Objective. To establish a PCR- SSP method for discriminating as many HLA- A* 02 alleles, which could easily be introduced into a routine laboratory. Methods. In this study we typed HLA- A* 02 polymorphisms by a sequen...Objective. To establish a PCR- SSP method for discriminating as many HLA- A* 02 alleles, which could easily be introduced into a routine laboratory. Methods. In this study we typed HLA- A* 02 polymorphisms by a sequence- specific primer (SSP) method, which involved round 1 and round 2 PCR reactions to detect 17 HLA- A* 02 alleles (they are HLA- A* 0201- 0217 alleles) covering exon 2 and exon 3. Results. We have found that DNA sample concentration and purity were the most important variables in determining the quality of the results. For identifying correct band size, the size marker used was important. We noticed that different PCR machines performed differently. By this method, we detected 20 HLA- A* 02 positive genomic DNA samples and found 4 kinds of HLA- A* 02 alleles. They were HLA- A* 0201, 0203, 0206 and 0210. Conclusion. The HLA- A* 02 PCR- SSP method was proven to be a reliable and easily applicable typing method. Our results suggest that the SSP described here provides an optimal HLA- A* 02 typing technique that may be useful in selecting donor- recipient pairs in bone marrow transplantation between unrelated individuals.展开更多
Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central ne...Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central nervous system and cause damage,leading to meningitis,encephalitis,meningoencephalitis,myelitis,or post-infectious demyelinating diseases.Although neuroinflammation initially has a protective function,chronic inflammation can contribute to the development of neurodegenerative diseases.Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis,respectively.Extracellular nucleotides,particularly adenosine triphosphate and its metabolites are released from activated,infected,and dying cells,acting as alarmins mediating neuroinflammation and neurodegeneration.When viruses infect central nervous system cells,adenosine triphosphate is released as an alarmin,triggering inflammatory responses.This process is mediated by purinergic receptors,divided into two families:P1,which responds to adenosine,and P2,activated by adenosine triphosphate and other nucleotides.This review highlights how specific viruses,such as human immunodeficiency virus type 1,Theiler's murine encephalomyelitis virus,herpes simplex virus type 1,Epstein-Barr virus,dengue virus,Zika virus,and severe acute respiratory syndrome coronavirus 2,can initiate inflammatory responses through the release of extracellular nucleotides,particularly adenosine triphosphate,which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders.A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.展开更多
Urban forests are essential components of green infrastructure,however,rapid urbanization-induced changes in landscape patterns may affect their ecosystem services through complex ecological processes.A total of 184 s...Urban forests are essential components of green infrastructure,however,rapid urbanization-induced changes in landscape patterns may affect their ecosystem services through complex ecological processes.A total of 184 sample plots in the built-up areas of Nanchang,China,were used as research sites.Urbanization intensities were categorized by the rate of impervious surface area,and forest types were classified into landscape and relaxation forest,attached forest(AF),road forest(RF),and ecological public welfare forest.This study aimed to explore the spatial variations in vegetation characteristics and landscape pattern indices of different forest types under rapid urbanization.The results indicated that the largest patch index(LPI),aggregation index(AI),and percentage of landscape(PLAND)in RF and AF were lower than those in the other forest types(p<0.05).With increasing urbanization intensity,the mean perimeter-area ratio increased by 130.84%,whereas the PLAND,LPI,and AI decreased by 22−86%(p<0.05).Redundancy analysis and variation partitioning suggested that the interpretation rate of landscape pattern indices for variations in vegetation characteristics increased from low to heavy urbanization areas.Especially,the landscape shape index,patch connection index,PLAND,and mean patch size were significantly correlated with vegetation characteristics(e.g.,tree richness,herb coverage,and tree height).In the future,appropriate landscape layout superiority cases should be considered in different urbanization areas and forest types;for instance,increasing the patch connection index will beneficially improve the diversity of trees and herbs in heavy urbanization areas and the RF.This study serves as a reference for maximizing the ecosystem services of urban forests.展开更多
Insight into the carbon turnover in soil aggregates and density fractions is essential for reducing the uncertainty in estimating carbon pools on the Tibetan Plateau,and how they vary with land use type is unclear.In ...Insight into the carbon turnover in soil aggregates and density fractions is essential for reducing the uncertainty in estimating carbon pools on the Tibetan Plateau,and how they vary with land use type is unclear.In this study,the effect of land use type on carbon storage and fractionation was quantified based on organic carbon and its ^(13)C abundance at the microscale of soil aggregates and density fractions in Tibetan alpine ecosystems.The sequence of soil aggregate destruction in the land use types of plantation(13.1%)<shrubland(32.7%)<grassland(47.9%)<farmland(61.8%)shows that plantations strengthen the soil structure.Plantation land had a greater contribution of light fraction organic carbon(28.3%)but a lower contribution of mineral-associated organic carbon(40.6%)to the carbon stock compared to farmland(13.5 and 70.3%).Interestingly,plantation land enhanced the aggregational differentiation of organic carbon and ^(13)C in each density fraction,whereas no such phenomenon existed in the soil organic carbon.Carbon isotope analyses revealed that carbon transfer in the plantation land occurred from the light fraction in macroaggregates(–24.9‰)to the mineral-associated fraction in microaggregates(–19.9‰).When compared to the other three land use types,the low transferability of carbon in aggregates and density fractions in plantation land provides a stable carbon pool for the Tibetan Plateau.This study shows that plantations can mitigate global climate change by slowing carbon transfer and increasing carbon storage at the microscale of aggregates and density fractions in alpine regions.展开更多
Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,t...Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,there is still not enough knowledge on the active ingredients and possible ways that QSDs might work to treat RA.This study systematically investigated the active ingredients and mechanisms of action of QSD for treating wind-cold-dampness arthralgia type RA.Methods:UHPLC-QE-MS and network pharmacology techniques were employed to predict the potential active constituents,targets,and associated signalling pathways.Then,the therapeutic effect of QSD was examined using a wind-cold-dampness arthralgia paralytic RA rat model.Finally,the complex mechanism was comprehensively elucidated by integrating transcriptomics and network pharmacology.The above mechanisms were also verified by molecular docking,immunohistochemistry and Western blot.Results:UHPLC-QE-MS and network pharmacology analysis revealed that ferulic acid,imperatorin,magnolol,quercetin,and scopoletin could be the primary constituents in QSD responsible for its anti-RA effects.Animal experiments showed that QSD can significantly inhibit rat joint swelling degree,decrease the content of serum rheumatoid factor(RF),interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,and anti-citrullinated protein antibodies(ACPA),and increase the content of IL-4,IL-10 to relieve the clinical symptoms of wind-cold-dampness arthralgia type RA.The mechanistic study showed that QSD may effectively inhibit rat synovial hyperplasia via promoting autophagy and apoptosis of synovial cells by regulating the PI3K/Akt/mTOR signalling pathway.Conclusion:This study identifies key active ingredients in QSD and elucidates its potential mechanism for treating wind-cold-dampness arthralgia type RA,providing a basis for the clinical application of QSD.展开更多
Nitrogen(N)enrichment has resulted in widespread alteration of grassland ecosystem processes and functions mainly through disturbance in soil enzyme activities.However,we lack a comprehensive understanding of how N de...Nitrogen(N)enrichment has resulted in widespread alteration of grassland ecosystem processes and functions mainly through disturbance in soil enzyme activities.However,we lack a comprehensive understanding of how N deposition affects specific key soil enzymes that mediate plant-soil feedback of grassland.Here,with a meta-analysis on 1446 cases from field observations in China,we show that N deposition differently affects soil enzymes associated with soil biochemical processes.Specifically,N-promoted C,N,and P-acquiring hydrolase activities significantly increased by 8.73%,7.67%,and 8.69%,respectively,related to an increase in microbial-specific enzyme secretion.The increased relative N availability and soil acidification were two potential mechanisms accounting for the changes in soil enzyme activities with N enrichment.The mixed N addition in combination of NH_(4)NO_(3) and urea showed greater stimulation effect on soil enzyme activities.However,the high rate and long-term N addition tended to weaken the positive responses of soil C-,Nand P-acquiring hydrolase activities to N enrichment.Spatially increased mean annual precipitation and temperature primarily promoted the positive effects of N enrichment on N-and P-acquiring hydrolase activities,and the stimulation of C-and N-acquiring hydrolase activities by N enrichment was intensified with the increase in soil depth.Finally,multimodal inference showed that grassland type was the most important regulator of responses of microbial C,N,and P-acquiring hydrolase activities to N enrichment.This meta-analysis provides a comprehensive insight into understanding the key role of N enrichment in shaping soil enzyme activities of grassland ecosystems.展开更多
BACKGROUND The incidence of type 2 diabetes mellitus(T2DM)in children and adolescents is increasing,yet there is limited information on the available pharmacological interventions to combat T2DM and prevent associated...BACKGROUND The incidence of type 2 diabetes mellitus(T2DM)in children and adolescents is increasing,yet there is limited information on the available pharmacological interventions to combat T2DM and prevent associated comorbidities.AIM To assess the effectiveness of current pharmacological treatments in managing T2DM in children and adolescents.The protocol of the study was registered in PROSPERO(CRD42022382165).METHODS Searches were performed in PubMed,EMBASE,Scopus,and ClinicalTrials.gov for publications between 1990 to September 2024 without language restrictions.Randomized control trials(RCTs)of pharmacotherapy in children and adolescents with T2DM(aged<19 years)were included.The primary outcome was a change in glycated hemoglobin(HbA1c)from baseline to follow-up.Secondary outcomes were changes in body weight,body mass index(BMI),total cholesterol,triglycerides,high density lipoprotein,and low-density lipoprotein from baseline,and incidence of adverse events during study periods.Screening,full-text review,data extraction,and assessments of risk of bias were done by two reviewers.Conflicts on each step were resolved by a third reviewer.Data analysis was performed using Review Manager Version 6.5(RevMan 6.5)and‘R’software via RStudio,‘meta’and‘netmeta’.RESULTS A total of 12 studies having low to moderate risk of bias with 1658 participants,and follow-up duration 12-52 weeks were included.In our network meta-analysis,compared to control(s),the reduction of HbA1c was sig-nificantly larger for dulaglutide[mean difference(MD),95%confidence interval:-1.20,-2.12 to-0.28],followed by dapagliflozin(-0.94,-1.44 to-0.44),liraglutide(-0.91,-1.37 to-0.45),empagliflozin(-0.87,-1.40 to-0.34),exenatide(-0.59,-1.07 to-0.11)and linagliptin(-0.45,-0.87 to-0.02)while other drugs had little or no effect.While liraglutide was associated with a change in body weight[MD-2.41(-4.68,-0.14)kg],no other drug treatment was associated with significant changes in body weight,BMI,and lipids.Apart from level 1 hypoglycemia with liraglutide[risk difference(RD):0.20,0.04-0.37]and minor adverse events with dulaglutide(RD:0.24,0.08-0.40),no other treatment was associated with excess risk of hypoglycemia or minor or major adverse events.CONCLUSION Pharmacotherapy of T2DM with dulaglutide,dapagliflozin,liraglutide,empagliflozin,exenatide,and linagliptin in children is associated with modest reduction of HbA1c.Larger RCTs with longer follow-up durations are needed to guide better therapeutic decision making.展开更多
Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization o...Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization of numerous TA systems in various bacteria,the investigation of these systems within Streptococcus suis is still limited.Here,we systematically analyzed the type Ⅱ TA systems of 95 S.suis genomes available in the GenBank database using TAfinder.A total of 612 putative type Ⅱ TA systems were retrieved and classified into 10 categories by phylogenetic analysis.Notably,an elevated occurrence of these TA systems was observed among the important prevalent serotypes 2,4,5,9,14,Chz,NCL1,and NCL3 strains.The following study identified the activities of TA systems using 2 strategies and confirmed the regulatory effect of HigBA on the type Ⅶ secretion system in S.suis by measuringβ-galactosidase activity and transcriptional changes.Moreover,we unveiled a hitherto uncharacterized,highly prevalent novel TA system,with the composition of antitoxin–toxin–antitoxin(SS-ATA),which regulates the downstream two-component signaling system.Altogether,this study systematically analyzed the type Ⅱ TA systems within S.suis,highlighting the widespread distribution of Hig BA and SS-ATA as important regulatory elements in S.suis.展开更多
Celiac disease(CD)is a systemic autoimmune disorder triggered by gluten ingestion ingenetically predisposed individuals.It is characterized by intestinal histological damage and the production of specific autoantibodi...Celiac disease(CD)is a systemic autoimmune disorder triggered by gluten ingestion ingenetically predisposed individuals.It is characterized by intestinal histological damage and the production of specific autoantibodies.The latest European Society for Paediatric Gastroenterology,Hepatology,and Nutrition(ESPGHAN)2020 guidelines have excluded human leukocyte antigen(HLA)genotyping from the no-biopsy diagnostic approach due to its weak positive predictive value,limited availability,and high cost in some countries.However,HLA genetic testing remains valuable in certain clinical contexts.This study provided practical indications for when to request and how to interpret HLA genotyping,emphasizing its continued relevance for CD diagnosis in specific cases.We also proposed a strategy for monitoring the risk of developing type 1 diabetes(T1D)in patients with CD,based on the risk stratification carried by different HLA genotypes.A retrospective analysis of 746 patients with CD and 627 controls was conducted at our hospital starting in2012,when HLA genotyping became mandatory for the diagnosis of CD.We identified key clinical scenarios where HLA testing remains useful.Several high risk HLA-DQ genotypes strongly associated with CD were highlighted,including HLA-DQ2.5/HLA-DQ2.2and HLA-DQ2.5/HLA-DQ2.5.Notably,while the HLA-DQ2.5/HLA-DQ2.2 genotype is linked to CD,it appears to confer protection against T1D.To support clinical practice,we presented a table clarifying commonly used HLA terminology,and another summarized the main clinical situations in which HLAgenotyping should still be considered.These findings underscore the dual role of HLA testing:Not only can it help rule out CD in selected cases,but it also identifies patients with CD at risk for T1D,guiding personalized monitoring strategies.展开更多
The information from sparsely logged wellbores is currently under-utilized in reservoir simulation models and their proxies using deep and machine learning (DL/ML).This is particularly problematic for large heterogene...The information from sparsely logged wellbores is currently under-utilized in reservoir simulation models and their proxies using deep and machine learning (DL/ML).This is particularly problematic for large heterogeneous gas/oil reservoirs being considered for repurposing as gas storage reservoirs for CH_(4),CO_(2) or H_(2) and/or enhanced oil recovery technologies.Lack of well-log data leads to inadequate spatial definition of complex models due to the large uncertainties associated with the extrapolation of petrophysical rock types (PRT) calibrated with limited core data across heterogeneous and/or anisotropic reservoirs.Extracting well-log attributes from the few well logs available in many wells and tying PRT predictions based on them to seismic data has the potential to substantially improve the confidence in PRT 3D-mapping across such reservoirs.That process becomes more efficient when coupled with DL/ML models incorporating feature importance and optimized,dual-objective feature selection techniques.展开更多
BACKGROUND Cotadutide(MEDI0382)is a twincretin that acts as an agonist for both the glucagon-like peptide-1 and glucagon receptors.Several randomized controlled trials(RCTs)have been published evaluating the use of co...BACKGROUND Cotadutide(MEDI0382)is a twincretin that acts as an agonist for both the glucagon-like peptide-1 and glucagon receptors.Several randomized controlled trials(RCTs)have been published evaluating the use of cotadutide in individuals with type 2 diabetes(T2D),showing promising results.However,the efficacy and safety of the drug use have been inadequately explored by systematic reviews and meta-analyses.AIM To assess the clinical efficacy and safety of cotadutide in individuals with T2D having overweight or obesity.METHODS The systematic reviews and meta-analyses have been registered with International Prospective Register of Systematic Reviews(CRD42024511703),and the protocol summary can be accessed online.Several databases and registries,including MEDLINE(via PubMed),Scopus,Web of Science,the Cochrane Central Register of Controlled Trials,and ClinicalTrials.gov,were systematically searched using related terms from their inception to May 15,2025,for RCTs involving individuals with T2D receiving cotadutide in the intervention group.Review Manager web was used to conduct meta-analysis using random-effects models.The co-primary outcomes of interest were the changes in glycated hemoglobin(HbA1c)and the percent changes in body weight from baseline.The results of the outcomes were expressed as mean differences(MDs)or risk ratios(RRs)with 95%confidence intervals(CIs).The analysis of outcomes was stratified according to whether the control group received a placebo,denoted as the placebo control group(PCG),or an active comparator,referred to as the active control group(ACG).RESULTS Nine RCTs(mostly phase 2 RCTs,n=1525)with study durations varying from 28 days to 54 weeks that met all the inclusion criteria were analyzed;five studies had a low overall risk of bias,while the other four had some concerns.Compared to the PCG,greater reductions in HbA1c were achieved with cotadutide 100μg(MD-0.77%,95%CI:-1.06 to-0.47),200μg(MD-0.68%,95%CI:-1.12 to-0.23),300μg(MD-0.67%,95%CI:-0.79 to-0.56),and 600μg(MD-0.69%,95%CI:-0.97 to-0.41).Cotadutide 100μg(MD-1.74%,95%CI:-3.23 to-0.25),200μg(MD-2.56%,95%CI:-3.37 to-1.75),300μg(MD-3.49%,95%CI:-4.14 to-2.84),and 600μg(MD-5.45%,95%CI:-7.17 to-3.73)achieved greater percent reductions in body weight from baseline.However,the certainty of evidence for HbA1c and percent body weight reductions was very low to low.Cotadutide,at all doses,also outperformed PCG in reducing fasting plasma glucose and absolute body weight.The changes in HbA1c,percent body weight,fasting plasma glucose,and absolute body weight were similar between the cotadutide group and the ACG.Compared to PCG,pooled doses of cotadutide increased the risks of treatment-emergent adverse events(AEs),treatment-related AEs,and discontinuation of the study drug due to AEs,but not for serious AEs.More subjects experienced overall gastrointestinal AEs,dyspepsia,nausea,vomiting,constipation,and decreased appetite with cotadutide than with PCG.Compared to the ACG,none of the AEs showed increased risk in the cotadutide group.CONCLUSION Cotadutide demonstrated glycemic control and weight-loss benefits in short-term,small RCTs(mostly phase 2).However,small sample sizes,very low to low certainty of evidence,and the absence of data on long-term cardiovascular and renal outcomes highlight substantial uncertainties,warranting cautious interpretation and further investigation in larger,longer-term trials to establish its safety and efficacy profile.展开更多
BACKGROUND Pyroptosis and ubiquitination have been identified as key processes influencing the pathogenesis of diabetes mellitus(DM).AIM To investigate the genes associated with the ubiquitin-proteasome system(UPS)and...BACKGROUND Pyroptosis and ubiquitination have been identified as key processes influencing the pathogenesis of diabetes mellitus(DM).AIM To investigate the genes associated with the ubiquitin-proteasome system(UPS)and pyroptosis in type 2 DM(T2DM),and elucidate their mechanisms of action in T2DM.METHODS The datasets GSE76894,GSE41762,and GSE86469 were utilized in this study.UPS-related genes(UPSGs)and pyroptosis-related genes(PRGs)were obtained from existing literature.Differential expression analysis was performed to identify differentially expressed genes(DEGs).DEGs were intersected with UPSGs and PRGs to identify differentially expressed UPSGs and PRGs.Ubiquitin-pyroptosisrelated biomarkers were determined using Spearman’s correlation,t-tests,and receiver operating characteristic curve analysis.Pathway enrichment of biomarkers was assessed using Gene Set Enrichment Analysis(GSEA).Single sample GSEA(ssGSEA)and Spearman’s correlation were used to analyze the relationship between biomarkers and immune cells.A competitive endogenous RNA network was constructed.Subsequently,drugs related to the biomarkers were identified and a gene-drug network was established.In dataset GSE86469,single-cell sequencing was utilized to determine cell types.Finally,the expression levels of biomarkers were validated through quantitative PCR(qPCR)and western blot analysis.RESULTS A total of 581 DEGs were identified in GSE76894.Four genes[ATP binding cassette subfamily C member 8(ABCC8),retinol binding protein 4(RBP4),Ras protein-specific guanine nucleotide-releasing factor 1(RASGRF1),and solute carrier family 34 member 2(SLC34A2)]were identified as ubiquitin-pyroptosis-related biomarkers in T2DM,based on consistent expression trends and significant differences in GSE76894 and GSE41762.These biomarkers were enriched in oxidative phosphorylation and mitogen-activated protein kinase signaling pathways,which are relevant to DM.ssGSEA revealed significant differences in the enrichment scores of nine immune cell types between groups.A total of 17 microRNAs(miRNAs)and 36 long non-coding RNAs(lncRNAs)were identified,forming numerous miRNA-lncRNA interactions.Additionally,22 drugs related to the biomarkers,such as gliclazide and tretinoin,were identified.In GSE86469,eight cell types,including alpha and beta cells,were characterized.qPCR and western blot analysis confirmed that the expression trends of RASGRF1 and SLC34A2 were consistent with the findings in GSE76894.CONCLUSION This study identified four ubiquitin-pyroptosis-related biomarkers(ABCC8,RBP4,RASGRF1,and SLC34A2)in T2DM through bioinformatics analysis,providing novel insights into the diagnosis and treatment of T2DM.展开更多
Objective To systematically evaluate the overall characteristics and quality of literature on economic evaluation of drugs for type 2 diabetes,and to provide recommendations for future research and related decision-ma...Objective To systematically evaluate the overall characteristics and quality of literature on economic evaluation of drugs for type 2 diabetes,and to provide recommendations for future research and related decision-making.Methods The economic evaluation literature on drugs for type 2 diabetes based on the Chinese population were searched from CNKI,Wanfang,VIP and PubMed databases.The literature that met the inclusion criteria was selected,and the key research elements were extracted.Meanwhile,the quality of health economics studies(QHES)was used to evaluate the quality of the literature.Results and Conclusion A total of 325 articles(296 in Chinese and 29 in English)were included.Most of the studies were conducted by medical institutions(247 articles,76.0%)and they used cost-effectiveness analysis(295 articles,90.8%).However,most of the included literature did not report study perspective(267 articles,90.2%).The average QHES score of the included literature was 57.29,and the quality of the literature was concentrated in“low quality”(123 articles,37.8%)and“average quality”(138 articles,42.5%).Literature published in English journals,or using modeling methods,or from universities had relatively higher quality.The quality of economic evaluation literature on drugs for type 2 diabetes based on the Chinese population is generally low at present.There are many problems,such as single research institutions and methods,lack of research perspectives,and no sensitivity analysis.展开更多
BACKGROUND Diabetes distress(DD),an emotional problem arising from the challenges of living with diabetes and the relentless burden of daily self-management,is common among patients with type 2 diabetes(T2D).South Asi...BACKGROUND Diabetes distress(DD),an emotional problem arising from the challenges of living with diabetes and the relentless burden of daily self-management,is common among patients with type 2 diabetes(T2D).South Asia has a high T2D burden,and many studies have reported varying prevalence rates of DD in this area.AIM To estimate the pooled prevalence of DD among patients with T2D in South Asia,as it is crucial for developing effective therapeutic strategies.METHODS This systematic review and meta-analysis included cross-sectional studies conducted in South Asian countries involving adults with T2D and reported the prevalence of DD.The studies were identified by searching multiple electronic databases and registries from the inception of each database to January 30,2025,using prespecified search terms.Four authors screened and extracted data independently.Meta-analyses were conducted using RStudio software with a random-effects model.The primary outcome was the pooled prevalence of DD.RESULTS Thirty-seven cross-sectional studies(28 from India,five from Bangladesh,and two each from Pakistan and Sri Lanka)with mostly high methodological quality involving 11500 subjects were included.The pooled prevalence of DD was 44%(95%confidence interval:35-53,I2=97.4%).The prevalence of DD was highest in Pakistan(85%),followed by India and Bangladesh(42%each),and Sri Lanka(25%).Emotional burden was the most prevalent form of DD(60%),followed by treatment regimen-related distress(51%),interpersonal distress(31%),and physician-related distress(17%).Meta-regression analysis revealed no significant associations between the prevalence of DD and publication year,sample size,proportion of females,age,duration of diabetes,insulin usage,glycated hemoglobin levels,or diabetic complications.CONCLUSION South Asians with T2D seem to experience a relatively high burden of DD,and the emotional burden is the most common form of DD in this area.Larger studies utilizing unique tools and involving a broader participant base from the region would provide better epidemiological data for effectively planning high-quality diabetes care in South Asian countries.展开更多
About 44%of the world’s cocoa is produced in one single country,Côte d’Ivoire.Providing this important raw material,most Ivorian cocoa farmers live in severe poverty,which,despite a multitude of sector interven...About 44%of the world’s cocoa is produced in one single country,Côte d’Ivoire.Providing this important raw material,most Ivorian cocoa farmers live in severe poverty,which,despite a multitude of sector interventions,is still widespread,affecting social and environmental sustainability in cocoa production.In this context,cocoa farmers are still often treated as a homogeneous group of small-scale producers(mainly males),resulting in interventions being conceptualized as one-size-fits-all approaches and failing to deliver support schemes that take farmers’specific conditions appropriately into account.Applying a broader typology approach that combines farm characteristics with farmers’characteristics,this study aims to delineate Ivorian cocoa farmers and their farms into specific types in order to improve advice for targeted sustainability interventions and living income(LI)potentials.Principal component analysis and hierarchical clustering analysis of a household dataset collected in 2022 in five cocoa-growing regions of Côte d’Ivoire were chosen to identify types of male-headed farms.To assure gender sensitive analysis,a female-headed farm type was created artificially.The specific characteristics of the identified types were captured using descriptive analysis.Descriptive statistics and non-parametric tests were then applied to examine the relationships between these farm types and various outcomes.Additionally,a binary logistic model was used to estimate the probability of these links in relation to variables relevant for achieving a LI.Finally,Spearman non-parametric correlation was used to identify eventual differences in the strength of relationships between key variables per farm type.Three different types of male-headed farms are identified:type 1(the most productive and diversified farms with larger size),type 2(middle-sized farms with strong focus on cash crops),and type 3(small-sized farms with a good level of diversification for self-consumption).The artificially created type 4 represents female-headed farms with the smallest size.On average,none of these farm types achieves a LI.However,type 1 shows the smallest LI gap,while type 4 is by far the worst.Our analyses reveal underlying socio-economic factors systematically disadvantaging female-headed cocoa farms,most notably limited access to land and other material assets.The key contribution of this study lies in the empirical identification of the different characteristics of farms in a given farming system,thereby identifying the need for targeted support interventions.Type-specific recommendations are made,showing pathways to provide tailored programs to farmers of different types in order to reduce their LI gaps.展开更多
INTRODUCTION Cardiovascular system involvement is an important determinant of long-term prognosis in patients with systemic lupus erythematosus(SLE).Aneurysmal dilatation of the aortic root combined with Stanford type...INTRODUCTION Cardiovascular system involvement is an important determinant of long-term prognosis in patients with systemic lupus erythematosus(SLE).Aneurysmal dilatation of the aortic root combined with Stanford type A aortic dissection(TAAD)is a highly catastrophic complication in these patients.展开更多
BACKGROUND Type 2 diabetes(T2D)is a major health concern globally and its prevalence is expected to continue to escalate.Lifestyle intervention is an integral part of T2D management.Meal replacements are often used as...BACKGROUND Type 2 diabetes(T2D)is a major health concern globally and its prevalence is expected to continue to escalate.Lifestyle intervention is an integral part of T2D management.Meal replacements are often used as part of lifestyle intervention programs in T2D and weight management programs.There are various trials being carried out to date;however,a thorough review regarding the usage of meal replacement on its types,dosage and associated outcomes and adverse events is still lacking.AIM To provide a comprehensive overview on existing studies regarding meal replacement usage among patients with T2D,and map out glycemic and weightrelated outcomes along with adverse effects incidences.METHODS This scoping review is conducted based on Arksey and O’Malley’s seminal framework for scoping reviews.A systematic search has been done for studies published between January 2020 and January 2024 across six online databases(Cochrane Library,PubMed,Science Direct,Scopus,Web of Science and Ebscohost Discovery)using specific keywords.Two researchers independently assessed the eligibility of the studies and extracted the data.The selected articles and extracted data were reviewed by all researchers.RESULTS The initial search resulted in an initial count of 53922 articles from which 133 articles were included in this review after eligibility screening.Included studies were categorized based on meal replacement type into low calorie/energy,low glycemic index,protein-rich,low-fat,diabetes-specific formulas,and combined lifestyle intervention programs.Fifty-nine studies reported improvements on hemoglobin A1c,and 70 studies reported positive changes in weight or BMI after the meal replacement intervention.The combination of meal replacements with education,counseling or structured lifestyle interventions has proved to be effective.Only 13 studies reported occurrence of adverse events related to the intervention.Most of the reported incidents were of mild occurrences with constipation being the most reported adverse event.CONCLUSION The results suggest that meal replacements,especially when combined with lifestyle intervention programs and counseling,are an effective and safe strategy in glycemic and weight management among patients with T2D.展开更多
Xiyu conglomerate is a significant and extensively distributed geological formation in western China.A clear understanding of its properties and the establishment of a classification system are essential for selecting...Xiyu conglomerate is a significant and extensively distributed geological formation in western China.A clear understanding of its properties and the establishment of a classification system are essential for selecting appropriate research methods to investigate its engineering mechanical behavior.Based on geological data from eight typical Xiyu conglomerate geological belts and seven hydropower projects,this study summarizes the main engineering geological characteristics,and analyzes the fabric characteristics of various components of the conglomerate through laboratory tests and statistical analysis.A comprehensive classification system is proposed for Xiyu conglomerate based on two key criteria:(1)grain size distribution,quantified by the d_(50)(median grain diameter),and(2)cementation type,identified via mineralogical and geochemical analysis.This system divides Xiyu conglomerate into nine distinct categories,each defined by specific engineering geological and petrofabric properties.The results reveal that,even within the same region,the grain size composition and distribution of Xiyu conglomerate are highly heterogeneous.While the chemical composition of the cementing materials is generally consistent,notable differences in cement properties arise primarily from variations in mineral content,particularly the proportion of calcareous material(dolomite,calcite,and quartz).Conglomerates with gray or grayish-blue matrices typically exhibit higher calcareous content,whereas those with earth-yellow or khaki matrices contain less calcareous material and are predominantly argillaceous-cemented.Additionally,Xiyu conglomerate shows higher porosity compared to conventional rocks.The proposed classification method based on engineering geological and fabric characteristics offers a geological basis for further determining the engineering mechanical properties of various Xiyu conglomerate types.This approach holds potential for addressing the challenges related to unclear classification and difficulty in accurately defining mechanical parameters for Xiyu conglomerate across different regions.展开更多
Objective:To assess the burden of Group B Streptococcus(GBS)and analyze the distribution of scrotypes in relation to their source.The review highlights data gaps in transmission dynamics and regional food consumption ...Objective:To assess the burden of Group B Streptococcus(GBS)and analyze the distribution of scrotypes in relation to their source.The review highlights data gaps in transmission dynamics and regional food consumption practices,which are esscntial for designing cffective public health strategies and advancing vaccine development.Methods:Scarches were conducted in Web of Science,MEDLINE,Science Direct,PubMcd,and Scopus databases to find studies related to GBS during 1990-2025.Eligible studies were those that described prevalence,scrotype distribution or scquence type(ST)of GBS in Southeast Asian countries.Random-cffects meta-analysis was used to pool data.Results:A total of 26 studies met the inclusion criteria from cight countries.The pooled estimate of maternal GBS colonization was 15.1%,with scrotypesII,v,ⅡI,V,and I a accounting for the majority of cases(91.24%)in the Southcast Asia studies.Data on ST was limited;however,ST1 was found to be predominant in Malaysia and Thailand,while ST283 was notably linked to the consumption of raw fish.Conclusions:The pooled estimate of the maternal colonization with GBS was 15.1%which is cquivalent to many other primary and review reports worldwide.Distribution of scrotype and ST is needed to be studied in Southcast Asian countries to devise cffective preventive measures.These findings underscore thc importance of surveillance and tailored prevention strategies to combat GBS infections in Southcast Asia.展开更多
文摘Objective. To establish a PCR- SSP method for discriminating as many HLA- A* 02 alleles, which could easily be introduced into a routine laboratory. Methods. In this study we typed HLA- A* 02 polymorphisms by a sequence- specific primer (SSP) method, which involved round 1 and round 2 PCR reactions to detect 17 HLA- A* 02 alleles (they are HLA- A* 0201- 0217 alleles) covering exon 2 and exon 3. Results. We have found that DNA sample concentration and purity were the most important variables in determining the quality of the results. For identifying correct band size, the size marker used was important. We noticed that different PCR machines performed differently. By this method, we detected 20 HLA- A* 02 positive genomic DNA samples and found 4 kinds of HLA- A* 02 alleles. They were HLA- A* 0201, 0203, 0206 and 0210. Conclusion. The HLA- A* 02 PCR- SSP method was proven to be a reliable and easily applicable typing method. Our results suggest that the SSP described here provides an optimal HLA- A* 02 typing technique that may be useful in selecting donor- recipient pairs in bone marrow transplantation between unrelated individuals.
基金supported by funds from the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico do Brasil(CNPq)(312286/2023-6,307201/2023-6,and Instituto Nacional Saude Cerebral INSC,No.406020/2022-1)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior(CAPES)Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro-FAPERJ(E-26/010.002260/2019,E-26/010.001652/2019,E-26/010.101036/2018,E-26/202.774/2018,E-26/210.240/2020,E-26/211.138/2021,26/210.823/2021,E-26/211.325/2021,E-26/210.779/2021,E-26/201.086/2022,E-26/210.312/2022,E-26/203.262/2023,E-26/200.195/2023)(to LEBS)。
文摘Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central nervous system and cause damage,leading to meningitis,encephalitis,meningoencephalitis,myelitis,or post-infectious demyelinating diseases.Although neuroinflammation initially has a protective function,chronic inflammation can contribute to the development of neurodegenerative diseases.Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis,respectively.Extracellular nucleotides,particularly adenosine triphosphate and its metabolites are released from activated,infected,and dying cells,acting as alarmins mediating neuroinflammation and neurodegeneration.When viruses infect central nervous system cells,adenosine triphosphate is released as an alarmin,triggering inflammatory responses.This process is mediated by purinergic receptors,divided into two families:P1,which responds to adenosine,and P2,activated by adenosine triphosphate and other nucleotides.This review highlights how specific viruses,such as human immunodeficiency virus type 1,Theiler's murine encephalomyelitis virus,herpes simplex virus type 1,Epstein-Barr virus,dengue virus,Zika virus,and severe acute respiratory syndrome coronavirus 2,can initiate inflammatory responses through the release of extracellular nucleotides,particularly adenosine triphosphate,which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders.A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.
基金supported by the National Natural Science Foundation of China(32460380,42007042)State Key Laboratory of Subtropical Silviculture(SKLSSKF2023-06)+2 种基金Natural Science Foundation of Jiangxi Province(20242BAB25389)National Undergraduate Innovation and Entrepreneurship Training Program(202410410029X)Jiangxi Province Graduate Student Innovation Special Fund Project(YC2024-S330).
文摘Urban forests are essential components of green infrastructure,however,rapid urbanization-induced changes in landscape patterns may affect their ecosystem services through complex ecological processes.A total of 184 sample plots in the built-up areas of Nanchang,China,were used as research sites.Urbanization intensities were categorized by the rate of impervious surface area,and forest types were classified into landscape and relaxation forest,attached forest(AF),road forest(RF),and ecological public welfare forest.This study aimed to explore the spatial variations in vegetation characteristics and landscape pattern indices of different forest types under rapid urbanization.The results indicated that the largest patch index(LPI),aggregation index(AI),and percentage of landscape(PLAND)in RF and AF were lower than those in the other forest types(p<0.05).With increasing urbanization intensity,the mean perimeter-area ratio increased by 130.84%,whereas the PLAND,LPI,and AI decreased by 22−86%(p<0.05).Redundancy analysis and variation partitioning suggested that the interpretation rate of landscape pattern indices for variations in vegetation characteristics increased from low to heavy urbanization areas.Especially,the landscape shape index,patch connection index,PLAND,and mean patch size were significantly correlated with vegetation characteristics(e.g.,tree richness,herb coverage,and tree height).In the future,appropriate landscape layout superiority cases should be considered in different urbanization areas and forest types;for instance,increasing the patch connection index will beneficially improve the diversity of trees and herbs in heavy urbanization areas and the RF.This study serves as a reference for maximizing the ecosystem services of urban forests.
基金financially supported by the National Natural Science Foundation of China (42477044,32171648 and U23A2017)the Hubei Provincial Science and Technology Program,China (2025AFD451 and 2022CFB030)。
文摘Insight into the carbon turnover in soil aggregates and density fractions is essential for reducing the uncertainty in estimating carbon pools on the Tibetan Plateau,and how they vary with land use type is unclear.In this study,the effect of land use type on carbon storage and fractionation was quantified based on organic carbon and its ^(13)C abundance at the microscale of soil aggregates and density fractions in Tibetan alpine ecosystems.The sequence of soil aggregate destruction in the land use types of plantation(13.1%)<shrubland(32.7%)<grassland(47.9%)<farmland(61.8%)shows that plantations strengthen the soil structure.Plantation land had a greater contribution of light fraction organic carbon(28.3%)but a lower contribution of mineral-associated organic carbon(40.6%)to the carbon stock compared to farmland(13.5 and 70.3%).Interestingly,plantation land enhanced the aggregational differentiation of organic carbon and ^(13)C in each density fraction,whereas no such phenomenon existed in the soil organic carbon.Carbon isotope analyses revealed that carbon transfer in the plantation land occurred from the light fraction in macroaggregates(–24.9‰)to the mineral-associated fraction in microaggregates(–19.9‰).When compared to the other three land use types,the low transferability of carbon in aggregates and density fractions in plantation land provides a stable carbon pool for the Tibetan Plateau.This study shows that plantations can mitigate global climate change by slowing carbon transfer and increasing carbon storage at the microscale of aggregates and density fractions in alpine regions.
基金the National Natural Science Foundation of China(82204935)the construction project of Zhao Feng National Old Pharmacist Inheritance Studio of State Administration of Traditional Chinese Medicine(National Traditional Chinese Medicine Education Letter[2024]255)+1 种基金the open project of the Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine in Shaanxi Province(KF202302)the project of Xi’an Municipal Bureau of Science and Technology(23YXYJ0042)for financial support.
文摘Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,there is still not enough knowledge on the active ingredients and possible ways that QSDs might work to treat RA.This study systematically investigated the active ingredients and mechanisms of action of QSD for treating wind-cold-dampness arthralgia type RA.Methods:UHPLC-QE-MS and network pharmacology techniques were employed to predict the potential active constituents,targets,and associated signalling pathways.Then,the therapeutic effect of QSD was examined using a wind-cold-dampness arthralgia paralytic RA rat model.Finally,the complex mechanism was comprehensively elucidated by integrating transcriptomics and network pharmacology.The above mechanisms were also verified by molecular docking,immunohistochemistry and Western blot.Results:UHPLC-QE-MS and network pharmacology analysis revealed that ferulic acid,imperatorin,magnolol,quercetin,and scopoletin could be the primary constituents in QSD responsible for its anti-RA effects.Animal experiments showed that QSD can significantly inhibit rat joint swelling degree,decrease the content of serum rheumatoid factor(RF),interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,and anti-citrullinated protein antibodies(ACPA),and increase the content of IL-4,IL-10 to relieve the clinical symptoms of wind-cold-dampness arthralgia type RA.The mechanistic study showed that QSD may effectively inhibit rat synovial hyperplasia via promoting autophagy and apoptosis of synovial cells by regulating the PI3K/Akt/mTOR signalling pathway.Conclusion:This study identifies key active ingredients in QSD and elucidates its potential mechanism for treating wind-cold-dampness arthralgia type RA,providing a basis for the clinical application of QSD.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA28110300)National Natural Science Foundation of China(No.U23A2004)+3 种基金Natural Science Foundation of Jilin Province,China(No.YDZJ202201ZYTS522)Science and Technology Cooperation Program between Jilin Province and Chinese Academy of Sciences(No.2023SYHZ0053)Innovation Team Program of Northeast Institute of Geography and Agroecology,Chinese Academy of Sciences(No.2023CXTD02)the European Commission under Marie Sk?odowska-Curie(No.101034371)。
文摘Nitrogen(N)enrichment has resulted in widespread alteration of grassland ecosystem processes and functions mainly through disturbance in soil enzyme activities.However,we lack a comprehensive understanding of how N deposition affects specific key soil enzymes that mediate plant-soil feedback of grassland.Here,with a meta-analysis on 1446 cases from field observations in China,we show that N deposition differently affects soil enzymes associated with soil biochemical processes.Specifically,N-promoted C,N,and P-acquiring hydrolase activities significantly increased by 8.73%,7.67%,and 8.69%,respectively,related to an increase in microbial-specific enzyme secretion.The increased relative N availability and soil acidification were two potential mechanisms accounting for the changes in soil enzyme activities with N enrichment.The mixed N addition in combination of NH_(4)NO_(3) and urea showed greater stimulation effect on soil enzyme activities.However,the high rate and long-term N addition tended to weaken the positive responses of soil C-,Nand P-acquiring hydrolase activities to N enrichment.Spatially increased mean annual precipitation and temperature primarily promoted the positive effects of N enrichment on N-and P-acquiring hydrolase activities,and the stimulation of C-and N-acquiring hydrolase activities by N enrichment was intensified with the increase in soil depth.Finally,multimodal inference showed that grassland type was the most important regulator of responses of microbial C,N,and P-acquiring hydrolase activities to N enrichment.This meta-analysis provides a comprehensive insight into understanding the key role of N enrichment in shaping soil enzyme activities of grassland ecosystems.
文摘BACKGROUND The incidence of type 2 diabetes mellitus(T2DM)in children and adolescents is increasing,yet there is limited information on the available pharmacological interventions to combat T2DM and prevent associated comorbidities.AIM To assess the effectiveness of current pharmacological treatments in managing T2DM in children and adolescents.The protocol of the study was registered in PROSPERO(CRD42022382165).METHODS Searches were performed in PubMed,EMBASE,Scopus,and ClinicalTrials.gov for publications between 1990 to September 2024 without language restrictions.Randomized control trials(RCTs)of pharmacotherapy in children and adolescents with T2DM(aged<19 years)were included.The primary outcome was a change in glycated hemoglobin(HbA1c)from baseline to follow-up.Secondary outcomes were changes in body weight,body mass index(BMI),total cholesterol,triglycerides,high density lipoprotein,and low-density lipoprotein from baseline,and incidence of adverse events during study periods.Screening,full-text review,data extraction,and assessments of risk of bias were done by two reviewers.Conflicts on each step were resolved by a third reviewer.Data analysis was performed using Review Manager Version 6.5(RevMan 6.5)and‘R’software via RStudio,‘meta’and‘netmeta’.RESULTS A total of 12 studies having low to moderate risk of bias with 1658 participants,and follow-up duration 12-52 weeks were included.In our network meta-analysis,compared to control(s),the reduction of HbA1c was sig-nificantly larger for dulaglutide[mean difference(MD),95%confidence interval:-1.20,-2.12 to-0.28],followed by dapagliflozin(-0.94,-1.44 to-0.44),liraglutide(-0.91,-1.37 to-0.45),empagliflozin(-0.87,-1.40 to-0.34),exenatide(-0.59,-1.07 to-0.11)and linagliptin(-0.45,-0.87 to-0.02)while other drugs had little or no effect.While liraglutide was associated with a change in body weight[MD-2.41(-4.68,-0.14)kg],no other drug treatment was associated with significant changes in body weight,BMI,and lipids.Apart from level 1 hypoglycemia with liraglutide[risk difference(RD):0.20,0.04-0.37]and minor adverse events with dulaglutide(RD:0.24,0.08-0.40),no other treatment was associated with excess risk of hypoglycemia or minor or major adverse events.CONCLUSION Pharmacotherapy of T2DM with dulaglutide,dapagliflozin,liraglutide,empagliflozin,exenatide,and linagliptin in children is associated with modest reduction of HbA1c.Larger RCTs with longer follow-up durations are needed to guide better therapeutic decision making.
基金supported by the National Key Research and Development Program of China(2022YFD1800904)the National Natural Science Foundation of China(31972650 and 32102673)+1 种基金the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(KYCX22_0780)the China Postdoctoral Science Foundation(2020M682297)。
文摘Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization of numerous TA systems in various bacteria,the investigation of these systems within Streptococcus suis is still limited.Here,we systematically analyzed the type Ⅱ TA systems of 95 S.suis genomes available in the GenBank database using TAfinder.A total of 612 putative type Ⅱ TA systems were retrieved and classified into 10 categories by phylogenetic analysis.Notably,an elevated occurrence of these TA systems was observed among the important prevalent serotypes 2,4,5,9,14,Chz,NCL1,and NCL3 strains.The following study identified the activities of TA systems using 2 strategies and confirmed the regulatory effect of HigBA on the type Ⅶ secretion system in S.suis by measuringβ-galactosidase activity and transcriptional changes.Moreover,we unveiled a hitherto uncharacterized,highly prevalent novel TA system,with the composition of antitoxin–toxin–antitoxin(SS-ATA),which regulates the downstream two-component signaling system.Altogether,this study systematically analyzed the type Ⅱ TA systems within S.suis,highlighting the widespread distribution of Hig BA and SS-ATA as important regulatory elements in S.suis.
基金Supported by Fondazione di Sardegna,No.2020.2284.
文摘Celiac disease(CD)is a systemic autoimmune disorder triggered by gluten ingestion ingenetically predisposed individuals.It is characterized by intestinal histological damage and the production of specific autoantibodies.The latest European Society for Paediatric Gastroenterology,Hepatology,and Nutrition(ESPGHAN)2020 guidelines have excluded human leukocyte antigen(HLA)genotyping from the no-biopsy diagnostic approach due to its weak positive predictive value,limited availability,and high cost in some countries.However,HLA genetic testing remains valuable in certain clinical contexts.This study provided practical indications for when to request and how to interpret HLA genotyping,emphasizing its continued relevance for CD diagnosis in specific cases.We also proposed a strategy for monitoring the risk of developing type 1 diabetes(T1D)in patients with CD,based on the risk stratification carried by different HLA genotypes.A retrospective analysis of 746 patients with CD and 627 controls was conducted at our hospital starting in2012,when HLA genotyping became mandatory for the diagnosis of CD.We identified key clinical scenarios where HLA testing remains useful.Several high risk HLA-DQ genotypes strongly associated with CD were highlighted,including HLA-DQ2.5/HLA-DQ2.2and HLA-DQ2.5/HLA-DQ2.5.Notably,while the HLA-DQ2.5/HLA-DQ2.2 genotype is linked to CD,it appears to confer protection against T1D.To support clinical practice,we presented a table clarifying commonly used HLA terminology,and another summarized the main clinical situations in which HLAgenotyping should still be considered.These findings underscore the dual role of HLA testing:Not only can it help rule out CD in selected cases,but it also identifies patients with CD at risk for T1D,guiding personalized monitoring strategies.
文摘The information from sparsely logged wellbores is currently under-utilized in reservoir simulation models and their proxies using deep and machine learning (DL/ML).This is particularly problematic for large heterogeneous gas/oil reservoirs being considered for repurposing as gas storage reservoirs for CH_(4),CO_(2) or H_(2) and/or enhanced oil recovery technologies.Lack of well-log data leads to inadequate spatial definition of complex models due to the large uncertainties associated with the extrapolation of petrophysical rock types (PRT) calibrated with limited core data across heterogeneous and/or anisotropic reservoirs.Extracting well-log attributes from the few well logs available in many wells and tying PRT predictions based on them to seismic data has the potential to substantially improve the confidence in PRT 3D-mapping across such reservoirs.That process becomes more efficient when coupled with DL/ML models incorporating feature importance and optimized,dual-objective feature selection techniques.
文摘BACKGROUND Cotadutide(MEDI0382)is a twincretin that acts as an agonist for both the glucagon-like peptide-1 and glucagon receptors.Several randomized controlled trials(RCTs)have been published evaluating the use of cotadutide in individuals with type 2 diabetes(T2D),showing promising results.However,the efficacy and safety of the drug use have been inadequately explored by systematic reviews and meta-analyses.AIM To assess the clinical efficacy and safety of cotadutide in individuals with T2D having overweight or obesity.METHODS The systematic reviews and meta-analyses have been registered with International Prospective Register of Systematic Reviews(CRD42024511703),and the protocol summary can be accessed online.Several databases and registries,including MEDLINE(via PubMed),Scopus,Web of Science,the Cochrane Central Register of Controlled Trials,and ClinicalTrials.gov,were systematically searched using related terms from their inception to May 15,2025,for RCTs involving individuals with T2D receiving cotadutide in the intervention group.Review Manager web was used to conduct meta-analysis using random-effects models.The co-primary outcomes of interest were the changes in glycated hemoglobin(HbA1c)and the percent changes in body weight from baseline.The results of the outcomes were expressed as mean differences(MDs)or risk ratios(RRs)with 95%confidence intervals(CIs).The analysis of outcomes was stratified according to whether the control group received a placebo,denoted as the placebo control group(PCG),or an active comparator,referred to as the active control group(ACG).RESULTS Nine RCTs(mostly phase 2 RCTs,n=1525)with study durations varying from 28 days to 54 weeks that met all the inclusion criteria were analyzed;five studies had a low overall risk of bias,while the other four had some concerns.Compared to the PCG,greater reductions in HbA1c were achieved with cotadutide 100μg(MD-0.77%,95%CI:-1.06 to-0.47),200μg(MD-0.68%,95%CI:-1.12 to-0.23),300μg(MD-0.67%,95%CI:-0.79 to-0.56),and 600μg(MD-0.69%,95%CI:-0.97 to-0.41).Cotadutide 100μg(MD-1.74%,95%CI:-3.23 to-0.25),200μg(MD-2.56%,95%CI:-3.37 to-1.75),300μg(MD-3.49%,95%CI:-4.14 to-2.84),and 600μg(MD-5.45%,95%CI:-7.17 to-3.73)achieved greater percent reductions in body weight from baseline.However,the certainty of evidence for HbA1c and percent body weight reductions was very low to low.Cotadutide,at all doses,also outperformed PCG in reducing fasting plasma glucose and absolute body weight.The changes in HbA1c,percent body weight,fasting plasma glucose,and absolute body weight were similar between the cotadutide group and the ACG.Compared to PCG,pooled doses of cotadutide increased the risks of treatment-emergent adverse events(AEs),treatment-related AEs,and discontinuation of the study drug due to AEs,but not for serious AEs.More subjects experienced overall gastrointestinal AEs,dyspepsia,nausea,vomiting,constipation,and decreased appetite with cotadutide than with PCG.Compared to the ACG,none of the AEs showed increased risk in the cotadutide group.CONCLUSION Cotadutide demonstrated glycemic control and weight-loss benefits in short-term,small RCTs(mostly phase 2).However,small sample sizes,very low to low certainty of evidence,and the absence of data on long-term cardiovascular and renal outcomes highlight substantial uncertainties,warranting cautious interpretation and further investigation in larger,longer-term trials to establish its safety and efficacy profile.
基金Supported by National Natural Science Foundation of China,No.82270863 and No.82470849Major Project of Anhui Provincial University Research Program,No.2023AH040400+1 种基金Joint Fund for Medical Artificial Intelligence,No.MAI2023Q026the Project of Health Commission Scientific Research in Anhui Province,No.AHWJ2024Aa20477.
文摘BACKGROUND Pyroptosis and ubiquitination have been identified as key processes influencing the pathogenesis of diabetes mellitus(DM).AIM To investigate the genes associated with the ubiquitin-proteasome system(UPS)and pyroptosis in type 2 DM(T2DM),and elucidate their mechanisms of action in T2DM.METHODS The datasets GSE76894,GSE41762,and GSE86469 were utilized in this study.UPS-related genes(UPSGs)and pyroptosis-related genes(PRGs)were obtained from existing literature.Differential expression analysis was performed to identify differentially expressed genes(DEGs).DEGs were intersected with UPSGs and PRGs to identify differentially expressed UPSGs and PRGs.Ubiquitin-pyroptosisrelated biomarkers were determined using Spearman’s correlation,t-tests,and receiver operating characteristic curve analysis.Pathway enrichment of biomarkers was assessed using Gene Set Enrichment Analysis(GSEA).Single sample GSEA(ssGSEA)and Spearman’s correlation were used to analyze the relationship between biomarkers and immune cells.A competitive endogenous RNA network was constructed.Subsequently,drugs related to the biomarkers were identified and a gene-drug network was established.In dataset GSE86469,single-cell sequencing was utilized to determine cell types.Finally,the expression levels of biomarkers were validated through quantitative PCR(qPCR)and western blot analysis.RESULTS A total of 581 DEGs were identified in GSE76894.Four genes[ATP binding cassette subfamily C member 8(ABCC8),retinol binding protein 4(RBP4),Ras protein-specific guanine nucleotide-releasing factor 1(RASGRF1),and solute carrier family 34 member 2(SLC34A2)]were identified as ubiquitin-pyroptosis-related biomarkers in T2DM,based on consistent expression trends and significant differences in GSE76894 and GSE41762.These biomarkers were enriched in oxidative phosphorylation and mitogen-activated protein kinase signaling pathways,which are relevant to DM.ssGSEA revealed significant differences in the enrichment scores of nine immune cell types between groups.A total of 17 microRNAs(miRNAs)and 36 long non-coding RNAs(lncRNAs)were identified,forming numerous miRNA-lncRNA interactions.Additionally,22 drugs related to the biomarkers,such as gliclazide and tretinoin,were identified.In GSE86469,eight cell types,including alpha and beta cells,were characterized.qPCR and western blot analysis confirmed that the expression trends of RASGRF1 and SLC34A2 were consistent with the findings in GSE76894.CONCLUSION This study identified four ubiquitin-pyroptosis-related biomarkers(ABCC8,RBP4,RASGRF1,and SLC34A2)in T2DM through bioinformatics analysis,providing novel insights into the diagnosis and treatment of T2DM.
文摘Objective To systematically evaluate the overall characteristics and quality of literature on economic evaluation of drugs for type 2 diabetes,and to provide recommendations for future research and related decision-making.Methods The economic evaluation literature on drugs for type 2 diabetes based on the Chinese population were searched from CNKI,Wanfang,VIP and PubMed databases.The literature that met the inclusion criteria was selected,and the key research elements were extracted.Meanwhile,the quality of health economics studies(QHES)was used to evaluate the quality of the literature.Results and Conclusion A total of 325 articles(296 in Chinese and 29 in English)were included.Most of the studies were conducted by medical institutions(247 articles,76.0%)and they used cost-effectiveness analysis(295 articles,90.8%).However,most of the included literature did not report study perspective(267 articles,90.2%).The average QHES score of the included literature was 57.29,and the quality of the literature was concentrated in“low quality”(123 articles,37.8%)and“average quality”(138 articles,42.5%).Literature published in English journals,or using modeling methods,or from universities had relatively higher quality.The quality of economic evaluation literature on drugs for type 2 diabetes based on the Chinese population is generally low at present.There are many problems,such as single research institutions and methods,lack of research perspectives,and no sensitivity analysis.
文摘BACKGROUND Diabetes distress(DD),an emotional problem arising from the challenges of living with diabetes and the relentless burden of daily self-management,is common among patients with type 2 diabetes(T2D).South Asia has a high T2D burden,and many studies have reported varying prevalence rates of DD in this area.AIM To estimate the pooled prevalence of DD among patients with T2D in South Asia,as it is crucial for developing effective therapeutic strategies.METHODS This systematic review and meta-analysis included cross-sectional studies conducted in South Asian countries involving adults with T2D and reported the prevalence of DD.The studies were identified by searching multiple electronic databases and registries from the inception of each database to January 30,2025,using prespecified search terms.Four authors screened and extracted data independently.Meta-analyses were conducted using RStudio software with a random-effects model.The primary outcome was the pooled prevalence of DD.RESULTS Thirty-seven cross-sectional studies(28 from India,five from Bangladesh,and two each from Pakistan and Sri Lanka)with mostly high methodological quality involving 11500 subjects were included.The pooled prevalence of DD was 44%(95%confidence interval:35-53,I2=97.4%).The prevalence of DD was highest in Pakistan(85%),followed by India and Bangladesh(42%each),and Sri Lanka(25%).Emotional burden was the most prevalent form of DD(60%),followed by treatment regimen-related distress(51%),interpersonal distress(31%),and physician-related distress(17%).Meta-regression analysis revealed no significant associations between the prevalence of DD and publication year,sample size,proportion of females,age,duration of diabetes,insulin usage,glycated hemoglobin levels,or diabetic complications.CONCLUSION South Asians with T2D seem to experience a relatively high burden of DD,and the emotional burden is the most common form of DD in this area.Larger studies utilizing unique tools and involving a broader participant base from the region would provide better epidemiological data for effectively planning high-quality diabetes care in South Asian countries.
基金This work was conducted in the frame of the accompanying research on strategies for improving farmer families’incomes and sustainable cocoa production funded by the German Federal Ministry for Economic Cooperation and Development(BMZ).
文摘About 44%of the world’s cocoa is produced in one single country,Côte d’Ivoire.Providing this important raw material,most Ivorian cocoa farmers live in severe poverty,which,despite a multitude of sector interventions,is still widespread,affecting social and environmental sustainability in cocoa production.In this context,cocoa farmers are still often treated as a homogeneous group of small-scale producers(mainly males),resulting in interventions being conceptualized as one-size-fits-all approaches and failing to deliver support schemes that take farmers’specific conditions appropriately into account.Applying a broader typology approach that combines farm characteristics with farmers’characteristics,this study aims to delineate Ivorian cocoa farmers and their farms into specific types in order to improve advice for targeted sustainability interventions and living income(LI)potentials.Principal component analysis and hierarchical clustering analysis of a household dataset collected in 2022 in five cocoa-growing regions of Côte d’Ivoire were chosen to identify types of male-headed farms.To assure gender sensitive analysis,a female-headed farm type was created artificially.The specific characteristics of the identified types were captured using descriptive analysis.Descriptive statistics and non-parametric tests were then applied to examine the relationships between these farm types and various outcomes.Additionally,a binary logistic model was used to estimate the probability of these links in relation to variables relevant for achieving a LI.Finally,Spearman non-parametric correlation was used to identify eventual differences in the strength of relationships between key variables per farm type.Three different types of male-headed farms are identified:type 1(the most productive and diversified farms with larger size),type 2(middle-sized farms with strong focus on cash crops),and type 3(small-sized farms with a good level of diversification for self-consumption).The artificially created type 4 represents female-headed farms with the smallest size.On average,none of these farm types achieves a LI.However,type 1 shows the smallest LI gap,while type 4 is by far the worst.Our analyses reveal underlying socio-economic factors systematically disadvantaging female-headed cocoa farms,most notably limited access to land and other material assets.The key contribution of this study lies in the empirical identification of the different characteristics of farms in a given farming system,thereby identifying the need for targeted support interventions.Type-specific recommendations are made,showing pathways to provide tailored programs to farmers of different types in order to reduce their LI gaps.
文摘INTRODUCTION Cardiovascular system involvement is an important determinant of long-term prognosis in patients with systemic lupus erythematosus(SLE).Aneurysmal dilatation of the aortic root combined with Stanford type A aortic dissection(TAAD)is a highly catastrophic complication in these patients.
文摘BACKGROUND Type 2 diabetes(T2D)is a major health concern globally and its prevalence is expected to continue to escalate.Lifestyle intervention is an integral part of T2D management.Meal replacements are often used as part of lifestyle intervention programs in T2D and weight management programs.There are various trials being carried out to date;however,a thorough review regarding the usage of meal replacement on its types,dosage and associated outcomes and adverse events is still lacking.AIM To provide a comprehensive overview on existing studies regarding meal replacement usage among patients with T2D,and map out glycemic and weightrelated outcomes along with adverse effects incidences.METHODS This scoping review is conducted based on Arksey and O’Malley’s seminal framework for scoping reviews.A systematic search has been done for studies published between January 2020 and January 2024 across six online databases(Cochrane Library,PubMed,Science Direct,Scopus,Web of Science and Ebscohost Discovery)using specific keywords.Two researchers independently assessed the eligibility of the studies and extracted the data.The selected articles and extracted data were reviewed by all researchers.RESULTS The initial search resulted in an initial count of 53922 articles from which 133 articles were included in this review after eligibility screening.Included studies were categorized based on meal replacement type into low calorie/energy,low glycemic index,protein-rich,low-fat,diabetes-specific formulas,and combined lifestyle intervention programs.Fifty-nine studies reported improvements on hemoglobin A1c,and 70 studies reported positive changes in weight or BMI after the meal replacement intervention.The combination of meal replacements with education,counseling or structured lifestyle interventions has proved to be effective.Only 13 studies reported occurrence of adverse events related to the intervention.Most of the reported incidents were of mild occurrences with constipation being the most reported adverse event.CONCLUSION The results suggest that meal replacements,especially when combined with lifestyle intervention programs and counseling,are an effective and safe strategy in glycemic and weight management among patients with T2D.
基金Xinjiang Water Science and Technology Special Project,Grant/Award Numbers:XSKJ-2022-05,XSKJ-2023-30State Grid Co.,LTD.Technology Project,Grant/Award Number:5108-202218280A-2-301-XG。
文摘Xiyu conglomerate is a significant and extensively distributed geological formation in western China.A clear understanding of its properties and the establishment of a classification system are essential for selecting appropriate research methods to investigate its engineering mechanical behavior.Based on geological data from eight typical Xiyu conglomerate geological belts and seven hydropower projects,this study summarizes the main engineering geological characteristics,and analyzes the fabric characteristics of various components of the conglomerate through laboratory tests and statistical analysis.A comprehensive classification system is proposed for Xiyu conglomerate based on two key criteria:(1)grain size distribution,quantified by the d_(50)(median grain diameter),and(2)cementation type,identified via mineralogical and geochemical analysis.This system divides Xiyu conglomerate into nine distinct categories,each defined by specific engineering geological and petrofabric properties.The results reveal that,even within the same region,the grain size composition and distribution of Xiyu conglomerate are highly heterogeneous.While the chemical composition of the cementing materials is generally consistent,notable differences in cement properties arise primarily from variations in mineral content,particularly the proportion of calcareous material(dolomite,calcite,and quartz).Conglomerates with gray or grayish-blue matrices typically exhibit higher calcareous content,whereas those with earth-yellow or khaki matrices contain less calcareous material and are predominantly argillaceous-cemented.Additionally,Xiyu conglomerate shows higher porosity compared to conventional rocks.The proposed classification method based on engineering geological and fabric characteristics offers a geological basis for further determining the engineering mechanical properties of various Xiyu conglomerate types.This approach holds potential for addressing the challenges related to unclear classification and difficulty in accurately defining mechanical parameters for Xiyu conglomerate across different regions.
文摘Objective:To assess the burden of Group B Streptococcus(GBS)and analyze the distribution of scrotypes in relation to their source.The review highlights data gaps in transmission dynamics and regional food consumption practices,which are esscntial for designing cffective public health strategies and advancing vaccine development.Methods:Scarches were conducted in Web of Science,MEDLINE,Science Direct,PubMcd,and Scopus databases to find studies related to GBS during 1990-2025.Eligible studies were those that described prevalence,scrotype distribution or scquence type(ST)of GBS in Southeast Asian countries.Random-cffects meta-analysis was used to pool data.Results:A total of 26 studies met the inclusion criteria from cight countries.The pooled estimate of maternal GBS colonization was 15.1%,with scrotypesII,v,ⅡI,V,and I a accounting for the majority of cases(91.24%)in the Southcast Asia studies.Data on ST was limited;however,ST1 was found to be predominant in Malaysia and Thailand,while ST283 was notably linked to the consumption of raw fish.Conclusions:The pooled estimate of the maternal colonization with GBS was 15.1%which is cquivalent to many other primary and review reports worldwide.Distribution of scrotype and ST is needed to be studied in Southcast Asian countries to devise cffective preventive measures.These findings underscore thc importance of surveillance and tailored prevention strategies to combat GBS infections in Southcast Asia.
