Renal effects and safety of tirzepatide in subjects with and without diabetes:A systematic review and meta-analysis

BACKGROUND Type 2 diabetes(T2D),as well as obesity,are risk factors for chronic kidney disease(CKD)and end-stage renal disease.The renal impacts of glucose-lowering and weight-lowering drugs and their potential benefits in preventing CKD often guide clinicians in choosing them appropriately.Only limited data based on randomized controlled trials(RCTs)is currently available on the renal effects and safety profile of tirzepatide.AIM To explore the renal benefits and safety of tirzepatide vs controls.METHODS RCTs involving patients receiving tirzepatide for any indication in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases.The co-primary outcomes were percent change from baseline(CFB)in urine albumin-to-creatinine ratio(UACR)and absolute CFB in estimated glomerular filtration rate(eGFR;in mL/min/1.73 m^(2));the secondary outcome was tirzepatide’s renal safety profile.RevMan web was used to conduct meta-analysis using random-effects models.Outcomes were presented as mean differences(MD)or risk ratios with 95%confidence intervals.RESULTS Fifteen RCTs(n=14471)with mostly low risk of bias(RoB)were included.Over 26-72 weeks,tirzepatide 10 mg[MD-26.95%(-40.13,-13.76),P<0.0001]and 15 mg[MD-18.03%(-28.58,-7.47),P=0.0008]were superior to placebo in percent reductions of UACR.Tirzepatide,at all doses,outperformed insulin in percent reductions of UACR.Compared to the placebo,the percent UACR reduction was greater in subjects with T2D than those with obesity but without T2D(MD-33.25%vs-7.93%;P=0.001).The CFB in eGFR with all doses of tirzepatide was comparable[5 mg:MD 0.36(-1.41,2.14);10 mg:MD 1.17(-0.22,2.56);15 mg:MD 1.42(-0.04,2.88)];P>0.05 for all vs insulin.Tirzepatide(pooled and separate doses)did not increase the risks of adverse renal events,urinary tract infection,nephrolithiasis,acute kidney injury,and renal cancer compared to the placebo,insulin,and glucagon-like peptide-1 receptor agonists.CONCLUSION Short-term data from RCTs with low RoB suggests that tirzepatide positively impacts UACR without detrimental effects on eGFR in subjects with T2D and obesity without T2D,with a reassuring renal safety profile.Larger RCTs are warranted to prove the longer-term renal benefits of tirzepatide,which might also prevent eGFR decline and worsening of CKD.

Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.

Petroleum geological characteristics and exploration targets of the oil-rich sags in the Central and West African Rift System

Based on seismic,drilling,and source rock analysis data,the petroleum geological characteristics and future exploration direction of the oil-rich sags in the Central and West African Rift System(CWARS)are discussed.The study shows that the Central African Rift System mainly develops high-quality lacustrine source rocks in the Lower Cretaceous,and the West African Rift System mainly develops high-quality terrigenous organic matter-rich marine source rocks in the Upper Cretaceous,and the two types of source rocks provide a material basis for the enrichment of oil and gas in the CWARS.Multiple sets of reservoir rocks including fractured basement and three sets of regional cap rocks in the Lower Cretaceous,the Upper Cretaceous,and the Paleogene are developed in the CWARS.Since the Late Mesozoic,due to the geodynamic factors including the dextral strike-slip movement of the Central African Shear Zone,the basins in different directions of the CWARS differ in terms of rifting stages,intervals of regional cap rocks,trap types and accumulation models.The NE-SW trending basins have mainly preserved one stage of rifting in the Early Cretaceous,with regional cap rocks developed in the Lower Cretaceous strata,forming traps of reverse anticlines,flower-shaped structures and basement buried hill,and two types of hydrocarbon accumulation models of"source and reservoir in the same formation,and accumulation inside source rocks"and"up-source and down-reservoir,and accumulation below source rocks".The NW–SE basins are characterized by multiple rifting stages superimposition,with the development of regional cap rocks in the Upper Cretaceous and Paleogene,forming traps of draping anticlines,faulted anticlines,antithetic fault blocks and the accumulation model of"down-source and up-reservoir,and accumulation above source rocks".The combination of reservoir and cap rocks inside source rocks of basins with multiple superimposed rifting stages,as well as the lithologic reservoirs and the shale oil inside source rocks of strong inversion basins are important fields for future exploration in basins of the CWARS.

Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus

Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus.It has affected over 768 million people worldwide,resulting in approx-imately 6900000 deaths.High-risk groups,identified by the Centers for Disease Control and Prevention,include individuals with conditions like type 2 diabetes mellitus(T2DM),obesity,chronic lung disease,serious heart conditions,and chronic kidney disease.Research indicates that those with T2DM face a hei-ghtened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals.Examining the renin-angiotensin system(RAS),a vital regulator of blood pressure and pulmonary stability,reveals the significance of the angiotensin-converting enzyme(ACE)and ACE2 enzymes.ACE converts angiotensin-I to the vasoconstrictor angiotensin-II,while ACE2 counters this by converting angiotensin-II to angiotensin 1-7,a vasodilator.Reduced ACE2 exp-ression,common in diabetes,intensifies RAS activity,contributing to conditions like inflammation and fibrosis.Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels,concerns arise regarding the potential elevation of ACE2 receptors on cell membranes,potentially facilitating COVID-19 entry.This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome cor-onavirus 2 infection and associated complications in T2DM.Potential treatment strategies,including recombinant human ACE2 therapy,broad-spectrum antiviral drugs,and epigenetic signature detection,are discussed as promising avenues in the battle against this pandemic.

Patterns and drivers of plant sexual systems in the dry-hot valley region of southwestern China

Sexual systems play important roles in angiosperm evolution and exhibit substantial variations among different floras. Thus, studying their evolution in a whole flora is crucial for understanding the formation and maintenance of plant biodiversity and predicting its responses to environmental change. In this study, we determined the patterns of plant sexual systems and their associations with geographic elements and various life-history traits in dry-hot valley region of southwestern China, an extremely vulnerable ecosystem. Of the 3166 angiosperm species recorded in this area, 74.5% were hermaphroditic,13.5% were monoecious and 12% were dioecious, showing a high incidence of diclinous species. Diclinous species were strongly associated with tropical elements, whereas hermaphroditic species were strongly associated with temperate and cosmopolitan elements. We also found that hermaphroditism was strongly associated with showy floral displays, specialist entomophily, dry fruits and herbaceous plants.Dioecy was strongly associated with inconspicuous, pale-colored flowers, generalist entomophily, fleshy fruits, and woody plants, whereas monoecy was strongly associated with inconspicuous, pale-colored flowers, anemophily, dry fruits, and herbaceous plants. In addition, hermaphroditic species with generalist entomophily tended to flower in the dry season, whereas diclinous species with specialist entomophily tended to flower in the rainy season. However, independent of sexual systems, plants that produce dry fruits tended to flower in the rainy season and set fruits in the dry season, but the opposite pattern was found for fleshy fruit-producing plants. Our results suggest that in the dry-hot valleys, plant sexual systems are associated with geographic elements as well as various life-history traits that are sensitive to environmental change.

A Special Issue:“Artificial Intelligence Applied in New-Type Power System”for Global Energy Interconnection

In recent years,artificial intelligence(AI)has been widely used in the field of electricity,such as load prediction,fault diagnosis of the power equipment,intelligent scheduling of power grids.However,the application of latest AI technology still has many technical difficulties to be solved.In the process of upgrading from the traditional power system to the new-type power system,AC grids,DC grids and micro grids coexist.In addition,there are huge amount of power equipment and electronic devices,and the coupling relationship is very complicated.Moreover,the high proportion of clean energy and flexible loads connected to the grid leads to the enhancement of the stochastic characteristics of the system.And short-term and ultra-short-term forecasts are much more difficult.Therefore,the editorial office of Global Energy Interconnection has planned the special issue of“Artificial Intelligence Applied in New-Type Power System”.

An early scoring system to predict mechanical ventilation for botulism: a single-center-based study

BACKGROUND: Early identification of patients requiring ventilator support will be beneficial for the outcomes of botulism. The present study aimed to establish a new scoring system to predict mechanical ventilation(MV) for botulism patients.METHODS: A single-center retrospective study was conducted to identify risk factors associated with MV in botulism patients from 2007 to 2022. Univariate analysis and multivariate logistic regression analysis were used to screen out risk factors for constructing a prognostic scoring system. The area under the receiver operating characteristic(ROC) curve was calculated.RESULTS: A total of 153 patients with botulism(66 males and 87 females, with an average age of 43 years) were included. Of these, 49 patients(32.0%) required MV, including 21(13.7%) with invasive ventilation and 28(18.3%) with non-invasive ventilation. Multivariate analysis revealed that botulinum toxin type, pneumonia, incubation period, degree of hypoxia, and severity of muscle involvement were independent risk factors for MV. These risk factors were incorporated into a multivariate logistic regression analysis to establish a prognostic scoring system. Each risk factor was scored by allocating a weight based on its regression coefficient and rounded to whole numbers for practical utilization([botulinum toxin type A: 1], [pneumonia: 2], [incubation period ≤1 day: 2], [hypoxia <90%: 2], [severity of muscle involvement: grade Ⅱ, 3;gradeⅢ, 7;grade IV, 11]). The scoring system achieved an area under the ROC curve of 0.82(95% CI 0.75–0.89, P<0.001). At the optimal threshold of 9, the scoring system achieved a sensitivity of 83.7% and a specificity of 70.2%.CONCLUSION: Our study identified botulinum toxin type, pneumonia, incubation period, degree of hypoxia, and severity of muscle involvement as independent risk factors for MV in botulism patients. A score ≥9 in our scoring system is associated with a higher likelihood of requiring MV in botulism patients. This scoring system needs to be validated externally before it can be applied in clinical settings.

Grassland-type ecosystem stability in China differs under the influence of drought and wet events

Ecological stability is a core issue in ecological research and holds significant implications forhumanity. The increased frequency and intensity of drought and wet climate events resulting from climatechange pose a major threat to global ecological stability. Variations in stability among different ecosystemshave been confirmed, but it remains unclear whether there are differences in stability within the sameterrestrial vegetation ecosystem under the influence of climate events in different directions and intensities.China's grassland ecosystem includes most grassland types and is a good choice for studying this issue.This study used the Standardized Precipitation Evapotranspiration Index-12 (SPEI-12) to identify thedirections and intensities of different types of climate events, and based on Normalized DifferenceVegetation Index (NDVI), calculated the resistance and resilience of different grassland types for 30consecutive years from 1990 to 2019 (resistance and resilience are important indicators to measurestability). Based on a traditional regression model, standardized methods were integrated to analyze theimpacts of the intensity and duration of drought and wet events on vegetation stability. The resultsshowed that meadow steppe exhibited the highest stability, while alpine steppe and desert steppe had thelowest overall stability. The stability of typical steppe, alpine meadow, temperate meadow was at anintermediate level. Regarding the impact of the duration and intensity of climate events on vegetationecosystem stability for the same grassland type, the resilience of desert steppe during drought was mainlyaffected by the duration. In contrast, the impact of intensity was not significant. However, alpine steppewas mainly affected by intensity in wet environments, and duration had no significant impact. Ourconclusions can provide decision support for the future grassland ecosystem governance.

Simulating Responses of Rice Yield and Nitrogen Fates to Ground Cover Rice Production System under Different Types of Precipitation Years

The Ground Cover Rice Production System(GCRPS)has considerable potential for securing rice production in hilly areas.However,its impact on yields and nitrogen(N)fates remains uncertain under varying rainfall conditions.A two-year field experiment(2021–2022)was conducted in Ziyang,Sichuan Province,located in the hilly areas of Southwest China.The experiment included two cultivation methods:conventional flooding paddy(Paddy,W1)and GCRPS(W2).These methods were combined with three N management practices:N1(no-N fertilizer),N2(135 kg/hm^(2)urea as a base fertilizer in both W1 and W2),and N3(135 kg/hm^(2)urea with split application for W1 and 67.5 kg/hm^(2)urea and chicken manure separately for W2).The WHCNS(Soil Water Heat Carbon Nitrogen Simulator)model was calibrated and validated to simulate ponding water depth,soil water storage,soil mineral N content,leaf area index,aboveground dry matter,crop N uptake,and rice yield.Subsequently,this model was used to simulate the responses of rice yield and N fates to GCRPS under different types of precipitation years using meteorological data from 1980 to 2018.The results indicated that the WHCNS model performed well in simulating crop growth and N fates for both Paddy and GCRPS.Compared with Paddy,GCRPS reduced N leaching(35.1%–54.9%),ammonia volatilization(0.7%–13.6%),N runoff(71.1%–83.5%),denitrification(3.8%–6.7%),and total N loss(33.8%–56.9%)for all precipitation year types.However,GCRPS reduced crop N uptake and yield during wet years,while increasing crop N uptake and yield during dry and normal years.Fertilizer application reduced the stability and sustainability of rice yield in wet years,but increased the stability and sustainability of rice yield in dry and normal years.In conclusion,GCRPS is more suitable for normal and dry years in the study region,leading to increased rice yield and reduced N loss.

Increasing dietary fiber intake for type 2 diabetes mellitus management: A systematic review

BACKGROUND Type 2 diabetes is a chronic,non-communicable disease with a substantial global impact,affecting a significant number of individuals.Its etiology is closely tied to imbalanced dietary practices and sedentary lifestyles.Conversely,increasing die-tary fiber(DF)intake has consistently demonstrated health benefits in numerous studies,including improvements in glycemic control and weight management.AIM To investigate the efficacy of DF interventions in the management of type 2 diabetes mellitus(T2DM).METHODS A systematic literature review was conducted to explore the association between DF intake and the management of T2DM.Following the inclusion and exclusion criteria,a total of 26 studies were included in this review.RESULTS The main strategies implied to increased DF intake were:High DF diet plus acarbose(2 studies);DF supplements(14 studies);and high DF diets(10 studies).Overall,most studies indicated that increased DF intake resulted in im-provements in glycemic control and weight management in T2DM patients.CONCLUSION DF represents a valuable strategy in the treatment of type 2 diabetes,improving health outcomes.DF intake offers the potential to improve quality of life and reduce complications and mortality associated with diabetes.Likewise,through supplements or enriched foods,DF contributes significantly to the control of several markers such as HbA1c,blood glucose,triglycerides,low-density lipoprotein,and body weight.

A systematic study of Erzhu Erchen decoction against damp-heat internalized type 2 diabetes based on data mining and experimental verification

Background:Erzhu Erchen decoction(EZECD),which is based on Erchen decoction and enhanced with Atractylodes lancea and Atractylodes macrocephala,is widely used for the treatment of dampness and heat(The clinical manifestations of Western medicine include thirst,inability to drink more,diarrhea,yellow urine,red tongue,et al.)internalized disease.Nevertheless,the mechanism of EZECD on damp-heat internalized Type 2 diabetes(T2D)remains unknown.We employed data mining,pharmacology databases and experimental verification to study how EZECD treats damp-heat internalized T2D.Methods:The main compounds or genes of EZECD and damp-heat internalized T2D were obtained from the pharmacology databases.Succeeding,the overlapped targets of EZECD and damp-heat internalized T2D were performed by the Gene Ontology,kyoto encyclopedia of genes and genomes analysis.And the compound-disease targets-pathway network were constructed to obtain the hub compound.Moreover,the hub genes and core related pathways were mined with weighted gene co-expression network analysis based on Gene Expression Omnibus database,the capability of hub compound and genes was valid in AutoDock 1.5.7.Furthermore,and violin plot and gene set enrichment analysis were performed to explore the role of hub genes in damp-heat internalized T2D.Finally,the interactions of hub compound and genes were explored using Comparative Toxicogenomics Database and quantitative polymerase chain reaction.Results:First,herb-compounds-genes-disease network illustrated that the hub compound of EZECD for damp-heat internalized T2D could be quercetin.Consistently,the hub genes were CASP8,CCL2,and AHR according to weighted gene co-expression network analysis.Molecular docking showed that quercetin could bind with the hub genes.Further,gene set enrichment analysis and Gene Ontology represented that CASP8,or CCL2,is negatively involved in insulin secretion response to the TNF or lipopolysaccharide process,and AHR or CCL2 positively regulated lipid and atherosclerosis,and/or including NOD-like receptor signaling pathway,and TNF signaling pathway.Ultimately,the quantitative polymerase chain reaction and western blotting analysis showed that quercetin could down-regulated the mRNA and protein experssion of CASP8,CCL2,and AHR.It was consistent with the results in Comparative Toxicogenomics Database databases.Conclusion:These results demonstrated quercetin could inhibit the expression of CASP8,CCL2,AHR in damp-heat internalized T2D,which improves insulin secretion and inhibits lipid and atherosclerosis,as well as/or including NOD-like receptor signaling pathway,and TNF signaling pathway,suggesting that EZECD may be more effective to treat damp-heat internalized T2D.

Safety of teplizumab in patients with high-risk for diabetes mellitus type 1:A systematic review

BACKGROUND The incidence of diabetes mellitus type 1(DM1)has been rising worldwide because of improvements in diagnostic techniques and improved access to care in countries with lower socioeconomic status.A new anti-CD4 antibody,Teplizumab,has been shown to delay the progression of DM1 and is the only medication approved for this indication.However,more information is needed about the safety profile of this drug.AIM To identify the odds ratios(OR)of systems-based adverse effects for Teplizumab when compared to Placebo.METHODS An extensive systematic review was conducted from the inception of the medication until December 31,2023.All clinical trials and studies that evaluated Teplizumab vs placebo were included in the initial review.The study protocol was designed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines guidelines and was registered in PROSPERO(ID:CRD42024496169).Crude OR were generated using RevMan Software version 5.4.RESULTS After screening and review,5 studies were selected to determine the risk of adverse effects of teplizumab compared to placebo.A total of 561 patients were included in the study population.Total adverse effects and system-based adverse effects were studied and reported.We determined that patients receiving Teplizumab had a higher risk of developing gastrointestinal(GI)(OR=1.60,95%CI:1.01-2.52,P=0.04),dermatological(OR=6.33,95%CI:4.05-9.88,P<0.00001)and hematological adverse effects(OR=19.03,95%CI:11.09-32.66,P<0.00001).These patients were also significantly likely to have active Epstein-Barr Virus infection(OR=3.16,95%CI:1.51-6.64,P<0.002).While our data showed that patients receiving Teplizumab did have a higher incidence of total adverse effects vs placebo,this finding did not reach statistical significance(OR=2.25,95%CI:0.80-6.29,P=0.12).CONCLUSION Our systematic review suggests that Teplizumab patients are at risk for significant adverse effects,primarily related to GI,dermatological,and hematological systems.The total adverse effect data is limited as study populations are small.More studies should be conducted on this medication to better inform the target population of potential adverse effects.

Evaluation of hybrid closed-loop insulin delivery system in type 1 diabetes in real-world clinical practice:One-year observational study

BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL systems on patient-reported outcomes(PROs)in patients with T1D in real-world clinical practice.In this independent study,we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic’s 670G HCL in real-world clinical practice.AIM To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with T1D.METHODS We evaluated 71 patients with T1D(mean age:45.5±12.1 years;59%females;body weight:83.8±18.7 kg,body mass index:28.7±5.6 kg/m2,A1C:7.6%±0.8%)who were treated with HCL at Joslin Clinic from 2017 to 2019.We measured A1C and percent of glucose time-in-range(%TIR)at baseline and 12 months.We measured percent time in auto mode(%TiAM)for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes management.RESULTS At 12 mo,A1C decreased by 0.3%±0.1%(P=0.001)and%TIR increased by 8.1%±2.5%(P=0.002).The average%TiAM was only 64.3%±32.8%and was not associated with A1C,%TIR or PROs.PROs,provided at baseline and at the end of the study,showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9%(P<0.001).Hypoglycemia fear survey/worry scale decreased significantly by 24.9%(P<0.000);Problem Areas In Diabetes reduced significantly by-17.2%(P=0.002).The emotional burden submodules of dietary diversity score reduced significantly by-44.7%(P=0.001).Furthermore,analysis of Clarke questionnaire showed no increase in awareness of hypoglycemic episodes.WHO-5 showed no improvements in subject’s wellbeing among participants after starting the 670G HCL system.Finally,analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality,sleep latency,or duration of sleep from baseline to 12 mo.CONCLUSION The use of HCL in real-world clinical practice for one year was associated with significant improvements in A1C,%TIR,physical functioning,hypoglycemia fear,emotional distress,and emotional burden related to diabetes management.However,these changes were not associated with time in auto mode.

Insights into glymphatic system dysfunction and glucose continuum

In this article,we comment on an original article published in a recent issue of the World Journal of Diabetes.That observational cross-sectional study focused on investigating the function of the glymphatic system and its clinical correlates in patients with different glucose metabolism states by using diffusion tensor imaging along the perivascular space(DTI-ALPS)index.It was shown that the cerebral glymphatic system may be dysfunctional in patients with type 2 diabetes.Various clinical variables affected the DTI-ALPS index in different glucose metabolism states.In conclusion,the study by Tian et al improves the under-standing of the pathophysiology of diabetes-associated brain damage and pro-vides insights for early diagnosis.

Combining GLP-1 receptor agonists and SGLT-2 inhibitors for cardiovascular disease prevention in type 2 diabetes:A systematic review with multiple network meta-regressions

BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are associated with significant cardiovascular benefit in type 2 diabetes(T2D).However,GLP-1RA or SGLT-2I alone may not improve some cardiovascular outcomes in patients with prior cardiovascular co-morbidities.AIM To explore whether combining GLP-1RA and SGLT-2I can achieve additional benefit in preventing cardiovascular diseases in T2D.METHODS The systematic review was conducted according to PRISMA recommendations.The protocol was registered on PROSPERO(ID:42022385007).A total of 107049 participants from eligible cardiovascular outcomes trials of GLP-1RA and SGLT-2I were included in network meta-regressions to estimate cardiovascular benefit of the combination treatment.Effect modification of prior myocardial infarction(MI)and heart failure(HF)was also explored to provide clinical insight as to when the INTRODUCTION The macro-and micro-vascular benefits of glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are independent of their glucose-lowering effects[1].In patients with type 2 diabetes(T2D),the major cardiovascular outcome trials(CVOT)showed that dipeptidyl peptidase-4 inhibitors(DPP-4I)did not improve cardiovascular outcomes[2],whereas cardiovascular benefit of GLP-1RA or SGLT-2I was significant[3,4].Further subgroup analyses indicated that the background cardiovascular risk should be considered when examining the cardiovascular outcomes of these newer glucose-lowering medications.For instance,prevention of major adverse cardiovascular events(MACE)was only seen in those patients with baseline atherosclerotic cardiovascular disease[3,4].Moreover,a series of CVOT conducted in patients with heart failure(HF)have demonstrated that(compared with placebo)SGLT-2I significantly reduced risk of hospitalization for HF or cardiovascular death,irrespective of their history of T2D[5-8].However,similar cardiovascular benefits were not observed in those with myocardial infarction(MI)[9,10].Cardiovascular co-morbidities are not only approximately twice as common but are also associated with dispropor-tionately worse cardiovascular outcomes in patients with T2D,compared to the general population[11].Therefore,it is of clinical importance to investigate whether the combination treatment of GLP-1RA and SGLT-2I could achieve greater cardiovascular benefit,particularly when considering patients with cardiovascular co-morbidities who may not gain sufficient cardiovascular protection from the monotherapies.This systematic review with multiple network meta-regressions was mainly aimed to explore whether combining GLP-1RA and SGLT-2I can provide additional cardiovascular benefit in T2D.Cardiovascular outcomes of these newer antidiabetic medications were also estimated under effect modification of prior cardiovascular diseases.This was to provide clinical insight as to when the combination treatment might be prioritized.

Risk assessment of high-speed railway CTC system based on improved game theory and cloud model

Purpose-In order to solve the problem of inaccurate calculation of index weights,subjectivity and uncertainty of index assessment in the risk assessment process,this study aims to propose a scientific and reasonable centralized traffic control(CTC)system risk assessment method.Design/methodologylapproach-First,system-theoretic process analysis(STPA)is used to conduct risk analysis on the CTC system and constructs risk assessment indexes based on this analysis.Then,to enhance the accuracy of weight calculation,the fuzzy analytical hierarchy process(FAHP),fuzzy decision-making trial and evaluation laboratory(FDEMATEL)and entropy weight method are employed to calculate the subjective weight,relative weight and objective weight of each index.These three types of weights are combined using game theory to obtain the combined weight for each index.To reduce subjectivity and uncertainty in the assessment process,the backward cloud generator method is utilized to obtain the numerical character(NC)of the cloud model for each index.The NCs of the indexes are then weighted to derive the comprehensive cloud for risk assessment of the CTC system.This cloud model is used to obtain the CTC system's comprehensive risk assessment.The model's similarity measurement method gauges the likeness between the comprehensive risk assessment cloud and the risk standard cloud.Finally,this process yields the risk assessment results for the CTC system.Findings-The cloud model can handle the subjectivity and fuzziness in the risk assessment process well.The cloud model-based risk assessment method was applied to the CTC system risk assessment of a railway group and achieved good results.Originality/value-This study provides a cloud model-based method for risk assessment of CTC systems,which accurately calculates the weight of risk indexes and uses cloud models to reduce uncertainty and subjectivity in the assessment,achieving effective risk assessment of CTC systems.It can provide a reference and theoretical basis for risk management of the CTC system.

Systematic Review of Community Type 2 Diabetes Structured Health Education (CT2DSHE)

Aim: This paper aims to evaluate disparities of type 2 diabetes structured health education programmes that is utilised within the communities. Design: systematic review, (a type of secondary research design) aiming to summarize the results of prior primary research studies on available evidence Community type 2 diabetes structured education (CT2DSHE). Methods: Research question: Type 2 diabetic structured health education within a community how effective is it? Qualitative Systematic review, defined as a way to get reliable and objective picture of current available evidence on the specific topic—(CT2DSHE), (Denscombe, 2021) through reflexivity synthesis of available data as an example. This is valuable in time constraints such as project assignments that must be met within specific time and also to bring together available evidence together [1]. Results: This review has shown that CT2DSHE is effective with seven out of the eleven authors supporting, three authors against and one was neutral, further showed that knowledge and skills acquired can last longer with patient activation improved among T2DM patients ideal for sustaining their self-management of T2DM. Conclusion: This research provides suggestive answers to the research question: “Type 2 diabetic structured health education within a community how effective is it?”, This has demonstrated CT2DSHE effectiveness in knowledge acquisition and improving T2DM awareness among T2DM patients, whilst evidencing long effects beyond the study times of 3 - 9 months period in relation to patient activation. Also Identified diabetes education self-management on newly diagnosed (DESMOND) patient as CT2DSHE program for recommendation. Patient or Public Contribution: This work aspires to contribute to CT2DSHE in these areas;Influencing policy decision-making for community diabetes care within the UK and world at large., Contributing to already vast knowledge on diabetes self-management and reasons why?, Influencing educators on how CT2DSHEP are designed, delivered by putting the patient at the Centre and bringing different perspectives on CT2DSHEP in one place that is serving users time of having to consult several resources especially busy clinicians [2] [3].

Microplastic Impacts on Greenhouse Gases Emissions in Terrestrial Ecosystems

Microplastics can influence global climate change by regulating the emissions of greenhouse gases from different ecosystems. The effects of microplastics in terrestrial ecosystems are still not well studied particularly greenhouse gases emissions. Thus, we conducted a laboratory experiment over a period of 90 days with two types of microplastics (differing in their chemical structure), high density polyethylene (HDPE) and low density polyethylene (LDPE), which were applied to the soil at a rate of 0% to 0.1% (w/w). The overarching aim was to investigate the effects of microplastic type, microplastic concentration and days of exposure on greenhouse gases emissions. We also used original and artificially weathered microplastics (the same HDPE and LDPE) to make a comparison of greenhouse gases emissions between the original microplastics treated soils and the soils treated with weathered microplastics. Our findings showed that HDPE and LDPE microplastics significantly increased the emissions of greenhouse gases from the soil than that of the control soils. Emissions were increased with the increases in the level of microplastic in the soil. The weathered microplastic emitted greater quantity of greenhouse gases compared to that of the original microplastics. In contrast to a low initial emission quantity, the emissions were gradually increased at the termination of the experiment. Our experiment on the emissions of greenhouse gases from the soil vis-à-vis microplastic additions indicated that the microplastic increased the emissions of greenhouse gases in terrestrial ecosystems, and pervasive microplastic impacts may have consequences for the global climate change. Greenhouse gases emissions from the soil not only depend on the type and concentration of the microplastic, but also on the days of exposure to the microplastic.

Distribution patterns of vegetation biomass and nutrients bio-cycle in alpine tundra ecosystem on Changbai Mountains,Northeast China

A study was conducted to test the correlation between biomass and elevation and the differences in concentration and storks of nutrients among five vegetation types （Felsenmeer alpine tundra vegetation-FA, Lithic alpine tundra vegetation-LA, Typical alpine tundra vegetation-TA, Meadow alpine tundra vegetation-MA, and Swamp alpine tundra vegetation-SA） on alpine tundra of Changbai Mountains, Jilin Province, China in growing seasons of 2003, 2004 and 2005. The biomass of 43 mono-species and soil nutrients in alpine tundra ecosystem were also investigated. Dominant species from Ericaceae （such as Rhododendron chrysanthum and Vaccinium jliginosum var. alpinum） were taken to analyze organ biomass distribution. Result showed that the biomass and elevation had a significant correlation （Biomass-237.3 in（Elevation） ＋494.36; R^2=0.8092; P〈0.05）. No significant differences were found in phosphorus and sulphur concentrations of roots, stems and leaves among the five vegetation types. There were significant differences in nitrogen and phosphorus stocks of roots, stems and leaves and in sulphur stock of stems and leaves among TA, MA, and SA vegetation types （p〈0.05）. The nutrient stock of five vegetations was averagely 72.46 kg.hm^-2, of which N, P, S were 48.55, 10.33 and 13.61 kg·hm^-2, respectively. Soil N and S concentrations in meadow alpine tundra soil type was significantly higher than those in other four soil types （Cold desert alpine tundra soil, Lithic alpine tundra soil, Peat alpine tundra soil, and Gray alpine tundra soil）. Phosphorous concentration in SA type was higher （p〈0.05） than in other types. Soil nutrient stock （0-20cm） was averagely 39.59 t.hm^-2, of which N, P, S were 23.74, 5.86, 9.99 t·hm^-2, respectively.

Spatial pattern of soil carbon and nutrient storage at the Alpine tun-dra ecosystem of Changbai Mountain, China

In August 2003, we investigated spatial pattern in soil carbon and nutrients in the Alpine tundra of Changbai Moun-tain, Jilin Province, China. The analytical results showed that the soil C concentrations at different depths were significantly (p<0.05) higher in Meadow alpine tundra vegetation than that in other vegetation types; the soil C (including inorganic carbon) concentrations at layer below 10 cm are significantly (p<0.05) higher than at layer of 1020 cm among the different vegetation types; the spatial distribution of soil N concentration at top surface of 0-10 cm depth was similar to that at 1020 cm; the soil P concentrations at different depths were significantly (p<0.05) lower at Lithic alpine tundra vegetation than that at other vegetation types; soil K concentration was significantly (p<0.05) higher in Felsenmeer alpine tundra vegetation and Lithic alpine tundra vegetation than that in Typical alpine tundra, Meadow alpine tundra, and Swamp alpine tundra vegetations.. However, the soil K had not significant change at different soil depths of each vegetation type. Soil S concentration was dramatically higher in Meadow alpine tundra vegetation than that in other vegetation types. For each vegetation type, the ratios of C: N, C: P, C: K and C: S generally decreased with soil depth. The ratio of C: N was significantly higher at 010 cm than that at 1020 cm for all vegetation types except at the top layer of the Swamp alpine tundra vegetation. Our study showed that soil C and nutrients storage were significantly spatial heterogeneity.