AIM To analyse the effect of mechanical bowel preparation vs no mechanical bowel preparation on outcome in patients undergoing elective colorectal surgery.METHODS Meta-analysis of randomised controlled trials and obse...AIM To analyse the effect of mechanical bowel preparation vs no mechanical bowel preparation on outcome in patients undergoing elective colorectal surgery.METHODS Meta-analysis of randomised controlled trials and observational studies comparing adult patients receiving mechanical bowel preparation with those receiving no mechanical bowel preparation, subdivided into those receiving a single rectal enema and those who received no preparation at all prior to elective colorectal surgery. RESULTS A total of 36 studies(23 randomised controlled trials and 13 observational studies) including 21568 patients undergoing elective colorectal surgery were included. When all studies were considered, mechanical bowel preparation was not associated with any significant difference in anastomotic leak rates(OR = 0.90, 95%CI: 0.74 to 1.10, P = 0.32), surgical site infection(OR = 0.99, 95%CI: 0.80 to 1.24, P = 0.96), intraabdominal collection(OR = 0.86, 95%CI: 0.63 to 1.17, P = 0.34), mortality(OR = 0.85, 95%CI: 0.57 to 1.27, P = 0.43), reoperation(OR = 0.91, 95%CI: 0.75 to 1.12, P = 0.38) or hospital length of stay(overall mean difference 0.11 d, 95%CI:-0.51 to 0.73, P = 0.72), when compared with no mechanical bowel preparation, nor when evidence from just randomized controlledtrials was analysed. A sub-analysis of mechanical bowel preparation vs absolutely no preparation or a single rectal enema similarly revealed no differences in clinical outcome measures. CONCLUSION In the most comprehensive meta-analysis of mechanical bowel preparation in elective colorectal surgery to date, this study has suggested that the use of mechanical bowel preparation does not affect the incidence of postoperative complications when compared with no preparation. Hence, mechanical bowel preparation should not be administered routinely prior to elective colorectal surgery.展开更多
Age-related macular degeneration(AMD)is the leading cause of irreversible blindness in adults over 50 years old.Genetic,epidemiological,and molecular studies are beginning to unravel the intricate mechanisms underlyin...Age-related macular degeneration(AMD)is the leading cause of irreversible blindness in adults over 50 years old.Genetic,epidemiological,and molecular studies are beginning to unravel the intricate mechanisms underlying this complex disease,which implicate the lipid-cholesterol pathway in the pathophysiology of disease development and progression.Many of the genetic and environmental risk factors associated with AMD are also associated with other complex degenerative diseases of advanced age,including cardiovascular disease(CVD).In this review,we present epidemiological findings associating AMD with a variety of lipid pathway genes,cardiovascular phenotypes,and relevant environmental exposures.Despite a number of studies showing significant associations between AMD and these lipid/cardiovascular factors,results have been mixed and as such the relationships among these factors and AMD remain controversial.It is imperative that researchers not only tease out the various contributions of such factors to AMD development but also the connections between AMD and CVD to develop optimal precision medical care for aging adults.展开更多
Postoperative sleep disturbance is a common occurrence with significant adverse effects on patients including delayed recovery,impairment of cognitive function,pain sensitivity and cardiovascular events.The developmen...Postoperative sleep disturbance is a common occurrence with significant adverse effects on patients including delayed recovery,impairment of cognitive function,pain sensitivity and cardiovascular events.The development of postoperative sleep disturbance is multifactorial and involves the surgical inflammatory response,the severity of surgical trauma,pain,anxiety,the use of anesthetics and environmental factors such as nocturnal noise and light levels.Many of these factors can be managed perioperatively to minimize the deleterious impact on sleep.Pharmacological and non-pharmacological treatment strategies for postoperative sleep disturbance include dexmedetomidine,zolpidem,melatonin,enhanced recovery after surgery(ERAS) protocol and controlling of environmental noise and light levels.It is likely that a combination of pharmacological and non-pharmacological therapies will have the greatest impact;however,further research is required before their use can be routinely recommended.展开更多
The eukaryotic actin cytoskeleton is required for numerous cellular processes, including cell shape, development and movement, gene expression and signal transduction, and response to biotic and abiotic stress. In rec...The eukaryotic actin cytoskeleton is required for numerous cellular processes, including cell shape, development and movement, gene expression and signal transduction, and response to biotic and abiotic stress. In recent years,research in both plants and animal systems have described a function for actin as the ideal surveillance platform, linking the function and activity of primary physiological processes to the immune system. In this review, we will highlight recent advances that have defined the regulation and breadth of function of the actin cytoskeleton as a network required for defense signaling following pathogen infection. Coupled with an overview of recent work demonstrating specific targeting of the plant actin cytoskeleton by a diversity of pathogens,including bacteria, fungi and viruses, we will highlight the importance of actin as a key signaling hub in plants, one that mediates surveillance of cellular homeostasis and the activation of specific signaling responses following pathogen perception. B4 ased on the studies highlighted herein, we propose a working model that posits changes in actin filament organization is in and of itself a highly specific signal, which induces, regulates and physically directs stimulus-specific signaling processes, most importantly, those associated with response to pathogens.展开更多
BACKGROUND Colorectal cancer(CRC)is the second leading cause of all cancer related deaths in the United States and Europe.Although the incidence has been decreasing for individuals’≥50,it has been on the rise for in...BACKGROUND Colorectal cancer(CRC)is the second leading cause of all cancer related deaths in the United States and Europe.Although the incidence has been decreasing for individuals’≥50,it has been on the rise for individuals<50.AIM To identify potential risk factors for early-onset CRC.METHODS A population-based cohort analysis using a national database,Explorys,screened all patients with an active electronic medical record from January 2012 to December 2016 with a diagnosis of CRC.Subgroups were stratified based on age(25–49 years vs≥50 years).Demographics,comorbidities,and symptom profiles were recorded and compared between both age groups.Furthermore,the younger group was also compared with a control group consisting of individuals aged 25-49 years within the same timeframe without a diagnosis of CRC.Twentydata points for CRC related factors were analyzed to identify potential risk factors specific to early-onset CRC.RESULTS A total of 68860 patients were identified with CRC,of which 5710(8.3%)were younger than 50 years old,with 4140(73%)between 40-49 years of age.Multivariable analysis was reported using odds ratio(OR)with 95%CI and demonstrated that several factors were associated with an increased risk of CRC in the early-onset group versus the later-onset group.These factors included:African-American race(OR 1.18,95%CI:1.09-1.27,P<0.001),presenting symptoms of abdominal pain(OR 1.82,95%CI:1.72-1.92,P<0.001),rectal pain(OR 1.50,95%CI:1.28-1.77,P<0.001),altered bowel function(OR 1.12,95%CI:1.05-1.19,P=0.0005),having a family history of any cancer(OR 1.78,95%CI:1.67-1.90,P<0.001),gastrointestinal(GI)malignancy(OR 2.36,95%CI:2.18-2.55,P<0.001),polyps(OR 1.41,95%CI:1.08-1.20,P<0.001),and obesity(OR 1.14,95%CI:1.08-1.20,P<0.001).Comparing the early-onset cohort versus the control group,factors that were associated with an increased risk of CRC were:male gender(OR 1.34,95%CI:1.27-1.41),P<0.001),Caucasian(OR 1.48,95%CI:1.40-1.57,P<0.001)and African-American race(OR 1.25,95%CI:1.17-1.35,P<0.001),presenting 展开更多
Acute myeloid leukemia(AML)is the most common form of acute leukemia in adults and the second most common form of acute leukemia in children.Despite this,very little improvement in survival rates has been achieved ove...Acute myeloid leukemia(AML)is the most common form of acute leukemia in adults and the second most common form of acute leukemia in children.Despite this,very little improvement in survival rates has been achieved over the past few decades.This is partially due to the heterogeneity of AML and the need for more targeted therapeutics than the traditional cytotoxic chemotherapies that have been a mainstay in therapy for the past 50 years.In the past 20 years,research has been diversifying the approach to treating AML by investigating molecular pathways uniquely relevant to AML cell proliferation and survival.Here we review the development of novel therapeutics in targeting apoptosis,receptor tyrosine kinase(RTK)signaling,hedgehog(HH)pathway,mitochondrial function,DNA repair,and c-Myc signaling.There has been an impressive effort into better understanding the diversity of AML cell characteristics and here we highlight important preclinical studies that have supported therapeutic development and continue to promote new ways to target AML cells.In addition,we describe clinical investigations that have led to FDA approval of new targeted AML therapies and ongoing clinical trials of novel therapies targeting AML survival pathways.We also describe the complexity of targeting leukemia stem cells(LSCs)as an approach to addressing relapse and remission in AML and targetable pathways that are unique to LSC survival.This comprehensive review details what we currently understand about the signaling pathways that support AML cell survival and the exceptional ways in which we disrupt them.展开更多
Gallbladder cancer is a rare,aggressive malignancy that has a poor overall prognosis.Effective treatment consists of early detection and surgical treatment.With the wide spread treatment of gallbladder disease with mi...Gallbladder cancer is a rare,aggressive malignancy that has a poor overall prognosis.Effective treatment consists of early detection and surgical treatment.With the wide spread treatment of gallbladder disease with minimally invasive techniques,the rate of incidental gallbladder cancer has seen an equitable rise along with stage migration towards earlier disease.Although the treatment remains mostly surgical,newer modalities such as regional therapy as well as directed therapy based on molecular medicine has led to improved outcomes in patients with advanced disease.We aim to summarize the management of gallbladder cancer along with the newer developments in this formidable disease process.展开更多
Novel applications of nanotechnology may lead to the release of engineered nanoparticles（ENPs）, which result in concerns over their potential environmental hazardous impact. It is essential for the research workers ...Novel applications of nanotechnology may lead to the release of engineered nanoparticles（ENPs）, which result in concerns over their potential environmental hazardous impact. It is essential for the research workers to be able to quantitatively characterise ENPs in the environment and subsequently to assist the risk assessment of the ENPs. This study hence explored the application of nanoparticle tracking system（NTA） to quantitatively describe the behaviour of the ENPs in natural sediment-water systems. The NTA allows the measurement of both particle number concentration（PNC） and particle size distribution（PSD） of the ENPs. The developed NTA method was applied to a range of gold and magnetite ENPs with a selection of surface properties. The results showed that the positively-charged ENPs interacted more strongly with the sediment than neutral and negatively-charged ENPs. It was also found that the citrate coated Au ENPs had a higher distribution percentage（53%） than 11-mercaptoundecanoic acid coated Au ENPs（20%） and citrate coated magnetite ENPs（21%）. The principles of the electrostatic interactions between hard（and soft） acids and bases（HSAB） are used to explain such behaviours; the hard base coating（i.e. citrate ions） will interact more strongly with hard acid（i.e. magnetite） than soft acid（i.e. gold）.The results indicate that NTA is a complementary method to existing approaches to characterise the fate and behaviour of ENPs in natural sediment.展开更多
The tumor microenvironment(TME) is complex and constantly evolving. This is due, in part, to the crosstalk between tumor cells and the multiple cell types that comprise the TME, which results in a heterogeneous popula...The tumor microenvironment(TME) is complex and constantly evolving. This is due, in part, to the crosstalk between tumor cells and the multiple cell types that comprise the TME, which results in a heterogeneous population of tumor cells and TME cells. This review will focus on two stromal cell types, the cancerassociated adipocyte(CAA) and the cancer-associated fibroblast(CAF). In the clinic, the presence of CAAs and CAFs in the TME translates to poor prognosis in multiple tumor types. CAAs and CAFs have an activated phenotype and produce growth factors, inflammatory factors, cytokines, chemokines, extracellular matrix components, and proteases in an accelerated and aberrant fashion. Through this activated state, CAAs and CAFs remodel the TME, thereby driving all aspects of tumor progression, including tumor growth and survival, chemoresistance, tumor vascularization, tumor invasion, and tumor cell metastasis. Similarities in the tumorpromoting functions of CAAs and CAFs suggest that a multipronged therapeutic approach may be necessary to achieve maximal impact on disease. While CAAs and CAFs are thought to arise from tissues adjacent to the tumor, multiple alternative origins for CAAs and CAFs have recently been identified. Recent studies from our lab and others suggest that the hematopoietic stem cell, through the myeloid lineage, may serve as a progenitor for CAAs and CAFs. We hypothesize that the multiple origins of CAAs and CAFs may contribute to the heterogeneity seen in the TME. Thus, a better understanding of the origin of CAAs and CAFs, how this origin impacts their functions in the TME, and thetemporal participation of uniquely originating TME cells may lead to novel or improved anti-tumor therapeutics.展开更多
AIM To investigate the relationship between vitamin D and liver fibrosis in hepatitis C-monoinfected or hepatitis C virus(HCV)-human immunodeficiency virus(HIV) coinfected patients. METHODS Pertinent studies were loca...AIM To investigate the relationship between vitamin D and liver fibrosis in hepatitis C-monoinfected or hepatitis C virus(HCV)-human immunodeficiency virus(HIV) coinfected patients. METHODS Pertinent studies were located by a library literature search in PubM ed/Embase/Cochrane/Scopus/LILACS by two individual reviewers. Inclusion criteria:(1) studies with patients with HCV or co-infected HCV/HIV;(2) studies with patients ≥ 18 years old;(3) studies that evaluated liver fibrosis stage, only based on liver biopsy; and(4) studies that reported serum or plasma 25(OH)D levels. Studies that included pediatric patients, other etiologies of liver disease, or did not use liver biopsy for fibrosis evaluation, or studies with inadequate data were excluded. Estimated measures of association reported in the literature, as well as corresponding measures of uncertainty, were recorded and corresponding odds ratios with 95%CI were included in a meta-analysis. RESULTS The pooled data of this systematic review showed that 9 of the 12 studies correlated advanced liver disease defined as a Metavir value of F3/4 with 25(OH) D level insufficiency. The meta-analysis indicated a significant association across studies.CONCLUSION Low vitamin D status is common in chronic Hepatitis C patients and is associated with advanced liver fibrosis.展开更多
The DNA topoisomerase enzymes are essential to cell function and are found ubiquitously in all domains of life. The various topoisomerase enzymes perform a wide range of functions related to the maintenance of DNA top...The DNA topoisomerase enzymes are essential to cell function and are found ubiquitously in all domains of life. The various topoisomerase enzymes perform a wide range of functions related to the maintenance of DNA topology during DNA replication, and transcription are the targets of a wide range of antimicrobial and cancer chemotherapeutic agents. Natural product-derived agents, such as the camptothecin, anthracycline, and podophyllotoxin drugs, have seen broad use in the treatment of many types of cancer. Selective targeting of the topoisomerase enzymes for cancer treatment continues to be a highly active area of basic and clinical research. The focus of this review will be to summarize the current state of the art with respect to clinically used topoisomerase inhibitors for targeted cancer treatment and to discuss the pharmacology and chemistry of promising new topoisomerase inhibitors in clinical and preclinical development.展开更多
The unique structure of zero-dimensional(0D)perovskite-analogues has attracted a great amount of research interest in recent years.To date,the current compositional library of 0D perovskites is largely limited to the ...The unique structure of zero-dimensional(0D)perovskite-analogues has attracted a great amount of research interest in recent years.To date,the current compositional library of 0D perovskites is largely limited to the lead-based Cs4PbX6(X=Cl,Br,and I)systems.In this work,we report a new synthesis of lead-free 0D Cs3BiX6(X=Cl,Br)perovskite-analogue nanocrystals(NCs)with a uniform cubic shape.We observe a broad photoluminescence peak centered at 390 nm for the 0D Cs3BiCl6 NCs at low temperatures.This feature originates from a self-trapped exciton mechanism.In situ thermal stability studies show that Cs3BiX6 NCs remain stable upon heating up to 200°C without crystal structural degradation.Moreover,we demonstrate that the Cs3BiX6 NCs can transform into other bismuth-based perovskite-analogues via facile anion exchange or metal ion insertion reactions.Our study presented here offers the opportunity for further understanding of the structure-property relationship of 0D perovskite-analogue materials,leading toward their future optoelectronic applications.展开更多
Assessing the adsorption properties of nanoporous materials and determining their structural characterization is critical for progressing the use of such materials for many applications, including gas storage. Gas ads...Assessing the adsorption properties of nanoporous materials and determining their structural characterization is critical for progressing the use of such materials for many applications, including gas storage. Gas adsorption can he used for this characterization because it assesses a broad range of pore sizes, from micropore to mesopore. In the past 20 years, key developments have been achieved both in the knowledge of the adsorption and phase behavior of fluids in ordered nanoporous materials and in the creation and advancement of state-of-the-art approaches based on statistical mechanics, such as molecular sim- ulation and density functional theory. Together with high-resolution experimental procedures for the adsorption of suhcritical and supercritical fluids, this has led to significant advances in physical adsorp- tion textural characterization. In this short, selective review paper, we discuss a few important and central features of the underlying adsorption mechanisms of fluids in a variety of nanoporous materials with well-defined pore structure. The significance of these features for advancing physical adsorption charac- terization and gas storage applications is also discussed.展开更多
AIM To compare outcomes in patients undergoing rectal resection by robotic total meso-rectal excision(RTME) vs laparoscopic total meso-rectal excision(LTME).METHODS Standard medical electronic databases such as Pub-Me...AIM To compare outcomes in patients undergoing rectal resection by robotic total meso-rectal excision(RTME) vs laparoscopic total meso-rectal excision(LTME).METHODS Standard medical electronic databases such as Pub-Med, MEDLINE, EMBASE and Scopus were searched to find relevant articles. The data retrieved from all types of included published comparative trials in pati-ents undergoing RTME vs LTME was analysed using the principles of meta-analysis. The operative, post-operative and oncological outcomes were evaluated to assess the effectiveness of both techniques of TME. The summated outcome of continuous variables was expressed as standardized mean difference(SMD) and dichotomous data was presented in odds ratio(OR).RESULTS One RCT(ROLARR trial) and 27 other comparative studies reporting the non-oncological and oncological outcomes following RTME vs LTME were included in this review. In the random effects model analysis using the statistical software Review Manager 5.3, the RTME was associated with longer operation time(SMD, 0.46; 95%CI: 0.25, 0.67; z = 4.33; P = 0.0001), early passage of first flatus(P = 0.002), lower risk of conversion(P = 0.00001) and shorter hospitalization(P = 0.01). The statistical equivalence was seen between RTME and LTME for non-oncological variables like blo-od loss, morbidity, mortality and re-operation risk. The oncological variables such as recurrence(P = 0.96), number of harvested nodes(P = 0.49) and positive circumferential resection margin risk(P = 0.53) were also comparable in both groups. The length of distal resection margins was similar in both groups. CONCLUSION RTME is feasible and oncologically safe but failed to demonstrate any superiority over LTME for many sur-gical outcomes except early passage of flatus, lower risk of conversion and shorter hospitalization.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)i...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy.Mechanisms of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell invasion.AIM To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19.METHODS ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel classifiers.RESULTS ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes.Strikingly,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis.ACE2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum.Hepatic ACE2 levels are also increased in COVID-19 pa展开更多
Primary molar ankylosis with infraocclusion can retard dental arch development and cause dental asymmetry. Despite its widespread prevalence, little is known about its molecular etiology and pathogenesis. To address t...Primary molar ankylosis with infraocclusion can retard dental arch development and cause dental asymmetry. Despite its widespread prevalence, little is known about its molecular etiology and pathogenesis. To address this, RNA sequencing was used to generate transcriptomes of furcal bone from infraoccluded(n = 7) and non-infraoccluded(n = 9) primary second molars, all without succeeding biscuspids. Of the 18 529 expressed genes, 432(2.3%) genes were differentially expressed between the two groups(false discovery rate < 0.05). Hierarchical clustering and principal component analysis showed clear separation in gene expression between infraoccluded and non-infraoccluded samples. Pathway analyses indicated that molar ankylosis is associated with the expression of genes consistent with the cellular inflammatory response and epithelial cell turnover. Independent validation using six expressed genes by immunohistochemical analysis demonstrated that the corresponding proteins are strongly expressed in the developing molar tooth germ, in particular the dental follicle and inner enamel epithelium. The descendants of these structures include the periodontal ligament, cementum, bone and epithelial rests of Malassez;tissues that are central to the ankylotic process.We therefore propose that ankylosis involves an increased inflammatory response associated with disruptions to the developmental remnants of the dental follicle and epithelial rests of Malassez.展开更多
In the late 1980s the first laparoscopic cholecystectomies were performed prompting a sudden rise in technological innovations as the benefits and feasibility of minimal access surgery became recognised.Monocular lapa...In the late 1980s the first laparoscopic cholecystectomies were performed prompting a sudden rise in technological innovations as the benefits and feasibility of minimal access surgery became recognised.Monocular laparoscopes provided only two-dimensional(2D) viewing with reduced depth perception and contributed to an extended learning curve.Attention turned to producing a usable three-dimensional(3D) endoscopic view for surgeons;utilising different technologies for image capture and image projection.These evolving visual systems have been assessed in various research environments with conflicting outcomes of success and usability,and no overall consensus to their benefit.This review article aims to provide an explanation of the different types of technologies,summarise the published literature evaluating 3D vs 2D laparoscopy,to explain the conflicting outcomes,and discuss the current consensus view.展开更多
Social determinants of health(SDOH)affect quality of life.We investigated SDOH impacts on self-perceived resilience among people with adult congenital heart disease(ACHD).Secondary analysis of data from two com-plemen...Social determinants of health(SDOH)affect quality of life.We investigated SDOH impacts on self-perceived resilience among people with adult congenital heart disease(ACHD).Secondary analysis of data from two com-plementary studies:a survey study conducted May 2021–June 2022 and a qualitative study conducted June 2020–August 2021.Resilience was assessed through CD-RISC10 score(range 0–40,higher scores reflect greater self-perceived resilience)and interview responses.Sociodemographic and SDOH(education,employment,living situa-tion,monetary stability,financial dependency,area deprivation index)data were collected by healthcare record review and self-report.We used linear regression with robust standard errors to analyze survey data and performed a thematic analysis of interview data.Survey participants(N=127)mean age was 42±14 years;51%were female,87%white.ACHD was moderate(75%)or complex(25%);41%functional class C or D.Resilience(mean 30±7)varied by monetary stability:compared to people with difficulty paying bills,resilience was 15.0 points higher(95%CI:6.9–23.1,p<0.001)for people reporting having enough money and 14.2 points higher(95%CI:5.9–22.4,p=0.001)for those reporting just enough money.Interview participants’(N=25)mean age was 32 years(range 22–44);52%were female,72%white.ACHD was moderate(56%)or complex(44%);76%functional class C or D.Participants discussed factors affecting resilience aligned with each of the major SDOH,prominently,economic stability and healthcare access and quality.Financial stability may be important for supporting self-perceived resi-lience in ACHD.This knowledge can inform the development of resilience interventions for this population.展开更多
文摘AIM To analyse the effect of mechanical bowel preparation vs no mechanical bowel preparation on outcome in patients undergoing elective colorectal surgery.METHODS Meta-analysis of randomised controlled trials and observational studies comparing adult patients receiving mechanical bowel preparation with those receiving no mechanical bowel preparation, subdivided into those receiving a single rectal enema and those who received no preparation at all prior to elective colorectal surgery. RESULTS A total of 36 studies(23 randomised controlled trials and 13 observational studies) including 21568 patients undergoing elective colorectal surgery were included. When all studies were considered, mechanical bowel preparation was not associated with any significant difference in anastomotic leak rates(OR = 0.90, 95%CI: 0.74 to 1.10, P = 0.32), surgical site infection(OR = 0.99, 95%CI: 0.80 to 1.24, P = 0.96), intraabdominal collection(OR = 0.86, 95%CI: 0.63 to 1.17, P = 0.34), mortality(OR = 0.85, 95%CI: 0.57 to 1.27, P = 0.43), reoperation(OR = 0.91, 95%CI: 0.75 to 1.12, P = 0.38) or hospital length of stay(overall mean difference 0.11 d, 95%CI:-0.51 to 0.73, P = 0.72), when compared with no mechanical bowel preparation, nor when evidence from just randomized controlledtrials was analysed. A sub-analysis of mechanical bowel preparation vs absolutely no preparation or a single rectal enema similarly revealed no differences in clinical outcome measures. CONCLUSION In the most comprehensive meta-analysis of mechanical bowel preparation in elective colorectal surgery to date, this study has suggested that the use of mechanical bowel preparation does not affect the incidence of postoperative complications when compared with no preparation. Hence, mechanical bowel preparation should not be administered routinely prior to elective colorectal surgery.
基金This work was supported by the National Institutes of Health National Eye Institute(EY014800)the National Institutes of Health National Eye Institute Ruth L.Kirschstein National Research Service Award T32(EY024234)+5 种基金an Unrestricted Grant from Research to Prevent Blindness,Inc.,New York,NY,to the Department of Ophthalmology&Visual Sciences,University of Utahthe ARVO Foundation for Eye ResearchThe Skaggs Foundation for ResearchThe Carl Marshall Reeves&Mildred Almen Reeves Foundation,Inc.the Center of Aging Pilot Award,Division of Geriatrics,University of Utahthe Macular Degeneration Foundation,Inc.
文摘Age-related macular degeneration(AMD)is the leading cause of irreversible blindness in adults over 50 years old.Genetic,epidemiological,and molecular studies are beginning to unravel the intricate mechanisms underlying this complex disease,which implicate the lipid-cholesterol pathway in the pathophysiology of disease development and progression.Many of the genetic and environmental risk factors associated with AMD are also associated with other complex degenerative diseases of advanced age,including cardiovascular disease(CVD).In this review,we present epidemiological findings associating AMD with a variety of lipid pathway genes,cardiovascular phenotypes,and relevant environmental exposures.Despite a number of studies showing significant associations between AMD and these lipid/cardiovascular factors,results have been mixed and as such the relationships among these factors and AMD remain controversial.It is imperative that researchers not only tease out the various contributions of such factors to AMD development but also the connections between AMD and CVD to develop optimal precision medical care for aging adults.
文摘Postoperative sleep disturbance is a common occurrence with significant adverse effects on patients including delayed recovery,impairment of cognitive function,pain sensitivity and cardiovascular events.The development of postoperative sleep disturbance is multifactorial and involves the surgical inflammatory response,the severity of surgical trauma,pain,anxiety,the use of anesthetics and environmental factors such as nocturnal noise and light levels.Many of these factors can be managed perioperatively to minimize the deleterious impact on sleep.Pharmacological and non-pharmacological treatment strategies for postoperative sleep disturbance include dexmedetomidine,zolpidem,melatonin,enhanced recovery after surgery(ERAS) protocol and controlling of environmental noise and light levels.It is likely that a combination of pharmacological and non-pharmacological therapies will have the greatest impact;however,further research is required before their use can be routinely recommended.
基金supported in part by a Barnett Rosenberg Fellowship in Biological Sciences from Michigan State Universitysupported by the National Science Foundation(IOS-1021044)
文摘The eukaryotic actin cytoskeleton is required for numerous cellular processes, including cell shape, development and movement, gene expression and signal transduction, and response to biotic and abiotic stress. In recent years,research in both plants and animal systems have described a function for actin as the ideal surveillance platform, linking the function and activity of primary physiological processes to the immune system. In this review, we will highlight recent advances that have defined the regulation and breadth of function of the actin cytoskeleton as a network required for defense signaling following pathogen infection. Coupled with an overview of recent work demonstrating specific targeting of the plant actin cytoskeleton by a diversity of pathogens,including bacteria, fungi and viruses, we will highlight the importance of actin as a key signaling hub in plants, one that mediates surveillance of cellular homeostasis and the activation of specific signaling responses following pathogen perception. B4 ased on the studies highlighted herein, we propose a working model that posits changes in actin filament organization is in and of itself a highly specific signal, which induces, regulates and physically directs stimulus-specific signaling processes, most importantly, those associated with response to pathogens.
文摘BACKGROUND Colorectal cancer(CRC)is the second leading cause of all cancer related deaths in the United States and Europe.Although the incidence has been decreasing for individuals’≥50,it has been on the rise for individuals<50.AIM To identify potential risk factors for early-onset CRC.METHODS A population-based cohort analysis using a national database,Explorys,screened all patients with an active electronic medical record from January 2012 to December 2016 with a diagnosis of CRC.Subgroups were stratified based on age(25–49 years vs≥50 years).Demographics,comorbidities,and symptom profiles were recorded and compared between both age groups.Furthermore,the younger group was also compared with a control group consisting of individuals aged 25-49 years within the same timeframe without a diagnosis of CRC.Twentydata points for CRC related factors were analyzed to identify potential risk factors specific to early-onset CRC.RESULTS A total of 68860 patients were identified with CRC,of which 5710(8.3%)were younger than 50 years old,with 4140(73%)between 40-49 years of age.Multivariable analysis was reported using odds ratio(OR)with 95%CI and demonstrated that several factors were associated with an increased risk of CRC in the early-onset group versus the later-onset group.These factors included:African-American race(OR 1.18,95%CI:1.09-1.27,P<0.001),presenting symptoms of abdominal pain(OR 1.82,95%CI:1.72-1.92,P<0.001),rectal pain(OR 1.50,95%CI:1.28-1.77,P<0.001),altered bowel function(OR 1.12,95%CI:1.05-1.19,P=0.0005),having a family history of any cancer(OR 1.78,95%CI:1.67-1.90,P<0.001),gastrointestinal(GI)malignancy(OR 2.36,95%CI:2.18-2.55,P<0.001),polyps(OR 1.41,95%CI:1.08-1.20,P<0.001),and obesity(OR 1.14,95%CI:1.08-1.20,P<0.001).Comparing the early-onset cohort versus the control group,factors that were associated with an increased risk of CRC were:male gender(OR 1.34,95%CI:1.27-1.41),P<0.001),Caucasian(OR 1.48,95%CI:1.40-1.57,P<0.001)and African-American race(OR 1.25,95%CI:1.17-1.35,P<0.001),presenting
文摘Acute myeloid leukemia(AML)is the most common form of acute leukemia in adults and the second most common form of acute leukemia in children.Despite this,very little improvement in survival rates has been achieved over the past few decades.This is partially due to the heterogeneity of AML and the need for more targeted therapeutics than the traditional cytotoxic chemotherapies that have been a mainstay in therapy for the past 50 years.In the past 20 years,research has been diversifying the approach to treating AML by investigating molecular pathways uniquely relevant to AML cell proliferation and survival.Here we review the development of novel therapeutics in targeting apoptosis,receptor tyrosine kinase(RTK)signaling,hedgehog(HH)pathway,mitochondrial function,DNA repair,and c-Myc signaling.There has been an impressive effort into better understanding the diversity of AML cell characteristics and here we highlight important preclinical studies that have supported therapeutic development and continue to promote new ways to target AML cells.In addition,we describe clinical investigations that have led to FDA approval of new targeted AML therapies and ongoing clinical trials of novel therapies targeting AML survival pathways.We also describe the complexity of targeting leukemia stem cells(LSCs)as an approach to addressing relapse and remission in AML and targetable pathways that are unique to LSC survival.This comprehensive review details what we currently understand about the signaling pathways that support AML cell survival and the exceptional ways in which we disrupt them.
文摘Gallbladder cancer is a rare,aggressive malignancy that has a poor overall prognosis.Effective treatment consists of early detection and surgical treatment.With the wide spread treatment of gallbladder disease with minimally invasive techniques,the rate of incidental gallbladder cancer has seen an equitable rise along with stage migration towards earlier disease.Although the treatment remains mostly surgical,newer modalities such as regional therapy as well as directed therapy based on molecular medicine has led to improved outcomes in patients with advanced disease.We aim to summarize the management of gallbladder cancer along with the newer developments in this formidable disease process.
基金CEFIC LRI,Natural Science Foundation of Jiangsu Province(No.BK20130186)the Fundamental Research Funds for the Central Universities(No.2013QNA18)for funding this project
文摘Novel applications of nanotechnology may lead to the release of engineered nanoparticles（ENPs）, which result in concerns over their potential environmental hazardous impact. It is essential for the research workers to be able to quantitatively characterise ENPs in the environment and subsequently to assist the risk assessment of the ENPs. This study hence explored the application of nanoparticle tracking system（NTA） to quantitatively describe the behaviour of the ENPs in natural sediment-water systems. The NTA allows the measurement of both particle number concentration（PNC） and particle size distribution（PSD） of the ENPs. The developed NTA method was applied to a range of gold and magnetite ENPs with a selection of surface properties. The results showed that the positively-charged ENPs interacted more strongly with the sediment than neutral and negatively-charged ENPs. It was also found that the citrate coated Au ENPs had a higher distribution percentage（53%） than 11-mercaptoundecanoic acid coated Au ENPs（20%） and citrate coated magnetite ENPs（21%）. The principles of the electrostatic interactions between hard（and soft） acids and bases（HSAB） are used to explain such behaviours; the hard base coating（i.e. citrate ions） will interact more strongly with hard acid（i.e. magnetite） than soft acid（i.e. gold）.The results indicate that NTA is a complementary method to existing approaches to characterise the fate and behaviour of ENPs in natural sediment.
基金Supported by In part by the NIH/NCI(R01 CA148772,ACL)the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs(Merit Awards,ACL)the Hollings Cancer Center(Translational Research Pilot Project,P30 CA138313,ACL)
文摘The tumor microenvironment(TME) is complex and constantly evolving. This is due, in part, to the crosstalk between tumor cells and the multiple cell types that comprise the TME, which results in a heterogeneous population of tumor cells and TME cells. This review will focus on two stromal cell types, the cancerassociated adipocyte(CAA) and the cancer-associated fibroblast(CAF). In the clinic, the presence of CAAs and CAFs in the TME translates to poor prognosis in multiple tumor types. CAAs and CAFs have an activated phenotype and produce growth factors, inflammatory factors, cytokines, chemokines, extracellular matrix components, and proteases in an accelerated and aberrant fashion. Through this activated state, CAAs and CAFs remodel the TME, thereby driving all aspects of tumor progression, including tumor growth and survival, chemoresistance, tumor vascularization, tumor invasion, and tumor cell metastasis. Similarities in the tumorpromoting functions of CAAs and CAFs suggest that a multipronged therapeutic approach may be necessary to achieve maximal impact on disease. While CAAs and CAFs are thought to arise from tissues adjacent to the tumor, multiple alternative origins for CAAs and CAFs have recently been identified. Recent studies from our lab and others suggest that the hematopoietic stem cell, through the myeloid lineage, may serve as a progenitor for CAAs and CAFs. We hypothesize that the multiple origins of CAAs and CAFs may contribute to the heterogeneity seen in the TME. Thus, a better understanding of the origin of CAAs and CAFs, how this origin impacts their functions in the TME, and thetemporal participation of uniquely originating TME cells may lead to novel or improved anti-tumor therapeutics.
文摘AIM To investigate the relationship between vitamin D and liver fibrosis in hepatitis C-monoinfected or hepatitis C virus(HCV)-human immunodeficiency virus(HIV) coinfected patients. METHODS Pertinent studies were located by a library literature search in PubM ed/Embase/Cochrane/Scopus/LILACS by two individual reviewers. Inclusion criteria:(1) studies with patients with HCV or co-infected HCV/HIV;(2) studies with patients ≥ 18 years old;(3) studies that evaluated liver fibrosis stage, only based on liver biopsy; and(4) studies that reported serum or plasma 25(OH)D levels. Studies that included pediatric patients, other etiologies of liver disease, or did not use liver biopsy for fibrosis evaluation, or studies with inadequate data were excluded. Estimated measures of association reported in the literature, as well as corresponding measures of uncertainty, were recorded and corresponding odds ratios with 95%CI were included in a meta-analysis. RESULTS The pooled data of this systematic review showed that 9 of the 12 studies correlated advanced liver disease defined as a Metavir value of F3/4 with 25(OH) D level insufficiency. The meta-analysis indicated a significant association across studies.CONCLUSION Low vitamin D status is common in chronic Hepatitis C patients and is associated with advanced liver fibrosis.
基金supported by faculty development program funding from University of Tennessee Health Science Center (UTHSC) College of Pharmacy to Kirk E. HevenerChimera is developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, USA (supported by U.S. National Institute of General Medical Sciences (NIGMS) P41GM103311)
文摘The DNA topoisomerase enzymes are essential to cell function and are found ubiquitously in all domains of life. The various topoisomerase enzymes perform a wide range of functions related to the maintenance of DNA topology during DNA replication, and transcription are the targets of a wide range of antimicrobial and cancer chemotherapeutic agents. Natural product-derived agents, such as the camptothecin, anthracycline, and podophyllotoxin drugs, have seen broad use in the treatment of many types of cancer. Selective targeting of the topoisomerase enzymes for cancer treatment continues to be a highly active area of basic and clinical research. The focus of this review will be to summarize the current state of the art with respect to clinically used topoisomerase inhibitors for targeted cancer treatment and to discuss the pharmacology and chemistry of promising new topoisomerase inhibitors in clinical and preclinical development.
基金support from Brown University startup funds and the National Science Foundation(OIA-1538893)K.H.-K.is supported by the U.S.Department of Education GAANN research fellowship(P200A150037)。
文摘The unique structure of zero-dimensional(0D)perovskite-analogues has attracted a great amount of research interest in recent years.To date,the current compositional library of 0D perovskites is largely limited to the lead-based Cs4PbX6(X=Cl,Br,and I)systems.In this work,we report a new synthesis of lead-free 0D Cs3BiX6(X=Cl,Br)perovskite-analogue nanocrystals(NCs)with a uniform cubic shape.We observe a broad photoluminescence peak centered at 390 nm for the 0D Cs3BiCl6 NCs at low temperatures.This feature originates from a self-trapped exciton mechanism.In situ thermal stability studies show that Cs3BiX6 NCs remain stable upon heating up to 200°C without crystal structural degradation.Moreover,we demonstrate that the Cs3BiX6 NCs can transform into other bismuth-based perovskite-analogues via facile anion exchange or metal ion insertion reactions.Our study presented here offers the opportunity for further understanding of the structure-property relationship of 0D perovskite-analogue materials,leading toward their future optoelectronic applications.
文摘Assessing the adsorption properties of nanoporous materials and determining their structural characterization is critical for progressing the use of such materials for many applications, including gas storage. Gas adsorption can he used for this characterization because it assesses a broad range of pore sizes, from micropore to mesopore. In the past 20 years, key developments have been achieved both in the knowledge of the adsorption and phase behavior of fluids in ordered nanoporous materials and in the creation and advancement of state-of-the-art approaches based on statistical mechanics, such as molecular sim- ulation and density functional theory. Together with high-resolution experimental procedures for the adsorption of suhcritical and supercritical fluids, this has led to significant advances in physical adsorp- tion textural characterization. In this short, selective review paper, we discuss a few important and central features of the underlying adsorption mechanisms of fluids in a variety of nanoporous materials with well-defined pore structure. The significance of these features for advancing physical adsorption charac- terization and gas storage applications is also discussed.
文摘AIM To compare outcomes in patients undergoing rectal resection by robotic total meso-rectal excision(RTME) vs laparoscopic total meso-rectal excision(LTME).METHODS Standard medical electronic databases such as Pub-Med, MEDLINE, EMBASE and Scopus were searched to find relevant articles. The data retrieved from all types of included published comparative trials in pati-ents undergoing RTME vs LTME was analysed using the principles of meta-analysis. The operative, post-operative and oncological outcomes were evaluated to assess the effectiveness of both techniques of TME. The summated outcome of continuous variables was expressed as standardized mean difference(SMD) and dichotomous data was presented in odds ratio(OR).RESULTS One RCT(ROLARR trial) and 27 other comparative studies reporting the non-oncological and oncological outcomes following RTME vs LTME were included in this review. In the random effects model analysis using the statistical software Review Manager 5.3, the RTME was associated with longer operation time(SMD, 0.46; 95%CI: 0.25, 0.67; z = 4.33; P = 0.0001), early passage of first flatus(P = 0.002), lower risk of conversion(P = 0.00001) and shorter hospitalization(P = 0.01). The statistical equivalence was seen between RTME and LTME for non-oncological variables like blo-od loss, morbidity, mortality and re-operation risk. The oncological variables such as recurrence(P = 0.96), number of harvested nodes(P = 0.49) and positive circumferential resection margin risk(P = 0.53) were also comparable in both groups. The length of distal resection margins was similar in both groups. CONCLUSION RTME is feasible and oncologically safe but failed to demonstrate any superiority over LTME for many sur-gical outcomes except early passage of flatus, lower risk of conversion and shorter hospitalization.
基金Supported by University of Edinburgh Hepatology Laboratory Internal Fundingthe Liver Endowment Funds of the Edinburgh&Lothian Health Foundation.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy.Mechanisms of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell invasion.AIM To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19.METHODS ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel classifiers.RESULTS ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes.Strikingly,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis.ACE2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum.Hepatic ACE2 levels are also increased in COVID-19 pa
基金supported by a grant from the Australian Society of Orthodontists Foundation for Research and Education(ASOFRE).
文摘Primary molar ankylosis with infraocclusion can retard dental arch development and cause dental asymmetry. Despite its widespread prevalence, little is known about its molecular etiology and pathogenesis. To address this, RNA sequencing was used to generate transcriptomes of furcal bone from infraoccluded(n = 7) and non-infraoccluded(n = 9) primary second molars, all without succeeding biscuspids. Of the 18 529 expressed genes, 432(2.3%) genes were differentially expressed between the two groups(false discovery rate < 0.05). Hierarchical clustering and principal component analysis showed clear separation in gene expression between infraoccluded and non-infraoccluded samples. Pathway analyses indicated that molar ankylosis is associated with the expression of genes consistent with the cellular inflammatory response and epithelial cell turnover. Independent validation using six expressed genes by immunohistochemical analysis demonstrated that the corresponding proteins are strongly expressed in the developing molar tooth germ, in particular the dental follicle and inner enamel epithelium. The descendants of these structures include the periodontal ligament, cementum, bone and epithelial rests of Malassez;tissues that are central to the ankylotic process.We therefore propose that ankylosis involves an increased inflammatory response associated with disruptions to the developmental remnants of the dental follicle and epithelial rests of Malassez.
文摘In the late 1980s the first laparoscopic cholecystectomies were performed prompting a sudden rise in technological innovations as the benefits and feasibility of minimal access surgery became recognised.Monocular laparoscopes provided only two-dimensional(2D) viewing with reduced depth perception and contributed to an extended learning curve.Attention turned to producing a usable three-dimensional(3D) endoscopic view for surgeons;utilising different technologies for image capture and image projection.These evolving visual systems have been assessed in various research environments with conflicting outcomes of success and usability,and no overall consensus to their benefit.This review article aims to provide an explanation of the different types of technologies,summarise the published literature evaluating 3D vs 2D laparoscopy,to explain the conflicting outcomes,and discuss the current consensus view.
基金This study is supported by K23HL15180(NIH/NHLBI,Steiner)a grant from the American College of Cardiology Foundation.
文摘Social determinants of health(SDOH)affect quality of life.We investigated SDOH impacts on self-perceived resilience among people with adult congenital heart disease(ACHD).Secondary analysis of data from two com-plementary studies:a survey study conducted May 2021–June 2022 and a qualitative study conducted June 2020–August 2021.Resilience was assessed through CD-RISC10 score(range 0–40,higher scores reflect greater self-perceived resilience)and interview responses.Sociodemographic and SDOH(education,employment,living situa-tion,monetary stability,financial dependency,area deprivation index)data were collected by healthcare record review and self-report.We used linear regression with robust standard errors to analyze survey data and performed a thematic analysis of interview data.Survey participants(N=127)mean age was 42±14 years;51%were female,87%white.ACHD was moderate(75%)or complex(25%);41%functional class C or D.Resilience(mean 30±7)varied by monetary stability:compared to people with difficulty paying bills,resilience was 15.0 points higher(95%CI:6.9–23.1,p<0.001)for people reporting having enough money and 14.2 points higher(95%CI:5.9–22.4,p=0.001)for those reporting just enough money.Interview participants’(N=25)mean age was 32 years(range 22–44);52%were female,72%white.ACHD was moderate(56%)or complex(44%);76%functional class C or D.Participants discussed factors affecting resilience aligned with each of the major SDOH,prominently,economic stability and healthcare access and quality.Financial stability may be important for supporting self-perceived resi-lience in ACHD.This knowledge can inform the development of resilience interventions for this population.
