Objective To investigate the protective effects and mechanisms of sulodexide on renal fibrosis induced by prolonged warm ischemia. Methods An in vivo ischemia-reperfusion injury (IRI) model was established in rats, which were randomly divided into Sham group, IRI 60 min group (IRI group), and IRI 60 min + sulodexide group (IRI+SDX group), with 20 rats in each group. Pathological examination was used to evaluate renal tissue injury and fibrosis levels in each group. Immunohistochemistry was performed to detect the expression levels of kidney injury molecule (KIM)-1, intercellular adhesion molecule (ICAM)-1, von Willebrand factor (vWF), transforming growth factor (TGF)-β, α-smooth muscle actin (SMA), and type I collagen (COL-1). Immunofluorescence staining was used to detect CD31 expression. Real-time quantitative polymerase chain reaction was employed to measure the expression of KIM-1, ICAM-1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in renal tissues. Transmission electron microscopy was used to observe the structure of the renal glycocalyx. Evans blue dye was injected to assess renal vascular permeability. Rat survival was recorded, and serum levels of syndecan (SDC)-1, heparan sulfate (HS) and serum creatinine were measured. An ex vivo perfusion model was also established, with rats randomly assigned to either the hypothermic oxygenated machine perfusion (HOPE) group or the HOPE+SDX group (five rats per group). Perfusion parameters were recorded after 2 hours of ex vivo perfusion. Results One day after reperfusion, compared with the Sham group, the IRI group exhibited more severe renal tissue injury, higher tubular injury scores, increased expression of KIM-1, ICAM-1 and vWF, decreased CD31 expression, elevated serum levels of SDC-1 and HS, increased vascular permeability, and higher expression of TNF-α, IL-1β and IL-6. Compared with the IRI group, the IRI+SDX group showed reduced renal tissue injury, lower tubular injury scores, decreased expression of KIM-1, ICAM-1 and vWF, increased CD31 expression, lower serum levels of SDC-1 and HS, decreased vascular permeability, and reduced expression of TNF-α, IL-1β and IL-6 (all P < 0.05). Ten days after reperfusion, renal tissue injury was further alleviated in the IRI+SDX group. Twenty-five days after reperfusion, the IRI+SDX group exhibited decreased expression of TGF-β, α-SMA, and COL-1, as well as reduced collagen deposition area (all P < 0.05). Compared with the HOPE group, the HOPE+SDX group showed increased renal perfusion flow and decreased intrarenal vascular resistance (both P < 0.01). Conclusions Sulodexide may alleviates renal IRI and fibrosis caused by prolonged warm ischemia by inhibiting inflammatory responses and protecting vascular endothelial glycocalyx.

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H₂O₂-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H⁺ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H₂O₂-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

Objective To investigate the risk factors for postoperative pulmonary embolism in patients with spontaneous cerebral hemorrhage,and construct and verify the nomogram model.Methods A retrospective cohort study was conducted on 558 patients admitted in the First Affiliated Hospital of Chongqing Medical University and the Three Gorges Hospital Affiliated to Chongqing University.And 393 of them who hospitalized from January 2015 to January 2021 were assigned into a modeling group,and the other 165 patients from February 2021 to January 2023 into a validation group.Univariate and multivariate stepwise logistic regression analyses were used to screen out the risk factors associated with pulmonary embolism after spontaneous cerebral hemorrhage surgery.Then a nomogram model was build based on these factors and verified.Results Based on age,blood loss,Glasgow coma scale(GCS)score,surgical treatments,levels of fibrin degradation products,D-dimer and hemoglobin,plasma osmolality,and deep vein thrombosis,a risk model of pulmonary embolism was built.Receiver operating characteristic(ROC)curve analysis showed the model had good discriminability for the presence of pulmonary embolism,and the area under the curve(AUC)value was 0.908.Hosmer-Lemeshow goodness-fit test indicated that the model had a good fit to the verification set(Chi-square=14.805,df=8,P=0.063),the correction curve was close to the ideal curve,and the prediction probability of the model was close to the actual occurrence probability,suggesting the model having good accuracy.Decision curve analysis revealed that the established nomogram model can get benefits under a large range of threshold probabilities.Conclusion We develop a prediction model for postoperative pulmonary embolism in patients with spontaneous cerebral hemorrhage after surgical treatment,which shows good prediction performance in both the training and validation groups,and can be used for accurate,prompt and quick identification for the occurrence of pulmonary embolism in clinical practice.

With the integration and application of various disciplines, traditional Chinese medicine′s auricular acupoint therapy has gained new opportunities for development. The effective activation of auricular acupoints is crucial as the initial step in auricular acupoint therapy. To address this issue, advanced techniques for physical stimulation, blending principles from traditional Chinese and Western medicine, have been developed. This paper explores the profound impact of magnetism on the structure and function of organisms from multiple dimensions, focusing on magnetobiology. It provides a comprehensive review of the clinical efficacy, research paradigm, challenges, and future prospects of auricular magnetic therapy. The article emphasizes the magnetic characteristics of organisms, particularly the nervous system′s high sensitivity to magnetic fields. It highlights the potential of modern magnetic stimulation techniques in treating brain diseases through auricular therapy. Additionally, the paper explores the research paradigm of auricular magnetic stimulation in conjunction with physical molecular dynamics simulation, materials engineering, mathematical modeling, and interdisciplinary biomedical technology. This endeavor is expected to provide valuable insights for optimizing the parameters of auricular magnetic stimulation and understanding its underlying principles. The multidisciplinary, cross-system, and multi-scale biophysical research paradigm introduces a new conceptual framework and investigative approach for auricular acupoint therapy, significantly enhancing the safety and efficacy of auricular magnetic stimulation therapy.

To investigate the value of self-developed air-free laparoscopic auxiliary instruments in the clinical application of thyroid diseases.The clinical data of 70 transaxillary and 45 transareolar air-free laparoscopic surgeries for thyroid cancer and 40 conventional open surgeries were retrospectively compared.The transaxillary and transareolar laparoscopic groups had significantly longer operative times than the open group,while the postoperative satisfaction was higher in the endoscopic group than in the open group.This set of instruments has advantage of novel design,scientific structure,safe application.It can be compatible with a variety of thyroid and breast air-free laparoscopic procedures,which can promote the development and popularization of laparoscopic technology.

Objective To explore the inhibitory effect of 17-DMAG on the growth and angiogenesis of PD-1 humanized mouse liver cancer transplantation tumors.Methods 30 PD-1 humanized mice were selected,and a human HepG2 cell suspension was injected into the subcutaneous tissue of the right inguinal region to construct a human liver cancer transplant tumor model.Tumor-bearing humanized mice were randomly divided into three groups(10 mice per group):① model group(injected with 10 mg/kg of physiological saline),②17-DMAG group(intraperitoneal injection of 17-DMAG at 25 mg/kg,3 times/week),and③cisplatin group(intraperitoneal injection of 20 mg/kg,2 times per week).The experiment lasted for 4 weeks.After injection,the length and shortest diameter of humanized mouse transplanted tumors were measured to calculate the volume,and tumor mass was measured to calculate the tumor inhibition rate.At the same time,immunohistochemical method were used to detect the expression of CD31(tumor microvessel density,MVD)and vascular endothelial growth factor(VEGF)in tumor tissue.Results The tumor volume and mass of the 17-DMAG group and cisplatin group were significantly reduced compared to those of the model group(P＜0.05),and the tumor inhibition rate of the 17-DMAG group was slightly higher than that of the cisplatin group.However,there were no significant differences in tumor mass,volume,and tumor inhibition rate between the 17-DMAG group and cisplatin group.The number of MVD-labeled microvessels and level of VEGF expression in the 17-DMAG group and cisplatin group were lower than those in the model group(P＜0.05),and those of the 17-DMAG group were also lower than those in the cisplatin group(P＜0.05).Conclusions 17-DMAG can inhibit the growth of humanized mouse liver cancer xenografts by reducing the expression of VEGF in liver cancer xenograft tissue,thereby inhibiting the generation of tumor neovascularization.

Objective:To explore the application of observation teaching discussion (OTD) in vascular surgery nursing intern teaching under the guidance of process-oriented guided inquiry learning (POGIL) theory.Methods:Forty nursing students who were doing their internship in The First Affiliated Hospital of Xi'an Jiaotong University from July 2022 to July 2023 were randomly divided into two groups using a random number table: control group (20 students, OTD teaching) and observation group (20 students, POGIL theory-guided teaching) . The two groups were compared for competence assessment scores before entering the department and 3 days prior to departure from the department, autonomous learning ability scale scores, Competency Inventory for Registered Nurses (CIRN) scores, and Chinese Problem Solving Inventory (CPSI) scores. T-tests and chi-square tests were conducted using SPSS 22.0. Results:Three days prior to departure from the department, the theoretical performance and practical performance were significantly better in the observation group [(91.67±5.22) and (89.69±4.36) points, respectively] than in the control group [(84.53±4.75) and (82.41±4.18) points, respectively] ( P<0.05). The observation group also performed significantly better than the control group in autonomous learning ability scale score [(139.52±13.52) vs. (128.86±10.76)], CIRN score [(207.73±6.23) vs. (195.67±5.98)], and CPSI score [(103.60±4.72) vs. (92.18±5.03)] (all P<0.05). Conclusions:The application of OTD in vascular surgery nursing intern teaching under the guidance of POGIL theory can improve the autonomous learning ability, core ability, and problem-solving ability of nursing interns.

Objective:To study the ultrasonographic manifestations of intercostal muscle and diaphragm involvement in Duchenne muscular dystrophy (DMD) and their correlations with functional status, and to explore the pattern of muscle damage in patients with DMD and the potential role of ultrasonography in assessing disease progression.Methods:A total of 28 patients with DMD who received treatment in the Third Medical Centre of PLA General Hospital from May to December 2023 were prospectively collected as DMD group, and 28 healthy children matched in age and sex were included as controls for a prospective study.Diaphragm thickening fraction (DTF) and intercostal muscle thickening fraction (ICMTF) were measured by B-mode and M-mode ultrasonography, and the muscle gray values were recorded. The differences between groups were compared, and the values of DTF and ICMTF in evaluating the structural and functional changes of respiratory muscle were analyzed.Results:Compared with the control group, the gray value of respiratory muscle was significantly decreased in DMD group, the diaphragm and intercostal muscle were significantly thickened at the end of inspiratory and expiratory periods, DTF was significantly decreased, and ICMTF was significantly increased (all P<0.001). Conclusions:Ultrasound can evaluate the structural changes of respiratory muscle in DMD, so as to clarify the relationship between the structure and function of respiratory muscle in DMD patients.

Objective : To identify the factors affecting microvascular complications among patients with type 2 diabetes (T2DM), so as to provide insights into the management of microvascular complications of T2DM. Methods: T2DM patients hospitalized in the Department of Endocrinology of a tertiary hospital in Weifang City, Shandong Province from January 2021 to January 2022 were enrolled, and subjects' basic information, lifestyle and medical history were collected using questionnaire surveys. Fasting insulin, fasting blood glucose and glycated hemoglobin were measured, and factors affecting microvascular complications were identified among T2DM patients using a multivariable logistic regression model and a decision tree model. Results: Totally 1 003 T2DM inpatients were enrolled, including 515 men (51.35%) and 488 women (48.65%), and the prevalence of microvascular complications was 40.18%. Multivariable logistic regression analysis showed that age of 60 years and older (OR=2.510, 95%CI: 1.441-4.374), T2DM duration of 10 years and longer (OR=3.205, 95%CI: 2.242-4.581), fasting insulin of lower than 3.21 μIU/mL (OR=1.749, 95%CI: 1.239-2.469), using of agents or insulin to control blood glucose (OR=1.880, 95%CI: 1.143-3.092), glycated hemoglobin level of 7% and higher (OR=1.751, 95%CI: 1.172-2.615) as factors affecting microvascular complications among T2DM patients. Decision tree analysis identified course of T2DM as a major factor affecting the risk of microvascular complications among T2DM patients, and the prevalence of microvascular complications was 70.22% among T2DM patients with disease course of 10 years and longer and fasting insulin of lower than 3.21 μIU/mL or 16.32 μIU/mL and higher, 44.23% among T2DM patients with disease course of 5 to 10 years and at ages of 60 years and older, and 43.10% among T2DM patients with disease course of less than 5 years and fasting insulin of lower than 3.21 μIU/mL. Conclusion Advanced age, long course of T2DM, low fasting insulin and high glycated hemoglobin may increase the risk of microvascular complications among T2DM patients.

Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8⁺ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8⁺ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.