Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated.Stem cell-based therapy,including human pluripotent stem cells(hPsCs)and multi...Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated.Stem cell-based therapy,including human pluripotent stem cells(hPsCs)and multipotent mesenchymal stem cells(MSCs),has recently emerged as a key player in regenerative medicine.hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body,including three germ layers.MsCs are multipotent progenitor cells possessing self-renewal ability(limited in vitro)and differentiation potential into mesenchymal lineages,according to the International Society for Cell and Gene Therapy(ISCT).This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow(BM),adipose tissue(AT),or the umbilical cord(UC)for the treatment of human diseases,including neurological disorders,pulmonary dysfunctions,metabolic/endocrine-related diseases,reproductive disorders,skin burns,and cardiovascular conditions.Moreover,we discuss our own clinical trial experiences on targeted therapies using MsCs in a clinical setting,and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications,with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications.The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment,AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration,and UC-MsCs are potentially good candidates for pulmonary disease and acute respiratory distress svndrometreatment.展开更多
Liver cirrhosis is a common and growing public health problem globally.The diagnosis of cirrhosis portends an increased risk of morbidity and mortality.Liver biopsy is considered the gold standard for diagnosis of cir...Liver cirrhosis is a common and growing public health problem globally.The diagnosis of cirrhosis portends an increased risk of morbidity and mortality.Liver biopsy is considered the gold standard for diagnosis of cirrhosis and staging of fibrosis.However,despite its universal use,liver biopsy is an invasive and inaccurate gold standard with numerous drawbacks.In order to overcome the limitations of liver biopsy,a number of non-invasive techniques have been investigated for the assessment of cirrhosis.This review will focus on currently available non-invasive markers of cirrhosis.The evidence behind the use of these markers will be highlighted,along with an assessment of diagnostic accuracy and performance characteristics of each test.Non-invasive markers of cirrhosis can be radiologic or serum-based.Radiologic techniques based on ultrasound,magnetic resonance imaging and elastography have been used to assess liver fibrosis.Serum-based biomarkers of cirrhosis have also been developed.These are broadly classified into indirect and direct markers.Indirect biomarkers reflect liver function,which may decline with the onset of cirrhosis.Direct biomarkers,reflect extracellular matrix turnover,and include molecules involved in hepatic fibrogenesis.On the whole,radiologic and serum markers of fibrosis correlate well with biopsy scores,especially when excluding cirrhosis or excluding fibrosis.This feature is certainly clinically useful,and avoids liver biopsy in many cases.展开更多
The product of the ∧0/b （-B/0） differential production cross-section and the branching fraction of the decay ∧0/b→ J/ψ pK-（-B/0→ J/ψ-K＊（892）0）is measured as a function of the beauty hadron transverse mome...The product of the ∧0/b （-B/0） differential production cross-section and the branching fraction of the decay ∧0/b→ J/ψ pK-（-B/0→ J/ψ-K＊（892）0）is measured as a function of the beauty hadron transverse momentum, PT, and rapidity, y. The kinematic region of the measurements is pT〈20 GeV/c and 2.0 〈g〈4.5.The measurements use a data sample corresponding to an integrated luminosity of 3fb-1 collected by the LHCb detector in pp collisions at centre-of-mass energies √s=7 TeV in 2011 and √s=8 TeV in 2012. Based on previous LHCb results of the fragmentation fraction ratio,f∧0/b/fd,the branching fraction of the decay ∧0/b→ J/ψ pK-is measured to be B（∧0/b→ J/ψ pK-）=（3.17±0.04±0.07±0.34＋0.45/-0.28）×10-4,where the first uncertainty is statistical, the second is systematic, the third is due to the uncertainty on the branching fraction of the decay -B/0 →J/ψ-K＊（892）0,and the fourth is due to the knowledge of f∧0/b/fd.The sum of the asymmetries in the production and decay between ∧0/b and ∧0/bis also measured as a function of PT and y.The previously published branching fraction of ∧0/b→ J/ψ pπ-,relative to that of ∧0/b→ J/ψ pK-,is updated. The branching fractions of ∧0/b→P＋c（→ J/ψp）K-are determined.展开更多
Hepatocellular carcinoma(HCC) is the most common primary malignancy of the liver. It is the second leading cause of cancer-related deaths worldwide, with a very poor prognosis. In the United States, there has been onl...Hepatocellular carcinoma(HCC) is the most common primary malignancy of the liver. It is the second leading cause of cancer-related deaths worldwide, with a very poor prognosis. In the United States, there has been only minimal improvement in the prognosis for HCC patients over the past 15 years. Details of the molecular mechanisms and other mechanisms of HCC progression remain unclear. Consequently, there is an urgent need for better understanding of these mechanisms. HCC is often diagnosed at advanced stages, and most patients will therefore need systemic therapy, with sorafenib being the most common at the present time. However, sorafenib therapy only minimally enhances patient survival. This review provides a summary of some of the known mechanisms that either cause HCC or contribute to its progression. Included in this review are the roles of viral hepatitis, non-viral hepatitis, chronic alcohol intake, genetic predisposition and congenital abnormalities, toxic exposures, and autoimmune diseases of the liver. Well-established molecular mechanisms of HCC progression such as epithelial-mesenchymal transition, tumor-stromal interactions and the tumor microenvironment, cancer stem cells, and senescence bypass are also discussed. Additionally, we discuss the roles of circulating tumor cells,immunomodulation, and neural regulation as potential new mechanisms of HCC progression. A better understanding of these mechanisms could have implications for the development of novel and more effective therapeutic and prognostic strategies, which are critically needed.展开更多
Indoleamine 2,3-dioxygenase 1(IDO1)is a rate-limiting metabolic enzyme that converts the essential amino acid tryptophan(Trp)into downstream catabolites known as kynurenines.Coincidently,numerous studies have demonstr...Indoleamine 2,3-dioxygenase 1(IDO1)is a rate-limiting metabolic enzyme that converts the essential amino acid tryptophan(Trp)into downstream catabolites known as kynurenines.Coincidently,numerous studies have demonstrated that IDO1 is highly expressed in multiple types of human cancer.Preclinical studies have further introduced an interesting paradox:while single-agent treatment with IDO1 enzyme inhibitor has a negligible effect on decreasing the established cancer burden,approaches combining select therapies with IDO1 blockade tend to yield a synergistic benefit against tumor growth and/or animal subject survival.Given the high expression of IDO1 among multiple cancer types along with the lack of monotherapeutic efficacy,these data suggest that there is a more complex mechanism of action than previously appreciated.Similar to the dual faces of the astrological Gemini,we highlight the multiple roles of IDO1 and review its canonical association with IDO1-dependent tryptophan metabolism,as well as documented evidence confirming the dispensability of enzyme activity for its immunosuppressive effects.The gene transcript levels for IDO1 highlight its strong association with T-cell infiltration,but the lack of a universal prognostic significance among all cancer subtypes.Finally,ongoing clinical trials are discussed with consideration of IDO1-targeting strategies that enhance the efficacy of immunotherapy for cancer patients。展开更多
AIM:To investigate the role of Rho-associated protein kinase (ROCK) inhibitor, Y27632, in mediating the production of extracellular matrix (ECM) components including fibronectin, matrix metallo-proteinase-2 (MMP-2) an...AIM:To investigate the role of Rho-associated protein kinase (ROCK) inhibitor, Y27632, in mediating the production of extracellular matrix (ECM) components including fibronectin, matrix metallo-proteinase-2 (MMP-2) and type I collagen as induced by connective tissue growth factor(CTGF) or transforming growth factor-β (TGF-β) in a human retinal pigment epithelial cell line, ARPE-19. METHODS:The effect of Y27632 on the CTGF or TGF-β induced phenotype in ARPE-19 cells was measured with immunocytochemistry as the change in F-actin. ARPE-19 cells were treated with CTGF (1, 10, 100ng/mL)and TGF-β (10ng/mL) in serum free media, and analyzed for fibronectin, laminin, and MMP-2 and type I collagen by RT-qPCR and immunocytochemistry. Cells were also pretreated with an ROCK inhibitor, Y27632, to analyze the signaling contributing to ECM production. ·RESULTS:Treatment of ARPE-19 cells in culture with TGF-β or CTGF induced an ECM change from a cobblestone morphology to a more elongated swirl pattern indicating a mesenchymal phenotype. RT-qPCR analysis and different gene expression analysis demonstrated an upregulation in expression of genes associated with cytoskeletal structure and motility. CTGFor TGF-β significantly increased expression of fibronectin mRNA (P =0.006, P =0.003 respectively), laminin mRNA (P =0.006, P =0.005), MMP-2 mRNA (P =0.006, P =0.001), COL1A1 mRNA (P =0.001, P =0.001), COL1A2 mRNA (P = 0.001, P =0.001). Preincubation of ARPE-19 with Y27632 (10mmol/L) significantly prevented CTGF or TGF-β induced fibronectin (P=0.005, P=0.003 respectively), MMP-2 (P = 0.003, P =0.002), COL1A1 (P =0.006, P =0.003), and COL1A2 (P =0.006, P =0.004) gene expression, but not laminin (P =0.375, P =0.516). CONCLUSION:Our study demonstrated that both TGF-β and CTGF upregulate the expression of ECM components including fibronectin, laminin, MMP-2 and type I collagen by activating the RhoA/ROCK signaling pathway. During this process, ARPE-19 cells were shown to change from an epithelial to a mesenchymal phenotype in vit展开更多
A jumping mechanism can be an efficient mode of motion for small robots to overcome large obstacles on the ground and rough terrain. In this paper, we present a 7 g prototype of locust-inspired jumping mechanism that ...A jumping mechanism can be an efficient mode of motion for small robots to overcome large obstacles on the ground and rough terrain. In this paper, we present a 7 g prototype of locust-inspired jumping mechanism that uses springs, wire, reduction gears, and a motor as the actuation components. The leg structure and muscles of a locust or grasshopper were mimicked using springs and wire, springs for passive extensor muscles, and a wire as a flexor muscle. A small motor was used to slowly charge the spring through a lever and gear system, and a cam with a special profile was used as a clicking mechanism for quick release of elastic energy stored in the springs to create a sudden kick for a quick jump. Performance analysis and experiments were conducted for comparison and performance estimation of the jumping mechanism prototype. Our prototype could produce standing jumps over obstacles that were about 14 times its own size （approximate to 71 cm） and a jumping distance of 20 times its own size （approximate to 100 cm）.展开更多
Cholangiocarcinoma is a rare malignancy of the biliary tract. Key factors in determining therapeutic options include knowledge of tumor extent, anatomy and obtaining tissue diagnosis. Endoscopically, there are three m...Cholangiocarcinoma is a rare malignancy of the biliary tract. Key factors in determining therapeutic options include knowledge of tumor extent, anatomy and obtaining tissue diagnosis. Endoscopically, there are three modalities available to make the diagnosis of cholangiocarcinoma. These include endoscopic retrograde cholangiopancreatography, endoscopic ultrasound with fine needle aspiration and cholangioscopy. Management of cholangiocarcinoma endoscopically is typically confined to stent placement for palliative purposes or as a bridge to surgery. In this article, we will review the endoscopic techniques available for the diagnosis and management of cholangiocarcinoma.展开更多
Malnutrition is associated with poor outcomes in critically ill patients. Although nutritional support is yet to be proven to improve mortality in non-malnourished critically ill patients, early enteral feeding is con...Malnutrition is associated with poor outcomes in critically ill patients. Although nutritional support is yet to be proven to improve mortality in non-malnourished critically ill patients, early enteral feeding is considered best practice. However, enteral feeding is often limited by delayed gastric emptying. The best method to clinically identify delayed gastric emptying and feed intolerance is unclear. Gastric residual volume （GRV） measured at the bedside is widely used as a surrogate marker for gastric emptying, but the value of GRV measurement has recently been disputed. While the mechanisms underlying delayed gastric emptying require further investigation, recent research has given a better appreciation of the pathophysiology. A number of pharmacological strategies are available to improve the success of feeding. Recent data suggest a combination of intravenous metoclopramide and en/thromycin to be the most successful treatment, but novel drug therapies should be explored. Simpler methods to access the duodenum and more distal small bowel for feed delivery are also under investigation. This review summarises current understanding of the factors responsible for, and mechanisms underlying feed intolerance in critical illness, together with the evidence for current practices. Areas requiring further research are also highlighted.展开更多
We briefly summarized how to design and fabricate an insect-mimicking flapping-wing system and demonstrate how to implement inherent pitching stability for stable vertical takeoff. The effect of relative locations of ...We briefly summarized how to design and fabricate an insect-mimicking flapping-wing system and demonstrate how to implement inherent pitching stability for stable vertical takeoff. The effect of relative locations of the Center of Gravity （CG） and the mean Aerodynamic Center （AC） on vertical flight was theoretically examined through static force balance considera- tion. We conducted a series of vertical takeoff tests in which the location of the mean AC was determined using an unsteady Blade Element Theory （BET） previously developed by the authors. Sequential images were captured during the takeoff tests using a high-speed camera. The results demonstrated that inherent pitching stability for vertical takeoff can be achieved by controlling the relative position between the CG and the mean AC of the flapping system.展开更多
AIM To investigate the role of minimally invasive surgery for gastric cancer and determine surgical, clinical, and oncological outcomes.METHODS This is a propensity score-matched case-control study, comparing three tr...AIM To investigate the role of minimally invasive surgery for gastric cancer and determine surgical, clinical, and oncological outcomes.METHODS This is a propensity score-matched case-control study, comparing three treatment arms: robotic gastrectomy(RG), laparoscopic gastrectomy(LG), open gastrectomy(OG). Data collection started after sharing a specific study protocol. Data were recorded through a tailored and protected web-based system. Primary outcomes: harvested lymph nodes, estimated blood loss, hospital stay, complications rate. Among the secondary outcomes, there are: operative time, R0 resections, POD of mobilization, POD of starting liquid diet and soft solid diet. The analysis includes the evaluation of type and grade of postoperative complications. Detailed information of anastomotic leakages is also provided.RESULTS The present analysis was carried out of 1026 gastrectomies. To guarantee homogenous distribution of cases, patients in the RG, LG and OG groups were 1:1:2 matched using a propensity score analysis with a caliper = 0.2. The successful matching resulted in a total sample of 604 patients(RG = 151; LG = 151; OG = 302). The three groups showed no differences in all baseline patients characteristics, type of surgery(P = 0.42) and stage of the disease(P = 0.16). Intraoperative blood loss was significantly lower in the LG(95.93 ± 119.22) and RG(117.91 ± 68.11) groups compared to the OG(127.26 ± 79.50, P = 0.002). The mean number of retrieved lymph nodes was similar between the RG(27.78 ± 11.45), LG(24.58 ± 13.56) and OG(25.82 ± 12.07) approach. A benefit in favor of the minimally invasive approaches was found in the length of hospital stay(P < 0.0001). A similar complications rate was found(P = 0.13). The leakage rate was not different(P = 0.78) between groups.CONCLUSION Laparoscopic and robotic surgery can be safely performed and proposed as possible alternative to open surgery. The main highlighted benefit is a faster postoperative functional recovery.展开更多
基金Thiswork is supportedby the Vingroup Scientific Research and Clinical Application Fund(Grantnumber:PRO.19.47).
文摘Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated.Stem cell-based therapy,including human pluripotent stem cells(hPsCs)and multipotent mesenchymal stem cells(MSCs),has recently emerged as a key player in regenerative medicine.hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body,including three germ layers.MsCs are multipotent progenitor cells possessing self-renewal ability(limited in vitro)and differentiation potential into mesenchymal lineages,according to the International Society for Cell and Gene Therapy(ISCT).This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow(BM),adipose tissue(AT),or the umbilical cord(UC)for the treatment of human diseases,including neurological disorders,pulmonary dysfunctions,metabolic/endocrine-related diseases,reproductive disorders,skin burns,and cardiovascular conditions.Moreover,we discuss our own clinical trial experiences on targeted therapies using MsCs in a clinical setting,and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications,with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications.The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment,AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration,and UC-MsCs are potentially good candidates for pulmonary disease and acute respiratory distress svndrometreatment.
文摘Liver cirrhosis is a common and growing public health problem globally.The diagnosis of cirrhosis portends an increased risk of morbidity and mortality.Liver biopsy is considered the gold standard for diagnosis of cirrhosis and staging of fibrosis.However,despite its universal use,liver biopsy is an invasive and inaccurate gold standard with numerous drawbacks.In order to overcome the limitations of liver biopsy,a number of non-invasive techniques have been investigated for the assessment of cirrhosis.This review will focus on currently available non-invasive markers of cirrhosis.The evidence behind the use of these markers will be highlighted,along with an assessment of diagnostic accuracy and performance characteristics of each test.Non-invasive markers of cirrhosis can be radiologic or serum-based.Radiologic techniques based on ultrasound,magnetic resonance imaging and elastography have been used to assess liver fibrosis.Serum-based biomarkers of cirrhosis have also been developed.These are broadly classified into indirect and direct markers.Indirect biomarkers reflect liver function,which may decline with the onset of cirrhosis.Direct biomarkers,reflect extracellular matrix turnover,and include molecules involved in hepatic fibrogenesis.On the whole,radiologic and serum markers of fibrosis correlate well with biopsy scores,especially when excluding cirrhosis or excluding fibrosis.This feature is certainly clinically useful,and avoids liver biopsy in many cases.
基金Supported by CERN and national agencies:CAPES,CNPq,FAPERJ and FINEP(Brazil)NSFC(China)+17 种基金CNRS/IN2P3(France)BMBF,DFG,HGF and MPG(Germany)INFN(Italy)FOM and NWO(The Netherlands)MNi SW and NCN(Poland)MEN/IFA(Romania)Min ES and FANO(Russia)Min ECo(Spain)SNSF and SER(Switzerland)NASU(Ukraine)STFC(United Kingdom)NSF(USA)supported by IN2P3(France),KIT and BMBF(Germany),INFN(Italy),NWOSURF(The Netherlands),PIC(Spain),Grid PP(United Kingdom)support from EPLANET,Marie Sk lodowska-Curie ActionsERC(European Union),Conseil général de Haute-Savoie,Labex ENIGMASS and OCEVU,RégionAuvergne(France),RFBR(Russia),Xunta GalGENCAT(Spain),Royal Society and Royal Commission for the Exhibition of 1851(United Kingdom)
文摘The product of the ∧0/b （-B/0） differential production cross-section and the branching fraction of the decay ∧0/b→ J/ψ pK-（-B/0→ J/ψ-K＊（892）0）is measured as a function of the beauty hadron transverse momentum, PT, and rapidity, y. The kinematic region of the measurements is pT〈20 GeV/c and 2.0 〈g〈4.5.The measurements use a data sample corresponding to an integrated luminosity of 3fb-1 collected by the LHCb detector in pp collisions at centre-of-mass energies √s=7 TeV in 2011 and √s=8 TeV in 2012. Based on previous LHCb results of the fragmentation fraction ratio,f∧0/b/fd,the branching fraction of the decay ∧0/b→ J/ψ pK-is measured to be B（∧0/b→ J/ψ pK-）=（3.17±0.04±0.07±0.34＋0.45/-0.28）×10-4,where the first uncertainty is statistical, the second is systematic, the third is due to the uncertainty on the branching fraction of the decay -B/0 →J/ψ-K＊（892）0,and the fourth is due to the knowledge of f∧0/b/fd.The sum of the asymmetries in the production and decay between ∧0/b and ∧0/bis also measured as a function of PT and y.The previously published branching fraction of ∧0/b→ J/ψ pπ-,relative to that of ∧0/b→ J/ψ pK-,is updated. The branching fractions of ∧0/b→P＋c（→ J/ψp）K-are determined.
文摘Hepatocellular carcinoma(HCC) is the most common primary malignancy of the liver. It is the second leading cause of cancer-related deaths worldwide, with a very poor prognosis. In the United States, there has been only minimal improvement in the prognosis for HCC patients over the past 15 years. Details of the molecular mechanisms and other mechanisms of HCC progression remain unclear. Consequently, there is an urgent need for better understanding of these mechanisms. HCC is often diagnosed at advanced stages, and most patients will therefore need systemic therapy, with sorafenib being the most common at the present time. However, sorafenib therapy only minimally enhances patient survival. This review provides a summary of some of the known mechanisms that either cause HCC or contribute to its progression. Included in this review are the roles of viral hepatitis, non-viral hepatitis, chronic alcohol intake, genetic predisposition and congenital abnormalities, toxic exposures, and autoimmune diseases of the liver. Well-established molecular mechanisms of HCC progression such as epithelial-mesenchymal transition, tumor-stromal interactions and the tumor microenvironment, cancer stem cells, and senescence bypass are also discussed. Additionally, we discuss the roles of circulating tumor cells,immunomodulation, and neural regulation as potential new mechanisms of HCC progression. A better understanding of these mechanisms could have implications for the development of novel and more effective therapeutic and prognostic strategies, which are critically needed.
基金supported by NIH grants R00 NS082381(DAW)and R01 NS097851-01(DAW)the Cancer Research Institute—Clinic and Laboratory Integration Program(DAW)+1 种基金the Robert H.Lurie Comprehensive Cancer Center—Zell Scholar Program of the Zell Family Foundation Gift(DAW)the Northwestern Brain Tumor Institute.
文摘Indoleamine 2,3-dioxygenase 1(IDO1)is a rate-limiting metabolic enzyme that converts the essential amino acid tryptophan(Trp)into downstream catabolites known as kynurenines.Coincidently,numerous studies have demonstrated that IDO1 is highly expressed in multiple types of human cancer.Preclinical studies have further introduced an interesting paradox:while single-agent treatment with IDO1 enzyme inhibitor has a negligible effect on decreasing the established cancer burden,approaches combining select therapies with IDO1 blockade tend to yield a synergistic benefit against tumor growth and/or animal subject survival.Given the high expression of IDO1 among multiple cancer types along with the lack of monotherapeutic efficacy,these data suggest that there is a more complex mechanism of action than previously appreciated.Similar to the dual faces of the astrological Gemini,we highlight the multiple roles of IDO1 and review its canonical association with IDO1-dependent tryptophan metabolism,as well as documented evidence confirming the dispensability of enzyme activity for its immunosuppressive effects.The gene transcript levels for IDO1 highlight its strong association with T-cell infiltration,but the lack of a universal prognostic significance among all cancer subtypes.Finally,ongoing clinical trials are discussed with consideration of IDO1-targeting strategies that enhance the efficacy of immunotherapy for cancer patients。
文摘AIM:To investigate the role of Rho-associated protein kinase (ROCK) inhibitor, Y27632, in mediating the production of extracellular matrix (ECM) components including fibronectin, matrix metallo-proteinase-2 (MMP-2) and type I collagen as induced by connective tissue growth factor(CTGF) or transforming growth factor-β (TGF-β) in a human retinal pigment epithelial cell line, ARPE-19. METHODS:The effect of Y27632 on the CTGF or TGF-β induced phenotype in ARPE-19 cells was measured with immunocytochemistry as the change in F-actin. ARPE-19 cells were treated with CTGF (1, 10, 100ng/mL)and TGF-β (10ng/mL) in serum free media, and analyzed for fibronectin, laminin, and MMP-2 and type I collagen by RT-qPCR and immunocytochemistry. Cells were also pretreated with an ROCK inhibitor, Y27632, to analyze the signaling contributing to ECM production. ·RESULTS:Treatment of ARPE-19 cells in culture with TGF-β or CTGF induced an ECM change from a cobblestone morphology to a more elongated swirl pattern indicating a mesenchymal phenotype. RT-qPCR analysis and different gene expression analysis demonstrated an upregulation in expression of genes associated with cytoskeletal structure and motility. CTGFor TGF-β significantly increased expression of fibronectin mRNA (P =0.006, P =0.003 respectively), laminin mRNA (P =0.006, P =0.005), MMP-2 mRNA (P =0.006, P =0.001), COL1A1 mRNA (P =0.001, P =0.001), COL1A2 mRNA (P = 0.001, P =0.001). Preincubation of ARPE-19 with Y27632 (10mmol/L) significantly prevented CTGF or TGF-β induced fibronectin (P=0.005, P=0.003 respectively), MMP-2 (P = 0.003, P =0.002), COL1A1 (P =0.006, P =0.003), and COL1A2 (P =0.006, P =0.004) gene expression, but not laminin (P =0.375, P =0.516). CONCLUSION:Our study demonstrated that both TGF-β and CTGF upregulate the expression of ECM components including fibronectin, laminin, MMP-2 and type I collagen by activating the RhoA/ROCK signaling pathway. During this process, ARPE-19 cells were shown to change from an epithelial to a mesenchymal phenotype in vit
文摘A jumping mechanism can be an efficient mode of motion for small robots to overcome large obstacles on the ground and rough terrain. In this paper, we present a 7 g prototype of locust-inspired jumping mechanism that uses springs, wire, reduction gears, and a motor as the actuation components. The leg structure and muscles of a locust or grasshopper were mimicked using springs and wire, springs for passive extensor muscles, and a wire as a flexor muscle. A small motor was used to slowly charge the spring through a lever and gear system, and a cam with a special profile was used as a clicking mechanism for quick release of elastic energy stored in the springs to create a sudden kick for a quick jump. Performance analysis and experiments were conducted for comparison and performance estimation of the jumping mechanism prototype. Our prototype could produce standing jumps over obstacles that were about 14 times its own size （approximate to 71 cm） and a jumping distance of 20 times its own size （approximate to 100 cm）.
文摘Cholangiocarcinoma is a rare malignancy of the biliary tract. Key factors in determining therapeutic options include knowledge of tumor extent, anatomy and obtaining tissue diagnosis. Endoscopically, there are three modalities available to make the diagnosis of cholangiocarcinoma. These include endoscopic retrograde cholangiopancreatography, endoscopic ultrasound with fine needle aspiration and cholangioscopy. Management of cholangiocarcinoma endoscopically is typically confined to stent placement for palliative purposes or as a bridge to surgery. In this article, we will review the endoscopic techniques available for the diagnosis and management of cholangiocarcinoma.
文摘Malnutrition is associated with poor outcomes in critically ill patients. Although nutritional support is yet to be proven to improve mortality in non-malnourished critically ill patients, early enteral feeding is considered best practice. However, enteral feeding is often limited by delayed gastric emptying. The best method to clinically identify delayed gastric emptying and feed intolerance is unclear. Gastric residual volume （GRV） measured at the bedside is widely used as a surrogate marker for gastric emptying, but the value of GRV measurement has recently been disputed. While the mechanisms underlying delayed gastric emptying require further investigation, recent research has given a better appreciation of the pathophysiology. A number of pharmacological strategies are available to improve the success of feeding. Recent data suggest a combination of intravenous metoclopramide and en/thromycin to be the most successful treatment, but novel drug therapies should be explored. Simpler methods to access the duodenum and more distal small bowel for feed delivery are also under investigation. This review summarises current understanding of the factors responsible for, and mechanisms underlying feed intolerance in critical illness, together with the evidence for current practices. Areas requiring further research are also highlighted.
基金Basic Science Research Program through the National Research Foundation of Korea (NRF)，The Ministry of Education,Science and Technology，The New & Renewable Energy R&D program of the Korea Institute of Energy Technology Evaluation and Planning (KETEP)，The Korea government Ministry of Knowledge Economy，M.J.Kim appreciates the financial support from National Science Foundation
文摘We briefly summarized how to design and fabricate an insect-mimicking flapping-wing system and demonstrate how to implement inherent pitching stability for stable vertical takeoff. The effect of relative locations of the Center of Gravity （CG） and the mean Aerodynamic Center （AC） on vertical flight was theoretically examined through static force balance considera- tion. We conducted a series of vertical takeoff tests in which the location of the mean AC was determined using an unsteady Blade Element Theory （BET） previously developed by the authors. Sequential images were captured during the takeoff tests using a high-speed camera. The results demonstrated that inherent pitching stability for vertical takeoff can be achieved by controlling the relative position between the CG and the mean AC of the flapping system.
基金Supported by CARIT Foundation(Fondazione Cassa di Risparmio di Terni e Narni),No.0024137
文摘AIM To investigate the role of minimally invasive surgery for gastric cancer and determine surgical, clinical, and oncological outcomes.METHODS This is a propensity score-matched case-control study, comparing three treatment arms: robotic gastrectomy(RG), laparoscopic gastrectomy(LG), open gastrectomy(OG). Data collection started after sharing a specific study protocol. Data were recorded through a tailored and protected web-based system. Primary outcomes: harvested lymph nodes, estimated blood loss, hospital stay, complications rate. Among the secondary outcomes, there are: operative time, R0 resections, POD of mobilization, POD of starting liquid diet and soft solid diet. The analysis includes the evaluation of type and grade of postoperative complications. Detailed information of anastomotic leakages is also provided.RESULTS The present analysis was carried out of 1026 gastrectomies. To guarantee homogenous distribution of cases, patients in the RG, LG and OG groups were 1:1:2 matched using a propensity score analysis with a caliper = 0.2. The successful matching resulted in a total sample of 604 patients(RG = 151; LG = 151; OG = 302). The three groups showed no differences in all baseline patients characteristics, type of surgery(P = 0.42) and stage of the disease(P = 0.16). Intraoperative blood loss was significantly lower in the LG(95.93 ± 119.22) and RG(117.91 ± 68.11) groups compared to the OG(127.26 ± 79.50, P = 0.002). The mean number of retrieved lymph nodes was similar between the RG(27.78 ± 11.45), LG(24.58 ± 13.56) and OG(25.82 ± 12.07) approach. A benefit in favor of the minimally invasive approaches was found in the length of hospital stay(P < 0.0001). A similar complications rate was found(P = 0.13). The leakage rate was not different(P = 0.78) between groups.CONCLUSION Laparoscopic and robotic surgery can be safely performed and proposed as possible alternative to open surgery. The main highlighted benefit is a faster postoperative functional recovery.
