificación , Factor de Crecimiento Nervioso/metabolismo , Regeneración Nerviosa/fisiología , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Proteínas del Tejido Nervioso/farmacología , Traumatismos de los Nervios Periféricos/metabolismo , Fagocitosis/efectos de los fármacos , Fagocitosis/fisiología , Ratas , Ratas Wistar , Receptores de Factor de Crecimiento Nervioso/antagonistas & inhibidores , Células de Schwann/fisiología , Nervio Ciático/lesiones , Nervio Ciático/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
The process of axonal regeneration after peripheral nerve injury (PNI) is slow and mostly incomplete. Previous studies have investigated the neuroprotective effects of fibroblast growth factor 10 (FGF10) against spinal cord injury and cerebral ischemia brain injury. However, the role of FGF10 in peripheral nerve regeneration remains unknown. In this study, we aimed to investigate the underlying therapeutic effects of FGF10 on nerve regeneration and functional recovery after PNI and to explore the associated mechanism. Our results showed that FGF10 administration promoted axonal regeneration and functional recovery after nerve damage. Moreover, exogenous FGF10 treatment also prevented SCs from excessive oxidative stress-induced apoptosis, which was probably related to the activation of phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) signaling. The inhibition of the PI3K/Akt pathway by the specific inhibitor LY294002 partially reversed the therapeutic effects of FGF10 both in vivo and in vitro. Thus, from our perspective, FGF10 may be a promising therapeutic drug for repairing sciatic nerve damage through countering excessive oxidative stress-induced SC apoptosis.
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With continuous minimization of nanodevices, the dimensions of metallic materials used in nanodevices decrease to a few nanometers. Understanding the structural stability and deformation behavior of these small-sized metallic materials is important for their practical applications. Here we report our atomic-resolution observation of the deformation processes of Ag nanowires with widths of â¼3 nm. The nanowires under tension experienced plastic deformation via partial dislocation activities, which led to deformation twinning in and homogeneous elongation of the nanowires, and surface atom diffusion that reduced the nanowires' width but did not contribute to the nanowire elongation. The diffusion of surface atoms was initiated at surface steps introduced by the partial dislocation activities, leading to fracture of the nanowires with relatively low homogeneous elongation.
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Seeking for effective drugs which are beneficial to facilitating axonal regrowth and elongation after peripheral nerve injury (PNI) has gained extensive attention. Fibroblast growth factor 21 (FGF21) is a metabolic factor that regulates blood glucose and lipid homeostasis. However, there is little concern for the potential protective effect of FGF21 on nerve regeneration after PNI and revealing related molecular mechanisms. Here, we firstly found that exogenous FGF21 administration remarkably promoted functional and morphologic recovery in a rat model of sciatic crush injury, manifesting as persistently improved motor and sensory function, enhanced axonal remyelination and regrowth and accelerated Schwann cells (SCs) proliferation. Furthermore, local FGF21 application attenuated the excessive activation of oxidative stress, which was accompanied with the activation of nuclear factor erythroid-2-related factor 2 (Nrf-2) transcription and extracellular regulated protein kinases (ERK) phosphorylation. We detected FGF21 also suppressed autophagic cell death in SCs. Additionally, treatment with the ERK inhibitor U0126 or autophagy inhibitor 3-MA partially abolishes anti-oxidant effect and reduces SCs death. Taken together, these results indicated that the role of FGF21 in remyelination and nerve regeneration after PNI was probably related to inhibit the excessive activation of ERK/Nrf-2 signalling-regulated oxidative stress and autophagy-induced cell death. Overall, our work suggests that FGF21 administration may provide a new therapy for PNI.