Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.

OBJECTIVE: CRISPR-Cas protects bacteria from exogenous DNA invasion and is associated with bacterial biofilm formation and pathogenicity. METHODS: We analyzed the type I-F CRISPR-Cas system of Legionella pneumophila WX48, including Cas1, Cas2-Cas3, Csy1, Csy2, Csy3, and Cas6f, along with downstream CRISPR arrays. We explored the effects of the CRISPR-Cas system on the in vitro growth, biofilm-forming ability, and pathogenicity of L. pneumophila through constructing gene deletion mutants. RESULTS: The type I-F CRISPR-Cas system did not affect the in vitro growth of wild-type or mutant strains. The biofilm formation and intracellular proliferation of the mutant strains were weaker than those of the wild type owing to the regulation of type IV pili and Dot/Icm type IV secretion systems. In particular, Cas6f deletion strongly inhibited these processes. CONCLUSION The type I-F CRISPR-Cas system may reduce biofilm formation and intracellular proliferation in L. pneumophila.
Legionella pneumophila/pathogenicity* ; CRISPR-Cas Systems ; Biofilms/growth & development* ; Phenotype ; Bacterial Proteins/metabolism* ; Gene Deletion

Objective To provide a scoping review of studies on the application of intelligent healthcare for continuity management in liver transplant patients,in order to provide a reference for the future development of intelligent liver transplant management.Methods A systematic search of relevant studies was conducted in PubMed,Embase,CINAHL,Web of Science,Cochrane Library,Scopus,CNKI,Wanfang Database,VIP Database,and CBM from the establishment of the databases to 30 September 2024.Following this search,the included literature was screened,summarized,and analyzed.Results A total of 19 papers were included.The intervention forms included application,intelligent medical device,and remote rehabilitation platform.The content elements included transplant health management,rehabilitation program planning,health data monitoring,telemedicine consultation,psychosocial support,and follow-up supervision.The evaluation indicators included physiological indicators,self-management ability,health-related quality of life,transplantation outcomes,patient satisfaction,and feasibility indicators.Conclusion The application of intelligent healthcare in the continuity management of liver transplantation patients is feasible and effective,and it is recommended that healthcare professionals integrate the diverse practice forms of intelligent healthcare,deepen the content elements and refine the evaluation indicator system based on the actual clinical situation,in order to improve the quality of the continuity management of liver transplantation patients.

Objective:To analyze the clinical characteristics and prognosis of dengue fever inpatients in Guangzhou area, so that to provide references for clinical diagnosis and treatment.Methods:The demographic data, laboratory findings, clinical manifestations, and outcomes of 116 dengue fever cases admitted to Guangzhou Red Cross Hospital, Jinan University and the First Affiliated Hospital, Jinan University from August 1st to December 21st, 2024 were retrospectively analyzed.Results:Among the 116 patients, 99 cases (85.34%) were classified as non-severe dengue, while 17(14.66%) progressed to severe dengue (SD). The cohort was comprised of 62(53.45%) males and 54(46.55%) females, with an age of 63.5(22.0) years, and the hospitalization duration was 6(4) days, with the fever duration of 6(2) days. Sixty-two patients (53.45%) were complicated with comorbidities, among which hypertension (66.13%(41/62)), diabetes mellitus (25.81%(16/62)) and coronary atherosclerotic heart disease (22.58%(14/62)) accounted for the highest proportion. Primary clinical manifestations included fever (113 cases, 97.41%), with 86.21%(100/116) experiencing fever ≥five days, followed by fatigue (92 cases, 79.31%), myalgia (65 cases, 56.03%), anorexia (56 cases, 48.28%), cough/sputum (55 cases, 47.41%), and headache (54 cases, 46.55%). Early laboratory findings revealed leukopenia (2.22(1.75)×10 9/L], lymphopenia (0.63(0.50)×10 9/L), and thrombocytopenia (77.00(57.00)×10 9/L). Among 17 SD cases, 17 cases experienced severe organ damage, two cases had severe gastrointestinal bleeding, and two cases had septic shock. Among the patients with severe organ damage, there were eight cases of severe cardiac injury, followed by six cases of severe respiratory system injury, four cases of multiple organ dysfunction syndrome, three cases of acute kidney injury, three cases of neurological injury, and three cases of disseminated intravascular coagulation. Severe cardiac injury was manifested with acute heart failure in five cases, malignant arrhythmia in three cases, stress cardiomyopathy in one case, and acute myocardial infarction in one case. Severe respiratory system injuries were manifested with acute respiratory distress syndrome in five cases, severe pneumonia in three cases, and acute pulmonary embolism in one case. Neurological damage was manifested with viral meningitis in one case, acute cerebral infarction in one case, and sensorineural hearing loss in one case. All patients were cured or discharged after symptomatic supportive treatment and active prevention and treatment of complications. Conclusions:In 2024, dengue fever inpatients in Guangzhou area predominantly consist of elderly patients, who are complicated with comorbidities and present a high proportion of severe cases. Severe patients are primarily characterized by organ damage, with cardiovascular system injury being the most common severe manifestation. Dengue patients have a good prognosis.

Objective:To analyze and summarize the clinical features and short-medium term follow-up results of children with multisystem inflammatory syndrome（MIS-C）following coronavirus infection.Methods:The data of six children with MIS-C admitted to the Intensive Care Unit of Shanghai Children's Medical Center from January to March 2023 were retrospectively analyzed.Results:All six cases were in shock，requiring vasoactive drugs，and one case required invasive mechanical ventilation.All the six patients had multiple organ function injury and increased inflammation indicators.After admission，they received organ support，glucocorticoids and gamma globulin treatment.Two patients were treated with biological agents.Both organ function and inflammation indicators showed significantly improvement after therapy.Six patients had mild coronary artery widening.All patients had good prognosis following short-medium term follow-up.Conclusion:Children with severe MIS-C may suffer life-threatening hemodynamic instability.Timely assessment，active anti-inflammatory and organ support therapy can obtain favorable prognosis.

Objective To provide a scoping review of studies on the application of intelligent healthcare for continuity management in liver transplant patients,in order to provide a reference for the future development of intelligent liver transplant management.Methods A systematic search of relevant studies was conducted in PubMed,Embase,CINAHL,Web of Science,Cochrane Library,Scopus,CNKI,Wanfang Database,VIP Database,and CBM from the establishment of the databases to 30 September 2024.Following this search,the included literature was screened,summarized,and analyzed.Results A total of 19 papers were included.The intervention forms included application,intelligent medical device,and remote rehabilitation platform.The content elements included transplant health management,rehabilitation program planning,health data monitoring,telemedicine consultation,psychosocial support,and follow-up supervision.The evaluation indicators included physiological indicators,self-management ability,health-related quality of life,transplantation outcomes,patient satisfaction,and feasibility indicators.Conclusion The application of intelligent healthcare in the continuity management of liver transplantation patients is feasible and effective,and it is recommended that healthcare professionals integrate the diverse practice forms of intelligent healthcare,deepen the content elements and refine the evaluation indicator system based on the actual clinical situation,in order to improve the quality of the continuity management of liver transplantation patients.

Tracheobronchial adenoid cystic carcinoma （TACC） is a low-grade malignant tumor originating from the airway mucosa. Despite its slow progression，it is characterized by high invasiveness，frequent recurrence，and a strong tendency for metastasis. Preclinical studies have shown that vascular-targeted therapy holds significant potential. However，an effective systemic treatment for TACC has not been established yet. This study explored TACC from the perspective of "Feiji" in traditional Chinese medicine （TCM） as the starting point. It deeply investigated the mechanisms of abnormal collaterals and tumor vascular recruitment and further elaborated on the theoretical connection between abnormal collaterals and tumor vascular recruitment. Firstly，collateral hyperactivity led to disordered and erratic pulmonary collaterals. Their abnormal structures were similar to the disorderly and tortuous nature of tumor （pseudo）angiogenesis. This resulted in imbalances in the functions of circulation，perfusion，and reverse injection of the pulmonary collaterals，and then led to unrestrained collateral dysfunction and the accumulation of pathogenic factors. Secondly，the remodeling of the extracellular matrix （ECM） and epithelial-mesenchymal transition （EMT） in TACC were critical processes in vascular co-option （VCO），representing the micro-level manifestation of the displacement of nutrient and defense. During this process，ECM remodeling made TACC cells more likely to hijack normal blood vessels，creating a complex vascular microenvironment conducive to tumor growth. In terms of treatment，this study proposed a TCM strategy of "regulating collaterals to expel pathogenic factors and nourishing collaterals to strengthen the healthy Qi"，and listed potential TCM. These were intended to regulate the Qi and blood in the collaterals，repair the functions of abnormal collaterals，and intervene in the vascular recruitment process of TACC. Future research should focus on improving the TCM clinical syndrome characteristics of TACC. Through modern molecular biology techniques，it is necessary to deeply analyze the micro-level pattern of vascular recruitment in TACC. This would enrich the understanding of the profound connection between abnormal collaterals and tumor vascular recruitment，providing empirical evidence for TCM-targeted therapies for vascular recruitment in TACC.

Individuals with congenital absence of the vas deferens (CAVD) may transmit cystic fibrosis (CF)-causing variants of the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene to their offspring through assisted reproductive technology (ART). We aimed to delineate the spectrum and estimate the prevalence of CF-causing variants in Chinese individuals with CAVD through a cohort analysis and meta-analysis. CFTR was sequenced in 145 Chinese individuals with CAVD. CFTR variants were classified as CF-causing or non-CF-causing variants regarding clinical significance. A comprehensive genotype analysis was performed in Chinese individuals with CAVD, incorporating previous studies and our study cohort. The prevalence of CF-causing variants was estimated through meta-analysis. In our cohort, 56 different CFTR variants were identified in 108 (74.5%) patients. Twenty variants were categorized as CF-causing and were detected in 28 (19.3%) patients. A comprehensive genotype analysis of 867 patients identified 174 different CFTR variants. Sixty-four were classified as CF-causing variants, 56.3% of which had not been previously reported in Chinese patients with CF. Meta-analysis showed that 14.8% (95% confidence interval [CI]: 11.0%-18.9%) CAVD cases harbored one CF-causing variant, and 68.6% (95% CI: 65.1%-72.0%) CAVD cases carried at least one CFTR variant. Our study underscores the urgent need for extensive CFTR screening, including sequencing of whole exons and flanking regions and detection of large rearrangements and deep intronic CF-causing variants, in Chinese individuals with CAVD before undergoing ART. The established CF-causing variants spectrum may aid in the development of genetic counseling strategies and preimplantation diagnosis to prevent the birth of a child with CF.
Adult ; Humans ; Male ; China ; Cohort Studies ; Cystic Fibrosis/genetics* ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics* ; Genotype ; Male Urogenital Diseases/genetics* ; Mutation ; Vas Deferens/abnormalities* ; East Asian People/genetics*

Objective:To understand the prevalence of frailty and the importance of its influencing factors in adult population in Shaanxi Province.Methods:The data were from Shaanxi baseline survey of natural population cohort study in northwest China during 2018-2019. The frailty index (FI) was constructed to evaluate the frailty status of the population, and XGboost model combined with Shapley method was used to analyze the importance of the sociodemographic and life behavior factors affecting the prevalence of frailty by gender and age.Results:A total of 25 079 subjects were included, in whom 964 (3.8%) had frailty, and there was no significant difference in the overall prevalence of frailty between women (3.9%) and men (3.8%) ( P=0.629), but there was a gender specific difference in the distribution of FI ( P<0.001), and the proportion of the pre-frailty in men was higher than that in women. The prevalence of frailty increased with age ( P<0.001), the prevalence of frailty were 1.3%, 2.5% and 7.8% in young, middle-aged and elderly women, respectively, and 1.9%, 2.7% and 5.5% in young, middle-aged and elderly men, respectively. Sociodemographic characteristics and lifestyle patterns were both influencing factors for the prevalence of frailty, but their importance varied with gender and age. The top five contributing factors were education level, staying up late, annual family income level, sedentary time and marital status in young women, and staying up late, smoking, annual family income level, sedentary time and drinking in young men. The top five contributing factors were education level, annual family income level, passive exposure to smoking, staying up late, and sedentary time in middle-aged women, and annual family income level, education level, sedentary time, staying up late and drinking in middle-aged men. The top five contributing factors were annual family income level, passive exposure to smoking, sedentary time, marital status, and smartphone use in elderly women, and education level, annual family income level, smoking, smartphone use and sedentary time in elderly men. Conclusions:There are gender specific differences in the distribution of FI in Shaanxi. The prevalence of frailty increased with age, but young and middle-aged people also have frailty risk. The prevalence of frailty in young men was mainly related to unhealthy life behaviors, such as staying up late, smoking, sedentary behavior and drinking, while the prevalence of frailty in middle-aged and elderly men and women were more affected by sociodemographic factors, such as education level, economic status and marital status.

Objective To investigate the effects of remimazolam(REM)on cerebral ischemia-reperfusion injury(CIRI)rats and the AMP-activated protein kinase(AMPK)/NOD-like receptor protein 3(NLRP3)signaling pathway.Methods One hundred rats were selected to construct the CIRI rat model(Mod)and stochastically separated into a Mod group,low,medium,and high dose remifentanil groups(REM-L,REM-M,REM-H),and high dose remifentanil+pathway inhibitor Compound C group(REM-H+Compound C),with 20 rats in each group.Another 20 healthy rats were included as the control(Ctrl)group.All rats were subjected to neurobehavioral scoring.The water content,infarct area,and oxidative stress indicators of brain tissue were detected.The morphology and apoptosis of brain tissue were observed by HE and TUNEL staining.Western blotting was applied to detect protein expression related to the AMPK/NLRP3 signaling pathway.Results Compared with the Mod group,with the increase of REM dose,the movement disorders in rats were alleviated,the overall structure of brain tissue gradually recovered,pathological damage was reduced,the area of cerebral infarction,brain water content,and apoptosis rate of brain tissue cells decreased,reactive oxygen species(ROS)level,malondialdehyde(MDA)content,and NLRP3 and Caspase-1 protein expression levels decreased,superoxide dismutase the(SOD)content and AMPK protein expression level increased(P＜0.05).Compared with the REM-H group,the REM-H+Compound C group showed aggravated motor disorders,and more severe pathological damage to brain tissue,the area of cerebral infarction,cerebral water content and apoptosis rate of brain tissue cells increased,the ROS level,MDA content and the protein expression of NLRP3 and Caspase-1 increased,while the content of SOD and the protein expression decreased(P＜0.05).Conclusion Remimazolam can enhance the antioxidant function of the body,reduce brain cell apoptosis,alleviate brain tissue injury,and thus have a certain protective effect on ischemia-reperfusion brain injury in rats,the mechanism of which may be related to the activation of the AMPK/NLRP3 signaling pathway.