Radiomics-based quantitative contrast-enhanced CT analysis of abdominal lymphadenopathy to differentiate tuberculosis from lymphoma

Dear Editor,Tuberculosis(TB)is a significant cause of morbidity and mortality in developing countries,with a global burden of∼10.0 million cases in 2019.China accounts for 8.4%of TB cases globally,ranking third after India and Indonesia[1].Abdominal TB is a common extrapulmonary manifestation,often presenting as lymphadenopathy.Accurate differentiation between abdominal tuberculosis lymphadenopathy(ATBL)and lymphoma holds significance for treatment decisions and prognosis.

Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic approach.Despite advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation exposure.Methods To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA extraction.Telomere length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational burden.Result Telomere elongation occurred during spaceflight and shortened after return to Earth.Cell-free DNA analysis revealed increased immune cell signatures post-flight.No significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was observed.The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight.Conclusion Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth.CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career astronauts.This study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

The significance of long non-coding RNAs in the pathogenesis,diagnosis and treatment of inflammatory bowel disease

Inflammatory bowel diseases(IBD)are a group of chronic relapsing gastrointestinal inflammatory diseases with significant global incidence.Although the pathomechanism of IBD has been extensively investigated,several aspects of its pathogenesis remain unclear.Long non-coding RNAs(lncRNAs)are transcripts with more than 200 nucleotides in length that have potential protein-coding functions.LncRNAs play important roles in biological processes such as epigenetic modification,transcriptional regulation and posttranscriptional regulation.In this review,we summarize recent advances in research on IBD-related lncRNAs from the perspective of the overall intestinal microenvironment,as well as their potential roles as immune regulators,diagnostic biomarkers and therapeutic targets or agents for IBD.

Double-blinded,randomized clinical trial of Gegen Qinlian decoction pinpoints Faecalibacterium as key gut bacteria in alleviating hyperglycemia

Background:Accumulating evidence suggests that metabolic disorders,including type 2 diabetes mellitus(T2DM),can be treated with traditional Chinese medicine formulas,such as the Gegen Qinlian decoction(GQD).This study elucidates the mechanisms by which gut microbes mediate the anti-diabetic effects of GQD.Methods:We conducted a double-blind randomized clinical trial involving 120 untreated participants with T2DM.During the 12-week intervention,anthropometric measurements and diabetic traits were recorded every 4 weeks.Fecal microbiota and serum metabolites were measured before and after the intervention using 16S rDNA sequencing,liquid chromatography-mass spectrometry,and Bio-Plex panels.Results:Anti-diabetic effects were observed in the GQD group in the human trial.Specifically,glycated hemoglobin,fasting plasma glucose,and two-hour postprandial blood glucose levels were significantly lower in the GQD group than in the placebo group.Additionally,Faecalibacterium was significantly enriched in the GQD group,and the short-chain fatty acid levels were higher and the serum inflammation-associated marker levels were lower in the GQD group compared to the placebo group.Moreover,Faecalibacterium abundance negatively correlated with the levels of serum hemoglobin,fasting plasma glucose,and pro-inflammatory cytokines.Finally,the diabetes-alleviating effect of Faecalibacterium was confirmed by oral administration of Faecalibacterium prausnitzi(DSMZ 17677)in T2DMmousemodel.Conclusions:GQD improved type 2 diabetes primarily by modulating the abundance of Faecalibacterium in the gut microbiota,alleviating metabolic disorders and the inflammatory state.

Accurate prediction of myopic progression and high myopia by machine learning

Background Myopia is a leading cause of visual impairment in Asia and worldwide.However,accurately predicting the progression of myopia and the high risk of myopia remains a challenge.This study aims to develop a predictive model for the development of myopia.Methods We first retrospectively gathered 612530 medical records from five independent cohorts,encompassing 227543 patients ranging from infants to young adults.Subsequently,we developed a multivariate linear regression algorithm model to predict the progression of myopia and the risk of high myopia.Result The model to predict the progression of myopia achieved an R^(2) value of 0.964 vs a mean absolute error(MAE)of 0.119D[95%confidence interval(CI):0.119,1.146]in the internal validation set.It demonstrated strong generalizability,maintaining consistent performance across external validation sets:R^(2)=0.950 vs MAE=0.119D(95%CI:0.119,1.136)in validation study 1,R^(2)=0.950 vs MAE=0.121D(95%CI:0.121,1.144)in validation study 2,and R^(2)=0.806 vs MAE=−0.066D(95%CI:−0.066,0.569)in the Shanghai Children Myopia Study.In the Beijing Children Eye Study,the model achieved an R^(2) of 0.749 vs a MAE of 0.178D(95%CI:0.178,1.557).The model to predict the risk of high myopia achieved an area under the curve(AUC)of 0.99 in the internal validation set and consistently high area under the curve values of 0.99,0.99,0.96 and 0.99 in the respective external validation sets.Conclusion Our study demonstrates accurate prediction of myopia progression and risk of high myopia providing valuable insights for tailoring strategies to personalize and optimize the clinical management of myopia in children.

Precision medicine in inflammatory bowel disease

Inflammatory bowel disease(IBD)is an incurable disease characterized by remission-relapse cycles throughout its course.Both Crohn's disease(CD)and ulcerative colitis(UC),the two main forms of IBD,exhibit tendency to develop complications and substantial heterogeneity in terms of frequency and severity of relapse,thus posing great challenges to the clinical management for IBD.Current treatment strategies are effective in different ways in induction and maintenance therapies for IBD.Recent advances in studies of genetics,pharmacogenetics,proteomics and microbiome provide a strong driving force for identifying molecular markers of prognosis and treatment response,which should help clinicians manage IBD patients more effectively,and then,improve clinical outcomes and reduce treatment costs of patients.In this review,we summarize and discuss precision medicine in IBD,focusing on predictive markers of disease course and treatment response,and monitoring indices during therapeutic drug monitoring.

SARS-CoV-2 pathogenesis in the gastrointestinal tract mediated by Spike-induced intestinal inflammation

Dear Editor,The pathogenesis of COVID-19 in the gastrointestinal(GI)tract is well-documented[1].However,due to a lack of simple animal models,the pathogenic mechanisms of SARS-CoV-2 in the GI tract is not well established.Currently,common animal models for COVID-19 include mice,rats,hamsters,ferrets and non-human primates.

Prealbumin as a prognostic indicator for hospital readmission of ulcerative colitis patients

Dear Editor,Inflammatory bowel diseases(IBD)such as ulcerative colitis(UC)and Crohn's disease are affecting increasing numbers of patients worldwide.1 These chronic diseases significantly impact patients'quality of life as they are incurable and disabling.1 Patients with IBD have had an increasing rate of hospitalizations,half of all UC patients are hospitalized at least once during their lifetime,and readmissions after a UC-related hospitalization are common.

Instructions to Authors

Introduction Submission/How to contact the editorial office All manuscripts are submitted and reviewed via the journal's web-based manuscript submission system:http://mc.manuscriptcentral.com/pcm.New authors should create an account prior to submitting a manuscript for consideration.Questions about submitting to the journal should be sent to the editorial office at pcm@precisionclinmed.com.

Circle-map profiling of extrachromosomal circular DNA as diagnostic biomarkers for lung cancer

Dear Editor:Lung cancer has the highest incidence rate among malignancies and remains the primary contributor to cancer-related mortality on a global scale[1].Early detection is the most efficacious approach for enhancing the prognosis and mitigating the mortality of patients with lung cancer[2].Currently,diagnosis of lung cancer is mainly by different types of imaging including low-dose spiral computed tomography(LDCT)combined with pathological assessment of biopsy,but prevalence of false-positive results and associated expenses may impede its becoming a standard screening technique[3].

Circulating metabolic signatures of heart failure in precision cardiology

Precision cardiology aims to implement personalized health care and precise medical decisions based on the specific characteristics of individuals.Metabolic remodeling plays a causal role in the pathogenesis of heart failure(HF).Changes in metabolic pathways such as substrate preference,high-energy phosphate metabolism and amino acid metabolism,are involved in pathological structural remodeling and functional impairment.These metabolic alterations are usually not restricted in the cardiac tissue,but also manifest in circulation.In clinical practice,blood sample is routinely used for HF screening.Metabolomics is an emerging omics technology that provides an efficient way to acquire dynamic metabolic profiles in circulation.An increasing number of metabolic biomarkers have been implicated in disease progression,making it possible to fight HF in a more effective and precise way.This review summarizes the modern analytical techniques in metabolomics as well as emerging circulating metabolites during the pathogenesis of HF,aiming to provide new insights into the prevention,diagnosis and treatment of HF in the era of precision medicine.

Trajectory of fecal lactoferrin for predicting prognosis in ulcerative colitis

Objectives:To investigate the characteristics and prognostic value of fecal lactoferrin trajectories in ulcerative colitis(UC).Methods:This study used data from the UNIFI trial(ClinicalTrials.gov,NCT02407236)and included patients who received ustekinumab during induction for trajectory modeling(n=637).Patients who received ustekinumab during maintenance therapy were used for 1-year outcome analyses(n=403).The levels of fecal lactoferrin,fecal calprotectin,and serum C-reactive protein were measured at weeks O,2,4,and 8.The trajectories of these biomarkers were developed using a latent class growth mixed model.Results:The trajectories of fecal lactoferrin,fecal calprotectin,and serum C-reactive protein were distinct,but all were associated with prior exposure to anti-tumor necrosis factor agents and vedolizumab.Furthermore,the fecal lactoferrin trajectory was the most valuable predictor of endoscopic,clinical,and histological remission.Compared to the high/moderate-rapid decrease trajectory group,the moderate-slow decrease,high-slow decrease,and high-stable groups had adjusted odds ratios(95%confidence interval)of o.38(0.18,0.78;P=0.010),0.47(0.23,0.93;P=0.032),and 0.33(0.17,0.63;P=0.001),respectively,of 1-year endoscopic remission.Patients with high/moderate-rapid decrease trajectories also had the highest likelihood of achieving clinical and histological remission.Finally,we developed a patient-stratification scheme based on fecal lactoferrin trajectories and concentrations.Patients with good,moderate,and poor prognoses in the scheme had a distinct probability of achieving 1-year endoscopic remission(52.7%,30.9%,and 12.8%,respectively).Conclusions:The trajectory of fecal lactoferrin is a valuable prognostic factor for 1-year remission in UC.

Impact of age and tumor size on the development of the Kasabach-Merritt phenomenon in patients with kaposiform hemangioendothelioma:a retrospective cohort study

Introduction The Kasabach–Merritt phenomenon(KMP)is a severe complication of kaposiform hemangioendothelioma(KHE).The risk factors for KMP need further investigation.Methods The medical records of patients with KHE were reviewed.Univariate and multivariate logistic regression models were used for the risk factors for KMP,and the area under the receiver operator characteristic(ROC)curve was used to assess the predictive power of risk factors.Results A total of 338 patients with KHE were enrolled.The incidence of KMP was 45.9%.Age of onset(P<0.001,odds ratio[OR]0.939;95%confidence interval[CI]0.914–0.966),lesion size(P<0.001,OR 1.944;95%CI 1.646–2.296),mixed type(P=0.030,OR 2.428;95%CI 1.092–5.397),deep type(P=0.010,OR 4.006;95%CI 1.389–11.556),and mediastinal or retroperitoneal lesion location(P=0.019,OR 11.864;95%CI 1.497–94.003)were correlated with KMP occurrence through multivariate logistic regression.ROC curve analysis revealed that the optimal cutoffs were 4.75 months for the age of onset(P<0.001,OR 7.206,95%CI 4.073–12.749)and a lesion diameter of 5.35 cm(P<0.001,OR 11.817,95%CI 7.084–19.714).Bounded by a lesion size of 5.35 cm,we found significant differences in tumor morphology,age of onset,treatments,and hematological parameters.Using an onset age of 4.75 months as a cutoff,we found significant differences in tumor morphology,lesion size,hematological parameters,and prognosis.Conclusion For KHE patients with an onset age<4.75 months and/or lesion diameter>5.35 cm,clinicians should be wary of the occurrence of KMP.Active management is recommended to improve the prognosis.

Construction of regulatory network for alopecia areata progression and identification of immune monitoring genes based on multiple machine-learning algorithms

Objectives Alopecia areata(AA)is an autoimmune-related non-cicatricial alopecia,with complete alopecia(AT)or generalized alopecia(AU)as severe forms of AA.However,there are limitations in early identification of AA,and intervention of AA patients who may progress to severe AA will help to improve the incidence rate and prognosis of severe AA.Methods We obtained two AA-related datasets from the gene expression omnibus database,identified the differentially expressed genes(DEGs),and identified the module genes most related to severe AA through weighted gene co-expression network analysis.Functional enrichment analysis,construction of a protein–protein interaction network and competing endogenous RNA network,and immune cell infiltration analysis were performed to clarify the underlying biological mechanisms of severe AA.Subsequently,pivotal immune monitoring genes(IMGs)were screened through multiple machine-learning algorithms,and the diagnostic effectiveness of the pivotal IMGs was validated by receiver operating characteristic.Results A total of 150 severe AA-related DEGs were identified;the upregulated DEGs were mainly enriched in immune response,while the downregulated DEGs were mainly enriched in pathways related to hair cycle and skin development.Four IMGs(LGR5,SHISA2,HOXC13,and S100A3)with good diagnostic efficiency were obtained.As an important gene of hair follicle stem cells stemness,we verified in vivo that LGR5 downregulation may be an important link leading to severe AA.Conclusion Our findings provide a comprehensive understanding of the pathogenesis and underlying biological processes in patients with AA,and identification of four potential IMGs,which is helpful for the early diagnosis of severe AA.

Workup of difficult-to-treat asthma:implications from treatable

Traditional stepwise approach usually adjusts the treatment regimen based on changes in asthma symptoms and severity to achieve good asthma control.However,due to the generalized heterogeneity and complexity of asthma,its therapeutic efficacy in difficultto-treat asthma is limited.Recently,a precision medicine approach based on the identification and intervention of treatable traits of chronic airway disease has been proposed and appears to be of greater benefit to asthmatics.We reported a 71-year-old male with uncontrolled asthma and multiple exacerbations over the past year.He complained of persistent dyspnea despite high-dose of inhaled corticosteroids plus other controllers.Does this patient have some potential treatable traits contributing to difficult-to-treat asthma?Through a multidimensional assessment of three domains including pulmonary,extrapulmonary,and behavioral/risk factors,15 treatable traits were identified in the patient,mainly including airflow limitation,eosinophilic airway inflammation,small airway dysfunction,exacerbation prone,dilated cardiomyopathy,diabetes mellitus,inhaler device polypharmacy,smoking,and the absence of an asthma action plan.After targeted treatment for these treatable traits,the patient experienced significant improvement in dyspnea and he could maintain good asthma control with low-dose inhaled corticosteroids and long-acting β_(2)-agonist.This study shows that,in response to the limitation of a stepwise approach to therapy,treatable traits is a new strategy where patients are individually assessed for a specified set of treatable problems,and an individualized treatment program is developed and implemented based on this multidimensional assessment,especially for difficult-to-treat asthma.

Pig-to-Human xenotransplantation:Moving toward organ customization

Dear Editor,Xenotransplantation is a potentially effective way to address the shortage of organ donors.The improvements in gene editing technology have accelerated a number of a breakthrough in genetically modifying pigs for xenotransplantation.In 2022,xenograft kidney transplantation entered the subclinical trial stage.

Overexpressed miR-539 exacerbates Pseudomonas aeruginosa puenmonia by promoting inflammatory responses

Dear Editor,Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that causes a series of life-threatening acute and/or chronic infections in humans,often in persons with immunodeficiency.P.aeruginosa has been listed as one of the priority bacteria that requires extensive research and urgent development of new antibiotic treatments by the World Health Organization(WHO)in 2017.1 In recent years,numerous studies have shown that miRNAs play an important role in infection and inflammatory responses.2,3 Our earlier researches suggest that miRNAs are a key regulator of the inflammatory responses and are involved in the clearance of P.aeruginosa in vitro and in vivo.

GLUE multimodal single cell data

Single cell sequencing can obtain genetic information of largescale cells at a single cell resolution.The technology has revolutionized life science research and accelerated discoveries in gene expression,cell development,immunology,and others.For instance,single cell transcriptomics has promoted our capability in presenting cell types and status.The outcome sequencing data from single cell technologies allows us to build a comprehensive reference atlas for human cells,enabling us to target complex diseases such as cancers.

Investigating association between gut microbiota and sarcopenia-related traits:a Mendelian randomization study

Background Observational studies have indicated a potential link between gut microbiota and sarcopenia.However,the underlying mechanisms and a causal relationship have not been established.Thus,the objective of this study is to examine the possible causal association between gut microbiota and sarcopenia-related traits,including low hand-grip strength and appendicular lean mass(ALM),to shed light on the gut–muscle axis.Methods To investigate the potential impact of gut microbiota on low hand-grip strength and ALM,we utilized a two-sample Mendelian randomization(MR)approach.Summary statistics were obtained from genome-wide association studies of gut microbiota,low hand-grip strength,and ALM.The primary MR analysis employed the random-effects inverse-variance weighted(IVW)method.To assess the robustness,we conducted sensitivity analyses using the MR pleiotropy residual sum and outlier(MR-PRESSO)test to detect and correct for horizontal pleiotropy,as well as the MR-Egger intercept test and leave-one-out analysis.Results Alcaligenaceae,Family XIII,and Paraprevotella were positively associated with the risk of low hand-grip strength(P-values<0.05).Streptococcaceae were negatively associated with low hand-grip strength(P-values<0.05).Eight bacterial taxa(Actinomycetales,Actinomycetaceae,Bacteroidaceae,Porphyromonadaceae,Prevotellaceae,Bacteroides,Marvinbryantia,and Phascolarctobacterium)were associated with a higher risk of ALM(P-values<0.05).Eubacterium fissicatena group was negatively associated with ALM(P-values<0.05).Conclusion We found several gut microbiota components causally associated with sarcopenia-related traits.Our findings provided insights into novel strategies for the prevention and treatment of sarcopenia through the regulation of the gut microbiota,contributing to a better understanding of the gut–muscle axis.

Impact of apolipoprotein A1 on tumor immune microenvironment, clinical prognosis and genomic landscape in hepatocellular carcinoma

Background:Current knowledge on apolipoprotein A1(APOA1)in hepatocellular carcinoma(HCC)is fragmented and even contradic-tory.Multi-dimensional analyses are required to comprehensively elucidate its value and underlying mechanism.Methods:We collected 49 RNA-seq datasets,40 cell line types data and 70 scRNA pan-cancer datasets public available,including 17 HCC datasets(1754 tumor samples),and enrolled 73 pairs of HCC tissue and 516 blood samples independently from our clinics.APOA1 impacting on the HCC tumor microenvironment(TME)was analyzed using intensive data mining.Methylation sequencing,flow cy-tometry,quantitative PCR,western blot,immunohistochemistry and clinical chemistry assays were conducted for wet experimental investigation.Results:The APOA1 ontology fingerprint indicated that it played various crucial biological roles in HCC,primarily involved in choles-terol efflux.Consistent findings at histology,serology,and clinical follow-up revealed that high APOA1 was a good prognosis indicator of HCc.Hypermethylation in the APOA1 promoter region was found in clinical samples which is in accordance with the reduction of APOA1 in HCC.The cell cycle,DNA replication,mismatch repair pathways,and tumor cell proliferation were less observed in the HCC APOAihigh subgroup.The favorable immunoregulatory abilities of APOA1 showed interesting findings:a positive correlation between APOA1 and anti-tumor immune cells(NK,CD8+T cells)and a negative association with immune cells exerting immunosuppressive effects,including M2 macrophages.Conclusion:This is an integrative multidimensional exploration of APOA1 using bioinformatics and experiments.Both the prognostic value and anti-tumor effects based on APOA1 panoramic exploration in the HCC TME demonstrate a new potential clinicai target for HCC assessment and intervention in the future.