BACKGROUND:It has been confirmed that the mixing of decellularized matrix and polymer electrospinning can not only improve the structural properties of fibers,but also preserve the biological decellularized of decellularized matrix.However,there is no relevant report on the preparation of skin tissue engineering scaffolds by electrospinning polyurethane and decellularized skin matrix. OBJECTIVE:To investigate the reparative effect of a decellularized skin matrix/polyurethane blended fibrous scaffold on rat skin defects. METHODS:Polyurethane electrospun fibrous scaffold and decellularized skin matrix/polyurethane blended fibrous scaffold were fabricated using the electrospinning technique.The fiber structure was observed under scanning electron microscope.Rat adipose mesenchymal stem cells were inoculated on two kinds of scaffolds respectively.The morphology of the scaffolds was observed under scanning electron microscope.Three full-thickness skin defects of 1 cm×1 cm were fabricated on the back of 10 SD rats.Polyurethane electrospun fibrous scaffolds(control group)and decellularized skin matrix/polyurethane blended fibrous scaffolds(experimental group)were implanted in two of the defects,and no material was implanted in the remaining defects(blank control group).The skin wound healing was observed at 1,2,and 3 weeks after operation.At 3 weeks after implantation,the wound was stained with hematoxylin and eosin and the scar area was calculated. RESULTS AND CONCLUSION:(1)Under scanning electron microscope,the two kinds of electrospun fibers were reticulated,and the rat adipose mesenchymal stem cells attached to the fibers on the two kinds of scaffolds,and the adhesion was good.(2)With the extension of the postoperative time,the skin wounds of each group gradually healed.By week 3 after the operation,the skin wounds of the experimental group and the control group were basically healed,and small ulcers could be seen on the wounds of the blank control group.Hematoxylin-eosin staining of skin wounds showed that the epidermal coverage of the wound was basically complete in the control group and the experimental group,and fibroblast growth and inflammatory cell infiltration could be seen in the dermis.In addition,the collagen fibers of the wound in the experimental group were abundant and arranged in a regular order,basically parallel to the epidermal surface.The wound epidermis of blank control group was still defective.The scar area of the experimental group was smaller than that of the other two groups(P<0.05,P<0.01).(3)These results indicate that the decellularized skin matrix/polyurethane blended fibrous scaffold can effectively repair full-thickness skin defects and improve scar formation in rats.

Objective:To explore the application value of machine learning algorithms in constructing a predictive model for cardiovascular toxicity in breast cancer patients receiving anthracycline-based chemotherapy.Methods:This study was a retrospective cohort study. The female patients with breast cancer who received anthracyclines in the Affiliated Cancer Hospital of Xinjiang Medical University from January 2020 to December 2023 were enrolled. The endpoint event was abnormal electrocardiogram (ECG). According to whether the patients had ECG abnormalities during chemotherapy, they were divided into the ECG abnormal group and the ECG normal group. The dataset was divided into the training set and the test set at a ratio of 8∶2, and logistic regression, random forest, extreme gradient boosting (XGBoost), support vector machine (SVM) and multilayer perceptron (MLP) were used to construct a risk prediction model for cardiovascular toxicity in breast cancer patients, and the receiver operating characteristic curve, calibration curve and clinical decision curve were used to evaluate the model.Results:A total of 731 female patients with breast cancer, aged (51.6±9.4) years, were enrolled. The follow-up time was (130.3±37.1) days. There were 333 cases in the ECG abnormal group and 398 cases in the ECG normal group. Seven factors influencing cardiovascular toxicity were identified, including age, menstrual history, diabetes, combination therapy with trastuzumab, combination therapy with dexrazoxane, creatine kinase isoenzymes, and α-hydroxybutyrate dehydrogenase. In the training set, the area under the curve ( AUC) for the logistic regression, random forest, XGBoost, SVM, and MLP models was 0.712, 0.863, 0.774, 0.813, and 0.733, respectively. In the test set, the AUC was 0.671, 0.778, 0.746, 0.771, and 0.705, respectively. Calibration curves and clinical decision curves showed that the random forest model performed the best. Conclusion:Models constructed with machine learning algorithms show promise in predicting cardiovascular toxicity in breast cancer patients receiving anthracycline-based chemotherapy, with the random forest prediction model performing the best.

Objective:To discuss the effects of microRNA(miR)-199a-5p overexpression on cell migration and apoptosis in the glioblastoma U251 cells,and to clarify the targeting regulatory relationship between miR-199a-5p and caveolin-1(CAV-1).Methods:The glioblastoma U251 cells and oligodendroglioma Hs683 cells were cultured in vitro.Western blotting method was used to detect the expression levels of CAV-1 protein in 2 kinds of cells;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of miR-199a-5p in 2 kinds of cells.The U251 cells were divided into blank group(non-transfection),mimics NC group(transfected with empty vector),and miR-199a-5p mimics group(transfected with miR-199a-5p mimics).The Hs683 cells were divided into blank group(no transfection),inhibitor NC group(transfected with empty vector),and miR-199a-5p inhibitor group(transfected with miR-199a-5p inhibitor).RT-qPCR method was used to detect the transfection efficiency of the cells in various groups;Western blotting method was used to detect the expression levels of CAV-1 protein in the cells in various groups.TargetScan database was used to predict the binding sites between miR-199a-5p and CAV-1 in the 3'untrans lated region(3'UTR);psiCHECKTM-2-CAV-1-WT and psiCHECKTM-2-CAV-1-Mut were co-transfected with miR-199a-5p mimics and mimics NC into the U251 cells,respectively,forming psiCHECKTM-2-CAV-1-WT+mimics NC group,psiCHECKTM-2-CAV-1-WT+miR-199a-5p mimics group,psiCHECKTM-2-CAV-1-Mut+mimics NC group,and psiCHECKTM-2-CAV1-Mut+miR-199a-5p mimics group;dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-199a-5p and CAV-1;cell scratch assay was used to detect the scratch healing rates of the U251 cells in various groups;flow cytometry was used to detect the apoptotic rates of the U251 cells in various groups.Results:The Western blotting and RT-qPCR results showed that compared with Hs683 cells,the expression level of CAV-1 protein in the U251 cells was significantly decreased(P<0.05);compared with U251 cells,the expression level of miR-199a-5p in the Hs683 cells was significantly increased(P<0.01).Compared with blank group and mimics NC group,the expression level of miR-199a-5p in the U251 cells in miR-199a-5p mimics group was significantly increased(P<0.01),the expression level of CAV-1 protein in the U251 cells in miR-199a-5p mimics group was significantly decreased(P<0.05).Compared with blank group,the expression levels of miR-199a-5p in the Hs683 cells in inhibitor NC group and miR-199a-5p inhibitor group were significantly decreased(P<0.01).No significant differences were observed in the expression levels of CAV-1 protein in the Hs683 cells among various groups(P>0.05).The dual-luciferase reporter gene assay results showed that psiCHECKTM-2-CAV-1-wild type(WT)and psiCHECKTM-2-CAV-1-mutant(Mut)expression vectors were successfully constructed;compared with psiCHECKTM-2-CAV-1-WT-mimics NC group,the relative luciferase activity of WT CAV-1 in the U251 cells in psiCHECKTM-2-CAV-1-WT-miR-199a-5p mimics group was significantly decreased(P<0.01).The cell scratch assay results showed that at 12,24,and 48 h after transfection,compared with blank group,the scratch healing rate of the U251 cells in miR-199a-5p mimics group was significantly decreased(P<0.05 or P<0.01).The flow cytometry results showed that compared with blank group and mimics NC group,the apoptotic rate of the U251 cells in miR-199a-5p mimics group was significantly increased(P<0.01).Conclusion:Transfection of mature miR-199a-5p mimics into the glioblastoma U251 cells can reduce the expression of CAV-1 protein,inhibit glioma cell migration,promote apoptosis,and suppress tumorigenesis and development.The targeting relationship between miR-199a-5p and CAV-1 may represent a potential mechanism for glioma development and could serve as a potential diagnostic and therapeutic target for glioma.

Abdominal aortic aneurysm(AAA) is a severe disease characterized by the localized dilation of the abdominal aorta, with an increasing global incidence and a high mortality rate once the aneurysm ruptures. The pathogenesis of AAA is complex, and current non-surgical treatments have limited efficacy, necessitating the exploration of new therapeutic targets. Ferroptosis is a form of programmed cell death that relies on iron and is non-apoptotic, primarily characterized by the uncontrolled peroxidation of lipids in the cell membrane. Studies have found that ferroptosis is significantly upregulated in AAA through differential gene expression analysis of AAA tissues, predominantly occurring in vascular smooth muscle cells(VSMCs). Ferroptosis accelerates the progression of AAA by promoting phenotypic switching and cell death of VSMCs and inducing vascular calcification. Additionally, ferroptosis exacerbates AAA by increasing reactive oxygen species production, altering the intracellular oxidative stress balance, and inducing inflammatory responses. Inhibiting ferroptosis-related pathways, such as by overexpressing glutathione peroxidase 4(GPX4) or using ferroptosis inhibitors, has been shown to effectively slow the progression of AAA in mice. This review summarizes the mechanisms by which ferroptosis contributes to AAA progression and its potential therapeutic targets, aiming to provide new insights for the prevention and treatment of AAA.

Lower extremity atherosclerotic occlusive disease(ASO)is a common peripheral arterial disease with a steadily increasing global incidence.As a key pathological change in ASO,arterial calcification plays a crucial role in its pathogenesis,diagnostic evaluation,treatment strategies,and prognosis.In recent years,with the continuous advancement of imaging and biomarker detection technologies,quantitative assessment and clinical research on arterial calcification have deepened,providing new perspectives for individualized diagnosis and treatment.This review begins with the pathophysiological mechanisms of arterial calcification and systematically summarizes current detection methods,its impact on endovascular therapy,and recent progress in prognostic evaluation,aiming to provide theoretical support and practical reference for precision treatment of ASO patients.

The glycocalyx(GC)constitutes an essential component of the vascular endothelial cell surface,facilitating vasodilation,regulating vascular permeability,modulating leukocyte adhesion,and exerting anti-inflammatory effects.Under the influence of diverse pathological factors,GC degradation is triggered,and endothelial cell dysfunction is mediated through various mechanisms such as oxidative stress,exacerbated inflammatory responses,abnormal mechanical transduction,and augmented white blood cell adhesion.Furthermore,dysfunctional endothelial cells can also lead to an intensification of GC degradation.In this paper,the potential correlation between GC degradation and endothelial cell dysfunction,along with related drug intervention studies,were summarized and analyzed,which provided ideas for subsequent drug research and pave the way for improving clinical efficacy of related diseases.

Traditional Chinese medicine(TCM) processing is a specialized pharmaceutical technique with the primary objective of reducing the toxicity of medicinal substances. Euphorbia pekinensis, E. ebracteolata, and E. fischeriana, all belonging to Euphorbiaceae, are classified as drastic purgative herbs, traditionally used for eliminating retained water, reducing swelling, resolving toxicity, and dispersing masses. However, these herbs are also associated with adverse effects such as abdominal pain and diarrhea. Accordingly, they are commonly processed with vinegar, milk, or Terminalia chebula decoction to reduce the toxicity. This review summarizes the chemical constituents, pharmacological activities, historical evolution of processing methods, and detoxification mechanisms of the three toxic Euphorbia species. The primary toxic constituents are terpenoids. Specifically, E. ebracteolata and E. fischeriana are rich in diterpenoids, while E. pekinensis contains diterpenoids, triterpenoids, and sesquiterpenoids. Studies have shown that vinegar processing promotes structural transformations of diterpenoids, including ether bond hydrolysis, lactone ring opening, esterification, oxidation, and epoxide ring cleavage, thereby reducing the content and toxicity of these compounds. Milk processing facilitates the dissolution of toxic components into the residual liquid of excipients, leading to decreases in their concentrations in the final decoction pieces. Processing with T. chebula decoction raises the levels of tannin-derived phenolic acids, which antagonize the adverse effects of the intestine. These findings reveal a shared detoxification pattern among the three toxic herbs. Accordingly, this review proposes the concept of a shared detoxification mechanism for toxic herbs belonging to the same family or genus. That is, toxic herbs belonging to the same taxon often exhibit similar toxicological profiles and can undergo detoxification through the same processing methods, reflecting common underlying mechanisms. Investigating such shared mechanisms across multiple species of the same genus offers a promising research strategy. Ultimately, the research into processing-induced detoxification mechanisms provides both theoretical and practical support for ensuring the safety of toxic TCM.
Euphorbia/classification* ; Drugs, Chinese Herbal/metabolism* ; Humans ; Animals ; Inactivation, Metabolic ; Medicine, Chinese Traditional

OBJECTIVES: To explore the efficacy and adverse reactions of nusinersen combined with risdiplam in the treatment of spinal muscular atrophy (SMA). METHODS: A retrospective analysis was conducted on the clinical data of 10 pediatric SMA patients treated with nusinersen combined with risdiplam at the Children's Medical Center of Xiangya Hospital, Central South University. RESULTS: Among the 10 SMA patients, there were 4 with type I, 4 with type II, and 2 with type III. Nine patients initially received nusinersen monotherapy, while 1 patient received nusinersen combined with risdiplam. The median duration of combination therapy with nusinersen and risdiplam for the 10 patients was 10.5 months (range: 0.5-20.0 months), with 6 patients undergoing combination therapy for more than 6 months, showing improvements in motor and/or respiratory function. The remaining 4 patients had combination treatment durations of 0.5, 1.0, 1.3, and 4.0 months, respectively, with no significant overall improvement. After combined treatment, 5 patients experienced skin hyperpigmentation, 2 had lumbar puncture site pain, 1 experienced vomiting, 1 had increased sputum production, and 1 had reduced total sleep time. All adverse reactions were mild and did not require medical intervention. CONCLUSIONS Nusinersen combined with risdiplam demonstrates efficacy in the treatment of SMA, and no significant adverse reactions have been observed.
Humans ; Oligonucleotides/adverse effects* ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Infant ; Muscular Atrophy, Spinal/drug therapy* ; Drug Therapy, Combination ; Child ; Azo Compounds ; Pyrimidines

Case 1 was a 7-year-old girl; Case 2 was her 3-year-old younger brother. Both children developed pink urine shortly after birth and exhibited blistering on photo-exposed areas (face and hands), followed by ulceration, crusting, scarring, and joint contractures leading to impaired mobility. Genetic testing in both patients identified a homozygous variant in the UROS gene, c.776T>C (p.Leu259Pro), confirming autosomal recessive congenital erythropoietic porphyria due to UROS mutations. This case report highlights that congenital erythropoietic porphyria should be considered in infants and young children with unexplained hemolytic anemia, pink urine, and severe photosensitive dermatitis. Early genetic testing is recommended to facilitate timely intervention and improve outcomes.
Humans ; Porphyria, Erythropoietic/genetics* ; Female ; Child ; Child, Preschool ; Male ; Siblings ; Mutation ; Uroporphyrinogen III Synthetase/genetics*

Objective:To summarize the clinical characteristics of patients with acute pancreatitis (AP) in plateau areas, and screen potential biomarkers for the pathogenesis of AP at high altitudes by metabolomics.Methods:A total of 42 patients with AP admitted to the Department of Gastroenterology in Lhasa People's Hospital from December 2023 to May 2024 were prospectively enrolled (AP group), and 33 healthy controls (Control group) were included during the same period. Demographic and clinical data were collected, and serum non-targeted metabolomics was performed based on ultra-performance liquid chromatography-mass spectrometry techniques. The serum metabolites map was evaluated by using principal component analysis, and a regression model with orthogonal partial least squares-discriminant analysis (OPLS-DA) was constructed to evaluate the explanatory power ( R2) and predictive power ( Q2) of these metabolites. The OPLS-DA-based dimensionality reduction was applied to compute variable importance in projection (VIP), while fold change (FC) values were used to assess the difference of metabolites between groups. A bidirectional clustering heat map was generated for samples and differential metabolites to evaluate sample similarity within groups. Additionally, a volcano plot was created to visualize differential metabolites, and the top five up-regulated and down-regulated metabolites distinguishing AP from healthy controls were selected. The receiver operating characteristic curve (ROC) was drawn, and the area under the curve (AUC), sensitivity and specificity based on ROC analysis were calculated to evaluate the differential power of differential metabolites. Results:The majority of participants were Tibetans in both the AP group (37 cases, 88.1%) and the control group (27 cases, 81.8%). The average age of AP patients was (50.45±17.85) years old, and the male to female ratio was 1.1∶1.0. The leading etiology was biliary disease (33 cases, 78.6%), and most patients encountered moderately severe disease (26 cases, 61.9%). The incidence of local complications was 83.3%, mainly thoracoabdominal effusion and peripancreatic effusion (30 cases, 71.4%). The incidence of systemic complications was 59.5%, mainly systemic inflammatory response syndrome (22 cases, 52.4%) and respiratory failure (15 cases, 35.7%). Principal component analysis showed significant differences in serum metabolites between groups. OPLS-DA showed that these metabolites effectively distinguished AP patients from healthy controls: R2=0.992 and Q2=0.913 in the positive ion mode, R2=0.983 and Q2=0.914 in the negative ion mode. There were 450 up-regulated and 366 down-regulated differential metabolites in AP group, respectively. Among them, gamma-glutamylleucine, cortisone, 4(15)-Copaen-11-ol, mytiloxanthin, and indole-3-glycol aldehyde were the top five up-regulated metabolites, while N-Acetyltryptophan, kynurenic acid, deoxyuridine monophosphate, pseudouridine, and farnesyl acetate were the top five down-regulated metabolites. ROC analysis of these markers showed that all AUC values were >0.8, with all P values <0.001, with both sensitivity and specificity exceeding 80%. Among them, N-Acetyltryptophan and farnesyl acetate possessed the best differential performance. Conclusions:Biliary causes are most frequent among AP patients in plateau area. The disease severity is mainly moderately severe, accompanied by high incidences of local and systemic complications. Some amino acids and prenol lipids could significantly distinguish AP patients from healthy controls, and might be involved in the pathogenesis of AP at high altitudes.