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Senecavirus A (SVA), also known as Seneca Valley virus, is a recently discovered picornavirus that can cause swine vesicular disease, posing a great threat to the global swine industry. It can replicate efficiently in cells, but the molecular mechanism remains poorly understood. This study determined the host's differentially expressed proteins (DEPs) during SVA infection using dimethyl labeling based on quantitative proteomics. Among the DE proteins, DDX21, a member of the DEAD (Asp-Glu-Ala-Asp)-box RNA helicase (DDX) family, was downregulated and demonstrated inhibiting SVA replication by overexpression and knockdown experiment. To antagonize this antiviral effect of DDX21, SVA infection induces the degradation of DDX21 by 2B and 3C proteins. The Co-IP results showed that 2B and 3C did not interact with DDX21, suggesting that the degradation of DDX21 did not depend on their interaction. Moreover, the 3C protein protease activity was necessary for the degradation of DDX21. Furthermore, our study revealed that the degradation of DDX21 by 2B and 3C proteins of SVA was achieved through the caspase pathway. These findings suggest that DDX21 was an effective antiviral factor for suppressing SVA infection and that SVA antagonized its antiviral effect by degrading DDX21, which will be useful to guide further studies into the mechanism of mutual regulation between SVA and the host.
Subject(s)
Antiviral Agents , Picornaviridae , Animals , Antiviral Agents/pharmacology , Caspases , Picornaviridae/genetics , Swine , Viral Proteins/metabolismABSTRACT
Circular RNAs (circRNAs) are a new class of noncoding RNAs that play vital roles in many biological processes. Virus infection induces modifications in cellular circRNA transcriptomes and expresses viral circRNAs. The outbreaks of Hydropericardium-hepatitis syndrome (HHS) caused by fowl adenovirus serotype 4 (FAdV-4) have resulted in huge economic losses to the poultry industry worldwide. To investigate the expression of circRNAs during FAdV-4 infection, we performed transcriptome analysis of FAdV-4-infected leghorn male hepatoma (LMH) cells. In total, 19,154 cellular circRNAs and 135 differentially expressed (DE) cellular circRNAs were identified. The characteristics of the DE cellular circRNAs were analyzed and most of them were related to multiple biological processes according to GO and KEGG enrichment analysis. The accuracy of 10 cellular circRNAs were verified by semiquantitative RT-PCR and sequencing. The change trend was consistent with the RNA sequencing results. Moreover, 2014 viral circRNAs were identified and 10 circRNAs were verified by the same methods. Our analysis showed that seven circRNAs with the same 3' terminal and variable 5' terminal regions were located at pTP protein and DNA pol protein of FAdV-4, which may be generated via alternative splicing events. Moreover, the expression level of viral circRNAs was closely related to the replication efficiency of the virus and partial of the viral circRNAs promoted the replication of FAdV-4. Competing endogenous RNA analysis further showed that the effects of cellular and viral circRNAs on host or viral genes may act via miRNAs. Collectively, our findings first indicate that FAdV-4 infection induced the differential expression of cellular circRNAs and FAdV-4 also expressed viral circRNAs, some of which affected FAdV-4 replication. These findings will provide new clues for further understanding FAdV-4 and provide a basis for investigating host-virus interactions.
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Objective:To explore diagnostic value of tumor necrosis factor-α (TNF-α) in patients with pulmonary infection after liver transplantation.Methods:The clinical data of 80 patients with pulmonary infection after liver transplantation in the the First Affiliated Hospital of Xinjiang Medical University from January 2016 to May 2019 were retrospectively analyzed. According to different pathogens, they were divided into bacteria infection group ( n=35) and non-bacteria infection group ( n=45). The general data, levels of serum TNF-α, C-reactive protein (CRP) and procalcitonin (PCT) were compared between the two groups. Logistic regression was performed to explore risk factors for pulmonary infection after liver transplantation. Receiver operating characteristic (ROC) curves were performed to analyze diagnostic value of TNF-α, CRP and PCT. Results:The levels of serum TNF-α, CRP and PCT in bacteria infection group were significantly higher than those in non-bacteria infection group ( P<0.05). Multivariate analysis showed that high TNF-α, CRP, and PCT levels were independent risk factors for bacterial pneumonia after liver transplantation. ROC analysis showed that sensitivity, specificity and areas under ROC curves (AUC) of TNF-α, CRP and PCT for diagnosis of bacterial pulmonary infection after liver transplantation were (80.12%, 72.12%, 80.18%), (83.45%, 73.46%, 83.38%) and (0.802, 0.751, 0.803), respectively. The AUC, sensitivity, and specificity between TNF-α and PCT for diagnosis of bacterial pulmonary infection after liver transplantation were similar ( P>0.05). The AUC, sensitivity and specificity of TNF-α for diagnosis of bacterial pulmonary infection after liver transplantation were better than those of CRP ( P<0.05). Conclusions:The diagnostic value of TNF-α for pulmonary infection after liver transplantation is similar to that of PCT, and is superior to CRP. It can be applied as a reliable index for identifying bacterial pneumonia and non-bacterial pneumonia.
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The upcoming flu season in the northern hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental co-infection of IAV with either pseudotyped or SARS-CoV-2 live virus, we found that IAV pre-infection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice co-infected with IAV in vivo. Moreover, such enhancement of SARS-CoV-2 infectivity was not seen with several other viruses probably due to a unique IAV segment as an inducer to elevate ACE2 expression. This study illustrates that IAV has a special nature to aggravate SARS-CoV-2 infection, and prevention of IAV is of great significance during the COVID-19 pandemic.
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ObjectiveOnly few studies have been published of the effect of microvascular invasion (MVI) on long-term prognosis of liver resection (LR) for multiple hepatocellular carcinomas (mHCCs). Therefore, we investigate the efficacy of MVI on long-term prognosis of the patients undergoing LR formHCCs.MethodsThe clinical data of 505 patients undergoing LR for mHCCs in the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University between March 2009 and March 2015 were retrospectively analyzed. Patients were divided into the MVI(+) group (n=279)and MVI (-) group (n=226), and146 patients in MVI (+) group and 124 patients in MVI (-) group received adjuvant transarterial chemoembolization (TACE). The Kaplan-Meier approach was used for survival analysis and the Cox proportional-hazards regression model was used forthe risk factors of long-term survival rate.ResultsThe early recurrence rate of MVI (+) group was significantly higher than that of MVI (-) group (60.4% vs 40.5%, P<0.01), and the 1-, 3-, 5-year overall survival rate of MVI (+) group was significantly lower than those in MVI (-) group (70.5%, 47.4%, 33.4% vs 86.6%, 66.8%, 50.1%, P<0.05). Among MVI (+) patients, the early recurrence rate and 1-, 3-, 5-year overall survival rate in the adjuvant TACE group were better than those in the control group (early recurrence rate 41.3% vs 39.3%, P<0.05; 1, 3, 5 year overall survival rate 92.8%, 72.5%, 53.1% vs 78.6%, 59.5%, 47.3%, P<0.05). Multivariate Cox model indicated that the Alpha-foetoprotein (AFP) level, maximum tumor diameter/minimum tumor diameter, MVI and adjuvant TACE were independent risk factors for early recurrence (HR=1.48, 1.51, 1.34, 0.76, P<0.05); maximum tumor diameter, intraoperative blood transfusion, MVI and adjuvant TACE were independent risk factors for postoperative overall survival (HR=1.75, 1.75, 1.36, 0.68, P<0.05).ConclusionMVI is a risk factor for early recurrence and poor long-term prognosis after LR for mHCCs. For mHCCs with MVI, adjuvant TACE after LR could reduce the early recurrence rate and improve the long-term survival rate.
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To investigate the potential toxic effects and mechanisms of Tris(1; 3-dichloro-2-propyl) phosphate (TDCIPP) on thyroid in female SD rats. Thirty-two 3-weeks-old female SD rats were randomly divided into normal group(treated with corn oil ), and low/moderate/high-dose group treated with TDCIPP (dissolved in corn oil )(n=8). All rats were treated with corn oil or TDCIPP (50, 100, 250 mg/(kg·d)) once a day during a 21-day period. All rats were sacrificed after the last administration. Serum thyroid stimulating hormone (TSH), 3,3',5-triiodothyronine (T3), 3,3',5,5'-tetraiodothyronine (T4), free 3,3',5,5'-tetraiodothyronine (FT4) were detected with ELISA kit. Morphology of thyroid was observed with hematoxylin and eosin (HE) staining. Expressions of genes and proteins correlate with thyroid were measured respectively by real-time fluorescence quantitative PCR and Western blot. Compared with control group, morphology of thyroid showed follicles irregular arrangement, hypocolloid, and follicular hyperplasia in TDCIPP treatment groups. The levels of serum TSH in low-dose TDCIPP group and T3 in high-dose TDCIPP group were significantly higher than those in control group(P<0.05). Thyroid stimulating hormone receptor (TSHR) mRNA expression was decreased distinctly in low-dose TDCIPP group, while the expression of thyroperoxidase (TPO) mRNA was increased notably in moderate and high-dose TDCIPP groups(P<0.05,P<0.01). Compared with control group, the level of TRβ protein was decreased significantly in moderate and high-dose TDCIPP groups, while the expressions of udp-glucuronosyl-transferases (UGTs) and cytochrome-p450-3A1 (CYP3A1) proteins were upregulated notably in TDCIPP treatment groups(P<0.05). Treated with 50 mg/(kg·d) TDCIPP can cause thyroid hyperplasia, change the levels of thyroid hormones, and disturb thyroid function, therefore, it has toxic effects on the thyroid.
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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. The noninvasive and accurate classification of NAFLD is still a challenging problem. In this study we pro- posed a new quantitative ultrasound (QUS) technique, which combined multiple QUS parameters for distinguishing steatosis stages. NAFLD was induced in the livers of 57 rats by gavage feeding with a high fat emulsion, while 8 rats were given a standard diet to serve as controls. Ex vivo ultrasound mea- surement was conducted for capturing the radiofrequency signal. Six QUS parameters were extracted and selected for linear combination. The results show that the overall performance of the combined parameter is better than that of the single QUS parameter. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) while using our proposed method to distinguish mild steatosis (stage S1) from the steatosis under stage S0 are 90.1%, 0.93, 0.88 and 0.97 respectively. In conclusion, the proposed method in this study can make up for the deficiency of single parameter and improve the quantitative staging ability of fatty liver, and thus could play an important role in the diagnosis of NAFLD.
Subject(s)
Image Processing, Computer-Assisted/methods , Liver/pathology , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Ultrasonography , Acoustics , Algorithms , Animals , Humans , Liver/diagnostic imaging , Models, Animal , Models, Statistical , ROC Curve , Rats , Reproducibility of Results , Scattering, RadiationABSTRACT
Objective Gastric cancer is the most common cancer in the world. In China, Patients with gastric cancer are mostly treated with platinum-based chemotherapy. Programmed cell death 4 (PDCD4) was found as an important proapoptosis recently, the aim of the present study was to investigate the role of PDCD4 reversed the apoptosis induced by cisplatin in gastric cancer cell. The study will provide the target marker for treatment and diagnosis of cisplatin resistance in gastric cancer.Methods Stable transfection with pCMV-PDCD4 vector into human cisplatin resistance gastric cancer cell line-SGC7901/DDP; the cells were divided into control group, over-expression group, control with cisplatin group, over-expression with cisplatin group for following experiments. Hoechst dying with immunofluorescence and flow cytometry were used to measure the cell apoptosis in vitro; Real-time PCR was used to detect the mRNA expression levels of PDCD4, and the protein levels of PDCD4, pAK, pGSK3β, BCL-2 and Bak were detected by Western blot. The cells were divided into vector group, PDCD4 group, PDCD4 with activator group for detect the level of PARP(C) by Western blot.Results Compared with control group, the Results of real-time PCR and western blot were showed the level of PDCD4 was augmented in over-expression group (also in the over-expression with cisplatin group), which was indicated stable transfection with PDCD4 was successful. Immunofluorescence (with hoechst dying) and flow cytometry demonstrated that PDCD4 facilitated cell apoptosis exposed to cisplatin. PDCD4 overexpression attenuated the protein levels of pAkt, pGSK3β and BCL-2, but increased the protein levels of BAK. Furthermore, incubation with SC-79 (the activator of Akt) reversed cell apoptosis induced by PDCD4.Conclusion Overexpression of PDCD4 promotes the apoptosis induced by cisplatin through pAKT/pGSK3β pathway, which is favorable to reverse cisplatin resistance in gastric cancer.
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A sensing system based on AuNP-AuNP-UCNP triple structure for efficient detection of dual targets was constructed. In the preparation of triple structure, the gold nanoparticles (AuNPs) and upconversion nanoparticles (NaYF4: Yb, Er, Gd, UCNPs) were synthesized and surface modified. Then the two nanoparticles and their aptamers were connected to form two kinds of optical fluorescent probes. A nucleic acid sequence that matches with two aptamers was designed, rendering the probes to get close based on the principle of complementary base pairing. On the basis of this, a sensing system with a triple structure was prepared,and its connecting effect was characterized by TEM. With this system, dual targets of bisphenol A and estradiol were efficiently and conveniently detected through quantitative determination by fluorescence and UV spectrophotometer. At reaction temperature of 30℃ and pH=7.8,this method exhibited good linear range for determination of bisphenol A and estradiol from 2 ng/mL to 200 ng/mL and from 10 ng/mL to 150 ng/mL, with limits of detection of 0.2 ng/mL and 0.5 ng/mL, respectively. This sensing system with the triple structure owned better specificity to structural and functional analogues, and showed good repeatability and stability. What's more,this sensing system was applied in actual water detection,with the recoveries between 86.1% and 107. 4%, and the relative standard deviation below 6. 8%. This method showed promising applications in other environmental estrogens in water samples.
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Prediction of protein-protein interactions (PPIs) is of great significance. To achieve this, we propose a novel computational method for PPIs prediction based on a similarity network fusion (SNF) model for integrating the physical and chemical properties of proteins. Specifically, the physical and chemical properties of protein are the protein amino acid mutation rate and its hydrophobicity, respectively. The amino acid mutation rate is extracted using a BLOSUM62 matrix, which puts the protein sequence into block substitution matrix. The SNF model is exploited to fuse protein physical and chemical features of multiple data by iteratively updating each original network. Finally, the complementary features from the fused network are fed into a label propagation algorithm (LPA) for PPIs prediction. The experimental results show that the proposed method achieves promising performance and outperforms the traditional methods for the public dataset of H. pylori, Human, and Yeast. In addition, our proposed method achieves average accuracy of 76.65%, 81.98%, 84.56%, 84.01% and 84.38% on E. coli, C. elegans, H. sapien, H. pylori and M. musculus datasets, respectively. Comparison results demonstrate that the proposed method is very promising and provides a cost-effective alternative for predicting PPIs. The source code and all datasets are available at http://pan.baidu.com/s/1dF7rp7N.
Subject(s)
Algorithms , Protein Interaction Maps , Amino Acid Sequence , Animals , Databases, Protein , Humans , Hydrophobic and Hydrophilic Interactions , Mutation RateABSTRACT
Objective To compare the safety and feasibility of laparoscopic splenectomy and esophagogastric devascularization (LS + ED) versus open splenectomy and esophagogastric devascularization (OS + ED) in treating portal hypertension using Meta-analysis.Methods Controlled trials comparing LS + ED and OS + ED in treating portal hypertension were electronically searched from Wan Fang Data Knowledge Service Platform,Medalink,CNKI,PubMed,Elsevier,SpringerLink and CBM disc.The most recent search was conducted in April 2015.All the relevant data and references were retrieved and screened.RevMan 5.2 was used for data analysis.Results Eventually,7 randomized controlled trials (RCTs) or high-quality case-controlled studies involving 468 patients were included into this study.Meta-analysis showed LS reduced blood loss [WMD =214.67,95% CI 198.74-230.60,P < 0.01],shortened flatus time [WMD =17.72,95% CI 12.39-23.04,P < 0.01] and postoperative hospital stay [WMD =3.75,95% CI 3.28-4.23,P < 0.01],while the duration of surgery was shorter in OS (P > 0.05).However,OS was comparable with LS in complication rates.Conclusions Comparing with OS,LS had the advantages of reducing intraoperative blood loss and shortening recovery time after operation.In patients with cirrhosis,portal hypertension and esophageal varices,laparoscopic splenectomy was safe and effective.
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Objective To study biomechanical properties such as range of motion (ROM), intervertebral disc stress, ligament tension of inferior cervical spinal segment after the treatment of Discover, Prodisc-C artificial intervertebral disc replacement, and anterior cervical discectomy and fusion (ACDF), as well as mechanical property changes of the prosthesis after implantation. Methods Three kinds of operation plan on C5-6 cervical disc degeneration were established: Discover model, Prodisc-C model and ACDF model, as well as C4-7 segment original model of cervical vertebra. Biomechanical property changes after operation in cervical spine C4-7 segment in sagittal, coronal and transverse section were analyzed. Results ROM changes of cervical segment C5-C6 were as following: in Discover model it increased by 12.7%-73.1%, Prodisc-C model increased by 74%-98%, ACDF decreased by 55.8%-71.8%. The stress of C4-5 intervertebral disc after Discover artificial disc replacement showed no obvious increase, while the stress of C6-7 intervertebral disc decreased by 33.2%-54.2% under flexion, extension and axial rotation conditions. The amplification of ligament tension in Discover model decreased by 30%-40% as compared to that in Prodisc-C model. The maximum stress of Discover model (36.72 MPa) appeared under flexion condition, which was smaller than that in Prodisc-C model. Conclusions Artificial disc replacement can help to keep movement performance for segment after surgery. As a newly developed artificial intervertebral disc prosthesis, Discover makes some progress in the aspect of decreasing ligament stress and maintaining spinal stability. The research findings will provide theoretical basis for the clinical study on ACDF and artificial cervical intervertebral disc replacement surgeries.
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Objective To establish a 3D finite element model of cervicothoracic spinal segments C5-T2 based on CT images and test its validity and effectiveness. Methods By using the Mimics, Geomagic and Hypermesh software, the 3D model of cervicothoracic spinal segments C5-T2 was reconstructed, repaired and pre-processed. Moment of ±0.5, 1, 1.5, 2 N•m were applied on top of the model to simulate loads produced during the flexion and extension movement of human body. The range of motion (ROM) of the segments C5-T2 during flexion and extension was calculated by ANSYS, and the reliability of the model was verified by comparing the experimental results in the previous literature with the finite element analysis results obtained in this study. Results Under the moment of 1 N•m, the ROMs of C5-6, C6-7, C7-T1 and T1-2 during flexion were 4.30°,3.21°,1.66° and 1.41°, and those during extension were 3.47°, 2.86°, 0.96° and 0.92°, respectively. The maximum stress during flexion appeared on the front of the vertebral body, while that during extension appeared on the back of the vertebral body. The trends of ROM and stress distributions were consistent with results reported in the previous literature. Conclusions The 3D model established in this study is accurate and realistic, and conforms to biomechanical properties of the cervicothoracic spine. The simulation results can be further used to explore clinical pathology of the spine and provide theoretical references for evaluation on cervicothoracic spine surgery.
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Objective To establish 3D finite element of human cervicothoracic spine C5-T2 based on CT images, and explore effects on stability of the cervicothoracic spine after total spondylectomy (TS) by using various combinations of internal fixation devices (pedicle screw, titanium mesh, steel plate), including the stress distributions on these internal fixation devices. Methods The intact finite element model of cervicothoracic spine C5-T2 was established and validated by comparing the model’s range of motion (ROM) with that of other in vitro experiments. Then four reconstruction models after TS of cervical spine segment C7 were established: TM+AP+DPS model (titanium mesh + anterior plate + posterior double-segmental pedicle screw), TM+AP+SPS model (titanium mesh + anterior plate + posterior single-segmental pedicle screw), TM+DPS model (titanium mesh + posterior double-segmental pedicle screw), AP+DPS model (anterior plate + posterior double-segmental pedicle screw). ROM of each reconstruction model under flexion, extension, lateral bending and rotation and stress distributions on these internal fixation devices were then analyzed. Results ROM of the reconstruction segments was greatly reduced by over 93% as compare to that of the intact model. Stress concentration phenomenon appeared on the titanium mesh in the TM+AP+SPS model. Conclusions The fixation effects of four reconstruction models are similar. Stresses on 3 DPS fixed-models are more evenly distributed, indicating that the overall stability of DPS fixed-model is superior to that of SPS fixed-model.
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The kinetic resolution of 2-substituted-2,3-dihydro-4-pyridones was realized via a Pd-catalyzed allylic substitution reaction using a commercially available (S)-P-Phos as a ligand, affording optically active dihydropyridones and C-allylated dihydropyridones in high yields and good enantioselectivities with the S-factor up to 43. With this protocol, a catalytic asymmetric total synthesis of indolizidine (-)-209I was realized for the first time.
Subject(s)
Alkaloids/chemical synthesis , Indolizidines/chemical synthesis , Palladium/chemistry , Pyridones/chemistry , Alkaloids/chemistry , Alkylation , Animals , Catalysis , Combinatorial Chemistry Techniques , Indolizidines/chemistry , Kinetics , Molecular Structure , Ranidae , Skin/chemistry , StereoisomerismABSTRACT
Objective To observe the changes of serum superoxide dismutase (SOD) levels in typeⅡdiabetic patients with peripheral arterial disease (PAD) before and after interventional therapy, and to investigate the effects of oxidative stress level and interventional treatment on serum SOD level. Methods During the period from July 2011 to December 2012 at authors’ hospital, a total of 40 patients with type Ⅱ angiography together with balloon dilation and/or stenting was carried out in 24 patients (group B, with Fontaine stage of Ⅱb - Ⅲ). Of the 24 patients in group B, lower limb arterial angiography together with balloon dilation was employed in 16 (group B1) and lower limb arterial angiography together with balloon dilation and stenting was adopted in 8 (group B2). Twenty healthy clinical subjects were used as control group (group C). Before interventional treatment, elbow venous blood samples of patients in group A and B were collected to determine serum lipid, HbA1c and SOD levels. The same tests were also carried out in the subjects of group C. During percutaneous lower extremity arterial intervention , through arterial sheath 3 ml arterial blood specimen was collected in all patients of both group A and B before intervention started. Twenty-four hours after the treatment, venous blood specimen was also collected in all patients to determine serum SOD levels. The results were statistically analyzed. Results Lower limb arterial angiography showed that no obvious arterial stenosis was seen in the patients of group A. The interventional procedures were all successfully completed in all patients of group B. SOD levels of group A, B and C were (46.1 ± 3.13)U/ml, (35.37 ± 3.58)U/ml and (60.50 ± 6.99)U/ml respectively. SOD levels of both group A and B were significantly lower than that of group C (t = 8.420, P < 0.01; t = 14.324, P < 0.01). The level of SOD in group A was significantly higher than that in group B (t = 10.092, P < 0.01). The ankle-brachium indexes (ABI) of group A, B and C were (0.70 ± 0.12), (0.58 ± 0.13) and (1.15 ± 0.07) respectively. ABI of group A and B was significantly lower than that of group C (t = 14.324, P < 0.01; t = 17.392, P < 0.01). ABI of group B was significantly lower than that of group A (t=3.027, P<0.05). SOD level bore a negative correlation with HbA1c level (r=-0.541, P<0.01). In both group A and group B, no significant difference in SOD level existed between the venous blood and arterial blood. The preoperative arterial SOD levels in group B1 and group B2 were (35.70 ± 3.04)U/ml, and (36.07 ± 2.14)U/ml respectively, and the difference between the two groups was not statistically significant. The preoperative SOD levels in the ischemic arterial region in group B1 and group B2 were (32.95 ± 3.52)U/ml and (33.59 ± 2.64)U/ml respectively, and the difference between the two groups was not statistically significant although these levels were significantly lower than the preoperative arterial SOD levels(t=2.741, P<0.05; t=2.704, P<0.05). After the interventional treatment, the SOD levels in the ischemic arterial region in group B1 and group B2 were (29.40 ± 5.49)U/ml and (26.68 ± 2.31)U/ml respectively, and the difference between the two groups was not statistically significant although these levels were significantly lower than the preoperative SOD levels in the ischemic arterial region (t = 2.536, P < 0.05; t = 5.005, P < 0.01). No statistically significant differences in SOD levels at each corresponding site existed between group B1 and group B2. Conclusion No significant difference in SOD level exists between the venous blood and the arterial blood. Serum SOD level carries a negative linear correlation with HbA1c level. Before interventional treatment , the SOD level in ischemic region is low, which becomes lower after the interventional procedure, which may be caused by the enhanced oxidative stress reaction that is resulted from the damage of the vascular wall due to interventional manipulations. The enhanced oxidative stress reaction may play an important role in the occurrence of restenosis.
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<p><b>OBJECTIVE</b>To investigate the preliminary efficacy and safety of ambrisentan, a selective endothelin receptor antagonist, in patients with pulmonary arterial hypertension (PAH).</p><p><b>METHODS</b>A total of 15 patients with PAH, including 10 patients with idiopathic PAH and 5 patients with associated connective-tissue disease, received 2.5 mg or 5 mg of ambrisentan once daily for 12 weeks. Before and after 12 weeks treatment, 6-minute walk test (6-MWD), WHO functional classification (WHO FC) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured.</p><p><b>RESULTS</b>After 12 weeks treatment, the 6-MWD was significantly increased [(376.5 ± 108.2) m vs.(460.3 ± 95.7) m, P = 0.021] and the systolic pulmonary artery was significantly decreased [(85.0 ± 33.3) mm Hg (1 mm Hg = 0.133 kPa)vs. (70.5 ± 30.5) mm Hg,P = 0.015] and NT-proBNP was significantly reduced [892.0 (99.0-2245.0) ng/L vs. 205.0 (56.0-534.0) ng/L, P = 0.026] than before treatment. WHO FC was improved in 4 patients after 12 weeks treatment. No patient was withdrawn from this study for safety reasons.</p><p><b>CONCLUSIONS</b>Ambrisentan treatment can effectively improve the exercise capacity, and reduce systolic pulmonary artery pressure and NT-proBNP in PAH patients. Ambrisentan use is safe and could be well tolerated in Chinese PAH patients.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Antihypertensive Agents , Therapeutic Uses , Familial Primary Pulmonary Hypertension , Hypertension, Pulmonary , Drug Therapy , Phenylpropionates , Therapeutic Uses , Prospective Studies , Pyridazines , Therapeutic Uses , Treatment OutcomeABSTRACT
Objective To study the use of early bile duct to bile duct end-to-end(side) anastomosis for extrahepatic bile duct injuries.Methods The clinical data of 25 patients with extrahepatic bile duct injuries with early bile duct to bile duct end-to-end(side) anastomosis were retrospectively analyzed.Results Bile duct injuries happened in laparoscopic cholecystectomy (n=17),laparoscopic exploration of common bile duct (n=1),laparotomy (n=5),and knife wound (n=2).All of the repairs were successfully carried out.Except for one patient who was lost to follow-up,the other patients were followed for over 2 years.There was no bile duct stenosis.One patient died after 5 months of repair in other hospital because of a recurrent bile duct calculus.Conclusions Early bile duct to bile duct end-to-end(side) anastomosis had a good long-term results.The operation needs to be done by a good surgeon or supervised by an experienced specialist in biliary surgery.A prolonged period of T tube stenting is a prerequisite for success.
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We recently demonstrated that cilnidipine, an L/N-type calcium channel blocker, elicits protective effects against glomerular podocyte injury, in particular, in obese hypertensive rats that express the N-type calcium channel (N-CC). Since the N-CC is known to be expressed in sympathetic nerve endings, we evaluated the reno-protective effects of cilnidipine in innervated and denervated spontaneously hypertensive rats (SHR). Male SHR were uninephrectomized and fed 4% high-salt diet (HS-UNX-SHR). Animals were divided into groups, as follows, and observed from 9 to 27 weeks of age: 1) vehicle (n = 14), 2) vehicle plus renal-denervation (n = 15), 3) cilnidipine (50 mg/kg per day, p.o.; n = 10), and 4) cilnidipine plus renal-denervation (n = 15). Renal denervation attenuated elevations in blood pressure, but failed to suppress urinary protein excretion and podocyte injury in HS-UNX-SHR. Cilnidipine in both innervated and denervated HS-UNX-SHR similarly induced significant antihypertensive effects, as well as suppressing the urinary protein excretion and podocyte injury, compared to vehicle-treated HS-UNX-SHR. These data indicate that renal nerves have a limited contribution to the cilnidipine-induced reno-protective effects in HS-UNX-SHR.