With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

ObjectiveTo explore the mechanism of action of Wendantang on ApoE^-/- hyperlipidemic mice using non-targeted metabolomics technology. MethodsMale C57BL/6J mice served as the normal control group （n=6）， and they were fed with regular chow， while male ApoE^-/- mice constituted the high-fat group （n=30）， and they were fed with a 60% high-fat diet. After 11 weeks of model establishment， the mice in the high-fat group were randomly divided into the model group， simvastatin group （3.3 mg·kg^-1）， and high-dose， medium-dose， and low-dose groups of Wendantang （26， 13， 6.5 g·kg^-1， respectively， in terms of crude drug amount）， with six mice in each group. The normal control group and the model group were gavaged with an equivalent volume of normal saline， and all groups continued to be fed their respective diets， receiving daily medication for 10 weeks with weekly body weight measurements. Serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， free fatty acids （NEFA）， blood glucose （GLU）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were detected in the mice. Pathological changes in liver tissue were observed using hematoxylin-eosin （HE） staining， and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS/MS） was employed for metabolomic analysis of mouse liver tissue. ResultsCompared to the normal control group， the model group exhibited significantly increased body weight， blood lipid levels， and liver function （P<0.05， P<0.01）， with disordered liver tissue structure， swollen hepatocytes， and accompanying vacuolar fatty degeneration and inflammatory cell infiltration. Compared to the model group， the simvastatin group and Wendantang groups showed significantly reduced body weight， TG， NEFA， GLU， ALT， and AST levels （P<0.05， P<0.01）， with a significant increase in HDL-C levels （P<0.05， P<0.01）， demonstrating a dose-dependent effect. The lesion of the liver tissue section was obviously improved after administration， tending towards a normal liver tissue morphology. Analysis of liver metabolites revealed 86 differential metabolites between the normal control group and the model group， with the high-dose group of Wendantang able to regulate 56 of these metabolites. Twenty-two differential metabolites associated with hyperlipidemia were identified， mainly including chenodeoxycholic acid， hyocholic acid， taurine， glycocholic acid， dihydroceramide， hydroxy sphingomyelin C14∶1， arachidonic acid， and linoleic acid， enriching 22 metabolic pathways， with 4 being the most significant （P<0.05）， namely primary bile acid biosynthesis， sphingolipid metabolism， unsaturated fatty acid biosynthesis， and linoleic acid metabolism pathways. ConclusionWendantang can improve blood lipid levels and liver function in ApoE^-/- hyperlipidemic mice， which may be related to the regulation of primary bile acid biosynthesis， sphingolipid metabolism， unsaturated fatty acid biosynthesis， and linoleic acid metabolism pathways.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

OBJECTIVES: To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students. METHODS: This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia. RESULTS: The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081). CONCLUSIONS Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans ; Myopia/etiology* ; Male ; Female ; Depression/physiopathology* ; Cross-Sectional Studies ; Sleep ; Adolescent ; Students ; Child ; Time Factors ; Sleep Duration

OBJECTIVE: To explore the clinical characteristics and prognosis of children with SIL-TAL1-positive T-cell acute lymphoblastic leukemia ( SIL-TAL1⁺ T-ALL). METHODS: The clinical data of 110 children with newly diagnosed T-ALL admitted to the pediatric department of our hospital from January 2010 to December 2018 were reviewed to compare the clinical characteristics, treatment response and prognosis between SIL-TAL1⁺ group and SIL-TAL1^-group. RESULTS: Among the 110 children with T-ALL, 25 cases (22.7%) were in the SIL-TAL1⁺ group and 85 cases (77.3%) in the SIL-TAL1^- group. The white blood cell (WBC) count in the SIL-TAL1⁺ group was significantly higher than that in the SIL-TAL1^- group (P < 0.05), while the other clinical characteristics and treatment response were not significantly different between the two groups. The 5-year overall survival (OS) rates of SIL-TAL1⁺ group and SIL-TAL1^- group were 80.0% and 75.5%, and 5-year disease-free survival (DFS) rates were 76.0% and 72.9%, respectively. There were no significant differences in OS rate and DFS rate between the two groups ( P >0.05). In children aged < 10 years, the 5-year OS rate of SIL-TAL1⁺ group and SIL-TAL1^- group was 100% and 75.1%, respectively, and the difference between the two groups was statistically significant (P < 0.05). CONCLUSION Although the WBC level is significantly higher in children with SIL-TAL1⁺ T-ALL than that in those with SIL-TAL1^- T-ALL, the treatment efficacy is similar between the two groups. In children aged < 10 years, the longterm survival rate is superior in the SIL-TAL1⁺ group.
Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; Prognosis ; Child ; Male ; Female ; Survival Rate ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; Child, Preschool ; Oncogene Proteins, Fusion ; Leukocyte Count

OBJECTIVES: Depressive and anxiety disorders are among the most common mental disorders worldwide and are associated with unhealthy lifestyle behaviors. The Life's Simple 7 (LS7) guideline proposed by the American Heart Association aims to reduce cardiovascular risk by improving behaviors such as diet and physical activity, but its impact on mental health is not yet fully clear. This study examined the association between LS7 scores and symptoms of anxiety and depression in adults undergoing routine health examinations. METHODS: Data were collected from individuals who underwent health examinations from May 2015 to December 2024 at the Health Management Center of the Third Xiangya Hospital. All participants completed the LS7 assessments, the Self-Rating Depression Scale (SDS), and the Self-Rating Anxiety Scale (SAS). Participants were categorized into 4 LS7 score groups: Low (≤7), average (8-9), good (10), and excellent (11-14). Those with SDS or SAS≥50 were classified as having mental disorder symptoms; with this group, SAS≥50 indicated anxiety, SDS≥50 indicated depression, and SDS and SAS≥50 indicated comorbid anxiety-depression. Binary logistic regression was used to assess associations between LS7 score and mental symptoms, calculating odds ratio (OR) and 95% confidence interval (CI). A restricted cubic spline (RCS) regression model was used to analyze the dose-response relationship between LS7 score (continuous variable) and the risk of mental symptoms. Nodes were set at the 5th, 35th, 65th, and 95th percentiles of the LS7 score, with the 5th percentile as the reference point. All models were adjusted for covariates such as gender, age, living alone, drinking status, education level, and sleep quality. Logistic regression framework was used to fit and calculate the adjusted OR (aOR) and 95% CI. Nonlinear relationship tests were also conducted. Subgroup analysis was performed to explore the interaction between gender, age, drinking habits, education level, and other factors and the LS7 score in influencing the risk of mental symptoms. RESULTS: A total of 5 449 participants were included; 1 363 (25.01%) had depressive symptoms, 398 (7.30%) had anxiety symptoms, and 259 (4.75%) had comorbid anxiety-depression. The prevalence of mental symptoms decreased significantly as LS7 scores increased. Univariate and multivariate Logistic regression indicated that LS7 score≥8 was protective against mental symptoms. Multivariate Logistic regression demonstrated moderate discriminative ability (AUC=0.672). Among individuals with anxiety, depression, or comorbid symptoms, LS7 score distributions showed a graded decrease from poor to excellent groups. After adjustment, an excellent LS7 score was associated with a 39% lower risk of depression (aOR=0.61, 95% CI 0.47 to 0.78, P<0.001), a 63% lower risk of anxiety (aOR=0.37, 95% CI 0.22 to 0.59, P<0.001), and a 66% lower risk of comorbid anxiety-depression (aOR=0.34, 95% CI 0.17 to 0.62, P=0.001). The AUC values of the anxiety model, depression model, and comorbid anxiety and depression model were 0.632, 0.672, and 0.619, respectively. All models demonstrated moderate discriminatory ability, which was statistically significant, but their capacity to distinguish cases from non-cases was limited. RCS analysis confirmed a linear inverse relationship between LS7 score and mental symptom risk. Not smoking and regular physical activity were the strongest protective behaviors. Subgroup analysis suggested stronger protective effects in men, younger adults (≤60), non-drinkers, and those with higher education levels, and revealed a significant interaction between alcohol use and LS7 score (P for interaction=0.021), indicating that alcohol consumption may weaken the protective effect of LS7. CONCLUSIONS Ideal healthy lifestyle behaviors, as reflected by higher LS7 scores, are associated with lower risks of anxiety and depression in adults. Promoting LS7-based lifestyle practices may serve as a practical and effective strategy for the prevention and management of anxiety and depression in both clinical and daily life settings.
Humans ; Cross-Sectional Studies ; Depression/epidemiology* ; Anxiety/epidemiology* ; Adult ; Male ; Female ; Middle Aged ; Healthy Lifestyle ; Risk Factors ; Anxiety Disorders/epidemiology* ; Exercise ; Physical Examination ; Aged

Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

G protein-coupled receptors (GPCRs) are the largest family of membrane proteins in eukaryotes, with nearly 800 genes coding for these proteins. They are involved in many physiological processes, such as light perception, taste and smell, neurotransmitter, metabolism, endocrine and exocrine, cell growth and migration. Importantly, GPCRs and their ligands are the targets of approximately one third of all marketed drugs. GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane. However, emerging evidence suggests that GPCRs are also localized on mitochondria, where they play critical roles in modulating mitochondrial functions. These mitochondrial GPCRs (mGPCRs) can influence processes such as mitochondrial respiration, apoptosis, and reactive oxygen species (ROS) production. By interacting with mitochondrial signaling pathways, mGPCRs contribute to the regulation of energy metabolism and cell survival. Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling, highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction. This expanding understanding of mGPCR function on mitochondria opens new avenues for research, particularly in the context of diseases where mitochondrial dysfunction plays a key role. Abnormalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease, diabetes, obesity and Alzheimer's disease. In this review, we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases. We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease, and to underscore their potential as therapeutic targets in the treatment of these conditions.