ObjectiveTo evaluate the effectiveness of exhalation-inhalation exercise on early pulmonary rehabi-litation for patients with acute exacerbation of chronic obstructive pulmonary disease （AECOPD）. MethodsA total of 120 participants with AECOPD were randomly divided into a treatment group and a control group， with 60 participants in each group. The control group treated with conventional western medicine， while the treatment group received exhalation-inhalation exercise training on the basis of conventional western medicine treatment， with 30 minutes per session and 5 sessions per week. The course of treatment for both groups was 12 weeks. The primary outcome was the 6-minute walking distance （6MWD）. The secondary outcomes included pulmonary function indexes including forced expiratory volume in one second/forced vital capacity （FEV1/FVC）， percentage of predicted forced expiratory volume in one second （FEV1%） and percentage of predicted forced vital capacity （FVC%）， St.George's Respiratory Questionnaire （SGRQ） score， modified Medical Research Council （mMRC） dyspnea scale score， COPD assessment test （CAT） score， hospital anxiety and depression scale-anxiety subscale ［HADS（A）］ score， and hospital anxiety and depression scale-depression subscale ［HADS（D）］ score. Meanwhile， safety of all participants was recorded and assessed. ResultsDuring the treatment， 12 participants dropped out from both the treatment group and the control group， with 48 participants in each group finally included in the analysis. The 6MWD of both groups after treatment was higher than that before treatment， and the 6MWD of the treatment group was higher than that of the control group （P＜0.05 or P＜0.01）. After treatment， the SGRQ score， mMRC score and CAT score of the treatment group were lower than those before treatment， while FEV1%， FVC% and FEV1/FVC were higher than those before treatment （P＜0.05）. Moreover， after treatment， the FEV1/FVC of the treatment group was higher than that of the control group， while the SGRQ score， mMRC score and CAT score were lower than those of the control group （P＜0.05 or P＜0.01）. There was no statistically significant difference in pulmonary function indexes， SGRQ score， mMRC score and CAT score after treatment in the control group （P＞0.05）. No statistically significant difference was observed in HADS（A） score and HADS（D） score after treatment within and between groups （P＞0.05）. The incidence of adverse reactions in the treatment group was 6.25% （3/48）， and 0 in the control group， with no statistically significant difference between groups （P＞0.05）. ConclusionExhalation-inhalation exercise for patients with AECOPD in early pulmonary rehabilitation can improve patients' exercise tole-rance， quality of life， clinical symptoms and pulmonary function， with good safety.

Objective To explore the independent risk factors for complicated coronary heart disease (CHD) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and to construct a risk prediction model. Methods A retrospective study was performed to analyze the clinical data of 308 OSAHS patients who visited Jiangsu Provincial People's Hospital from January 2021 to June 2025. The patients were divided into the CHD group (n=80) and non-CHD group (n=228) according to the presence or absence of complicated CHD. Independent risk factors were identified using univariate analysis and multivariate logistic regression, and a nomogram prediction model was constructed. The model was evaluated using the calibration curve, Hosmer-Lemeshow test, Decision Curve Analysis (DCA) curve, and Receiver Operating Characteristic (ROC) curve. Results The incidence of CHD in OSAHS patients was 25.97%. Age, history of hypertension, oxygen desaturation index (ODI), severe polysomnography (PSG) grade, decreased high-density lipoprotein cholesterol, elevated homocysteine, and elevated troponin I were independent risk factors for OSAHS complicated with CHD (P<0.05). The nomogram model demonstrated good calibration (Hosmer-Lemeshow test, P=0.995), and the DCA curve showed high clinical net benefit. The area under the ROC curve was 0.940 (95% CI: 0.908~0.972), with a sensitivity of 0.842 and a specificity of 0.900. Conclusion Age, history of hypertension, ODI, PSG grade, high-density lipoprotein cholesterol, homocysteine, and troponin I are independent risk factors for CHD in OSAHS patients. The prediction model constructed based on these factors can provide a reliable tool for clinical nurses to early identify high-risk individuals and formulate targeted intervention strategies.

Objective To identify the independent predictors of programmed death-1 (PD-1) inhibitor-related endocrine adverse events and construct a clinically usable risk prediction model. Methods A total of 302 patients with solid tumors treated with PD-1 inhibitors were retrospectively enrolled. According to the presence or absence of endocrine immune-related adverse events (irAEs), the patients were divided into case group and control group. The clinical and laboratory indexes were compared between the two groups. Multivariable logistic regression was used to confirm independent predictors of endocrine irAEs. The nomogram was constructed, while the receiver operating characteristic (ROC) curve was used to test the prediction performance of the model. Results The overall incidence of endocrine irAEs was 21.9% (66/302), and the incidence of hypothyroidism was 19.5% (59/302). The age, PD-1 inhibitors, free thyroxine, thyroid peroxidase antibody (TPOAb), thyroglobulin, amylase, lymphocyte subset CD3 expression were statistically different between the two groups (P＜0.05). Multivariable logistic regression showed that higher expression of lymphocyte subset CD3 was a protective factor to prevent endocrine irAEs occurrence (P＝0.004), while age＜60 years, higher TPOAb and use of pembrolizumab were independent risk factors of endocrine irAEs (P＜0.05). The nomogram model thus constructed, and when the threshold probability of the model exceeded 0.1, its net benefit was higher. ROC curve showed that the AUC of the model to predict endocrine irAEs was 0.760. The prediction result of the model was highly consistent with the actual result. Conclusions The age, type of PD-1 inhibitor, baseline TPOAb level, and baseline CD3 expression can independently predict endocrine irAEs occurrence or not. The nomogram model based on this model has good predictive efficiency, which can provide reference for early identification of high-risk patients and immunotherapy management.

To investigate the incidence of postoperative neuropsychic dysfunction (PND) in Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) and to analyze its influencing factors.

ObjectiveBola-like short peptides exhibit novel self-assembly properties due to the formation of peptide dimers via hydrogen bonding interactions between their C-terminals. In this configuration, hydrophilic amino acids are distributed at both terminals, making these peptides behave similarly to Bola peptides. The electrostatic repulsive interactions arising from the hydrophilic amino acids at each terminal can be neutralized, thereby greatly promoting the lateral association of β-sheets. Consequently, assemblies with significantly larger widths are typically the dominant nanostructures for Bola-like peptides. To investigate the effect of hydrophilic amino acids on the self-assembly behavior of Bola-like peptides, the peptides Ac-RI₃-CONH₂ and Ac-HI₃-CONH₂ were designed and synthesized using the Bola-like peptide Ac-KI₃-CONH₂ as a template. Their self-assembly behavior was systematically examined. MethodsAtomic force microscopy (AFM) and transmission electron microscopy (TEM) were employed to characterize the morphology and size of the assemblies. The secondary structures of the assemblies were analyzed using circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy. Small-angle neutron scattering (SANS) was used to obtain detailed structural information at a short-length scale. Based on these experimental results, the effects of hydrophilic amino acids on the self-assembly behavior of Bola-like short peptides were systematically analyzed, and the underlying formation mechanism was explored. ResultsThe aggregation process primarily involved three steps. First, peptide dimers were formed through hydrogen bonding interactions between their C-terminals. Within these dimers, the hydrophilic amino acids K, R, and H were positioned at both terminals, enabling the peptides to self-assemble in a manner similar to Bola peptides. Next, β-sheets were formed via hydrogen bonding interactions along the peptide backbone. Finally, self-assemblies were generated through the lateral association of β-sheets. The results demonstrated that both Ac-KI₃-CONH₂ and Ac-RI₃-CONH₂ could self-assemble into double-layer nanotubes with diameters of approximately 200 nm. These nanotubes were formed by the edge fusion of helical ribbons, which initially emerged from twisted ribbons. Notably, the primary assemblies of these peptides exhibited opposite chirality: nanofibers formed by Ac-KI₃-CONH₂ displayed left-handed chirality, whereas those formed by Ac-RI₃-CONH₂ exhibited right-handed chirality. This reversal in torsional direction was primarily attributed to the different abilities of K and R to form hydrogen bonds with water. In contrast, Ac-HI₃-CONH₂ formed narrower twisted ribbons with a significantly reduced width of approximately 30 nm, which was attributed to the strong steric hindrance caused by the imidazole rings. The multilayer height of these ribbons was mainly due to the unique structure of the imidazole rings, which can function as both hydrogen bond donors and acceptors, thereby promoting aggregate growth in the vertical direction. ConclusionThe final morphology of the self-assemblies resulted from a delicate balance of various non-covalent interactions. By altering the types of hydrophilic amino acid residues in Bola-like short peptides, the relative strength of non-covalent interactions that drive assembly formation can be effectively regulated, allowing precise control over the morphology and chirality of the assemblies. This study provides a simple and effective approach for constructing diverse self-assemblies and lays a theoretical foundation for the development of functional biomaterials.

OBJECTIVES: To explore the risk factors of feeding intolerance (FI) in critically ill children receiving enteral nutrition (EN) and to construct a prediction nomogram model for FI. METHODS: A retrospective study was conducted to collect data from critically ill children admitted to the Pediatric Intensive Care Unit of Xiangya Hospital, Central South University, between January 2015 and October 2020. The children were randomly divided into a training set (346 cases) and a validation set (147 cases). The training set was further divided into a tolerance group (216 cases) and an intolerance group (130 cases). Multivariate logistic regression analysis was used to screen for risk factors for FI in critically ill children receiving EN. A nomogram was constructed using R language, which was then validated on the validation set. The model's discrimination, calibration, and clinical net benefit were evaluated using receiver operating characteristic curves, calibration curves, and decision curves. RESULTS: Duration of bed rest, shock, gastrointestinal decompression, use of non-steroidal anti-inflammatory drugs, and combined parenteral nutrition were identified as independent risk factors for FI in critically ill children receiving EN (P<0.05). Based on these factors, a nomogram prediction model for FI in critically ill children receiving EN was developed. The area under the receiver operating characteristic curve for the training set and validation set was 0.934 (95%CI: 0.906-0.963) and 0.852 (95%CI: 0.787-0.917), respectively, indicating good discrimination of the model. The Hosmer-Lemeshow goodness-of-fit test showed that the model had a good fit (χ 2=12.559, P=0.128). Calibration curve and decision curve analyses suggested that the model has high predictive efficacy and clinical application value. CONCLUSIONS Duration of bed rest, shock, gastrointestinal decompression, use of non-steroidal anti-inflammatory drugs, and combined parenteral nutrition are independent risk factors for FI in critically ill children receiving EN. The nomogram model developed based on these factors exhibits high predictive efficacy and clinical application value.
Humans ; Critical Illness ; Enteral Nutrition/adverse effects* ; Male ; Risk Factors ; Female ; Child, Preschool ; Infant ; Nomograms ; Retrospective Studies ; Child ; Logistic Models

In recent years, as a new omics field, metabolomics has been proved to be of great value in the study of the mechanism of occurrence and progression, the screening of new biomarkers and the development of novel therapeutic strategies in many diseases including tumors. In this review, we briefly summarized the research methods and techniques of metabolomics, and focused on the latest research progress of metabolomics in the pathogenesis of hematological malignancies represented by leukemia, lymphoma and multiple myeloma, screening of biomarkers for diagnosis and prognosis, and development of new therapeutic strategies. This article proposes the limitations of metabolomics and future research strategies, and provides a new exploration direction for accurate diagnosis and treatment as well as prognosis evaluation of hematological malignancies.
Humans ; Metabolomics/methods* ; Hematologic Neoplasms/diagnosis* ; Biomarkers, Tumor

OBJECTIVE: To investigate the predictive role of the modified Endothelial Activation and Stress Index (mEASIX) in the efficacy of chimeric antigen receptor T-cell (CAR-T) therapy and cytokine release syndrome (CRS). METHODS: The clinical data of 70 relapsed and refractory (R/R) B-cell tumor patients who were treated with CAR-T therapy from September 1, 2018 to February 28, 2023 in the Department of Hematology, Affiliated Hospital of Xuzhou Medical University, were retrospectively analyzed. The value of log-2 mEASIX before conditioning (-7 d) was calculated, and the patients were divided into a low-mEASIX group (42 patients) and a high-mEASIX group (28 patients) based on the cut-off value of 5.443 determined by the receiver operating characteristic (ROC) curve. Eventually, the predictive role of mEASIX before conditioning on the efficacy of CAR-T cell therapy and CRS was analyzed. RESULTS: The high-mEASIX group exhibited significantly worse median overall survival (OS) and median progression-free survival (PFS) in comparison to the low mEASIX group (OS: 3.2 months vs not reached, P < 0.01; PFS: 1.3 months vs 6.0 months, P =0.009). The incidence of grade ≥2 CRS in the high-mEASIX group was substantially higher than that in the low-mEASIX group (57.1% vs 19.0%, P =0.007). The degree of remission after CAR-T therapy (P =0.001), whether CRS occurs or not (P =0.041), the lactate dehydrogenase (LDH) level before conditioning (P =0.046), and the mEASIX score before conditioning (P =0.047) were independent influencing factors for the OS of patients receiving CAR-T cell therapy. CONCLUSION The mEASIX score before conditioning can predict OS and the incidence of grade ≥2 CRS in patients with relapsed and refractory B-cell tumors who receive CAR-T cell therapy.
Cytokine Release Syndrome/therapy* ; Immunotherapy, Adoptive/methods* ; Humans ; Lymphoma, B-Cell/therapy* ; Retrospective Studies ; Hematology ; China ; Receptors, Chimeric Antigen/blood* ; Predictive Value of Tests

Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.

Simultaneous management of intestinal mucosal barrier dysfunction and gut microbiota dysregulation represents a significant challenge in the treatment of inflammatory bowel disease (IBD). Herein, we report a novel system that integrates multi-enzyme mimicking cerium single-atom nanocatalysts (CeSACs) with Lactobacillus reuteri probiotics (LR@CeSACs) for multipronged management of IBD. In this system, CeSACs demonstrate robust multi-enzyme activities across a broad pH range, effectively scavenging elevated reactive oxygen species, downregulating pro-inflammatory cytokines, and suppressing the expression of fibrosis-related genes. Moreover, probiotics promote the targeting and retention of the CeSACs for sustained catalytic antioxidant therapy. In turn, the inflammation relief enabled by CeSACs promotes bacterial viability, allowing for the rapid reshaping of intestinal barrier function and the restoration of gut microbiota. Therefore, LR@CeSACs exhibit excellent catalytic anti-inflammatory and anti-fibrotic therapeutic effects, as well as a certain prophylactic effect, as demonstrated in several murine models.