Over the past two decades, genome-wide association study(GWAS) has identified numerous genetic variants and loci associated with heritable diseases. With the gradual maturation and saturation of GWAS methodologies, transcriptome-wide association study(TWAS) offers a novel perspective by linkinggenetic phenotypes to gene expression levels. By integrating TWAS with other multi-omics analyses, researchers can gain a deeper understanding of heritable diseases. This article provides an overview of recent groundbreaking and representative TWAS methods and tools, analyzes their strengths and limitations, and discusses future trends in TWAS development.

Objective To explore the relationship between pathogenic microorganism types,age and season in 2 188 children with respiratory tract infections.Methods A total of 2 188 children with respiratory tract in-fections admitted to the Department of Pediatrics,962 Hospital,Joint Logistic Support Force of PLA from June 2023 to May 2024 were selected as the study subjects.Targeted next generation sequencing(tNGS)tech-nology was used to detect 107 common pathogenic microorganism in children with respiratory tract infections,including Haemophilus influenzae,rhinovirus,Moraxella catarrhalis,Mycoplasma pneumoniae,Staphylococcus aureus,Streptococcus pneumoniae,human parainfluenza virus,human respiratory syncytial virus,etc.The re-spiratory tract infection situation and epidemiological characteristics of children in Harbin were analyzed.Re-sults Among 2 188 pediatric patients,98.5%(2 156/2 188)tested positive for pathogenic microorganism,with Haemophilus influenzae accounting for the highest proportion of 33.5%(732/2 188),followed by rhino-virus of 25.0%(547/2 188)and Moraxella catarrhalis of 24.8%(543/2 188).The positive rates of Hae-mophilus influenzae and human adenovirus in male children were higher than those in female children(P<0.05),while there were no statistically significant differences in the positive positive rates of other pathogenic microorganism between male and female children(P>0.05).Except for human adenovirus and influenza A virus,which showed no statistically significant differences in positive rates among different age groups(P>0.05),there were statistically significant differences in the positive rates of other pathogenic microorganism a-mong different age groups(P<0.05).The positive rates of pathogenic microorganism in preschool children were relatively high.There were no statistically significant differences in the positive rates of Streptococcus and Staphylococcus aureus in different seasons(P>0.05),while there were statistically significant differences in the positive rates of other pathogenic microorganism in different seasons(P<0.05).The positive rates of Haemophilus influenzae,Streptococcus pneumoniae,human metapneumovirus,human parainfluenza virus and SARS-Cov-2 were the highest in summer(P<0.05).Conclusion 2 188 children with respiratory tract infec-tions were mainly caused by pathogenic microorganism such as Haemophilus influenzae,rhinovirus,and Moraxella catarrhalis,etc.Preschool children is a susceptible group,and the prevalence of pathogenic microor-ganism varies seasonally.In clinical practice,relevant prevention and control measures should be developed based on this characteristic to reduce the incidence of diseases.

Acute ischemic stroke is the most common type of stroke, characterized by high mortality, disability, and recurrence rates. Intravenous thrombolysis is the core treatment method. Among them, alteplase is effective as the standard drug, but it has limitations such as narrow time window, high risk of bleeding, and the need for continuous infusion. The new generation of improved drug tenecteplase has the advantages of single intravenous injection and higher fibrin specificity, making it a potential alternative drug to alteplase. In addition, endovascular therapy compensates for the low recanalization rate of large vessel occlusion on the basis of intravenous thrombolysis. This article reviews the clinical progress of teneplase in the treatment of acute ischemic stroke, aiming to provide reference for optimizing the treatment plan of acute ischemic stroke.

BACKGROUND: The use of potentially inappropriate medications (PIMs) is a major concern for medication safety as it may entail more harm than potential benefits for older adults. This study aimed to explore the prescribing rate, healthcare utilization, and expenditure of older adults using PIMs in China. METHODS: A cross-sectional analysis was conducted using a national representative database of all medical insurance beneficiaries across China, extracting ambulatory visit records of adults aged 65 years and above between 2015 and 2017. Descriptive analysis was conducted to measure the rate of patients exposed to PIM, prescribing rate of each PIM, average annual outpatient visits per patient, average total medication costs for each visit, average annual cost of PIMs for each patient, and average annual medication costs for each patient. Generalized linear model with logit link function and binomial distribution was used to examine the adjusted associations between PIMs and independent variables. RESULTS: In total, 845,278 (33.2%) participants were identified to be exposed to at least one PIM. Patients aged 75-84 years (38.1%, 969,809/2,545,430) and ≥85 years (37.9%, 964,718/2,545,430) were more likely to be prescribed with PIMs. Beneficiaries of the Urban Employee Basic Medical Insurance (UEBMI) and living in eastern and southern regions were more frequently prescribed with PIMs. Compared with patients without PIM exposure (7.5 visits, drug cost of RMB 1545.0 Yuan), patients with PIM exposure showed higher adjusted average annual number of outpatient visits (10.7 visits, β = 3.228, 95% confidence interval [CI] = 3.196-3.261) and higher annual drug costs (RMB 2461.8 Yuan, Coef. = 916.864, 95% CI = RMB 906.292-927.436 Yuan). CONCLUSIONS The results showed that the use of PIM among older adults was common in China. This study suggests that the use of PIM could be considered as a clear target, pending multidimensional efforts, to promote rational prescribing for older adults.
Humans ; Aged ; Cross-Sectional Studies ; Aged, 80 and over ; Male ; Female ; China ; Inappropriate Prescribing/economics* ; Patient Acceptance of Health Care/statistics & numerical data* ; Potentially Inappropriate Medication List/statistics & numerical data* ; Health Expenditures/statistics & numerical data*

Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver injuries, including steatosis to steatohepatitis (MASH), liver fibrosis, cirrhosis, and relevant complications. The liver mainly comprises hepatocytes, liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), immune cells (T cells, B cells), and hepatic stellate cells (HSCs). Crosstalk among these different liver cells, endogenous aberrant glycolipid metabolism, and altered gut dysbiosis are involved in the pathophysiology of MASLD. This review systematically examines advances in understanding the molecular pathogenesis of MASLD, with a focus on emerging therapeutic targets and translational clinical trials. We first delineate the crucial regulatory mechanisms involving diverse liver cells and the gut-liver axis in MASLD development. These cell-specific pathogenic insights offer valuable perspectives for advancing precision medicine approaches in MASLD treatment. Furthermore, we evaluate potential therapeutic targets and summarize clinical trials currently underway. By comprehensively updating the MASLD pathophysiology and identifying promising strategies, this review aims to facilitate the development of novel pharmacotherapies for this increasingly prevalent condition.
Humans ; Fatty Liver/therapy* ; Animals ; Liver/pathology* ; Kupffer Cells/metabolism* ; Hepatocytes/metabolism* ; Hepatic Stellate Cells/metabolism*

BACKGROUND: Bile acids (BAs) facilitate the progression of gastric intestinal metaplasia (GIM). Long non-coding RNAs (lncRNAs) dysregulation was observed along with the initiation of gastric cancer. However, how lncRNAs function in GIM remains unclear. This study aimed to explore the role and mechanism of lncRNA PVT1 in GIM, and provide a potential therapeutic target for GIM treatment. METHODS: We employed RNA sequencing (RNA-seq) to screen dysregulated lncRNAs in gastric epithelial cells after BA treatment. Bioinformatics analysis was conducted to reveal the regulatory mechanism. PVT1 expression was detected in 21 paired biopsies obtained under endoscopy. Overexpressed and knockdown cell models were established to explore gene functions in GIM. Molecular interactions were validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (Ch-IP). The levels of relative molecular expression were detected in GIM tissues. RESULTS: We confirmed that lncRNA PVT1 was upregulated in BA-induced GIM model. PVT1 promoted the expression of intestinal markers such as CDX2 , KLF4 , and HNF4α . Bioinformatics analysis revealed that miR-34b-5p was a putative target of PVT1 . miR-34b-5p mimics increased CDX2 , KLF4 , and HNF4α levels. Restoration of miR-34b-5p decreased the pro-metaplastic effect of PVT1 . The interactions between PVT1 , miR-34b-5p, and the downstream target HNF4α were validated. Moreover, HNF4α could transcriptionally activated PVT1 , sustaining the GIM phenotype. Finally, the activation of the PVT1 /miR-34b-5p/ HNF4α loop was detected in GIM tissues. CONCLUSIONS BAs facilitate GIM partially via a PVT1/miR-34b-5p/HNF4α positive feedback loop. PVT1 may become a novel target for blocking the continuous development of GIM and preventing the initiation of gastric cancer in patients with bile reflux.
Humans ; RNA, Long Noncoding/metabolism* ; MicroRNAs/metabolism* ; Hepatocyte Nuclear Factor 4/genetics* ; Bile Acids and Salts ; Kruppel-Like Factor 4 ; Metaplasia/metabolism*

Objective To investigate the correlation between changes in physiological indicators and altitude,age,and sex among ethnic Tibetan college students living in Xizang on long-term basis upon their first ever visit to a low-altitude region,thereby providing health guidance for long-term residents of high-altitude regions when they visit low-altitude environments for the first time.Methods A cluster random sampling method was used to select 170 healthy first-year college students of Tibetan ethnicity(85 males and 85 females),from Xizang Minzu University.The participants did not have any respiratory,circulatory,or nervous system diseases,nor any family history of such conditions.Based on their responses to questionnaires and the monitoring data of their physiological indicators,an analysis was conducted to assess the incidence and duration of deacclimatization symptoms among these Tibetan college students during the first month after their arrival at a low-altitude region.In addition,the R programming language and the SPSS software were used to analyze the correlation between changes in blood pressure,heart rate,and body weight and the participants'age,sex,and the altitude of their long-term residence in Xizang before and after their arrival at a low-altitude region.Results Statistical analysis revealed that Tibetan college students experienced deacclimatization symptoms within the first week of their first ever visit to a low-altitude region,primarily characterized by dizziness,fatigue,and drowsiness.The incidence was 41.9％among female students and 22.5％among male students.Furthermore,after arriving at low-altitude region,the participants experience an initial decrease followed by a recovery in both blood pressure and heart rate.They gained an average of 1.5 kg in body mass compared with their initial measurements upon arrival in a low-altitude region.Significant differences in blood pressure,heart rate,and body mass were observed among Tibetan students of different sexes and altitudes of their long-term residence in Xizang after their arrival in a low-altitude region.Conclusion After arriving at a low-altitude region,Tibetan college students exhibit marked changes in physiological indicators,showing strong correlations between systolic blood pressure,body mass,etc.,and sex,altitude,and other parameters.

Objective To determine the time point when porcine pancreatic elastase(PPE)induced abdominal aortic aneurysm(AAA)reaches the regression phase in mice and observe the histological characteristics of AAA in regression phase.Methods AAAs were induced by transient intraluminal infusion of PPE in C57BL/6J mice.The diameters of the mouse abdominal aortas were measured before PPE infusion and sacrifice time,day 14 for AAA progression phase or day 56 for regression phase after PPE infusion,respectively.The histological characteristics of the aneurysm lesion site on day 14 and day 56 after surgery were compared and analyzed.Results The diameters of the abdominal aortas were significantly increased in both day 14 and day 56 after PPE infusion groups(diameter growth rate 147％and 155％,respectively)as compared to the baseline diameters.In the day 14 group,the infused aortas showed typical AAA characteristics,such as elastin break/degradation,medial smooth muscle cells depletion,and inflammatory cell diffused infiltration.In the day 56 group after PPE infusion,although the artery diameter did not change significantly as compared to the day 14 group,histology showed that elastin was partially repaired,new smooth muscle cells were added to the damaged aorta media,the infiltrated inflammatory cells were significantly subsided,and the adventitia neovascularization was reduced,showing a significant feature of the disease regression phase.Conclusion In the PPE-induced mouse AAA model,day 56 after surgery is an appropriate time point for observing aneurysm regression,and the histological characteristics of the regression are obvious.

Glioma is the most common primary tumor of the brain,accounting for 81%of central nervous system(CNS)malignant tumors.The degree of malignancy is high,and the current treatment methods are limited.In recent years,with the in-depth study of intestinal flora and brain-gut axis,it has been found that the diversity of gut microbiota plays an important role in the regulation of glioma.The mechanism is that the intestinal flora affects the development of glioma through the role of immune regulation and metabolites.In addition,it has been con-firmed that there is a certain correlation between some probiotics and glioma,which provides a new application prospect for the treatment of glioma.This paper discusses the main intestinal bacteria that regulate gliomas as well as the role and regulatory mechanisms of intestinal flora in the development of gliomas,and provides ideas for the discovery of new targets for glioma treatment and further improvement of treatment options.

Heracleum candicans is extensively utilized for its abundant medicinal components,which are applied in various treatments,including insecticides,hemostatic agents,dispersing wind,relieving cough,and alleviating rheumatic pain.This paper reviewed the various chemical constituents and pharmacological effects of Heracleum candicans.It aims to provide new insights for its promotion and application,as well as to provide a basis for establishing quality standards for Heracleum candicans.