OBJECTIVE: Observational studies have shown inconsistent associations of loneliness or social isolation (SI) with ischemic heart disease (IHD), with unknown mediators. METHODS: Using data from genome-wide association studies of predominantly European ancestry, we performed a bidirectional two-sample Mendelian Randomization (MR) study to estimate causal effects of loneliness ( N = 487,647) and SI traits on IHD ( N = 184,305). SI traits included whether individuals lived alone, participated in various types of social activities, and how often they had contact with friends or family ( N = 459,830 to 461,369). A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators, including metabolic, behavioral and psychological factors. RESULTS: Loneliness increased IHD risk ( OR= 2.129; 95% confidence interval [ CI]: 1.380 to 3.285), mediated by body fat percentage, waist-hip ratio, total cholesterol, and low-density lipoprotein cholesterol. For SI traits, only fewer social activities increased IHD risk ( OR= 1.815; 95% CI: 1.189 to 2.772), mediated by hypertension, high-density lipoprotein cholesterol, triglycerides, fasting insulin, and smoking cessation. No reverse causality of IHD with loneliness and SI was found. CONCLUSION These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD, with several mediators as prioritized targets for intervention.
Loneliness/psychology* ; Humans ; Mendelian Randomization Analysis ; Social Isolation ; Myocardial Ischemia/etiology* ; Male ; Female ; Middle Aged ; Genome-Wide Association Study ; Risk Factors ; Aged

Objective To investigate the status of hearing impaired children's hearing device independence skills,and to explore the ways to improve their self-use of hearing equipment.Methods This study surveyed 64 re-habilitation teachers and 411 parents of children with hearing impairment aged 0-12 years.Through face-to-face or remote telephone interview,3 good habits(A asking parents for advice before removing the HA,B putting the de-vice into a moisture-proof box after removing it,C bringing batteries to school and knowing where are them)and 3 key abilities[D wearing the device independently,E replacing the battery independently,and F independently handle foreign bodies in the ear mold(Fa)and water vapor(Fb)]was investigated.The age when mastering skills or de-veloping habits difference of hearing impaired children in different groups were compared.Results ① The ratio of ability D in the bilateral CI group and the bilateral HA group of preschool children was 30.97％and 18.57％respec-tively.Among elementary school children,85.29％and 90.70％had this ability respectively.② The ratio of ability E in the bilateral CI group,the bilateral HA group and the bimodel group were 11.50％,15.71％and 16.49％,re-spectively.Among elementary school children,64.71％,53.49％and 68.52％had this ability,respectively.③Among preschool children,there was no statistical difference in age when different equipment groups developed the three good habits and acquired ability D and E(P＞0.05).④ Among primary school children,there was a statisti-cal difference in the age when different equipment groups formed habit A(P＜0.05),and the age when double CI group had this ability was slightly earlier than the double HA group.There was no significant difference in other abilities among age groups(P＞0.05).Conclusion The age at which hearing impaired children develop the three good habits precedes the age at which they master the key skills,which accords with the law of skill acquisition and development of ordinary children.Corresponding teaching process should be based on the age and ability of hearing-impaired children without considering the type of equipment.

Objective:To investigate the clinical value of filling ultrasound combined with microflow imaging（MFI）in diagnosing small intestinal polyps for Peutz-Jeghers syndrome（P-JS）patients.Methods:From February 2022 to October 2024，86 P-JS patients were consecutively enrolled in the Air Force Special Medical Center. All patients underwent a filling ultrasound with oral 2.5% mannitol solution and MFI examination，with final polyp confirmation by enteroscopy. Polyps were categorized based on image quality（good or poor）and diameter（classified into different ranges）. The relationships between ultrasound characteristics，blood perfusion，and small intestine polyps were analyzed. ROC curve analysis was performed to evaluate the diagnostic efficacy of filling ultrasound alone and in combination with MFI for small intestine polyps.Results:Oral mannitol filling of the small intestine was successfully demonstrated. Multiple small intestinal polyps were detected in 82 patients，and no polyps in 4 patients. Filling ultrasound significantly improved the detection rate of small intestinal polyps in P-JS patients，especially for polyps ≤ 35 mm（ P<0.05）. However，there was no significant difference between the detection rate of polyps >35 mm and that of conventional ultrasound（ P>0.05）. In the case of poor image quality，filling ultrasound combined with MFI further improved the detection rate of ≤35 mm polyps（ P<0.05）. The results of the multivariate analysis showed that the maximum polyp diameter（ P=0.030）and blood flow pattern（ P=0.016）showed by MFI were influencing factors for the diagnosis P-JS small intestinal polyps. The diagnostic efficacies of filling ultrasound and filling ultrasound combined with MFI were good. The diagnostic AUC value，accuracy，sensitivity，and specificity of filling ultrasound were 0.887，0.863，0.850，and 0.765，respectively，while the diagnostic AUC value，accuracy，sensitivity，and specificity of filling ultrasound with MFI were 0.913，0.927，0.969 and 0.923，respectively. Conclusions:Filling ultrasound with oral 2.5% mannitol solution combined with MFI significantly optimizes the detection efficiency of small intestinal polyps in P-JS patients，providing strong support for clinical diagnosis.

OBJECTIVE: To investigate the anti-tumor effects of cinobufacini (CINO) on hepatocellular carcinoma (HCC) induced by des-gamma-carboxy-prothrombin (DCP) and to uncover the underlying mechanisms. METHODS: The inhibitory effect of CINO on HCC cell proliferation was evaluated using the cell counting kit-8 method, and the apoptosis rate was quantified using flow cytometry. Immunofluorescence and Western blot analyses were used to investigate the differential expression of proteins associated with cell growth, apoptosis, migration, and invasion pathways after CINO treatment. The therapeutic potential of CINO for HCC was confirmed, and the possibility of combining cinobufacini with c-Met inhibitor for the treatment of primary HCC was further validated by in vivo experiments. RESULTS: Under the induction of DCP, CINO inhibited the activity of HCC cells, induced apoptosis, and inhibited migration and invasion. Upon the induction of DCP, CINO regulated c-Met activation and the activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways. In a mouse model of HCC, CINO exhibited significant antitumor effects by inhibiting the phosphorylation of c-Met and the downstream PI3K/AKT and MEK/ERK pathways in tumor tissues. CONCLUSIONS CINO inhibited HCC cell growth, promoted apoptosis, and suppressed HCC cell invasion and migration by targeting c-Met and PI3K/AKT and MEK/ERK signaling pathways under DCP induction.
Carcinoma, Hepatocellular/drug therapy* ; Proto-Oncogene Proteins c-met/metabolism* ; Liver Neoplasms/drug therapy* ; Signal Transduction/drug effects* ; Animals ; Humans ; Cell Movement/drug effects* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Amphibian Venoms/therapeutic use* ; Cell Line, Tumor ; Neoplasm Metastasis ; Cell Survival/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Neoplasm Invasiveness ; Mice, Inbred BALB C ; Mice, Nude ; Mice ; Male ; Bufanolides/therapeutic use* ; Protein Precursors ; Prothrombin ; Biomarkers

OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

Objective To explore the risk factors for medium-and long-term mortality in patients with severe community-acquired pneumonia(SCAP)based on the Medical Information Mart for Intensive Care Ⅳ(MIMIC-Ⅳ),construct a prognostic model and evaluate its predictive efficacy.Methods In this retrospective cohort study,1943 SCAP patients from the U.S.MIMIC-Ⅳdatabase(2008-2019)were randomly divided into training(n=1363)and validation(n=580)sets(7:3 ratio).Primary and secondary endpoints were 1-year and 30-/90-day all-cause mortality,respectively.Prognostic factors were selected using LASSO regression and multivariable Cox proportional hazards modeling,and a visual nomogram model was built.Model performance was assessed via C-index,receiver operator characteristic(ROC)curves,and calibration curves,and compared with the CURB-65 score.Risk stratification was validated using Kaplan-Meier analysis.Results The 30-day,90-day,and 1-year all-cause mortality rates for SCAP patients were 25.9％,34.5％,and 42.6％,respectively.Seven independent risk factors were identified:age(HR=1.037),heart rate(HR=1.007),red blood cell distribution width(RDW,HR=1.092),Acute Physiology Score Ⅲ(APS-Ⅲ,HR=1.013),cerebrovascular disease(HR=1.453),liver disease(HR=1.272),and malignancy(HR=2.007).Based on these factors,Cox regression model was constructed and nomogram was drawn,C-indices of training set and validation set were 0.710 and 0.688,respectively.For 1-year mortality prediction,the model achieved superior area under the ROC curve(AUC)values(training set:0.768;validation set:0.738)compared with CURB-65 score(training set:0.648;validation set:0.616).Kaplan-Meier survival analysis revealed significantly worse survival in high-risk group than low-risk group(P<0.0001).Conclusions Age,heart rate,RDW,APS-Ⅲ,cerebrovascular disease,liver disease,and malignant tumor were medium-and long-term mortality risk factors in SCAP patients.The prognostic model constructed based on these factors has high predictive power and provides an important clinical diagnosis and treatment reference.

Objective: To examine the association of joint effect of overweight and obesity with dyslipidemia on left ventricular hypertrophy (LVH) in children, so as to provide scientific evidence for the prevention of early cardiovascular damage in children. Methods: Data were obtained from the second followup crosssectional survey of Huantai Childhood Cardiovascular Health Cohort study in 2021, comprising 1 047 children aged 10-15 years with complete information. Based on overweight and obesity status and dyslipidemia status, all participants were divided into four groups:normal weight with normal lipid levels, normal weight with dyslipidemia, overweight and obesity with normal lipid levels, and overweight and obesity with dyslipidemia. Left ventricular mass index (LVMI) levels and prevalence of LVH across four groups were compared. Multivariate Logistic regression model was used to examine the association of joint effect of overweight and obesity with dyslipidemia on LVH in children. Results: There were significant differences in LVMI levels [(28.66±7.10, 29.63±4.71,31.49±5.86,32.65±4.80)g/m2.7] and prevalence of LVH (4.28%, 12.50%, 22.74%, 31.30%) across four groups (F/χ2=50.76, 90.92, P<0.05). After adjustment for confounding variables such as gender,age,screen time,sleep duration,fruit and vegetable intake,carbonated beverage consumption,physical activity and elevated blood pressure, compared to children with both normal weight and normal lipid levels, the risk of LVH in children with dyslipidemia alone increased (OR=3.27, 95%CI=1.57-6.82，P<0.05). Children with overweight and obesity alone also had a significantly increased risk of LVH (OR=6.33, 95%CI=3.76-10.66), and the highest risk was observed in those with both overweight and obesity with dyslipidemia (OR=9.66, 95%CI=5.35-17.43) (P<0.05). Conclusions The joint effect of overweight and obesity with dyslipidemia is positively correlated with LVH in children. To prevent LVH in children, both overweight and obesity with dyslipidemia should be paid attention to.

Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy,driven by multiple gene mutations and characterized by high incidence and mortality rates. Mesenchymal stem cells (MSCs),which possess self-renewal and multidirectional differentiation potentials,play crucial roles within the bone marrow microenvironment. Emerging research has demonstrated that MSCs contribute to AML development through various mechanisms,including mitochondrial transfer,transmission of extracellular vesicles,adipogenic differentiation,and secretion of pro-cancer proteins. This review provides a comprehensive summary of the involvement of MSCs in the AML bone marrow microenvironment and offers insights for developing novel therapeutic strategies targeting MSCs in AML treatment.

Objective:To explore the therapeutic effect of CD5L targeted therapy on a rat model of collagen-induced arthritis (CIA).Methods:The CIA rat model was established and treated with anti-CD5L antibody. The clinical arthritis score and tissue swelling degree of rats were evaluated. Twenty-four SD rats were randomly divided into the control group, the model group, the isotype control group and the CD5L antibody group. HE staining and safranin fast green staining were used to observe the synovial inflammation and cartilage erosion in the ankle joint of CIA rats. Micro-CT was used to scan the feet of CIA rats to detect bone mineral density and bone destruction. The levels of TNF-α, IL-6 and IL-8 in serum were detected by enzyme-linked immunosorbent assay (ELISA). All experimental data conforming to normal distribution were compared between groups by one-way ANOVA, and Dunnet t test was used to compare the two groups. Results:CD5L antibody improved joint swelling and deformity in CIA rats. The statistics of arthritis scores in rats showed that there was a statistically significant difference in arthritis scores between the CD5L antibody group and the isotype antibody group of rats from Day 23[Day 23 (6.6±0.5) vs. (8.2±0.7), t=-7.07, P<0.05; Day 26 (7.0±0.6) vs. (8.4±0.5), t=-7.59, P<0.05; Day 29 (7.6±0.4) vs. (9.4±0.8), t=-6.96, P<0.05; Day 32 (7.8±0.5) vs.(9.6±1.1), t=-6.50, P<0.05; Day 35 (8.2±0.7) vs. (10.4±0.7), t=-5.88, P<0.05]. The HE staining results showed that there was a statistically significant difference in the HE staining score between the CD5L antibody group and the isotype antibody group of rats [(2.5±0.6) vs. (5.0±0.8), t=-6.73, P<0.05]. The results of safranin fixation green staining showed that there was a statistically significant difference in the safranin fixation green staining score between the CD5L antibody group and the isotype antibody group of rats [(1.8±0.8) vs. (3.5±0.6), t=-5.22, P<0.05]. The Micro-CT imaging results showed that there was a statistically significant difference in bone mineral density between the CD5L antibody group and the isotype antibody group of rats [(5 618±128)g/cm 3vs. (5 202±39)g/cm 3, t=8.06, P<0.01]. The ELISA results showed that there were statistically significant differences in the contents of TNF-α, IL-6 and IL-8 in the serum of rats between the CD5L antibody group and the isotype antibody group [TNF-α: (164±22)pg/ml vs. (213±17)pg/ml, t=5.05, P<0.05; IL-6: (186±17)pg/ml vs. (230.7±25.3)pg/ml, t=4.78, P<0.05; IL-8: (384±21)pg/ml vs. (456±44)pg/ml, t=-5.21, P<0.05]. Conclusion:Targeting CD5L can effectively alleviate synovial inflammation and bone destruction in CIA rats. CD5L may be used as a potential therapeutic target for rheumatoid arthritis.

Microbial detection and control of traditional Chinese medicine(TCM) decoction pieces are crucial for the quality control of TCM preparations. It is also a key area of research in the measurement technology and equipment development for TCM manufacturing. Guided by TCM manufacturing measurement methodologies, this study presented a design of a novel portable microbial detection device, using Atractylodis Macrocephalae Rhizoma decoction pieces as a demonstration. Immunomagnetic separation technology was employed for specific isolation and labeling of target microorganisms. Enzymatic signal amplification was utilized to convert weak biological signals into colorimetric signals, constructing an optical biosensor. A self-developed smartphone APP was further applied to analyze the colorimetric signals and quantify target concentrations. A portable and automated detection system based on Arduino microcontroller was developed to automatically perform target microbial separation/extraction, as well as mimetic enzyme labeling and catalytic reactions. The developed equipment specifically focuses on the rapid and quantitative microbial analysis of TCM active pharmaceutical ingredients, intermediates in TCM manufacturing, and final TCM products. Experimental results demonstrate that the equipment could detect Salmonella in samples within 2 h, with a detection limit as low as 5.1 × 10~3 CFU·mL~(-1). The equipment enables the rapid detection of microorganisms in TCM decoction pieces, providing a potential technical solution for on-site rapid screening of microbial contamination indicators in TCM. It has broad application prospects in measurement technology for TCM manufacturing and offers strong technical support for the modernization, industrialization, and intelligent development of TCM.
Drugs, Chinese Herbal/analysis* ; Atractylodes/microbiology* ; Rhizome/microbiology* ; Biosensing Techniques/methods* ; Medicine, Chinese Traditional ; Colorimetry/instrumentation* ; Quality Control