Current Medical Science最新文献

Objective: Traditional Chinese medicine exhibits positive therapeutic effects as a primary or adjunctive treatment for diabetic nephropathy (DN). This study aimed to evaluate the impact and mechanism of action of Xiaoke decoction (XKD), a traditional Chinese medicine, on renal function in DN rats.

Methods: A rat model of DN was established, and the rats were divided into five groups (n = 7 per group): normal control group (NC), DN model group (DN), low-dose XKD treatment group (DN + XKD-L, 1.5 g/kg/d), high-dose XKD treatment group (DN + XKD-H, 6 g/kg/d), and cyclooxygenase-2 (COX-2) inhibitor (NS398) treatment group (DN + NS398, 8 mg/kg/d). Medications were administered via gavage for 12 consecutive weeks, while equal volumes of normal saline were given to the NC and DN groups. A glucometer was used to detect changes in blood glucose (BG). Enzyme-linked immunosorbent assay (ELISA) and an automatic biochemical analyzer were employed to measure levels of insulin, serum creatinine (Scr), blood urea nitrogen (BUN), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and 24-h urine protein quantity (UP/24 h) in rats. Renal tissue sections from different treatment groups were prepared, with tissue lesions examined via periodic acid-Schiff (PAS) and hematoxylin-eosin (HE) staining. Tissue inflammation and lipid deposition were evaluated using ELISA and Oil Red O staining. Immunohistochemistry and Western blotting were used to detect changes in the expression levels of COX-2 and low-density lipoprotein receptor (LDLr) in tissues, and to clarify the regulatory mechanism of XKD on renal function in DN rats.

Results: XKD, particularly at the high dose (XKD-H, 6 g/kg/d), significantly reduced BG, insulin levels, renal weight ratio, Scr, BUN, and UP/24 h in DN rats. DN rats showed significant renal lesions, and XKD gavage (especially XKD-H) markedly improved these pathological changes. In DN rats, XKD significantly decreased the protein expression levels of COX-2 and LDLr, downregulated the levels of inflammatory factors and lipid factors, reduced lipid deposition in renal tissues, and ameliorated structural abnormalities in glomeruli, basement membranes, and renal tubules.

Conclusions: XKD alleviates renal tissue damage by regulating the COX-2-mediated LDLr pathway, thereby reducing the release of inflammatory factors and lipid accumulation in DN rats and protecting renal function.

Objective: This study aimed to develop an effective predictive tool that combines radiomics and clinical information to predict the survival outcomes of patients with advanced non-small cell lung cancer (NSCLC) undergoing chemoimmunotherapy.

Methods: Data were collected from 201 patients with advanced NSCLC who received first-line chemoimmunotherapy across three institutions: those from Centers I & II (n = 164) were randomly split in a 7:3 ratio into training (n = 115) and validation (n = 49) cohorts, and those form Center III (n = 37) were designated as the external test cohort. The analysis was conducted using CT images and clinical data obtained before and after induction chemoimmunotherapy. We developed multiple intratumoral and peritumoral radiomics-based models, along with clinical prediction model that integrated patients' baseline clinicopathological characteristics with plasma biomarker profiles, to predict progression-free survival (PFS). Based on expectations derived from prior established models, a stepwise backward elimination approach was utilized to select candidate submodels for the combined model construction. This combined model was internally validated using time-dependent ROC curves in training and validation sets and externally validated in the external test set.

Results: The combined model was constructed by integrating four candidate sub-models (DeltaSub, Clinical, P4mm, and Habitat) selected through the stepwise regression analysis. The combined model demonstrated superior performance compared to conventional models that utilized only clinical features, as well as Classical-Pre, Classical-Post, delta intratumor feature-based, and peritumor feature-based models. The combined model demonstrated satisfactory predictive performance across all three datasets, achieving a C-index of 0.849 (95% CI: 0.812-0.885) in the training set, 0.744 (95% CI: 0.664-0.842) in the validation set, and 0.731 (95% CI: 0.639-0.824) in the external test set for PFS.

Conclusions: We developed a novel radiomic-clinical model to predict PFS for advanced NSCLC patients treated with first-line chemoimmunotherapy. This model enhanced survival assessment through comprehensive feature integration.

Objective: This study aimed to evaluate the potential of a collagen-coated, 3D-printed tracheal scaffold (3D-TechTra) integrated with human umbilical cord mesenchymal stem cells (hUC-MSCs) for tracheal tissue regeneration.

Methods: The thermoplastic polyurethane/polylactic acid (TPU/PLA) scaffold was engineered to optimize mechanical properties and biocompatibility, with the goal of mimicking the structural and tensile characteristics of native tracheal tissue. Subsequently, preclinical experiments were conducted using rabbit models: the performance of the collagen-coated TPU/PLA scaffold with hUC-MSCs was compared with that of uncoated scaffolds and collagen-only scaffolds. In vitro tests were also performed to assess the adhesion, proliferation, and differentiation of hUC-MSCs on the scaffold. For in vivo evaluation, multiple analytical methods were employed, including immunohistological analysis (to detect glycosaminoglycan deposition and extracellular matrix remodeling), radiographic and endoscopic evaluations (to assess tracheal contour and airway obstruction), and survival analysis (to monitor animal outcomes and systemic toxicity).

Results: In vitro, hUC-MSCs successfully adhered to and proliferated on the TPU/PLA scaffold, and differentiated into adipogenic, osteogenic, and chondrogenic lineages, which supported the potential for tissue-specific regeneration; in vivo, compared with uncoated or collagen-only scaffolds, the collagen-coated TPU/PLA scaffold integrated with hUC-MSCs exhibited enhanced integration with host tissues, superior biocompatibility, and reduced tracheal stenosis, while also preserving airway patency, alleviating inflammation, and facilitating epithelial regeneration, smooth muscle formation, and vascularization. Immunohistological analysis further revealed significant glycosaminoglycan deposition and extracellular matrix remodeling in the hUC-MSC-treated group, and radiographic and endoscopic evaluations confirmed preserved tracheal contour and reduced airway obstruction; additionally, survival analysis showed significantly improved outcomes in animals treated with the collagen-coated TPU/PLA scaffold containing hUC-MSCs, with no systemic toxicity observed.

Conclusions: This study demonstrated the synergistic potential of TPU/PLA scaffolds, collagen coatings, and hUC-MSCs, providing valuable evidence for advancing the application of these components in tracheal tissue engineering.

Objective: To develop a novel prognostic scoring system for severe cytokine release syndrome (CRS) in patients with B-cell acute lymphoblastic leukemia (B-ALL) treated with anti-CD19 chimeric antigen receptor (CAR)-T-cell therapy, aiming to optimize risk mitigation strategies and improve clinical management.

Methods: This single-center retrospective cohort study included 125 B-ALL patients who received anti-CD19 CAR-T-cell therapy from January 2017 to October 2023. These cases were selected from a cohort of over 500 treated patients on the basis of the availability of comprehensive baseline data, documented CRS grading, and at least 3 months of follow-up. Data on patient demographics, treatment history, laboratory parameters, CAR-T-cell characteristics, safety, and efficacy endpoints were collected. CRS severity was graded according to the 2019 ASTCT consensus criteria. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with CRS severity, and a prognostic model was constructed.

Results: The overall incidence of CRS was 67.2%, with 13.6% having grade ≥ 3 (severe) CRS. Higher baseline and post-lymphodepletion minimal residual disease (MRD) levels and neutropenia on day 7 post-infusion were significantly associated with severe CRS. Inflammatory markers (CRP, ferritin, and IL-6) and coagulation dysfunction (APTT) on day 7 post-infusion were also predictive of CRS severity. The prognostic model incorporating these factors demonstrated robust discriminatory ability, with an area under the ROC curve of 0.875.

Conclusion: This study developed a novel prognostic scoring system for severe CRS in Chinese B-ALL patients receiving anti-CD19 CAR-T-cell therapy. The model integrates clinical and laboratory parameters to facilitate early identification and management of severe CRS. Further validation in larger, prospective cohorts is warranted.

Artificial intelligence (AI) serves as a key technology in global industrial transformation and technological restructuring and as the core driver of the fourth industrial revolution. Currently, deep learning techniques, such as convolutional neural networks, enable intelligent information collection in fields such as tongue and pulse diagnosis owing to their robust feature-processing capabilities. Natural language processing models, including long short-term memory and transformers, have been applied to traditional Chinese medicine (TCM) for diagnosis, syndrome differentiation, and prescription generation. Traditional machine learning algorithms, such as neural networks, support vector machines, and random forests, are also widely used in TCM diagnosis and treatment because of their strong regression and classification performance on small structured datasets. Future research on AI in TCM diagnosis and treatment may emphasize building large-scale, high-quality TCM datasets with unified criteria based on syndrome elements; identifying algorithms suited to TCM theoretical data distributions; and leveraging AI multimodal fusion and ensemble learning techniques for diverse raw features, such as images, text, and manually processed structured data, to increase the clinical efficacy of TCM diagnosis and treatment.

Objective: Conjunctival vascularization and fibroblasts are important factors leading to filtering bleb scarring after glaucoma filtering surgery. Previous studies have shown that nintedanib can inhibit the transformation of conjunctival fibroblasts into myofibroblasts, alleviating scar formation. This study aimed to investigate the effect of nintedanib on vascular endothelial growth factor (VEGF)-induced neovascularization of human conjunctival vascular endothelial cells and to reveal the molecular mechanisms involved.

Methods: Primary human conjunctival vascular endothelial cells were cultured with VEGF alone or in combination with nintedanib, and cell proliferation and migration were measured via cell counting kit-8 and scratch assays, respectively. The effect of nintedanib on human conjunctival vascular endothelial cell tube formation was also assayed. The phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) were measured via Western blotting.

Results: VEGF (120 ng/mL) significantly promoted the proliferation of human conjunctival vascular endothelial cells. Nintedanib inhibited the VEGF-induced proliferation of these cells while also suppressing cell migration (P < 0.0001) and vascularization (P < 0.01). Furthermore, nintedanib reduced ERK1/2 (P < 0.01) and JNK phosphorylation (P < 0.001).

Conclusion: Our study provides new evidence that nintedanib inhibits the proliferation, migration, and neovascularization of human conjunctival vascular endothelial cells and downregulates the expression of p-ERK and p-JNK in the MAPK pathway.

Objective: The aim of this study was to explore the influence of working length (determined by the screw position) on the stiffness and interfragmentary strain (IFS) of femoral locking compression plate (LCP) external fixators for lower tibial fractures under full weight-bearing conditions, with the goal of providing a reference basis for clinical applications.

Methods: Finite element analysis software was used to construct a model of a lower tibial fracture with external femoral LCP fixation. The models were divided into four groups according to the different working lengths (external femoral locking plate fixation 1 [EF1], EF2, EF3, and EF4). Stress distribution clouds, fracture end displacements, stiffness and IFS were tested for each model group at different loads.

Results: Compared with those in the EF1 group, the stiffnesses in the EF2, EF3, and EF4 groups decreased by 28%, 31%, and 37%, respectively, under axial compression loading. Compared with those in the EF1 group, the stiffnesses in the EF2, EF3, and EF4 groups decreased by 19%, 33%, and 35%, respectively, under axial torsion loading. Compared with those in the EF1 group, the stiffnesses in the EF2, EF3, and EF4 groups decreased by 32%, 33%, and 35%, respectively, under a three-point bending load. The IFS of the four finite element models increased with the working length of the plate, with EF1 (76%) < EF2 (107%) < EF3 (110%) < EF4 (122%). Finite element analysis revealed that under full weight-bearing conditions, the structural stiffness of the femoral LCP external fixator decreased with increasing working length, leading to an increase in the IFS, which resulted in an IFS that exceeded the ideal range required for secondary healing.

Conclusion: For unstable lower tibial fractures, screws in the femoral LCP external fixator should be placed as close to the fracture end as possible to increase stability and promote fracture healing.

Objective: This study investigates the role of miR-144-5p in doxorubicin (DOX)-induced heart failure and explores its potential mechanisms by targeting ACSM1 and inhibiting lipid peroxidation.

Methods: Bioinformatics analysis was performed using the gene expression omnibus dataset GSE136547 to identify differentially expressed miRNAs in heart failure. DOX-induced in vitro and in vivo heart failure models were used to study the effects of miR-144-5p on cardiomyocyte viability, apoptosis, and lipid peroxidation. The targeting relationship between miR-144-5p and ACSM1 was verified using dual-luciferase reporter assays. Cardiac function was assessed by echocardiography, and biochemical markers of heart failure were measured using ELISA. The GO and KEGG enrichment analyses of ACSM1 were performed via the bioinformatic tools GeneMANIA and STRING.

Results: miR-144-5p was significantly upregulated in DOX-treated cardiomyocytes and mouse hearts. Inhibition of miR-144-5p attenuated DOX-induced cardiomyocyte apoptosis, lipid peroxidation, and cardiac dysfunction. ACSM1 was identified as a direct target of miR-144-5p, and its expression was downregulated by DOX. Silencing ACSM1 abolished the protective effects of the miR-144-5p inhibitor on the viability, apoptosis, and lipid peroxidation of cardiomyocytes. Furthermore, miR-144-5p inhibition improved cardiac function in DOX-treated mice, as evidenced by reduced left ventricular dysfunction and decreased levels of heart failure markers (BNP, LDH, Ang II, and ALD).

Conclusions: Our findings demonstrate that inhibiting miR-144-5p alleviates DOX-induced heart failure by targeting ACSM1 and suppressing lipid peroxidation. The miR-144-5p/ACSM1 axis may represent a novel therapeutic target for heart failure. Future studies should focus on further elucidating the mechanisms underlying this axis and exploring its potential clinical applications.

Objective: To investigate the curative effect of the Qifangfeixian granule on interstitial lung disease (ILD).

Methods: This study combined animal experiments and clinical trials. Pathological changes in bleomycin (BLM)-induced pulmonary fibrosis in mice were assessed using hematoxylin and eosin (H&E), Masson, and Sirius Red staining. In the clinical study, 40 ILD patients were enrolled, with 20 in the control group and 20 in the treatment group. The treatment group received Qifangfeixian granules in addition to standard therapy for 12 weeks. Pulmonary function parameters, including forced vital capacity (FVC, L), FVC_pred%, diffusing capacity for carbon monoxide (DLCO, mmol/min/kPa), and DLCO_pred%, were measured before and after treatment.

Results: Compared with those of the control group, the inflammatory infiltration and collagen fibres in the BLM group were significantly increased, and the inflammatory infiltration and collagen fibres in the BLM group were significantly reduced after Qifangfeixian granule treatment. Compared with those in the control group, the lung function parameters in the treatment group were significantly improved. Specifically, the FVC increased by +0.10 ± 0.18 L in the treatment group, whereas the control group showed a decrease of -0.05 ± 0.21 L (P = 0.008). Additionally, FVC_pred% was improved significantly in the treatment group (+2.6% ± 5.3%) compared with the control group (-2.0% ± 6.7%, P = 0.009).

Conclusion: Qifangfeixian granules can improve not only the pulmonary fibrosis of BLM-induced model mice but also the pulmonary function of patients with ILD in practice, and their clinical efficacy is accurate.

Objective: Although immune dysregulation is implicated in the pathogenesis of endometriosis (EMs), the specific role of prostate transmembrane protein androgen induced 1 (PMEPA1) in modulating the function of regulatory T cells (Tregs) remains inadequately understood. This study aimed to elucidate the regulatory mechanisms by which PMEPA1 influences the activity of Tregs, thereby facilitating the invasion of endometrial stromal cells (ESCs).

Methods: Single-cell RNA sequencing (scRNA-seq) was performed on matched ectopic ovarian lesions and eutopic endometria from 3 patients. Clinical specimens from patients with EMs and control subjects were examined for PMEPA1 expression. Primary human Tregs isolated from peripheral blood mononuclear cells were subjected to PMEPA1 overexpression (via plasmid) or knockdown (via siRNA). Modulation of the PI3K pathway was conducted via the activator 740Y-P or the inhibitor LY294002. The secretion of IL-10 and TGF-β by Tregs was quantified using an enzyme-linked immunosorbent assay. Ectopic ESCs cocultured with modified Tregs were assessed for their proliferation, migration, and invasion capabilities.

Results: scRNA-seq data revealed significant upregulation of PMEPA1 in Tregs from ectopic ovarian lesions compared with paired eutopic endometria. PMEPA1 expression was increased in the ectopic lesions and peritoneal fluid mononuclear cells of patients with EMs. Tregs overexpressing PMEPA1 demonstrated reduced secretion of IL-10 and TGF-β but exhibited hyperactivation of the PI3K/AKT signaling pathway. Treatment with LY294002 ameliorated the impairment in cytokine secretion. Coculture experiments with Tregs expressing high levels of PMEPA1 resulted in increased invasion, migration, and proliferation of ESCs.

Conclusion: PMEPA1 impairs Treg-mediated immunosuppression by hyperactivating the PI3K/AKT pathway, thereby facilitating the invasiveness of ESCs in EMs.