Objective Older patients with colorectal cancer undergoing first-line chemotherapy are prone to myelosuppression, which can lead to treatment delays, dose adjustments, and adverse outcomes such as infection and bleeding; however, individualized risk prediction tools with external validation remain lacking. This study aimed to identify routine clinical predictors using a multi-algorithm consensus strategy, construct and compare risk prediction models for grade u22652 chemotherapy-induced myelosuppression in this population, and evaluate the external generalizability and clinical utility of the leading model. Methods In this retrospective cohort study leveraging data from two hospitals, we adopted a predictive model development and independent external validation design. A total of 553 older patients receiving first-line chemotherapy were enrolled, including 442 from Guangu2019anmen Hospital (development cohort) and 111 from Gansu Provincial Cancer Hospital (external validation cohort). The primary endpoint was grade u22652 myelosuppression per Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Nineteen candidate predictors underwent consensus selection via least absolute shrinkage and selection operator logistic regression, the Boruta algorithm, and random forest permutation importance, with final core predictors determined by bootstrap inclusion frequency and prespecified clinical retention rules. Nine models were constructed: conventional logistic regression, LASSO logistic regression, elastic net logistic regression, random forest, extreme gradient boosting, categorical boosting, radial basis function support vector machine, linear discriminant analysis, and explainable boosting machine (EBM). Five repeated 10-fold stratified cross-validation generated out-of-fold predictions in the development cohort, and locked models were applied to the external validation cohort. Model performance was assessed by area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), Brier score, calibration intercept, calibration slope, Hosmer-Lemeshow test, and decision curve analysis. Results The incidence of grade u22652 myelosuppression was 26.2% (116/442) in the development cohort and 27.0% (30/111) in the external validation cohort (Pu0026gt;0.05). Nine core predictors were selected: albumin, carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 125, body surface area, tumor location, chemotherapy cycle, chemotherapy regimen, and age-adjusted Charlson comorbidity index. The EBM was identified as the leading model based on balanced discrimination, calibration, and interpretability. In the development cohort, EBM achieved an out-of-fold AUROC of 0.720 (95%CI: 0.676 to 0.772), AUPRC of 0.421, Brier score of 0.176, calibration intercept of 0.035, and calibration slope of 0.778, with no significant miscalibration (Hosmer-Lemeshow P=0.087). In external validation, EBM yielded an AUROC of 0.714 (95%CI: 0.595 to 0.834), AUPRC of 0.641, Brier score of 0.164, calibration intercept of 0.155, and calibration slope of 0.778, though calibration remained suboptimal (Pu0026lt;0.001). At the optimal threshold of 0.28 derived from the development cohort, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score in the external validation cohort were 0.667, 0.741, 0.488, 0.857, and 0.563, respectively. Decision curve analysis indicated superior net benefit over treat-all or treat-none strategies across threshold probabilities of 0.06 to 0.48 (development cohort) and 0.18 to 0.60 (external validation cohort). Interpretation revealed albumin as the strongest contributor, followed by carcinoembryonic antigen, carbohydrate antigen 19-9, and carbohydrate antigen 125; lower albumin, smaller body surface area, u22655 chemotherapy cycles, and the FOLFIRI regimen were associated with increased risk, while tumor markers exhibited nonlinear associations with predicted risk. Conclusion Nine routine clinical parameters selected by a multi-algorithm consensus strategy enable construction of a prediction model for grade u22652 myelosuppression during first-line chemotherapy in older patients with colorectal cancer. The finalized EBM model demonstrates moderate discrimination and clinical net benefit in both development and external validation cohorts but exhibits residual calibration drift externally. It may serve as an adjunctive tool for clinical risk stratification rather than a standalone decision-making instrument at this stage.
Objective Inducing tumor cell senescence represents a promising strategy in cancer therapy. This study aimed to elucidate the expression profile, biological functions, and molecular regulatory mechanisms of centrosomal protein 55 (CEP55) in glioma, thereby providing novel therapeutic targets and a theoretical basis for targeted glioma treatment. Methods Human glioma cell lines U251 and U87 were divided into negative control (NC), CEP55 knockdown (siCEP55-1, siCEP55-2), and forkhead box M1 (FOXM1) overexpression groups, with three biological replicates per group. CEP55 was knocked down via siRNA transfection, and FOXM1 was overexpressed using lentiviral vectors. mRNA and protein levels of CEP55 and FOXM1 were assessed by qRT-PCR and Western blotting. The mRNA expression of senescence-associated genes, including insulin-like growth factor binding protein 3 (IGFBP3), interleukin 6 (IL6), serpin family E member 1 (SERPINE1), cell division cycle 25A (CDC25A), C-X-C motif chemokine ligand 8 (CXCL8), MYC, ZFP36 ring finger protein like 1 (ZFP36L1), and ZFP36 ring finger protein like 2 (ZFP36L2), was measured by qRT-PCR. Whole-transcriptome profiling was performed by RNA sequencing (RNA-seq). Differentially expressed genes were identified using the DESeq2 package following gene quantification, and subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Cell cycle distribution was analyzed by flow cytometry, mitochondrial morphology was observed via transmission electron microscopy, and reactive oxygen species (ROS) levels were quantified using the DCFH-DA fluorescent probe. Senescent cells were identified by senescence-associated u03B2-galactosidase (SA-u03B2-gal) staining. Chromatin immunoprecipitation (ChIP) assay was employed to verify the binding of FOXM1 to the CEP55 promoter. Bioinformatics analysis was performed to evaluate the correlation between CEP55 expression and prognosis using data from The Cancer Genome Atlas (TCGA). A subcutaneous xenograft tumor model was established by injecting U87 cells into nude mice. Ten 6-week-old female BALB/c nude mice (body weight 18 to 22 g) were stratified and randomly assigned to the NC group or siCEP55-1 group (n=5), receiving subcutaneous inoculation of cell suspensions into the right flank. Upon tumor formation, xenografts were excised to measure longitudinal and transverse diameters. Results CEP55 expression was significantly elevated in glioma tissues compared to normal tissues, and patients with high CEP55 expression exhibited markedly shorter overall survival than those with low expression (Pu0026lt;0.001). Transfection with siCEP55-1/2 significantly downregulated CEP55 mRNA and protein levels in U251 and U87 cells (Pu0026lt;0.001) and induced prominent G0/G1 phase arrest (Pu0026lt;0.05). RNA-seq analysis identified 524 differentially expressed genes (249 upregulated, 275 downregulated), with upregulated genes significantly enriched in cellular senescence, mitogen-activated protein kinase signaling, and transcriptional dysregulation in cancer pathways. CEP55 knockdown led to significant upregulation of senescence-related genes (IGFBP3, IL6, SERPINE1, CDC25A, CXCL8, MYC, ZFP36L1; Pu0026lt;0.01), pronounced mitochondrial fragmentation, elevated intracellular ROS levels (Pu0026lt;0.01), increased SA-u03B2-gal-positive cell proportion (Pu0026lt;0.01), and markedly suppressed xenograft growth with reduced tumor volumes (P=0.006). FOXM1 expression correlated positively with CEP55 levels (r=0.898, Pu0026lt;0.0001). FOXM1 overexpression significantly upregulated CEP55 expression (Pu0026lt;0.001), and ChIP assays confirmed direct binding of FOXM1 to the CEP55 promoter region. Conclusion CEP55 is directly transcriptionally activated by FOXM1 and promotes glioma progression by suppressing cellular senescence signaling pathways.
Objective Porphyromonas gingivalis(P. gingivalis) is a key oral pathogen. While Crp/Fnr family transcription factors are widespread in bacteria and P. gingivalis encodes three members (PG1053, PG1573, and PG0396)u2014with PG1053 involved in nitrosative stress and PG1573 in iron acquisition and biofilm regulationu2014PG0396 harbors a helix-turn-helix domain distinct from the other two, suggesting non-redundant regulatory functions. However, whether PG0396 acts as a transcriptional regulator and how its biological pathways compare to known members remain unclear. This study aimed to characterize the role of PG0396 in virulence regulation and pathogenesis to elucidate the functional specialization within this family. Methods A PG0396 deletion mutant (u0394PG0396:: ermF) was constructed in P. gingivalis W83 via homologous recombination, using a PG2125 deletion mutant (u0394PG2125::ermF) as a control. Growth kinetics were monitored by optical density at 600 nm[OD(600)] every 2 h for 24 h. Oxidative stress tolerance was assessed in BHI-HV medium supplemented with 0.25 mmol/L H2O2. Arginine- and lysine-specific gingipain activities (Rgp and Kgp) were measured using chromogenic substrates BAPNA and ALNA, respectively. Hemagglutination titers against sheep erythrocytes were determined by serial dilution. Eighteen 6- to 8-week-old male SPF C57BL/6 mice were randomized into three groups (n=6 each): control (pulp exposure + sterile saline), W83 group (pulp exposure + W83 suspension), and u0394PG0396 group (pulp exposure+ u0394PG0396 suspension). Following pulp exposure of the right mandibular first molar, OD(600)=1.0 bacterial suspensions or saline were applied via cotton pellet compression for 3 min, followed by drying, application of a self-etching adhesive, light-curing for 20 s, and resin restoration. Alveolar bone loss was quantified by micro-computed tomography. Serum interleukin-6 and P. gingivalis-specific IgG levels were measured by ELISA on days 0, 7, 14, and 21 post-inoculation. Transcriptomic profiling of u0394PG0396 and W83 was performed with subsequent GO and KEGG enrichment analyses. Recombinant His-PG0396 protein was purified and its binding to target gene promoters was verified by electrophoretic mobility shift assay. Results Compared with the W83 strain, u0394PG0396 showed no significant difference in growth curves in BHI-HV medium, consistent with the phenotype of the u0394PG2125 control strain. Under 0.25 mmol/L H2O2 stress, u0394PG0396 entered the stationary phase roughly 4 h eralier than the W83 strain. Gingipain activities were significantly elevated in u0394PG0396: OD(405) values for Rgp increased by around 60% (Pu0026lt;0.05), and OD(405) values for Kgp rose by about 34% after 120 min of incubation (Pu0026lt;0.05); no significant alterations were detected in the u0394PG2125 mutant. Hemagglutination titer decreased from 1:8 to 1:4. In the murine apical periodontitis model, alveolar bone loss volume in the u0394PG0396 group was 85% greater than that in the W83 group (0.280u00B10.062 vs 0.151u00B10.019 mm3, Pu0026lt;0.05). Serum IL-6 levels in the u0394PG0396 group were significantly higher than those in the W83 group on days 14 and 21 post-modeling (Pu0026lt;0.05), and serum P. gingivalis-specific IgG levels were also significantly elevated on day 21 (Pu0026lt;0.05). Transcriptome sequencing revealed 30 differentially expressed genes in u0394PG0396 (10 upregulated, 20 downregulated), which were mainly enriched in pathways related to oxidative stress response and lipopolysaccharide biosynthesis. Electrophoretic mobility shift assay (EMSA) confirmed that His-PG0396 specifically bound to the promoter regions of the differentially expressed genes PG1777 and PG0901. Conclusion PG0396 functions as a Crp/Fnr family transcription factor in P. gingivalis that negatively regulates oxidative stress responses, gingipain activity, and pathogenicity in experimental apical periodontitis.
Abstract Objective From the perspective of the Dual-Factor Model of Mental Health(DFM), this study aimed to validate the applicability of this model among non-military undergraduates students in military academies and, on this basis, to develop an other-rated screening checklist for identifying psychological -focused, individuals, thereby providing a novel assessment tool and practical evidence for the safety management of non-military undergraduates students in military academies. Methods A cluster sampling method was adopted. In January 2024, non-military undergraduate students from the National University of Defense Technology and the Army Medical University were recruited as study subjects, yielding a total of 1 003 valid samples. The Depression Anxiety Stress Scale-21 (DASS-21), Warwick-Edinburgh Mental Well-being Scale (WEMWBS), Satisfaction with Life Scale (SWLS), and Positive Affect and Negative Affect Scale (PANAS) were administered. Structural equation modeling was employed to examine the structural validity of the dual-factor model of mental health. Intensity sampling was used, and semi-structured in-depth interviews were conducted with 10 administrators responsible for non-military undergraduate students. Grounded theory three-level coding was applied to extract the item pool, yielding 73 open codes, 14 axial codes, and 3 selective codes. 8 experts in psychology and management were invited to participate in three rounds of Delphi consultation to screen items, ultimately forming an other-rated screening checklist for identifying psychologically at-risk individuals. Results The dual-factor model of mental health, with positive and negative factors as latent variables, positive mental health and life satisfaction as observed variables of the positive factor, and depression and anxiety as observed variables of the negative factor, demonstrated good model fit (χ²/df=2.059). The final other-rated screening checklist for identifying psychologically at-risk civilian undergraduate students in military academies comprised 49 items, encompassing three core dimensions: external manifestations, predisposing factors, and stressors. The mean importance scores of the items ranged from 3.88 to 5.00. Conclusion The dual-factor model of mental health is applicable to civilian undergraduate students in military academies. The other-rated screening checklist for identifying psychologically at-risk civilian undergraduate students in military academies can serve as an other-rated screening tool for this population.
Abstract Objective To address cumulative radiation exposure from repeated scans during CT-guided percutaneous lung biopsy, this study evaluated the impact of low-dose and ultra-low-dose CT combined with a 1024×1024 matrix and deep learning reconstruction algorithms on image quality and radiation dose, investigating the clinical feasibility of this protocol in meeting localization requirements for puncture procedures. Methods In this prospective non-randomized controlled trial, 100 consecutive patients undergoing CT-guided thoracic biopsy were enrolled at the Department of Radiology, First Affiliated Hospital of Dalian Medical University, between April and December 2025. Multiple repeated localizations were performed during the procedure. The standard-dose (CD) protocol utilized 120 kV, 180 mA, a 512×512 reconstruction matrix, and ClearView reconstruction at 60% strength (CD-CV60 group). Low-dose (LD) protocols employed 120 kV with automatic tube current modulation (O-Dose coefficient 1.0), a 1024×1024 matrix, and ClearInfinity reconstruction at 40%, 60%, and 80% strength (LD-CI40, LD-CI60, LD-CI80 groups). Ultra-low-dose (ULD) protocols used 120 kV with automatic tube current modulation (O-Dose coefficient 0.7), a 1024×1024 matrix, and ClearInfinity reconstruction at 40%, 60%, and 80% strength (ULD-CI40, ULD-CI60, ULD-CI80 groups); Except for the tube-current setting and reconstruction parameters, all other scanning parameters remained identical across protocols. CT attenuation values and standard deviation (SD) of the aorta and chest wall fat were measured to calculate signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Subjective image quality, including lesion margin delineation, homogeneity of lesion density, and artifact severity, was assessed using a 5-point Likert scale. Volume CT dose index (CTDIvol), dose-length product (DLP), effective dose (ED), and size-specific dose estimate (SSDE) were recorded. Results Interobserver agreement for lesion-margin delineation, lesion-density homogeneity, and artifact severity was good, with linearly weighted κ values of 0.801 (95%CI: 0.753 to 0.844), 0.758 (95%CI: 0.709 to 0.805), and 0.815 (95%CI: 0.768 to 0.859), respectively. Mean CTDIvol for CD, LD, and ULD protocols were 11.13 mGy, 3.98 mGy, and 2.01 mGy, respectively; the corresponding DLP values were 389.55, 139.13, and 70.35 mGy/cm; the ED values were 5.45, 1.95, and 0.98 mSv; and corresponding SSDE values were 14.37 mGy, 5.27 mGy, and 2.60 mGy. Compared to the CD protocol, CTDIvol was reduced by 64.2% and 81.9% in the LD and ULD protocols, respectively, DLP was reduced by 64.2% and 81.9%, ED by 64.2% and 82.0%, and SSDE by 63.3% and 81.9%, respectively. Regarding objective quality, background SD progressively decreased with increasing ClearInfinity strength in LD and ULD protocols, whereas SNR and CNR generally increased. SNR and CNR in LD-CI60, LD-CI80, ULD-CI60, and ULD-CI80 groups were significantly higher than those in the CD-CV60 group (P<0.05). For subjective quality, most metrics initially improved then declined as ClearInfinity strength increased. Among LD and ULD protocols, images reconstructed with 60% ClearInfinity demonstrated superior subjective scores; notably, lesion density homogeneity in the LD-CI60 group was significantly higher than in CD-CV60 (P<0.05), while other 60% reconstruction groups showed no statistically significant differences compared to CD-CV60. These 60% reconstruction images consistently outperformed their respective 40% and 80% counterparts within the same dose protocol (P<0.05).The mean difference in patient-level composite image-quality scores between the ULD-CI60 and CD-CV60 groups (ULD-CI60-CD-CV60) was -0.002 points (95%CI:-0.100 to 0.097), and the lower limit of the 95%CI was higher than the prespecified noninferiority margin of -0.5 points. Postoperative complications occurred in 33 patients (33.0%), comprising isolated pneumothorax (14 cases, 14.0%), isolated pulmonary hemorrhage (12 cases, 12.0%), and combined pneumothorax with hemorrhage (7 cases, 7.0%); no severe complications such as air embolism occurred. Conclusion During CT-guided percutaneous lung biopsy, the ULD-CI60 protocol achieves image quality sufficient for puncture localization and path planning while reducing radiation dose by approximately 81.9%.
Abstract Objective Ischemic stroke is one of the major neurological diseases leading to death and long-term disability. Although reperfusion can restore blood flowing ischemic brain tissue, it can further induce oxidative stress, blood-brain barrier disruption, and neuronal apoptosis; therefore, identifying safe and effective neuroprotective agents is of great clinical significance. This study investigated whether idebenone attenuates cerebral ischemia-reperfusion injury in rats by inhibiting neuronal apoptosis through the glycogen synthase kinase-3 beta (GSK-3β)/β-catenin signaling pathway. Methods A middle cerebral artery occlusion/reperfusion (MCAO/R) model was established in 87 adult male SD rats (body weight 250 to 300 g) by inserting a suture into the internal carotid artery via the left common carotid artery to occlude the left middle cerebral artery for 2 h, followed by suture withdrawal and 50 h of reperfusion. ① Pharmacodynamic evaluation experiment: Rats were randomly divided into sham operation (Sham) group, ischemia/reperfusion (I/R) group, and I/R+idebenone (IDB) group, with 21 rats per group. Neurological function was assessed using the Modified Neurological Severity Score (mNSS); brain water content was measured by the wet-dry weight method and brain index was calculated; cerebral infarct area was detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining and 7.0 T magnetic resonance imaging (MRI); blood-brain barrier permeability was assessed by Evans Blue (EB) extravasation staining; neuronal morphology was observed by HE staining; neuronal apoptosis was detected by TUNEL; and the expression of Bcl-2, Bax, and cytochrome c (Cyt c) was detected by Western blotting. ②LRP5/6 co-receptor inhibition experiment: Molecular docking was used to predict the binding of IDB to Frizzled-5. Rats were randomly divided into Sham group, I/R group, I/R+IDB group, and I/R+IDB+Dickkopf-1 (DKK-1) group, with 3 rats per group, and Western blotting was used to detect the expression of total GSK-3β, phosphorylated GSK-3β (Ser9), total β-catenin, and phosphorylated β-catenin (Ser33/Ser37/Thr41).③ GSK-3β inhibition experiment: Using the highly selective GSK-3β inhibitor TDZD-8, rats were randomly divided into Sham group, I/R group, I/R+IDB group, and I/R+IDB+TDZD-8 group, with 3 rats per group, and Western blotting was used to detect the expression of total GSK-3β, phosphorylated GSK-3β (Ser9), total β-catenin, and phosphorylated β-catenin (Ser33/Ser37/Thr41). Results ① Pharmacodynamic results showed that compared with the Sham group, the I/R group had significantly increased cerebral EB extravasation, neuronal morphological damage, and percentage of TUNEL-positive cells(P<0.01), accompanied by a decreased Bcl-2/Bax ratio and elevated cytoplasmic Cyt c(P<0.001), indicating that the MCAO/R model caused significant neurological and tissue damage. Compared with the I/R group, the I/R+IDB group showed a decreased mNSS score (P<0.001), reduced brain water content (P<0.001) and brain index (P<0.01), improved MRI-related infarct indicators (P<0.05), smaller corrected cerebral infarct area by TTC (P<0.01), reduced EB extravasation (P<0.001), increased proportion of surviving neurons (P<0.001), and fewer TUNEL-positive cells (P<0.05); Bcl-2 expression and the Bcl-2/Bax ratio were increased, Bax expression was decreased (P<0.05), mitochondrial Cyt c was increased (P<0.05), and cytoplasmic Cyt c was decreased (P<0.01). ② LRP5/6 co-receptor inhibition experiment: Molecular docking confirmed that idebenone had potential binding ability to the Frizzled-5 receptor, with a binding energy of -5.6 kcal/mol. Compared with the I/R group, the I/R+IDB group showed increased phosphorylated GSK-3β (Ser9) and decreased phosphorylated β-catenin (Ser33/Ser37/Thr41) (all P<0.05). After combined intervention with DKK-1, these changes persisted, with no statistically significant difference compared with the I/R+IDB group. ③ GSK-3β inhibition experiment revealed that compared with the I/R group, I/R+IDB alone upregulated GSK-3β phosphorylation (P<0.01) and decreased intracellular phosphorylated β-catenin expression (P<0.05), and TDZD-8 intervention showed a similar regulatory trend to IDB; there was no statistically significant difference in the phosphorylation levels of the above proteins between the I/R+IDB+TDZD-8 group and the I/R+IDB group, and no obvious additive effect was observed. Conclusion Idebenone can alleviate neurological deficits, brain edema, cerebral infarction, blood-brain barrier disruption, and neuronal apoptosis after cerebral ischemia-reperfusion in rats, and its effects may be related to inhibiting GSK-3β activity and stabilizing β-catenin signaling; however, whether it directly acts on Frizzled-5 and the dependence on upstream receptors require further verification.
Objective Stroke has become the leading cause of death and disability among Chinese adults. The long-term rehabilitation and secondary prevention of elderly patients are highly dependent on proactive health behaviors, yet existing studies largely overlook group heterogeneity. Based on Penderu2019s Health Promotion Model, this study used latent profile analysis to explore the latent classes of proactive health behaviors among elderly stroke patients and their influencing factors, so as to provide evidence for stratified precision nursing. Methods This study adopted a cross-sectional design, from July to December 2025, 403 elderly stroke patients were selected by convenience sampling from Hefei First Peopleu2019s Hospital. The survey instruments included a general information questionnaire, the Active Health Behavior Scale for Patients with Chronic Diseases (AHBS), the Self-Efficacy for Managing Chronic Disease 6-Item Scale (SES6C), the Social Support Rating Scale (SSRS), and the Brief Illness Perception Questionnaire (BIPQ). Latent profile analysis (LPA) was used to identify the latent classes of proactive health behaviors, with AIC, BIC, aBIC, entropy, LMR, and BLRT used to determine the optimal model. Univariate analysis and multinomial logistic regression (with the low proactive health behavior-passive compliance type as reference) were used to explore the influencing factors. Results The proactive health behavior score of the 403 patients was 59.42u00B112.56. LPA identified three latent classes: low proactive health behavior-passive compliance (53.6%), moderate proactive health behavior-cognitive-behavioral imbalance (20.8%), and high proactive health behavior-active engagement (25.6%). The model demonstrated a good fit (AIC=9467.672, BIC=9555.648, aBIC=9485.840, entropy=0.953, LMR and BLRT: Pu0026lt;0.001). Multinomial logistic regression analysis revealed that, with the low proactive health behavior-passive compliance class as the reference, monthly income of 1000 to 2999 yuan (OR=0.139, 95%CI: 0.029 to 0.659), monthly income of 3000 to 5000 yuan (OR=0.119, 95%CI: 0.023 to 0.605), chronic disease management self-efficacy score (OR=1.238, 95%CI: 1.141 to 1.343), illness perception score (OR=1.246, 95%CI: 1.181 to 1.314), and social support score (OR=1.337, 95%CI: 1.250 to 1.431) were associated with classification into the moderate proactive health behavior-cognitive-behavioral imbalance class. Furthermore, primary school education or below (OR=0.030, 95%CI: 0.008 to 0.118), junior or senior high school education (OR=0.305, 95%CI: 0.098 to 0.939), monthly income of 1000 to 2999 yuan (OR=0.063, 95%CI: 0.015 to 0.263), monthly income of 3000 to 5000 yuan (OR=0.219, 95%CI: 0.052 to 0.923), living with spouse (OR=20.693, 95%CI: 2.620 to 163.263), living with children (OR=8.693, 95%CI: 1.523 to 49.625), family history of stroke (OR=5.688, 95%CI: 1.875 to 17.259), having 3 to 5 chronic diseases (OR=4.998, 95%CI: 1.409 to 17.656), chronic disease management self-efficacy score (OR=1.107, 95%CI: 1.046 to 1.173), illness perception score (OR=1.209, 95%CI: 1.125 to 1.301), and social support score (OR=1.383, 95%CI: 1.286 to 1.489) were associated with classification into the high proactive health behavior-active engagement class (all Pu0026lt;0.05). Conclusion Elderly stroke patients showed obvious group heterogeneity in proactive health behaviors. Multiple sociodemographic and psychological factors influenced their profile types, and clinical practice should implement stratified individualized interventions based on latent profile characteristics.
Objective To compare the clinical and radiological outcomes of uniportal endoscopic unilateral laminotomy for bilateral decompression (UE-ULBD) versus biportal endoscopic unilateral laminotomy for bilateral decompression (BE-ULBD) within 3 predefined decompression boundaries for degenerative lumbar spinal stenosis (DLSS). Methods This study adopted a retrospective cohort study design. Medical records of DLSS patients who underwent UE-ULBD or BE-ULBD at the Department of Orthopedics, Daping Hospital, Army Medical University from January 2022 to October 2023 were collected. After applying inclusion and exclusion criteria, 69 patients who completed follow-up and had complete medical records were enrolled and divided into 2 groups according to surgical approach: the UE-ULBD group (n=34) and the BE-ULBD group (n=35). All patients had more than 6 months of follow-up, with a mean followup duration of (9.84u00B12.25) months. Three decompression boundaries were strictly followed intraoperatively. Clinical outcomes were assessed using VAS and ODI; operative time was also recorded. Radiological outcomes were evaluated by measuring the dural sac cross-sectional area, multifidus cross-sectional area, medial facet angle, facet joint width, and articular surface length on imaging. Results No statistically significant differences were found between the two groups in demographic parameters including age, sex, disease duration, surgical approach side, and surgical segment. ODI and VAS scores improved significantly in both groups compared with preoperative values (Pu0026lt;0.05). The BE-ULBD group had a shorter operative time than the UE-ULBD group (Pu0026lt;0.001), whereas the latter showed significantly less postoperative paraspinal multifidus swelling (15.41u00B17.20 vs 111.3u00B126.08 mm2, Pu0026lt;0.001). No statistically significant differences were observed between the two groups in dural sac expansion area (90.29u00B116.07 vs 92.83u00B111.93 mm2, P=0.459), bilateral medial facet angle increase (ipsilateral: 40.82u00B14.41 vs 41.47u00B14.19u00B0, P=0.529; contralateral: 16.96u00B16.81 vs 18.18u00B15.05u00B0, P=0.401), facet joint articular surface length resection range (ipsilateral: 2.17u00B11.06 vs 2.64u00B11.01 mm, P=0.061; contralateral: 1.38u00B10.64 vs 1.41u00B10.77 mm, P=0.838), or facet joint width resection range (ipsilateral: 1.98u00B11.02 mm vs 1.87u00B11.01 mm, P=0.678; contralateral: 2.02u00B11.07 vs 2.07u00B10.66 mm, P=0.833). Conclusion When three decompression boundaries are strictly adhered to intraoperatively, both UE-ULBD and BE-ULBD can achieve equivalent radiological decompression effects and similar facet joint resection rates, with both yielding good clinical outcomes. BE-ULBD offers higher surgical efficiency, whereas UE-ULBD causes less paraspinal soft tissue damage.
Objective Against the backdrop of increasing social mobility and changing social interaction patterns in China, older adultsu2019 interpersonal interaction patterns and sources of social support are undergoing transformation, and self-rated interpersonal relationships may represent an important psychosocial factor influencing mental health in later life. This study aimed to examine the association between self-rated interpersonal relationships and depressive symptoms among older adults, and to analyze the heterogeneity of this association across subgroups with different characteristics, so as to provide scientific evidence for developing precision prevention and intervention strategies for late-life depression. Methods Using data from the 2022 China Family Panel Studies (CFPS), we conducted a cross-sectional study including 4609 participants aged u226560 years with complete data on key variables. Depressive symptoms were assessed with the 8-item Center for Epidemiologic Studies Depression Scale (CES-D8), with a score u0026gt;16 defined as having depressive symptoms. Self-rated interpersonal relationship score was treated as the independent variable and categorized into low (0 to 5), medium (6 to 7), and high (8 to 10) groups. Chi-square tests and multivariable logistic regression models were used; after controlling for confounders including age, sex, household registration (hukou), marital status, education, insurance, and physical exercise, we analyzed the association between self-rated interpersonal relationships and depressive symptoms, and further performed Spearman correlation and subgroup stratification analyses. Results The detection rate of depressive symptoms among older adults in China was 25.86%. The detection rates in the low, medium, and high self-rated interpersonal relationship groups were 33.48%, 27.08%, and 22.14%, respectively. Multivariable logistic regression analysis showed that, after adjusting for confounders, the high-score group had lower likelihood of experiencing depressive symptoms compared with the low-score group (OR=0.58, 95%CI: 0.50 to 0.68, Pu0026lt;0.001), with a dose-response relationship (chi-square test for trend Pu0026lt;0.001). Correlation analysis indicated that self-rated interpersonal relationship score was significantly negatively correlated with the total CES-D8 scores and all item scores (r=-0.12, 95%CI: -0.149 to -0.092, Pu0026lt;0.001); the correlations were stronger for the three items u201Cfeeling lonelyu201D, u201Cfeeling happy about lifeu201D and u201Cfeeling sadu201D. Subgroup analysis revealed that, compared with the low-score group, the high-score group showed a consistent association with lower likelihood of depressive symptoms across all subgroups except those with university education or higher (Pu0026lt;0.05), while the medium-score group showed a protective effect only in the female subgroup (OR=0.748, 95%CI: 0.559 to 0.999, Pu0026lt;0.05). Conclusion Good self-rated interpersonal relationships represent an independent protective factor against depressive symptoms among Chinese older adults, showing a dose-effect relationship and playing a prominent role in alleviating core affective symptoms such as loneliness and sadness. This protective effect varies across older adults with different characteristics, suggesting that differentiated strategies should be implemented in interventions for depressive symptoms in older adults.
Objective Elderly patients with chronic obstructive pulmonary disease (COPD) often have limited respiratory function and multi-system decline. Traditional assessment methods cannot comprehensively reflect their overall functional status, and the characteristics of intrinsic capacity in this population remain unclear. This study aimed to identify latent classes of intrinsic capacity in elderly COPD patients and analyze influencing factors, providing a basis for early clinical identification and precise intervention. Methods A cross-sectional design was used. From July 2025 to January 2026, 423 elderly COPD patients hospitalized in the Department of Respiratory and Critical Care Medicine, Department of Geriatrics, and Department of Cardiology at the main campus and Binhu campus of Hefei First Peopleu2019s Hospital were selected by convenience sampling. Face-to-face surveys were conducted using the Intrinsic Capacity Assessment Tool, a general information questionnaire, the Lubben Social Network Scale (LSNS-6), and the Chinese Adult Sedentary Behavior Questionnaire. Latent class analysis was used to identify intrinsic capacity categories, and univariate and multinomial logistic regression were used to analyze influencing factors. Results The overall decline rate of intrinsic capacity in elderly COPD patients was 92.9%. Three latent classes were identified: overall preserved (n=145), functionally imbalanced (n=178), and overall impaired (n=100). Significant differences were found among the three groups in sex, age, smoking status, marital status, living arrangement, disease duration, number of comorbidities, medication use, number of hospitalizations for COPD in the past year, long-term home oxygen therapy, mMRC grade, LSNS-6 total score, family network score, friend network score, and total sedentary behavior score (Pu0026lt;0.05). Multinomial logistic regression analysis showed that family network score (OR=0.765, 95%CI: 0.598 to 0.978), friend network score (OR=0.561, 95% CI: 0.442 to 0.712), Chinese Adult Sedentary Behavior Questionnaire total score (OR=1.414, 95%CI: 1.030 to 1.940), age 70 to 79 years (OR=2.788, 95%CI: 1.093 to 7.111), having u22652 other chronic diseases (OR=6.981, 95%CI: 1.701 to 28.643), long-term home oxygen therapy (OR=3.297, 95%CI: 1.147 to 9.478), and mMRC grade 2 to 4 (OR=4.060, 95%CI: 1.186 to 13.907) were independent influencing factors for the functionally imbalanced group (Pu0026lt;0.05). Family network score (OR=0.716, 95%CI: 0.542 to 0.945), friend network score (OR=0.396, 95%CI: 0.286 to 0.549), Chinese Adult Sedentary Behavior Questionnaire total score (OR=1.586, 95%CI: 1.121 to 2.245), age 70 to 79 years (OR=5.370, 95%CI: 1.400 to 20.598), age u226580 years (OR=12.169, 95%CI: 2.042 to 72.511), and long-term home oxygen therapy (OR=4.695, 95%CI: 1.345 to 16.391) were independent influencing factors for the overall impaired class (Pu0026lt;0.05). Conclusion There is significant heterogeneity in the intrinsic capacity of elderly COPD patients, which can be classified into three latent classes. Social isolation, sedentary behavior, age, number of comorbidities, mMRC grade, and long-term home oxygen therapy are closely associated with intrinsic capacity. It is recommended that intrinsic capacity classification be incorporated into routine assessment for elderly COPD patients, and for those with functionally imbalanced and overall impaired group, comprehensive intervention strategies such as enhancing social support, reducing sedentary behavior, and optimizing oxygen therapy management should be prioritized to delay the decline of intrinsic capacity.
Abstract Objective Older patients with colorectal cancer undergoing first-line chemotherapy are prone to myelosuppression, which can lead to treatment delays, dose adjustments, and adverse outcomes such as infection and bleeding; however, individualized risk prediction tools with external validation remain lacking. This study aimed to identify routine clinical predictors using a multi-algorithm consensus strategy, construct and compare risk prediction models for grade ≥2 chemotherapy-induced myelosuppression in this population, and evaluate the external generalizability and clinical utility of the leading model. Methods In this retrospective cohort study leveraging data from two hospitals, we adopted a predictive model development and independent external validation design. A total of 553 older patients receiving first-line chemotherapy were enrolled, including 442 from Guang’anmen Hospital (development cohort) and 111 from Gansu Provincial Cancer Hospital (external validation cohort). The primary endpoint was grade ≥2 myelosuppression per Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Nineteen candidate predictors underwent consensus selection via least absolute shrinkage and selection operator logistic regression, the Boruta algorithm, and random forest permutation importance, with final core predictors determined by bootstrap inclusion frequency and prespecified clinical retention rules. Nine models were constructed: conventional logistic regression, LASSO logistic regression, elastic net logistic regression, random forest, extreme gradient boosting, categorical boosting, radial basis function support vector machine, linear discriminant analysis, and explainable boosting machine (EBM). Five repeated 10-fold stratified cross-validation generated out-of-fold predictions in the development cohort, and locked models were applied to the external validation cohort. Model performance was assessed by area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), Brier score, calibration intercept, calibration slope, Hosmer-Lemeshow test, and decision curve analysis. Results The incidence of grade ≥2 myelosuppression was 26.2% (116/442) in the development cohort and 27.0% (30/111) in the external validation cohort (P>0.05). Nine core predictors were selected: albumin, carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 125, body surface area, tumor location, chemotherapy cycle, chemotherapy regimen, and age-adjusted Charlson comorbidity index. The EBM was identified as the leading model based on balanced discrimination, calibration, and interpretability. In the development cohort, EBM achieved an out-of-fold AUROC of 0.720 (95%CI: 0.676 to 0.772), AUPRC of 0.421, Brier score of 0.176, calibration intercept of 0.035, and calibration slope of 0.778, with no significant miscalibration (Hosmer-Lemeshow P=0.087). In external validation, EBM yielded an AUROC of 0.714 (95%CI: 0.595 to 0.834), AUPRC of 0.641, Brier score of 0.164, calibration intercept of 0.155, and calibration slope of 0.778, though calibration remained suboptimal (P<0.001). At the optimal threshold of 0.28 derived from the development cohort, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score in the external validation cohort were 0.667, 0.741, 0.488, 0.857, and 0.563, respectively. Decision curve analysis indicated superior net benefit over treat-all or treat-none strategies across threshold probabilities of 0.06 to 0.48 (development cohort) and 0.18 to 0.60 (external validation cohort). Interpretation revealed albumin as the strongest contributor, followed by carcinoembryonic antigen, carbohydrate antigen 19-9, and carbohydrate antigen 125; lower albumin, smaller body surface area, ≥5 chemotherapy cycles, and the FOLFIRI regimen were associated with increased risk, while tumor markers exhibited nonlinear associations with predicted risk. Conclusion Nine routine clinical parameters selected by a multi-algorithm consensus strategy enable construction of a prediction model for grade ≥2 myelosuppression during first-line chemotherapy in older patients with colorectal cancer. The finalized EBM model demonstrates moderate discrimination and clinical net benefit in both development and external validation cohorts but exhibits residual calibration drift externally. It may serve as an adjunctive tool for clinical risk stratification rather than a standalone decision-making instrument at this stage.
Objective With accelerating population aging, the phenomenon of u201Cold-to-old caregivingu201Du2014where individuals aged 60 years or older care for another elderly patientu2014has become increasingly prevalent among families of older cancer patients. While caregiving burden and inadequate care capacity among these caregivers represent growing challenges, the underlying mechanistic pathways linking these factors remain insufficiently understood. This study aimed to elucidate the mediating roles of psychological capital and social networks in the relationship between caregiving burden and care capacity among older adult caregivers, providing an evidence base for developing integrated psychosocial interventions to improve home-based care quality. Methods A cross-sectional design was employed, utilizing convenience sampling to recruit participants from the Radiation Oncology Department of The First Affiliated Hospital of Anhui Medical University between July 2025 and January 2026. A total of 344 valid caregiver-patient dyads were ultimately enrolled. Data were collected using a general information questionnaire (capturing sociodemographic and clinical characteristics), including the Aged Care Aptitude Assessment Scale, Caregiver Burden Scale for Cancer Patients, Positive Psychological Capital Questionnaire and Lubben Social Network Scale-6. Pearson correlation analysis was performed to examine interrelationships among care capacity, caregiving burden, psychological capital, and social networks. Chain mediation analysis was subsequently conducted, adjusting for relevant covariates. Results The mean caregiving capacity score among the 344 caregivers was 95.50u00B112.18, indicating a below-medium level. The mean caregiving burden score was 54.86u00B16.56 (mild-to-moderate burden), Positive psychological capital was 106.47u00B114.79 (medium level), and social network score was 12.85u00B14.15, approaching the threshold for social isolation risk. After adjusting for covariates, multiple regression analysis revealed that caregiving burden significantly and negatively predicted both psychological capital (u03B2=-0.215, Pu0026lt;0.001) and social networks (u03B2=-0.228, Pu0026lt;0.001), while psychological capital positively predicted social networks (u03B2 =0.450, Pu0026lt;0.001). Caregiving burden also exerted a significant negative direct effect on caregiving capacity (u03B2 =-0.092, P=0.016), whereas psychological capital (u03B2 =0.574, Pu0026lt;0.001) and social networks (u03B2 =0.167, Pu0026lt;0.001) significantly and positively predicted caregiving capacity. The chain mediation model demonstrated significant indirect effects. The total effect of burden on capacity was -0.270 (95%CI: -0.369 to -0.171), with a direct effect of -0.092 (95%CI: -0.167 to -0.017). The total indirect effect was -0.178 (95%CI: -0.255 to -0.102), accounting for 65.9% of the total effect. Specifically, the mediating effect via psychological capital alone was -0.124 (95%CI: -0.191 to -0.060; 45.9% of total effect), via social networks alone was -0.038 (95%CI: -0.070 to -0.014; 14.1% of total effect), and the chain mediation effect through both psychological capital and social networks sequentially was -0.016 (95%CI: -0.030 to -0.005; 5.9% of total effect). Conclusion Psychological capital and social networks serve as significant sequential mediators in the relationship between caregiving burden and care capacity among older adult caregivers of cancer patients. These findings underscore the necessity for clinical healthcare providers to implement integrated psychosocial support strategies targeting both psychological resilience and social connectivity to mitigate the adverse impact of caregiving burden and enhance the quality of home-based care for this vulnerable population.
Objective Chronic obstructive pulmonary disease (COPD) is difficult to recognize early, and its oxidative stress, iron metabolism disorder, and lipid peroxidation are closely associated with ferroptosis. Screening stable ferroptosis-related biomarkers may help elucidate the molecular mechanisms of COPD and improve auxiliary diagnosis. This study aimed to screen key ferroptosis biomarkers in COPD based on bioinformatics, machine learning, and single-cell transcriptomic analyses, construct a combined diagnostic model, and validate their expression in cigarette smoke-exposed mice. Methods Two lung tissue bulk transcriptomic datasets, GSE178513 (3 normal, 6 COPD) and GSE106986 (5 normal, 14 COPD), and a single-cell transcriptomic dataset GSE279570 (7 normal, 11 COPD) were obtained from the Gene Expression Omnibus (GEO). Combined with 484 ferroptosis-related genes from the FerrDb database, differential analysis, functional enrichment analysis, and weighted gene co-expression network analysis were performed to screen candidate genes. Seurat, Monocle2, and CellChat were used to analyze cell clustering, pseudotime trajectories, and cell communication among 64620 high-quality cells. The least absolute shrinkage and selection operator (LASSO) regression was used to select feature genes, and the combined model was evaluated using receiver operating characteristic curves, calibration curves, and decision curve analysis. Male C57BL/6 mice aged 6 to 8 weeks were randomly divided into control and COPD groups (n=8 per group) using a random number table. The COPD group was exposed to cigarette smoke for 12 consecutive weeks. Lung function testing, hematoxylin-eosin staining, RT-qPCR, Western blotting, and immunohistochemistry were used to assess lung function, lung histopathology, and key gene expression. Results Five ferroptosis-related key genes were identified: SPATA2, CEMIP, FABP4, DPP4, and IL6. Their expression in COPD lung tissues was significantly higher than in normal controls (P allu0026lt;0.05). Single-cell analysis revealed that IL6 and FABP4 increased along the pseudotime trajectory from monocytes to type 2 conventional dendritic cells, and enhanced communication between macrophages and Club cells was observed in the COPD group (Pu0026lt;0.01). The area under the curve of the 5-gene combined model was 0.921. Compared with the control group, mice in the COPD group showed decreased forced expiratory volume in 0.3 s (FEV0.3) (P=0.0314), increased forced vital capacity (FVC) (P=0.0287), a reduced FEV0.3/FVC ratio (P=0.0048), and emphysema-like pathological changes. The mRNA and protein expression of all five genes was increased (Pu0026lt;0.05). Conclusion SPATA2, CEMIP, FABP4, DPP4, and IL6 are candidate biomarkers associated with ferroptosis, inflammation, and abnormal lipid metabolism in COPD. The 5-gene combined model showed good discriminatory performance in the training data, and the abnormally high expression was validated in vivo in mice, providing clues for mechanistic studies and the screening of auxiliary diagnostic biomarkers for COPD.
Population aging and changes in the chronic disease spectrum have gradually made geriatric multimorbidity a central issue confronting stroke care and geriatric medicine. Brain-heart multimorbidity is one of the most clinically representative and challenging phenotypes of geriatric multimorbidity, characterized by a deep intertwining of cerebrovascular and cardiovascular diseases across risk factors, pathological basis, acute events, long-term prognosis, and treatment strategies. Drawing on conceptual evolution and clinical phenotypes, this review classifies brain-heart multimorbidity into 3 clinical subtypes: brain-heart co-occurrence, brain-heart interaction, and brain-heart conflict. Taking atherosclerosis as the core pathological basis, this review systematically examines the pathophysiological mechanisms underlying brain-heart multimorbidity, including immune-mediated inflammation, endothelial injury, thrombosis, neuroendocrine dysregulation, and gut microbiota imbalance. On this basis, it analyzes critical gaps in China regarding epidemiological evidence, mechanistic research, clinical diagnosis and treatment models, polypharmacy management, and health service systems. This review proposes that prevention and treatment of brain-heart multimorbidity urgently need to shift from the traditional single-disease, single-system paradigm to a new framework of multiple coexisting diseases, whole-course management, and individualized decision-making. Such a framework should be anchored in multidisciplinary collaboration and integrate mechanistic research with real-world evidence to build a brain-heart multimorbidity prevention and treatment system tailored to Chinau2019s national conditions. As a microcosm of geriatric multimorbidity, this conceptual shift can provide methodological insights for moving geriatric multimorbidity from stacked single-disease management toward integrated multi-system governance, and is of great significance for reducing the burden of cardiovascular and cerebrovascular events in older adults and maintaining functional independence and quality of life.
Objective Oxidative stress-induced cardiomyocyte apoptosis is a central event in myocardial ischemia-reperfusion (MIR) injury. MicroRNA-27b (miR-27b) is aberrantly expressed in this process, yet its role and regulatory mechanism in MIR injury remain to be elucidated. This study aims to clarify the molecular mechanism by which miR-27b regulates H2O2-induced cardiomyocyte apoptosis via the PPAR-u03B3/Bcl-2 signaling pathway, thereby providing a novel target for intervention in MIR injury. Methods u2460 Healthy male C57BL/6J mice (10 to 12 weeks old, weighing 24 to 30 g) were randomly divided into a MIR group and a sham operation group, with 6 animals in each group. The MIR group underwent ligation of the left anterior descending coronary artery for 45 min followed by reperfusion to induce myocardial injury, while the Sham group underwent the identical surgical procedure without ligation. The heart was harvested 24 h postoperatively, and the entire heart was sectioned and stained with TTC for 30 min to assess infarct size. The ischemic myocardial tissue from the anterior wall of the left ventricle was used for total RNA extraction. u2461 Primary neonatal mouse ventricular cells (PNMVCs) were isolated from 1-to 3-day-old mice and transfected for 24 h with miR-27b mimics or anti-miR-27b oligonucleotides (AMO-miR-27b). The cells were subsequently treated with 100 u03BCmol/L hydrogen peroxide (H2O2) for 24 h to induce cardiomyocyte apoptosis. Transfected cardiomyocytes were treated with the PPAR-u03B3 antagonist T0070907 (10.0 nmol/L), and apoptosis was assessed 48 h later. Cell experiments were divided into normal control group, H2O2 model group, miR-27b mimic transfection+H2O2 group, AMO-miR-27b transfection+H2O2 group, AMO-miR-27b+H2O2+T0070907 group, and negative control (NC) +H2O2 group. RT-qPCR was performed to measure the expression levels of miR-27b and PPAR-u03B3. Cell viability was assessed using MTT assay. Cell apoptosis was quantified by TUNEL assay combined with DAPI staining. Western blotting was employed to detect the expression of PPAR-u03B3, Bcl-2, Bax, and Cyt-c, and other related proteins. Results u2460 Compared with the Sham group, the MIR group exhibited significantly larger infarct size in TTC-stained heart sections, and upregulated miR-27b expression in the ischemic myocardial tissue of the left ventricular anterior wall (Pu0026lt;0.05). u2461 Compared to the normal control group, miR-27b expression levels were significantly upregulated in H2O2-treated PNMVCs (Pu0026lt;0.01). Overexpression of miR-27b in PNMVCs induced cardiomyocyte damage, as evidenced by decreased cell viability[(48.75u00B15.55)% vs (87.20u00B13.52)%, Pu0026lt;0.01] and increased cell apoptosis [(41.08u00B12.84)% vs (1.75u00B10.29)%, Pu0026lt;0.01], accompanied by reduced expression of PPAR-u03B3 at both mRNA (Pu0026lt;0.01) and protein levels (Pu0026lt;0.01). In contrast, inhibition of miR-27b expression enhanced PPAR-u03B3 expression at both mRNA (Pu0026lt;0.05) and protein levels (Pu0026lt;0.01). MTT assay showed that AMO-miR-27b attenuated H2O2-induced decrease in cell viability [(79.46u00B16.41)% vs (60.29u00B14.83)%, Pu0026lt;0.01]; TUNEL assay further demonstrated that after AMO-miR-27b transfection, H2O2-induced cardiomyocyte apoptosis was significantly reduced [(19.60u00B12.95)% vs (42.96u00B15.80)%, Pu0026lt;0.01]. H2O2 treatment caused significantly decreased Bcl-2 levels (Pu0026lt;0.01) and elevated Bax levels (Pu0026lt;0.01) in cardiomyocytes, which were reversed by AMO-miR-27b. Furthermore, cytoplasmic Cyt-c protein levels were significantly increased in cardiomyocytes after H2O2 exposure (Pu0026lt;0.01), and the downregulatory effect of AMO-miR-27b on cytoplasmic Cyt-c (Pu0026lt;0.05) and its protective effect against cardiomyocyte apoptosis (Pu0026lt;0.01) were abolished by the PPAR-u03B3 antagonist T0070907. Conclusion MiR-27b is highly expressed in myocardial tissues and cardiomyocytes after oxidative stress injury, which exacerbates tissue damage and cell apoptosis. Suppression of the PPAR-u03B3/Bcl-2 signaling pathway may be a primary mechanism underlying this effect, suggesting that targeted inhibition of miR-27b may be a potential novel strategy for MIR injury intervention.
Objective Helicobacter pylori (H. pylori) infection is a major cause of chronic gastritis. This study aims to determine whether H. pylori infection induces the expression of G protein-coupled receptor class C group 5 member C (GPRC5C) in gastric epithelial cells, to verify the regulatory role of the upstream NF-u03BAB signaling pathway, and to elucidate the biological function of GPRC5C in H. pylori-associated gastritis, thereby providing a potential new therapeutic target for the prevention and treatment of this disease. Methods A total of 190 SPF-grade female C57BL/6J mice (6 to 8 weeks old, weighing 18 to 22 g) were randomly divided into an uninfected control group (gavaged with PBS) and an H. pylori-infected group (gavaged with H. pylori), with 95 mice per group. The mice were gavaged 5 times consecutively, twice a day. To establish a chronic in vivo infection model, 5 mice from each group were randomly euthanized weekly from week 1 to week 19 post-infection, for 19 weeks. The expression of GPRC5C in mouse gastric mucosal tissues was examined by quantitative real-time PCR, Western blotting, and immunohistochemical staining. Human gastric tissue specimens were obtained from normal gastric tissues at least 5 cm from the tumor margin in gastric cancer patients hospitalized in Department of General Surgery of First Affiliated Hospital of Army Medical University. Immunohistochemical staining was employed to evaluate the protein expression of GPRC5C in human gastric tissues. Mouse primary gastric epithelial cells were isolated from gastric tissues of uninfected mice by enzymatic digestion and mechanical dissociation, followed by filtration to prepare single-cell suspensions, which were then purified by CD326 based magnetic-activated cell sorting (MACS) system. An H. pylori infection model was established in both the GES-1 cell line and mouse primary gastric epithelial cells. The expression of GPRC5C in GES-1 cells and mouse primary gastric epithelial cells was examined by qRT-PCR and Western blotting. Signaling pathway blocking experiments were performed to screen and verify the intracellular signaling pathway activated during H. pylori-induced GPRC5C expression in gastric epithelial cells. Dual-luciferase reporter gene assay was used to analyze the GPRC5C promoter activity of the full-length and truncated sequences of GPRC5C promoter region after H. pylori infection, and to determine the effect of signaling pathway inhibitors on GPRC5C promoter activity. Furthermore, another female C57BL/6J WT mice and Gprc5c-/- mice (n=5, 6 to 8 weeks old, weighing 18 to 22 g) were used to establish the H. pylori infection model. Gastric tissue inflammation was observed after HE staining to preliminarily investigate the effector function of GPRC5C in H. pylori infection-associated gastritis. Results Compared with the uninfected group, the mRNA levels of GPRC5C in mouse gastric mucosal tissues were significantly upregulated at week 14 post-H. pylori infection (Pu0026lt;0.0001), and the protein levels were also elevated in both mouse and human gastric mucosal tissues. In vitro experiments showed that, compared with the corresponding uninfected group, H. pylori infection upregulated the expression of GPRC5C at both mRNA and protein levels in GES-1 cells and mouse primary gastric epithelial cells, with mRNA expression levels increased 4.1-fold and 3.1-fold, respectively (Pu0026lt;0.01). This upregulation was dependent on the bacterial dose and infection duration (Pu0026lt;0.05). In terms of the underlying mechanism, pretreatment with an NF-u03BAB signaling pathway inhibitor significantly suppressed H. pylori-induced GPRC5C upregulation in gastric epithelial cells, with an inhibitory rate of 64.0% (Pu0026lt;0.01). Dual-luciferase reporter assay revealed that H. pylori infection significantly increased GPRC5C promoter activity to 4.1 times of that in the uninfected group (Pu0026lt;0.001). When the NF-u03BAB signaling pathway was blocked, this promoter activity was significantly suppressed, with an inhibitory rate of 66.1% (P=0.0002); In functional validation, compared with H. pylori-infected WT mice, Gprc5c-/- mice exhibited significantly reduced gastric inflammation after infection (Pu0026lt;0.001). Conclusion H. pylori infection induces GPRC5C expression in gastric epithelial cells through activation of the NF-u03BAB signaling pathway, thereby promoting the progression of H. pylori-associated gastritis.
Objective Early-life developmental factors may influence the risk of cerebrovascular disease in adulthood,but the causal relationship between birth weight and different subtypes of ischemic stroke remains unclear.This study used Mendelian randomization(MR)to investigate the causal association between birth weight and the risk of ischemic stroke(IS)and its major clinical subtypes in adulthood.Methods A two-stage analytical design combining univariable and multivariable MR(UVMR and MVMR)was adopted.Birth weight data were obtained from the Early Growth Genetics(EGG)Consortium,with a sample size of 143 677.Stroke outcome data were obtained from the GIGASTROKE consortium,with a total sample size of approximately 1.29 million,including overall IS and 3 major clinical subtypes:cardioembolism(CE),large artery atherosclerosis(LAA),and small vessel disease(SVD).To ensure sufficient instrumental variables in the multivariable analysis,the screening threshold for birth weight instruments was set at P＜1×10-5.Adult body mass index(BMI)and systolic blood pressure(SBP)were included as covariates in the MVMR model to adjust for adult body size and blood pressure.Causal inference was mainly performed using the random-effects inverse variance weighted(IVW)method.F-statistics,MR-Egger intercept test,and MR-Plelotropy RESidual Sum and Outlier(MR-PRESSO)test were used to assess instrument strength,horizontal pleiotropy,and potential outlier loci.The significance threshold was set at P＜0.012 5 after Bonferroni correction.Fetal-only genetic effect estimates derived from structural equation modeling were further used in a supplementary sensitivity analysis to preliminarily assess the potential influence of maternal genetic effects on the results.Results In the univariable analysis,no significant causal association was observed between birth weight and IS or any of its subtypes.The multivariable analysis included 19 to 21 independent core single-nucleotide polymorphisms(SNPs).The univariable F-statistics were all＞10,whereas the conditional F-statistic for birth weight was＜10,suggesting a potential risk of weak instruments in the conditional model.After adjusting for adult BMI and SBP,MVMR analysis showed that genetically predicted higher birth weight was associated with a reduced risk of LAA(OR=0.736,95％CI:0.587 to 0.922,P=0.007 6).No significant associations were observed with IS(OR=0.943,95％CI:0.869 to 1.023,P=0.156 6),CE(OR=1.018,95％CI:0.857 to 1.210,P=0.836 9),or SVD(OR=0.850,95％CI:0.688 to 1.050,P=0.132 3).Supplementary sensitivity analysis using fetal-only genetic effect estimates within the multivariable framework showed a direction consistent with the main analysis for the association between birth weight and reduced LAA risk.However,because only a limited number of core SNPs were available and the association reached nominal significance(P=0.033),this result was used only to support the directional consistency of the main analysis.Conclusion After adjusting for adult BMI and SBP,genetically predicted higher birth weight is associated with a reduced risk of LAA in adulthood,whereas no significant causal associations are observed with the risk of overall IS,CE,or SVD in adulthood.
Objective On the land battlefield,non-compressible torso hemorrhage is the leading cause of preventable death from combat injuries,yet frontline military physicians generally lack effective endovascular hemostatic skills.This study aims to develop a standardized training program for resuscitative endovascular balloon occlusion of the aorta(REBOA)by combining intelligent sensor-equipped simulation manikins with animal models,and to verify its efficacy in improving REBOA proficiency among frontline medical physicians with no prior interventional experience,with a goal of addressing the bottleneck in extending advanced combat casualty care to the frontline.Methods A self-controlled before-and-after study design was adopted.Twenty on-duty primary-level military physicians from the Army(representing 18 brigade-and regiment-level medical units)were enrolled in June 2023.The participants first completed 10 full-procedure practice sessions on an intelligent simulator to establish skill acquisition curves;subsequently underwent stepwise reinforcement training in femoral artery puncture and catheterization using 10 experimental pigs(weighing 30 to 40 kg);and finally,were assessed using 10 porcine hemorrhagic models(weighing 30 to 40 kg).Digital subtraction angiography(DSA)was applied to observe the accuracy of balloon position.Training effectiveness was evaluated by comparative analysis of trainees'procedural time at different stages of simulator practice,puncture time and procedural success rate during REBOA training on the porcine model,as well as puncture time,balloon positioning accuracy,procedural success rate,and complications during assessment on the porcine hemorrhagic model.Results All the 20 trainees successfully completed the training.① Skill acquisition efficiency:During the simulator training phase,the single-operator procedural time was decreased from 10.8±1.2 min at the first attempt to 5.3±0.4 min at the tenth attempt(P＜0.001);The goodness-of-fit of the single-phase decay model was R2=0.98,indicating that skill plateau was reached after the 7th practice session.② Real-world transfer capability:The trainees completed stepwise skill intensive practice on live experimental pigs,with a mean femoral artery puncture duration of 4.8±1.2 min and a success rate of 95％(19/20);Under DSA fluoroscopy guidance,the mean time for balloon positioning at aortic Zone Ⅰ(timed from balloon entry into the arterial sheath)was 3.8±0.9 min,with a success rate of 95％(19/20).In the assessment on the live porcine hemorrhagic model,the average total procedure time was 7.8±1.4 min(95％CI:7.2 to 8.4);19 out of 20 trainees(95％)achieved visual confirmation of successful hemostasis of the contralateral femoral artery.③ Safety:The complication rate during the assessment phase was 10％(2/20),and the overall pass rate in the final comprehensive evaluation reached 90％(18/20).Conclusion Junior military physicians with no prior interventional experience can acquire preliminary proficiency in REBOA technique through the training program of intelligent sensor-equipped simulator combined with animal model;This program provides a replicable training pathway for disseminating REBOA technology to grassroots units.
Objective To address the dilemma of insufficient recognition of the minority class caused by class imbalance in predicting depression tendency among college students,and systematically compare the predictive performance of 7 oversampling,undersampling,and hybrid sampling methods combined with 12 machine learning models on a class-imbalanced dataset of music APP listening habits and depression tendency in them,providing a reference for method selection in handling class-imbalanced data.Methods This study adopted a cross-sectional study design.Data were collected from questionnaire surveys of college students from 29 provinces,autonomous regions,and municipalities in China in 2023,with college students primarily being undergraduate and postgraduate students aged 18 to 24 years.Univariate analysis was used to screen 10 features significantly associated with depression tendency in the participants.Three oversampling methods including synthetic minority over-sampling technique(SMOTE),adaptive synthetic sampling approach(ADASYN),and synthetic minority over-sampling technique for regression with Gaussian noise(SMOGN),2 undersampling methods including edited nearest neighbors(ENN)and Tomek Links,and 2 hybrid sampling methods including SMOTEENN and ADASYN-Tomek were applied to process the raw data.The raw data and processed data were respectively used to construct prediction models with 12 classification algorithms,including logistic regression(LR),support vector machine(SVM),random forest(RF),decision tree(DT),Light Gradient Boosting Machine(LightGBM),K-Nearest Neighbors(KNN),eXtreme Gradient Boosting(XGBoost),Lasso logistic regression(LASSO),ridge regression(Ridge),elastic net(ENet),multilayer perceptron(MLP),and stacking ensemble model(Stacking).Area under the receiver operating characteristic curve(AUC),Recall,F1-score,and balanced accuracy were selected as evaluation metrics to assess model performance.The optimal model was screened by comparing various combinations of class-imbalance handling techniques and machine learning strategies.SHapley Additive exPlanations(SHAP)analysis was applied for interpretability analysis for the optimal model.Results Univariate analysis identified 10 features significantly associated with depression tendency in college students:gender,grade,major category,preference for Children's songs,approximate length since music listening habits,preference for Chinese style songs,usual music styles,daily listening duration,period of listening during a day,and frequency of comments on music APP.The comparison of 84 combined models with the 12 models based on raw data showed that hybrid sampling outperformed single sampling methods among the 7 resampling strategies;among the 12 classification algorithms,the stacking ensemble model demonstrated better comprehensive performance than individual classifiers.The combination of SMOTEENN hybrid sampling with Stacking achieved the best performance(AUC=0.95,F1=0.89,Recall=0.88,balanced accuracy=0.89).SHAP analysis showed that"usual listening style"contributed the highest in predicting depression tendency among college students.Conclusion Based on the comparison of 84 combination models,the SMOTEENN+stacking ensemble model can accurately predict depression tendency in college students.The comparative analysis provides a methodological basis and practical reference for method selection in class-imbalanced data scenarios and for early identification of mental health risk based on music listening behavior data.
Objective Medical undergraduates are burdened with academic and career pressures,and their mental health deserves close attention.This study aims to analyze the current status of mental health among these students and examine how academic-career experience,interpersonal relationships and family finance influence their mental health,as well as the underlying pathways of action.Methods A multicenter cross-sectional survey was performed from April to September 2025.A total of 1 853 undergraduates were recruited from one medical university each in Southwest,Northwest and East China by convenience sampling.Chinese College Students Mental Health Scale(CCSMHS)was used to assess mental health status.Demographic data were collected,including gender,grade,major category,only-child status,and family residence.Academic-career experiences encompassed major satisfaction,course difficulty,academic pressure,attitude toward employment prospects,and career planning clarity.Interpersonal relationships involved relationships with classmates,typical responses to interpersonal conflicts,and psychological feelings brought by romantic relationships.Family financial factors included family atmosphere,family members' usual pratices when disagreement arise,monthly family income,monthly living expenses,and the impact of family economic status on study and life.The scores of each dimension of the scale for medical undergraduate were compared with the norms for ordinary college students.Intergroup difference tests were performed to analyze disparities in psychological scores among students with different demographic characteristics.Spearman correlation analysis was employed to explore correlations between mental health status and its influencing factors.SPSS Amos 28 was applied to construct a structural equation model for mediating effect analysis,and the Bootstrap method with 5 000 resamples was adopted to test the significance of mediating effect.Results A total of 13.00％of the participants were at high risk for mental health problems.Compared with the norms for ordinary college students,medical students had significantly higher scores in the inferiority and paranoia dimensions(P＜0.001),lower scores in 9 dimensions including anxiety,depression,sexual dysfunction,obsession,dependence,impulsivity,psychotic tendency,social withdrawal,and social aggression(P＜0.05),but somatization showed no significant intergroup difference(P=0.824).Female students,freshmen and non-clinically majors presented significantly higher overall scores of psychological symptoms(P＜0.05).There were no statistically significant differences in scores between only-child and non-only-child students or between urban and rural students.Spearman correlation analysis revealed that academic-career experiences,interpersonal relationships,and family financial factors were all significantly correlated with inferiority and paranoia(P＜0.001).The structural equation model showed good fit(x2/df=2.880,CFI=0.980,TLI=0.972,RMSEA=0.032).Academic-career experiences positively predicted mental health(β=1.501,95％CI:0.828 to 2.178,P＜0.001),and also positively predicted interpersonal relationships(β=0.211,95％CI:0.161 to 0.263,P＜0.001).Interpersonal relationships positively predicted mental health(β=6.027,95％CI:3.875 to 8.499,P＜0.001).The indirect effect of academic-career experiences on mental health through interpersonal relationships was significant(β=1.274,95％CI:0.829 to 1.855,P＜0.001),accounting for 34.68％of the total effect.Conclusion Most medical undergraduates maintain good mental health,with stratified differences by gender,grade and major.Academic-career experiences,interpersonal relationships and family finances are all influencing factors for their mental health;interpersonal relationships exert a mediating role between academic-career experiences and mental well-being.Positive academic-career experiences can directly improve their mental health,and can also indirectly reduce psychological distress through good interpersonal relationships.Accordingly,medical universities should improve interpersonal support systems and implement targeted tiered psychological interventions.
