ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture （消肿止痛合剂， XZM） in the treatment of diabetes foot ulcer （DFU）. MethodsFifty SD rats were randomly divided into blank group， model group， XZM group， inhibitor group， XZM plus inhibitor group （combination group）， with 10 rats in each group. Except for the blank group， rats were fed with high-sugar， high-fat， high-cholesterol diet， intraperitoneally injected with streptozotocin， and subjected to skin defect to establish DFU model. After successful modeling， the XZM group and the combination group were given 1 ml/（100 g·d）of XZM by gavage， while the blank group， model group， and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later， the inhibitor group and the combination group were intraperitoneally injected with 5 mg/（kg·d） of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration， the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin （HE） staining. The microvascular density （MVD） in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction （RT-PCR） and western blotting were used to detect the mRNA and protein levels of Notch1 homolog （Notch1）， Delta-like ligand 4 （Dll4）， Delta-like ligand 4 （VEGF）， and angiopoietin 2 （Ang-2）， respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group， the epidermis exhibited excessive keratinization， vacuolar cytoplasm， and a large number of inflammatory cells infiltrating the tissue， while in the XZM group， a large amount of scab formation was observed in the epidermis， with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group， partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group， the MVD in the wound tissue increased in the model group， as well as the mRNA expression and protein levels of Notch1 and Dll4， while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the MVD in the wound tissue of all medication groups significantly increased， and the mRNA and protein levels of Notch1 and Dll4 decreased， while VEGFA and Ang-2 mRNA expression and protein levels increased （P＜0.05 or P＜0.01）. Compared to the XZM group， the inhibitor group and the combination group showed decreased MVD in wound tissue， increased Notch1 and Dll4 mRNA and protein levels， and decreased expression of VEGFA and Ang-2 mRNA and proteins （P＜0.05 or P＜0.01）. ConclusionXZM can effectively promote wound healing in DFU rats， and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue， therey promoting angiogenesis.

Fifty whitespotted bamboo sharks (Chiloscyllium playgiosum) of both sexes were used to establish a large capacity variable domain of the new antigen receptor (VNAR) library with a total capacity of over 10⁹ colony-forming units (CFU). It was applied to screen VNARs against human serum albumin (HSA) and human transcription factor EB (TFEB), respectively. Meanwhile, VNAR libraries specific to HSA and TFEB with capacities above 10⁸ CFU were obtained following conventional immunization. These two approaches were systematically studied in terms of VNAR yield and composition. By comparing the VNAR sequences obtained from naïve and antigen-immunized libraries, we found that the complementary-determining region 3 (CDR3) of the former differs in composition from that of the latter. It shares a higher degree of homology with the naïve library. Meanwhile, the binding efficiency assessed by ELISA is also different between the naïve and antigen-immunized libraries. The binding of VNARs from the TFEB-immunized library appeared to surpass that observed with the naïve libraries, whereas the performance of VNARs from the HSA-immunized library indicated that both the immunized and naïve libraries for HSA had positive binding responses in polyclonal and monoclonal ELISA. The results are useful to develop novel diagnostic and therapeutic products based on shark VNARs.

A redox-responsive hyaluronic acid-vitamin E polyethylene glycol succinate nanoparticle loaded with paclitaxel (HA-SS-TPGS@PTX) was designed to investigate its mechanism for overcoming multidrug resistance (MDR) in non-small cell lung cancer (NSCLC) in vitro. HA-SS-TPGS@PTX nanoparticles were prepared using an emulsion-ultrasonication method. Techniques such as flow cytometry and confocal laser scanning microscopy (CLSM) were employed to study their effects on apoptosis induction, mitochondrial function, and the regulation of P-glycoprotein (P-gp) expression in PTX-resistant lung cancer cells (A549/T). Results showed that HA-SS-TPGS@PTX nanoparticles significantly inhibited the proliferation of A549/T cells in vitro, with an IC50 of 1.35 μg/mL. The nanoparticles entered the cells via CD44 receptor-mediated endocytosis. The high intracellular concentration of glutathione (GSH) triggered the release of PTX and TPGS, which subsequently induced a decrease in mitochondrial membrane potential, leading to apoptosis. Meanwhile, HA-SS-TPGS@PTX also inhibited P-gp expression and ATP consumption, thereby blocking drug efflux. The design of HA-SS-TPGS@PTX provides a new strategy for overcoming MDR in NSCLC.

In recent years,public hesitancy to vaccinate has come to the fore and can hinder the advancement of immunization programs.It is important to increase public confidence in vaccines and to rationally and effectively promote the immunization behavior of the population.Based on behavioral economics theory,it combines the anchoring effect,loss aversion,two-systems theory,and the herd effect to explore the irrational factors and decision-making preferences behind the public's vaccination decisions,and then proposes discourse strategies for effective boosting to increase the public's confidence in vaccination.

In recent years,public hesitancy to vaccinate has come to the fore and can hinder the advancement of immunization programs.It is important to increase public confidence in vaccines and to rationally and effectively promote the immunization behavior of the population.Based on behavioral economics theory,it combines the anchoring effect,loss aversion,two-systems theory,and the herd effect to explore the irrational factors and decision-making preferences behind the public's vaccination decisions,and then proposes discourse strategies for effective boosting to increase the public's confidence in vaccination.

In recent years,public hesitancy to vaccinate has come to the fore and can hinder the advancement of immunization programs.It is important to increase public confidence in vaccines and to rationally and effectively promote the immunization behavior of the population.Based on behavioral economics theory,it combines the anchoring effect,loss aversion,two-systems theory,and the herd effect to explore the irrational factors and decision-making preferences behind the public's vaccination decisions,and then proposes discourse strategies for effective boosting to increase the public's confidence in vaccination.

In the context of the emphasis on the claims of multiple subjects in fourth-generation educational evaluation, the subjective experience of students has gradually become one of the key contents of educational evaluation. However, there is still a vague understanding of the conceptual source, specific definition, and measurement indicators of the student experience theory, and a more systematic theoretical system has not yet been formed. With the UE user experience thinking in the business field as the core meta-theory, this article integrates value-added evaluation and the idea of three-source flow, elaborates on the core concept connotation of compound student experience teaching evaluation, and builds a five-dimensional evaluation model for student experience with "aesthetic experience, interactive experience, emotional experience, behavioral experience, and discursive experience" as the first-level indicators based on literature research, expert interviews, and multi-round group discussions. It is hoped that student evaluation will force teachers to improve the contents and form of teaching and help to achieve breakthrough reform of the teaching system as a whole.

In response to the major national strategic needs of "Healthy China" and "Chengdu-Chongqing Economic Circle", and in strict accordance with the requirements of "New Medicine" construction, Chongqing University builds the medical discipline with a high starting point, develops high-quality medical education, and promotes the exploration and practice of elite education of clinical medical talents in the cross-disciplinary context of medicine and engineering. From the perspective of SWOT, this study analyzed the situations and trends of clinical medical education in "Double First Class" universities which newly established the medical discipline. Combined with the training model of clinical talent class in Chongqing University and the practices of "Four Capacity-Buildings", "Four Integration-Measures", and "Three Optimization-Mechanisms", we discuss the thoughts and strategies of cultivating clinical medical talents in the background of "New Medicine" construction and in the cross-disciplinary context of medicine and engineering.

Objective:To explore the effects of dopamine receptor D2(DRD2)on astrocytic dedifferentiation based on SOX2-regulated genes in neural stem cells(NSCs)and astrocytes.Methods:Immunofluorescence staining and SOX2-GFP mice were used to examine the lineage differentiation of SOX2-positive cells during the development of cere-bral cortex.Primary NSCs/astrocytes culture,ChIP-seq and Western Blot were adopted to analyze and verify the expres-sion of candidate genes.Pharmacological manipulation,neurosphere formation,photochemical ischemia,immunofluo-rescence staining and behavior tests were adopted to evaluate the effects of activating DRD2 signaling on astrocytic dedif-ferentiation.Results:Immunofluorescence staining demonstrated the NSC-astrocyte switch of SOX2-expression in the normal development of cerebral cortex.ChIP-seq revealed enrichment of DRD2 signaling by SOX2-bound enhancers in NSCs and SOX2-bound promoters in astrocytes.Western Blot and immunofluorescence staining verified the expression of DRD2 in NSCs and reactive astrocytes.Application of quinagolide hydrocholoride(QH),an agonist of DRD2,signifi-cantly promoted astrocytic dedifferentiation both in vitro and in vivo following ischemia.In addition,quinagolide hydro-choloride treatment improved locomotion recovery.Conclusion:Activating DRD2 signaling facilitates astrocytic dedif-ferentiation and may be used to treat ischemic stroke.