OBJECTIVE To compare the efficacy and safety of evolocumab and probucol in patients with ultra-high-risk atherosclerotic cardiovascular disease （ASCVD） following percutaneous coronary intervention （PCI）. METHODS A retrospective analysis was conducted on 156 ultra-high-risk ASCVD patients who underwent PCI in our institution between January 1， 2023 and December 31， 2024. According to the lipid-lowering regimen， the patients were categorized into evolocumab group （ n ＝86） and probucol group （ n ＝70）. Changes in lipid parameters [total cholesterol （TC）， low-density lipoprot ein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， triglycerides， lipoprotein （a）， and lipid goal achievement rate ] ， inflammatory markers [interleukin-6 （IL-6） and C-reactive protein （CRP） ] ， and cardiac function indices （left ventricular ejection fraction， left ventricular end-systolic diameter， left ventricular end-diastolic diameter， and N-terminal pro-B-type natriuretic peptide） were compared between two groups at baseline and after 6 months of treatment. The incidence of adverse clinical events during treatment， including acute myocardial infarction， in-stent restenosis， acute heart failure， cerebral hemorrhage， and stroke， was also evaluated. RESULTS No statistically significant differences were observed between the two groups at baseline （ P ＞0.05）. After 6 months of treatment， both groups demonstrated significant improvements in lipid profiles （except HDL-C） and inflammatory markers compared to those at baseline （ P ＜0.05）. The evolocumab group exhibited greater reductions in TC， LDL-C， IL-6， and CRP， along with a higher lipid target achievement rate， compared with the probucol group （ P ＜0.05）. There were no statistically significant differences in the cardiac function-related indicators before and after treatment between the two groups， nor in the incidence of adverse events during the treatment （ P ＞0.05）. CONCLUSIONS For ultra-high-risk ASCVD patients after PCI， both of the above treatment options are associated with improvements in blood lipid and inflammatory response， with good safety during short-term follow-up. Evolocumab shows superior efficacy in TC， LDL-C and inflammatory markers reduction and lipid target achievement， compared to probucol.

Objective:To explore the relationship between autistic trait and pain empathy among college students, as well as the mediating role of personal pain perception.Methods:From October to December 2023, a cross-sectional survey was conducted among 1 195 college students using the autism spectrum quotient, pain sensitivity questionnaire, fear of pain questionnaire, pain catastrophizing scale and empathy for pain scale.SPSS 27.0 software was used for descriptive statistics and correlation analysis.A structural equation model was constructed using Mplus 8.3 to examine the mediating effect of personal pain perception, which was composed of pain sensitivity, fear and catastrophizing cognition.Results:Autistic trait(22.00(18.00, 26.00))was significantly positively correlated with pain sensitivity (55.00(43.00, 70.00)), fair of pain (69.00(60.00, 78.00)), and pain catastrophizing cognition (16.00(8.00, 23.00)) ( r=0.112, 0.154, 0.204, all P<0.001).Autistic trait was also significantly positively correlated with affective distress(62.00(46.00, 80.00), r=0.162, P<0.001) and vicarious pain (14.00(8.00, 20.00), r=0.096, P<0.001) of pain empathy.Pain sensitivity, fear of pain and pain catastrophizing cognition were significantly positively correlated with affective distress( r=0.244, 0.332, 0.375, all P<0.001) and vicarious pain ( r=0.210, 0.232, 0.285, all P<0.001) of pain empathy.The effects of autistic trait on affective distress and vicarious pain dimensions of pain empathy were fully mediated by personal pain perception, with the mediating effects of 0.115( P<0.001, 95% CI=0.073-0.165) and 0.085( P<0.001, 95% CI=0.053-0.124). Conclusions:The autistic trait of college students can predict the affective distress and vicarious pain of pain empathy indirectly through personal pain perception.

Objective:To summarize the clinical and genetic characteristics of 23 children with pathogenic ACAN gene variants, enhance the understanding of this disorder, and explore possible regulatory mechanisms. Methods:A retrospective case series summary.The clinical characteristics and genetic analysis results of 23 children with ACAN gene variants treated in the Department of Endocrinology, Genetics and Metabolism, Children′s Hospital of Soochow University from January 2016 and September 2024 were analyzed retrospectively.Transcriptome sequencing was performed on peripheral blood samples from 3 of affected children and 3 age-matched healthy children as controls.Differentially expressed genes (DEGs) in the peripheral blood transcriptome profiles were identified.Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted to explore the potential signaling pathways involved. Results:Among the 23 cases, there were 13 males and 10 females, aged from 2 years and 8 months to 12 years old, with 11 cases presenting advanced bone age.Thirteen cases were treated with growth hormone (GH), including 6 cases who received concomitant gonadotropin-releasing hormone analogue therapy.The treatment duration ranged from 3 to 70 months, resulting in varying degrees of height improvement in all treated patients.Transcriptomic analysis identified 811 DEGs, with 516 up-regulated and 295 down-regulated.GO and KEGG enrichment analyses revealed that the heterozygous ACAN variants were significantly associated with FcγR-mediated phagocytosis, nuclear factor-κB signaling pathway, the intestinal immune network for IgA production, rheumatoid arthritis, and systemic lupus erythematosus signaling pathways. Conclusions:The predominant clinical manifestations of patients with ACAN gene variants are short stature and advanced bone age.Although GH provocation tests may indicate normal GH levels, GH therapy can be effective in improving height.Immune-related factors may play a role in the pathogenesis of this disorder.

The high incidence of bleeding after peripherally inserted central catheter (PICC) catheterization increases the risk of puncture site infection and unplanned extubation. Hemostatic dressings should be used in the early stages of catheterization to reduce blood infiltration. However, new hemostatic dressings have various types and advantages, which makes them difficult to choose dressings for medical staff. This paper introduces the types and hemostatic characteristics of novel functional hemostatic dressings, reviews the hemostatic mechanism and hemostatic effect of chitosan, cyanoacrylate gum, alginate, gelatin sponge and oxycellulose dressings in PICC puncture respectively, and prospects the development of new functional hemostatic dressings. It is expected that future hemostatic dressings will move towards multifunctionality and compositeness.
Humans ; Bandages ; Catheterization, Peripheral/instrumentation* ; Hemorrhage/prevention & control* ; Hemostatics/therapeutic use*

Normal heart function depends on complex regulation by the brain, and abnormalities in the brain‒heart axis affect various diseases, such as myocardial infarction and anxiety disorders. However, systematic tracking of the brain regions associated with the input and output of the heart is lacking. In this study, we injected retrograde transsynaptic pseudorabies virus (PRV) and anterograde transsynaptic herpes simplex virus (HSV) into the left ventricular wall of mice to identify the whole-brain regions associated with the input to and output from the heart. We successfully detected PRV and HSV expression in at least 170 brain subregions in both male and female mice. Sex differences were discovered mainly in the hypothalamus and medulla, with male mice exhibiting greater correlation and hierarchical clustering than female mice, indicating reduced similarity and increased modularity of virus expression patterns in male mice. Further graph theory and multiple linear regression analysis of different injection timelines revealed that hub regions of PRV had highly similar clusters, with different brain levels, suggesting a top-down, hierarchically transmitted neural control pattern of the heart. Hub regions of HSV had scattered clusters, with brain regions gathered in the cortex and brainstem, suggesting a bottom-up, leapfrog, multipoint neural sensing pattern of the heart. Both patterns contain many hub brain regions that have been previously overlooked in brain‒heart axis studies. These results provide brain targets for future research and will lead to deeper insight into the brain mechanisms involved in specific heart conditions.
Animals ; Male ; Female ; Heart/physiology* ; Mice ; Herpesvirus 1, Suid ; Brain/physiology* ; Mice, Inbred C57BL ; Brain Mapping ; Efferent Pathways/physiology* ; Afferent Pathways/physiology* ; Simplexvirus ; Sex Characteristics

Objective To investigate the expression level of centromere protein(CENP)Ⅰin lung adenocarcinoma cells,to study the effects of CENPⅠon the proliferation,invasion,migration,apoptosis,and epithelial-mesenchymal transition(EMT)of lung adenocarci-noma cells,and to explore the possible mechanisms related to its occurrence.Methods The expression of CENPⅠmRNA and protein in four types of lung adenocarcinoma cells and normal alveolar epithelial cells were detected by quantitative real-time polymerase chain reaction(RT-qPCR)and Western blotting.The expression of CENPⅠin H1650 cells was knocked down by the siRNA technique,The transfection efficiency was detected by RT-qPCR and Western blotting.The effects of knock-down CENPⅠon proliferation,cell cycle,apoptosis,invasion and migration of H1650 cells were detected by the cell counting kit-8 assay,the transwell assay,and flow cytometry.Western blotting was used to detect the expression of E-cadherin,N-cadherin,vimentin,Ki-67,cyclin D1,Bcl-2,PI3K,AKT,mTOR,p-PI3K,p-AKT,and p-mTOR.Results After the knock-down of CENPⅠ,the proliferative ability of the H1650 cells significantly decreased,the number of apoptotic cells significantly decreased,and the cell invasion and migration abilities significantly decreased(P<0.01).E-cadherin expression was upregulated and N-cadherin,vimentin,Ki-67,cyclin D1,Bcl-2,p-PI3K,p-AKT,and p-mTOR expres-sion were down-regulated in the CENTI group compared with the control group(P<0.05).The expression of p-PI3K,p-AKT,and p-mTOR in the si-CENPⅠ+IGF-1 group was upregulated compared to that in the si-CENPⅠgroup(P<0.05).Conclusion High expression of CENPⅠin lung adenocarcinoma cells promotes the proliferation,invasion,and migration of lung adenocarcinoma H1650 cells and EMT inhibits apoptosis,which may be related to the activation of the PI3K/AKT/mTOR signaling pathway.

Objective:To explore the relationship between autistic trait and pain empathy among college students, as well as the mediating role of personal pain perception.Methods:From October to December 2023, a cross-sectional survey was conducted among 1 195 college students using the autism spectrum quotient, pain sensitivity questionnaire, fear of pain questionnaire, pain catastrophizing scale and empathy for pain scale.SPSS 27.0 software was used for descriptive statistics and correlation analysis.A structural equation model was constructed using Mplus 8.3 to examine the mediating effect of personal pain perception, which was composed of pain sensitivity, fear and catastrophizing cognition.Results:Autistic trait(22.00(18.00, 26.00))was significantly positively correlated with pain sensitivity (55.00(43.00, 70.00)), fair of pain (69.00(60.00, 78.00)), and pain catastrophizing cognition (16.00(8.00, 23.00)) ( r=0.112, 0.154, 0.204, all P<0.001).Autistic trait was also significantly positively correlated with affective distress(62.00(46.00, 80.00), r=0.162, P<0.001) and vicarious pain (14.00(8.00, 20.00), r=0.096, P<0.001) of pain empathy.Pain sensitivity, fear of pain and pain catastrophizing cognition were significantly positively correlated with affective distress( r=0.244, 0.332, 0.375, all P<0.001) and vicarious pain ( r=0.210, 0.232, 0.285, all P<0.001) of pain empathy.The effects of autistic trait on affective distress and vicarious pain dimensions of pain empathy were fully mediated by personal pain perception, with the mediating effects of 0.115( P<0.001, 95% CI=0.073-0.165) and 0.085( P<0.001, 95% CI=0.053-0.124). Conclusions:The autistic trait of college students can predict the affective distress and vicarious pain of pain empathy indirectly through personal pain perception.

BACKGROUND: Regulatory dendritic cell (DCreg) subset exhibits a unique capacity for inducing immune tolerance among the variety subsets of dendritic cells (DCs) within gut-associated lymphoid tissues (GALTs). Fms-like tyrosine kinase 3 ligand (FLT3L) is involved in the differentiation of DCregs and the subsequent expansion of regulatory T-cells (Tregs) mediated by DCregs, though the precise mechanism remains poorly understood. This study aimed to explore the expansion mechanism of Treg induced by DCreg and the role of FLT3L in this process. METHODS: DCregs were distinguished from other DC subsets isolated from GALTs of BALB/c mice through a mixed lymphocyte reaction assay. The functions and mechanisms by which FLT3L promoted Treg expansion via DCregs were investigated in vitro through co-culture experiments involving DCregs and either CD4 + CD25 - T-cells or CD4 + CD25 + T-cells. Additionally, an in vivo experiment was conducted using a dextran sulfate sodium (DSS)-induced colitis model in mice. RESULTS: CD103 + CD11b + DC exhibited DCreg-like functionality and was identified as DCreg for subsequent investigation. Analysis of Foxp3 + Treg percentages within a co-culture system of CD4 + CD25 - T-cells and DCregs, with or without FLT3L, demonstrated the involvement of the FLT3/FLT3L axis in driving the differentiation of precursor T-cells into Foxp3 + Tregs induced by DCregs. Cell migration and co-culture assays revealed that the FLT3/FLT3L axis enhanced DCreg migration toward Tregs via the Rho pathway. Additionally, it was observed that DCregs could promote Treg proliferation through the Notch pathway, as inhibition of Notch signaling by DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) suppressed Treg expansion within the co-culture system of DCregs and CD4 + T-cells or CD4 + CD25 + T-cells. Furthermore, the FLT3/FLT3L axis influenced JAG1 expression in DCregs, indirectly modulating Treg expansion. In vivo experiments further established that FLT3L promoted DCreg expansion and restored Treg balance in DSS-induced colitis models, thereby ameliorating colitis symptoms in mice. CONCLUSION The FLT3/FLT3L axis is integral to the maintenance of DCreg function in Treg expansion.
Animals ; T-Lymphocytes, Regulatory/immunology* ; Dendritic Cells/immunology* ; Mice ; Mice, Inbred BALB C ; Membrane Proteins/metabolism* ; Receptors, Notch/metabolism* ; Lymphoid Tissue/metabolism* ; Signal Transduction/physiology* ; Coculture Techniques ; Flow Cytometry

OBJECTIVE: To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01). RESULTS: The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P = 0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P < 0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients (P = 0.002), while TP53 (P = 0.024) and BCL2 (P = 0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years (HR = 3.439, 95%CI: 1.318~9.874), presence of B symptoms (HR = 2.871, 95%CI = 1.133~7.307), and elevated lactate dehydrogenase (HR = 3.528, 95%CI = 1.231~10.66) as independent adverse prognostic factors. CONCLUSION Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Middle Aged ; Female ; Male ; Retrospective Studies ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; High-Throughput Nucleotide Sequencing ; Young Adult ; Adolescent ; Genetic Variation

Background Kurtosis reflecting noise's temporal structure is an effective metric for evaluating noise-induced hearing loss (NIHL), and its threshold is still unclear. Objective To explore the energy range of kurtosis and the threshold of NIHL induced by kurtosis in this energy rangeMethods Using cross-sectional design, 4631 noise-exposed workers in manufacturing industry were selected. The hearing loss and noise exposure data of each worker were collected. Logistic regression model was used to establish the dose-response relationship between noise exposure and hearing loss and estimate the range of energy effects. Restricted cubic spline model was utilized to analyze the dose-response relationship curves of kurtosis to noise-induced hearing loss (NIHI) and high-frequency noise-induced hearing loss (HFNIHL) under different 8 h equivalent sound levels (L_{EX,8 h}), as well as to estimate the kurtosis effect threshold. Results The logistic regression model analysis showed that the prevalence of NIHI and HFNIHL increased significantly with increase of L_{EX,8 h} for steady noise; when L_{EX,8 h} of non-steady noise was 80-100 dB(A), the risk of hearing loss increased with an increase in kurtosis (P<0.05). The restricted cubic spline model showed that when L_{EX,8 h} of non-steady noise was 0-80 dB(A) or >100 dB(A), there was no significant relationship between kurtosis and NIHI or HFNIHL. When L_{EX,8 h} was 80-100 dB(A), there was a significant nonlinear dose-response relationship between kurtosis and NIHL or HFNIHL (P <0.001), and kurtosis > 28.08 exerted effect in elevating NIHI or HFNIHL. Conclusion The effect threshold of kurtosis on NIHL is 28.08 when non-steady noise levels are in the range of 80-100 dB(A). The effect threshold of kurtosis needs further verification.