Despite existing curative options like surgical removal,tissue destruction techniques,and liver transplantation for early-stage hepatocellular carcinoma(HCC),the rising incidence and mortality rates of this global hea...Despite existing curative options like surgical removal,tissue destruction techniques,and liver transplantation for early-stage hepatocellular carcinoma(HCC),the rising incidence and mortality rates of this global health burden necessitate continuous exploration of novel therapeutic strategies.This review critically assesses the dynamic treatment panorama for HCC,focusing specifically on the burgeoning role of immunotherapy in two key contexts:early-stage HCC and downstaging advanced HCC to facilitate liver transplant candidacy.It delves into the unique immunobiology of the liver and HCC,highlighting tumor-mediated immune evasion mechanisms.Analyzing the diverse immunothera-peutic approaches including checkpoint inhibitors,cytokine modulators,vaccines,oncolytic viruses,antigen-targeting antibodies,and adoptive cell therapy,this review acknowledges the limitations of current diagnostic markers alpha-fetoprotein and glypican-3 and emphasizes the need for novel biomarkers for patient selection and treatment monitoring.Exploring the rationale for neoadjuvant and adjuvant immunotherapy in early-stage HCC,current research is actively exploring the safety and effectiveness of diverse immunothera-peutic approaches through ongoing clinical trials.The review further explores the potential benefits and challenges of combining immunotherapy and liver transplant,highlighting the need for careful patient selection,meticulous monitoring,and novel strategies to mitigate post-transplant complications.Finally,this review delves into the latest findings from the clinical research landscape and future directions in HCC management,paving the way for optimizing treatment strategies and improving long-term survival rates for patients with this challenging malignancy.展开更多
As a promising optical and piezoelectric crystal,efficient growth of LGN single crystal is crucial for its practical applications.Herein,a langanite(La_(3)Ga_(5.5)Nb_(0.5)O_(14),LGN)crystal with high quality was succe...As a promising optical and piezoelectric crystal,efficient growth of LGN single crystal is crucial for its practical applications.Herein,a langanite(La_(3)Ga_(5.5)Nb_(0.5)O_(14),LGN)crystal with high quality was successfully grown by the Bridgman method along the Z direction.In order to prepare high-purity polycrystalline precursors for LGN crystal growth,the sintering conditions of LGN polycrystalline precursors were studied in detail.The melting point of LGN was also measured to provide a reference for the crystal growth temperature.For the[001]oriented wafer,the full width at half maximum(EWHM)value of the nigh-resolution X-ray diffraction(HRXRD)analysis is 38.52",demonstrating that the LGN crystal exhibits excellent crystalline quality.In addition,we also measured the thermal properties and transmission spectrum of the as-grown LGN crystal.It is found that the absorption peak at 1.85μm of the LGN crystal grown in air using the Bridgman method disappears compared with previous reports(grown in N_(2+)(1-3)vol%O_(2)atmosphere),which is attributed to the oxygen-enriched growth environment.Similar phenomenon also occurs in other LGS-type disordered crystals.It is believed that these findings may expand the potential applications of LGS series crystals at 1.85μm.展开更多
Bleeding and coagulopathy are critical issues complicating pediatric liver transplantation and contributing to morbidity and mortality in the cirrhotic child. The complexity of coagulopathy in the pediatric patient is...Bleeding and coagulopathy are critical issues complicating pediatric liver transplantation and contributing to morbidity and mortality in the cirrhotic child. The complexity of coagulopathy in the pediatric patient is illustrated by the interaction between three basic models. The first model, "developmental hemostasis", demonstrates how a different balance between pro- and anticoagulation factors leads to a normal hemostatic capacity in the pediatric patient at various ages. The second, the "cell based model of coagulation", takes into account the interaction between plasma proteins and cells. In the last, the concept of "rebalanced coagulation" highlights how the reduction of both pro- and anticoagulation factors leads to a normal, although unstable, coagulation profile. This new concept has led to the development of novel techniques used to analyze the coagulation capacity of whole blood for all patients. For example, viscoelastic methodologies are increasingly used on adult patients to test hemostatic capacity and to guide transfusion protocols. However, results are often confounding or have limited impact on morbidity and mortality. Moreover, data from pediatric patients remain inadequate. In addition, several interventions have been proposed to limit blood loss during transplantation, including the use of antifibrinolytic drugs and surgical techniques, such as the piggyback and lowering the central venous pressure during the hepatic dissection phase. The rationale for the use of these interventions is quite solid and has led to their incorporation into clinical practice; yet few of them have been rigorously tested in adults, let alone in children. Finally, the postoperative period in pediatric cohorts of patients has been characterized by an enhanced risk of hepatic vessel thrombosis. Thrombosis in fact remains the primary cause of early graft failure and re-transplantation within the first 30 d following surgery, and it occurs despite prolongation of standard coagulation assays. Data, however, are currently lacking regarding the use of anti-aggregation/anticoagulation therapies and how to best monitor for thrombosis in the early postoperative period in pediatric patients. Therefore, further studies are necessary to elucidate the interaction between the development of the coagulation system and cirrhosis in children. Moreover, strategies to optimize blood transfusion and anticoagulation must be tested specifically in pediatric patients. In conclusion, data from the adult world can be translated with difficulty into the pediatric field as indication for transplantation, baseline pathologies and levels of pro- and anticoagulation factors are not comparable between the two populations.展开更多
Purpose:Compared with healthy individuals,patients with peripheral artery disease(PAD)generally have a very high risk of subclinical Coronary artery disease(CAD)and cardiovascular events.To determine the correlation b...Purpose:Compared with healthy individuals,patients with peripheral artery disease(PAD)generally have a very high risk of subclinical Coronary artery disease(CAD)and cardiovascular events.To determine the correlation between CAD in PAD patients,thereby promoting the lifetime of PAD patients and reducing the serious impacts of CAD.Methods:This clinical-based cross-sectional study comprised 100 consecutive patients in India from 2014 to 2016.In this research,PAD patients were screened for CAD by treadmill stress test and cardiac colour Doppler examination.In addition,this study performed coronary angiography followed by peripheral angiography for patients who could not perform the treadmill test.Results:With the statistical results,the study observed a high prevalence of CAD in PAD patients that can be detected only with angiography.Further,30.93%of asymptomatic CAD prevalence was observed in PAD patients.The study strengthens the need for coronary angiography in all symptomatic lower limb PAD cases to detect early CAD,particularly in patients with diabetes and dyslipidemia.Conclusion:There exists a strong correlation between PAD and CAD.Hence,precise diagnosis followed by supervision of PAD patients is significant for avoiding local progression of cardiovascular risk.展开更多
This study addresses firstly the soil fabric variations of loose and dense compacted soil samples during a single wetting/drying cycle at suctions between 0 and 287.9 MPa using mainly the mercury intrusion porosimetry...This study addresses firstly the soil fabric variations of loose and dense compacted soil samples during a single wetting/drying cycle at suctions between 0 and 287.9 MPa using mainly the mercury intrusion porosimetry（MIP） tests.Two suction techniques were employed to apply this wide suction range：the osmotic technique for suctions less than 8.5 MPa,and the vapor equilibrium or salt solution technique for suctions higher than 8.5 MPa.Secondly,the soil water retention curves（SWRCs） were predicted by the MIP test results for both loose and dense soil samples.A reasonable correspondence between MIP results and SWRCs was found on the wetting path at lower suctions close to saturation and on drying path at higher suctions.展开更多
Hepatitis C virus(HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders in...Hepatitis C virus(HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.展开更多
Solar cells were fabricated from (Muscovite/ TiO2/Dye/Al), the effect of temperature, concen- tration and light intensity on the electrical prop- erties of (Muscovite/TiO2/Dye/Al) was studied. The relationship between...Solar cells were fabricated from (Muscovite/ TiO2/Dye/Al), the effect of temperature, concen- tration and light intensity on the electrical prop- erties of (Muscovite/TiO2/Dye/Al) was studied. The relationship between current and voltage was found to be algorism, which is in agreement with the ordinary relation for solar cells. When dye concentration was increased the conductivity, fill factor and efficiency were also increased. This result is found to be in conformity with the theoretical relations. The small energy gaps for their samples show that they are semiconductors. The maximum efficiency obtained is 33.2%.展开更多
Taiwan,China is located at the high-risk region of natural disasters with the frequently occurred earthquakes.The importance of the disaster prevention education on campus is made even more obvious by the fact that na...Taiwan,China is located at the high-risk region of natural disasters with the frequently occurred earthquakes.The importance of the disaster prevention education on campus is made even more obvious by the fact that natural disasters often occur during the school days.Given the leading roles the school administrators and teachers playing in the disaster prevention education of their pupils,this study purposed to investigate how disaster prevention literacy was among them and how disaster prevention literacy differed across various background variables of them.Furthermore,the current study also examined if disaster prevention literacy changed by participation in the disaster prevention education program.The results suggested that,among three dimensions of disaster prevention literacy(i.e.,knowledge,attitude,&skills)the participants were highest on disaster prevention skills and lowest on disaster prevention knowledge.Additionally,three dimensions of disaster prevention literacy of the participants differed by school level,age,years of service,personal disaster experience,and school disaster-stricken status.The participation in the disaster prevention education program was also related to participants'disaster prevention literacy.The implications of the above findings were discussed and the recommendations were also made for future disaster prevention education programs and research.展开更多
AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC)stage C hepatocellular carcinoma(HCC)and to ascertain the factors predicting the achievement of disease control(DC).METHOD...AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC)stage C hepatocellular carcinoma(HCC)and to ascertain the factors predicting the achievement of disease control(DC).METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation.Demographic,clinical and tumor features,along with the best tumor response and overall survival were recorded.RESULTS One hundred and ten BCLC stage C patients were included in the analysis;the median overall survival was 13.4 mo(95%CI:10.6-17.0).Only alphafetoprotein(AFP)serum level>200 ng/m L and DC could independently predict survival but in a time dependent manner,the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up(HR=5.073,95%CI:2.159-11.916,P=0.0002),whereas the latter showed a protective effect against death after one year(HR=0.110,95%CI:0.038-0.314,P<0.0001).Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC(OR=0.263,95%CI:0.111-0.622,P=0.002).CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments.The reverse and time dependent effect of AFP serum level and DC on patients'survival confers them as useful predictive tools for treatment management and clinical decisions.展开更多
Emerging evidence suggests that plasma membrane calcium ATPases (PMCAs) play a key role as regulators of calcium-triggered signal transduction pathways via interaction with partner proteins. PMCAs regulate these pathw...Emerging evidence suggests that plasma membrane calcium ATPases (PMCAs) play a key role as regulators of calcium-triggered signal transduction pathways via interaction with partner proteins. PMCAs regulate these pathways by targeting specific proteins to cellular sub-domains where the levels of intracellular freecalcium are kept low by the calcium ejection properties of PMCAs. According to this model, PMCAs have been shown to interact functionally with the calcium-sensitive proteins neuronal nitric oxide synthase, calmodulindependent serine protein kinase, calcineurin and endothelial nitric oxidase synthase. Transgenic animals with altered expression of PMCAs are being used to evaluate the physiological significance of these interactions. To date, PMCA interactions with calcium-dependent partner proteins have been demonstrated to play a crucial role in the pathophysiology of the cardiovascular system via regulation of the nitric oxide and calcineurin/nuclear factor of activated T cells pathways. This new evidence suggests that PMCAs play a more sophisticated role than the mere ejection of calcium from the cells, by acting as modulators of signaling transduction pathways.展开更多
Titanium powder was rapidly solidified by using shock-wave consolidation technique.The critical parameters were controlled by intrumented detonics and pin-oscillography.The compacted specimens were investigated for cr...Titanium powder was rapidly solidified by using shock-wave consolidation technique.The critical parameters were controlled by intrumented detonics and pin-oscillography.The compacted specimens were investigated for crystal structure and microstructural strengthening by using standard diagnostic techniques.The density of the final product was found to be greater than 96% of the theoretical value.X-ray diffraction pattern reveals intact crystalline structure without the presence of any undesired phases.The particle size reduction indicated by XRD was supported by laser diffraction based particle size analyzer.Results from energy dispersive spectroscopy ruled out the possibility of any segregation within the compacts.Scanning electron microscopy showed crack-free,voids-free,melt-free,fracture-less compacts of titanium with a unidirectional dendrite orientation without any grain-growth.展开更多
AIM： TO determine the DNA binding activity and protein levels of the Ku70/80 heterodimer, the functional mediator of the NHEJ activity, in human colorectal carcinogenesis. METHODS： The Ku70/80 DNA-binding activity w...AIM： TO determine the DNA binding activity and protein levels of the Ku70/80 heterodimer, the functional mediator of the NHEJ activity, in human colorectal carcinogenesis. METHODS： The Ku70/80 DNA-binding activity was determined by electrophoretic mobility shift assays in 20 colon adenoma and 15 colorectal cancer samples as well as matched normal colonic tissues. Nuclear and cytoplasmic protein expression was determined by immunohistochemistry and Western blot analysis. RESULTS： A statistical found in both adenomas y significant difference was and carcinomas as compared to matched normal colonic mucosa （P〈0.00）. However, changes in binding activity were not homogenous with approximately 50% of the tumors showing a clear increase in the binding activity, 30% displaying a modest increase and 15% showing a decrease of the activity.Tumors, with increased DNA-binding activity, also showed a statistically significant increase in Ku70 and Ku86 nuclear expression, as determined by Western blot and immunohistochemical analyses （P〈0.001）. Cytoplasmic protein expression was found in pathological samples, but not in normal tissues either from tumor patients or from healthy subjects. CONCLUSION： Overall, our DNA-binding activity and protein level are consistent with a substantial activation of the NHEJ pathway in colorectal tumors. Since the NHEJ is an error prone mechanism, its abnormal activation can result in chromosomal instability and ultimately lead to tumorigenesis.展开更多
文摘Despite existing curative options like surgical removal,tissue destruction techniques,and liver transplantation for early-stage hepatocellular carcinoma(HCC),the rising incidence and mortality rates of this global health burden necessitate continuous exploration of novel therapeutic strategies.This review critically assesses the dynamic treatment panorama for HCC,focusing specifically on the burgeoning role of immunotherapy in two key contexts:early-stage HCC and downstaging advanced HCC to facilitate liver transplant candidacy.It delves into the unique immunobiology of the liver and HCC,highlighting tumor-mediated immune evasion mechanisms.Analyzing the diverse immunothera-peutic approaches including checkpoint inhibitors,cytokine modulators,vaccines,oncolytic viruses,antigen-targeting antibodies,and adoptive cell therapy,this review acknowledges the limitations of current diagnostic markers alpha-fetoprotein and glypican-3 and emphasizes the need for novel biomarkers for patient selection and treatment monitoring.Exploring the rationale for neoadjuvant and adjuvant immunotherapy in early-stage HCC,current research is actively exploring the safety and effectiveness of diverse immunothera-peutic approaches through ongoing clinical trials.The review further explores the potential benefits and challenges of combining immunotherapy and liver transplant,highlighting the need for careful patient selection,meticulous monitoring,and novel strategies to mitigate post-transplant complications.Finally,this review delves into the latest findings from the clinical research landscape and future directions in HCC management,paving the way for optimizing treatment strategies and improving long-term survival rates for patients with this challenging malignancy.
基金Project supported by the National Key R&D Program of China(2022YFB3204000)National Natural Science Foundation of China(51832009)。
文摘As a promising optical and piezoelectric crystal,efficient growth of LGN single crystal is crucial for its practical applications.Herein,a langanite(La_(3)Ga_(5.5)Nb_(0.5)O_(14),LGN)crystal with high quality was successfully grown by the Bridgman method along the Z direction.In order to prepare high-purity polycrystalline precursors for LGN crystal growth,the sintering conditions of LGN polycrystalline precursors were studied in detail.The melting point of LGN was also measured to provide a reference for the crystal growth temperature.For the[001]oriented wafer,the full width at half maximum(EWHM)value of the nigh-resolution X-ray diffraction(HRXRD)analysis is 38.52",demonstrating that the LGN crystal exhibits excellent crystalline quality.In addition,we also measured the thermal properties and transmission spectrum of the as-grown LGN crystal.It is found that the absorption peak at 1.85μm of the LGN crystal grown in air using the Bridgman method disappears compared with previous reports(grown in N_(2+)(1-3)vol%O_(2)atmosphere),which is attributed to the oxygen-enriched growth environment.Similar phenomenon also occurs in other LGS-type disordered crystals.It is believed that these findings may expand the potential applications of LGS series crystals at 1.85μm.
文摘Bleeding and coagulopathy are critical issues complicating pediatric liver transplantation and contributing to morbidity and mortality in the cirrhotic child. The complexity of coagulopathy in the pediatric patient is illustrated by the interaction between three basic models. The first model, "developmental hemostasis", demonstrates how a different balance between pro- and anticoagulation factors leads to a normal hemostatic capacity in the pediatric patient at various ages. The second, the "cell based model of coagulation", takes into account the interaction between plasma proteins and cells. In the last, the concept of "rebalanced coagulation" highlights how the reduction of both pro- and anticoagulation factors leads to a normal, although unstable, coagulation profile. This new concept has led to the development of novel techniques used to analyze the coagulation capacity of whole blood for all patients. For example, viscoelastic methodologies are increasingly used on adult patients to test hemostatic capacity and to guide transfusion protocols. However, results are often confounding or have limited impact on morbidity and mortality. Moreover, data from pediatric patients remain inadequate. In addition, several interventions have been proposed to limit blood loss during transplantation, including the use of antifibrinolytic drugs and surgical techniques, such as the piggyback and lowering the central venous pressure during the hepatic dissection phase. The rationale for the use of these interventions is quite solid and has led to their incorporation into clinical practice; yet few of them have been rigorously tested in adults, let alone in children. Finally, the postoperative period in pediatric cohorts of patients has been characterized by an enhanced risk of hepatic vessel thrombosis. Thrombosis in fact remains the primary cause of early graft failure and re-transplantation within the first 30 d following surgery, and it occurs despite prolongation of standard coagulation assays. Data, however, are currently lacking regarding the use of anti-aggregation/anticoagulation therapies and how to best monitor for thrombosis in the early postoperative period in pediatric patients. Therefore, further studies are necessary to elucidate the interaction between the development of the coagulation system and cirrhosis in children. Moreover, strategies to optimize blood transfusion and anticoagulation must be tested specifically in pediatric patients. In conclusion, data from the adult world can be translated with difficulty into the pediatric field as indication for transplantation, baseline pathologies and levels of pro- and anticoagulation factors are not comparable between the two populations.
文摘Purpose:Compared with healthy individuals,patients with peripheral artery disease(PAD)generally have a very high risk of subclinical Coronary artery disease(CAD)and cardiovascular events.To determine the correlation between CAD in PAD patients,thereby promoting the lifetime of PAD patients and reducing the serious impacts of CAD.Methods:This clinical-based cross-sectional study comprised 100 consecutive patients in India from 2014 to 2016.In this research,PAD patients were screened for CAD by treadmill stress test and cardiac colour Doppler examination.In addition,this study performed coronary angiography followed by peripheral angiography for patients who could not perform the treadmill test.Results:With the statistical results,the study observed a high prevalence of CAD in PAD patients that can be detected only with angiography.Further,30.93%of asymptomatic CAD prevalence was observed in PAD patients.The study strengthens the need for coronary angiography in all symptomatic lower limb PAD cases to detect early CAD,particularly in patients with diabetes and dyslipidemia.Conclusion:There exists a strong correlation between PAD and CAD.Hence,precise diagnosis followed by supervision of PAD patients is significant for avoiding local progression of cardiovascular risk.
文摘This study addresses firstly the soil fabric variations of loose and dense compacted soil samples during a single wetting/drying cycle at suctions between 0 and 287.9 MPa using mainly the mercury intrusion porosimetry（MIP） tests.Two suction techniques were employed to apply this wide suction range：the osmotic technique for suctions less than 8.5 MPa,and the vapor equilibrium or salt solution technique for suctions higher than 8.5 MPa.Secondly,the soil water retention curves（SWRCs） were predicted by the MIP test results for both loose and dense soil samples.A reasonable correspondence between MIP results and SWRCs was found on the wetting path at lower suctions close to saturation and on drying path at higher suctions.
文摘Hepatitis C virus(HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.
文摘Solar cells were fabricated from (Muscovite/ TiO2/Dye/Al), the effect of temperature, concen- tration and light intensity on the electrical prop- erties of (Muscovite/TiO2/Dye/Al) was studied. The relationship between current and voltage was found to be algorism, which is in agreement with the ordinary relation for solar cells. When dye concentration was increased the conductivity, fill factor and efficiency were also increased. This result is found to be in conformity with the theoretical relations. The small energy gaps for their samples show that they are semiconductors. The maximum efficiency obtained is 33.2%.
文摘Taiwan,China is located at the high-risk region of natural disasters with the frequently occurred earthquakes.The importance of the disaster prevention education on campus is made even more obvious by the fact that natural disasters often occur during the school days.Given the leading roles the school administrators and teachers playing in the disaster prevention education of their pupils,this study purposed to investigate how disaster prevention literacy was among them and how disaster prevention literacy differed across various background variables of them.Furthermore,the current study also examined if disaster prevention literacy changed by participation in the disaster prevention education program.The results suggested that,among three dimensions of disaster prevention literacy(i.e.,knowledge,attitude,&skills)the participants were highest on disaster prevention skills and lowest on disaster prevention knowledge.Additionally,three dimensions of disaster prevention literacy of the participants differed by school level,age,years of service,personal disaster experience,and school disaster-stricken status.The participation in the disaster prevention education program was also related to participants'disaster prevention literacy.The implications of the above findings were discussed and the recommendations were also made for future disaster prevention education programs and research.
文摘AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC)stage C hepatocellular carcinoma(HCC)and to ascertain the factors predicting the achievement of disease control(DC).METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation.Demographic,clinical and tumor features,along with the best tumor response and overall survival were recorded.RESULTS One hundred and ten BCLC stage C patients were included in the analysis;the median overall survival was 13.4 mo(95%CI:10.6-17.0).Only alphafetoprotein(AFP)serum level>200 ng/m L and DC could independently predict survival but in a time dependent manner,the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up(HR=5.073,95%CI:2.159-11.916,P=0.0002),whereas the latter showed a protective effect against death after one year(HR=0.110,95%CI:0.038-0.314,P<0.0001).Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC(OR=0.263,95%CI:0.111-0.622,P=0.002).CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments.The reverse and time dependent effect of AFP serum level and DC on patients'survival confers them as useful predictive tools for treatment management and clinical decisions.
基金Supported by The Breast Cancer Campaign and the Research Institute in Healthcare Sciences (Armesilla AL)The Wellcome Trust (Emerson M)
文摘Emerging evidence suggests that plasma membrane calcium ATPases (PMCAs) play a key role as regulators of calcium-triggered signal transduction pathways via interaction with partner proteins. PMCAs regulate these pathways by targeting specific proteins to cellular sub-domains where the levels of intracellular freecalcium are kept low by the calcium ejection properties of PMCAs. According to this model, PMCAs have been shown to interact functionally with the calcium-sensitive proteins neuronal nitric oxide synthase, calmodulindependent serine protein kinase, calcineurin and endothelial nitric oxidase synthase. Transgenic animals with altered expression of PMCAs are being used to evaluate the physiological significance of these interactions. To date, PMCA interactions with calcium-dependent partner proteins have been demonstrated to play a crucial role in the pathophysiology of the cardiovascular system via regulation of the nitric oxide and calcineurin/nuclear factor of activated T cells pathways. This new evidence suggests that PMCAs play a more sophisticated role than the mere ejection of calcium from the cells, by acting as modulators of signaling transduction pathways.
文摘Titanium powder was rapidly solidified by using shock-wave consolidation technique.The critical parameters were controlled by intrumented detonics and pin-oscillography.The compacted specimens were investigated for crystal structure and microstructural strengthening by using standard diagnostic techniques.The density of the final product was found to be greater than 96% of the theoretical value.X-ray diffraction pattern reveals intact crystalline structure without the presence of any undesired phases.The particle size reduction indicated by XRD was supported by laser diffraction based particle size analyzer.Results from energy dispersive spectroscopy ruled out the possibility of any segregation within the compacts.Scanning electron microscopy showed crack-free,voids-free,melt-free,fracture-less compacts of titanium with a unidirectional dendrite orientation without any grain-growth.
基金Supported by Italian Ministero della Salute, IRCCS, RC0302TG13 by Ministero dell'Istruzíone, Università e Ricerca scientifica e tecnologica (MIUR), COFIN2002, to the Universita Campus Bio-Medico
文摘AIM： TO determine the DNA binding activity and protein levels of the Ku70/80 heterodimer, the functional mediator of the NHEJ activity, in human colorectal carcinogenesis. METHODS： The Ku70/80 DNA-binding activity was determined by electrophoretic mobility shift assays in 20 colon adenoma and 15 colorectal cancer samples as well as matched normal colonic tissues. Nuclear and cytoplasmic protein expression was determined by immunohistochemistry and Western blot analysis. RESULTS： A statistical found in both adenomas y significant difference was and carcinomas as compared to matched normal colonic mucosa （P〈0.00）. However, changes in binding activity were not homogenous with approximately 50% of the tumors showing a clear increase in the binding activity, 30% displaying a modest increase and 15% showing a decrease of the activity.Tumors, with increased DNA-binding activity, also showed a statistically significant increase in Ku70 and Ku86 nuclear expression, as determined by Western blot and immunohistochemical analyses （P〈0.001）. Cytoplasmic protein expression was found in pathological samples, but not in normal tissues either from tumor patients or from healthy subjects. CONCLUSION： Overall, our DNA-binding activity and protein level are consistent with a substantial activation of the NHEJ pathway in colorectal tumors. Since the NHEJ is an error prone mechanism, its abnormal activation can result in chromosomal instability and ultimately lead to tumorigenesis.
