Bioengineered skin organoids:from development to applications

Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical concerns.The inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic changes.This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages.Furthermore,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic devices.The review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.

Age and mean platelet volume-based nomogram for predicting the therapeutic efficacy of metoprolol in Chinese pediatric patients with vasovagal syncope

Background Vasovagal syncope(VVS)is the most common type of orthostatic intolerance in children.We investigated whether platelet-related factors related to treatment efficacy in children suffering from VVS treated with metoprolol.Methods Metoprolol-treated VVS patients were recruited.The median duration of therapy was three months.Patients were followed and divided into two groups,treament-effective group and treatment-ineffective group.Logistic and least absolute shrinkage selection operator regressions were used to examine treatment outcome variables.Receiver-operating characteristic(ROC)curves,precision-recall(PR)curves,calibration plots,and decision curve analyses were used to evaluate the nomogram model.Results Among the 72 patients who complete the follow-up,treatment-effective group and treatment-ineffective group included 42(58.3%)and 30(41.7%)cases,respectively.The patients in the treatment-effective group exhibited higher mean platelet volume(MPV)[(11.0±1.0)fl vs.(9.8±1.0)fl,P<0.01]and platelet distribution width[12.7%(12.3%,14.3%)vs.11.3%(10.2%,12.2%),P<0.01]than those in the treatment-ineffective group.The sex ratio was significantly different(P=0.046).A fit model comprising age[odds ratio(OR)=0.766,95%confidence interval(CI)=0.594-0.987]and MPV(OR=5.613,95%CI=2.297-13.711)might predict therapeutic efficacy.The area under the curve of the ROC and PR curves was computed to be 0.85 and 0.9,respectively.The P value of the Hosmer-Lemeshow test was 0.27.The decision curve analysis confirmed that managing children with VVS based on the predictive model led to a net advantage ranging from 0.01 to 0.58.The nomogram is convenient for clinical applications.Conclusion A novel nomogram based on age and MPV can predict the therapeutic benefits of metoprolol in children with VVS.

Associations of polygenic risk scores with risks of stroke and its subtypes in Chinese

Background and purpose Previous studies,mostly focusing on the European population,have reported polygenic risk scores(PRSs)might achieve risk stratification of stroke.We aimed to examine the association strengths of PRSs with risks of stroke and its subtypes in the Chinese population.Methods Participants with genome-wide genotypic data in China Kadoorie Biobank were split into a potential training set(n=22191)and a population-based testing set(n=72150).Four previously developed PRSs were included,and new PRSs for stroke and its subtypes were developed.The PRSs showing the strongest association with risks of stroke or its subtypes in the training set were further evaluated in the testing set.Cox proportional hazards regression models were used to estimate the association strengths of different PRSs with risks of stroke and its subtypes(ischaemic stroke(IS),intracerebral haemorrhage(ICH)and subarachnoid haemorrhage(SAH)).Results In the testing set,during 872919 person-years of follow-up,8514 incident stroke events were documented.The PRSs of any stroke(AS)and IS were both positively associated with risks of AS,IS and ICH(p<0.05).The HR for per SD increment(HR_(SD))of PRSAS was 1.10(95%CI 1.07 to 1.12),1.10(95%CI 1.07 to 1.12)and 1.13(95%CI 1.07 to 1.20)for AS,IS and ICH,respectively.The corresponding HR_(SD) of PRS_(IS) was 1.08(95%CI 1.06 to 1.11),1.08(95%CI 1.06 to 1.11)and 1.09(95%CI 1.03 to 1.15).PRS_(ICH) was positively associated with the risk of ICH(HR_(SD)=1.07,95%CI 1.01 to 1.14).PRSS_(AH) was not associated with risks of stroke and its subtypes.The addition of current PRSs offered little to no improvement in stroke risk prediction and risk stratification.Conclusions In this Chinese population,the association strengths of current PRSs with risks of stroke and its subtypes were moderate,suggesting a limited value for improving risk prediction over traditional risk factors in the context of current genome-wide association study under-representing the East Asian population.

When smoke meets gut:deciphering the interactions between tobacco smoking and gut microbiota in disease development

Tobacco smoking is a prevalent and detrimental habit practiced worldwide,increasing the risk of various diseases,including chronic obstructive pulmonary disease(COPD),cardiovascular disease,liver disease,and cancer.Although previous research has explored the detrimental health effects of tobacco smoking,recent studies suggest that gut microbiota dysbiosis may play a critical role in these outcomes.Numerous tobacco smoke components,such as nicotine,are found in the gastrointestinal tract and interact with gut microbiota,leading to lasting impacts on host health and diseases.This review delves into the ways tobacco smoking and its various constituents influence gut microbiota composition and functionality.We also summarize recent advancements in understanding how tobacco smoking-induced gut microbiota dysbiosis affects host health.Furthermore,this review introduces a novel perspective on how changes in gut microbiota following smoking cessation may contribute to withdrawal syndrome and the degree of health improvements in smokers.

Advances in microbubble-assisted ultrasound-guided gene therapy:Mechanisms and applications

Gene therapy,as one of the popular therapies nowadays,has been applied with great success in various diseases.Nevertheless,there are also concerns about the safety,therapeutic efficacy,and applicability of gene therapy.Microbubble-assisted ultrasound-guided gene therapy offers the following incomparable advantages over conventional methods.Initially,this strategy enables the therapeutic nucleic acids to effectively cross the barriers like cell membrane,blood-brain barrier,and blood-retinal barrier that exist in the body and reach regions that cannot be accessed by conventional methods,which extends the scope of applications of gene therapy.Next,it is possible to restrict the zone of gene transfection to the lesion area by controlling the irradiation coverage of ultrasound,hence effectively controlling the risk of off-targeting.Additionally,with the support of various imaging techniques like ultrasound imaging and magnetic resonance imaging,the procedure of gene therapy can be under image guidance,which will dramatically improve the safety of gene therapy.This review will highlight on the advances in ultrasound-enhanced gene delivery strategy,attention to the relevant mechanisms of the strategy,the derived technologies and the related cutting-edge applications.Moreover,we will also have a discussion on the limitations and future prospects associated with this gene delivery strategy.

Prevalence and Risk Factors for Chronic Obstructive Pulmonary Disease Among Adults Aged 50 and Above-10 CKB Study Areas,China,2020–2021

What is already known about this topic?The prevalence of COPD in Chinese individuals aged 50 years and above was obviously higher than that in younger adults,but the risk factors for this age group were unclear.What is added by this report?The prevalence was estimated at 12.8%and 5.7%for males and females over 50 in 2020–2021,with confirmed risk factors of cigarette smoking,a family history of respiratory diseases,respiratory symptoms,and a history of cough or respiratory diseases during childhood.What are the implications for public health practice?The findings may help clinicians and the public identify individuals at high risk of COPD and take targeted measures in a timely manner.

The Association Between Preserved Ratio Impaired Spirometry and Mortality –– 10 CKB Study Areas, China, 2004–2022

What is already known about this topic?China has the world’s most significant public health and economic burden of chronic respiratory disease.However,the association between preserved ratio impaired spirometry(PRISm)and mortality risk is unknown.What is added by this report?The PRISm group exhibited a 37%higher risk of allcause mortality than the normal group,and the risks of death from cardiovascular diseases,neoplasms,respiratory diseases,and infectious and parasitic diseases were also increased in PRISm.Moreover,the presence of respiratory symptoms or disease was associated with an increased risk of mortality in PRISm.What are the implications for public health practice?It is imperative to enhance public awareness of PRISm and to implement measures to facilitate the regression of PRISm toward normal lung function.

MicroRNA–disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice

Abdominal aortic aneurysm(AAA)is a permanent dilatation of the abdominal aorta and is highly lethal.The main purpose of the current study is to search for noninvasive medical therapies for AAA,for which there is currently no effective drug therapy.Network medicine represents a cuttingedge technology,as analysis and modeling of disease networks can provide critical clues regarding the etiology of specific diseases and therapeutics that may be effective.Here,we proposed a novel algorithm to quantify disease relations based on a large accumulated microRNA–disease association dataset and then built a disease network covering 15 disease classes and 304 diseases.Analysis revealed some patterns for these diseases.For instance,diseases tended to be clustered and coherent in the network.Surprisingly,we found that AAA showed the strongest similarity with rheumatoid arthritis and systemic lupus erythematosus,both of which are autoimmune diseases,suggesting that AAA could be one type of autoimmune diseases in etiology.Based on this observation,we further hypothesized that drugs for autoimmune diseases could be repurposed for the prevention and therapy of AAA.Finally,animal experiments confirmed that methotrexate,a drug for autoimmune diseases,was able to alleviate the formation and development of AAA.

A shared role of the myocardin-family transcriptional coactivators in cardiomyocyte maturation

Dear Editor,In development,after cells make a commitment to their fates,they undergo a continuous and adaptive maturation process to eventually reach their terminal states.Cell maturity often decays during aging and pathogenesis.The immature phenotypes of stem cell-differentiated cells deposit a major bottleneck in regenerative medicine.

Gut microbiota,immunity,and bile acid metabolism:decoding metabolic disease interactions

In recent decades,the global prevalence of metabolic syndrome has surged,posing a significant public health challenge.Metabolic disorders,encompassing diabetes,obesity,nonalcoholic fatty liver disease,and polycystic ovarian syndrome,have been linked to alterations in the gut microbiota.Nonetheless,the connection between gut microbiota and host metabolic diseases warrants further investigation.In this review,we delve into the associations between various metabolic disorders and the gut microbiota,focusing on immune responses and bile acid(BA)metabolism.Notably,T helper cells,innate lymphoid cells,macrophages,and dendritic cells have been shown to modulate host metabolism through interactions with intestinal microorganisms and the release of cytokines.Furthermore,secondary BA metabolites,derived from the microbiota,are involved in the pathogenesis of metabolic diseases via the farnesoid X receptor and Takeda G protein-coupled receptor 5.By covering both aspects of this immune system-microorganism axis,we present a comprehensive overview of the roles played by the gut microbiota,microbiota-derived BA metabolites,and immune responses in metabolic diseases,as well as the interplay between these systems.

Insights into postural orthostatic tachycardia syndrome after COVID-19 in pediatric patients

The pandemic caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)profoundly threatened human health globally and greatly impacted the world economy[1].While most patients recovered,some suffered from chronic symptoms after the acute phase of coronavirus disease 2019(COVID-19).

LLMs in medicine:The need for advanced evaluation systems for disruptive technologies

In an era of rapid advancements in artificial intelligence(AI),the potential role of large language models(LLMs)in the medical field is receiving increasing attention.The progression of this technology not only highlights upcoming revolutionary changes in medical services but also offers unprecedented opportunities for the health care sector.1 LLMs’formidable capability to process natural language opens vast prospects for application in the medical field,including in the contexts of emergency triage,geriatric care,and digital medical workflows.

Gut microbial-host-isozymes are new targets for diseases

Gut microbiota can interact with the host through lots of media including small molecular metabolites and proteins(Cani,2019;Fan and Pedersen,2021;Krautkramer et al.,2021).Recently,a new interaction pattern was identified,i.e.,gut microbiota can mimic the function of the host by producing a variety of enzymes with functions homologous to host enzymes.

心脏纤维化机制研究的全新视角

Cardiac fibrosis is the excessive deposition of extracellular matrix(ECM)proteins in heart tissues leading to functional and electrophysiological abnormalities.Being a common pathology in different diseased conditions,cardiac fibrosis has been regarded as an appropriate(reparative)or inappropriate(reactive)pathological response.