The human liver is usually perceived as a non-immunological organ engaged primarily in metabolic, nutrient storage and detoxification activities. However, we now know that the healthy liver is also a site of complex i...The human liver is usually perceived as a non-immunological organ engaged primarily in metabolic, nutrient storage and detoxification activities. However, we now know that the healthy liver is also a site of complex immunological activity mediated by a diverse immune cell repertoire as well as non-hematopoietic cell populations. In the nondiseased liver, metabolic and tissue remodeling functions require elements of inflammation. This inflammation, in combination with regular exposure to dietary and microbial products, creates the potential for excessive immune activation. In this complex microenvironment, the hepatic immune system tolerates harmless molecules while at the same time remaining alert to possible infectious agents, malignant cells or tissue damage. Upon appropriate immune activation to challenge by pathogens or tissue damage, mechanisms to resolve inflammation are essential to maintain liver homeostasis. Failure to clear ＇dangerous＇ stimuli or regulate appropriately activated immune mechanisms leads to pathological inflammation and disrupted tissue homeostasis characterized by the progressive development of fibrosis, cirrhosis and eventual liver failure. Hepatic inflammatory mechanisms therefore have a spectrum of roles in the healthy adult liver; they are essential to maintain tissue and organ homeostasis and, when dysregulated, are key drivers of the liver pathology associated with chronic infection, autoimmunity and malignancy. In this review, we explore the changing perception of inflammation and inflammatory mediators in normal liver homeostasis and propose targeting of liver-specific immune regulation pathways as a therapeutic approach to treat liver disease.展开更多
Hepatic fibrosis is a pathological lesion, characterized by the progressive accumulation of extracellularmatrix （ECM） in the perisinusoidal space and it is a major problem in chronic liver diseases. Phenotypicactiva...Hepatic fibrosis is a pathological lesion, characterized by the progressive accumulation of extracellularmatrix （ECM） in the perisinusoidal space and it is a major problem in chronic liver diseases. Phenotypicactivation of hepatic stellate cells （HSC） plays a central role in the progression of hepatic fibrosis. Retardation of proliferation and clearance of activated HSCs from the injured liver is an appropriate therapeuticstrategy for the resolution and treatment of hepatic fibrosis. Clearance of activated HSCs from the injuredliver by autophagy inhibitors, proapoptotic agents and senescence inducers with the high affinity towardthe activated HSCs may be the novel therapeutic strategy for the treatment of hepatic fibrosis in the nearfuture.展开更多
Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with live...Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease(CHD),abnormalities of cardiac function and structure(e.g.,left ventricular dysfunction and hypertrophy,and heart failure),valvular heart disease(e.g.,aortic valve sclerosis)and arrhythmias(e.g.,atrial fibrillation).Experimental evidence suggests that NAFLD itself,especially in its more severe forms,exacerbates systemic/hepatic insulin resistance,causes atherogenic dyslipidemia,and releases a variety of pro-inflammatory,pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications.Collectively,these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications.The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular,cardiac and arrhythmic complications,to briefly examine the putative biological mechanisms underlying this association,and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications.展开更多
Background:Since its discovery in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 2180000 people worldwide and has caused more than 150000 deaths as of April 16,2020.SAR...Background:Since its discovery in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 2180000 people worldwide and has caused more than 150000 deaths as of April 16,2020.SARS-CoV-2,which is the virus causing coronavirus disease 2019(COVID-19),uses the angiotensin-converting enzyme 2(ACE2)as a cell receptor to invade human cells.Thus,ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection.This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.Methods:We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger(ages≤49 years)and older(ages>49 years)persons using two-sided Student's t test.We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson's correlation test.Results:ACE2 expression levels were the highest in the small intestine,testis,kidneys,heart,thyroid,and adipose tissue,and were the lowest in the blood,spleen,bone marrow,brain,blood vessels,and muscle.ACE2 showed medium expression levels in the lungs,colon,liver,bladder,and adrenal gland.ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue.In the skin,digestive system,brain,and blood vessels,ACE2 expression levels were positively associated with immune signatures in both males and females.In the thyroid and lungs,ACE2 expression levels were positively and negatively associated with immune signatures in males and females,respectively,and in the lungs they had a positive and a negative correlation in the older and younger groups,respectively.Conclusions:Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes,ages,and races equally.The different host immune responses to SARS-CoV-2 infection may partially explain why males and females,young and old persons infected with this vi展开更多
AIM:To study secretion patterns of proand anti-in-flammatory cytokines, and activation of various cellular subsets of leukocytes in peripheral blood.METHODS: We have conducted a prospective obser-vational study. One h...AIM:To study secretion patterns of proand anti-in-flammatory cytokines, and activation of various cellular subsets of leukocytes in peripheral blood.METHODS: We have conducted a prospective obser-vational study. One hundred and eight patients with a diagnosis of acute pancreatitis and onset of the disease within last 72 h were included in this study. The mRNA expression of 25 different types of cytokines in white blood cells was determined by quantitative real time polymerase chain reaction. Levels of 8 different cytokines in blood serum were measured by enzymelinked immunosorbent assay. Clinical data and cytokine expression results were subjected to statistical analysis.RESULTS: Severe and necrotizing acute pancreatitis (AP) is characterized by the significant depletion of circulating lymphocytes. Severe acute pancreatitis is as-sociated with a typical systemic inflammatory response syndrome and over-expression of pro-inflammatory cy-tokines [interleukin (IL)-6, IL-8, macrophage migration inhibitory factor (MIF)]. Serum IL-6 and MIF concentra-tions are the best discriminators of severe and necrotiz-ing AP as well as possible fatal outcome during the early course of the disease. CONCLUSION: Deregulation of cellular immune sys-tem is a key event leading to severe and necrotizing AP. IL-6 and MIF could be used as early predictors of complications.展开更多
Bone is the second most commonly transplanted tissue worldwide,with over four million operations using bone grafts or bone substitute materials annually to treat bone defects.However,significant limitations affect cur...Bone is the second most commonly transplanted tissue worldwide,with over four million operations using bone grafts or bone substitute materials annually to treat bone defects.However,significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma,cancer,infection and arthritis.Developing bioactive three-dimensional(3D)scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering(BTE).A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts.However,individual groups of materials including polymers,ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone.Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds.This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers,hydrogels,metals,ceramics and bio-glasses in BTE.Scaffold fabrication methodology,mechanical performance,biocompatibility,bioactivity,and potential clinical translations will be discussed.展开更多
AIM:To assess expression of matrix metalloproteinases 2(MMP2)and MMP9 in gastric cancer,superficial gastritis and normal mucosa,and to measure metalloproteinase activity.METHODS:MMP2 and MMP9 mRNA expression was deter...AIM:To assess expression of matrix metalloproteinases 2(MMP2)and MMP9 in gastric cancer,superficial gastritis and normal mucosa,and to measure metalloproteinase activity.METHODS:MMP2 and MMP9 mRNA expression was determined by quantitative real-time polymerase chain reaction.Normalization was carried out using three different factors.Proteins were analyzed by quantitative gelatin zymography(qGZ).RESULTS:18S ribosomal RNA(18SRNA)was very highly expressed,while hypoxanthine ribosyltransferase-1(HPRT-1)was moderately expressed.MMP2 was highly expressed,while MMP9 was not detected or lowly expressed in normal tissues,moderately or highly expressed in gastritis and highly expressed in cancer.Relative expression of 18SRNA and HPRT-1 showed no significant differences.Significant differences in MMP2 and MMP9 were found between cancer and normal tissue,but not between gastritis and normal tissue.Absolute quantification of MMP9 echoed this pattern,but differential expression of MMP2 proved conflictive.Analysis by qGZ indicated significant differences between cancer and normal tissue in MMP-2,total MMP-9,250 and 110 kDa bands.CONCLUSION:MMP9 expression is enhanced in gastric cancer compared to normal mucosa;interpretation of differential expression of MMP2 is difficult to establish.展开更多
A foundation of the modern technology that uses single-crystal silicon has been the growth of highquality single-crystal Si ingots with diameters up to 12 inches or larger. For many applications of graphene, large-are...A foundation of the modern technology that uses single-crystal silicon has been the growth of highquality single-crystal Si ingots with diameters up to 12 inches or larger. For many applications of graphene, large-area high-quality(ideally of single-crystal) material will be enabling. Since the first growth on copper foil a decade ago, inch-sized single-crystal graphene has been achieved. We present here the growth, in 20 min, of a graphene film of(5 ×50) cm^2 dimension with >99% ultra-highly oriented grains.This growth was achieved by:(1) synthesis of metre-sized single-crystal Cu(1 1 1) foil as substrate;(2)epitaxial growth of graphene islands on the Cu(1 1 1) surface;(3) seamless merging of such graphene islands into a graphene film with high single crystallinity and(4) the ultrafast growth of graphene film.These achievements were realized by a temperature-gradient-driven annealing technique to produce single-crystal Cu(1 1 1) from industrial polycrystalline Cu foil and the marvellous effects of a continuous oxygen supply from an adjacent oxide. The as-synthesized graphene film, with very few misoriented grains(if any), has a mobility up to ~23,000 cm^2 V^(-1)s^(-1)at 4 K and room temperature sheet resistance of ~230 Ω/□. It is very likely that this approach can be scaled up to achieve exceptionally large and high-quality graphene films with single crystallinity, and thus realize various industrial-level applications at a low cost.展开更多
The red blood cell distribution width(RDW) is a simple, rapid, inexpensive and straightforward hematological parameter, reflecting the degree of anisocytosis in vivo. The currently available scientific evidence sugges...The red blood cell distribution width(RDW) is a simple, rapid, inexpensive and straightforward hematological parameter, reflecting the degree of anisocytosis in vivo. The currently available scientific evidence suggests that RDW assessment not only predicts the risk of adverse outcomes(cardiovascular and all-cause mortality, hospitalization for acute decompensation or worsened left ventricular function) in patients with acute and chronic heart failure(HF), but is also a significant and independent predictor of developing HF in patients free of this condition. Regarding the biological interplay between impaired hematopoiesis and cardiac dysfunction, many of the different conditions associated with increased heterogeneity of erythrocyte volume(i.e., ageing, inflammation, oxidative stress, nutritional deficiencies and impaired renal function), may be concomitantly present in patients with HF, whilst anisocytosis may also directly contribute to the development and worsening of HF. In conclusion, the longitudinal assessment of RDW changes over time may be considered an efficient measure to help predicting the risk of both development and progression of HF.展开更多
To assess “predictors” of esophageal varices (EV) and variceal bleeding using non-invasive markers in Albanian patients diagnosed with liver cirrhosis. METHODSOne hundred thirty-nine newly diagnosed cirrhotic patien...To assess “predictors” of esophageal varices (EV) and variceal bleeding using non-invasive markers in Albanian patients diagnosed with liver cirrhosis. METHODSOne hundred thirty-nine newly diagnosed cirrhotic patients without variceal bleeding were included in this analysis. Model for end-stage liver disease (MELD), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AST/ALT), AST to platelet ratio index (APRI), platelet count to spleen diameter (PC/SD), fibrosis-4-index (FIB-4), fibrosis index (FI) and King’s Score were measured for all participants. All patients underwent endoscopic assessment within two days of hospitalization. The major end point was the first esophageal variceal bleeding (EVB) event. The diagnostic performance of “predictors” for the presence of EV and EVB were assessed by sensitivity and specificity values obtained from the receiver operating characteristics procedure. RESULTSFIB-4 was the only strong and significant “predictor” of esophageal varices (multivariable-adjusted OR = 1.57 for one unit increment; 95%CI: 1.15-2.14). Furthermore, a cut-off value of 3.23 for FIB-4 was a significant predictor of esophageal varices, with a sensitivity of 72%, a specificity of 58% and a proportion of area under the curve (AUC) of 66% (P = 0.01). During the follow-up (median: 31.5 mo; interquartile range: 11-59 mo), 34 patients (24%) experienced a first EVB. FIB-4 was a poor predictor of EVB (the AUC was only 51%) for a cut-off value of 5.02. Furthermore, the AUC of AST/ALT, APRI, PC/SD, FI, MELD and King’s Score ranged from 45% to 55%. None of the non-invasive markers turned out to be a useful predictor of EVB. CONCLUSIONDespite the low diagnostic accuracy, FIB-4 appears the most efficient non-invasive liver fibrosis marker which can be used as an initial screening tool for cirrhotic patients.展开更多
Baicalein, wogonin, and their glycosides are major bioactive compounds found in the medicinal plant Scutellaria baicalensis Georgi. These flavones can induce apoptosis in a variety of cancer cell lines but have no eff...Baicalein, wogonin, and their glycosides are major bioactive compounds found in the medicinal plant Scutellaria baicalensis Georgi. These flavones can induce apoptosis in a variety of cancer cell lines but have no effect on normal cells. Furthermore, they have many additional benefits for human health, such as antioxidant, antiviral, and liver-protective properties. Here, we report the isolation and characterization of two CYP450 enzymes, SbCYP82D1.1 and SbCYP82D2, which function as the flavone 6-hydroxylase （F6H） and flavone 8-hydroxylase （F8H）, respectively, in S. baicalensis. SbCYP82D1.1 has broad substrate speci- ficity for flavones such as chrysin and apigenin and is responsible for biosynthesis of baicalein and scutel- larein in roots and aerial parts of S. baicalensis, respectively. When the expression of SbCYP82D1.1 is knocked down, baicalin and baicalein levels are reduced significantly while chrysin glycosides accumulate in hairy roots. SbCYP82D2 is an F8H with high substrate specificity, accepting only chrysin as its substrate to produce norwogonin, although minor 6-hydroxylation activity can also be detected. Phylogenetic analysis suggested that SbCYP82D2 might have evolved from SbCYP82D1.1 via gene duplication followed by neofunctionalization, whereby the ancestral F6H activity is partially retained in the derived SbCYP82D2.展开更多
Helicobacter pylori(H. pylori) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gast...Helicobacter pylori(H. pylori) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gastro-intestinal diseases, but also with extra gastric diseases. Despite such associations, the bacterium frequently persists in the human host without inducing disease, and it has been suggested that H. pylori may also play a beneficial role in health. To understand how H. pylori can produce such diverse effects in the human host, several studies have focused on understanding the local and systemic effects triggered by this bacterium. One of the main mechanisms by which H. pylori is thought to damage the host is by inducing local and systemic inflammation. However, more recently, studies are beginning to focus on the effects of H. pylori and its metabolism on the gastric and intestinal microbiome. The objective of this review is to discuss how H. pylori has co-evolved with humans, how H. pylori presence is associated with positive and negative effects in human health and how inflammation and/or changes in the microbiome are associated with the observed outcomes.展开更多
Frequent activation of phosphatidylinositol-3 kinases(PI3K)/Akt/m TOR signaling pathway in gastric cancer(GC) is gaining immense popularity with identification of mutations and/or amplifications of PIK3 CA gene or los...Frequent activation of phosphatidylinositol-3 kinases(PI3K)/Akt/m TOR signaling pathway in gastric cancer(GC) is gaining immense popularity with identification of mutations and/or amplifications of PIK3 CA gene or loss of function of PTEN,a tumor suppressor protein,to name a few; both playing a crucial role in regulating this pathway. These aberrations result in dysregulation of this pathway eventually leading to gastric oncogenesis,hence,there is a need for targeted therapy for more effective anticancer treatment. Several inhibitors are currently in either preclinical or clinical stages for treatment of solid tumors like GC. With so many inhibitors under development,further studies on predictive biomarkers are needed to measure the specificity of any therapeutic intervention. Herein,we review the common dysregulation of PI3K/Akt/m TOR pathway in GC and the various types of single or dual pathway inhibitors under development that might have a superior role in GC treatment. We also summarize the recent developments in identification of predictive biomarkers and propose use of predictive biomarkers to facilitate more personalized cancer therapy with effective PI3K/Akt/m TOR pathway inhibition.展开更多
The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical te...The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive （second generation） biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials （third generation） are designed to be not only osteo- conductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineer- ing and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental ＂origin＂ require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.展开更多
Scutellaria baicalensis Georgi is important in Chinese traditional medicine where preparations of dried roots,"Huang Qin," are used for liver and lung complaints and as complementary cancer treatments. We re...Scutellaria baicalensis Georgi is important in Chinese traditional medicine where preparations of dried roots,"Huang Qin," are used for liver and lung complaints and as complementary cancer treatments. We report a high-quality reference genome sequence for S. baicalensis where 93% of the 408.14-Mb genome has been assembled into nine pseudochromosomes with a super-N50 of 33.2 Mb. Comparison of this sequence with those of closely related species in the order Lamiales, sesamum indicum and Salvia splendens,revealed that a specialized metabolic pathway for the synthesis of 4'-deoxyflavone bioactives evolved in the genus Scu-tellaria. We found that the gene encoding a specific cinnamate coenzyme A ligase likely obtained its newfunc- tion following recent mutations, and that four genes encoding enzymes in the 4'-deoxyflavone pathway are present as tandem repeats in the genome of S. baicalensis. Further analyses revealed that gene duplications, segmental duplication, gene amplification, and point mutations coupled to gene neo- and subfunctionaliza-tions were involved in the evolution of 4'-deoxyflavone synthesis in the genus Scutellaria. Our study not only provides significant insight into the evolution of specific flavone biosynthetic pathways in the mint family, Lamiaceae, but also will facilitate the development of tools for enhancing bioactive productivity by metabolic engineering in microbes or by molecular breeding in plants. The reference genome of S. baicalensis is also useful for improving the genome assemblies for other members of the mint family and offers an important foundation for decoding the synthetic pathways of bioactive compounds in medicinal plants.展开更多
There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels,and molecular mediators directed aga...There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels,and molecular mediators directed against harmful stimuli, is closely associated with many human diseases.As a result, biomimetic nanoparticles mimicking immune cells can help achieve molecular imaging and precise drug delivery to these inflammatory sites. This review is focused on inflammation-targeting biomimetic nanoparticles and will provide an in-depth look at the design of these nanoparticles to maximize their benefits for disease diagnosis and treatment.展开更多
AIM: To assess the impact of percutaneous cardiac support in cardiogenic shock(CS) complicating acute myocardial infarction(AMI), treated with percutaneous coronary intervention. METHODS: We selected all of the studie...AIM: To assess the impact of percutaneous cardiac support in cardiogenic shock(CS) complicating acute myocardial infarction(AMI), treated with percutaneous coronary intervention. METHODS: We selected all of the studies published from January 1st, 1997 to May 15 st, 2015 that compared the following percutaneous mechanical support in patients with CS due to AMI undergoing myocardial revascularization:(1) intra-aortic balloon pump(IABP) vs Medical therapy;(2) percutaneous left ventricular assist devices(PLVADs) vs IABP;(3) complete extracorporeal life support with extracorporeal membrane oxygenation(ECMO) plus IABP vs IABP alone; and(4) ECMO plus IABP vs ECMO alone, in patients with AMI and CS undergoing myocardial revascularization. We evaluated the impact of the support devices on primary and secondary endpoints. Primary endpoint was the inhospital mortality due to any cause during the same hospital stay and secondary endpoint late mortality at 6-12 moof follow-up. RESULTS: One thousand two hundred and seventytwo studies met the initial screening criteria. After detailed review, only 30 were selected. There were 6 eligible randomized controlled trials and 24 eligible observational studies totaling 15799 patients. We found that the inhospital mortality was:(1) significantly higher with IABP support vs medical therapy(RR = +15%, P = 0.0002);(2) was higher, although not significantly, with PLVADs compared to IABP(RR = +14%, P = 0.21); and(3) significantly lower in patients treated with ECMO plus IABP vs IABP(RR =-44%, P = 0.0008) or ECMO(RR =-20%, P = 0.006) alone. In addition, Trial Sequential Analysis showed that in the comparison of IABP vs medical therapy, the sample size was adequate to demonstrate a significant increase in risk due to IABP. CONCLUSION: Inhospital mortality was significantly higher with IABP vs medical therapy. PLVADs did not reduce early mortality. ECMO plus IABP significantly reduced inhospital mortality compared to IABP.展开更多
Over the last 20 years, silicon photonics has revolutionized the field of integrated optics, providing a novel and powerful platform to build mass-producible optical circuits. One of the most attractive aspects of sil...Over the last 20 years, silicon photonics has revolutionized the field of integrated optics, providing a novel and powerful platform to build mass-producible optical circuits. One of the most attractive aspects of silicon photonics is its ability to provide extremely small optical components, whose typical dimensions are an order of magnitude smaller than those of optical fiber devices. This dimension difference makes the design of fiberto-chip interfaces challenging and, over the years, has stimulated considerable technical and research efforts in the field. Fiber-to-silicon photonic chip interfaces can be broadly divided into two principle categories:in-plane and out-of-plane couplers. Devices falling into the first category typically offer relatively high coupling efficiency, broad coupling bandwidth(in wavelength), and low polarization dependence but require relatively complex fabrication and assembly procedures that are not directly compatible with wafer-scale testing.Conversely, out-of-plane coupling devices offer lower efficiency, narrower bandwidth, and are usually polarization dependent. However, they are often more compatible with high-volume fabrication and packaging processes and allow for on-wafer access to any part of the optical circuit. In this paper, we review the current state-of-the-art of optical couplers for photonic integrated circuits, aiming to give to the reader a comprehensive and broad view of the field, identifying advantages and disadvantages of each solution. As fiber-to-chip couplers are inherently related to packaging technologies and the co-design of optical packages has become essential, we also review the main solutions currently used to package and assemble optical fibers with silicon-photonic integrated circuits.展开更多
AIM：To evaluate the diagnostic role of serum RASSF1A promoter hypermethylation in gastric and colorectal adenocarcinoma. METHODS：Methylation-specific polymerase chain reaction （MSPCR） was used to examine the promo...AIM：To evaluate the diagnostic role of serum RASSF1A promoter hypermethylation in gastric and colorectal adenocarcinoma. METHODS：Methylation-specific polymerase chain reaction （MSPCR） was used to examine the promoter methylation status of the serum RASSF1A gene in 47 gastric adenocarcinoma patients, 45 colorectal adenocarcinoma patients, 60 patients with benign gastrointestinal disease （30 with benign gastric disease and 30 with benign colorectal disease）, and 30 healthy donor controls. Apaired study of RASSF1A promoter methylation status in primary tumor, adjacent normal tissue, and postopertive serum were conducted in 25 gastric and colorectal adenocarcinoma patients who later were underwent surgical therapy. RESULTS：The frequencies of detection of serum RASSF1A promoter hypermethylation in gastric （34.0%） and colorectal （28.9%） adenocarcinoma patients were significantly higher than those in patients with benign gastric （3.3%） or colorectal （6.7%） disease or in healthy donors （0%） （P 〈 0.01）. The methylation status of RASSF1A promoter in serum samples was consistent with that in paired primary tumors, and the MSPCR results for RASSF1A promoter methylation status in paired preoperative samples were consistent with those in postoperative serum samples. The serum RASSF1A promoter hypermethylation did not correlate with patient sex, age, tumor differentiation grade, surgical therapy, or serum carcinoembryonic antigen level. Although the serum RASSF1A promoter hypermethylation frequency tended to be higher in patients with distant metastases, there was no correlation between methylation status and metastasis. CONCLUSION：Aberrant CpG island methylation within the promoter region of RASSF1A is a promising biomarker for gastric and colorectal cancer.展开更多
基金We acknowledge funding from Science Foundation Ireland （grant # 12/IA/1667） and the Health Research Board （grant # HRA-POR-2013- 424）. In addition, we gratefully acknowledge the on-going research contributions from the Liver Transplant Unit at St. Vincent＇s University Hospital.
文摘The human liver is usually perceived as a non-immunological organ engaged primarily in metabolic, nutrient storage and detoxification activities. However, we now know that the healthy liver is also a site of complex immunological activity mediated by a diverse immune cell repertoire as well as non-hematopoietic cell populations. In the nondiseased liver, metabolic and tissue remodeling functions require elements of inflammation. This inflammation, in combination with regular exposure to dietary and microbial products, creates the potential for excessive immune activation. In this complex microenvironment, the hepatic immune system tolerates harmless molecules while at the same time remaining alert to possible infectious agents, malignant cells or tissue damage. Upon appropriate immune activation to challenge by pathogens or tissue damage, mechanisms to resolve inflammation are essential to maintain liver homeostasis. Failure to clear ＇dangerous＇ stimuli or regulate appropriately activated immune mechanisms leads to pathological inflammation and disrupted tissue homeostasis characterized by the progressive development of fibrosis, cirrhosis and eventual liver failure. Hepatic inflammatory mechanisms therefore have a spectrum of roles in the healthy adult liver; they are essential to maintain tissue and organ homeostasis and, when dysregulated, are key drivers of the liver pathology associated with chronic infection, autoimmunity and malignancy. In this review, we explore the changing perception of inflammation and inflammatory mediators in normal liver homeostasis and propose targeting of liver-specific immune regulation pathways as a therapeutic approach to treat liver disease.
文摘Hepatic fibrosis is a pathological lesion, characterized by the progressive accumulation of extracellularmatrix （ECM） in the perisinusoidal space and it is a major problem in chronic liver diseases. Phenotypicactivation of hepatic stellate cells （HSC） plays a central role in the progression of hepatic fibrosis. Retardation of proliferation and clearance of activated HSCs from the injured liver is an appropriate therapeuticstrategy for the resolution and treatment of hepatic fibrosis. Clearance of activated HSCs from the injuredliver by autophagy inhibitors, proapoptotic agents and senescence inducers with the high affinity towardthe activated HSCs may be the novel therapeutic strategy for the treatment of hepatic fibrosis in the nearfuture.
基金Supported by(in part)the Southampton National Institute for Health Research Biomedical Research Centre(Byrne CD)grants from the School of Medicine of the Verona University(Targher GT)
文摘Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease(CHD),abnormalities of cardiac function and structure(e.g.,left ventricular dysfunction and hypertrophy,and heart failure),valvular heart disease(e.g.,aortic valve sclerosis)and arrhythmias(e.g.,atrial fibrillation).Experimental evidence suggests that NAFLD itself,especially in its more severe forms,exacerbates systemic/hepatic insulin resistance,causes atherogenic dyslipidemia,and releases a variety of pro-inflammatory,pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications.Collectively,these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications.The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular,cardiac and arrhythmic complications,to briefly examine the putative biological mechanisms underlying this association,and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications.
基金This work was supported by the China Pharmaceutical University(grant number 3150120001 to XW)。
文摘Background:Since its discovery in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 2180000 people worldwide and has caused more than 150000 deaths as of April 16,2020.SARS-CoV-2,which is the virus causing coronavirus disease 2019(COVID-19),uses the angiotensin-converting enzyme 2(ACE2)as a cell receptor to invade human cells.Thus,ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection.This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.Methods:We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger(ages≤49 years)and older(ages>49 years)persons using two-sided Student's t test.We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson's correlation test.Results:ACE2 expression levels were the highest in the small intestine,testis,kidneys,heart,thyroid,and adipose tissue,and were the lowest in the blood,spleen,bone marrow,brain,blood vessels,and muscle.ACE2 showed medium expression levels in the lungs,colon,liver,bladder,and adrenal gland.ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue.In the skin,digestive system,brain,and blood vessels,ACE2 expression levels were positively associated with immune signatures in both males and females.In the thyroid and lungs,ACE2 expression levels were positively and negatively associated with immune signatures in males and females,respectively,and in the lungs they had a positive and a negative correlation in the older and younger groups,respectively.Conclusions:Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes,ages,and races equally.The different host immune responses to SARS-CoV-2 infection may partially explain why males and females,young and old persons infected with this vi
文摘AIM:To study secretion patterns of proand anti-in-flammatory cytokines, and activation of various cellular subsets of leukocytes in peripheral blood.METHODS: We have conducted a prospective obser-vational study. One hundred and eight patients with a diagnosis of acute pancreatitis and onset of the disease within last 72 h were included in this study. The mRNA expression of 25 different types of cytokines in white blood cells was determined by quantitative real time polymerase chain reaction. Levels of 8 different cytokines in blood serum were measured by enzymelinked immunosorbent assay. Clinical data and cytokine expression results were subjected to statistical analysis.RESULTS: Severe and necrotizing acute pancreatitis (AP) is characterized by the significant depletion of circulating lymphocytes. Severe acute pancreatitis is as-sociated with a typical systemic inflammatory response syndrome and over-expression of pro-inflammatory cy-tokines [interleukin (IL)-6, IL-8, macrophage migration inhibitory factor (MIF)]. Serum IL-6 and MIF concentra-tions are the best discriminators of severe and necrotiz-ing AP as well as possible fatal outcome during the early course of the disease. CONCLUSION: Deregulation of cellular immune sys-tem is a key event leading to severe and necrotizing AP. IL-6 and MIF could be used as early predictors of complications.
文摘Bone is the second most commonly transplanted tissue worldwide,with over four million operations using bone grafts or bone substitute materials annually to treat bone defects.However,significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma,cancer,infection and arthritis.Developing bioactive three-dimensional(3D)scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering(BTE).A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts.However,individual groups of materials including polymers,ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone.Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds.This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers,hydrogels,metals,ceramics and bio-glasses in BTE.Scaffold fabrication methodology,mechanical performance,biocompatibility,bioactivity,and potential clinical translations will be discussed.
基金Supported by The National Council on Science and Technology (CONACYT:85675 and 79628)Institute of Public Health(POA: 2008-2010)Research Office of Veracruzana University and Public Education Secretariat(SEP-PROMEP-UV:PTC-319)
文摘AIM:To assess expression of matrix metalloproteinases 2(MMP2)and MMP9 in gastric cancer,superficial gastritis and normal mucosa,and to measure metalloproteinase activity.METHODS:MMP2 and MMP9 mRNA expression was determined by quantitative real-time polymerase chain reaction.Normalization was carried out using three different factors.Proteins were analyzed by quantitative gelatin zymography(qGZ).RESULTS:18S ribosomal RNA(18SRNA)was very highly expressed,while hypoxanthine ribosyltransferase-1(HPRT-1)was moderately expressed.MMP2 was highly expressed,while MMP9 was not detected or lowly expressed in normal tissues,moderately or highly expressed in gastritis and highly expressed in cancer.Relative expression of 18SRNA and HPRT-1 showed no significant differences.Significant differences in MMP2 and MMP9 were found between cancer and normal tissue,but not between gastritis and normal tissue.Absolute quantification of MMP9 echoed this pattern,but differential expression of MMP2 proved conflictive.Analysis by qGZ indicated significant differences between cancer and normal tissue in MMP-2,total MMP-9,250 and 110 kDa bands.CONCLUSION:MMP9 expression is enhanced in gastric cancer compared to normal mucosa;interpretation of differential expression of MMP2 is difficult to establish.
基金supported by National Key R&D Program of China (2016YFA0300903, 2016YFA0300802, 2014CB932500 and 2016YFA0200101)National Natural Science Foundation of China (51522201, 11474006, 11327902, 11234001, 21525310, 91433102 and 21573186)+1 种基金Postdoctoral Innovative Personnel Support Program (BX201700014)National Program for Thousand Young Talents of China and the Institute for Basic Science (IBS-R019-D1) of Korea
文摘A foundation of the modern technology that uses single-crystal silicon has been the growth of highquality single-crystal Si ingots with diameters up to 12 inches or larger. For many applications of graphene, large-area high-quality(ideally of single-crystal) material will be enabling. Since the first growth on copper foil a decade ago, inch-sized single-crystal graphene has been achieved. We present here the growth, in 20 min, of a graphene film of(5 ×50) cm^2 dimension with >99% ultra-highly oriented grains.This growth was achieved by:(1) synthesis of metre-sized single-crystal Cu(1 1 1) foil as substrate;(2)epitaxial growth of graphene islands on the Cu(1 1 1) surface;(3) seamless merging of such graphene islands into a graphene film with high single crystallinity and(4) the ultrafast growth of graphene film.These achievements were realized by a temperature-gradient-driven annealing technique to produce single-crystal Cu(1 1 1) from industrial polycrystalline Cu foil and the marvellous effects of a continuous oxygen supply from an adjacent oxide. The as-synthesized graphene film, with very few misoriented grains(if any), has a mobility up to ~23,000 cm^2 V^(-1)s^(-1)at 4 K and room temperature sheet resistance of ~230 Ω/□. It is very likely that this approach can be scaled up to achieve exceptionally large and high-quality graphene films with single crystallinity, and thus realize various industrial-level applications at a low cost.
文摘The red blood cell distribution width(RDW) is a simple, rapid, inexpensive and straightforward hematological parameter, reflecting the degree of anisocytosis in vivo. The currently available scientific evidence suggests that RDW assessment not only predicts the risk of adverse outcomes(cardiovascular and all-cause mortality, hospitalization for acute decompensation or worsened left ventricular function) in patients with acute and chronic heart failure(HF), but is also a significant and independent predictor of developing HF in patients free of this condition. Regarding the biological interplay between impaired hematopoiesis and cardiac dysfunction, many of the different conditions associated with increased heterogeneity of erythrocyte volume(i.e., ageing, inflammation, oxidative stress, nutritional deficiencies and impaired renal function), may be concomitantly present in patients with HF, whilst anisocytosis may also directly contribute to the development and worsening of HF. In conclusion, the longitudinal assessment of RDW changes over time may be considered an efficient measure to help predicting the risk of both development and progression of HF.
文摘To assess “predictors” of esophageal varices (EV) and variceal bleeding using non-invasive markers in Albanian patients diagnosed with liver cirrhosis. METHODSOne hundred thirty-nine newly diagnosed cirrhotic patients without variceal bleeding were included in this analysis. Model for end-stage liver disease (MELD), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AST/ALT), AST to platelet ratio index (APRI), platelet count to spleen diameter (PC/SD), fibrosis-4-index (FIB-4), fibrosis index (FI) and King’s Score were measured for all participants. All patients underwent endoscopic assessment within two days of hospitalization. The major end point was the first esophageal variceal bleeding (EVB) event. The diagnostic performance of “predictors” for the presence of EV and EVB were assessed by sensitivity and specificity values obtained from the receiver operating characteristics procedure. RESULTSFIB-4 was the only strong and significant “predictor” of esophageal varices (multivariable-adjusted OR = 1.57 for one unit increment; 95%CI: 1.15-2.14). Furthermore, a cut-off value of 3.23 for FIB-4 was a significant predictor of esophageal varices, with a sensitivity of 72%, a specificity of 58% and a proportion of area under the curve (AUC) of 66% (P = 0.01). During the follow-up (median: 31.5 mo; interquartile range: 11-59 mo), 34 patients (24%) experienced a first EVB. FIB-4 was a poor predictor of EVB (the AUC was only 51%) for a cut-off value of 5.02. Furthermore, the AUC of AST/ALT, APRI, PC/SD, FI, MELD and King’s Score ranged from 45% to 55%. None of the non-invasive markers turned out to be a useful predictor of EVB. CONCLUSIONDespite the low diagnostic accuracy, FIB-4 appears the most efficient non-invasive liver fibrosis marker which can be used as an initial screening tool for cirrhotic patients.
文摘Baicalein, wogonin, and their glycosides are major bioactive compounds found in the medicinal plant Scutellaria baicalensis Georgi. These flavones can induce apoptosis in a variety of cancer cell lines but have no effect on normal cells. Furthermore, they have many additional benefits for human health, such as antioxidant, antiviral, and liver-protective properties. Here, we report the isolation and characterization of two CYP450 enzymes, SbCYP82D1.1 and SbCYP82D2, which function as the flavone 6-hydroxylase （F6H） and flavone 8-hydroxylase （F8H）, respectively, in S. baicalensis. SbCYP82D1.1 has broad substrate speci- ficity for flavones such as chrysin and apigenin and is responsible for biosynthesis of baicalein and scutel- larein in roots and aerial parts of S. baicalensis, respectively. When the expression of SbCYP82D1.1 is knocked down, baicalin and baicalein levels are reduced significantly while chrysin glycosides accumulate in hairy roots. SbCYP82D2 is an F8H with high substrate specificity, accepting only chrysin as its substrate to produce norwogonin, although minor 6-hydroxylation activity can also be detected. Phylogenetic analysis suggested that SbCYP82D2 might have evolved from SbCYP82D1.1 via gene duplication followed by neofunctionalization, whereby the ancestral F6H activity is partially retained in the derived SbCYP82D2.
基金Supported by Comisión Nacional de Investigación Científica y Tecnológica-Fondos de Financiamiento de Centros de Investigación en áreas Prioritarias,No.15130011(to Quest AF)Fondo Nacional de Desarrollo Científico y Tecnológico,No.1170925(to Quest AF)and No.1171615(to Valenzuela MA)Fondo para la Investigación en Odontología Universidad de Chile,No.17/020(to Bravo D)
文摘Helicobacter pylori(H. pylori) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gastro-intestinal diseases, but also with extra gastric diseases. Despite such associations, the bacterium frequently persists in the human host without inducing disease, and it has been suggested that H. pylori may also play a beneficial role in health. To understand how H. pylori can produce such diverse effects in the human host, several studies have focused on understanding the local and systemic effects triggered by this bacterium. One of the main mechanisms by which H. pylori is thought to damage the host is by inducing local and systemic inflammation. However, more recently, studies are beginning to focus on the effects of H. pylori and its metabolism on the gastric and intestinal microbiome. The objective of this review is to discuss how H. pylori has co-evolved with humans, how H. pylori presence is associated with positive and negative effects in human health and how inflammation and/or changes in the microbiome are associated with the observed outcomes.
基金Supported by National Medical Research Council IRG and NUHS Bench-to-Bedside grants(to Sethi G)grants from the National Medical Research Council of Singapore(R-713-000-177-511)+1 种基金the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiative to Cancer Science Institute of SingaporeNational University of Singapore and by the NCIS Yong Siew Yoon Research Grant through donations from the Yong Loo Lin Trust(to Kumar AP)
文摘Frequent activation of phosphatidylinositol-3 kinases(PI3K)/Akt/m TOR signaling pathway in gastric cancer(GC) is gaining immense popularity with identification of mutations and/or amplifications of PIK3 CA gene or loss of function of PTEN,a tumor suppressor protein,to name a few; both playing a crucial role in regulating this pathway. These aberrations result in dysregulation of this pathway eventually leading to gastric oncogenesis,hence,there is a need for targeted therapy for more effective anticancer treatment. Several inhibitors are currently in either preclinical or clinical stages for treatment of solid tumors like GC. With so many inhibitors under development,further studies on predictive biomarkers are needed to measure the specificity of any therapeutic intervention. Herein,we review the common dysregulation of PI3K/Akt/m TOR pathway in GC and the various types of single or dual pathway inhibitors under development that might have a superior role in GC treatment. We also summarize the recent developments in identification of predictive biomarkers and propose use of predictive biomarkers to facilitate more personalized cancer therapy with effective PI3K/Akt/m TOR pathway inhibition.
文摘The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive （second generation） biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials （third generation） are designed to be not only osteo- conductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineer- ing and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental ＂origin＂ require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.
基金National Key R&D Program of China (2018YFC1706200,2018YFD1000701-4)the National Natural Science Foundation of China (31870282, 31700268 and 31788103)+2 种基金the Fund of Chinese Academy of Sciences (QYZDY-SSW-SMC026 and 153D31KYSB20160074)the Chenshan Special Fund for Shanghai Landscaping Administration Bureau Program (G182401, G172402, G182402, G192413, and G192414)the CAS/JIC and Center of Excellence for Plant and Microbial Sciences (CEPAMS) joint foundation through support to Q.Z., X.Y.C., J.Y., and C.M. Q.Z. and J.Y. were also supported by the Youth Innovation Promotion Association, Chinese Academy of Sciences.
文摘Scutellaria baicalensis Georgi is important in Chinese traditional medicine where preparations of dried roots,"Huang Qin," are used for liver and lung complaints and as complementary cancer treatments. We report a high-quality reference genome sequence for S. baicalensis where 93% of the 408.14-Mb genome has been assembled into nine pseudochromosomes with a super-N50 of 33.2 Mb. Comparison of this sequence with those of closely related species in the order Lamiales, sesamum indicum and Salvia splendens,revealed that a specialized metabolic pathway for the synthesis of 4'-deoxyflavone bioactives evolved in the genus Scu-tellaria. We found that the gene encoding a specific cinnamate coenzyme A ligase likely obtained its newfunc- tion following recent mutations, and that four genes encoding enzymes in the 4'-deoxyflavone pathway are present as tandem repeats in the genome of S. baicalensis. Further analyses revealed that gene duplications, segmental duplication, gene amplification, and point mutations coupled to gene neo- and subfunctionaliza-tions were involved in the evolution of 4'-deoxyflavone synthesis in the genus Scutellaria. Our study not only provides significant insight into the evolution of specific flavone biosynthetic pathways in the mint family, Lamiaceae, but also will facilitate the development of tools for enhancing bioactive productivity by metabolic engineering in microbes or by molecular breeding in plants. The reference genome of S. baicalensis is also useful for improving the genome assemblies for other members of the mint family and offers an important foundation for decoding the synthetic pathways of bioactive compounds in medicinal plants.
基金supported by the National Natural Science Foundation of China (81472757, 81773283, 81361140344, 81600175 and 81671815)the National Basic Research Program of China (973 Program, 2013CB932502)
文摘There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels,and molecular mediators directed against harmful stimuli, is closely associated with many human diseases.As a result, biomimetic nanoparticles mimicking immune cells can help achieve molecular imaging and precise drug delivery to these inflammatory sites. This review is focused on inflammation-targeting biomimetic nanoparticles and will provide an in-depth look at the design of these nanoparticles to maximize their benefits for disease diagnosis and treatment.
文摘AIM: To assess the impact of percutaneous cardiac support in cardiogenic shock(CS) complicating acute myocardial infarction(AMI), treated with percutaneous coronary intervention. METHODS: We selected all of the studies published from January 1st, 1997 to May 15 st, 2015 that compared the following percutaneous mechanical support in patients with CS due to AMI undergoing myocardial revascularization:(1) intra-aortic balloon pump(IABP) vs Medical therapy;(2) percutaneous left ventricular assist devices(PLVADs) vs IABP;(3) complete extracorporeal life support with extracorporeal membrane oxygenation(ECMO) plus IABP vs IABP alone; and(4) ECMO plus IABP vs ECMO alone, in patients with AMI and CS undergoing myocardial revascularization. We evaluated the impact of the support devices on primary and secondary endpoints. Primary endpoint was the inhospital mortality due to any cause during the same hospital stay and secondary endpoint late mortality at 6-12 moof follow-up. RESULTS: One thousand two hundred and seventytwo studies met the initial screening criteria. After detailed review, only 30 were selected. There were 6 eligible randomized controlled trials and 24 eligible observational studies totaling 15799 patients. We found that the inhospital mortality was:(1) significantly higher with IABP support vs medical therapy(RR = +15%, P = 0.0002);(2) was higher, although not significantly, with PLVADs compared to IABP(RR = +14%, P = 0.21); and(3) significantly lower in patients treated with ECMO plus IABP vs IABP(RR =-44%, P = 0.0008) or ECMO(RR =-20%, P = 0.006) alone. In addition, Trial Sequential Analysis showed that in the comparison of IABP vs medical therapy, the sample size was adequate to demonstrate a significant increase in risk due to IABP. CONCLUSION: Inhospital mortality was significantly higher with IABP vs medical therapy. PLVADs did not reduce early mortality. ECMO plus IABP significantly reduced inhospital mortality compared to IABP.
基金Engineering and Physical Sciences Research Council(EPSRC)(EP/L00044X/1)
文摘Over the last 20 years, silicon photonics has revolutionized the field of integrated optics, providing a novel and powerful platform to build mass-producible optical circuits. One of the most attractive aspects of silicon photonics is its ability to provide extremely small optical components, whose typical dimensions are an order of magnitude smaller than those of optical fiber devices. This dimension difference makes the design of fiberto-chip interfaces challenging and, over the years, has stimulated considerable technical and research efforts in the field. Fiber-to-silicon photonic chip interfaces can be broadly divided into two principle categories:in-plane and out-of-plane couplers. Devices falling into the first category typically offer relatively high coupling efficiency, broad coupling bandwidth(in wavelength), and low polarization dependence but require relatively complex fabrication and assembly procedures that are not directly compatible with wafer-scale testing.Conversely, out-of-plane coupling devices offer lower efficiency, narrower bandwidth, and are usually polarization dependent. However, they are often more compatible with high-volume fabrication and packaging processes and allow for on-wafer access to any part of the optical circuit. In this paper, we review the current state-of-the-art of optical couplers for photonic integrated circuits, aiming to give to the reader a comprehensive and broad view of the field, identifying advantages and disadvantages of each solution. As fiber-to-chip couplers are inherently related to packaging technologies and the co-design of optical packages has become essential, we also review the main solutions currently used to package and assemble optical fibers with silicon-photonic integrated circuits.
文摘AIM：To evaluate the diagnostic role of serum RASSF1A promoter hypermethylation in gastric and colorectal adenocarcinoma. METHODS：Methylation-specific polymerase chain reaction （MSPCR） was used to examine the promoter methylation status of the serum RASSF1A gene in 47 gastric adenocarcinoma patients, 45 colorectal adenocarcinoma patients, 60 patients with benign gastrointestinal disease （30 with benign gastric disease and 30 with benign colorectal disease）, and 30 healthy donor controls. Apaired study of RASSF1A promoter methylation status in primary tumor, adjacent normal tissue, and postopertive serum were conducted in 25 gastric and colorectal adenocarcinoma patients who later were underwent surgical therapy. RESULTS：The frequencies of detection of serum RASSF1A promoter hypermethylation in gastric （34.0%） and colorectal （28.9%） adenocarcinoma patients were significantly higher than those in patients with benign gastric （3.3%） or colorectal （6.7%） disease or in healthy donors （0%） （P 〈 0.01）. The methylation status of RASSF1A promoter in serum samples was consistent with that in paired primary tumors, and the MSPCR results for RASSF1A promoter methylation status in paired preoperative samples were consistent with those in postoperative serum samples. The serum RASSF1A promoter hypermethylation did not correlate with patient sex, age, tumor differentiation grade, surgical therapy, or serum carcinoembryonic antigen level. Although the serum RASSF1A promoter hypermethylation frequency tended to be higher in patients with distant metastases, there was no correlation between methylation status and metastasis. CONCLUSION：Aberrant CpG island methylation within the promoter region of RASSF1A is a promising biomarker for gastric and colorectal cancer.
