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ObjectiveTo investigate the mechanism of icariin in ameliorating efferocytosis dysfunction and inflammatory response of alveolar macrophages induced by cigarette smoke extract via the peroxisome proliferator-activated receptor gamma （PPARγ） signaling pathway. MethodThe untreated rat alveolar macrophages （NR8383） were taken as the blank group. The NR8383 cells treated with 10% cigarette smoke extract were divided into model， low-， medium-， and high-dose （10， 20， 40 μmol·L-1） icariin， PPARγ inhibitor， and PPARγ inhibitor + low-， medium-， and high-dose icariin groups. Alamar blue colorimetry was employed to examine the proliferation and toxicity of icariin on NR8383 cells. The efferocytosis rate of NR8383 cells was detected by flow cytometry. Enzyme-linked immunosorbent assay was employed to measure the levels of tumor necrosis factor-alpha （TNF-α）， transforming growth factor-β1 （TGF-β1）， and milk fat globule-epidermal growth factor 8 （MFG-E8）. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were employed to determine the protein and mRNA levels， respectively， of PPARγ， CD36， and RAS-related C3 botulinum toxin substrate 1 （Rac1）. ResultThe efferocytosis dysfunction model of NR8383 was established with the cigarette smoke extract. Compared with the blank control group， the model group showed decreased efferocytosis rate （P<0.05）， elevated TNF-α level （P<0.05）， lowered TGF-β1 and MFG-E8 levels （P<0.01）， and down-regulated mRNA and protein levels of PPARγ， CD36， and Rac1 （P<0.05， P<0.01）. Compared with the model group， the treatment with icariin increased the efferocytosis rate （P<0.05， P<0.01）， lowered the TNF-α level （P<0.01）， elevated TGF-β1 and MFG-E8 levels （P<0.05）， and up-regulated the protein and mRNA levels of PPARγ， CD36， and Rac1 （P<0.05， P<0.01）. Compared with icariin alone， PPARγ inhibitor + icariin decreased the efferocytosis rate （P<0.05） and down-regulated the protein and mRNA levels of PPARγ （P<0.05， P<0.01）. In addition， PPARγ inhibitor + low-dose icariin down-regulated the protein level of CD36 （P<0.01） and PPARγ inhibitor + low-/medium-dose icariin up-regulated the protein level of Rac1 （P<0.05）. ConclusionIcariin ameliorates the cigarette smoke extract-induced efferocytosis dysfunction of alveolar macrophage by regulating the PPARγ signaling pathway and cytoskeletal structure rearrangement.
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Neutrophils are predominant leukocytes in the circulation, which are essential for killing invading pathogens via the activation of effector responses and the production of reactive oxygen species (ROS), also named as "oxidative burst." When infected, activated neutrophils fight bacteria, fungi, and viruses through oxidative burst, phagocytosis, degranulation, and the production of neutrophil extracellular traps (NETs) in a neutrophil death process named as "NETosis" (Mutua and Gershwin, 2021). NETs, consisting of DNA fibers decorated with modified histones and numerous antimicrobial proteins from cytoplasmic granules and the nucleus, can either be beneficial or detrimental (Mutua and Gershwin, 2021). Several pathways can lead to this death process. In response to various stimuli, NETosis traps and clears pathogens, facilitating phagocytosis by other neutrophils and phagocytes. However, excessive NETosis often results in disease due to increasing the pro-inflammatory response and perpetuating the inflammatory condition (Hellebrekers et al., 2018; Hidalgo et al., 2019; Klopf et al., 2021). Accordingly, inhibiting aberrant NETosis may alleviate the severity of various autoimmune and inflammatory diseases.
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DNA , Extracellular Traps/metabolism , Neutrophils/metabolism , Reactive Oxygen Species/metabolism , Respiratory BurstABSTRACT
Objective:To investigate the risk factors on androgenetic alopecia (AGA) of primary healthcare staffs.Methods:Primary healthcare staffs were investigated by a questionnaire.Results:A total of 934 healthcare staffs (550 males and 384 females) were surveyed, of which 238 cases were diagnosed as AGA. 68.8% of AGA patients had poor mental health self-assessment; 52.94% of AGA patients had a family history; the prevalence in the people who usually had the night shift was 26.03%, which was higher than that in the people who had no night shift.Conclusions:The prevalence of AGA in healthcare staffs is higher than the national average, which might be related to working pressure, mental status, night shifts, genetic and alcohol drinking.
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Objective:To study the clinical efficacy of nanocrystalline needles combined with 5% minoxidil tincture in the treatment of androgenetic alopecia of male.Methods:A total of 60 patients with androgenetic alopecia were randomly divided into treatment group and control group, with 30 patients in each group. The control group was treated with 5% minoxidil tincture 2 times a day. On the basis of the control group, the treatment group was treated with nanocrystalline needles combined with 5% minoxidil tincture for 10 minutes 2 times a week. The clinical effects of different treatments were compared after six months.Results:There was a significant difference in overall response rate between the treatment group and the control group (80.00% vs. 53.30%, P<0.05). The improvement of the each clinical features of image by dermoscopy in patients with hair loss disease included more than 20% of hair diameter diminish, vellus hair increased, partly acomia and yellow dot sign had a significant difference between the treatment group and the control group ( P<0.05). Conclusion:Nanocrystalline needles combined with 5% minoxidil tincture has a good clinical effect in the treatment of androgenetic alopecia.
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Serum amyloid A(SAA) is a novel marker widely used in the acute infection disease, especially viral infection. SAA has shown a cerntain value in assisting the clinical diagnosis, discrimination of severity and monitoring of progress and outcome of COVID-19. This paper introduces the application of SAA structural, function andits dynamic detection in the diagnosis of COVID-19, and the significance of combined detection with COVID-19 antibodies, nucleic acid and other diagnostic indicators.
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Objective@#To detect the expressions of epidermal growth factor-like domain 7 (EGFL7) and P185 protein in breast cancer tissues and serum, and to analyze the correlation between the expression levels of EGFL7 and P185 in tissues and clinicopathological parameters of breast cancer patients.@*Methods@#Sixty patients with breast cancer in Hunan Cancer Hospital from March 2016 to March 2018 were collected as observation group, and 60 patients with breast benign lesions in the hospital during the same period were selec-ted as control group. The expressions of EGFL7 and P185 protein in tissues of patients in the two groups were detected by immunohistochemical two-step method, and the levels of EGFL7 and P185 protein in serum of patients in the two groups were detected by enzyme-linked immunosorbent assay (ELISA). The relationships between the expressions of EGFL7 and P185 protein and clinicopathological parameters of breast cancer patients were analyzed.@*Results@#The positive rates of EGFL7 in tissues in the observation group and the control group were 65.00% (39/60) and 28.33% (17/60), and there was a significant difference between the two groups (χ2=16.205, P<0.001). The positive rates of P185 in tissues in the two groups were 43.33% (26/60) and 15.00% (9/60), and there was a significant difference between the two groups (χ2=11.657, P=0.001). The serum levels of EGFL7 protein in the observation group and the control group were (3.39±0.38) μg/ml and (2.75±0.31) μg/ml respectively, with a significant difference (t=10.109, P<0.001). The serum levels of P185 protein in the two groups were (7.12±0.75) μg/ml and (6.08±0.62) μg/ml respectively, with a significant difference (t=8.279, P<0.001). The positive expression of EGFL7 protein was closely related to tumor size (χ2=6.128, P=0.013), TNM stage (χ2=7.781, P=0.005) and metastasis (χ2=5.444, P=0.020). The positive expression of P185 protein was closely related to tumor size (χ2=8.910, P=0.003) and TNM stage (χ2=8.024, P=0.005).@*Conclusion@#The levels of EGFL7 and P185 protein are high in breast cancer tissues and serum, and their positive expressions are related to tumor size and TNM stage. EGFL7 and P185 proteins play important roles in the progression of breast cancer.
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Objective To detect the expressions of epidermal growth factor-like domain 7 (EGFL7) and P185 protein in breast cancer tissues and serum,and to analyze the correlation between the expression levels of EGFL7 and P185 in tissues and clinicopathological parameters of breast cancer patients. Methods Sixty patients with breast cancer in Hunan Cancer Hospital from March 2016 to March 2018 were collected as observation group,and 60 patients with breast benign lesions in the hospital during the same period were selec-ted as control group. The expressions of EGFL7 and P185 protein in tissues of patients in the two groups were detected by immunohistochemical two-step method,and the levels of EGFL7 and P185 protein in serum of patients in the two groups were detected by enzyme-linked immunosorbent assay (ELISA). The relationships between the expressions of EGFL7 and P185 protein and clinicopathological parameters of breast cancer patients were analyzed. Results The positive rates of EGFL7 in tissues in the observation group and the control group were 65. 00％ (39 / 60)and 28. 33％ (17 / 60),and there was a significant difference between the two groups (χ2 = 16. 205,P < 0. 001). The positive rates of P185 in tissues in the two groups were 43. 33％ (26 / 60)and 15. 00％ (9 / 60),and there was a significant difference between the two groups (χ2 = 11. 657,P = 0. 001). The serum levels of EGFL7 protein in the observation group and the control group were (3. 39 ± 0. 38)μg/ ml and (2. 75 ± 0. 31)μg/ ml respectively,with a significant difference (t = 10. 109,P < 0. 001). The serum levels of P185 protein in the two groups were (7. 12 ± 0. 75)μg/ ml and (6. 08 ± 0. 62)μg/ ml respectively, with a significant difference (t = 8. 279,P < 0. 001). The positive expression of EGFL7 protein was closely related to tumor size (χ2 = 6. 128,P = 0. 013),TNM stage (χ2 = 7. 781,P = 0. 005)and metastasis (χ2 =5. 444,P = 0. 020). The positive expression of P185 protein was closely related to tumor size (χ2 = 8. 910, P = 0. 003)and TNM stage (χ2 = 8. 024,P = 0. 005). Conclusion The levels of EGFL7 and P185 protein are high in breast cancer tissues and serum,and their positive expressions are related to tumor size and TNM stage. EGFL7 and P185 proteins play important roles in the progression of breast cancer.
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Objective To compare and study the two kinds of quality control methodologies related to intelligent quality management system ( iQM) and traditional quality control , and the quality control performance of iQM equivalent to traditional quality control were evaluated , ensuring the accuracy of the results of blood gas testing.Methods Beijing Chaoyang Hospital of Capital Medical University , Beijing Tiantan Hospital of Capital Medical University , Shanghai Longhua Hospital of Shanghai University of Chinese Medicine, and Sichuan Provincial People′s Hospital, these 4 medical institutions were selected to implement this study.During the period from June 2016 to December 2016, in the routine detection of total 3 712 specimen, the iQM and traditional quality control modes were used simultaneously to calculate the mean values of all blood gas parameters quality controls , SD, CV (%) and Sigma values, to evaluate the quality control performance and difference of the two quality control modes .Results During the process of testing blood gas samples from 3 712 specimen in 4 hospitals, iQM process control solution ( PCS) A, B, C ran 1 089, 7 678 and 154 quality control samples respectively , and 732 external quality control samples were run by traditional quality control mode .Considering the most sensitive parameters of blood gas testing pO 2, iQM PCS A, B, C′s Sigma value are higher than 8, however, the traditional quality control′s Sigma value are less than 6; For parameters pCO2, pO2and Na+, there exists significant difference between two quality control methods (P＝0.004 8,P＝0.000 1,P＝0.004 4,P＜0.01), other parameters pH, K+, Ca ++, Glu, Lac and Hct, there exists no significant difference between two quality control methods (P＝0.250 6, P＝0.062 3,P＝0.034 0,P＝0.346 9,P＝0.186 3,P＝0.823 1,P＞0.01).Totally 22 errors detected by iQM, includes 14 micro-clots and 8 interferences samples, which were not detected by traditional quality control .Conclusions The error in blood gas analysis mainly comes from the pre-analytical phase.iQM enhanced specimen inspection capabilities and make up for the inability of traditional quality control to monitor the quality of specimens , enabling full-scale, real-time, and dynamic monitoring of each specimen , powerful error detection capabilities , and automatic error correction capabilities . Besides, automatic documentation saves staff much time.The system can effectively ensure the accuracy of blood gas test results, meet the quality requirements of related laws and regulations and related industry standards , and also can meet the clinical intended use , providing new ideas for POCT quality management and improvement.
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Objective To analyze the effect of Ziniliangxue compound in treating psoriasis vulgaris patients with clinical efficacy and serum IL-8, IL-17, IL-23.MethodsIn the control group were treated with routine treatment, in the experimental group were treated with Ziniliangxue compound treatment, effect of serum IL-8, IL-17, IL-23 and in the clinical effect of the two groups were compared.ResultsIn the observation group of patients with clinical curative effect total have efficiency (88.57%) was significantly higher than that of control group in patients with clinical efficacy in patients with total efficiency (65.71%), the difference has statistical significance (P<0.05);after treatment, the observe of serum IL-8(14.211±2.314), IL-17(12.643±1.232) and IL-23(12.856±1.321)were significantly better than the control of serum IL-8(17.653±2.512), IL-17(19.432±1.685) and IL-23(19.786±1.754), the difference has statistical significance (P< 0.05).ConclusionZiniliangxue compound on psoriasis vulgaris clinical treatment effect and can effectively reduce the patients serum IL-8, IL-17, IL-23 levels.It is worthy of clinical application.
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Objective To determine whether the antiserum produced by immunizing mice with conotoxin GI coupled with bovine serum albumin (BSA) could neutralize GI conotoxin.Methods The GI-BSA was prepared by glutaraldehyde-coupled method,and the mice were immunized with the GI-BSA to produce antiserum.The antibody neutralization assay was used to test the detoxication of the antiserum.Results The SDS-PAGE protein electrophoresis showed that the coupling reaction of GI hapten with BSA was successful.The two distinct protein bands of GI-BSA were more than 120×103.Each mouse was immunized four times with 99 μg every two weeks.After the fourth immunization,the serum neutralization titer was more than 1:64 000.After the intraperitoneal injection of the mixture of 100 or 200 μl of the antiserum and different doses of GI,75% of the mice survived in the group with 100 μl of the antiserum and 1× LD50 GI(16.3 μg/kg).The same percentage of mice also survived in the group of with 200 μl of serum and 25.8 μg/kg of GI.Conclusion The antiserum produced by immunizing mice with GI-BSA exhibits significant detoxication activity to conotoxin GI.
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Objective To assess the relationships between area strain (AS) and eccentric index (EI) of atherosclerotic plaques as seen by intravascular ultrasonic elastography (IVUSE),and to reveal the effect of EI on the plaques stability.Methods Forty purebred New Zealand rabbits were fed with a high-cholesterol diet;the abdominal aorta endothelium was balloon-injured after 2 weeks;at the end of week 12,2 plaques with moderate echo from each rabbit were chosen for in situ imaging,and 2 consecutive frames near the end-diastole images in situ were used to construct an IVUS elastogram.Results The eccentric plaques showed significantly greater area stain (AS) than the centripetal plaques [4.77(2.92,8.01)% vs 3.27(2.15,4.82)%,P=0.029] with smaller plaque area and plaque burden (P<0.05).The plaque AS was positively correlated with EI (r=0.392,P=0.003).The eccentric plaques showed significantly greater AS in the shoulder than in body [4.98(3.17,8.48)% vs 4.64(2.51,5.92)%,P=0.008].Conclusions The EI is one of influential factors on plaque AS.Eccentric plaques may be more vulnerable than centripetal plaques,especially in the shoulder of eccentric plaques which have greater AS than their body.
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Objective To assess the relationship between plaque burden (PB) and area strain (AS) by intravascular ultrasonic elastography (IVUSE).Methods Forty purebred New Zealand rabbits were fed with a high-cholesterol diet.And the abdominal aorta endothelium was balloon-injured after 2 weeks.At the end of the 12th week,2 plaques with moderate echo from each rabbit were chosen for in situ imaging,and 2 consecutive frames near the end-diastole images in situ were used to construct an IVUS elastogram.Cross-sectional external elastic membrane area (EEMare),lumen area (Lumenarea),plaque area (PA),PB,external elastic membrane volume (EEMvolume),lumen volume (Lumenvolume),plaque volume (PV),plaque volume burden (PVB),maximal plaque thickness (Tmax) and minimal plaque thickness (Tmin),eccentric index (EI),remodeling index (RI) and AS were measured and calculated,respectively.According to the PB,the plaques were divided into low PB group (PB≤40 ％) and high PB group (PB＞ 40 ％).The differences of all above parameters between the two groups were compared,and the relationship between the plaque morphological and mechanical parameters were analyzed.Results PA,PV,PB,PVB,Tmin,Tmax,Lumenarea,Lumenvolume and EI were different between the 2 groups (all P＜0.01).On stepwise multiple regression analysis,the regression equation were built,(Y)=-6.921+10.430X1 +12.207X2((Y):AS,X1:EI,X2:PB,R2 =0.272,P＜0.001).After eliminating the effect of EI on the AS,the lower PB group had obviously smaller AS than higher PB group (P =0.010).Conclusion The PB has effect on plaque mechanical stability.The plaques with higher burden are more vulnerable than those with lower burden.
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Objective To assess the relationship between plaque burden (PB) and area strain (AS) by intravascular ultrasonic elastography (IVUSE).Methods Forty purebred New Zealand rabbits were fed with a high-cholesterol diet.And the abdominal aorta endothelium was balloon-injured after 2 weeks.At the end of the 12th week,2 plaques with moderate echo from each rabbit were chosen for in situ imaging,and 2 consecutive frames near the end-diastole images in situ were used to construct an IVUS elastogram.Cross-sectional external elastic membrane area (EEMare),lumen area (Lumenarea),plaque area (PA),PB,external elastic membrane volume (EEMvolume),lumen volume (Lumenvolume),plaque volume (PV),plaque volume burden (PVB),maximal plaque thickness (Tmax) and minimal plaque thickness (Tmin),eccentric index (EI),remodeling index (RI) and AS were measured and calculated,respectively.According to the PB,the plaques were divided into low PB group (PB≤40 ％) and high PB group (PB＞ 40 ％).The differences of all above parameters between the two groups were compared,and the relationship between the plaque morphological and mechanical parameters were analyzed.Results PA,PV,PB,PVB,Tmin,Tmax,Lumenarea,Lumenvolume and EI were different between the 2 groups (all P＜0.01).On stepwise multiple regression analysis,the regression equation were built,(Y)=-6.921+10.430X1 +12.207X2((Y):AS,X1:EI,X2:PB,R2 =0.272,P＜0.001).After eliminating the effect of EI on the AS,the lower PB group had obviously smaller AS than higher PB group (P =0.010).Conclusion The PB has effect on plaque mechanical stability.The plaques with higher burden are more vulnerable than those with lower burden.
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Objective To learn the significance of detection of high sensitive troponin T and creatine kinase isoenzyme in diagnosis of pediatric myocarditis.To provide reliable laboratory diagnosis method for the disease.Methods 23 cases of pediatric myocarditis,28 cases of viral myocarditis with capillary bronchitis and 61.cases of myocarditis with neonatal pneumonia were selected as the research objects;and 48 cases of healthy control group,55 cases of capillary bronchitis and 49 cases of neonatal pneumonia were also selected.Blood samples were collected from all the patients and healthy controls,and the levels of high sensitive serum troponin T and creatine kinase isoenzyme were also measured.Results There was no significant difference in the detection results of high sensitive troponin T and creatine kinase isoenzyme between the healthy control group,children with capillary bronchitis and neonatal pneumonia (all P ＞ 0.05);high sensitive troponin T and creatine kinase isoenzyme detection results of myocarditis,myocarditis complicated with bronchiolitis,myocarditis complicated with neonatal pneumonia were higher than those in healthy control group,the differences were statistically significant (t =13.723,6.628,10.079,9.475,17.650,15.364,all P ＜ 0.05).The abnormal rates of combined detection of children with myocarditis,myocarditis combined with capillary bronchitis,myocarditis combined with neonatal pneumonia were higher than those of single detection of high sensitive troponin T and single detection of creatine kinase isoenzyme (x2 =7.426,6.310,6.720,4.308,4.381,6.900,all P ＜0.05).The high sensitive troponin T and creatine kinase isoenzyme in the children with the age of 1-12 months and 1-3 were lower than those with the age of ＜ 1 month,the differences were statistically significant (t =3.498,4.043,4.202,4.132,all P ＜ 0.05).Conclusion The simultaneous detection of high sensitive troponin T and creatine kinase isoenzyme can be used in the diagnosis of pediatric myocarditis,with good clinical application value.
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Aim To explore the lipid-lowering mecha-nisms of curcumin from the molecular levels and pro-vide scientific basis for clinical development of lipid-lowering drugs.Methods Using oil red O staining and enzymic to determinate the levels of cholesterol in HepG2 cells.Moreover,uptaking of DiI-LDL was also measured.The expressions of mRNA and protein were detected by RT-Q-PCR and Western blot.Results The red lipid droplets and the levels of TC and FC sig-nificantly increased in HepG2 cells after treated with curcumin.The orange red fluorescence was higher than that of control.Curcumin could promote the expression levels of mRNA and protein of SREBP2 and LDLR, what′s more,curcumin could reduce the expression of the mature PCSK9 level and IDOL protein.Conclu-sion Curcumin accelerates LDL-C uptake probably via downregulating the expression of PCSK9 and IDOL in HepG2 cells.
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Objective To compare the outcome of double Endobutton plate versus clavicular hook plate (CHP) in treatment of Tossy grade Ⅲ acromioclavicular dislocation.Methods A cohort of 82 patients with Tossy grade Ⅲ acromiocavicular dislocation treated between January 2010 and August 2012 were reviewed retrospectively.Based on the treatment choices,the patients were divided into double Endobutton group (36 cases) and CHP group (46 cases).Operative situation,in-hospital parameters,and postoperative visual analogue scale (VAS) of the shoulder,shoulder abduction-rise or anteflexionrise,Constant-Murley shoulder score as well as complications were evaluated.Results There were no statistical differences between the two groups in aspects of operation time,intraoperative blood loss,and length of stay.Mean time to return to work was (13.1 ± 1.4) weeks in double Endobutton group,shorter than (15.5 ±2.6) weeks in CHP group (P ＜0.01).No statistical difference was observed for postoperative complications between the two groups.At postoperative 12 months,VAS was lower in double Endobutton group [(2.1 ± 0.7) points] vs CHP group [(2.9 ± 0.8) points,P ＜ 0.05],but abductionrise and anteflexion-rise were higher in double Endobutton group [(138.6 ± 15.7) °,(140.3 ± 17.6) °] vs CHP group [(91.7 ±8.4)°,(96.7 ± 10.5)°,P＜0.05].Conclusion To treat Tossy grade Ⅲ acromioclavicular dislocation,double Endobutton plate is associated with less shoulder pain,quicker recovery,better shoulder function restoration compared with CHP and there is no need for a second surgery to remove it.
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According to the educational objectives of biotechnology in local universities, the fundamental ideas about reforming the experimental teaching in biotechnology were discussed from the multiple aspects including the resetting of experimental curses system , the contents and methods of teaching and the approaches of examining and assessing. The final aim is to train out more innovative biotechnological talents through systematic and standardized practice of innovative teaching to meet the needs of China during this economical and societal development.
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Objective To investigate blood flow dynamics adjacent to regional myocardial segments in coronary artery disease(CAD) patients and to explore the association of the two CAD features.Methods In 43 CAD patients,velocity vector imaging (VVI) was used to evaluate the wall motion and classify normal myocardial segments (NS),relatively abnormal and obviously abnormal wall motion segments (RS and OS) by systolic peak strain (Ss).Vector flow mapping (VFM) was used to show blood flow dynamics in the heart chamber,including blood flow (Q) heading towards or away from the apex during a heart beat and time to every peak flow (T).Results Compared with NS,both RS and OS showed a higher systole Q + (blood flow heading towards the apex during systole) and lower diastole Q + (blood flow heading towards the apex during diastole) and shortened T2 (adjusted time interval between E and A peaks).Systole Q + was positively correlated with Ss but negatively with segmental ejection fraction (SEF).Diastole Q + was negatively correlated with early and late diastolic peak velocity (Ve and Va) but positively with Ve/Va.T2 was negatively correlated with Ve but positively with Ve/Va and early diastolic peak strain rate (SRe).Conclusions VFM might be a new tool to quantitatively assess change in regional blood flow dynamics in patients with CAD.
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Background and purpose: Sorafenib hepatocellular carcinoma assessment randomized protocol (SHARP) and sorafenib in patients in Asia-Pacific region with hepatocellular carcinoma (ORIENTAL) had indicated that multi-kinase inhibitor sorafenib could prolong overall survival (OS) and time to progression (TTP) as well as improve progress free survival (PFS) in patients with advanced stage hepatocellular carcinoma. Drug-related adverse events in the course of treatment restricted its clinical application to a certain degree. This study was aimed to summerize the adverse events as well as the management of sorafenib in our clinic. Methods: Twenty-five cases clinically diagnosed as advanced hepatocellular carcinoma were enrolled from January 2008 to October 2009. All the patients who received sorafenib treatment met inclusion criteria as followed: (1) Progression of disease after trans-hepatic arterial chemoembolization therapy; (2) Extensive portal vein cancerous thrombus formation; (3) Portal zone or retroperitoneal lymph node metastasis or multiple remote metastasis, such as lung or bone; (4) Diffused poor blood supply to tumor; (5) Inform consent was obtained. All adverse events with different grade were observed during the beginning 12 weeks, and clinical treatment were carried out relatively. Results: Total of 25 cases were enrolled. Nine patients died of the disease, 3 of them died during the first 12 weeks, 3 patients abandoned sorafenib treatment, among them 2 died before the finish of 12 weeks treatment and 1 patient discontinued 5 months after the sorafenib treatment. Twenty cases finally assigned. Number of patients encountered drug-related adverse events were: HFSR (hand-foot-skin-reaction) 4(4/20), diarrhea 4(4/20), alopecia 5(5/20), rasb 4(4/20), fatigue 8(8/20), leukopenia and Thrombocytopenia 4(4/20), elevated blood pressure 1(1/20) and abdominal pain 1(1/20). After clinical management, 20 patients' sorafenib treatment were eventually not affected by adverse events. Conclusion: Sorafenib was well-tolerated and is a safe option of treatment for patients with advanced hepatocellular carcinoma.
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AIM: To explore the expressive role of lipoprotein-associated phospholipase A_2, high sensitive C-reactive protein and matrix metalloproteinase-9 in vulnerable atherosclerotic plaques in a rabbit model. METHODS: Forty eight New Zealand white male rabbits were randomly divided into 4 groups (12 rabbits each): control group, stable plaque group, p53 group, and p53+drug group. Rabbits in control group were fed with a regular diet and underwent sham operation. Rabbits in stable plaque group, p53 group and p53+drug group underwent balloon induced arterial wall injury and then were fed on a diet with 1% cholesterol. The animals were all fed for 3 months, then the rabbits in p53 group and p53+drug group underwent Ad5-CMV p53 transfection at 10th week. Before killed, the animals in p53+drug group underwent pharmacological triggering with Russell's viper venom (RVV) and histamine to induce the rupture of the atherosclerotic plaques. At the 1st day and before sacrifice, the serum was collected for measuring Lp-PLA_2, hs-CRP, MMP-9, HDL, LDL and VLDL. The expressions of Lp-PLA_2, hs-CRP and MMP-9 in tissues were determined by the methods of hybridization and immunohistochemistry. RESULTS: At the end of 12th week, the serum and tissue levels of Lp-PLA_2 and MMP-9 in stable plaque group, p53 group and p53+drug group were significant different from those in control group and in each group at the first day (P<0.05). The serum levels of Lp-PLA_2 and hs-CRP in p53 group and p53+drug group were significantly higher than those in control group and stable group (P<0.05). The serum levels of Lp-PLA_2, hs-CRP and MMP-9 were all significantly different between p53 group and p53+drug group (P<0.05). At the end of 12th week, pathological results showed that 4 groups were normal artery, stable plaque, vulnerable plaque and rupture plaque, respectively. The fabric cap was thicker in plaque groups than that in normal group (P<0.05). The rupture and formation of thrombus were more significant in p53+drug group than those in p53 group. The serum level of Lp-PLA_2 had negative interrelated relationship with fabric cap in plaque groups (r=-0.710, P<0.01), and hs-CRP, MMP-9 had no interrelated relationships with fabric cap in plaque groups. CONCLUSION: Base on the successful establishment of the atherosclerotic plaque animal model, serum Lp-PLA_2 shows better interrelated relationships to plaques stability. Combination with hs-CRP and MMP-9, we can exactly evaluate the nature of plaques.