Advanced glycation end products (AGEs) are produced through the non enzymatic glycation and oxidation of proteins, lipids and nucleic acids. Enhanced formation of AGEs occurs particularly in conditions associated with...Advanced glycation end products (AGEs) are produced through the non enzymatic glycation and oxidation of proteins, lipids and nucleic acids. Enhanced formation of AGEs occurs particularly in conditions associated with hyperglycaemia such as diabetes mellitus (DM). AGEs are believed to have a key role in the development and progression of cardiovascular disease in patients with DM through the modification of the structure, function and mechanical properties of tissues through crosslinking intracellular as well as extracellular matrix proteins and through modulating cellular processes through binding to cell surface receptors [receptor for AGEs (RAGE)]. A number of studies have shown a correlation between serum AGE levels and the development and severity of heart failure. Moreover, some studies have suggested that therapies targeted against AGEs may have therapeutic potential in patients with heart failure (HF). The purpose of this review is to discuss the role of AGEs in cardiovascular disease and in particular in heart failure, focussing on both cellular mechanisms of action as well as highlighting how targeting AGEs may represent a novel therapeutic strategy in the treatment of HF.展开更多
Osteoporosis has become a serious health problem throughout the world which is associated with an increased risk of bone fractures and mortality among the people of middle to old ages.Diabetes is also a major health p...Osteoporosis has become a serious health problem throughout the world which is associated with an increased risk of bone fractures and mortality among the people of middle to old ages.Diabetes is also a major health problem among the people of all age ranges and the sufferers due to this abnormality increasing day by day.The aim of this review is to summarize the possible mechanisms through which diabetes may induce osteoporosis.Diabetes mellitus generally exerts its effect on different parts of the body including bone cells specially the osteoblast and osteoclast,muscles,retina of the eyes,adipose tissue,endocrine system specially parathyroid hormone(PTH) and estrogen,cytokines,nervous system and digestive system.Diabetes negatively regulates osteoblast differentiation and function while positively regulates osteoclast differentiation and function through the regulation of different intermediate factors and thereby decreases bone formation while increases bone resorption.Some factors such as diabetic neuropathy,reactive oxygen species,Vitamin D,PTH have their effects on muscle cells.Diabetes decreases the muscle strength through regulating these factors in various ways and ultimately increases the risk of fall that may cause bone fractures.展开更多
Nicotiflorin is a flavonoid extracted from Carthamus tinctorius.Previous studies have shown its cerebral protective effect,but the mechanism is undefined.In this study,we aimed to determine whether nicotiflorin protec...Nicotiflorin is a flavonoid extracted from Carthamus tinctorius.Previous studies have shown its cerebral protective effect,but the mechanism is undefined.In this study,we aimed to determine whether nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis through the JAK2/STAT3 pathway.The cerebral ischemia/reperfusion injury model was established by middle cerebral artery occlusion/reperfusion.Nicotiflorin（10 mg/kg） was administered by tail vein injection.Cell apoptosis in the ischemic cerebral cortex was examined by hematoxylin-eosin staining and terminal deoxynucleotidyl transferase d UTP nick end labeling assay.Bcl-2 and Bax expression levels in ischemic cerebral cortex were examined by immunohistochemial staining.Additionally,p-JAK2,p-STAT3,Bcl-2,Bax,and caspase-3 levels in ischemic cerebral cortex were examined by western blot assay.Nicotiflorin altered the shape and structure of injured neurons,decreased the number of apoptotic cells,down-regulates expression of p-JAK2,p-STAT3,caspase-3,and Bax,decreased Bax immunoredactivity,and increased Bcl-2 protein expression and immunoreactivity.These results suggest that nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis via the JAK2/STAT3 pathway.展开更多
Objective To study the relationship between cartilage end plate calcification and intervertebral disc degeneration Methods An experimental model of cervical disc degeneration in rabbits was established by resecti...Objective To study the relationship between cartilage end plate calcification and intervertebral disc degeneration Methods An experimental model of cervical disc degeneration in rabbits was established by resection of the cervical supraspinous and interspinous ligaments and detachment of the posterior paravertebral muscles from the cervical vertebrae Mechanical instability in the cervical spine elicited by this surgical intervention accelerated the process of intervertebral disc degeneration The extent of intervertebral disc degeneration was graded in morphologically, and the thicknesses of the calcified layer and the uncalcified layer of the cartilage end plate were measured in each degenerated cervical disc Results In less severely degenerative cervical discs, the morphology of the cartilage end plate showed nearly normal construction, and the tidemark was clear In severely degenerative discs, the matrix and cells showed fibrosis, the tidemark advanced, and the calcified cartilage thickened There exists a positive correlation between the thickness of the calcified layer of the cartilage end plate and the degree of cervical disc degeneration Conclusion The calcification of the cartilage end plate is the key factor that initiates and promotes cervical disc degeneration展开更多
It was previously understood that body weight gain and obesity observed in type 2 diabetes mellitus(T2DM) could be beneficial since body weight increase elevated bone mineral density and thus helped maintain the skele...It was previously understood that body weight gain and obesity observed in type 2 diabetes mellitus(T2DM) could be beneficial since body weight increase elevated bone mineral density and thus helped maintain the skeletal framework.However,a number of recent findings in humans and rodents have revealed that T2 DM is not only associated with trabecular defects but also increases cortical porosity,and compromised bone cell function and bone mechanical properties.Hyperglycemia and insulin resistance in T2 DM may further induce osteoblast apoptosis and uncoupling bone turnover.Prolonged accumulation of advanced glycation end products and diminished activity of lysyl oxidase,an essential enzyme for collagen cross-link,can lead to structural abnormalities of bone collagen fibrils,brittle matrix,and fragility fractures.Our studies in T2 DM rats showed that dyslipidemia,which often occurs in T2 DM,could obscure the T2DM-associated changes in bone microstructure and osteopenia.Longitudinal bone growth regulated by the growth plate chondrocytes is also impaired by T2 DM since differentiation of growth plate chondrocytes is arrested and retained in the resting state while only a small number of cells undergo hypertrophic differentiation.Such a delayed chondrocyte differentiation may have also resulted from premature apoptosis of the growth plate chondrocytes.Nevertheless,the underlying cellular and molecular mechanisms of insulin resistance in osteoblasts,osteoclasts,osteocytes,and growth plate chondrocytes remain to be investigated.展开更多
The effect of quenching rate on the electrical conductivity and microstructure of thick plates of incumbent AA7050 was investigated by employing Jominy end quench test. The electrical conductivity measurement and micr...The effect of quenching rate on the electrical conductivity and microstructure of thick plates of incumbent AA7050 was investigated by employing Jominy end quench test. The electrical conductivity measurement and microstructural observation were conducted at different distances from the quenched end. The results indicate that the average cooling rates decrease with increasing the distance from the quenched end of the bar in the quench sensitive temperature range. However, the electrical conductivity increases with the increase of distance from the quenched end. The surface parts of the plate were fully recrystallized, while partial recrystallization took place at the quarter and center parts of the plate. The quench induced grain boundary precipitates became remarkably coarser and discontinuously distributed with increasing distance from the quenched end of the bar. Plenty of heterogeneous precipitates were observed to nucleate on A13Zr dispersoids when the distance from the quenched end was greater than 38mm.展开更多
Many high quality studies have emerged from public databases,such as Surveillance,Epidemiology,and End Results(SEER),National Health and Nutrition Examination Survey(NHANES),The Cancer Genome Atlas(TCGA),and Medical I...Many high quality studies have emerged from public databases,such as Surveillance,Epidemiology,and End Results(SEER),National Health and Nutrition Examination Survey(NHANES),The Cancer Genome Atlas(TCGA),and Medical Information Mart for Intensive Care(MIMIC);however,these data are often characterized by a high degree of dimensional heterogeneity,timeliness,scarcity,irregularity,and other characteristics,resulting in the value of these data not being fully utilized.Data-mining technology has been a frontier field in medical research,as it demonstrates excellent performance in evaluating patient risks and assisting clinical decision-making in building disease-prediction models.Therefore,data mining has unique advantages in clinical big-data research,especially in large-scale medical public databases.This article introduced the main medical public database and described the steps,tasks,and models of data mining in simple language.Additionally,we described data-mining methods along with their practical applications.The goal of this work was to aid clinical researchers in gaining a clear and intuitive understanding of the application of data-mining technology on clinical big-data in order to promote the production of research results that are beneficial to doctors and patients.展开更多
Periodontitis is the commonest oral disease affecting population worldwide. This disease is notorious for the devastation of tooth supporting structures, ensuing in the loss of dentition. The etiology for this disease...Periodontitis is the commonest oral disease affecting population worldwide. This disease is notorious for the devastation of tooth supporting structures, ensuing in the loss of dentition. The etiology for this disease is bacterial biofilm, which accumulates on the teeth as dental plaque. In addition to the biofilm microorganisms, other factors such as environmental, systemic and genetic are also responsible in progression of periodontitis. Diabetes mellitus (DM) is metabolic disorder which has an impact on the global health. DM plays a crucial role in the pathogenesis of periodontitis. Periodontitis is declared as the “sixth” major complication of DM. Evidence based literature has depicted an enhanced incidence and severity of periodontitis in subjects with DM. A “two way” relationship has been purported between periodontitis and DM. Mutual management of both conditions is necessary. Periodontal therapy (PT) may assist to diminish the progression of DM and improve glycemic control. Various advanced technological facilities may be utilized for the purpose of patient education and disease management. The present paper clarifies the etio-pathogenesis of periodontitis, establishing it as a complication of DM and elaborating the various mechanisms involved in the pathogenesis. The role of PT in amelioration of DM and application of digital communication will be discussed. Overall, it is judicious to create an increased patient cognizance of the periodontitis-DM relationship. Conjunctive efforts must be undertaken by the medical and oral health care professionals for the management of periodontitis affected DM patients.展开更多
Endoscopic retrograde cholangiopancreatography(ERCP) has become an important therapeutic modality for biliary and pancreatic disorders. Perforation is one of the most feared complications of ERCP and endoscopic sphinc...Endoscopic retrograde cholangiopancreatography(ERCP) has become an important therapeutic modality for biliary and pancreatic disorders. Perforation is one of the most feared complications of ERCP and endoscopic sphincterotomy. A MEDLINE search was performedfrom 2000-2014 using the keywords "perforation", "ERCP" and "endoscopic sphincterotomy". All articles including more than nine cases were reviewed. The incidence of ERCP-related perforations was low(0.39%, 95%CI: 0.34-0.69) with an associated mortality of 7.8%(95%CI: 3.80-13.07). Endoscopic sphincterotomy was responsible for 41% of perforations, insertion and manipulations of the endoscope for 26%, guidewires for 15%, dilation of strictures for 3%, other instruments for 4%, stent insertion or migration for 2% and in 7% of cases the etiology was unknown. The diagnosis was made during ERCP in 73% of cases. The mechanism, site and extent of injury, suggested by clinical and radiographic findings, should guide towards operative or non-operative management. In type I perforations early surgical repair is indicated, unless endoscopic closure can be achieved. Patients with type II perforations should be treated initially non-operatively. Non-operative treatment includes biliary stenting, fasting, intravenous fluid resuscitation, nasogastric drainage, broad spectrum antibiotics, percutaneous drainage of fluid collections. Non-operative treatment was successful in 79% of patients with type II injuries, with an overall mortality of 9.4%. Non-operative treatment was sufficient in all patients with type III injuries. Surgical technique depends on timing, site and size of defect and clinical condition of the patient. In conclusion, diagnosis is based on clinical suspicion and clinical and radiographic findings. Whilst surgery is usually indicated in patients with type I injuries, patients with type II or III injuries should be treated initially non-operatively. A minority of them will finally require surgical intervention.展开更多
The Aiketik Group, distributed at the western end of the South TianshanMountains, China, is an important lithostratigraphic unit involved in the South Tianshan orogen. Itis separated from the adjacent rocks by faults....The Aiketik Group, distributed at the western end of the South TianshanMountains, China, is an important lithostratigraphic unit involved in the South Tianshan orogen. Itis separated from the adjacent rocks by faults. Generally, the geologists ascribed it to the UpperCarboniferous according to Pseudostaffella sp., Profusulinella sp. and Fusulinella sp. found fromthe limestone and sandy limestone of Aiketik. Our radiolarian fossils were obtained from the chertsamples collected from the Haladaok section located at the upper Tuoshihan River. The fossils mainlyinclude Albaillella undulata Deflandre, Albaillella paradoxa Deflandre, Albaillella sp. aff. A.paradoxa Deflandre, Albaillella sp. cf. A. deflandrei Gourmelon, Albaillella sp., Albaillellaexcelsa Ishiga, Kito and Imoto (?), Belowea variabilis (Ormiston et Lane), Callella cf. C.parvispinosa Won, Entactinia cf. E. tortispina Ormiston et Lane, Entactinia aff. E. tortispinaOrmiston et Lane, Entactinia variospina Won, Entactinia sp., Eostylodictya rota (Won),Latentifistula impella (Ormistone et Lane) (?), Latentifistula turgita Omiston et Lane,Latentifistulidae gen. et. sp. indet. and Polyentactinia cf. aranea Gourmelon. Among them,Albaillella excelsa Ishiga, Kito and Imoto (?) is a Late Permian species with some elementsuncertain as there is only one poorly-preserved fossil of this species found so far. And tworadiolarian assemblages can be identified from the other fossils. One is the early EarlyCarboniferous assemblage represented by Albaillella undulata Deflandre, Albaillella paradoxa andAlbaillella sp. cf. A. deflandrei Gourmelon. And the other is the late Early Carboniferousassemblage represented by Eostylodictya rota (Won). This is the first discovery of radiolarianfossils in the Aiketik Group, also the first discovery of Late Permian radiolarian fossils in theSouth Tianshan Mountains. Meanwhile, this is the current westernmost sampling site of radiolarianfossils in the South Tianshan Mountains.展开更多
Background Advanced glycation end products （AGEs） play a critical role in the development of diabetic nephropathy. Reactive oxygen species （ROS） may play a critical role in AGEs induced growth factor expression. I...Background Advanced glycation end products （AGEs） play a critical role in the development of diabetic nephropathy. Reactive oxygen species （ROS） may play a critical role in AGEs induced growth factor expression. In this study, the effects of AGEs on transforming growth factor β1 （TGF-β1）, connective tissue growth factor （CTGF） and fibronectin （Fn） mRNA expression and oxidative stress in cultured NRK-49F cells were examined. Methods NRK-49F cells were incubated with medium containing different doses of AGEs （50, 100 or 200 μg/ml） for 24 hours, or with AGEs 100 μg/ml for different times （0, 12, 24 or 48 hours）. Cells in the serum-free medium or medium containing 25 mmol/L glucose were controls. Cells were treated with 25 mmol/L glucose and 100 μg/ml AGEs for 24 hours to determine the effects between AGEs and glucose. We clarified the role of antioxidant by pretreating cells with N-acetylcysteine （10 mmol/L）, ginkgo biloba extract （50 or 100 mg/L） for 24 hours and with 100 μg/ml AGEs for further 24 hours. Alamarblue dye assay was used to analyze cell growth; intracellular ROS generation was measured by flow cytometry; intracellular glutathione by fluorescence spectrophotometry; expressions of TGF-β1, CTGF and Fn mRNA by semiquantitative RT-PCR. Results AGEs significantly increased the expressions of TGF-β1, CTGF, Fn mRNA and intracellular ROS generation, and decreased the glutathion level in NRK-49F cells in dose- and time-dependent manners. High glucose and AGEs together significantly increased the expression of TGF-β1, CTGF and Fn mRNA, compared with AGEs and high glucose separately. Preincubation with N-acetylcysteine or ginkgo biloba extract increased GSH level, suppressed AGEs-induced oxidative stress and TGF-β1, CTGF and Fn mRNA overexpression. Conclusions AGEs can significantly increase expression of TGF-β1, CTGF, Fn mRNA in NRK-49F cells through enhancement of oxidative stress. The accumulation of AGEs may play a pivotal role in the pathogenesis of tubulointerst展开更多
Objective:To investigate the effects of puerarin on the activity of superoxide dismutase(SOD), and expressions of advanced glycation end-product(AGE) receptor(RAGE) and vascular endothelial growth factor(VEGF) in reti...Objective:To investigate the effects of puerarin on the activity of superoxide dismutase(SOD), and expressions of advanced glycation end-product(AGE) receptor(RAGE) and vascular endothelial growth factor(VEGF) in retinas of streptozotocin(STZ)-induced early diabetic rats. Methods:Diabetic rat models were established by inducing diabetes via intra-peritoneal injection of STZ.Rats were randomly divided into normal(control),diabetic(DM),and DM+ puerarin groups.After intra-gastric administration of puerarin(500 mg/kg/day for 4 weeks),levels of SOD and malondialdehyde(MDA) were determined in serum and retina.mRNA and protein expression levels of RAGE and VEGF in retinas were determined by real-lime polymerase chain reaction(RT-PCR)(mRNA) and Western blot analysis(protein levels).Results:There was significantly lower SOD activity and significantly higher MDA in serum and retinas of the DM group compared with the two other groups(P【0.05).After treatment with puerarin,SOD activity increased and MDA content decreased in this group(P【0.05).mRNA and protein expression levels of RACE and VECF in the DM group were significantly higher than those of the other groups (P【0.05),and decreased after puerarin treatment(P【0.05).Conclusions:Puerarin is able to enhance SOD activity,and inhibit RAGE and VEGF expressions in retinas of STZ-induced early diabetic ruts.展开更多
Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ ...Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ on diabetic rats with ED and its potential mechanism viathe assessment of advanced glycosylation end products （AGEs）, autophagy, mTOR and the NO-cGMP pathway. Icarisid Ⅱ was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid Ⅱ group, rats were administered icarisid Ⅱ intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure （ICP/MAP）. AGE concentrations, nitric oxide synthase （NOS） activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 Iocalisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid Ⅱ increased ICP/MAP values, the smooth muscle cell （SMC） growth curve, S phase and SMC/collagen fibril （SMC/CF） proportions and decreased Beclin 1 （P〈0.05）. Icarisid Ⅱ significantly increased the proliferative index and p-p70S6K（Thr389） levels and decreased the numbers of autophagosomes and the levels of LC3-11 （P〈0.01）. Icarisid Ⅱ decreased AGE concentrations and increased cGMP concentration, NOS activity （P〈0.05） and cNOS levels （P〈0.01） in the diabetic ED group. Therefore, Icarisid Ⅱ constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.展开更多
Diabetic nephropathy is the kidney disease that occurs as a result of diabetes.Cardiovascular and renal complications share common risk factors such as blood pressure,blood lipids,and glycemic control.Thus,chronic kid...Diabetic nephropathy is the kidney disease that occurs as a result of diabetes.Cardiovascular and renal complications share common risk factors such as blood pressure,blood lipids,and glycemic control.Thus,chronic kidney disease may predict cardiovascular disease in the general population.The impact of diabetes on renal impairment changes with increasing age.Serum markers of glomerular filtration rate and microalbuminuria identify renal impairment in different segments of the diabetic population,indicating that serum markers as well as microalbuminuria tests should be used in screening for nephropathy in diabetic older people.The American Diabetes Association and the National Institutes of Health recommend Estimated glomerular filtration rate(eGFR) calculated from serum creatinine at least once a year in all people with diabetes for detection of kidney dysfunction.eGFR remains an independent and significant predictor after adjustment for conventional risk factors including age,sex,duration of diabetes,smoking,obesity,blood pressure,and glycemic and lipid control,as well as presence of diabetic retinopathy.Cystatin-C(Cys C) may in future be the preferred marker of diabetic nephropathy due differences in measurements of serum creatinine by various methods.The appropriate reference limit for Cys C in geriatric clinical practice must be defined by further research.Various studies have shown the importance of measurement of albuminuria,eGFR,serum creatinine and hemoglobin level to further enhance the prediction of end stage renal disease.展开更多
With the significant improvement of microgrid technology, microgrid has gained large-scale application.However, the existence of intermittent distributed generations, nonlinear loads and various electrical and electro...With the significant improvement of microgrid technology, microgrid has gained large-scale application.However, the existence of intermittent distributed generations, nonlinear loads and various electrical and electronic devices causes power quality problem in microgrid, especially in islanding mode. An accurate and fast disturbance detection method which is the premise of power quality control is necessary. Aiming at the end effect and the mode mixing of original Hilbert-Huang transform(HHT), an improved HHT with adaptive waveform matching extension is proposed in this paper. The innovative waveform matching extension method considers not only the depth of waveform, but also the rise time and fall time. Both simulations and field experiments have verified the correctness and validity of the improved HHT for power quality disturbance detection in microgrid.展开更多
A deduced cutting force prediction model for circular end milling process is presented in this paper. Traditional researches on cutting force model usually focus on linear milling process which does not meet other cut...A deduced cutting force prediction model for circular end milling process is presented in this paper. Traditional researches on cutting force model usually focus on linear milling process which does not meet other cutting conditions, especially for circular milling process. This paper presents an improved cutting force model for circular end milling process based on the typical linear milling force model. The curvature effects of tool path on chip thickness as well as entry and exit angles are analyzed, and the cutting force model of linear milling process is then corrected to fit circular end milling processes. Instantaneous cutting forces during circular end milling process are predicted according to the proposed model. The deduced cutting force model can be used for both linear and circular end milling processes. Finally, circular end milling experiments with constant and variable radial depth were carried out to verify the availability of the proposed method. Experiment results show that measured results and simulated results corresponds well with each other.展开更多
文摘Advanced glycation end products (AGEs) are produced through the non enzymatic glycation and oxidation of proteins, lipids and nucleic acids. Enhanced formation of AGEs occurs particularly in conditions associated with hyperglycaemia such as diabetes mellitus (DM). AGEs are believed to have a key role in the development and progression of cardiovascular disease in patients with DM through the modification of the structure, function and mechanical properties of tissues through crosslinking intracellular as well as extracellular matrix proteins and through modulating cellular processes through binding to cell surface receptors [receptor for AGEs (RAGE)]. A number of studies have shown a correlation between serum AGE levels and the development and severity of heart failure. Moreover, some studies have suggested that therapies targeted against AGEs may have therapeutic potential in patients with heart failure (HF). The purpose of this review is to discuss the role of AGEs in cardiovascular disease and in particular in heart failure, focussing on both cellular mechanisms of action as well as highlighting how targeting AGEs may represent a novel therapeutic strategy in the treatment of HF.
文摘Osteoporosis has become a serious health problem throughout the world which is associated with an increased risk of bone fractures and mortality among the people of middle to old ages.Diabetes is also a major health problem among the people of all age ranges and the sufferers due to this abnormality increasing day by day.The aim of this review is to summarize the possible mechanisms through which diabetes may induce osteoporosis.Diabetes mellitus generally exerts its effect on different parts of the body including bone cells specially the osteoblast and osteoclast,muscles,retina of the eyes,adipose tissue,endocrine system specially parathyroid hormone(PTH) and estrogen,cytokines,nervous system and digestive system.Diabetes negatively regulates osteoblast differentiation and function while positively regulates osteoclast differentiation and function through the regulation of different intermediate factors and thereby decreases bone formation while increases bone resorption.Some factors such as diabetic neuropathy,reactive oxygen species,Vitamin D,PTH have their effects on muscle cells.Diabetes decreases the muscle strength through regulating these factors in various ways and ultimately increases the risk of fall that may cause bone fractures.
基金financially supported by the Natural Science Foundation of Education Department of Sichuan Province of China,No.14ZB0152the Joint Research Program of Luzhou and Southwest Medical University,in China,No.14JC0120
文摘Nicotiflorin is a flavonoid extracted from Carthamus tinctorius.Previous studies have shown its cerebral protective effect,but the mechanism is undefined.In this study,we aimed to determine whether nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis through the JAK2/STAT3 pathway.The cerebral ischemia/reperfusion injury model was established by middle cerebral artery occlusion/reperfusion.Nicotiflorin（10 mg/kg） was administered by tail vein injection.Cell apoptosis in the ischemic cerebral cortex was examined by hematoxylin-eosin staining and terminal deoxynucleotidyl transferase d UTP nick end labeling assay.Bcl-2 and Bax expression levels in ischemic cerebral cortex were examined by immunohistochemial staining.Additionally,p-JAK2,p-STAT3,Bcl-2,Bax,and caspase-3 levels in ischemic cerebral cortex were examined by western blot assay.Nicotiflorin altered the shape and structure of injured neurons,decreased the number of apoptotic cells,down-regulates expression of p-JAK2,p-STAT3,caspase-3,and Bax,decreased Bax immunoredactivity,and increased Bcl-2 protein expression and immunoreactivity.These results suggest that nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis via the JAK2/STAT3 pathway.
文摘Objective To study the relationship between cartilage end plate calcification and intervertebral disc degeneration Methods An experimental model of cervical disc degeneration in rabbits was established by resection of the cervical supraspinous and interspinous ligaments and detachment of the posterior paravertebral muscles from the cervical vertebrae Mechanical instability in the cervical spine elicited by this surgical intervention accelerated the process of intervertebral disc degeneration The extent of intervertebral disc degeneration was graded in morphologically, and the thicknesses of the calcified layer and the uncalcified layer of the cartilage end plate were measured in each degenerated cervical disc Results In less severely degenerative cervical discs, the morphology of the cartilage end plate showed nearly normal construction, and the tidemark was clear In severely degenerative discs, the matrix and cells showed fibrosis, the tidemark advanced, and the calcified cartilage thickened There exists a positive correlation between the thickness of the calcified layer of the cartilage end plate and the degree of cervical disc degeneration Conclusion The calcification of the cartilage end plate is the key factor that initiates and promotes cervical disc degeneration
基金Supported by Grants from the Cluster and Program Management Office(CPMO),National Science and Technology Development Agency(P-11-00639)the Thailand Research Fund(TRF)-Mahidol University through the TRF Senior Research Scholar Grant(RTA5780001 to NC)+2 种基金the Faculty of Allied Health Sciences,Burapha University and Thailand Research Fund through TRF Research Career Development Grant(RSA5780041 to KW)the Research and Development Fund Burapha University(05/2557 to KW)the Faculty of Allied Health Sciences,Burapha University Research Grant of Fiscal Year 2015(AHS05/2558 to KW)
文摘It was previously understood that body weight gain and obesity observed in type 2 diabetes mellitus(T2DM) could be beneficial since body weight increase elevated bone mineral density and thus helped maintain the skeletal framework.However,a number of recent findings in humans and rodents have revealed that T2 DM is not only associated with trabecular defects but also increases cortical porosity,and compromised bone cell function and bone mechanical properties.Hyperglycemia and insulin resistance in T2 DM may further induce osteoblast apoptosis and uncoupling bone turnover.Prolonged accumulation of advanced glycation end products and diminished activity of lysyl oxidase,an essential enzyme for collagen cross-link,can lead to structural abnormalities of bone collagen fibrils,brittle matrix,and fragility fractures.Our studies in T2 DM rats showed that dyslipidemia,which often occurs in T2 DM,could obscure the T2DM-associated changes in bone microstructure and osteopenia.Longitudinal bone growth regulated by the growth plate chondrocytes is also impaired by T2 DM since differentiation of growth plate chondrocytes is arrested and retained in the resting state while only a small number of cells undergo hypertrophic differentiation.Such a delayed chondrocyte differentiation may have also resulted from premature apoptosis of the growth plate chondrocytes.Nevertheless,the underlying cellular and molecular mechanisms of insulin resistance in osteoblasts,osteoclasts,osteocytes,and growth plate chondrocytes remain to be investigated.
基金Project (50904010) supported by the National Natural Science Foundation of ChinaProject (2010DFB50340) supported by the China International Science and Technology Cooperation
文摘The effect of quenching rate on the electrical conductivity and microstructure of thick plates of incumbent AA7050 was investigated by employing Jominy end quench test. The electrical conductivity measurement and microstructural observation were conducted at different distances from the quenched end. The results indicate that the average cooling rates decrease with increasing the distance from the quenched end of the bar in the quench sensitive temperature range. However, the electrical conductivity increases with the increase of distance from the quenched end. The surface parts of the plate were fully recrystallized, while partial recrystallization took place at the quarter and center parts of the plate. The quench induced grain boundary precipitates became remarkably coarser and discontinuously distributed with increasing distance from the quenched end of the bar. Plenty of heterogeneous precipitates were observed to nucleate on A13Zr dispersoids when the distance from the quenched end was greater than 38mm.
基金the National Social Science Foundation of China(No.16BGL183).
文摘Many high quality studies have emerged from public databases,such as Surveillance,Epidemiology,and End Results(SEER),National Health and Nutrition Examination Survey(NHANES),The Cancer Genome Atlas(TCGA),and Medical Information Mart for Intensive Care(MIMIC);however,these data are often characterized by a high degree of dimensional heterogeneity,timeliness,scarcity,irregularity,and other characteristics,resulting in the value of these data not being fully utilized.Data-mining technology has been a frontier field in medical research,as it demonstrates excellent performance in evaluating patient risks and assisting clinical decision-making in building disease-prediction models.Therefore,data mining has unique advantages in clinical big-data research,especially in large-scale medical public databases.This article introduced the main medical public database and described the steps,tasks,and models of data mining in simple language.Additionally,we described data-mining methods along with their practical applications.The goal of this work was to aid clinical researchers in gaining a clear and intuitive understanding of the application of data-mining technology on clinical big-data in order to promote the production of research results that are beneficial to doctors and patients.
文摘Periodontitis is the commonest oral disease affecting population worldwide. This disease is notorious for the devastation of tooth supporting structures, ensuing in the loss of dentition. The etiology for this disease is bacterial biofilm, which accumulates on the teeth as dental plaque. In addition to the biofilm microorganisms, other factors such as environmental, systemic and genetic are also responsible in progression of periodontitis. Diabetes mellitus (DM) is metabolic disorder which has an impact on the global health. DM plays a crucial role in the pathogenesis of periodontitis. Periodontitis is declared as the “sixth” major complication of DM. Evidence based literature has depicted an enhanced incidence and severity of periodontitis in subjects with DM. A “two way” relationship has been purported between periodontitis and DM. Mutual management of both conditions is necessary. Periodontal therapy (PT) may assist to diminish the progression of DM and improve glycemic control. Various advanced technological facilities may be utilized for the purpose of patient education and disease management. The present paper clarifies the etio-pathogenesis of periodontitis, establishing it as a complication of DM and elaborating the various mechanisms involved in the pathogenesis. The role of PT in amelioration of DM and application of digital communication will be discussed. Overall, it is judicious to create an increased patient cognizance of the periodontitis-DM relationship. Conjunctive efforts must be undertaken by the medical and oral health care professionals for the management of periodontitis affected DM patients.
文摘Endoscopic retrograde cholangiopancreatography(ERCP) has become an important therapeutic modality for biliary and pancreatic disorders. Perforation is one of the most feared complications of ERCP and endoscopic sphincterotomy. A MEDLINE search was performedfrom 2000-2014 using the keywords "perforation", "ERCP" and "endoscopic sphincterotomy". All articles including more than nine cases were reviewed. The incidence of ERCP-related perforations was low(0.39%, 95%CI: 0.34-0.69) with an associated mortality of 7.8%(95%CI: 3.80-13.07). Endoscopic sphincterotomy was responsible for 41% of perforations, insertion and manipulations of the endoscope for 26%, guidewires for 15%, dilation of strictures for 3%, other instruments for 4%, stent insertion or migration for 2% and in 7% of cases the etiology was unknown. The diagnosis was made during ERCP in 73% of cases. The mechanism, site and extent of injury, suggested by clinical and radiographic findings, should guide towards operative or non-operative management. In type I perforations early surgical repair is indicated, unless endoscopic closure can be achieved. Patients with type II perforations should be treated initially non-operatively. Non-operative treatment includes biliary stenting, fasting, intravenous fluid resuscitation, nasogastric drainage, broad spectrum antibiotics, percutaneous drainage of fluid collections. Non-operative treatment was successful in 79% of patients with type II injuries, with an overall mortality of 9.4%. Non-operative treatment was sufficient in all patients with type III injuries. Surgical technique depends on timing, site and size of defect and clinical condition of the patient. In conclusion, diagnosis is based on clinical suspicion and clinical and radiographic findings. Whilst surgery is usually indicated in patients with type I injuries, patients with type II or III injuries should be treated initially non-operatively. A minority of them will finally require surgical intervention.
基金the Chinese Nationa1Natural Science Foun dation (Grant 40072077) the Tarim Oil Field Company,Petro China(Grant2098050230).
文摘The Aiketik Group, distributed at the western end of the South TianshanMountains, China, is an important lithostratigraphic unit involved in the South Tianshan orogen. Itis separated from the adjacent rocks by faults. Generally, the geologists ascribed it to the UpperCarboniferous according to Pseudostaffella sp., Profusulinella sp. and Fusulinella sp. found fromthe limestone and sandy limestone of Aiketik. Our radiolarian fossils were obtained from the chertsamples collected from the Haladaok section located at the upper Tuoshihan River. The fossils mainlyinclude Albaillella undulata Deflandre, Albaillella paradoxa Deflandre, Albaillella sp. aff. A.paradoxa Deflandre, Albaillella sp. cf. A. deflandrei Gourmelon, Albaillella sp., Albaillellaexcelsa Ishiga, Kito and Imoto (?), Belowea variabilis (Ormiston et Lane), Callella cf. C.parvispinosa Won, Entactinia cf. E. tortispina Ormiston et Lane, Entactinia aff. E. tortispinaOrmiston et Lane, Entactinia variospina Won, Entactinia sp., Eostylodictya rota (Won),Latentifistula impella (Ormistone et Lane) (?), Latentifistula turgita Omiston et Lane,Latentifistulidae gen. et. sp. indet. and Polyentactinia cf. aranea Gourmelon. Among them,Albaillella excelsa Ishiga, Kito and Imoto (?) is a Late Permian species with some elementsuncertain as there is only one poorly-preserved fossil of this species found so far. And tworadiolarian assemblages can be identified from the other fossils. One is the early EarlyCarboniferous assemblage represented by Albaillella undulata Deflandre, Albaillella paradoxa andAlbaillella sp. cf. A. deflandrei Gourmelon. And the other is the late Early Carboniferousassemblage represented by Eostylodictya rota (Won). This is the first discovery of radiolarianfossils in the Aiketik Group, also the first discovery of Late Permian radiolarian fossils in theSouth Tianshan Mountains. Meanwhile, this is the current westernmost sampling site of radiolarianfossils in the South Tianshan Mountains.
文摘Background Advanced glycation end products （AGEs） play a critical role in the development of diabetic nephropathy. Reactive oxygen species （ROS） may play a critical role in AGEs induced growth factor expression. In this study, the effects of AGEs on transforming growth factor β1 （TGF-β1）, connective tissue growth factor （CTGF） and fibronectin （Fn） mRNA expression and oxidative stress in cultured NRK-49F cells were examined. Methods NRK-49F cells were incubated with medium containing different doses of AGEs （50, 100 or 200 μg/ml） for 24 hours, or with AGEs 100 μg/ml for different times （0, 12, 24 or 48 hours）. Cells in the serum-free medium or medium containing 25 mmol/L glucose were controls. Cells were treated with 25 mmol/L glucose and 100 μg/ml AGEs for 24 hours to determine the effects between AGEs and glucose. We clarified the role of antioxidant by pretreating cells with N-acetylcysteine （10 mmol/L）, ginkgo biloba extract （50 or 100 mg/L） for 24 hours and with 100 μg/ml AGEs for further 24 hours. Alamarblue dye assay was used to analyze cell growth; intracellular ROS generation was measured by flow cytometry; intracellular glutathione by fluorescence spectrophotometry; expressions of TGF-β1, CTGF and Fn mRNA by semiquantitative RT-PCR. Results AGEs significantly increased the expressions of TGF-β1, CTGF, Fn mRNA and intracellular ROS generation, and decreased the glutathion level in NRK-49F cells in dose- and time-dependent manners. High glucose and AGEs together significantly increased the expression of TGF-β1, CTGF and Fn mRNA, compared with AGEs and high glucose separately. Preincubation with N-acetylcysteine or ginkgo biloba extract increased GSH level, suppressed AGEs-induced oxidative stress and TGF-β1, CTGF and Fn mRNA overexpression. Conclusions AGEs can significantly increase expression of TGF-β1, CTGF, Fn mRNA in NRK-49F cells through enhancement of oxidative stress. The accumulation of AGEs may play a pivotal role in the pathogenesis of tubulointerst
文摘Objective:To investigate the effects of puerarin on the activity of superoxide dismutase(SOD), and expressions of advanced glycation end-product(AGE) receptor(RAGE) and vascular endothelial growth factor(VEGF) in retinas of streptozotocin(STZ)-induced early diabetic rats. Methods:Diabetic rat models were established by inducing diabetes via intra-peritoneal injection of STZ.Rats were randomly divided into normal(control),diabetic(DM),and DM+ puerarin groups.After intra-gastric administration of puerarin(500 mg/kg/day for 4 weeks),levels of SOD and malondialdehyde(MDA) were determined in serum and retina.mRNA and protein expression levels of RAGE and VEGF in retinas were determined by real-lime polymerase chain reaction(RT-PCR)(mRNA) and Western blot analysis(protein levels).Results:There was significantly lower SOD activity and significantly higher MDA in serum and retinas of the DM group compared with the two other groups(P【0.05).After treatment with puerarin,SOD activity increased and MDA content decreased in this group(P【0.05).mRNA and protein expression levels of RACE and VECF in the DM group were significantly higher than those of the other groups (P【0.05),and decreased after puerarin treatment(P【0.05).Conclusions:Puerarin is able to enhance SOD activity,and inhibit RAGE and VEGF expressions in retinas of STZ-induced early diabetic ruts.
文摘Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ on diabetic rats with ED and its potential mechanism viathe assessment of advanced glycosylation end products （AGEs）, autophagy, mTOR and the NO-cGMP pathway. Icarisid Ⅱ was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid Ⅱ group, rats were administered icarisid Ⅱ intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure （ICP/MAP）. AGE concentrations, nitric oxide synthase （NOS） activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 Iocalisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid Ⅱ increased ICP/MAP values, the smooth muscle cell （SMC） growth curve, S phase and SMC/collagen fibril （SMC/CF） proportions and decreased Beclin 1 （P〈0.05）. Icarisid Ⅱ significantly increased the proliferative index and p-p70S6K（Thr389） levels and decreased the numbers of autophagosomes and the levels of LC3-11 （P〈0.01）. Icarisid Ⅱ decreased AGE concentrations and increased cGMP concentration, NOS activity （P〈0.05） and cNOS levels （P〈0.01） in the diabetic ED group. Therefore, Icarisid Ⅱ constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.
文摘Diabetic nephropathy is the kidney disease that occurs as a result of diabetes.Cardiovascular and renal complications share common risk factors such as blood pressure,blood lipids,and glycemic control.Thus,chronic kidney disease may predict cardiovascular disease in the general population.The impact of diabetes on renal impairment changes with increasing age.Serum markers of glomerular filtration rate and microalbuminuria identify renal impairment in different segments of the diabetic population,indicating that serum markers as well as microalbuminuria tests should be used in screening for nephropathy in diabetic older people.The American Diabetes Association and the National Institutes of Health recommend Estimated glomerular filtration rate(eGFR) calculated from serum creatinine at least once a year in all people with diabetes for detection of kidney dysfunction.eGFR remains an independent and significant predictor after adjustment for conventional risk factors including age,sex,duration of diabetes,smoking,obesity,blood pressure,and glycemic and lipid control,as well as presence of diabetic retinopathy.Cystatin-C(Cys C) may in future be the preferred marker of diabetic nephropathy due differences in measurements of serum creatinine by various methods.The appropriate reference limit for Cys C in geriatric clinical practice must be defined by further research.Various studies have shown the importance of measurement of albuminuria,eGFR,serum creatinine and hemoglobin level to further enhance the prediction of end stage renal disease.
基金supported by National High Technology Research and Development Program of China(863 Program)(No.2015AA050104)National Natural Science Foundation of China(No.51577068)
文摘With the significant improvement of microgrid technology, microgrid has gained large-scale application.However, the existence of intermittent distributed generations, nonlinear loads and various electrical and electronic devices causes power quality problem in microgrid, especially in islanding mode. An accurate and fast disturbance detection method which is the premise of power quality control is necessary. Aiming at the end effect and the mode mixing of original Hilbert-Huang transform(HHT), an improved HHT with adaptive waveform matching extension is proposed in this paper. The innovative waveform matching extension method considers not only the depth of waveform, but also the rise time and fall time. Both simulations and field experiments have verified the correctness and validity of the improved HHT for power quality disturbance detection in microgrid.
基金co-supported by Open National Natural Science Foundation of China(No.51005183)National Science and Technology Major Project(No.2011ZX04016031)China Postdoctoral Science Foundation(No.2012M521804)
文摘A deduced cutting force prediction model for circular end milling process is presented in this paper. Traditional researches on cutting force model usually focus on linear milling process which does not meet other cutting conditions, especially for circular milling process. This paper presents an improved cutting force model for circular end milling process based on the typical linear milling force model. The curvature effects of tool path on chip thickness as well as entry and exit angles are analyzed, and the cutting force model of linear milling process is then corrected to fit circular end milling processes. Instantaneous cutting forces during circular end milling process are predicted according to the proposed model. The deduced cutting force model can be used for both linear and circular end milling processes. Finally, circular end milling experiments with constant and variable radial depth were carried out to verify the availability of the proposed method. Experiment results show that measured results and simulated results corresponds well with each other.
