Objective To determine whether relative abundance of epidermal growth factor receptor (EGFR) mutations in plasma predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in...Objective To determine whether relative abundance of epidermal growth factor receptor (EGFR) mutations in plasma predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced lung adenocarcinoma. Methods In this prospective study,adult patients with advanced lung adenocarcinoma were enrolled in our hospital from 1 April 2016 to 1 January 2017. EGFR mutations in tumortissues were detected by ADx-amplification refractory mutationsystem (ADx-ARMS). EGFR mutations of plasmafree tumor DNA were detected by ADx-ARMS and ADxsuperamplification refractory mutation system (ADx-SuperARMS)at the same time. Patients with EGFR-mutantin tumor tissues and receiving EGFR-TKIs were finallyenrolled. Plasma mutation-positive patients with bothmethods were high abundance group. Patients with positivemutations by ADx-SuperARMS but negative of ADx-ARMS were medium abundance group.展开更多
This paper discusses the utilization of latent variable modeling related to occupational health and safety in the mining industry.Latent variable modeling,which is a statistical model that relates observable and laten...This paper discusses the utilization of latent variable modeling related to occupational health and safety in the mining industry.Latent variable modeling,which is a statistical model that relates observable and latent variables,could be used to facilitate researchers’understandings of the underlying constructs or hypothetical factors and their magnitude of effect that constitute a complex system.This enhanced understanding,in turn,can help emphasize the important factors to improve mine safety.The most commonly used techniques include the exploratory factor analysis(EFA),the confirmatory factor analysis(CFA)and the structural equation model with latent variables(SEM).A critical comparison of the three techniques regarding mine safety is provided.Possible applications of latent variable modeling in mining engineering are explored.In this scope,relevant research papers were reviewed.They suggest that the application of such methods could prove useful in mine accident and safety research.Application of latent variables analysis in cognitive work analysis was proposed to improve the understanding of human-work relationships in mining operations.展开更多
Diabetic neuropathy is one of the most serious complications of diabetes, and its increase shows no sign of stopping. Furthermore, current clinical treatments do not yet approach the best effectiveness. Thus, the deve...Diabetic neuropathy is one of the most serious complications of diabetes, and its increase shows no sign of stopping. Furthermore, current clinical treatments do not yet approach the best effectiveness. Thus, the development of better strategies for treating diabetic neuropathy is an urgent matter. In this review, we first discuss the advantages and disadvantages of some major mouse models of diabetic neuropathy and then address the targets for mechanism-based treatment that have been studied. We also introduce our studies on each part. Using stem cells as a source of neurotrophic factors to target extrinsic factors of diabetic neuropathy, we found that they present a promising treatment.展开更多
Retaining walls have been used in many construction projects such as for road and inclined surfaces protection. The damage caused by an earthquake depends on the fundamental frequency, amplitude and the duration of th...Retaining walls have been used in many construction projects such as for road and inclined surfaces protection. The damage caused by an earthquake depends on the fundamental frequency, amplitude and the duration of the seismic motion. These parameters strongly depend on the seismic properties of the layers that are near the surface. In the study of retaining walls, in addition to the infl uence of soil, the infl uence of topography is also important. In the present study, site response analysis is performed by using fi nite element software PLAXIS to obtain the eff ect of various factors such as embedded length of the sheet pile, underground water table, length and angle of the nail, shear wave velocity of soil on site eff ect and dynamic response. Moreover, for better understanding of the eff ect of the above parameters, the stability analysis was performed by using shear reduction method. The results show that an increase in the embedded length of the sheet pile and the length of nailing causes an increase in the amplifi cation factor. Moreover, for shear-wave velocity in the range of 200- 600 m/s, the amplifi cation factor increases with increase of the shear-wave velocity due to the decrease of nonlinear behavior.展开更多
In some densely-populated countries, farmland has been widely cadmium (Cd) contaminated, and the utilization of the contaminated farmland for crop production is currently unavoidable. This necessitates the use of low-...In some densely-populated countries, farmland has been widely cadmium (Cd) contaminated, and the utilization of the contaminated farmland for crop production is currently unavoidable. This necessitates the use of low-Cd crops (i.e., pollution-safe cultivars, the crop varieties with the ability to accumulate a low level of Cd in their edible parts when grown on polluted soil) in these areas and highlights the importance of knowledge on phenotypic variation in crop Cd accumulation for food Cd risk control. Studies on phenotypic variation in heavy metal accumulation started decades ago for a wide range of crops, and synthesis of the scattered experimental results in the literature is in need. We built a Low-Cd Crops Database based on literature research, and relevant meta-analysis was performed to quantitatively explore the phenotypic variation in Cd uptake and translocation of rice and wheat. Considerable variability existed among rice (median grain Cd bioconce nt ration factor (BCF) of 0.10) and wheat (median grain Cd BCF of 0.21) phenotypes in grain Cd accumulation, and this variability was labile to soil pH and the level of Cd stress. Wheat statistically had a higher root-to-shoot Cd-translocating ability than rice, highlighting potential food Cd risks and the importance of growing low-Cd wheat in slightly Cd-contaminated regions. Meanwhile, no correlations were detected among soil-to-root, root-to-shoot, and shoot-to-grain translocation factors, implying that Cd uptake and internal translocation in crops were probably controlled by different underlying gene tic mechanisms. Root-to-shoot Cd transport could be a favorable target trait for selecting and breeding low-Cd rice and wheat. In all, this review provides a comprehensive low-Cd crop list for remediation practice and a systematic meta-analysis inferring food Cd risks based on plant capacity for Cd accumulation and desired traits for low-Cd crop breeding.展开更多
Objective: To test the hypothesis that the inhibition of endoplasmic reticulum(ER) stress-induced apoptosis in oxidized low-density lipoproteins(ox-LDL)-induced human aortic-vascular smooth muscle cells(HA-VSMCs) was ...Objective: To test the hypothesis that the inhibition of endoplasmic reticulum(ER) stress-induced apoptosis in oxidized low-density lipoproteins(ox-LDL)-induced human aortic-vascular smooth muscle cells(HA-VSMCs) was associated with suppression of the protein kinase RNA-like ER kinase(PERK)-eukaryotic translation initiation factor 2α(e IF2α)-activating transcription factor 4(ATF4)-CCAAT/enhancer binding protein homologous protein(CHOP) signaling pathway by Pollen Typhae total flavone(PTF). Methods: Primary HA-VSMCs were cultured and identified. The cultured HA-VSMCs were randomized into 5 groups, including a normal control group, an ox-LDL group(70 μg/m L high ox-LDL), an HPTF group(70 μg/m L high ox-LDL+500 μg/m L PTF), an MPTF group(70 μg/m L high ox-LDL+250 μg/m L PTF), and a LPTF group(70 μg/m L high ox-LDL+100 μg/m L PTF) in the first part;and a normal control group, an ox-LDL group(70 μg/mL high ox-LDL), an MPTF group(70 μg/m L high ox-LDL+250 μg/m L PTF), a sh RNA group(transducted with PERK shRNA lentiviral particles), a scramble shRNA group(transducted with control shRNA lentiviral particles), an MPTF+ox-LDL+shRNA group(250 μg/mL PTF+70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) and an ox-LDL+shRNA group(70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) in the second part. The protein expression levels of ER-associated apoptosis proteins were detected by Western blot, and their m RNA expression levels were detected by quantitative real-time reverse transcription-polymerase chain reaction. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay was applied to test cel viability, and the level of apoptosis was monitored by flow cytometry. Results: The MTT assay and flow cytometry showed that the ox-LDL group had a significant increase in apoptosis, which was attenuated in PTF treatment groups and sh RNA groups. Moreover, the ox-LDL group had increased protein and m RNA levels of binding immunoglobulin protein and ER-associated apoptosis proteins, such as PERK,展开更多
The neuroprotective function of macrophage migration inhibitory factor(MIF)in ischemic stroke was rarely evaluated.This study aimed to investigate the effects of early treadmill exercise on recovery from ischemic stro...The neuroprotective function of macrophage migration inhibitory factor(MIF)in ischemic stroke was rarely evaluated.This study aimed to investigate the effects of early treadmill exercise on recovery from ischemic stroke and to determine whether these effects are associated with the expression levels of MIF and brain-derived neurotrophic factor(BDNF)in the ischemic area.A total of 40 male Sprague-Dawley rats were randomly assigned to the ischemia and exercise group[middle cerebral artery occlusion(MCAO)-Ex,n=10),ischemia and sedentary group(MCAO-St,n=10),sham-surgery and exercise group(Sham-Ex,n=10),or sham-surgery and sedentary group(Sham-St,n=10).The MCAO-Ex and MCAO-St groups were subjected to MCAO for 60 minutes,whereas the Sham-Ex and Sham-St groups were subjected to an identical operation without MCAO.Rats in the MCAO-Ex and Sham-Ex groups then ran on a treadmill for 30 minutes once a day for 5 consecutive days.After reperfusion,the hanging time tested by the wire hang test was longer and the relative fractional anisotropy determined by MRI was higher in the peri-infarct region of the MCAO-Ex group compared with the MCAO-St group.The expression levels of MIF and BDNF in the peri-infarct region were upregulated in the MCAO-Ex group.Increased MIF and BDNF levels were positively correlated with relative fractional anisotropy changes in the peri-infarct region.There was no significant difference in the levels of MIF and BDNF in the peri-infarct region between the Sham-Ex and Sham-St groups.Our study demonstrated that early exercise(initiated 48 hours after the MCAO)could improve motor and neuronal recovery after ischemic stroke.Furthermore,the increased levels of MIF and BDNF in the peri-infarct region(penumbra)may be one of the mechanisms of enhanced neurological function recovery.All experiments were approved by the Institutional Animal Care and Use Committee in Asan Medical Center in South Korea(2016-12-126).展开更多
Soil heavy metal pollution, influenced by both natural and anthropogenic factors, significantly reduces environmental quality. In this study, Cr, Ni, Cu, As, Cd, and Pb in eight different land-use soils from Patuakhal...Soil heavy metal pollution, influenced by both natural and anthropogenic factors, significantly reduces environmental quality. In this study, Cr, Ni, Cu, As, Cd, and Pb in eight different land-use soils from Patuakhali District in Bangladesh were assessed. Concentrations of Cr, Ni, Cu, As, Cd, and Pb in soils were 1-87, 5-271, 4-181, 0-80, 0.2-24.0, and 5-276 mg kg-1, respectively, measured using an inductively coupled plasma-mass spectrometer. The enrichment factor, pollution load index (PLI), and contamination factor (CJ) of metal i were used to assess the ecological risk posed by metals in soils. The PLI ranged from 0.78 to 2.66, indicating baseline levels to progressive deterioration of soil due to metal contamination. However, C;of Cd ranged from 1.8 to 12.0, which showed that the studied soils were strongly impacted by Cd. Considering the severity of the potential ecological risk of a single metal, the descending order was Cd > As > Pb > Cu > Ni > Cr. Soils under all land uses showed moderate to very high potential ecological risk.展开更多
Interleukin-1βis a potent proinflammatory cytokine that plays a key role in the pathogenesis of the brain aging and diverse range of neurological diseases including Alzheimer’s disease,Parkinson’s disease,stroke an...Interleukin-1βis a potent proinflammatory cytokine that plays a key role in the pathogenesis of the brain aging and diverse range of neurological diseases including Alzheimer’s disease,Parkinson’s disease,stroke and persistent pain.Activated microglia are the main cellular source of interleukin-1βin the brain.Cathepsin B is associated with the production and secretion of interleukin-1βthrough pyrin domain-containing protein 3 inflammasome-independent processing of procaspase-3 in the phagolysosomes.The leakage of cathepsin B from the endosomal-lysosomal system during aging is associated with the proteolytic degradation of mitochondrial transcription factor A,which can stabilize mitochondrial DNA.Therefore,microglial cathepsin B could function as a major driver for inflammatory brain diseases and brain aging.Orally active and blood-brain barrier-permeable specific inhibitors for cathepsin B can be potentially effective new pharmaceutical interventions against inflammatory brain diseases and brain aging.展开更多
Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin an...Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression o展开更多
The role of vascular endothelial growth factor A in platelet adhesion in cerebral microvessels in the early stage of subarachnoid hemorrhage remains unclear.In this study,the endovascular puncture method was used to p...The role of vascular endothelial growth factor A in platelet adhesion in cerebral microvessels in the early stage of subarachnoid hemorrhage remains unclear.In this study,the endovascular puncture method was used to produce a rat model of subarachnoid hemorrhage.Then,30 minutes later,vascular endothelial growth factor A antagonist anti-vascular endothelial growth factor receptor 2 antibody,10μg,was injected into the right ventricle.Immunohistochemistry and western blot assay were used to assess expression of vascular endothelial growth factor A,occludin and claudin-5.Immunohistochemical double labeling was conducted to examine co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen.TUNEL was used to detect apoptosis in the hippocampus.Neurological score was used to assess behavioral performance.After subarachnoid hemorrhage,the expression of vascular endothelial growth factor A increased in the hippocampus,while occludin and claudin-5 expression levels decreased.Co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells increased,whereas behavioral performance was markedly impaired.After treatment with anti-vascular endothelial growth factor receptor 2 antibody,occludin and claudin-5 expression recovered,while co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells decreased.Furthermore,behavioral performance improved notably.Our findings suggest that increased vascular endothelial growth factor A levels promote platelet adhesion and contribute to early brain injury after subarachnoid hemorrhage.This study was approved by the Biomedical Ethics Committee,Medical College of Xi’an Jiaotong University,China in December 2015.展开更多
OBJECTIVE:To determine the therapeutic effect and potential mechanism of Huatan Tongluo decoction on rats with collagen-induced arthritis.METHODS:Forty specific pathogen-free Wistar rats were selected,and 10 were rand...OBJECTIVE:To determine the therapeutic effect and potential mechanism of Huatan Tongluo decoction on rats with collagen-induced arthritis.METHODS:Forty specific pathogen-free Wistar rats were selected,and 10 were randomly selected as the control(group 1).The remaining rats were injected intradermally with emulsified type II bovine collagen at the tail base and back,followed by a booster 7 d post first immunization.After establishing collagen-induced arthritis(CIA),rats were randomly divided into three groups(n=10).The rats were treated orally for 30 d as follows:group 1,saline;group 2,model(saline);group 3,tripterygium polyglycoside(TP;7.81 mg/kg,positive control);group 4,Huatan Tongluo decoction(HTTL;7.5 g/kg).Body weight,ankle swelling and arthritis index were measured over the course of the study.The rats were sacrificed 30 d after treatment.Morphological changes in the synovium were observed by hematoxylin and eosin staining.Pannus formation and synovial thickness in the left ankle were observed by color Doppler ultrasoundVascular endothelial growth factor(VEGF)and VEGFR2 protein levels were measured by immunohistochemistry.VEGF/VEGFR2 mRNA levels were measured by real-time quantitative polymerase chain reaction.RESULTS:Compared with the model group,a significantly lower arthritis index was observed in the positive control group(P<0.05)and HTTL group(P<0.01),after treatment.Both positive control and HTTL reduced intra-articular pannus formation and synovial thickening.Furthermore,VEGF mRNA,and VEGFR2 protein and mRNA levels were significantly downregulated(P<0.05)in the treatment groups.CONCLUSION:Inhibition of the expression of VEGF and VEGFR2 in synovial tissues and the formation of pannus and synovial hyperplasia may be part of the mechanism of HTTL for relieving the symptoms of rheumatoid arthritis in CIA rats.展开更多
Acacetin(5,7-dihydroxy-4′-methoxyflavone),a potential neuroprotective agent,has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions.However,whether acacetin has an effect on inflammatory co...Acacetin(5,7-dihydroxy-4′-methoxyflavone),a potential neuroprotective agent,has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions.However,whether acacetin has an effect on inflammatory corpuscle 3(NLRP3)after cerebral ischemia-reperfusion injury has not been fully determined.This study used an improved suture method to establish a cerebral ischemia-reperfusion injury model in C57BL/6 mice.After ischemia with middle cerebral artery occlusion for 1 hour,reperfusion with intraperitoneal injection of 25 mg/kg of acacetin(acacetin group)or an equal volume of saline(0.1 mL/10 g,middle cerebral artery occlusion group)was used to investigate the effect of acacetin on cerebral ischemia-reperfusion injury.Infarct volume and neurological function scores were determined by 2,3,5-triphenyltetrazolium chloride staining and the Zea-Longa scoring method.Compared with the middle cerebral artery occlusion group,neurological function scores and cerebral infarction volumes were significantly reduced in the acacetin group.To understand the effect of acacetin on microglia-mediated inflammatory response after cerebral ischemia-reperfusion injury,immunohistochemistry for the microglia marker calcium adapter protein ionized calcium-binding adaptor molecule 1(Iba1)was examined in the hippocampus of ischemic brain tissue.In addition,tumor necrosis factor-α,interleukin-1β,and interleukin-6 expression in ischemic brain tissue of mice was quantified by enzyme-linked immunosorbent assay.Expression of Iba1,tumor necrosis factor-α,interleukin-1βand interleukin-6 was significantly lower in the acacetin group compared with the middle cerebral artery occlusion group.Western blot assay results showed that expression of Toll-like receptor 4,nuclear factor kappa B,NLRP3,procaspase-1,caspase-1,pro-interleukin-1β,and interleukin-1βwere significantly lower in the acacetin group compared with the middle cerebral artery occlusion group.Our findings indicate that acacetin has a protective effect on cerebral ischemia-repe展开更多
A three-stage method is proposed to study the convergence clubs for the dynamic total factor carbon productivity (DCP) and the initial conditions. The first stage is to measure the DCP that reflects the initial differ...A three-stage method is proposed to study the convergence clubs for the dynamic total factor carbon productivity (DCP) and the initial conditions. The first stage is to measure the DCP that reflects the initial difference. The second stage is to identify the convergence club of DCP. The last stage is to examine the initial factors that may affect the formation of the convergence club. Construction industry data from 30 provinces in mainland China from 2005 to 2016 were adopted to conduct an empirical study. The empirical results showed that (1) the arithmetic mean value of China’s provincial DCP showed an upward trend and the standard deviation showed an expanding trend.(2) There are five convergence clubs, but 13 provinces failed to converge to any club.(3) The higher the degree of construction industry marketization in 2005, the greater the probability that the provinces belong to a club with higher DCP. To improve the DCP, the effective diffusion of low-carbon construction technologies and the market-oriented reform of state-owned construction companies should be promoted. The three-stage method can also be applied to study different industries in different countries or regions.展开更多
BACKGROUND Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Berberine (BBR) has been used to treat patients with IBS, but the underlying therapeutic mechanism is little u...BACKGROUND Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Berberine (BBR) has been used to treat patients with IBS, but the underlying therapeutic mechanism is little understood. We believe that BBR achieves its therapeutic effect on IBS by preventing stress intestinal inflammation and visceral hypersensitivity and reducing bowel motility. AIM To test the hypothesis that BBR achieves its therapeutic effect on IBS by preventing subclinical inflammation of the intestinal mucosa and reducing visceral hypersensitivity and intestinal motility. METHODS IBS was induced in rats via water avoidance stress (WAS). qRT-PCR and histological analyses were used to evaluate the levels of cytokines and mucosal inflammation, respectively. Modified ELISA and qRT-PCR were used to evaluate the nuclear factor kappa-B (NF-κB) signal transduction pathway. Colorectal distention test, gastrointestinal transit measurement, Western blot, and qRT-PCR were used to analyze visceral sensitivity, intestinal motility, the expression of Ckit (marker of Cajal mesenchymal cells), and the expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB.RESULTS WAS led to mucosal inflammation, visceral hyperalgesia, and high intestinal motility. Oral administration of BBR inhibited the NF-κB signal transduction pathway, reduced the expression of pro-inflammatory cytokines [interleukin (IL)- 1β, IL-6, interferon-γ, and tumor necrosis factor-α], promoted the expression of anti-inflammatory cytokines (IL-10 and transforming growth factor-β), and improved the terminal ileum tissue inflammation. BBR inhibited the expression of BDNF, TrkB, and C-kit in IBS rats, leading to the reduction of intestinal motility and visceral hypersensitivity. The therapeutic effect of BBR at a high dose (100 mg/kg) was superior to than that of the low-dose (25 mg/kg) group. CONCLUSION BBR reduces intestinal mucosal inflammation by inhibiting the intestinal NF-κB signal pathway in the IBS rats. BBR reduces the 展开更多
Objective Epidermal growth factor receptor(EGFR) and vascular endothelial growth factor(VEGF) inhibitors are two targeted therapies for metastatic colorectal cancer(mCRC). However, few studies have focused on the safe...Objective Epidermal growth factor receptor(EGFR) and vascular endothelial growth factor(VEGF) inhibitors are two targeted therapies for metastatic colorectal cancer(mCRC). However, few studies have focused on the safety and efficacy of combined targeted therapy against those of a single inhibition therapy of EFGR or VEGF. This meta-analysis aimed to compare the anti-tumor activity of the combined inhibition therapy and single inhibition therapy in patients with mCRC. Methods We searched PubMed, Medline, the Cochrane library, Embase, and annual meeting proceedings for relevant clinical trials. Objective response rate(ORR), progression-free survival(PFS), overall survival(OS), and adverse events were extracted and calculated.Results Nine trials comprising 3977 patients were selected for the analysis. The combined inhibition therapy showed a 3.7% improvement in ORR compared with single inhibition, and this difference was statistically significant [hazard ratio(HR)= 1.33;95% confidence interval(CI), 1.01–1.74;P = 0.04]. Subgroup analysis showed that the combined EGFR and VEGF inhibitor therapy had an 11.65% improvement in ORR compared with VEGF inhibitor therapy(OR = 2.14;95% CI, 1.34–3.40;P = 0.001). EGFR and VEGF inhibitor therapy and chemotherapy had an 18.08% improvement in ORR compared with chemotherapy(OR = 2.21;95% CI, 1.05–4.64;P = 0.04). Moreover, EGFR and VEGF inhibitor therapy significantly improved PFS compared with VEGF inhibitor therapy(OR = 0.82;95% CI, 0.69–0.97;P = 0.02). VEGF inhibitor therapy and chemotherapy significantly improved PFS compared with EGFR and VEGF inhibitor therapy and chemotherapy(OR = 1.20;95% CI, 1.11–1.30;P = 0.00). In addition, EGFR and VEGF inhibitor therapy showed improved OS compared with VEGF inhibitor therapy(HR = 0.78, 95% CI: 0.65–0.94;P = 0.008). Finally, the combined inhibition therapy showed an obviously increased risk of cutaneous and mucosal effects(RR = 6.45;95% CI: 2.71–15.36;P < 0.01), diarrhea/abdominal pain(RR = 1.97;95% CI: 1.45–2.68;P < 0.01),展开更多
Background: Spinal cord injury (SCI) is a worldwide medical concern. This study aimed to elucidate the mechanism underlying protective effect of hyperbaric oxygen (HBO) against SCI-induced neurologic defects in rats v...Background: Spinal cord injury (SCI) is a worldwide medical concern. This study aimed to elucidate the mechanism underlying protective effect of hyperbaric oxygen (HBO) against SCI-induced neurologic defects in rats via exploring the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis and expression of brain-derived neurotrophic factor (BDNF). Methods: An acute SCI rat model was established in Sprague-Dawley rats using the Allen method. Sixty rats were divided into four groups (w = 15 in each group): sham-operated, SCI, SCI treated with HBO (SCI + HBO), and SCI treated with both HBO and AMD3100 (an antagonist of CXCR4;SCI + HBO + AMD) groups. The rats were treated with HBO twice a day for 3 days and thereafter once a day after the surgery for up to 28 days. Following the surgery, neurologic assessments were performed with the Basso-Bettie-Bresnahan (BBB) scoring system on postoperative day (POD) 7, 14, 21, and 28. Spinal cord tissues were harvested to assess the expression of SDF-1, CXCR4, and BDNF at mRNA and protein levels, using quantitative real-time polymerase chain reaction, Western blot analysis, and histopathologic analysis. Results: HBO treatment recovered SCI-induced descent of BBB scores on POD 14,(1.25±0.75 vs. 1.03 ±0.66, P< 0.05), 21 (5.27± 0.89 vs. 2.56± 1.24, P< 0.05), and 28 (11.35±0.56 vs. 4.23± 1.20, P<0.05) compared with the SCI group. Significant differences were found in the mRNA levels of SDF-1 (mRNA: day 21, SCI + HBO vs. SCI + HBO + AMD, 2.89± 1.60 vs. 1.56±0.98, P<0.05), CXCR4 (mRNA: day 7, SCI + HBO vs. SCI, 2.99± 1.60 vs. 1.31 ±0.98, P<0.05;day 14, SCI + HBO vs. SCI + HBO + AMD, 4.18± 1.60 vs. 0.80±0.34, P<0.05;day 21, SCI + HBO vs. SCI, 2.10±1.01 vs.1.15±0.03, P<0.05), and BDNF (mRNA: day 7, SCI + HBO vs. SCI, 3.04±0.41 vs. 2.75±0.31, P<0.05;day 14, SCI + HBO vs. SCI, 3.88± 1.59 vs. 1.11 ±0.40, P<0.05), indicating the involvement of SDF-1/CXCR4 axis in the protective effect of HBO. Conclusions: HBO might promote the recovery of neurologic func展开更多
Hepatocyte nuclear factor 4-alpha(HNF4α)is a highly conserved member of nuclear receptor superfamily of ligand-dependent transcription factors that is expressed in liver and gastrointestinal organs(pancreas,stomach,a...Hepatocyte nuclear factor 4-alpha(HNF4α)is a highly conserved member of nuclear receptor superfamily of ligand-dependent transcription factors that is expressed in liver and gastrointestinal organs(pancreas,stomach,and intestine).In liver,HNF4αis best known for its role as a master regulator of liver-specific gene expression and essential for adult and fetal liver function.Dysregulation of HNF4αexpression has been associated with many human diseases such as ulcerative colitis,colon cancer,maturity-onset diabetes of the young,liver cirrhosis,and hepatocellular carcinoma.However,the precise role of HNF4αin the etiology of these human pathogenesis is not well understood.Limited information is known about the role of HNF4αisoforms in liver and gastrointestinal disease progression.There is,therefore,a critical need to know how disruption of the expression of these isoforms may impact on disease progression and phenotypes.In this review,we will update our current understanding on the role of HNF4αin human liver and gastrointestinal diseases.We further provide additional information on possible use of HNF4αas a target for potential therapeutic approaches.展开更多
Objective:To compare the effects of laparoscopic surgery and traditional open surgery on serum growth factor, immunoglobulin and related factors in patients with hepatocellular carcinoma after operation.Methods: 60 pa...Objective:To compare the effects of laparoscopic surgery and traditional open surgery on serum growth factor, immunoglobulin and related factors in patients with hepatocellular carcinoma after operation.Methods: 60 patients with hepatocellular carcinoma admitted to our hospital from 2014 to 2018 were randomly divided into the control group and the observation group, with 30 cases in each group. Patients in the control group underwent traditional open radical hepatectomy, while patients in the observation group underwent laparoscopic radical hepatectomy. Before and after the operation, the levels of Alpha-alanine aminotransferase (ALT), aspartate aminotransferase (AST), vascular endothelial growth factor (VEGF), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), immunoglobulin A (IgA), immunoglobulin M (IgM), immunoglobulin G (IgG), matrix metalloproteinase-13 (MMP-13), Procalcitonin (PCT) and C-reactive protein (CRP) were compared between the patients in the two groups.Results:The levels of ALT, AST, VEGF, aFGF, bFGF, IgA, IgM, and IgG of patients in the control group were significantly decreased after the operation, but the levels of MMP-13, PCT and CRP increased significantly. The serum levels of ALT, AST, VEGF, aFGF, bFGF, IgA, IgM, and IgG of patients in the observation group were significantly decreased after operation, but the levels of MMP-13, PCT and CRP increased significantly. The above indexes of patients in the observation group were better than those in the control group (P<0.05).Conclusion: Laparoscopic hepatectomy has a good clinical effect. It can significantly reduce the level of growth factor in serum of patients. It has less damage to immune function than open surgery and can reduce the level of inflammatory stress caused by operation.展开更多
文摘Objective To determine whether relative abundance of epidermal growth factor receptor (EGFR) mutations in plasma predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced lung adenocarcinoma. Methods In this prospective study,adult patients with advanced lung adenocarcinoma were enrolled in our hospital from 1 April 2016 to 1 January 2017. EGFR mutations in tumortissues were detected by ADx-amplification refractory mutationsystem (ADx-ARMS). EGFR mutations of plasmafree tumor DNA were detected by ADx-ARMS and ADxsuperamplification refractory mutation system (ADx-SuperARMS)at the same time. Patients with EGFR-mutantin tumor tissues and receiving EGFR-TKIs were finallyenrolled. Plasma mutation-positive patients with bothmethods were high abundance group. Patients with positivemutations by ADx-SuperARMS but negative of ADx-ARMS were medium abundance group.
基金Natural Sciences and Engineering Research Council of Canada(NSERC)(ID:236482)for supporting this research.
文摘This paper discusses the utilization of latent variable modeling related to occupational health and safety in the mining industry.Latent variable modeling,which is a statistical model that relates observable and latent variables,could be used to facilitate researchers’understandings of the underlying constructs or hypothetical factors and their magnitude of effect that constitute a complex system.This enhanced understanding,in turn,can help emphasize the important factors to improve mine safety.The most commonly used techniques include the exploratory factor analysis(EFA),the confirmatory factor analysis(CFA)and the structural equation model with latent variables(SEM).A critical comparison of the three techniques regarding mine safety is provided.Possible applications of latent variable modeling in mining engineering are explored.In this scope,relevant research papers were reviewed.They suggest that the application of such methods could prove useful in mine accident and safety research.Application of latent variables analysis in cognitive work analysis was proposed to improve the understanding of human-work relationships in mining operations.
文摘Diabetic neuropathy is one of the most serious complications of diabetes, and its increase shows no sign of stopping. Furthermore, current clinical treatments do not yet approach the best effectiveness. Thus, the development of better strategies for treating diabetic neuropathy is an urgent matter. In this review, we first discuss the advantages and disadvantages of some major mouse models of diabetic neuropathy and then address the targets for mechanism-based treatment that have been studied. We also introduce our studies on each part. Using stem cells as a source of neurotrophic factors to target extrinsic factors of diabetic neuropathy, we found that they present a promising treatment.
文摘Retaining walls have been used in many construction projects such as for road and inclined surfaces protection. The damage caused by an earthquake depends on the fundamental frequency, amplitude and the duration of the seismic motion. These parameters strongly depend on the seismic properties of the layers that are near the surface. In the study of retaining walls, in addition to the infl uence of soil, the infl uence of topography is also important. In the present study, site response analysis is performed by using fi nite element software PLAXIS to obtain the eff ect of various factors such as embedded length of the sheet pile, underground water table, length and angle of the nail, shear wave velocity of soil on site eff ect and dynamic response. Moreover, for better understanding of the eff ect of the above parameters, the stability analysis was performed by using shear reduction method. The results show that an increase in the embedded length of the sheet pile and the length of nailing causes an increase in the amplifi cation factor. Moreover, for shear-wave velocity in the range of 200- 600 m/s, the amplifi cation factor increases with increase of the shear-wave velocity due to the decrease of nonlinear behavior.
基金This work was financially supported by the National Key Research and Development Program of China (No. 2018YFD0800306)the Hebei Science Fund for Distinguished Young Scholars, China (No. D2018503005).
文摘In some densely-populated countries, farmland has been widely cadmium (Cd) contaminated, and the utilization of the contaminated farmland for crop production is currently unavoidable. This necessitates the use of low-Cd crops (i.e., pollution-safe cultivars, the crop varieties with the ability to accumulate a low level of Cd in their edible parts when grown on polluted soil) in these areas and highlights the importance of knowledge on phenotypic variation in crop Cd accumulation for food Cd risk control. Studies on phenotypic variation in heavy metal accumulation started decades ago for a wide range of crops, and synthesis of the scattered experimental results in the literature is in need. We built a Low-Cd Crops Database based on literature research, and relevant meta-analysis was performed to quantitatively explore the phenotypic variation in Cd uptake and translocation of rice and wheat. Considerable variability existed among rice (median grain Cd bioconce nt ration factor (BCF) of 0.10) and wheat (median grain Cd BCF of 0.21) phenotypes in grain Cd accumulation, and this variability was labile to soil pH and the level of Cd stress. Wheat statistically had a higher root-to-shoot Cd-translocating ability than rice, highlighting potential food Cd risks and the importance of growing low-Cd wheat in slightly Cd-contaminated regions. Meanwhile, no correlations were detected among soil-to-root, root-to-shoot, and shoot-to-grain translocation factors, implying that Cd uptake and internal translocation in crops were probably controlled by different underlying gene tic mechanisms. Root-to-shoot Cd transport could be a favorable target trait for selecting and breeding low-Cd rice and wheat. In all, this review provides a comprehensive low-Cd crop list for remediation practice and a systematic meta-analysis inferring food Cd risks based on plant capacity for Cd accumulation and desired traits for low-Cd crop breeding.
基金Supported by the National Natural Science Foundation of China(No.81573922)the Traditional Chinese Medicine Scientific Research Project of Guangdong Province,China(No.20151076)the Sanming Project of Medicine in Shenzhen,China(No.SZSM201612033).
文摘Objective: To test the hypothesis that the inhibition of endoplasmic reticulum(ER) stress-induced apoptosis in oxidized low-density lipoproteins(ox-LDL)-induced human aortic-vascular smooth muscle cells(HA-VSMCs) was associated with suppression of the protein kinase RNA-like ER kinase(PERK)-eukaryotic translation initiation factor 2α(e IF2α)-activating transcription factor 4(ATF4)-CCAAT/enhancer binding protein homologous protein(CHOP) signaling pathway by Pollen Typhae total flavone(PTF). Methods: Primary HA-VSMCs were cultured and identified. The cultured HA-VSMCs were randomized into 5 groups, including a normal control group, an ox-LDL group(70 μg/m L high ox-LDL), an HPTF group(70 μg/m L high ox-LDL+500 μg/m L PTF), an MPTF group(70 μg/m L high ox-LDL+250 μg/m L PTF), and a LPTF group(70 μg/m L high ox-LDL+100 μg/m L PTF) in the first part;and a normal control group, an ox-LDL group(70 μg/mL high ox-LDL), an MPTF group(70 μg/m L high ox-LDL+250 μg/m L PTF), a sh RNA group(transducted with PERK shRNA lentiviral particles), a scramble shRNA group(transducted with control shRNA lentiviral particles), an MPTF+ox-LDL+shRNA group(250 μg/mL PTF+70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) and an ox-LDL+shRNA group(70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) in the second part. The protein expression levels of ER-associated apoptosis proteins were detected by Western blot, and their m RNA expression levels were detected by quantitative real-time reverse transcription-polymerase chain reaction. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay was applied to test cel viability, and the level of apoptosis was monitored by flow cytometry. Results: The MTT assay and flow cytometry showed that the ox-LDL group had a significant increase in apoptosis, which was attenuated in PTF treatment groups and sh RNA groups. Moreover, the ox-LDL group had increased protein and m RNA levels of binding immunoglobulin protein and ER-associated apoptosis proteins, such as PERK,
基金the Basic Science Research Program through the National Research Foundation of Korea(NRF)the Ministry of Education,No.2016R1A2B4012772(to DYK).
文摘The neuroprotective function of macrophage migration inhibitory factor(MIF)in ischemic stroke was rarely evaluated.This study aimed to investigate the effects of early treadmill exercise on recovery from ischemic stroke and to determine whether these effects are associated with the expression levels of MIF and brain-derived neurotrophic factor(BDNF)in the ischemic area.A total of 40 male Sprague-Dawley rats were randomly assigned to the ischemia and exercise group[middle cerebral artery occlusion(MCAO)-Ex,n=10),ischemia and sedentary group(MCAO-St,n=10),sham-surgery and exercise group(Sham-Ex,n=10),or sham-surgery and sedentary group(Sham-St,n=10).The MCAO-Ex and MCAO-St groups were subjected to MCAO for 60 minutes,whereas the Sham-Ex and Sham-St groups were subjected to an identical operation without MCAO.Rats in the MCAO-Ex and Sham-Ex groups then ran on a treadmill for 30 minutes once a day for 5 consecutive days.After reperfusion,the hanging time tested by the wire hang test was longer and the relative fractional anisotropy determined by MRI was higher in the peri-infarct region of the MCAO-Ex group compared with the MCAO-St group.The expression levels of MIF and BDNF in the peri-infarct region were upregulated in the MCAO-Ex group.Increased MIF and BDNF levels were positively correlated with relative fractional anisotropy changes in the peri-infarct region.There was no significant difference in the levels of MIF and BDNF in the peri-infarct region between the Sham-Ex and Sham-St groups.Our study demonstrated that early exercise(initiated 48 hours after the MCAO)could improve motor and neuronal recovery after ischemic stroke.Furthermore,the increased levels of MIF and BDNF in the peri-infarct region(penumbra)may be one of the mechanisms of enhanced neurological function recovery.All experiments were approved by the Institutional Animal Care and Use Committee in Asan Medical Center in South Korea(2016-12-126).
基金The authors thank the authority of Patuakhali Science and Technology University (PSTU), Bangladesh, and Yokohama National University, Japan, for providing laboratory facilities. The samples collected from Bangladesh were brought to Japan based on the permission issued by the Yokohama Plant Protection Station (Nos. 25Y324 and 25Y1009). The authors are also delighted to express their gratitude and sincerest thanks to Prof. Dr. Mohammad Shams-Ud-Din (Vice Chancellor, PSTU), for his valuable suggestions, cooperation, and provision of funding to conduct this research. Furthermore, we are thankful for the kind help from the members of the Soil Science Department, PSTU, Bangladesh, during field sampling.
文摘Soil heavy metal pollution, influenced by both natural and anthropogenic factors, significantly reduces environmental quality. In this study, Cr, Ni, Cu, As, Cd, and Pb in eight different land-use soils from Patuakhali District in Bangladesh were assessed. Concentrations of Cr, Ni, Cu, As, Cd, and Pb in soils were 1-87, 5-271, 4-181, 0-80, 0.2-24.0, and 5-276 mg kg-1, respectively, measured using an inductively coupled plasma-mass spectrometer. The enrichment factor, pollution load index (PLI), and contamination factor (CJ) of metal i were used to assess the ecological risk posed by metals in soils. The PLI ranged from 0.78 to 2.66, indicating baseline levels to progressive deterioration of soil due to metal contamination. However, C;of Cd ranged from 1.8 to 12.0, which showed that the studied soils were strongly impacted by Cd. Considering the severity of the potential ecological risk of a single metal, the descending order was Cd > As > Pb > Cu > Ni > Cr. Soils under all land uses showed moderate to very high potential ecological risk.
基金This project was founded by JSPS KAKENHI,No.24390416,JP15H05015,15K15684 and JP16H01304(all to HN).
文摘Interleukin-1βis a potent proinflammatory cytokine that plays a key role in the pathogenesis of the brain aging and diverse range of neurological diseases including Alzheimer’s disease,Parkinson’s disease,stroke and persistent pain.Activated microglia are the main cellular source of interleukin-1βin the brain.Cathepsin B is associated with the production and secretion of interleukin-1βthrough pyrin domain-containing protein 3 inflammasome-independent processing of procaspase-3 in the phagolysosomes.The leakage of cathepsin B from the endosomal-lysosomal system during aging is associated with the proteolytic degradation of mitochondrial transcription factor A,which can stabilize mitochondrial DNA.Therefore,microglial cathepsin B could function as a major driver for inflammatory brain diseases and brain aging.Orally active and blood-brain barrier-permeable specific inhibitors for cathepsin B can be potentially effective new pharmaceutical interventions against inflammatory brain diseases and brain aging.
基金the National Natural Science Foundation of China,No.81430102(to QGW).
文摘Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression o
基金the National Natural Science Foundation of China, No. 81471179 (to JNS).
文摘The role of vascular endothelial growth factor A in platelet adhesion in cerebral microvessels in the early stage of subarachnoid hemorrhage remains unclear.In this study,the endovascular puncture method was used to produce a rat model of subarachnoid hemorrhage.Then,30 minutes later,vascular endothelial growth factor A antagonist anti-vascular endothelial growth factor receptor 2 antibody,10μg,was injected into the right ventricle.Immunohistochemistry and western blot assay were used to assess expression of vascular endothelial growth factor A,occludin and claudin-5.Immunohistochemical double labeling was conducted to examine co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen.TUNEL was used to detect apoptosis in the hippocampus.Neurological score was used to assess behavioral performance.After subarachnoid hemorrhage,the expression of vascular endothelial growth factor A increased in the hippocampus,while occludin and claudin-5 expression levels decreased.Co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells increased,whereas behavioral performance was markedly impaired.After treatment with anti-vascular endothelial growth factor receptor 2 antibody,occludin and claudin-5 expression recovered,while co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells decreased.Furthermore,behavioral performance improved notably.Our findings suggest that increased vascular endothelial growth factor A levels promote platelet adhesion and contribute to early brain injury after subarachnoid hemorrhage.This study was approved by the Biomedical Ethics Committee,Medical College of Xi’an Jiaotong University,China in December 2015.
基金National Natural Science Foundation of China Funded project:Study on the Relation between Rheumatic Arthralgia Induced by Phlem and Blood Stasis and Joints Angiogenesis of Rheumatoid Arthritis(No.81473574)Internal Project of Xiamen Hospital of Traditional Chinese Medicine Funded Project:Investigating the Therapeutic Effect and Mechanism of Resolving Phlegm and Turbidity Decoction(No.2015003)Nature Science Foundation of Fujian Province Funded Project:Studies on siRNA Drugs by Down-Regulation of both c-FLIPL and MADD for Targeted Ovarian Cancer Therapy(No.2015J01347).
文摘OBJECTIVE:To determine the therapeutic effect and potential mechanism of Huatan Tongluo decoction on rats with collagen-induced arthritis.METHODS:Forty specific pathogen-free Wistar rats were selected,and 10 were randomly selected as the control(group 1).The remaining rats were injected intradermally with emulsified type II bovine collagen at the tail base and back,followed by a booster 7 d post first immunization.After establishing collagen-induced arthritis(CIA),rats were randomly divided into three groups(n=10).The rats were treated orally for 30 d as follows:group 1,saline;group 2,model(saline);group 3,tripterygium polyglycoside(TP;7.81 mg/kg,positive control);group 4,Huatan Tongluo decoction(HTTL;7.5 g/kg).Body weight,ankle swelling and arthritis index were measured over the course of the study.The rats were sacrificed 30 d after treatment.Morphological changes in the synovium were observed by hematoxylin and eosin staining.Pannus formation and synovial thickness in the left ankle were observed by color Doppler ultrasoundVascular endothelial growth factor(VEGF)and VEGFR2 protein levels were measured by immunohistochemistry.VEGF/VEGFR2 mRNA levels were measured by real-time quantitative polymerase chain reaction.RESULTS:Compared with the model group,a significantly lower arthritis index was observed in the positive control group(P<0.05)and HTTL group(P<0.01),after treatment.Both positive control and HTTL reduced intra-articular pannus formation and synovial thickening.Furthermore,VEGF mRNA,and VEGFR2 protein and mRNA levels were significantly downregulated(P<0.05)in the treatment groups.CONCLUSION:Inhibition of the expression of VEGF and VEGFR2 in synovial tissues and the formation of pannus and synovial hyperplasia may be part of the mechanism of HTTL for relieving the symptoms of rheumatoid arthritis in CIA rats.
基金the Natural Science Foundation of Xinjiang Uygur Autonomous Region of China,No.2016D01C120(to JB).
文摘Acacetin(5,7-dihydroxy-4′-methoxyflavone),a potential neuroprotective agent,has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions.However,whether acacetin has an effect on inflammatory corpuscle 3(NLRP3)after cerebral ischemia-reperfusion injury has not been fully determined.This study used an improved suture method to establish a cerebral ischemia-reperfusion injury model in C57BL/6 mice.After ischemia with middle cerebral artery occlusion for 1 hour,reperfusion with intraperitoneal injection of 25 mg/kg of acacetin(acacetin group)or an equal volume of saline(0.1 mL/10 g,middle cerebral artery occlusion group)was used to investigate the effect of acacetin on cerebral ischemia-reperfusion injury.Infarct volume and neurological function scores were determined by 2,3,5-triphenyltetrazolium chloride staining and the Zea-Longa scoring method.Compared with the middle cerebral artery occlusion group,neurological function scores and cerebral infarction volumes were significantly reduced in the acacetin group.To understand the effect of acacetin on microglia-mediated inflammatory response after cerebral ischemia-reperfusion injury,immunohistochemistry for the microglia marker calcium adapter protein ionized calcium-binding adaptor molecule 1(Iba1)was examined in the hippocampus of ischemic brain tissue.In addition,tumor necrosis factor-α,interleukin-1β,and interleukin-6 expression in ischemic brain tissue of mice was quantified by enzyme-linked immunosorbent assay.Expression of Iba1,tumor necrosis factor-α,interleukin-1βand interleukin-6 was significantly lower in the acacetin group compared with the middle cerebral artery occlusion group.Western blot assay results showed that expression of Toll-like receptor 4,nuclear factor kappa B,NLRP3,procaspase-1,caspase-1,pro-interleukin-1β,and interleukin-1βwere significantly lower in the acacetin group compared with the middle cerebral artery occlusion group.Our findings indicate that acacetin has a protective effect on cerebral ischemia-repe
基金This work was supported by the International Cooperation Training Program for Graduate Students at Tongji University [Grant number: 2018XKJC-004].
文摘A three-stage method is proposed to study the convergence clubs for the dynamic total factor carbon productivity (DCP) and the initial conditions. The first stage is to measure the DCP that reflects the initial difference. The second stage is to identify the convergence club of DCP. The last stage is to examine the initial factors that may affect the formation of the convergence club. Construction industry data from 30 provinces in mainland China from 2005 to 2016 were adopted to conduct an empirical study. The empirical results showed that (1) the arithmetic mean value of China’s provincial DCP showed an upward trend and the standard deviation showed an expanding trend.(2) There are five convergence clubs, but 13 provinces failed to converge to any club.(3) The higher the degree of construction industry marketization in 2005, the greater the probability that the provinces belong to a club with higher DCP. To improve the DCP, the effective diffusion of low-carbon construction technologies and the market-oriented reform of state-owned construction companies should be promoted. The three-stage method can also be applied to study different industries in different countries or regions.
基金the National Natural Science Foundation of China, No. 81800489Shenzhen Health and Family Planning System Research Project, No. SZXJ2017030Technical Research and Development Project of Shenzhen, Nos. JCYJ20170307100538697 and JCYJ20170307100911479.
文摘BACKGROUND Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Berberine (BBR) has been used to treat patients with IBS, but the underlying therapeutic mechanism is little understood. We believe that BBR achieves its therapeutic effect on IBS by preventing stress intestinal inflammation and visceral hypersensitivity and reducing bowel motility. AIM To test the hypothesis that BBR achieves its therapeutic effect on IBS by preventing subclinical inflammation of the intestinal mucosa and reducing visceral hypersensitivity and intestinal motility. METHODS IBS was induced in rats via water avoidance stress (WAS). qRT-PCR and histological analyses were used to evaluate the levels of cytokines and mucosal inflammation, respectively. Modified ELISA and qRT-PCR were used to evaluate the nuclear factor kappa-B (NF-κB) signal transduction pathway. Colorectal distention test, gastrointestinal transit measurement, Western blot, and qRT-PCR were used to analyze visceral sensitivity, intestinal motility, the expression of Ckit (marker of Cajal mesenchymal cells), and the expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB.RESULTS WAS led to mucosal inflammation, visceral hyperalgesia, and high intestinal motility. Oral administration of BBR inhibited the NF-κB signal transduction pathway, reduced the expression of pro-inflammatory cytokines [interleukin (IL)- 1β, IL-6, interferon-γ, and tumor necrosis factor-α], promoted the expression of anti-inflammatory cytokines (IL-10 and transforming growth factor-β), and improved the terminal ileum tissue inflammation. BBR inhibited the expression of BDNF, TrkB, and C-kit in IBS rats, leading to the reduction of intestinal motility and visceral hypersensitivity. The therapeutic effect of BBR at a high dose (100 mg/kg) was superior to than that of the low-dose (25 mg/kg) group. CONCLUSION BBR reduces intestinal mucosal inflammation by inhibiting the intestinal NF-κB signal pathway in the IBS rats. BBR reduces the
基金the National Natural Science Foundation of China (No. 81372396)Natural Science Foundation of Jiangsu Province (No. BK20141016 and BK20141017).
文摘Objective Epidermal growth factor receptor(EGFR) and vascular endothelial growth factor(VEGF) inhibitors are two targeted therapies for metastatic colorectal cancer(mCRC). However, few studies have focused on the safety and efficacy of combined targeted therapy against those of a single inhibition therapy of EFGR or VEGF. This meta-analysis aimed to compare the anti-tumor activity of the combined inhibition therapy and single inhibition therapy in patients with mCRC. Methods We searched PubMed, Medline, the Cochrane library, Embase, and annual meeting proceedings for relevant clinical trials. Objective response rate(ORR), progression-free survival(PFS), overall survival(OS), and adverse events were extracted and calculated.Results Nine trials comprising 3977 patients were selected for the analysis. The combined inhibition therapy showed a 3.7% improvement in ORR compared with single inhibition, and this difference was statistically significant [hazard ratio(HR)= 1.33;95% confidence interval(CI), 1.01–1.74;P = 0.04]. Subgroup analysis showed that the combined EGFR and VEGF inhibitor therapy had an 11.65% improvement in ORR compared with VEGF inhibitor therapy(OR = 2.14;95% CI, 1.34–3.40;P = 0.001). EGFR and VEGF inhibitor therapy and chemotherapy had an 18.08% improvement in ORR compared with chemotherapy(OR = 2.21;95% CI, 1.05–4.64;P = 0.04). Moreover, EGFR and VEGF inhibitor therapy significantly improved PFS compared with VEGF inhibitor therapy(OR = 0.82;95% CI, 0.69–0.97;P = 0.02). VEGF inhibitor therapy and chemotherapy significantly improved PFS compared with EGFR and VEGF inhibitor therapy and chemotherapy(OR = 1.20;95% CI, 1.11–1.30;P = 0.00). In addition, EGFR and VEGF inhibitor therapy showed improved OS compared with VEGF inhibitor therapy(HR = 0.78, 95% CI: 0.65–0.94;P = 0.008). Finally, the combined inhibition therapy showed an obviously increased risk of cutaneous and mucosal effects(RR = 6.45;95% CI: 2.71–15.36;P < 0.01), diarrhea/abdominal pain(RR = 1.97;95% CI: 1.45–2.68;P < 0.01),
基金a grant from the International Science and Technology Cooperation Program of Ministry of Science and Tech no logy of China (No. 2012DFA31240).
文摘Background: Spinal cord injury (SCI) is a worldwide medical concern. This study aimed to elucidate the mechanism underlying protective effect of hyperbaric oxygen (HBO) against SCI-induced neurologic defects in rats via exploring the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis and expression of brain-derived neurotrophic factor (BDNF). Methods: An acute SCI rat model was established in Sprague-Dawley rats using the Allen method. Sixty rats were divided into four groups (w = 15 in each group): sham-operated, SCI, SCI treated with HBO (SCI + HBO), and SCI treated with both HBO and AMD3100 (an antagonist of CXCR4;SCI + HBO + AMD) groups. The rats were treated with HBO twice a day for 3 days and thereafter once a day after the surgery for up to 28 days. Following the surgery, neurologic assessments were performed with the Basso-Bettie-Bresnahan (BBB) scoring system on postoperative day (POD) 7, 14, 21, and 28. Spinal cord tissues were harvested to assess the expression of SDF-1, CXCR4, and BDNF at mRNA and protein levels, using quantitative real-time polymerase chain reaction, Western blot analysis, and histopathologic analysis. Results: HBO treatment recovered SCI-induced descent of BBB scores on POD 14,(1.25±0.75 vs. 1.03 ±0.66, P< 0.05), 21 (5.27± 0.89 vs. 2.56± 1.24, P< 0.05), and 28 (11.35±0.56 vs. 4.23± 1.20, P<0.05) compared with the SCI group. Significant differences were found in the mRNA levels of SDF-1 (mRNA: day 21, SCI + HBO vs. SCI + HBO + AMD, 2.89± 1.60 vs. 1.56±0.98, P<0.05), CXCR4 (mRNA: day 7, SCI + HBO vs. SCI, 2.99± 1.60 vs. 1.31 ±0.98, P<0.05;day 14, SCI + HBO vs. SCI + HBO + AMD, 4.18± 1.60 vs. 0.80±0.34, P<0.05;day 21, SCI + HBO vs. SCI, 2.10±1.01 vs.1.15±0.03, P<0.05), and BDNF (mRNA: day 7, SCI + HBO vs. SCI, 3.04±0.41 vs. 2.75±0.31, P<0.05;day 14, SCI + HBO vs. SCI, 3.88± 1.59 vs. 1.11 ±0.40, P<0.05), indicating the involvement of SDF-1/CXCR4 axis in the protective effect of HBO. Conclusions: HBO might promote the recovery of neurologic func
文摘Hepatocyte nuclear factor 4-alpha(HNF4α)is a highly conserved member of nuclear receptor superfamily of ligand-dependent transcription factors that is expressed in liver and gastrointestinal organs(pancreas,stomach,and intestine).In liver,HNF4αis best known for its role as a master regulator of liver-specific gene expression and essential for adult and fetal liver function.Dysregulation of HNF4αexpression has been associated with many human diseases such as ulcerative colitis,colon cancer,maturity-onset diabetes of the young,liver cirrhosis,and hepatocellular carcinoma.However,the precise role of HNF4αin the etiology of these human pathogenesis is not well understood.Limited information is known about the role of HNF4αisoforms in liver and gastrointestinal disease progression.There is,therefore,a critical need to know how disruption of the expression of these isoforms may impact on disease progression and phenotypes.In this review,we will update our current understanding on the role of HNF4αin human liver and gastrointestinal diseases.We further provide additional information on possible use of HNF4αas a target for potential therapeutic approaches.
基金Industrial Technology Innovation Project of Suzhou in 2017(SYSD2017187)The Second batch of'Science and Education Promoting Health'Projects in Wujiang District of Suzhou City in 2017(wk201708).
文摘Objective:To compare the effects of laparoscopic surgery and traditional open surgery on serum growth factor, immunoglobulin and related factors in patients with hepatocellular carcinoma after operation.Methods: 60 patients with hepatocellular carcinoma admitted to our hospital from 2014 to 2018 were randomly divided into the control group and the observation group, with 30 cases in each group. Patients in the control group underwent traditional open radical hepatectomy, while patients in the observation group underwent laparoscopic radical hepatectomy. Before and after the operation, the levels of Alpha-alanine aminotransferase (ALT), aspartate aminotransferase (AST), vascular endothelial growth factor (VEGF), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), immunoglobulin A (IgA), immunoglobulin M (IgM), immunoglobulin G (IgG), matrix metalloproteinase-13 (MMP-13), Procalcitonin (PCT) and C-reactive protein (CRP) were compared between the patients in the two groups.Results:The levels of ALT, AST, VEGF, aFGF, bFGF, IgA, IgM, and IgG of patients in the control group were significantly decreased after the operation, but the levels of MMP-13, PCT and CRP increased significantly. The serum levels of ALT, AST, VEGF, aFGF, bFGF, IgA, IgM, and IgG of patients in the observation group were significantly decreased after operation, but the levels of MMP-13, PCT and CRP increased significantly. The above indexes of patients in the observation group were better than those in the control group (P<0.05).Conclusion: Laparoscopic hepatectomy has a good clinical effect. It can significantly reduce the level of growth factor in serum of patients. It has less damage to immune function than open surgery and can reduce the level of inflammatory stress caused by operation.