The subversive nature of information war lies not only in the information itself, but also in the circulation and application of information. It has always been a challenge to quantitatively analyze the function and e...The subversive nature of information war lies not only in the information itself, but also in the circulation and application of information. It has always been a challenge to quantitatively analyze the function and effect of information flow through command, control, communications, computer, kill, intelligence,surveillance, reconnaissance (C4KISR) system. In this work, we propose a framework of force of information influence and the methods for calculating the force of information influence between C4KISR nodes of sensing, intelligence processing,decision making and fire attack. Specifically, the basic concept of force of information influence between nodes in C4KISR system is formally proposed and its mathematical definition is provided. Then, based on the information entropy theory, the model of force of information influence between C4KISR system nodes is constructed. Finally, the simulation experiments have been performed under an air defense and attack scenario. The experimental results show that, with the proposed force of information influence framework, we can effectively evaluate the contribution of information circulation through different C4KISR system nodes to the corresponding tasks. Our framework of force of information influence can also serve as an effective tool for the design and dynamic reconfiguration of C4KISR system architecture.展开更多
Background: Acute Kidney Injury (AKI) stands as a prominent postoperative complication in on-pump cardiac surgery, with repercussions on morbidity, mortality, and hospitalization duration. Current diagnostic criteria ...Background: Acute Kidney Injury (AKI) stands as a prominent postoperative complication in on-pump cardiac surgery, with repercussions on morbidity, mortality, and hospitalization duration. Current diagnostic criteria relying on serum creatinine levels exhibit a delayed identification of AKI, prompting an exploration of alternative biomarkers. Aims and Objectives: This study is designed to overcome diagnostic constraints and explore the viability of serum Cystatin C as an early predictor of Acute Kidney Injury (AKI) in individuals undergoing on-pump cardiac surgery. The investigation aims to establish the relationship between serum Cystatin C levels and the onset of AKI in patients subjected to on-pump cardiac surgery. Primary objectives involve the assessment of the diagnostic effectiveness of serum Cystatin C, its comparison with serum creatinine, and the exploration of its potential for the early identification and treatment of AKI. Methodology: Conducted as a single-center study at the cardiac surgery department of BSMMU in Bangladesh from September 2020 to August 2022, a comparative cross-sectional analysis involved 31 participants categorized into No AKI and AKI groups based on Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Data collection encompassed preoperative, post-CBP (cardiopulmonary bypass) conclusion at 2 hours, postoperative day 1, and postoperative day 2 intervals. Statistical analyses included Chi-squared tests, independent Student’s t-tests, and one-sample t-tests. Significance was set at P Results: The study revealed no significant differences in baseline characteristics between the No AKI and AKI groups, except for CPB time and cross-clamp time. Serum Cystatin C levels in the AKI group exhibited statistical significance at various time points, highlighting its potential as an early detector. Conversely, Serum Creatinine levels in the AKI group showed no statistical significance. The Receiver Operating Characteristic (ROC) curve analysis further supported the efficacy of serum Cystatin C, with an Area under the ROC Curve of 0.864 and a cut-off value of 0.55 (p Conclusion: This study supports the superior utility of serum Cystatin C as an early detector of AKI in on-pump cardiac surgery patients compared to serum creatinine. Its ability to identify AKI several hours earlier may contribute to reduced morbidity, mortality, and healthcare costs. The findings underscore the significance of exploring novel biomarkers for improved post-cardiac surgery renal function assessment.展开更多
Verticillium longisporum(Vl43)is a soilborne hemibiotrophic fungal pathogen causing stem striping on oilseed rape(OSR)and severe yield losses.Breeding for resistant varieties is the most promising approach to control ...Verticillium longisporum(Vl43)is a soilborne hemibiotrophic fungal pathogen causing stem striping on oilseed rape(OSR)and severe yield losses.Breeding for resistant varieties is the most promising approach to control this disease.Here,we report the identification of Hva22c as a novel susceptibility factor and its potential for improving OSR resistance.Hva22c is a member of the Hva22 gene family,originally described for barley(Hordeum vulgare).Several Hva22 members have been located at the endoplasmic reticulum.Hva22c is up-regulated in response to Vl43 in both Arabidopsis and OSR.We demonstrate that knock-out of Hva22c in OSR by CRISPR/Cas9 and its homolog in Arabidopsis by T-DNA insertion reduced plants’susceptibility to Vl43 infection and impaired the development of disease symptoms.To understand the underlying mechanism,we analysed transcriptomic data from infected and non-infected roots of hva22c knock-out and wild type plants.We identified a homozygous mutant with frame-shifts in all four BnHva22c loci displaying a vastly altered transcriptional landscape at 6 dpi.Significantly,a large set of genes was suppressed under mock conditions including genes related to the endomembrane systems.Among the up-regulated genes we found several defense-related and phytohormone-responsive genes when comparing mutant to the wild type.These results demonstrate that Hva22c is functionally required for a fully compatible plant-fungus interaction.Its loss of function reduces plant susceptibility,most likely due to endoplasmatic reticulum and Golgi dysfunction accompanied by additionally activated defense responses.These findings can help improve OSR resistance to V.longisporum infection.展开更多
Land surface temperature(LST) directly affects the energy balance of terrestrial surface systems and impacts regional resources, ecosystem evolution, and ecosystem structures. Xinjiang Uygur Autonomous Region is locat...Land surface temperature(LST) directly affects the energy balance of terrestrial surface systems and impacts regional resources, ecosystem evolution, and ecosystem structures. Xinjiang Uygur Autonomous Region is located at the arid Northwest China and is extremely sensitive to climate change. There is an urgent need to understand the distribution patterns of LST in this area and quantitatively measure the nature and intensity of the impacts of the major driving factors from a spatial perspective, as well as elucidate the formation mechanisms. In this study, we used the MOD11C3 LST product developed on the basis of Moderate Resolution Imaging Spectroradiometer(MODIS) to conduct regression analysis and determine the spatiotemporal variation and differentiation pattern of LST in Xinjiang from 2000 to 2020. We analyzed the driving mechanisms of spatial heterogeneity of LST in Xinjiang and the six geomorphic zones(the Altay Mountains, Junggar Basin, Tianshan Mountains, Tarim Basin, Turpan-Hami(Tuha) Basin, and Pakakuna Mountain Group) using geographical detector(Geodetector) and geographically weighted regression(GWR) models. The warming rate of LST in Xinjiang during the study period was 0.24℃/10a, and the spatial distribution pattern of LST had obvious topographic imprints, with 87.20% of the warming zone located in the Gobi desert and areas with frequent human activities, and the cooling zone mainly located in the mountainous areas. The seasonal LST in Xinjiang was at a cooling rate of 0.09℃/10a in autumn, and showed a warming trend in other seasons. Digital elevation model(DEM), latitude, wind speed, precipitation, normalized difference vegetation index(NDVI), and sunshine duration in the single-factor and interactive detections were the key factors driving the LST changes. The direction and intensity of each major driving factor on the spatial variations of LST in the study area were heterogeneous. The negative feedback effect of DEM on the spatial differentiation of LST was the strongest. Lower latitudes, lower vegetation coverage, lower levels of precipitation, and longer sunshine duration increased LST. Unused land was the main heat source landscape, water body was the most important heat sink landscape, grassland and forest land were the land use and land cover(LULC) types with the most prominent heat sink effect, and there were significant differences in different geomorphic zones due to the influences of their vegetation types, climatic conditions, soil types, and human activities. The findings will help to facilitate sustainable climate change management, analyze local climate and environmental patterns, and improve land management strategies in Xinjiang and other arid areas.展开更多
BACKGROUND Hepatitis C is the leading cause of chronic liver disease worldwide and it significantly contributes to the burden of hepatocellular carcinoma(HCC).However,there are marked variations in the incidence and m...BACKGROUND Hepatitis C is the leading cause of chronic liver disease worldwide and it significantly contributes to the burden of hepatocellular carcinoma(HCC).However,there are marked variations in the incidence and mortality rates of HCC across different geographical regions.With the advent of new widely available treatment modalities,such as direct-acting antivirals,it is becoming increasingly imperative to understand the temporal and geographical trends in HCC mortality associated with Hepatitis C.Furthermore,gender disparities in HCC mortality related to Hepatitis C are a crucial,yet underexplored aspect that adds to the disease's global impact.While some studies shed light on gender-specific trends,there is a lack of comprehensive data on global and regional mortality rates,particularly those highlighting gender disparities.This gap in knowledge hinders the development of targeted interventions and resource allocation strategies.DISCUSSION The results of our study show an overall decline in the mortality rates of patients with hepatitis C-related HCC over the last two decades.Notably,females exhibited a remarkable decrease in mortality compared to males.Regionally,East Asia and the Pacific displayed a significant decline in mortality,while Europe and Central Asia witnessed an upward trend.Latin America and the Caribbean also experienced an increase in mortality rates.However,no significant difference was observed in the Middle East and North Africa.North America exhibited a notable upward trend.South Asia and Sub-Saharan Africa significantly declined throughout the study period.This raises the hope of identifying areas for implementing more targeted resources.Despite some progress,multiple challenges remain in meeting the WHO 2030 goal of eliminating viral hepatitis[24].展开更多
Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to...Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (EGCG) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EGCG dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EGCG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EGCG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.展开更多
This study assesses the projected changes in the climate zoning of Côte d’Ivoire using the hierarchical classification of principal components (HCPC) method applied to the daily precipitation data of an ensemble...This study assesses the projected changes in the climate zoning of Côte d’Ivoire using the hierarchical classification of principal components (HCPC) method applied to the daily precipitation data of an ensemble of 14 CORDEX-AFRICA simulations under RCP4.5 and RCP8.5 scenarios. The results indicate the existence of three climate zones in Côte d’Ivoire (the coastal, the centre and the north) over the historical period (1981-2005). Moreover, CORDEX simulations project an extension of the surface area of drier climatic zones while a reduction of wetter zones, associated with the appearance of an intermediate climate zone with surface area varying from 77,560 km<sup>2</sup> to 134,960 km<sup>2</sup> depending on the period and the scenario. These results highlight the potential impacts of climate change on the delimitation of the climate zones of Côte d’Ivoire under the greenhouse gas emission scenarios. Thus, there is a reduction in the surface areas suitable for the production of cash crops such as cocoa and coffee. This could hinder the country’s economy and development, mainly based on these cash crops.展开更多
Objective:To evaluate the effects of Catalpa bignonioides fruit extract on the promotion of muscle growth and muscular capacity in vitro and in vivo.Methods:Cell viability was measured using the 3-(4,5-dimethylthiazol...Objective:To evaluate the effects of Catalpa bignonioides fruit extract on the promotion of muscle growth and muscular capacity in vitro and in vivo.Methods:Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Cell proliferation was assessed using a 5-bromo-2’-deoxyuridine(BrdU)assay kit.Western blot analysis was performed to determine the protein expressions of related factors.The effects of Catalpa bignonioides extract were investigated in mice using the treadmill exhaustion test and whole-limb grip strength assay.Chemical composition analysis was performed using high-performance liquid chromatography(HPLC).Results:Catalpa bignonioides extract increased the proliferation of C2C12 mouse myoblasts by activating the Akt/mTOR signaling pathway.It also induced metabolic changes,increasing the number of mitochondria and glucose metabolism by phosphorylating adenosine monophosphate-activated protein kinase.In an in vivo study,the extract-treated mice showed improved motor abilities,such as muscular endurance and grip strength.Additionally,HPLC analysis showed that vanillic acid may be the main component of the Catalpa bignonioides extract that enhanced muscle strength.Conclusions:Catalpa bignonioides improves exercise performance through regulation of growth and metabolism in skeletal muscles,suggesting its potential as an effective natural agent for improving muscular strength.展开更多
Primary Budd-Chiari syndrome (BCS) is a spontaneously fatal disease characterized by an obstruction of the hepatic venous outflow tract due to thrombosis or a primary disease of the venous wall. The primary form of BC...Primary Budd-Chiari syndrome (BCS) is a spontaneously fatal disease characterized by an obstruction of the hepatic venous outflow tract due to thrombosis or a primary disease of the venous wall. The primary form of BCS is extremely rare. This is a disease mainly affecting young adults of both sexes. Clinical manifestations are variable;they can be asymptomatic, acute, or subacute but mostly chronic. Several causes have been identified, such as myeloproliferative syndrome, antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria, and inherited thrombotic disorders. Data on primary BCS in Sub-Saharan Africa is rare as most publications available are case reports. In these reports, the causes are unknown with poor prognosis in most cases often leading to patient death. We herein present a case report of a male patient diagnosed with a primary BCS at Yaoundé General Hospital (Cameroon) caused by a Protein C deficiency who presented with ascites decompensating liver cirrhosis. Treatment was based on anticoagulants, diuretics and laxatives administration. Two years after the diagnosis, the patient is alive with clinical and paraclinical improvement.展开更多
Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various disea...Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various diseases,including ischemic stroke and neurodegenerative diseases.However,whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear.Therefore,in the present study,we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms.We established a traumatic brain injury rat model using a modified weight drop method.P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury.Severe neurological deficits were found in rats after traumatic brain injury,with deterioration in balance,walking function,and learning memory.Furthermore,hematoxylin and eosin staining showed significant neuronal cell damage,while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis.The presence of autolysosomes was observed using transmission electron microscope.P7C3-A20 treatment reversed these pathological features.Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)autophagy protein,apoptosis-related proteins(namely,Bcl-2/adenovirus E1B 19-kDa-interacting protein 3[BNIP3],and Bcl-2 associated x protein[Bax]),and elevated ubiquitin-binding protein p62(p62)autophagy protein expression.Thus,P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.展开更多
The effects of ultrafine WC(WC_(UF),0.5μm) or W(1μm) and C(0.3μm)(W+C)_(UF) additives on the densification,microstructure and mechanical properties of coarse-grained cemented carbides were compared systematically.O...The effects of ultrafine WC(WC_(UF),0.5μm) or W(1μm) and C(0.3μm)(W+C)_(UF) additives on the densification,microstructure and mechanical properties of coarse-grained cemented carbides were compared systematically.Overall,the cemented carbides with WC_(UF)/(W+C)_(UF) additives are almost fully densification to be higher than 99%,and the average grain size is kept above 2.8μm.The WC_(UF) additive assists grains to(truncated)trigonal prism shape by two dimensional(2D) growth,whereas the(W+C)_(UF) additive assists grains to rounded shape by three dimensional(3D) growth,lowers WC contiguity and increases face-centered-cubic Co.The hardness and bending strength of(75WC_(C)-15WC_(UF))-10Co are 86.6 HRA and 2 272 MPa,respectively,both higher than those of(75WC_(C)-15(W+C)_(UF))-10Co,which could be ascribed to the enhanced densification and unblemished grains.However,the fracture toughness of the(75WC_(C)-15(W+C)_(UF))-10Co is 23.5 MPa·m^(1/2),higher than that of the(75WC_(C)-15WC_(UF))-10Co due to the uniform WC-Co structure and flexible binder phase.展开更多
Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In ...Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.展开更多
In this article,we study Kahler metrics on a certain line bundle over some compact Kahler manifolds to find complete Kahler metrics with positive holomorphic sectional(or bisectional)curvatures.Thus,we apply a strateg...In this article,we study Kahler metrics on a certain line bundle over some compact Kahler manifolds to find complete Kahler metrics with positive holomorphic sectional(or bisectional)curvatures.Thus,we apply a strategy to a famous Yau conjecture with a co-homogeneity one geometry.展开更多
Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were establi...Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.展开更多
Pancreatic surgery units undertake several complex operations,albeit with consi-derable morbidity and mortality,as is the case for the management of complicated acute pancreatitis or chronic pancreatitis.The centralis...Pancreatic surgery units undertake several complex operations,albeit with consi-derable morbidity and mortality,as is the case for the management of complicated acute pancreatitis or chronic pancreatitis.The centralisation of pancreatic surgery services,with the development of designated large-volume centres,has contribu-ted to significantly improved outcomes.In this editorial,we discuss the complex associations between diabetes mellitus(DM)and pancreatic/periampullary disease in the context of pancreatic surgery and overall management of complex pancreatitis,highlighting the consequential needs and the indispensable role of specialist diabetes teams in support of tertiary pancreatic services.Type 3c pan-creatogenic DM,refers to DM developing in the setting of exocrine pancreatic disease,and its identification and management can be challenging,while the glycaemic control of such patients may affect their course of treatment and outcome.Adequate preoperative diabetes assessment is warranted to aid identification of patients who are likely to need commencement or escalation of glucose lowering therapy in the postoperative period.The incidence of new onset diabetes after pancreatic resection is widely variable in the literature,and depends on the type and extent of pancreatic resection,as is the case with pancreatic parenchymal loss in the context of severe pancreatitis.Early involvement of a specialist diabetes team is essential to ensure a holistic management.In the current era,large volume pancreatic surgery services commonly abide by the principles of enhanced recovery after surgery,with inclusion of provisions for optimisation of the perioperative glycaemic control,to improve outcomes.While various guidelines are available to aid perioperative management of DM,auditing and quality improvement platforms have highlighted deficiencies in the perioperative management of diabetic patients and areas of required improvement.The need for perioperative support of diabetic patients by specialist diabetes teams is uniformly underlined,a fact that becomes clearly more prominent at all different stages in the setting of pancreatic surgery and the management of complex pancreatitis.Therefore,pancreatic surgery and tertiary pancreatitis services must be designed with a provision for support from specialist diabetes teams.With the ongoing accumulation of evidence,it would be reasonable to consider the design of specific guidelines for the glycaemic management of these patients.展开更多
BACKGROUND Obesity is an independent risk factor for the development of hepatocellular carcinoma(HCC)and may influence its outcomes.However,after diagnosis of HCC,like other malignancies,the obesity paradox may exist ...BACKGROUND Obesity is an independent risk factor for the development of hepatocellular carcinoma(HCC)and may influence its outcomes.However,after diagnosis of HCC,like other malignancies,the obesity paradox may exist where higher body mass index(BMI)may in fact confer a survival benefit.This is frequently observed in patients with advanced HCC and cirrhosis,who often present late with advanced tumor features and cancer related weight loss.AIM To explore the relationship between BMI and survival in patients with cirrhosis and HCC.METHODS This is a retrospective cohort study of over 2500 patients diagnosed with HCC between 2009-2019 at two United States academic medical centers.Patient and tumor characteristics were extracted manually from medical records of each institutions'cancer registries.Patients were stratified according to BMI classes:<25 kg/m^(2)(lean),25-29.9 kg/m^(2)(overweight),and>30 kg/m^(2)(obese).Patient and tumor characteristics were compared according to BMI classification.We performed an overall survival analysis using Kaplan Meier by the three BMI classes and after adjusting for Milan criteria.A multivariable Cox regression model was then used to assess known risk factors for survival in patients with cirrhosis and HCC.RESULTS A total of 2548 patients with HCC were included in the analysis of which 11.2%(n=286)were classified as noncirrhotic.The three main BMI categories:Lean(n=754),overweight(n=861),and obese(n=933)represented 29.6%,33.8%,and 36.6%of the total population overall.Within each BMI class,the non-cirrhotic patients accounted for 15%(n=100),12%(n=94),and 11%(n=92),respectively.Underweight patients with a BMI<18.5 kg/m^(2)(n=52)were included in the lean cohort.Of the obese cohort,42%(n=396)had a BMI≥35 kg/m^(2).Out of 2262 patients with cirrhosis and HCC,654(29%)were lean,767(34%)were overweight,and 841(37%)were obese.The three BMI classes did not differ by age,MELD,or Child-Pugh class.Chronic hepatitis C was the dominant etiology in lean compared to the overweight and obese patients(71%,62%,49%,P<0.001).Lean patients had significantly larger tumors compared to the other two BMI classes(5.1 vs 4.2 vs 4.2 cm,P<0.001),were more likely outside Milan(56%vs 48%vs 47%,P<0.001),and less likely to undergo transplantation(9%vs 18%vs 18%,P<0.001).While both tumor size(P<0.0001)and elevated alpha fetoprotein(P<0.0001)were associated with worse survival by regression analysis,lean BMI was not(P=0.36).CONCLUSION Lean patients with cirrhosis and HCC present with larger tumors and are more often outside Milan criteria,reflecting cancer related cachexia from delayed diagnosis.Access to care for hepatitis C virus therapy and liver transplantation confer a survival benefit,but not overweight or obese BMI classifications.展开更多
BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.Howeve...BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.However,conventional diagnostic methods such as electrocardiography,echocardiography,and cardiac biomarkers have certain limitations,such as low sensitivity,specificity,availability,and cost-effectiveness.Therefore,there is a need for simple,noninvasive,and reliable biomarkers to diagnose CHD and HF.AIM To investigate serum cystatin C(Cys-C),monocyte/high-density lipoprotein cholesterol ratio(MHR),and uric acid(UA)diagnostic values for CHD and HF.METHODS We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023.The patients were divided into CHD(n=20),HF(n=20),CHD+HF(n=20),and control groups(n=20).The serum levels of Cys-C,MHR,and UA were measured using immunonephelometry and an enzymatic method,respectively,and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Serum levels of Cys-C,MHR,and UA were significantly higher in the CHD,HF,and CHD+HF groups than those in the control group.The serum levels of Cys-C,MHR,and UA were significantly higher in the CHD+HF group than those in the CHD or HF group.The ROC curve analysis showed that serum Cys-C,MHR,and UA had good diagnostic performance for CHD and HF,with areas under the curve ranging from 0.78 to 0.93.The optimal cutoff values of serum Cys-C,MHR,and UA for diagnosing CHD,HF,and CHD+HF were 1.2 mg/L,0.9×10^(9),and 389μmol/L;1.4 mg/L,1.0×10^(9),and 449μmol/L;and 1.6 mg/L,1.1×10^(9),and 508μmol/L,respectively.CONCLUSION Serum Cys-C,MHR,and UA are useful biomarkers for diagnosing CHD and HF,and CHD+HF.These can provide information for decision-making and risk stratification in patients with CHD and HF.展开更多
BACKGROUND Cholangiocarcinoma is the second most common primary liver malignancy.Its incidence and mortality rates have been increasing in recent years.Hepatitis C virus(HCV)infection is a risk factor for development ...BACKGROUND Cholangiocarcinoma is the second most common primary liver malignancy.Its incidence and mortality rates have been increasing in recent years.Hepatitis C virus(HCV)infection is a risk factor for development of cirrhosis and cholan-giocarcinoma.Currently,surgical resection remains the only curative treatment option for cholangiocarcinoma.We aim to study the impact of HCV infection on outcomes of liver resection(LR)in intrahepatic cholangiocarcinoma(ICC).AIM To study the outcomes of curative resection of ICC in patients with HCV(i.e.,HCV+)compared to patients without HCV(i.e.,HCV-).METHODS We conducted a systematic review and meta-analysis of randomized controlled trials(RCTs)and observational studies to assess the outcomes of LR in ICC in HCV+patients compared to HCV-patients in tertiary care hospitals.PubMed,EMBASE,The Cochrane Library and Scopus were systematically searched from inception till August 2023.Included studies were RCTs and non-RCTs on patients≥18 years old with a diagnosis of ICC who underwent LR,and compared outcomes between patients with HCV+vs HCV-.The primary outcomes were overall survival(OS)and recurrence-free survival.Secondary outcomes include perioperative mortality,operation duration,blood loss,intrahepatic and extrahepatic recurrence.RESULTS Seven articles,published between 2004 and 2021,fulfilled the selection criteria.All of the studies were retrospective studies.Age,incidence of male patients,albumin,bilirubin,platelets,tumor size,incidence of multiple tumors,vascular invasion,bile duct invasion,lymph node metastases,and stage 4 disease were comparable between HCV+and HCV-group.Alanine transaminase[MD 22.20,95%confidence interval(CI):13.75,30.65,P<0.00001]and aspartate transaminase levels(MD 27.27,95%CI:20.20,34.34,P<0.00001)were significantly higher in HCV+group compared to HCV-group.Incidence of cirrhosis was significantly higher in HCV+group[odds ratio(OR)5.78,95%CI:1.38,24.14,P=0.02]compared to HCV-group.Incidence of poorly differentiated disease was significantly higher in HCV+group(OR 2.55,95%CI:1.34,4.82,P=0.004)compared to HCV-group.Incidence of simultaneous hepatocellular carcinoma lesions was significantly higher in HCV+group(OR 8.31,95%CI:2.36,29.26,P=0.001)compared to HCV-group.OS was significantly worse in the HCV+group(hazard ratio 2.05,95%CI:1.46,2.88,P<0.0001)compared to HCV-group.CONCLUSION This meta-analysis demonstrated significantly worse OS in HCV+patients with ICC who underwent curative resection compared to HCV-patients.展开更多
BACKGROUND QTc interval prolongation with an increased risk of torsade de pointes(Tsd)has been described in coronavirus disease 2019(COVID-19)patients treated with hydroxychloroquine(HCQ)and azithromycin(AZI)in Wester...BACKGROUND QTc interval prolongation with an increased risk of torsade de pointes(Tsd)has been described in coronavirus disease 2019(COVID-19)patients treated with hydroxychloroquine(HCQ)and azithromycin(AZI)in Western countries.In the DR Congo,few studies have evaluated the safety of this association or proposed new molecules.AIM To determine the incidence of QTc prolongation and Tsd in COVID-19 patients treated with HCQ-AZIs vs doubase C(new molecule).METHODS In present randomized clinical trial,we have included patients with mild or moderate COVID-19 treated with either HCQ-AZI or doubase C.Electrocardiogram(ECG)changes on day 14 of randomization were determined based on pretreatment tracing.Prolonged QTc was defined as≥500 ms on day 14 or an increase of≥80 ms compared to pretreatment tracing.Patients with cardiac disease,those undergoing other treatments likely to prolong QTc,and those with disturbed ECG tracings were excluded from the study.RESULTS The study included 258 patients(mean age 41±15 years;52%men;3.4%diabetics,11.1%hypertensive).Mild and moderate COVID-19 were found in 93.5%and 6.5%of patients,respectively.At baseline,all patients had normal sinus rhythm,a mean heart rate 78±13/min,mean PR space 170±28 ms,mean QRS 76±13 ms,and mean QTc 405±30 ms.No complaints suggesting cardiac involvement were reported during or after treatment.Only four patients(1.5%)experienced QTc interval prolongation beyond 500 ms.Similarly,only five patients(1.9%)had an increase in the QTc interval of more than 80 ms.QTc prolongation was more significant in younger patients,those with high viral load at baseline,and those receiving HCQ-AZI(P<0.05).None of the patients developed Tsd.CONCLUSION QTc prolongation without Tsd was observed at a lower frequency in patients treated with HCQ-AZI vs doubase C.The absence of comorbidities and concurrent use of other products that are likely to cause arrhythmia may explain our results.展开更多
This study assessed the contribution of climate projections to improving rainfall information for cocoa crops in the central and southern regions of Côte d’Ivoire. Particular attention was paid to fourteen local...This study assessed the contribution of climate projections to improving rainfall information for cocoa crops in the central and southern regions of Côte d’Ivoire. Particular attention was paid to fourteen localities in these two climatic zones. Simulation data were obtained from the CORDEX ensemble and observation data from CHIRPS. They cover the period 1991-2005 for the reference period and the future period from 2021 to 2050 for the RCP4.5 and RCP8.5 scenarios. In addition, the study was based on the water requirements necessary during the critical phase of the cocoa tree (the flowering phase) for a good yield from the cocoa production chain on the one hand, and on a selection of three climate indices CDD, CWD and r95PTOT to study their spatio-temporal changes over two future periods 2021-2035 (near future) and 2036-2050 (medium-term) on the other. These climatic indices influence cocoa cultivation and their use in studies of climatic impacts on agriculture is of prime importance. The analysis of their spatio-temporal changes in this work also contributes to providing climate services based on rainfall, to which cocoa crops are highly sensitive. Our results show that the CDD and CWD indices vary from one region to another depending on latitude. For the fourteen localities studied, the number of consecutive dry days (CDD) could increase between now and 2050, while the number of consecutive wet days (CWD) could decrease over the period 2021-2035 and then increase over the period 2036-2050. The localities of Tabou, Aboisso and San-Pedro record high numbers of CDD index and CWD index for both projection scenarios. In comparison with the RCP4.5 and RCP8.5 scenarios, these results show that the RCP8.5 scenarios are having an impact on cocoa growing in Côte d’Ivoire.展开更多
基金supported by the Natural Science Foundation Research Plan of Shanxi Province (2023JCQN0728)。
文摘The subversive nature of information war lies not only in the information itself, but also in the circulation and application of information. It has always been a challenge to quantitatively analyze the function and effect of information flow through command, control, communications, computer, kill, intelligence,surveillance, reconnaissance (C4KISR) system. In this work, we propose a framework of force of information influence and the methods for calculating the force of information influence between C4KISR nodes of sensing, intelligence processing,decision making and fire attack. Specifically, the basic concept of force of information influence between nodes in C4KISR system is formally proposed and its mathematical definition is provided. Then, based on the information entropy theory, the model of force of information influence between C4KISR system nodes is constructed. Finally, the simulation experiments have been performed under an air defense and attack scenario. The experimental results show that, with the proposed force of information influence framework, we can effectively evaluate the contribution of information circulation through different C4KISR system nodes to the corresponding tasks. Our framework of force of information influence can also serve as an effective tool for the design and dynamic reconfiguration of C4KISR system architecture.
文摘Background: Acute Kidney Injury (AKI) stands as a prominent postoperative complication in on-pump cardiac surgery, with repercussions on morbidity, mortality, and hospitalization duration. Current diagnostic criteria relying on serum creatinine levels exhibit a delayed identification of AKI, prompting an exploration of alternative biomarkers. Aims and Objectives: This study is designed to overcome diagnostic constraints and explore the viability of serum Cystatin C as an early predictor of Acute Kidney Injury (AKI) in individuals undergoing on-pump cardiac surgery. The investigation aims to establish the relationship between serum Cystatin C levels and the onset of AKI in patients subjected to on-pump cardiac surgery. Primary objectives involve the assessment of the diagnostic effectiveness of serum Cystatin C, its comparison with serum creatinine, and the exploration of its potential for the early identification and treatment of AKI. Methodology: Conducted as a single-center study at the cardiac surgery department of BSMMU in Bangladesh from September 2020 to August 2022, a comparative cross-sectional analysis involved 31 participants categorized into No AKI and AKI groups based on Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Data collection encompassed preoperative, post-CBP (cardiopulmonary bypass) conclusion at 2 hours, postoperative day 1, and postoperative day 2 intervals. Statistical analyses included Chi-squared tests, independent Student’s t-tests, and one-sample t-tests. Significance was set at P Results: The study revealed no significant differences in baseline characteristics between the No AKI and AKI groups, except for CPB time and cross-clamp time. Serum Cystatin C levels in the AKI group exhibited statistical significance at various time points, highlighting its potential as an early detector. Conversely, Serum Creatinine levels in the AKI group showed no statistical significance. The Receiver Operating Characteristic (ROC) curve analysis further supported the efficacy of serum Cystatin C, with an Area under the ROC Curve of 0.864 and a cut-off value of 0.55 (p Conclusion: This study supports the superior utility of serum Cystatin C as an early detector of AKI in on-pump cardiac surgery patients compared to serum creatinine. Its ability to identify AKI several hours earlier may contribute to reduced morbidity, mortality, and healthcare costs. The findings underscore the significance of exploring novel biomarkers for improved post-cardiac surgery renal function assessment.
基金supported by Bundesministerium für Bildung und Forschung(BMBF,Grant no.031B0033C)Bundesministerium für Ernahrung und Landwirtschaft(BMEL,Grant no.22006516)Bundesanstalt für Landwirtschaft and Ernahrung(BLE,Grant No.2814IP004)。
文摘Verticillium longisporum(Vl43)is a soilborne hemibiotrophic fungal pathogen causing stem striping on oilseed rape(OSR)and severe yield losses.Breeding for resistant varieties is the most promising approach to control this disease.Here,we report the identification of Hva22c as a novel susceptibility factor and its potential for improving OSR resistance.Hva22c is a member of the Hva22 gene family,originally described for barley(Hordeum vulgare).Several Hva22 members have been located at the endoplasmic reticulum.Hva22c is up-regulated in response to Vl43 in both Arabidopsis and OSR.We demonstrate that knock-out of Hva22c in OSR by CRISPR/Cas9 and its homolog in Arabidopsis by T-DNA insertion reduced plants’susceptibility to Vl43 infection and impaired the development of disease symptoms.To understand the underlying mechanism,we analysed transcriptomic data from infected and non-infected roots of hva22c knock-out and wild type plants.We identified a homozygous mutant with frame-shifts in all four BnHva22c loci displaying a vastly altered transcriptional landscape at 6 dpi.Significantly,a large set of genes was suppressed under mock conditions including genes related to the endomembrane systems.Among the up-regulated genes we found several defense-related and phytohormone-responsive genes when comparing mutant to the wild type.These results demonstrate that Hva22c is functionally required for a fully compatible plant-fungus interaction.Its loss of function reduces plant susceptibility,most likely due to endoplasmatic reticulum and Golgi dysfunction accompanied by additionally activated defense responses.These findings can help improve OSR resistance to V.longisporum infection.
基金supported by the Third Xinjiang Scientific Expedition Program(2021xjkk0801).
文摘Land surface temperature(LST) directly affects the energy balance of terrestrial surface systems and impacts regional resources, ecosystem evolution, and ecosystem structures. Xinjiang Uygur Autonomous Region is located at the arid Northwest China and is extremely sensitive to climate change. There is an urgent need to understand the distribution patterns of LST in this area and quantitatively measure the nature and intensity of the impacts of the major driving factors from a spatial perspective, as well as elucidate the formation mechanisms. In this study, we used the MOD11C3 LST product developed on the basis of Moderate Resolution Imaging Spectroradiometer(MODIS) to conduct regression analysis and determine the spatiotemporal variation and differentiation pattern of LST in Xinjiang from 2000 to 2020. We analyzed the driving mechanisms of spatial heterogeneity of LST in Xinjiang and the six geomorphic zones(the Altay Mountains, Junggar Basin, Tianshan Mountains, Tarim Basin, Turpan-Hami(Tuha) Basin, and Pakakuna Mountain Group) using geographical detector(Geodetector) and geographically weighted regression(GWR) models. The warming rate of LST in Xinjiang during the study period was 0.24℃/10a, and the spatial distribution pattern of LST had obvious topographic imprints, with 87.20% of the warming zone located in the Gobi desert and areas with frequent human activities, and the cooling zone mainly located in the mountainous areas. The seasonal LST in Xinjiang was at a cooling rate of 0.09℃/10a in autumn, and showed a warming trend in other seasons. Digital elevation model(DEM), latitude, wind speed, precipitation, normalized difference vegetation index(NDVI), and sunshine duration in the single-factor and interactive detections were the key factors driving the LST changes. The direction and intensity of each major driving factor on the spatial variations of LST in the study area were heterogeneous. The negative feedback effect of DEM on the spatial differentiation of LST was the strongest. Lower latitudes, lower vegetation coverage, lower levels of precipitation, and longer sunshine duration increased LST. Unused land was the main heat source landscape, water body was the most important heat sink landscape, grassland and forest land were the land use and land cover(LULC) types with the most prominent heat sink effect, and there were significant differences in different geomorphic zones due to the influences of their vegetation types, climatic conditions, soil types, and human activities. The findings will help to facilitate sustainable climate change management, analyze local climate and environmental patterns, and improve land management strategies in Xinjiang and other arid areas.
基金The present study did not require institutional review board oversight because Global Burden of Disease Study 2019 database is de-identified and freely accessible.It does not identify hospitals,health care providers,or patients.
文摘BACKGROUND Hepatitis C is the leading cause of chronic liver disease worldwide and it significantly contributes to the burden of hepatocellular carcinoma(HCC).However,there are marked variations in the incidence and mortality rates of HCC across different geographical regions.With the advent of new widely available treatment modalities,such as direct-acting antivirals,it is becoming increasingly imperative to understand the temporal and geographical trends in HCC mortality associated with Hepatitis C.Furthermore,gender disparities in HCC mortality related to Hepatitis C are a crucial,yet underexplored aspect that adds to the disease's global impact.While some studies shed light on gender-specific trends,there is a lack of comprehensive data on global and regional mortality rates,particularly those highlighting gender disparities.This gap in knowledge hinders the development of targeted interventions and resource allocation strategies.DISCUSSION The results of our study show an overall decline in the mortality rates of patients with hepatitis C-related HCC over the last two decades.Notably,females exhibited a remarkable decrease in mortality compared to males.Regionally,East Asia and the Pacific displayed a significant decline in mortality,while Europe and Central Asia witnessed an upward trend.Latin America and the Caribbean also experienced an increase in mortality rates.However,no significant difference was observed in the Middle East and North Africa.North America exhibited a notable upward trend.South Asia and Sub-Saharan Africa significantly declined throughout the study period.This raises the hope of identifying areas for implementing more targeted resources.Despite some progress,multiple challenges remain in meeting the WHO 2030 goal of eliminating viral hepatitis[24].
文摘Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (EGCG) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EGCG dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EGCG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EGCG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.
文摘This study assesses the projected changes in the climate zoning of Côte d’Ivoire using the hierarchical classification of principal components (HCPC) method applied to the daily precipitation data of an ensemble of 14 CORDEX-AFRICA simulations under RCP4.5 and RCP8.5 scenarios. The results indicate the existence of three climate zones in Côte d’Ivoire (the coastal, the centre and the north) over the historical period (1981-2005). Moreover, CORDEX simulations project an extension of the surface area of drier climatic zones while a reduction of wetter zones, associated with the appearance of an intermediate climate zone with surface area varying from 77,560 km<sup>2</sup> to 134,960 km<sup>2</sup> depending on the period and the scenario. These results highlight the potential impacts of climate change on the delimitation of the climate zones of Côte d’Ivoire under the greenhouse gas emission scenarios. Thus, there is a reduction in the surface areas suitable for the production of cash crops such as cocoa and coffee. This could hinder the country’s economy and development, mainly based on these cash crops.
基金supported by Korea Environment Industry&Technology Institute through Project to make multi-ministerial national biological research resources more advanced Project,funded by Korea Ministry of Environment(grant number RS-2023-00230403).
文摘Objective:To evaluate the effects of Catalpa bignonioides fruit extract on the promotion of muscle growth and muscular capacity in vitro and in vivo.Methods:Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Cell proliferation was assessed using a 5-bromo-2’-deoxyuridine(BrdU)assay kit.Western blot analysis was performed to determine the protein expressions of related factors.The effects of Catalpa bignonioides extract were investigated in mice using the treadmill exhaustion test and whole-limb grip strength assay.Chemical composition analysis was performed using high-performance liquid chromatography(HPLC).Results:Catalpa bignonioides extract increased the proliferation of C2C12 mouse myoblasts by activating the Akt/mTOR signaling pathway.It also induced metabolic changes,increasing the number of mitochondria and glucose metabolism by phosphorylating adenosine monophosphate-activated protein kinase.In an in vivo study,the extract-treated mice showed improved motor abilities,such as muscular endurance and grip strength.Additionally,HPLC analysis showed that vanillic acid may be the main component of the Catalpa bignonioides extract that enhanced muscle strength.Conclusions:Catalpa bignonioides improves exercise performance through regulation of growth and metabolism in skeletal muscles,suggesting its potential as an effective natural agent for improving muscular strength.
文摘Primary Budd-Chiari syndrome (BCS) is a spontaneously fatal disease characterized by an obstruction of the hepatic venous outflow tract due to thrombosis or a primary disease of the venous wall. The primary form of BCS is extremely rare. This is a disease mainly affecting young adults of both sexes. Clinical manifestations are variable;they can be asymptomatic, acute, or subacute but mostly chronic. Several causes have been identified, such as myeloproliferative syndrome, antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria, and inherited thrombotic disorders. Data on primary BCS in Sub-Saharan Africa is rare as most publications available are case reports. In these reports, the causes are unknown with poor prognosis in most cases often leading to patient death. We herein present a case report of a male patient diagnosed with a primary BCS at Yaoundé General Hospital (Cameroon) caused by a Protein C deficiency who presented with ascites decompensating liver cirrhosis. Treatment was based on anticoagulants, diuretics and laxatives administration. Two years after the diagnosis, the patient is alive with clinical and paraclinical improvement.
基金supported by National Natural Science Foundation of China,No.32102745(to XL).
文摘Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various diseases,including ischemic stroke and neurodegenerative diseases.However,whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear.Therefore,in the present study,we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms.We established a traumatic brain injury rat model using a modified weight drop method.P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury.Severe neurological deficits were found in rats after traumatic brain injury,with deterioration in balance,walking function,and learning memory.Furthermore,hematoxylin and eosin staining showed significant neuronal cell damage,while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis.The presence of autolysosomes was observed using transmission electron microscope.P7C3-A20 treatment reversed these pathological features.Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)autophagy protein,apoptosis-related proteins(namely,Bcl-2/adenovirus E1B 19-kDa-interacting protein 3[BNIP3],and Bcl-2 associated x protein[Bax]),and elevated ubiquitin-binding protein p62(p62)autophagy protein expression.Thus,P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.
基金Funded by the Technology Innovation Leading Program of Shaanxi(No.2022QFY08-02)。
文摘The effects of ultrafine WC(WC_(UF),0.5μm) or W(1μm) and C(0.3μm)(W+C)_(UF) additives on the densification,microstructure and mechanical properties of coarse-grained cemented carbides were compared systematically.Overall,the cemented carbides with WC_(UF)/(W+C)_(UF) additives are almost fully densification to be higher than 99%,and the average grain size is kept above 2.8μm.The WC_(UF) additive assists grains to(truncated)trigonal prism shape by two dimensional(2D) growth,whereas the(W+C)_(UF) additive assists grains to rounded shape by three dimensional(3D) growth,lowers WC contiguity and increases face-centered-cubic Co.The hardness and bending strength of(75WC_(C)-15WC_(UF))-10Co are 86.6 HRA and 2 272 MPa,respectively,both higher than those of(75WC_(C)-15(W+C)_(UF))-10Co,which could be ascribed to the enhanced densification and unblemished grains.However,the fracture toughness of the(75WC_(C)-15(W+C)_(UF))-10Co is 23.5 MPa·m^(1/2),higher than that of the(75WC_(C)-15WC_(UF))-10Co due to the uniform WC-Co structure and flexible binder phase.
基金supported by the Fundamental Research Program of Shanxi Province of China,No.20210302124277the Science Foundation of Shanxi Bethune Hospital,No.2021YJ13(both to JW)。
文摘Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.
文摘In this article,we study Kahler metrics on a certain line bundle over some compact Kahler manifolds to find complete Kahler metrics with positive holomorphic sectional(or bisectional)curvatures.Thus,we apply a strategy to a famous Yau conjecture with a co-homogeneity one geometry.
基金supported by the National Natural Science Foundation of China(81971875,82300661)Natural Science Foundation of Anhui province(2308085QH246)+3 种基金Natural Science Foundation of the Anhui Higher Education Institutions(KJ2021A0205)Basic and Clinical Cooperative Research Program of Anhui Medical University(2019xkjT002,2019xkjT022,2022xkjT013)Talent Training Program,School of Basic Medical Sciences,Anhui Medical University(2022YPJH102)National College Students Innovation and Entrepreneurship Training Program of China(202210366024)。
文摘Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.
文摘Pancreatic surgery units undertake several complex operations,albeit with consi-derable morbidity and mortality,as is the case for the management of complicated acute pancreatitis or chronic pancreatitis.The centralisation of pancreatic surgery services,with the development of designated large-volume centres,has contribu-ted to significantly improved outcomes.In this editorial,we discuss the complex associations between diabetes mellitus(DM)and pancreatic/periampullary disease in the context of pancreatic surgery and overall management of complex pancreatitis,highlighting the consequential needs and the indispensable role of specialist diabetes teams in support of tertiary pancreatic services.Type 3c pan-creatogenic DM,refers to DM developing in the setting of exocrine pancreatic disease,and its identification and management can be challenging,while the glycaemic control of such patients may affect their course of treatment and outcome.Adequate preoperative diabetes assessment is warranted to aid identification of patients who are likely to need commencement or escalation of glucose lowering therapy in the postoperative period.The incidence of new onset diabetes after pancreatic resection is widely variable in the literature,and depends on the type and extent of pancreatic resection,as is the case with pancreatic parenchymal loss in the context of severe pancreatitis.Early involvement of a specialist diabetes team is essential to ensure a holistic management.In the current era,large volume pancreatic surgery services commonly abide by the principles of enhanced recovery after surgery,with inclusion of provisions for optimisation of the perioperative glycaemic control,to improve outcomes.While various guidelines are available to aid perioperative management of DM,auditing and quality improvement platforms have highlighted deficiencies in the perioperative management of diabetic patients and areas of required improvement.The need for perioperative support of diabetic patients by specialist diabetes teams is uniformly underlined,a fact that becomes clearly more prominent at all different stages in the setting of pancreatic surgery and the management of complex pancreatitis.Therefore,pancreatic surgery and tertiary pancreatitis services must be designed with a provision for support from specialist diabetes teams.With the ongoing accumulation of evidence,it would be reasonable to consider the design of specific guidelines for the glycaemic management of these patients.
基金Supported by in part David W Crabb Professorship Endowment at Indiana University School of Medicine and an intramural grant from the Atrium Health Center for Outcomes Research and Evaluation(CORE)(to deLemos AS).
文摘BACKGROUND Obesity is an independent risk factor for the development of hepatocellular carcinoma(HCC)and may influence its outcomes.However,after diagnosis of HCC,like other malignancies,the obesity paradox may exist where higher body mass index(BMI)may in fact confer a survival benefit.This is frequently observed in patients with advanced HCC and cirrhosis,who often present late with advanced tumor features and cancer related weight loss.AIM To explore the relationship between BMI and survival in patients with cirrhosis and HCC.METHODS This is a retrospective cohort study of over 2500 patients diagnosed with HCC between 2009-2019 at two United States academic medical centers.Patient and tumor characteristics were extracted manually from medical records of each institutions'cancer registries.Patients were stratified according to BMI classes:<25 kg/m^(2)(lean),25-29.9 kg/m^(2)(overweight),and>30 kg/m^(2)(obese).Patient and tumor characteristics were compared according to BMI classification.We performed an overall survival analysis using Kaplan Meier by the three BMI classes and after adjusting for Milan criteria.A multivariable Cox regression model was then used to assess known risk factors for survival in patients with cirrhosis and HCC.RESULTS A total of 2548 patients with HCC were included in the analysis of which 11.2%(n=286)were classified as noncirrhotic.The three main BMI categories:Lean(n=754),overweight(n=861),and obese(n=933)represented 29.6%,33.8%,and 36.6%of the total population overall.Within each BMI class,the non-cirrhotic patients accounted for 15%(n=100),12%(n=94),and 11%(n=92),respectively.Underweight patients with a BMI<18.5 kg/m^(2)(n=52)were included in the lean cohort.Of the obese cohort,42%(n=396)had a BMI≥35 kg/m^(2).Out of 2262 patients with cirrhosis and HCC,654(29%)were lean,767(34%)were overweight,and 841(37%)were obese.The three BMI classes did not differ by age,MELD,or Child-Pugh class.Chronic hepatitis C was the dominant etiology in lean compared to the overweight and obese patients(71%,62%,49%,P<0.001).Lean patients had significantly larger tumors compared to the other two BMI classes(5.1 vs 4.2 vs 4.2 cm,P<0.001),were more likely outside Milan(56%vs 48%vs 47%,P<0.001),and less likely to undergo transplantation(9%vs 18%vs 18%,P<0.001).While both tumor size(P<0.0001)and elevated alpha fetoprotein(P<0.0001)were associated with worse survival by regression analysis,lean BMI was not(P=0.36).CONCLUSION Lean patients with cirrhosis and HCC present with larger tumors and are more often outside Milan criteria,reflecting cancer related cachexia from delayed diagnosis.Access to care for hepatitis C virus therapy and liver transplantation confer a survival benefit,but not overweight or obese BMI classifications.
文摘BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.However,conventional diagnostic methods such as electrocardiography,echocardiography,and cardiac biomarkers have certain limitations,such as low sensitivity,specificity,availability,and cost-effectiveness.Therefore,there is a need for simple,noninvasive,and reliable biomarkers to diagnose CHD and HF.AIM To investigate serum cystatin C(Cys-C),monocyte/high-density lipoprotein cholesterol ratio(MHR),and uric acid(UA)diagnostic values for CHD and HF.METHODS We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023.The patients were divided into CHD(n=20),HF(n=20),CHD+HF(n=20),and control groups(n=20).The serum levels of Cys-C,MHR,and UA were measured using immunonephelometry and an enzymatic method,respectively,and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Serum levels of Cys-C,MHR,and UA were significantly higher in the CHD,HF,and CHD+HF groups than those in the control group.The serum levels of Cys-C,MHR,and UA were significantly higher in the CHD+HF group than those in the CHD or HF group.The ROC curve analysis showed that serum Cys-C,MHR,and UA had good diagnostic performance for CHD and HF,with areas under the curve ranging from 0.78 to 0.93.The optimal cutoff values of serum Cys-C,MHR,and UA for diagnosing CHD,HF,and CHD+HF were 1.2 mg/L,0.9×10^(9),and 389μmol/L;1.4 mg/L,1.0×10^(9),and 449μmol/L;and 1.6 mg/L,1.1×10^(9),and 508μmol/L,respectively.CONCLUSION Serum Cys-C,MHR,and UA are useful biomarkers for diagnosing CHD and HF,and CHD+HF.These can provide information for decision-making and risk stratification in patients with CHD and HF.
文摘BACKGROUND Cholangiocarcinoma is the second most common primary liver malignancy.Its incidence and mortality rates have been increasing in recent years.Hepatitis C virus(HCV)infection is a risk factor for development of cirrhosis and cholan-giocarcinoma.Currently,surgical resection remains the only curative treatment option for cholangiocarcinoma.We aim to study the impact of HCV infection on outcomes of liver resection(LR)in intrahepatic cholangiocarcinoma(ICC).AIM To study the outcomes of curative resection of ICC in patients with HCV(i.e.,HCV+)compared to patients without HCV(i.e.,HCV-).METHODS We conducted a systematic review and meta-analysis of randomized controlled trials(RCTs)and observational studies to assess the outcomes of LR in ICC in HCV+patients compared to HCV-patients in tertiary care hospitals.PubMed,EMBASE,The Cochrane Library and Scopus were systematically searched from inception till August 2023.Included studies were RCTs and non-RCTs on patients≥18 years old with a diagnosis of ICC who underwent LR,and compared outcomes between patients with HCV+vs HCV-.The primary outcomes were overall survival(OS)and recurrence-free survival.Secondary outcomes include perioperative mortality,operation duration,blood loss,intrahepatic and extrahepatic recurrence.RESULTS Seven articles,published between 2004 and 2021,fulfilled the selection criteria.All of the studies were retrospective studies.Age,incidence of male patients,albumin,bilirubin,platelets,tumor size,incidence of multiple tumors,vascular invasion,bile duct invasion,lymph node metastases,and stage 4 disease were comparable between HCV+and HCV-group.Alanine transaminase[MD 22.20,95%confidence interval(CI):13.75,30.65,P<0.00001]and aspartate transaminase levels(MD 27.27,95%CI:20.20,34.34,P<0.00001)were significantly higher in HCV+group compared to HCV-group.Incidence of cirrhosis was significantly higher in HCV+group[odds ratio(OR)5.78,95%CI:1.38,24.14,P=0.02]compared to HCV-group.Incidence of poorly differentiated disease was significantly higher in HCV+group(OR 2.55,95%CI:1.34,4.82,P=0.004)compared to HCV-group.Incidence of simultaneous hepatocellular carcinoma lesions was significantly higher in HCV+group(OR 8.31,95%CI:2.36,29.26,P=0.001)compared to HCV-group.OS was significantly worse in the HCV+group(hazard ratio 2.05,95%CI:1.46,2.88,P<0.0001)compared to HCV-group.CONCLUSION This meta-analysis demonstrated significantly worse OS in HCV+patients with ICC who underwent curative resection compared to HCV-patients.
文摘BACKGROUND QTc interval prolongation with an increased risk of torsade de pointes(Tsd)has been described in coronavirus disease 2019(COVID-19)patients treated with hydroxychloroquine(HCQ)and azithromycin(AZI)in Western countries.In the DR Congo,few studies have evaluated the safety of this association or proposed new molecules.AIM To determine the incidence of QTc prolongation and Tsd in COVID-19 patients treated with HCQ-AZIs vs doubase C(new molecule).METHODS In present randomized clinical trial,we have included patients with mild or moderate COVID-19 treated with either HCQ-AZI or doubase C.Electrocardiogram(ECG)changes on day 14 of randomization were determined based on pretreatment tracing.Prolonged QTc was defined as≥500 ms on day 14 or an increase of≥80 ms compared to pretreatment tracing.Patients with cardiac disease,those undergoing other treatments likely to prolong QTc,and those with disturbed ECG tracings were excluded from the study.RESULTS The study included 258 patients(mean age 41±15 years;52%men;3.4%diabetics,11.1%hypertensive).Mild and moderate COVID-19 were found in 93.5%and 6.5%of patients,respectively.At baseline,all patients had normal sinus rhythm,a mean heart rate 78±13/min,mean PR space 170±28 ms,mean QRS 76±13 ms,and mean QTc 405±30 ms.No complaints suggesting cardiac involvement were reported during or after treatment.Only four patients(1.5%)experienced QTc interval prolongation beyond 500 ms.Similarly,only five patients(1.9%)had an increase in the QTc interval of more than 80 ms.QTc prolongation was more significant in younger patients,those with high viral load at baseline,and those receiving HCQ-AZI(P<0.05).None of the patients developed Tsd.CONCLUSION QTc prolongation without Tsd was observed at a lower frequency in patients treated with HCQ-AZI vs doubase C.The absence of comorbidities and concurrent use of other products that are likely to cause arrhythmia may explain our results.
文摘This study assessed the contribution of climate projections to improving rainfall information for cocoa crops in the central and southern regions of Côte d’Ivoire. Particular attention was paid to fourteen localities in these two climatic zones. Simulation data were obtained from the CORDEX ensemble and observation data from CHIRPS. They cover the period 1991-2005 for the reference period and the future period from 2021 to 2050 for the RCP4.5 and RCP8.5 scenarios. In addition, the study was based on the water requirements necessary during the critical phase of the cocoa tree (the flowering phase) for a good yield from the cocoa production chain on the one hand, and on a selection of three climate indices CDD, CWD and r95PTOT to study their spatio-temporal changes over two future periods 2021-2035 (near future) and 2036-2050 (medium-term) on the other. These climatic indices influence cocoa cultivation and their use in studies of climatic impacts on agriculture is of prime importance. The analysis of their spatio-temporal changes in this work also contributes to providing climate services based on rainfall, to which cocoa crops are highly sensitive. Our results show that the CDD and CWD indices vary from one region to another depending on latitude. For the fourteen localities studied, the number of consecutive dry days (CDD) could increase between now and 2050, while the number of consecutive wet days (CWD) could decrease over the period 2021-2035 and then increase over the period 2036-2050. The localities of Tabou, Aboisso and San-Pedro record high numbers of CDD index and CWD index for both projection scenarios. In comparison with the RCP4.5 and RCP8.5 scenarios, these results show that the RCP8.5 scenarios are having an impact on cocoa growing in Côte d’Ivoire.