Life's essential 8 and risk of subclinical atherosclerosis progression: a prospective cohort study

BACKGROUND Previous studies have demonstrated the benefits of ideal cardiovascular health(CVH) in reducing cardiovascular risk.However,its role in subclinical atherosclerosis(SA) progression remains unclear.We aim to examine the association of CVH,estimated by the American Heart Association's new Life's Essential 8(LE8),with the progression of SA.METHODS This prospective cohort study was conducted among 972 asymptomatic Chinese participants and followed up for5.7 years.The LE8 score(range,0–100) consisted of blood pressure,lipids,glucose,body mass index,smoking status,diet health,physical activity and sleep health was evaluated in 1998 and 2008–2009.Progression of SA was determined by carotid plaque and coronary artery calcification(CAC) in 2008–2009 and 2013–2014.Log-binomial regression model was used to estimate the association of LE8 score with SA progression.RESULTS Each 10 points increment in LE8 score was associated with 15.2%(RR:0.848,95% CI:0.797–0.902),17.7%(RR:0.823,95% CI:0.766–0.884) and 12.0%(RR:0.880,95% CI:0.845–0.916) lower risks of carotid plaque,CAC and overall SA progression,respectively.Compared with participants with non-ideal CVH at both visits,the participants with ideal CVH at both visits had39.1%(RR:0.609,95% CI:0.494–0.752),41.0%(RR:0.590,95% CI:0.456–0.764) and 29.7%(RR:0.703,95% CI:0.598–0.825) lower risks of carotid plaque,CAC and overall SA progression,respectively.CONCLUSIONS Higher LE8 scores were associated with lower risks of SA progression.Besides,long-term maintenance of optimal CVH was more beneficial to prevent SA progression.

Prospect Theory Based Individual Irrationality Modelling and Behavior Inducement in Pandemic Control

Understanding and modeling individuals’behaviors during epidemics is crucial for effective epidemic control.However,existing research ignores the impact of users’irrationality on decision-making in the epidemic.Meanwhile,existing disease control methods often assume users’full compliance with measures like mandatory isolation,which does not align with the actual situation.To address these issues,this paper proposes a prospect theorybased framework to model users’decision-making process in epidemics and analyzes how irrationality affects individuals’behaviors and epidemic dynamics.According to the analysis results,irrationality tends to prompt conservative behaviors when the infection risk is low but encourages risk-seeking behaviors when the risk is high.Then,this paper proposes a behavior inducement algorithm to guide individuals’behaviors and control the spread of disease.Simulations and real user tests validate our analysis,and simulation results show that the proposed behavior inducement algorithm can effectively guide individuals’behavior.

Discussion on the application prospect of the transient electromagnetic method based on the dual launcher and mine advanced detection

The dual transmitter implements the equivalent anti-magnetic flux transient electromagnetic method, which can effectively reduce the scope of the transient electromagnetic detection blind area. However, this method is rarely reported in the detection of pipelines in urban geophysical exploration and the application of coal mines. Based on this, this paper realizes the equivalent anti-magnetic flux transient electromagnetic method based on the dual launcher. The suppression effect of this method on the blind area is analyzed by physical simulation. And the detection experiment of underground pipelines is carried out outdoors. The results show that the dual launcher can significantly reduce the turn-off time, thereby effectively reducing the impact of the blind area on the detection results, and the pipeline detection results verify the device’s effectiveness. Finally, based on the ground experimental results, the application prospect of mine advanced detection is discussed. Compared with other detection fields, the formation of blind areas is mainly caused by the equipment. If the dual launcher can be used to reduce the blind area, the accuracy of advanced detection can be improved more effectively. The above research results are of great significance for improving the detection accuracy of the underground transient electromagnetic method.

Plant-based dietary patterns and risk of esophageal cancer:A prospective cohort study spanning 17 years

Objective: Plant-based diets have multiple health benefits for cancers;however, little is known about the association between plant-based dietary patterns and esophageal cancer(EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC.Methods: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index(PDI), healthful plant-based diet index(h PDI), and unhealthful plant-based diet index(u PDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios(HRs) and 95% confidence intervals(95% CIs) of EC across 3plant-based diet indices and further stratified the analysis by subgroups.Results: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50(95% CI, 0.32-0.77) for h PDI. In addition, the HR per 10-point increase in the h PDI score was 0.42(95% CI, 0.27-0.66) for ECs. Conversely, u PDI was positively associated with the risk of EC, and the HR was 1.80(95% CI, 1.16-2.82). The HR per 10-point increase in the u PDI score was 1.90(95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses.Conclusions: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.

The Effect of Blood Lipid Profiles on Chronic Kidney Disease in a Prospective Cohort:Based on a Regression Discontinuity Design

Objective Previous studies on the association between lipid profiles and chronic kidney disease(CKD)have yielded inconsistent results and no defined thresholds for blood lipids.Methods A prospective cohort study including 32,351 subjects who completed baseline and follow-up surveys over 5 years was conducted.Restricted cubic splines and Cox models were used to examine the association between the lipid profiles and CKD.A regression discontinuity design was used to determine the cutoff value of lipid profiles that was significantly associated with increased the risk of CKD.Results Over a median follow-up time of 2.2(0.5,4.2)years,648(2.00%)subjects developed CKD.The lipid profiles that were significantly and linearly related to CKD included total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),TC/HDL-C,and TG/HDL-C,whereas lowdensity lipoprotein cholesterol(LDL-C)and LDL-C/HDL-C were nonlinearly correlated with CKD.TC,TG,TC/HDL-C,and TG/HDL-C showed an upward jump at the cutoff value,increasing the risk of CKD by 0.90%,1.50%,2.30%,and 1.60%,respectively,whereas HDL-C showed a downward jump at the cutoff value,reducing this risk by 1.0%.Female and participants with dyslipidemia had a higher risk of CKD,while the cutoff values for the different characteristics of the population were different.Conclusion There was a significant association between lipid profiles and CKD in a prospective cohort from Northwest China,while TG,TC/HDL-C,and TG/HDL-C showed a stronger risk association.The specific cutoff values of lipid profiles may provide a clinical reference for screening or diagnosing CKD risk.

Who can benefit more from its twelve-week treatment:A prospective cohort study of blonanserin for patients with schizophrenia

BACKGROUND Blonanserin(BNS)is a well-tolerated and effective drug for treating schizophrenia.AIM To investigate which types of patients would obtain the most benefit from BNS treatment.METHODS A total of 3306 participants were evaluated in a 12-week,prospective,multicenter,open-label post-marketing surveillance study of BNS.Brief psychiatric rating scale(BPRS)scores were calculated to evaluate the effectiveness of BNS,and its safety was assessed with the incidence of adverse drug reactions.Linear regression was used to screen the influencing factors for the reduction of BPRS total score,and logistic regression was used to identify patients with a better response to BNS.RESULTS The baseline BPRS total score(48.8±15.03)decreased to 27.7±10.08 at 12 weeks(P<0.001).Extrapyramidal symptoms(14.6%)were found to be the most frequent adverse drug reactions.The acute phase,baseline BPRS total score,current episode duration,number of previous episodes,dose of concomitant antipsychotics,and number of types of sedative-hypnotic agents were found to be independent factors affecting the reduction of BPRS total score after treatment initiation.Specifically,patients in the acute phase with baseline BPRS total score≥45,current episode duration<3 months,and≤3 previous episodes derived greater benefit from 12-week treatment with BNS.CONCLUSION Patients in the acute phase with more severe symptoms,shorter current episode duration,fewer previous episodes,and a lower psychotropic drug load derived the greatest benefit from treatment with BNS.

Life cycle assessment as a prospective tool for sustainable agriculture and food planning at a local level

Owing to the far-reaching environmental consequences of agriculture and food systems,such as their contribution to climate change,there is an urgent need to reduce their impact.International and national governments set sustainability targets and implement corresponding measures.Nevertheless,critics of the globalized system claim that a territorial administrative scale is better suited to address sustainability issues.Yet,at the subnational level,local authorities rarely apply a systemic environmental assessment to enhance their action plans.This paper employs a territorial life cycle assessment methodology to improve local environmental agri-food planning.The objective is to identify significant direct and indirect environmental hotspots,their origins,and formulate effective mitigation strategies.The methodology is applied to the administrative department of Finistere,a strategic agricultural region in North-Western France.Multiple environmental criteria including climate change,fossil resource scarcity,toxicity,and land use are modeled.The findings reveal that the primary environmental hotspots of the studied local food system arise from indirect sources,such as livestock feed or diesel consumption.Livestock reduction and organic farming conversion emerge as the most environmentally efficient strategies,resulting in a 25%decrease in the climate change indicator.However,the overall modeled impact reduction is insufficient following national objectives and remains limited for the land use indicator.These results highlight the innovative application of life cycle assessment led at a local level,offering insights for the further advancement of systematic and prospective local agri-food assessment.Additionally,they provide guidance for local authorities to enhance the sustainability of planning strategies.

Hybrid argon plasma coagulation for the treatment of Barrett’s esophagus:A prospective,multicenter study

BACKGROUND The incidence of Barrett’s esophagus(BE)in China is lower compared to the Western populations.Hence,studies conducted in the Chinese population has been limited.The current treatment options available for BE treatment includes argon plasma coagulation(APC),radiofrequency ablation and cryoablation,all with varying degrees of success.AIM To determine the efficacy and safety of HybridAPC in the treatment of BE.METHODS The study cohort consisted of patients with BE who underwent HybridAPC ablation treatment.These procedures were performed by seven endoscopists from different tertiary hospitals.The duration of the procedure,curative rate,complications and recurrent rate by 1-year follow-up were recorded.RESULTS Eighty individuals were enrolled for treatment from July 2017 to June 2020,comprising of 39 males and 41 females with a median age of 54 years(range,30 to 83 years).The technical success rate of HybridAPC was 100%and the overall curative rate was 98.15%.No severe complications occurred during the operation.BE cases were classified as short-segment BE and long-segment BE.Patients with short-segment BE were all considered cured without complications.Thirty-six patients completed the one-year follow-up without recurrence.Twenty-four percent had mild dysplasia which were all resolved with one post-procedural treatment.The mean duration of the procedure was 10.94±6.52 min.CONCLUSION Treatment of BE with HybridAPC was found to be a simple and quick procedure that is safe and effective during the short-term follow-up,especially in cases of short-segment BE.This technique could be considered as a feasible alternative ablation therapy for BE.

Effects of strengthening prospective nursing practice on sleep quality,anxiety,and depression of awake patients in intensive care unit

BACKGROUND The intensive care unit(ICU)is a specialized hospital department.Awake patients in the ICU frequently encounter adverse psychological states,such as anxiety and fear,often accompanied by poor sleep quality.This situation has garnered significant attention within the medical community.AIM To investigate the impact of prospective nursing intervention strategies on the sleep quality and negative emotional state of conscious ICU patients.METHODS One hundred and twenty ICU awake patients admitted to our hospital were selected and randomly divided into control(n=60)and observation(n=60)groups.Patients in the control group were cared for using the conventional nursing model,while patients in the observation group were cared for using the prospective nursing model.Sleep improvement was assessed using the International Standardized Sleep Efficiency Formula and Pittsburgh Sleep Quality Index(PSQI).The PSQI,Generalized Anxiety Disorder 7-item(GAD-7)scale,Self-Depression Scale(SDS),and satisfaction before and after treatment were used to assess the negative emotional states of patients under the two care models.RESULTS Patient satisfaction in the observation group was significantly higher than in the control group.The GAD-7 and SDS scores in the observation group were significantly lower than those in the control group,and the total effective rate of sleep improvement in the observation group was significantly higher than in the control group.After treatment,the PSQI scores of the two groups significantly decreased(P<0.05).The decrease in the observation group was more significan than that in the control group,and the difference between the two groups was statistically significant.CONCLUSION Prospective nursing interventions can improve sleep quality and psychological levels and significantly affect conscious patients in the ICU,which is worthy of clinical application.

Application prospects of urine-derived stem cells in neurological and musculoskeletal diseases

Urine-derived stem cells(USCs)are derived from urine and harbor the potential of proliferation and multidirectional differentiation.Moreover,USCs could be reprogrammed into pluripotent stem cells[namely urine-derived induced pluripotent stem cells(UiPSCs)]through transcription factors,such as octamer binding transcription factor 4,sex determining region Y-box 2,kruppel-like factor 4,myelocytomatosis oncogene,and Nanog homeobox and protein lin-28,in which the first four are known as Yamanaka factors.Mounting evidence supports that USCs and UiPSCs possess high potential of neurogenic,myogenic,and osteogenic differentiation,indicating that they may play a crucial role in the treatment of neurological and musculoskeletal diseases.Therefore,we summarized the origin and physiological characteristics of USCs and UiPSCs and their therapeutic application in neurological and musculoskeletal disorders in this review,which not only contributes to deepen our understanding of hallmarks of USCs and UiPSCs but also provides the theoretical basis for the treatment of neurological and musculoskeletal disorders with USCs and UiPSCs.

Assessment of CO_(2)storage prospect based on physical properties of Rio Bonito Formation rock units

The physical properties of the rock units associated with the Rio Bonito Formation are presented in this study with the focus on modelling reservoir quality based on petrophysics-derived parameters to evaluate CO_(2)storage potentials.It involves the modelling of the reservoir depths,thicknesses,flow zone indicators(FZI),and effective permeability(Keff)and presenting the CO_(2)storage efficiency factors peculiar to the rock units of the study location.Research results presented by this study for the stated objectives are not quite common in the region.Keff values range from 200 mD to higher than 2000 mD,and FZI values are generally above 1.0 mm and up to 13.0 mm within the portions covered by the drilled wells.The sandstone units recorded are up to 20 m thick in some cases.The Keff and FZI models indicate the sandstone reservoirs as permeable units to support the injection and circulation of CO_(2)within the potential reservoir units of the Rio Bonio Formation across São Paulo State.Apart from some points in the southeastern part of the study location,where the Rio Bonito are delineated at depths less than 800 m(minimum CO_(2)storage depth based on best practices),other portions are deeper,ranging from 950 m to 3500 m.Thin-bedded layers will affect the integrity of the rocks as CO_(2)storage tanks or reservoir seals/traps/overburden within the region.Sandstone bed thicknesses are up to 20 m in some cases.However,hybrid CO_(2)reservoir units are feasible,especially in portions where thin siltstone layers are sandwiched between sandstone units to provide considerable thicknesses based on CO_(2)storage standards.The current study shows that useable areas considering reservoir thickness,depth,and other physical qualities will significantly control the CO_(2)storage efficiency of the study location.Further studies featuring a detailed geophysical exploration of the site to confirm the availability and saturations of preexisting fluid(hydrocarbon and water)are encouraged to boost CO_(2)storage in the region.The related research-based results,as mentioned above,may be combined with the results of this research to determine the area's potentials for CO_(2)storage or hydrocarbon production with CO_(2)storage options.

In silico prospective analysis of the medicinal plants activity on the CagA oncoprotein from Helicobacter pylori

BACKGROUND Colonization with Helicobacter pylori(H.pylori)has a strong correlation with gastric cancer,and the virulence factor CagA is implicated in carcinogenesis.Studies have been conducted using medicinal plants with the aim of eliminating the pathogen;however,the possibility of blocking H.pylori-induced cell differentiation to prevent the onset and/or progression of tumors has not been addressed.This type of study is expensive and time-consuming,requiring in vitro and/or in vivo tests,which can be solved using bioinformatics.Therefore,prospective computational analyses were conducted to assess the feasibility of interaction between phenolic compounds from medicinal plants and the CagA oncoprotein.AIM To perform a computational prospecting of the interactions between phenolic compounds from medicinal plants and the CagA oncoprotein of H.pylori.METHODS In this in silico study,the structures of the phenolic compounds(ligands)kaempferol,myricetin,quercetin,ponciretin(flavonoids),and chlorogenic acid(phenolic acid)were selected from the PubChem database.These phenolic compounds were chosen based on previous studies that suggested medicinal plants as non-drug treatments to eliminate H.pylori infection.The three-dimensional structure model of the CagA oncoprotein of H.pylori(receptor)was obtained through molecular modeling using computational tools from the I-Tasser platform,employing the threading methodology.The primary sequence of CagA was sourced from GenBank(BAK52797.1).A screening was conducted to identify binding sites in the structure of the CagA oncoprotein that could potentially interact with the ligands,utilizing the GRaSP online platform.Both the ligands and receptor were prepared for molecular docking using AutoDock Tools 4(ADT)software,and the simulations were carried out using a combination of ADT and AutoDock Vina v.1.2.0 software.Two sets of simulations were performed:One involving the central region of CagA with phenolic compounds,and another involving the carboxy-terminus region of CagA with phenolic compounds.The receptor-ligand complexes were then analyzed using PyMol and BIOVIA Discovery Studio software.RESULTS The structure model obtained for the CagA oncoprotein exhibited high quality(C-score=0.09)and was validated using parameters from the MolProbity platform.The GRaSP online platform identified 24 residues(phenylalanine and leucine)as potential binding sites on the CagA oncoprotein.Molecular docking simulations were conducted with the three-dimensional model of the CagA oncoprotein.No complexes were observed in the simulations between the carboxy-terminus region of CagA and the phenolic compounds;however,all phenolic compounds interacted with the central region of the oncoprotein.Phenolic compounds and CagA exhibited significant affinity energy(-7.9 to-9.1 kcal/mol):CagA/kaempferol formed 28 chemical bonds,CagA/myricetin formed 18 chemical bonds,CagA/quercetin formed 16 chemical bonds,CagA/ponciretin formed 13 chemical bonds,and CagA/chlorogenic acid formed 17 chemical bonds.Although none of the phenolic compounds directly bound to the amino acid residues of the K-Xn-R-X-R membrane binding motif,all of them bound to residues,mostly positively or negatively charged,located near this region.CONCLUSION In silico,the tested phenolic compounds formed stable complexes with CagA.Therefore,they could be tested in vitro and/or in vivo to validate the findings,and to assess interference in CagA/cellular target interactions and in the oncogenic differentiation of gastric cells.

Gold Mineralisation in the Intiédougou Prospect (Diébougou District) in Southwest Burkina Faso, West African Craton

The Intiédougou located in the Houndé Birimian greenstone belt has been the subject of several mining and geoscience studies that have led to the discovery of mineralized gold targets. One of these mineralized targets has prompted work that raises the issue of control factors for the gold mineralization of the prospect. The methodology used in this study combines a study of core drill hole data located in the area and laboratory studies. The Intiédougou sector is based on andesito-basaltic, andesitic interstratified volcanoclastite rocks and Tarkwaïen type detrital sedimentary rocks caught in a vice in the volcano-sedimentary unit. Lithostructural analysis of the sector shows that the subvolcanic rocks bearing gold mineralization are subjected to heterogeneous ductile to brittle deformations and affected by hydrothermalism evolving at stages marked by large fissure fillings. These hydrothermal phases evolve in the zones of expansion created by the brittle deformations that have contributed to the deposits of different types of gold-enriched sulphides. These different phases of hydrothermal destabilization generally of low degree accompany the tardi to post-eburnean brittle tectonics. This deformation system is favorable to the establishment of gold mineralization in the form of vein bodies. The overimposition of deformed and altered areas suggests a genetic relationship between deformation and hydrothermal activity. In conclusion, the mineralization of Intiédougou in vein styles, set up in a volcanic arc environment with a paragenesis of gold-pyrite deposit ± chalcopyrite would be controlled by the structural aspect and accompanied by hydrothermal alteration.

Geological Interpretation and Identification of Albian-Aged Petroleum Prospects in Block A, San Pedro Margin (Côte d’Ivoire)

The study aims to identify Albian-age oil prospects in Block A of the San Pedro margin, Côte d’Ivoire, by conducting a detailed geological interpretation. The objective is to confirm the presence of oil reservoirs trapped by favorable geological structures, identifiable through geophysical and seismic methods. The methodological approach is based on a combined analysis of studies and seismic data. Drilling data from well PA, including well logs and end-of-well reports, were used to characterize the lithological formations encountered, particularly those of the Albian. 3D seismic profiles were interpreted to identify structures conducive to hydrocarbon accumulation. Isochrone, isovelocity, and isobath maps were developed to refine the interpretation. Sedimentological analyses revealed five sandy/gritty levels between 2610 m and 3100 m, interspersed with clay, limestone, and siltstone beds. The seismic profiles highlighted two main prospects. These prospects exhibit favorable geological structures, including normal faults and structural traps that provide oil traps.

Prospects in the application of ultrasensitive chromosomal aneuploidy detection in precancerous lesions of gastric cancer

Gastric cancer(GC)is a prevalent malignant tumor within the digestive system,with over 40%of new cases and deaths related to GC globally occurring in China.Despite advancements in treatment modalities,such as surgery supplemented by adjuvant radiotherapy or chemotherapeutic agents,the prognosis for GC remains poor.New targeted therapies and immunotherapies are currently under invest-igation,but no significant breakthroughs have been achieved.Studies have indicated that GC is a heterogeneous disease,encompassing multiple subtypes with distinct biological characteristics and roles.Consequently,personalized treatment based on clinical features,pathologic typing,and molecular typing is crucial for the diagnosis and management of precancerous lesions of gastric cancer(PLGC).Current research has categorized GC into four subtypes:Epstein-Barr virus-positive,microsatellite instability,genome stability,and chromosome instability(CIN).Technologies such as multi-omics analysis and gene sequencing are being employed to identify more suitable novel testing methods in these areas.Among these,ultrasensitive chromosomal aneuploidy detection(UCAD)can detect CIN at a genome-wide level in subjects using low-depth whole genome sequencing technology,in conjunction with bioinformatics analysis,to achieve qualitative and quantitative detection of chromosomal stability.This editorial reviews recent research advancements in UCAD technology for the diagnosis and management of PLGC.

Development and prospect of marine husbandry in Tianjin

Under the background of a new round of transformation and upgrading of the marine fishery industrial structure and the"speed up and upgrading"of the national marine ranching,this paper uses the method of combining practical experience,literature review,and field research to describe the development of marine ranching at home and abroad,and summarizes the practice process and achievements of Tianjin marine ranch:one national and two provincial marine ranch demonstration areas,16 ecotype reef areas,one seafood demonstration area,and one floating fish reef demonstration area were built,with a total scale of 26.9 km^(2),and a total of 134900 m^(2) fish reefs.This paper emphatically analyzed the construction experience and characteristics of the Tianjin Dashentang Marine Ranch demonstration area.Combined with the development orientation and objectives of Tianjin marine ranch,it is proposed to unify understanding,perfect development concept,accelerate the pace of scientific research,and adhere to ecological priority.In future,the construction of Tianjin marine ranch should encourage innovation to achieve leap-forward development,explore a new model of fishery development based on the'Economic Union',with'marine ranching-ecological farming-leisure tourism-featured products'as the main body.Based on relevant experience at home and abroad,the industrialization model of marine ranch with Tianjin characteristics should be established,which aims to provide strong support for the construction of"blue granary"in Tianjin,the implementation of Tianjin's coastal ranching strategy,and the promotion of Tianjin coastal ecosystem reconstruction and fishery resource recovery.

The Awkward Sharing Economy:Its Status Quo and Prospect

This paper comprehensively analyzes the origins,current situation,and prospects of the sharing economy.The primary purpose is to present the issues and challenges confronting the sharing economy at its current,awkward stage of development and to make reasonable speculations about its future.The research is based on academic literature on the sharing economy from both domestic and international sources.The findings indicate that despite current shortcomings in the regulatory system,industry structure,and user behavior,the scope of the sharing economy’s applications could still expand,and its technology could continue to advance.Overall,the prospects for the sharing economy are likely to be promising.

Leucocyte telomere length,brain volume and risk of dementia:a prospective cohort study

Background The evidence regarding the association between leucocyte telomere length(LTL)and brain health is sparse and inconclusive.Aims To investigate the associations of LTL with brain structure and the risk of dementia based on a large-scale prospective study.Methods LTL in the peripheral blood was measured by the quantitative polymerase chain reaction(qPCR)assay from 439961 individuals in the UK Biobank recruited between 2006 and 2010 and followed up until 2020.Electronic health records were used to record the incidence of dementia,including Alzheimer’s disease(AD)and vascular dementia(VD).The brain structure,including total and regional brain volume,of 38740 participants was then assessed by magnetic resonance imaging(MRI).Results During a median follow-up of 11.6 years,a total of 5820(1.3%)dementia cases were documented.The restricted cubic spline model showed significant overall associations between LTL and the risk of dementia and AD(p for overall<0.05).The multivariable adjusted hazard ratios(HRs)for the lowest LTL tertile compared with the highest LTL tertile were 1.14(95%confidence interval(CI):1.06 to 1.21)for dementia,1.28(95%CI:1.12 to 1.46)for AD and 1.18(95%CI:0.98 to 1.42)for VD.Furthermore,we found that shorter LTL was associated with smaller total brain volume(β=−0.0128,p=0.003),white matter volume(β=−0.0224,p<0.001),hippocampus volume(β=−0.0172,p<0.001),thalamus volume(β=−0.0239,p<0.001)and accumbens(β=−0.0155,p=0.001).Conclusions Shorter LTL is associated with total and regional brain structure and a higher risk of incident dementia and AD,implying the potential of telomere length as a predictive biomarker of brain health.

Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome:a prospective multicenter single-arm interventional study

OBJECTIVE To evaluate the feasibility and tolerability of metoprolol standard dosing pathway(MSDP)in Chinese patients with acute coronary syndrome(ACS).METHODS In this multicenter,prospective,open label,single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals.A total of 998 hospitalized patients aged≥18 years and diagnosed with ACS were included.The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines.The primary endpoint was the percentage of patients achieving the target dose at discharge(V2).The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge(V4),and percentage of patients experiencing bradycardia(heart rate<50 beats/min),hypotension(blood pressure<90/60 mmHg)and transient cardiac dysfunction at V2 and V4.RESULTS Of the 998 patients,29.46%of patients achieved the target dose(≥95 mg/d)at V2.The total population was divided into two groups:target group(patients achieving the target dose at V2)and non-target group(patients not achieving the target dose at V2).There was significant difference in the reduction of heart rate from baseline to discharge in the two groups(-4.97±11.90beats/min vs.-2.70±9.47 beats/min,P=0.034).There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2(0 vs.0,P=1.000)and V4(0.81%vs.0.33%,P=0.715).There was no significant difference in the proportion of hypotension between the two groups at V2(0.004%vs.0.004%,P=1.000)and V4(0 vs.0.005%,P=0.560).No transient cardiac dysfunction occurred in two groups during the study.A total of five adverse events(1.70%)and one serious adverse event(0.34%)were related to the pathway in target group.CONCLUSIONS In Chinese ACS patients,the feasibility and tolerability of the MSDP have been proved to be acceptable.

Microneedles for Enhanced Topical Treatment of Skin Disorders:Applications,Challenges,and Prospects

Microneedles(MNs)can be used for the topical treatment of skin disorders as they directly deliver therapeutics to the site of skin lesions,resulting in increased therapeutic efficacy while having minimum side effects.MNs are used to deliver different kinds of therapeutics(e.g.,small molecules,macromolecules,nanomedicines,living cells,bacteria,and exosomes)for treating various skin disorders,including superficial tumors,wounds,skin infections,inflammatory skin diseases,and abnormal skin appearance.The therapeutic efficacy of MNs can be improved by integrating the advantages of multiple therapeutics to perform combination therapy.Through careful designing,MNs can be further modified with biomimetic structures for the responsive drug release from internal and external stimuli and to enhance the transdermal delivery efficiency for robust therapeutic outcomes.Some studies have proposed the use of drug-free MNs as a promising mechanotherapeutic strategy to promote wound healing,scar removal,and hair regeneration via a mechanical communication pathway.Although MNs have several advantages,the practical application of MNs suffers from problems related to industrial manufacture and clinical evaluation,making it difficult for clinical translation.In this study,we summarized the various applications,emerging challenges,and developmental prospects of MNs in skin disorders to provide information on ways to advance clinical translation.