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OBJECTIVE To investigate the effect of gene polymorphism on opioid-induced constipation. METHODS The target genes related to opioid-induced constipation were screened out through searching guidelines， databases and evidence-based medical data， and then 100 cancer pain patients who received opioid drugs for analgesia were included as the study subjects. According to whether there were adverse effects of constipation after medication or not， they were divided into test group and control group， with 50 cases in each group. The target gene was detected by PCR or fluorescence in situ hybridization. The SNPStats program was used to carry out Hardy-Weinberg balance test and correlation analysis between gene polymorphism and opioid-induced constipation. The multivariate Logistic regression analysis was used to explore the relevant predictive factors of opioid-induced constipation， and receiver operating characteristic （ROC） curve of subjects was drawn to analyze the effectiveness of each predictive factor in predicting opioid-induced constipation. RESULTS CYP2D6， CYP3A5*3， ABCB1 and OPRM1 were selected as target genes for detection. The results of genotype detection showed that the frequency distribution of CYP2D6 （rs1065852， rs1135822， rs16947， rs28371725， rs28371735）， CYP3A5*3 （058rs776746）， ABCB1 （062rs1045642）， OPRM1 （047rs1799971） alleles were consistent with Hardy-Weinbergbalance test. The correlation analysis results showed that the proportion of genotype GG and AG in CYP3A5*3 （058rs776746， 163.com A＞G） and genotype AA and AG in OPRM1 （047rs1799971， A＞G） of patients was significantly higher in test group than that in the control group （P＜0.05）. Multivariate Logistic regression analysis showed that medication duration， CYP3A5*3 and OPRM1 gene polymorphism could be used as predictors of opioid- induced constipation in patients （P＜0.05）. The ROC curve analysis results showed that the areas under the ROC curves for medication duration and CYP3A5*3， OPRM1 gene polymorphism were 0.648， 0.640 and 0.670， respectively， with the optimal cutoff values of 124.0， 0.5 and 0.5， respectively. CONCLUSIONS Genotype GG and AG in CYP3A5*3 （058rs776746，A＞G） and genotype AA and AG in OPRM1 （047rs1799971，A＞G） are associated with opioid-induced constipation， which are expected to become clinical predictors of opioid-induced constipation， and more attention should be paid to the occurrence of constipation in patients who have been taking opioids for a long time.
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Objective:To investigate the epidemiological characteristics of lower extremity deep vein thrombosis (DVT) in patients with femoral fracture.Methods:Retrospectively analyzed were the data of 2,571 patients with femoral fracture who had been treated at the Third Hospital of Hebei Medical University from January 2019 to December 2019. There were 1,079 males and 1,492 females, aged from 14 to 96 years (average, 67.1 years). There were 1,158 femoral neck fractures, 951 femoral intertrochanteric fractures, 309 femoral shaft fractures, and 153 femoral condylar fractures. 2,414 patients were treated surgically while 157 patients non-surgically. Color Doppler ultrasonography of both lower extremities was performed to determine the occurrence of DVT before operation and every week after operation for patients undergoing surgical treatment, and within 48 hours after admission and every week during hospitalization for those undergoing non-surgical treatment. The incidence and location of DVT were recorded for different femoral fractures.Results:The incidence of DVT in this cohort was 35.5%(913/2,517), that of proximal DVT 5.3%(135/2,571), and that of distal DVT 30.3% (778/2,571). In patients with femoral neck fracture, femoral intertrochanteric fracture, femoral shaft fracture and femoral condylar fracture, the incidence of DVT was respectively 28.8% (334/1,158), 44.7% (425/951), 30.7% (95/309) and 38.6% (59/153), the incidence of proximal DVT was respectively 2.7% (31/1,158), 5.6%(53/951), 9.7% (30/309) and 13.7% (21/153), and the incidence of distal DVT was respectively 26.2% (303/1,158), 39.1% (372/951), 21.0% (65/309) and 24.8%(38/153). The incidence of DVT in the femoral vein and above, popliteal vein, tibiofibular vein and intermuscular vein in this cohort was respectively 2.3%(60/2,571), 2.9%(75/2,571), 6.4%(165/2,571) and 23.8%(613/2,571).Conclusions:The incidence of DVT may be high in patients with femoral fracture, and the proximal DVT with a high risk of pulmonary embolism may occur more in patients with femoral condylar fracture.
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Objective:To evaluate the effect of sevoflurane on necroptosis in isolated hippocampal neurons and the relationship with ryanodine receptor.Methods:Primarily cultured hippocampal neurons of fetal rats of Sprague-Dawley rats were inoculated in culture wells (100 μl/well) or culture flasks (3 ml/bottle) at a density of 5×10 5 cells/ml at 7 days of culture and divided into 3 groups ( n=24 each) using a random number table method: control group (group C), sevoflurane group (group S) and ryanodine receptor antagonist group (group R). Group C received routine culture.Ryanodine receptor antagonist Dantrolene at a final concentration of 3 μmol/L was added in group R. Thirty minutes later, the cells were placed in the incubator containing 2% sevoflurane and cultured for 5 h at 37 ℃ in S and R groups.Then cells were collected, the morphology of neurons was observed with an inverted microscope, the concentrations of free calcium ion ([Ca 2+ ] i) in cytoplasm were determined by flow cytometry, the expression of ryanodine receptor and phosphorylated MLKL protein (p-MLKL) was detected by Western blot, the expression of RIP3 was measured by immunofluorescence, and necroptosis rate was calculated. Results:Compared with group C, the [Ca 2+ ] i were significantly increased, the expression of ryanodine receptor and p-MLKL was up-regulated, and the necroptosis rate was increased in S and R groups ( P<0.05). Compared with group S, the expression of ryanodine receptor and p-MLKL was significantly down-regulated, and the [Ca 2+ ] i and necroptosis rate were decreased in group R ( P<0.05). There was no obvious abnormality in the morphology of neurons in group C. The cell body of neurons were shrunk, the processes were broken, and the network between processes was sparse in group S. The cell body was round, and the morphology was close to normal in group R. Conclusion:Sevoflurane can cause necroptosis in isolated hippocampal neurons of rats, and the mechanism is related to up-regulating the expression of ryanodine receptors and leading to calcium overload.
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Consensus and guidelines regarding point-of-care ultrasound (POCUS) carried out by neonatologists in neonatal intensive care unit (NICU) have been published in many countries. This review summarizes the development, advantages, limitations, and current issues of POCUS in NICU, aiming to promote the establishment of systematic training courses, accelerate the development of POCUS in NICU in China, and ensure the effectiveness and safety of POCUS implementation.
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Objective:To determine the median effective concentration (EC 50) of ropivacaine producing sensory-motor separation when used for femoral nerve block performed under ultrasound guidance. Methods:American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients of both sexes, aged 18-64 yr, with body mass index of 18-30 kg/m 2, scheduled for elective arthroscopic knee surgery under general anesthesia, were enrolled in this study. Femoral nerve block was performed under ultrasound guidance.After successful location, ropivacaine 22 ml was injected with the initial concentration of 0.50%, and the ratio between the two consecutive concentrations was 1.1.The EC 50 of ropivacaine was determined by up-and-down sequential method.The positive response was considered as sensory block without motor block.The negative response was considered as sensory and motor block.When a negative response was found, the concentration was decreased in the next patient.When a positive response occurred, the concentration was increased in the next patient.Probit analysis was used to calculate the EC 50 and 95% confidence interval of ropivacaine producing sensory-motor separation when used for femoral nerve block which was performed under ultrasound guidance. Results:The EC 50 of ropivacaine producing sensory-motor separation was 0.186%, and the 95% confidence interval was 0.155%-0.205% when used for ultrasound-guided femoral nerve block. Conclusion:The EC 50 of ropivacaine producing sensory-motor separation is 0.186% when used for femoral nerve block performed under ultrasound guidance.
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To study the effect of microgravity on peripheral oxygen saturation (SpO ) in rats, tail-suspended rats were applied to simulate microgravity environment. SpO and arterial oxygen saturation (SaO ) were measured by pulse oximeter and arterial blood gas analyzer (ABGA) respectively on the 14th day, 21st day and 28th day in tail-suspended group and control group. Paired -test shows that SpO was significantly lower than SaO in tail-suspended group on the 14th day ( < 0.05), the 21st day ( < 0.05) and the 28th day ( < 0.01). The ANOVA results shows that modeling time had significant effect on SpO value but no effect on SaO value in tail-suspended group. These results indicate that pulse oximeter may be not suitable for oxygen saturation test in microgravity environment.
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Objective To investigate the risk assessment ,prevention and management for perioperative stroke in elderly patients with hip fractures. Methods A total of 179 patients aged 65 years and older were admitted to our department due to hip fracture. In managements of perioperative stroke ,the preoperative risk assessment and the management of stroke ,identifying the risk population for stroke prevention ,controlling risk factors of the preoperative stroke ,intraoperative monitoring , postoperative treatment ,etc.were studied retrospectively.The incidence of perioperative stroke was recorded and analyzed. Results Of 179 patients with hip fracture ,overviews of diagnosis and treatment were as follows.Twenty-four (24/179 ,13.41% ) cases did not receive operative treatments.Head and neck CT angiography(CTA)-showed severe stenosis or occlusion of intracranial artery and internal carotid artery were in 9(5.03% ,9/179)patients ,of whom the 5(2.79% ,5/179) cases underwent cerebrovascular digital subtraction angiography (DSA ) ,balloon dilation and stent implantation ,then received the operation for hip fracture 10 days later ,finally were discharged uneventfully.1 (0.56% ,1/179 ) patient underwent orthopaedic surgery due to the results of DSA showing no indication of interventional therapy ,and was discharged unevenfully.3 (1.68% ,3/179 ) patients refused to receive the further DSA examination or interventional therapy ,strongly demanded for orthopaedic surgery and would take the surgical risk ,and were discharged uneventfully.2(1.12% , 2/179)patients were found to have cerebral aneurysm diagnosed by CTA and DSA ,and underwent surgery for hipfracture without special treatment.2(1.12% ,2/179)patients were diagnosed as new occurrence of cerebral infarction before the operation ,and received head and carotid stenting at the department of cerebrovascular surgery ,followed by combined antithrombotic therapy of aspirin , clopidogrel and low molecular weight heparin for 4 weeks ,then underwent orthopaedic surgery for hip fracture.2 (1.12% ,2/179 ) patients were diagnosed as new cerebral infarction after orthopaedic surgery ,then were transferred to the department of neurology for treatment. Conclusions The thorough preoperative risk assessment and management of stroke ,reasonable perioperative antiplatelet and anticoagulation therapy ,intense intraoperative monitoring and active postoperative complications management make it possible for high-risk and new ischemic stroke patients with hip fractures to receive early orthopaedic treatment.
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Objective To establish a arsenic cerium catalytic rate method for determination of urinary iodine,and increase the linear range of urinary iodine determination.Methods Standard series and urine samples after digestion treatment,were tested using dynamics function of spectrophotometer to record the curve of absorbance value (A) change with time (t) during arsenic cerium catalytic reaction for each measurement system,choice (A1,t1) and (A 2,t2) on this curve and calculating the reaction rate (v),v =(lgA1-lgA2)/(t2-t1).Through the determination of the standard series it could calculate regression equation of iodine concentration (C) with X:C =a ± bX,X =1 000 (v-v0),and the v0 is the reaction rate of reagent blank.Results (① C and X were positively correlated.The standard series linear range was 0-1 200 pμg/L and correlation coefficient r was higher than 0.999 1.The minimum detection limit was 3.9 μg/L (0.25 ml urine).②)Precision:5 urine samples (A,B,C,D,E) were selected within the range of 0-1 200 μg/L and the measured value were (72.3 ± 2.7),(148.2 ± 5.2),(210.5 ± 4.4),(562.7 ± 6.8),and (899.3 ± 8.0) μg/L.The relative standard deviation (RSD) was between 0.9％-3.8％.(③)Accuracy:4 samples (A,B,C,D) were measured for standard addition recovery test,recovery was between 94.2％-107.2％;urinary iodine standard material [the given values were (67.9 ± 9.0),(142.0 ± 10.0),(195.0 ± 10.0),(558.0 ± 17.0),(885.0 ± 28.0) μg/L] were determined and the results were in the range of uncertainty of the standard material.④Method contrast:with the national health standard method (method for determination of iodine in urine by arsenic cerium catalytic spectrophotometry) to determinate 120 urine samples,the results showed that there were 60 urine samples within 0-300 μg/L,60 urine samples were more than 300 μg/L.Then rate method was used to test the 120 urine samples.For the 60 samples within the scope of 0-300 μg/L,the determination results of the two methods were positively correlated (r =0.994,P ＜ 0.01);the results of the rate method were lower than those of the standard method and the difference was statistically significant (t =2.047,P ＜ 0.05).But the average deviation was only 2.1 μg/L,for the determination of urine iodine there was no practical significance;for the 60 samples higher than 300 μg/L,the determination results of the two methods were positively correlated (r =0.993,P ＜ 0.01) and the difference was not statistically significant (t =-1.092,P ＞ 0.05).Conclusions Arsenic cerium catalytic rate method has increased the linear range of urinary iodine determination.Using this method,the vast majority samples can be tested directly without dilution,thereby reducing the workload for determination of urine iodine.
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Objective: To investigate the effects of γ-tocotrienol (γ-T3) on the invasion and migration of human gastric cancer SGC-7901 cells as well as its possible molecular mechanism. Methods: The different concentrations (0, 15, 30, 45, 60, and 100 μmol/L) of γ-T3 were used to treat SGC-7901 cells. Then the proliferation, migration and invasion of SGC-7901 cells were detected by CCK-8 assay, cell scratch wound healing assay and Transwell invasion assay, respectively. Furthermore, the expressions of cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF- κB) signal pathway proteins were detected by Western blotting. Results: After treatment with different concentrations (15-100 μmol/L ) of γ-T3 for 24, 48 and 72 h, the proliferation of SGC-7901cells was evidently inhibited in a time- and dose-dependent manner (all P<0.01). After treatment with γ-T3 (15-60 μmol/L) alone or combined with tumor necrosis factor-alpha (TNF-α) (10 ng/mL) for 24 h, the migration and invasion abilities of SGC-7901 cells were significantly inhibited (all P<0.01). The expressions of NF-κB, NF-κB p65 and COX-2 proteins were significantly down-regulated in SGC-7901 cells after γ-T3 (15-60 μmol/L) treatment for 24 h (all P<0.01). Conclusion: γ-T3 can inhibit the invasion and migration of human gastric cancer SGC-7901 cells. Its mechanism may be associated with blocking NF-κB signal pathway and reducing the expression of COX-2 protein.
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The problem of pediatric drugs has been the challenges facing the world. The two most important issues are the lack of appropriate drug dosage forms for children and the safety and effectiveness data of drug use in children. How to encourage produc?tion enterprises to produce drug varieties,specifications and dosage forms suitable for children use,guide drug manufacturers to ob?tain drug use data are the most important work for pediatric drugs.Based on the literature home and abroad,we analyze the regulatory policies for the research and development(RD)and application of pediatric drugs in the USA,EU and Japan,which have made great efforts to encourage enterprises to conduct pediatric research. Their successful experiences are summarized and can be used as refer?ence for the establishment of the policies adaptive to the situation of China for the RD of pediatric drugs.
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Objective:To discuss the application of antithrombotic drugs in myocardial infarction patients with thrombocytopenia. Methods:The therapy for one myocardial infarction patient with primary thrombocytopenia was discussed and summarized. Based on the related literatures, the characteristics of case, application status and adverse reactions of antithrombotic drugs and anticoagulant drugs were summarized. Results: The adjustment of antithrombotic drug treatment regimen for the patient was reasonable. Conclu-sion:Antithrombotic drugs applied in acute myocardial infarction patients with thrombocytopenia are safe. If patients complicate with other diseases, individualized antithrombotic therapy should be carried out according to particular case.
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Objective To study the efficacy of L-3,5-diiodotyrosine (DIT) and inorganic iodine (KIO3) in iodine-deficiency Wistar rats.Methods Sixty Wistar rats,weighting about 160-180 g,were divided into two groups according to body weight by the random number table method:iodine-deficiency model (40 rats) was fed with low-iodine food (the iodine content was 35.9 μg/kg);optimal-iodine model (20 rats) was fed with low-iodine food and given with KIO3 water (the iodine content was 18 mg/L) 0.5 ml by intragastric once a day.Model was established for 3 months.Iodine-deficiency model was subdivided into low iodine (LI) group,KIO3 group and DIT group,eight,nine,ten rats in each group;from optimal-iodine model,nine rats were randomly selected as optimal iodine (NI) group.LI group was fed with low-iodine food;KIO3 group was fed with low-iodine food and given with KIO3 water (the iodine content was 18 mg/L) 0.5 ml by intragastric once a day;DIT group was fed with low-iodine food and given with DIT water (the iodine content was 18 mg/L) 0.5 ml by intragastric once a day;NI group was fed with low-iodine food and given with KIO3 water (the iodine content was 18 mg/L) 0.5 ml by intragastric once a day.After 3 months,24-hour urine of the rats was collected.According to the method for determination of iodine in urine by As3 +-Ce4+ catalytic spectrophotometry (WS/T 107-2006),iodine content in urine was detected.Rats were anesthetized intraperitoneally with 25％ urethane,blood from abdominal aortic was collected to determinate the serum thyroid hormone [total triiodothyronine (TT3),total thyroxine (TT4),free triiodothyronine (FT3),free thyroxine (FT4)] level in rats by automatic electrochemical luminescence immunoassay.All the rats were sacrificed to analyze the thyroid weight.Results ① The urine iodine showed significant differences in the four groups (x2 =25.24,P ＜ 0.05).The median of urine iodine concentration in the LI,NI,KIO3 and DIT groups were 3.00,286.14,223.37,214.33 μg/L,respectively.The urine iodine concentration in LI group was significantly lower than those of other three groups (all P ＜ 0.05).② The serum TT3,TT4,FT3,FT4 levels showed significant differences in the four groups (F =63.48,140.73,130.20,365.27,all P ＜ 0.05).And the hormone levels in KIO3 group were lower than those of the DIT group [TT3:(1.57 ± 0.20) vs.(1.97 ± 0.18) mmol/L,TT4:(51.23 ± 4.90) vs.(71.94 ± 5.27) mmol/L,FT3:(5.34 ± 0.45) vs.(6.98 ± 0.33) pmol/L,FT4:(26.18 ± 2.30) vs.(35.47 ± 2.28) pmol/L,all P ＜ 0.05].③The color of thyroid in KIO3 and DIT groups became pale pink.The absolute and relative thyroid weight showed significant differences in the four groups (F =225.05,345.40,all P ＜ 0.05).The absolute thyroid weight [(31.76 ± 1.75) mg] and relative thyroid weight [(11.69 ± 3.47) mg/100 g] in DIT group was lower than that of the KIO3 group [(36.31 ± 5.23) mg,(12.83 ± 4.38) mg/100 g,all P ＜ 0.05].Conclusion Animal experimental results show that DIT has a better iodine-supplementing efficacy than that of KIO3.
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<p><b>OBJECTIVE</b>To improve the radio frequency (RF) transmission distance of the wireless terminal of the medical internet of things (LOT), to realize the real-time and efficient data communication, the intelligent relay system based on STM32F103 single chip microcomputer (SCM) is proposed.</p><p><b>METHODS</b>The system used nRF905 chip to achieve the collection, of medical and health information of patients in the 433 MHz band, used SCM to control the serial port to Wi-Fi module to transmit information from 433 MHz to 2.4 GHz wireless Wi-Fi band, and used table look-up algorithm of ready list to improve the efficiency of data communications.</p><p><b>RESULTS</b>The design can realize real-time and efficient data communication.</p><p><b>CONCLUSION</b>The relay which is easy to use with high practical value can extend the distance and mode of data transmission and achieve real-time transmission of data.</p>
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Humans , Algorithms , Communication , Internet , Medical Informatics , Microcomputers , Radio Waves , Wireless TechnologyABSTRACT
Objective:To compare lumbar fusion effect of unilateral and bilateral internal fixation for lumbar disc herniation, to explore more effective, reliable treatment. Methods:112 cases of lumbar selects my courtyard 2007 April-2010 year in April admitted to the disc herniation were randomly grouped, unilateral group and bilateral group with 56 cases in each group, respectively, to take unilateral or bilateral internal fixation for the treatment of lumbar fusion operation, compared two groups of patients and the therapy effect. Results:the unilateral group operation time, amount of bleeding during the operation and hospitalization expenses below the bilateral group, there was significant difference(t=8.857, t=9.620, t=12.338;P0.05);the two group patients after VAS and ODI were significantly decreased (P0.05);the unilateral group at the end of the follow-up of 50 cases of intervertebral fusion, the fusion rate was 96.2%, the bilateral group interbody fusion in 52 cases, the fusion rate was 100%, two groups of patients at the end of the follow-up intervertebral fusion rate has no obvious statistical difference (x2=0.372, P<0.05);unilateral group were no significant complications, bilateral group were found 1 cases of intervertebral fusion device implant bone absorption, 1 cases highlight the root symptoms, complication rate was 3.8%, the two groups of patients with complications were no significant statistical difference. Conclusion:Lumbar unilateral and bilateral internal fixation can effectively improve the patients with lumbar disc herniation pain symptoms, and has good fusion degree, high security, and unilateral internal fixation operation time is shorter, less blood loss and the burden of patients is smaller, need operation treatment for severe lumbar disc herniation, fusion and unilateral internal fixation for the treatment of recommend the use of lumbar.
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Objective To investigate the effect of emodin on insulin resistance and leptin in rat with nonalcoholic fatty liver disease (NAFLD) and to explore the mechanisms of emodin treating NAFLD.Methods Forty two Spraque-Dawley rats were numbered according to their body weights,and were randomly divided into two groups(group A:8 rats; group M:34 rats) by random number table method.The rats in group A was fed with ordinary diets and Group M with improved high fat diets.Four weeks later,when hepatic steatosis in group M were identified,the remaining 32 rats in group M were numbered according to their body weights,and were divided randomly into 4 subgroups (group M1,M2,M3 and M4) by random number table method,with 8 rats in each subgroup.The feeding of all rats was unchanged.The rats in group M2,M3 and M4 were separately intervened with emodin by low doses,emodin by high doses and metformin.Emodin and metformin were dissolved by 0.5％ sodium carboxymethyl cellulose.The rats in group A and M1 was fed with 0.5％ sodium carboxymethyl cellulose by gavage.Four weeks later,all rats were executed.The serum glucose was measured with automatic biochemical analyzer.The serum insulin and leptin were measured by radioimmunoassay (RIA).Insulin resistance was estimated by insulin resistance index of homeostasis model assessment (HOMA-IR) and insulin sensitivity index (ISI).Liver biopsy tissues were treated by Hematoxylin-eosin (HE) staining to evaluate the degree of steatosis and inflammation of liver.Results Compared with group M1,the low and high dosage emodin improved insulin resistance which was represent by serum insulin,HOMA-IR,and ISI(P ＜0.05,P ＜0.01).The serum leptin in group M1 was higher than that in group A (P ＜0.01).The serum leptin in groups M2 and M3 was lower than that in group M1(P ＜0.05,P ＜0.01).Correlation analysis showed that the serum leptin was positively correlated with HOMA-IR(r =0.746,P ＜0.05),and negatively correlated with ISI(r =-0.731,P ＜ 0.05)in group M1.Compared with group M1,the low and high dosage emodin together had the respective effect of ameliorating steatosis(P ＜0.05,P ＜0.01),and they also reduced the hepatic inflammatory activity(P ＜ 0.01).Conclusions Reducing serum leptin and improving insulin resistance may be the mechanisms of emodin treating NAFLD.
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AIM: To investigate the effect of vasodilator-stimulated phosphoprotein (VASP) phosphorylation on the cell migration induced by platelet-derived growth factor BB (PDGF-BB), and to identify which phosphorylation site was more important among the three phosphorylation sites, namely Ser157,Ser239 and Thr278. METHODS: Two phosphorylation mutants of VASP, pcDNA3.1(+)/VASP-S157A and pcDNA3.1(+)/VASP-S239A, were constructed and respectively transfected into the cultured ECV304 cells by means of liposome. The stable expression cells were screened by using antibiotic G418. Protein expression of VASP was measured by Western blotting. The ECV304 cell migration was evaluated using Transwell chamber. RESULTS: Compared to control group, the cell migration was significantly inhibited in ECV304 transfected with VASP-S157A and VASP-S239A (P<0.05), although slight differences existed between VASP-S157A and VASP-S239A transfected cells (P>0.05). CONCLUSION: VASP mutation on the phosphorylation sites of Ser157 and Ser239 inhibits cell migration, and the phosphorylation sites of Ser157 and Ser239 both greatly affect the function of VASP.
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To obtain higher potency and specificity, a series of 7-alkoxy analogues of illudalic acid was synthesized on the base of structure-activity relationship (SAR). All of these compounds exhibited submicromolar inhibition of the enzyme when tested against human leukocyte common antigen-related phosphatase (LAR) (for example, for 15e, IC50 = 180 nmol x L(-1)). They represent the most potent small-molecule inhibitors of LAR so far. These analogues also display excellent selectivity for LAR over other protein tyrosine phosphatases (PTPs) except for the highly homologous PTPsigma. The compound 15f is of 120-fold selectivity for LAR versus PTP-1B inhibition. The development of potent enzyme-specific inhibitors is so important that they may serve both as tools to study the role of LAR and as therapeutic agents for treatment of type II diabetes.