Objective To explore the functional impact of A-to-I editing in the seed region of miR-411 during post-myocardial infarction (MI) fibrosis and elucidate its therapeutic potential. Methods Integrating GEO database with myocardial RNA-seq data from MI mouse models, we identified dynamic A-to-I RNA editing in small noncoding RNAs across MI progression (1 day to 8 weeks post-MI). Four miRNAs exhibited differential editing rates between MI and controls, with miR-411 showing progressive editing enhancement at seed region position 4 (P＜0.01). This editing event was validated in both murine MI models and human heart failure specimens. Results The A-to-I editing ratio change of the 4th nucleotide in the seed region of miR-411 mainly occurs in cardiac fibroblasts rather than cardiomyocytes, and the editing at this site depends on ADAR2 rather than ADAR1. Edited miR-411 (ED-miR-411) diverged from wild-type miR-411 (WT-miR-411) in suppressing collagen-related pathways (extracellular matrix [ECM]-receptor interaction, collagen-containing ECM, ECM organization; P＜0.01) in cardiac fibroblasts. Mechanistically, dual-luciferase assays confirmed ED-miR-411 directly targeted the 3′UTR and suppressed expression of type Ⅱ transforming growth factor (TGF)-beta receptor (TGFBR2) and CD44, which were key drivers of TGF-β-mediated fibroblast activation. ED-miR-411 overexpression blunted TGF-β-induced collagen synthesis and myofibroblast proliferation (P＜0.05). In vivo, intramyocardial delivery of ED-miR-411 mimics at 1 week post-MI reduced fibrosis by 40% and improved ejection fraction by 15% (P＜0.01 vs controls), whereas WT-miR-411 showed no therapeutic effect. Conclusions A-to-I editing of miR-411 emerges as an endogenous anti-fibrotic mechanism by repressing TGFBR2 and CD44, thereby disrupting TGF-β signaling and ECM dysregulation. Our findings highlight ED-miR-411 as a novel RNA-based therapeutic candidate to mitigate post-infarction cardiac remodeling.

The repair of bone defects is heavily influenced by the dynamic osteogenic microenvironment. Static scaffolds constructed by traditional 3D printing technology cannot simulate the dynamic nature of the microenvironment during bone defect repair due to the fixed structure, uncontrollable release of active factors, and difficult regeneration of blood vessels, among other factors. Breaking through the limitations of these static scaffolds and realizing the intelligent and dynamic regulation of the osteogenic microenvironment is a key scientific issue in the field of bone tissue engineering. 4D printing technology combines the dynamic responsiveness of bone restoration materials with the concept of intelligent design to regulate the micro and macro structure of scaffolds. This technology provides a new method for bone tissue engineering by responding to endogenous and exogenous stimuli and creating a better osteogenic microenvironment through functionalized design, including drug delivery and antibacterial function. However, this technology currently suffers from challenges related to dynamic response material design, insufficient precision of printing technology, and mismatches between multi-stimulus response systems, metabolic rhythms of bone tissue, and functionalized composite scaffolds. Future research should focus on the development of smart response materials with excellent dynamic responses and bioactivity, the creation of new printing technologies, and the design of personalized and precise bone repair solutions. The aim of this paper is to review the current research status of 4D printing for bone tissue engineering in terms of material types, response mechanisms, and applications to provide a theoretical basis for the development and clinical application of functional bone repair materials in the future.

Histopathological examination is currently the gold standard for the diagnosis of metabolic associated fatty liver disease （MAFLD）； however， due to its invasiveness， high risks， and low feasibility， application of noninvasive indicators in the staging and classification of MAFLD has become a research hotspot. This article systematically reviews the efficacy of dynamic changes in various noninvasive markers in reflecting histological changes and clinical outcome events in MAFLD patients， in order to provide theoretical support for dynamic monitoring and individualized management of the disease.

Gastric ulcer （GU） is a high-incidence digestive system disease characterized pathologically by disruption of gastric mucosal integrity， with clinical features including a prolonged course and periodic recurrence. Modern medicine attributes its pathogenesis to the dynamic imbalance between aggressive and defensive factors，while traditional Chinese medicine （TCM） posits its development as closely linked to spleen deficiency. Current therapies combining acid suppressants and antibiotics face challenges such as high recurrence rates，poor mucosal healing，and adverse drug reactions. Long-term use may induce metabolic disturbances like hypergastrinemia and reduced intestinal microbiota diversity. Therefore，exploring safer and longer-lasting therapeutic strategies has become a critical focus. TCM has extensive clinical experience and unique advantages in GU prevention and treatment. Studies demonstrate that the classic formula Shenling Baizhu San exhibits therapeutic properties of "invigorating spleen and tonifying Qi to restore physiological balance and eliminating dampness and regulating middle energizer to unblock Qi movement"， enabling a holistic approach targeting both symptoms and root causes in GU with spleen deficiency as the core pathology by suppressing aggressive factors and strengthening defensive factors. Experimental research reveals its mechanisms involve enhancing the physicochemical barrier of the mucus layer，repairing epithelial barriers and microcirculation，modulating gastric acid secretion and gastrointestinal motility，and regulating microecological barriers and mucosal immunity. Clinical evidence confirms its synergistic effects in promoting ulcer healing，improving Helicobacter pylori eradication rates，and reducing recurrence risks. This review examined the etiology and pathogenesis of GU and systematically evaluated Shenling Baizhu San from three perspectives-clinical application，pharmacological effects， and experimental research-to provide insights for optimizing integrated traditional Chinese and Western medicine protocols and expanding its clinical applications.

Objective To investigate the changes and diagnostic value of serum hypoxia inducible factor 1 subunit alpha(HIF-1α)and Toll-like receptor 4(TLR4)levels in patients with chronic obstructive pulmonary disease(COPD)complicated with pulmonary Aspergillosis infection.Methods A total of 240 COPD patients who visited Xi'an Qinhuang Hospital(hereinafter referred to as the hospital)from December 2020 to Decem-ber 2023 were selected as the study subjects in the study,and another 218 volunteers who underwent physical examinations at the hospital were selected as the control group.The COPD patients were separated into an in-fected group(124 cases)and an uninfected group(116 cases)based on whether they had pulmonary Aspergil-losis infection.Enzyme-linked immunosorbent assay was applied to detect the levels of HIF-1α and TLR4 in patients.Fully automated biochemical analyzer was applied to detect lactate dehydrogenase(LDH)and albu-min(ALB)levels.Multivariate Logistic regression was applied to analyze the influencing factors of infection in COPD patients.Pearson correlation was applied to analyze the correlation between HIF-1α and TLR4 levels in the infected group.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic val-ue of HIF-1α and TLR4 levels for the occurrence of infection in COPD patients.Results Compared with the control group,the COPD group showed an increase in HIF-1α and TLR4 levels(P＜0.05).Compared with the uninfected group,the proportion of dyspnea,antibiotics＞3 types,the duration of antibiotic use ≥ 14 days,mechanical ventilation procedures,the longer glucocorticosteroid(GC)use time,and levels of LDH,HIF-1α,TLR4 in the infected group were higher(P＜0.05),while the level of ALB was lower(P＜0.05).The types of antibiotics＞3 types,the duration of antibiotic use ≥ 14 days,the duration of GC use,and elevat-ed levels of LDH,HIF-1α,and TLR4 were independent risk factors for infection in COPD patients(P＜0.05),while elevated level of ALB was an independent protective factor for infection in COPD patients(P＜0.05).The levels of HIF-1α and TLR4 in the infected group were positively correlated(r=0.453,P＜0.001).The area under the curve(AUC)of HIF-1α and TLR4 in diagnosing infection in COPD patients alone was 0.816 and 0.813,and the AUC of their combined diagnosis was 0.930,which was better than their indi-vidual diagnoses(Zcombination-HIF-1α=4.923,Z combination-TLR4=5.192,P＜0.001,P＜0.001).Conclusion The levels of HIF-1α and TLR4 increase in COPD patients,and further increase after infection with pulmonary Aspergil-lus.They are independent risk factors for infection in patients,and the two are positively correlated.The combined di-agnosis of pulmonary aspergillosis has certain value and provides a theoretical basis for clinical diagnosis.

Objective:To observe the clinical efficacy of posterior vertebral column resection (PVCR) combined with double row nanomimetic bone column implantation and internal fixation in the treatment of stage Ⅲ Kümmell's disease plus kyphosis.Methods:A retrospective study was conducted to analyze the clinical data of the 12 patients with stage Ⅲ Kümmell's disease plus kyphosis who had been admitted to Department of Spine Surgery, Zhengzhou Orthopedic Hospital from March 2017 to September 2023. There were 2 males and 10 females, with an age of (63.4±6.4) years and a disease duration of (8.6±5.1) months. The injured segment was T 11 in 1 patient, T 12 in 5 ones, and L 1 in 6 ones. The preoperative spinal nerve injury was graded according to American Spinal Injury Association (ASIA): grade D in 5 cases and grade E in 7 cases. All the patients were treated with PVCR combined with double row nanomimetic bone column implantation and internal fixation. The operation time, intraoperative blood loss, shortening rate of the osteotomy area, complications during follow-up, and spinal nerve recovery at the last follow-up were recorded. The visual analogue scale (VAS) pain scores, Oswestry Disability Indexes (ODIs), and local kyphosis Cobb angles were compared between pre-surgery, 2 weeks after surgery, and the last follow-up. Results:Incisions in all the 12 patients healed at the primary stage. Their operation duration was (268.4±26.5) min, intraoperative blood loss (994.9±180.4) mL, shortening rate of the osteotomy area 3.94%±7.58%, and follow-up duration (24.1±13.5) months. At 2 weeks after surgery and the last follow-up, the VAS pain scores [(3.08±0.79) points and (1.17±0.58) points] and ODIs (27.59%±6.10% and 16.67%±2.22%) were significantly lower than those before surgery [(8.08±0.79) points and 73.14%±5.64%], and the values at the last follow-up were further significantly lower than those at 2 weeks after surgery (all P<0.05). There was no statistically significant difference in the Cobb angle at the last follow-up (5.29°±1.30°) compared with 2 weeks after surgery (4.74°±1.31°) ( P>0.05), but there was a statistically significant difference compared with the preoperative value (49.41°±4.40°) ( P<0.05). At the last follow-up, the ASIA grading in all the 12 patients recovered to grade E, with good bone healing at the fixation segment. No screw loosening or fracture was found. Two patients had a biomimetic bone column sinking of 3.5 and 4.0 mm, respectively, but their Marchi's grading was still 0. During the follow-up period, one patient developed proximal junctional kyphosis, and one patient developed an osteoporotic fracture of the proximal vertebral body at the fixed level. Conclusions:In the treatment of stage Ⅲ Kümmell's disease plus kyphosis, PVCR combined with double row nanomimetic bone column implantation and internal fixation can significantly correct the kyphosis and improve clinical symptoms, leading to good clinical efficacy.

Pulmonary siderosis caused by iron and its compound dust is prone to misdiagnosis and underdiagnosis due to its insidious exposure pathways and non-specific imaging manifestations. This study analyzes the occupational histories and clinical data of six patients with occupational pulmonary siderosis diagnosed at Qingdao Central Hospital between January 2017 and December 2023, summarizes its characteristics, and evaluates the value of AI-assisted diagnosis. All six patients were male, with five being welders. The median dust exposure duration was 9.4 years, and the median latency period was 8.4 years. The main symptoms were chest tightness, cough, and shortness of breath. High-kilovolt chest radiographs were negative in four cases and showed thickened bronchovascular markings in two cases. High-resolution computed tomography (HRCT) revealed centrilobular nodules and tree-in-bud opacities in all cases. Pulmonary siderosis caused by iron and its compound dust is characterized by mild symptoms and a favorable prognosis. Comprehensive assessment and HRCT are crucial for early diagnosis. The development of AI models could enhance diagnostic recognition efficiency and promote precision diagnosis in the future.

Objective:To investigate the efficacy of a decellularized extracellular matrix (dECM)-quaternized chitosan (QCS)-gelatin (Gel) composite scaffold loaded with growth factors in repairing diabetic foot wounds in a rat model.Methods:A dECM-QCS-Gel composite scaffold (referred to as GDQ scaffold) was fabricated using a 3D bioprinter. Forty 8-week-old male Sprague-Dawley (SD) rats were selected to establish a diabetic foot wound model with a diameter of approximately 1 cm. Based on the treatment methods for diabetic foot wounds, the rats were divided into five groups: Control group (no treatment), Exosome group (wound covered with exosome suspension), Exosome+GDQ group (wound covered with GDQ scaffold loaded with exosome suspension), GDQ group (wound covered with GDQ scaffold alone), and Growth factor+GDQ group (wound covered with GDQ scaffold loaded with recombinant human basic fibroblast growth factor suspension). The wound healing rate was measured. Histological analysis was performed by HE staining and Masson staining. ELISA kits were used to determine the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10 in wound tissues from each group. Protein expression levels of MIP-1 and MIP-2 genes were also assessed.Results:The wound healing rate of the growth factor+GDQ group on the 21st d was 94.89%±1.21%, which was higher than that of the exosome+GDQ group ( P<0.05). With increasing repair time, the expression levels of TNF-α, IL-1β and IL-6 in each group all decreased, while IL-10 increased in all groups ( P<0.05). Among them, the exosome+GDQ group (TNF-α: 46.54±1.26 pg/ml, IL-1β: 225.79±7.29 pg/ml, IL-6: 142.81±4.02 pg/ml and IL-10: 117.36±0.95 pg/ml, P<0.001) and the growth factor+GDQ group (TNF-α : 40.01±1.64 pg/ml, IL-1β: 209.15±2.98 pg/ml, IL-6: 138.50±2.61 pg/ml and IL-10: 127.66±1.23 pg/ml, P<0.05); The levels of TNF-α and IL-1β in the exosome+GDQ group were both lower than those in the exosome+GDQ group ( P<0.05), and IL-10 was higher than that in the exosome+GDQ group ( P<0.05). On the 7th d the control group showed the highest expression levels of MIP-1α and MIP-2. All other groups had lower levels, with the growth factor+GDQ group showing the lowest among them. On the 21st d, the inflammatory protein expression in the growth factor+GDQ group had further decreased and remained lower than in all other experimental groups. Conclusions:The GDQ composite scaffold, when combined with bioactive factors, can synergistically reduce inflammation in diabetic foot wounds and promote wound healing. The scaffold loaded with basic fibroblast growth factor demonstrated superior therapeutic efficacy compared to the scaffold loaded with exosomes.

Colorectal cancer is a common malignant tumor of the digestive tract. In recent years, with the advancement of surgical concepts and techniques, and remarkable achievements in basic value research and clinical transformation, the clinical treatment of colorectal cancer has made considerable progress. With the deepening application of the "precision medicine" concept, the transformation of the comprehensive diagnostic and therapeutic system for colorectal cancer is not only manifested in core aspects such as the optimization of preoperative neoadjuvant therapy regimens, precise selection of chemotherapy and targeted drugs, and intelligent upgrades of surgical decision-making systems, but also extends to the construction of prognostic prediction models and innovations in immunotherapy strategies. This marks the official entry of colorectal cancer diagnosis and treatment into the precision medicine era. Although surgery remains the cornerstone of colorectal cancer treatment, its potential limitations cannot be overlooked while pursuing therapeutic efficacy. With the continuous development of precision medicine theory and clinical practice, the concept of precision surgery has been integrated into various stages, including preoperative evaluation and adjuvant therapy. It provides critical support for determining surgical timing, formulating surgical plans, and optimizing intraoperative procedures, thereby reshaping the clinical paradigm of colorectal cancer management. Consequently, clinical surgeons must proactively acquire precision medicine expertise and actively engage in related research and clinical practice. The authors synthesize recent global research progress in precision diagnosis and treatment of colorectal cancer through literature review, combined with their team's clinical experience to forecast future developmental trajectories, aiming to provide valuable insights and practical references for surgical colleagues in this evolving field.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.