BACKGROUND:Peripheral nerve axon rupture seriously affects patients' physical function and mental health.Microsurgery,nerve autograft,nerve allograft,fibrin glue and catheter technology are the main treatments for peripheral nerve injury,each of which has its own advantages and disadvantages,but the overall treatment effect is not satisfactory.Despite the clinical success of Schwann cells in promoting axonal regeneration,there are still many challenges in the treatment with Schwann cells,such as slow expansion of Schwann cells,immune rejection,and low survival rate of transplanted cells.OBJECTIVE:To summarize the role and mechanism of Schwann cells in promoting the regeneration of peripheral nerve axons,and the difficulties and challenges of Schwann cells in the process of nerve regeneration treatment.METHODS:PubMed,Medline,WanFang,VIP,and CNKI were searched by computer using the search terms of"Schwann cells,synaptic Schwann cell,macrophage,peripheral nerve axon rupture,Wallerian degeneration,Peripheral nerve axon regeneration,Central nervous system repair"in English and Chinese.Literature related to Schwann cell proliferation and differentiation,promotion of peripheral nerve regeneration,and clinical applications was retrieved from database inception to October 2024,and a total of 95 articles were finally included for review.RESULTS AND CONCLUSION:Schwann cells interact with macrophages,T cells and other cells,to initiate the regeneration process through signaling pathways,including Krox20/C-Jun,NRG-1/ErbB,Notch,MAPK,and PI3K/Akt/mTOR,synthesize and release nerve growth factors,and thus promote regeneration of the peripheral nervous system.Schwann cells have been experimentally demonstrated to have great potential in peripheral nerve repair and are expected to become the key target of therapeutic intervention.However,there are still problems such as difficulties in cell harvest and culture,as well as the occurrence of other diseases during the treatment process.

BACKGROUND:Peripheral nerve axon rupture seriously affects patients' physical function and mental health.Microsurgery,nerve autograft,nerve allograft,fibrin glue and catheter technology are the main treatments for peripheral nerve injury,each of which has its own advantages and disadvantages,but the overall treatment effect is not satisfactory.Despite the clinical success of Schwann cells in promoting axonal regeneration,there are still many challenges in the treatment with Schwann cells,such as slow expansion of Schwann cells,immune rejection,and low survival rate of transplanted cells.OBJECTIVE:To summarize the role and mechanism of Schwann cells in promoting the regeneration of peripheral nerve axons,and the difficulties and challenges of Schwann cells in the process of nerve regeneration treatment.METHODS:PubMed,Medline,WanFang,VIP,and CNKI were searched by computer using the search terms of"Schwann cells,synaptic Schwann cell,macrophage,peripheral nerve axon rupture,Wallerian degeneration,Peripheral nerve axon regeneration,Central nervous system repair"in English and Chinese.Literature related to Schwann cell proliferation and differentiation,promotion of peripheral nerve regeneration,and clinical applications was retrieved from database inception to October 2024,and a total of 95 articles were finally included for review.RESULTS AND CONCLUSION:Schwann cells interact with macrophages,T cells and other cells,to initiate the regeneration process through signaling pathways,including Krox20/C-Jun,NRG-1/ErbB,Notch,MAPK,and PI3K/Akt/mTOR,synthesize and release nerve growth factors,and thus promote regeneration of the peripheral nervous system.Schwann cells have been experimentally demonstrated to have great potential in peripheral nerve repair and are expected to become the key target of therapeutic intervention.However,there are still problems such as difficulties in cell harvest and culture,as well as the occurrence of other diseases during the treatment process.

Chronic heart failure （CHF） is a major global public health problem， and myocardial infarction is one of its main causes. The mouse model of heart failure induced by coronary artery ligation is widely used in the study of CHF， while the TCM syndrome attributes of this model have not yet been clarified. According to the theory of correspondence between prescriptions and syndromes， the method of syndrome identification by prescription efficacy is an important means of current syndrome research of animal models. This method deduces the syndrome characteristics of animal models through prescription efficacy. Taking the four basic syndrome elements of Qi， blood， Yin and Yang as the classification reference， this study used coronary artery ligation to construct a mouse model of CHF and treated the model with four representative TCM injections with the effects of replenishing Qi， warming Yang， nourishing Yin， and activating blood and enalapril. Echocardiography， tongue color parameters， histopathology， serum N-terminal pro-brain natriuretic peptide （NT-proBNP） and cardiac troponin Ⅰ （cTnⅠ） levels， and systematically explored the TCM syndrome attributes of this model. The results showed that the coronary ligation model presented an obvious cardiac function decline， myocardial fibrosis， infarct size expansion， and purple dark tongue， which were consistent with the basic syndrome characteristics of blood stasis in CHF. Danhong injection had significant effects of improving the cardiac function， alleviating myocardial fibrosis， and reducing serum NT-proBNP and cTnⅠ levels. Huangqi Injection and Shenfu injection can improve the cardiac function and tongue color parameters， with limited effects. The effect of Shenmai injection group was not obvious. This study verifies that the established model conforms to blood stasis syndrome through the method of syndrome identification by prescription efficacy， which provides an experimental basis for the study of TCM syndrome mechanism of CHF.

ObjectiveTo investigate the epidemiological characteristics and influencing factors of depressive symptoms among middle school (junior, senior, and vocational high school) students in Yunnan Province, China, and to inform evidence-based intervention strategies for adolescent mental health. MethodsA cross-sectional survey was conducted between October and November 2023 using stratified random cluster sampling. Students from eight counties (districts) across four prefectures (cities) in Yunnan Province were included. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Multivariate logistic regression analysis was performed to examine factors associated with depressive symptoms, with stratified analyses conducted by gender, educational stage, and ethnicity. ResultsA total of 4 672 questionnaires were distributed, with 4 670 valid questionnaires retrieved, yielding a valid response rate of 99.96%. The surveyed participants were predominantly female students (50.81%), junior high school students (49.13%), ethnic minorities (52.78%), and urban residents (79.29%). The mean CES-D score for middle school students in Yunnan Province was (15.31±10.83). Female students had a significantly higher mean score (16.63±11.41) than male students (13.95±10.02) (P<0.001). Senior high school students had a significantly higher mean score (16.61±10.61) compared to both junior high school students (14.74±11.45) and vocational high school students (13.10±7.71) (all pairwise comparisons P<0.001). The prevalence of depressive symptoms among middle school students in Yunnan Province was 28.18%. The prevalence was significantly higher in females (34.09%) than in males (22.07%). By school type, the detection rate was highest among senior high school students (33.39%), followed by junior high school students (26.29%) and vocational high school students (17.27%) (P<0.05). Multivariate logistic regression analysis showed that female gender (OR=2.16, 95%CI: 1.86‒2.50), being in junior high school (OR=2.43, 95%CI: 1.84‒3.20) or senior high school (OR=2.27, 95%CI: 1.73‒2.98), not living with parents (OR=1.24, 95%CI: 1.07‒1.44), irregular breakfast consumption (OR=1.52, 95%CI: 1.33‒1.75), lack of moderate-to-vigorous physical activity (MVPA) (OR=1.69, 95%CI: 1.37‒2.09), sleep duration ≤5 h per night (OR=2.52, 95%CI: 2.02‒3.14) or 6‒7 h per night (OR=1.47, 95%CI: 1.25‒1.73), smoking (OR=1.86, 95%CI: 1.56‒2.23), and alcohol consumption (OR=1.81, 95%CI: 1.54‒2.13) were positively associated with depressive symptoms. In contrast, screen time ≤1 h (OR=0.71, 95%CI: 0.59‒0.86) was negatively associated with depressive symptoms. Stratified analyses showed that female students not living with parents (OR=1.29, 95%CI: 1.06‒1.58), senior high school students (OR=1.51, 95%CI: 1.21‒1.88), and Han Chinese students (OR=1.37, 95%CI: 1.11‒1.69) were more likely to experience depressive symptoms. Han Chinese students who smoked were also more likely to have depressive symptoms (OR=1.72, 95%CI: 1.34‒2.21). In contrast, male students with screen time ≤1 h (OR=0.71, 95%CI: 0.53‒0.95) and ethnic minority students (OR=0.74, 95%CI: 0.58‒0.95) were less likely to experience depressive symptoms. Regardless of gender, irregular breakfast consumption, lack of MVPA, sleep duration less than 8 h per night, smoking, and alcohol consumption were all positively associated with depressive symptoms (P<0.05). Among both junior and senior high school students, irregular breakfast consumption, lack of MVPA, smoking, and alcohol consumption were positively associated with depressive symptoms (all P<0.05), while screen time ≤1 h was negatively associated with depressive symptoms (all P<0.05). For junior high school students, engaging in 1‒2 days of MVPA per week, screen time more than 2 h per day, and sleep duration 6‒7 h per night were all positively associated with depressive symptoms (all P<0.05). Among junior high, senior high, and vocational high school students, sleep duration ≤5 h per night was positively associated with depressive symptoms (P<0.05). For both Han Chinese and ethnic minority students, irregular breakfast consumption, lack of MVPA, sleep duration less than 8 h per night, and alcohol consumption were all positively associated with depressive symptoms (all P<0.05). ConclusionThe prevalence of depressive symptoms among middle school students in Yunnan Province is comparable to that in central China and higher than that in northern regions. Prevention and control efforts should prioritize female students and those in junior and senior high school stages. Universal improvements in lifestyle behaviors among middle school students, such as regular breakfast consumption, MVPA, sufficient sleep (≥8 h), and abstinence from smoking and alcohol. Particular attention should be given to limiting excessive screen time among junior high school students and addressing the mental health needs of females not living with their parents, senior high school students, and Han Chinese students.

OBJECTIVE To innovatively apply the pre-intelligent precision dosing and verification system （hereinafter referred to as “the system”）， and to provide a reference for the high-level “intelligent” transformation of inpatient pharmacy. METHODS The limitations of the triple-serial dispensing mode， which comprised the automatic medicine packaging machine （ATC）， intelligent tablet dispensing table （ITDT） and medication detection machine （MDM）， were analyzed. The application of the system and the adoption of the barcode scanning verification method optimized the pre-dosing management， whole-tablet drug dispensing process and ATC temporary dosing management. The comparative analysis was conducted to assess dosing time， labor cost and packaging error of the eight-month period， before and after the system application. RESULTS The triple-serial dispensing mode had a weak ability to avoid error risks in the manual dosing stage， and also had errors in the verification stage. Through the innovative application system， the pre-dosing management had been upgraded， the whole-tablet drug dispensing process had been optimized， and the ATC temporary dosing management had been improved. The average time required for each drug for pre-dosing， whole-tablet drug dispensing and ATC temporary dosing was significantly shortened after the application of the system， compared with before the application of the system （P＜0.001）. The number of pharmacists was reduced from two to one. The error rate of ATC decreased significantly from 0.220‰ to 0.029‰ （P＜0.001）. Specifically， the rate of pharmacist-related errors （pre-dosing error， ITDT dosing error， and ATC temporary dosing error） decreased from 0.116‰ to 0.001‰ （P＜0.001）， and machine-related errors decreased from 0.096‰ to 0.023‰ （P＜0.001）. CONCLUSIONS This innovative integration mode greatly improves the working efficiency and quality of inpatient pharmacy. It enhances refined management of drug expiration and inventory， saves time and labor costs， improves the accuracy of drug dispensing， and ensures patient medication safety.

Intricate and complex interactions between tumor cells and tumor microenvironment(TME)are essential driving factors in tumor development and metastasis.In recent years,modulation of TME to reverse tumor progression has garnered significant attention as a therapeutic strategy.For precise and targeted tumor treatment,there is an urgent need for accurate and effective TME tar-get molecules and relevant prediction model.Fibronectin,a protein with multiple domains in extracellular matrix(ECM),plays a cru-cial role in physiological and pathological processes.Particularly,Fibronectin extra domain B(FN-EDB)in fibronectin is pivotal in regulating interaction between ECM and cells.During active tissue remodeling processes,especially in angiogenesis,FN-EDB expres-sion tends to increase.Studies have indicated that FN-EDB is involved in regulating various key aspects of tumorigenesis,including promoting tumor cell invasion and metastasis,influencing development of immune evasion mechanisms,enhancing tumor angiogene-sis,and contributing to development of chemoresistance.Therefore,targeting FN-EDB as a potential therapeutic target for cancer treat-ment and developing relevant therapeutic drugs hold significant importance and promising clinical prospects.This article reviews roles of FN-EDB in TME in recent years and research progress on tumor immunotherapy targeting this molecule,with aim of providing new insights and strategies for cancer treatment.

Aim To investigate the protective and reparative effect of empagliflozin on oxidized-low density lipo-protein(ox-LDL)-induced injury in human umbilical vein endothelial cells(HUVEC)and its mechanism of action.Methods Primary HUVEC were cultured in vitro.ox-LDL was used to induce HUVEC injury model,and the cell sur-vival rate was measured by CCK-8 assay.EDU method was used to detect cell proliferation.Western blot was used to detect the protein levels of Ki-67,Bcl-2,cleaved Caspase-3,Bax,endothelial nitric oxide synthase(eNOS),intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule 1(VCAM-1)and epidermal growth factor receptor(EGFR)in HUVEC.RT-qPCR was used to detect the mRNA expression levels of interleukin-6(IL-6)and tumor necro-sis factor-α(TNF-α)in HUVEC.Using Swiss targets,GeneCards databases,gene ontology(GO)and Kyoto encyclope-dia of genes and genomes(KEGG),protein-protein interaction(PPI)network analysis,and ClickDocking(https://mcule.com/apps/1-click-docking/)to predict the target of empagliflozin.Results CCK-8 results showed that 0.025 μmol/L empagliflozin significantly alleviated ox-LDL-induced HUVEC injury(P＜0.01).EDU results showed that ox-LDL treatment for 24 h significantly inhibited the proliferation of HUVEC(P＜0.01),while empagliflozin treatment sig-nificantly alleviated the inhibition of cell proliferation(P＜0.01).The results of Western blot showed ox-LDL treatment significantly decreased the protein expression levels of Ki-67,Bcl-2,and eNOS,and increased the protein expression levels ofcleaved Caspase-3,Bax,ICAM-1,and VCAM-1 in HUVEC(all P＜0.05).However,empagliflozin treatment reversed these changes(all P＜0.05).RT-qPCR results showed that ox-LDL treatment increased the mRNA expression levels of IL-6 and TNF-α in HUVEC(P＜0.01),while empagliflozin treatment decreased their expression levels(P＜0.05).However,after adding EGFR agonist NSC 228155,the protective effect of empagliflozin against ox-LDL-mediated HUVEC injury was significantly reversed(P＜0.05).Conclusion Empagliflozin can significantly reduce ox-LDL-in-duced HUVEC injury,which may be related to EGFR signaling pathway.

Aim To investigate the protective and reparative effect of empagliflozin on oxidized-low density lipo-protein(ox-LDL)-induced injury in human umbilical vein endothelial cells(HUVEC)and its mechanism of action.Methods Primary HUVEC were cultured in vitro.ox-LDL was used to induce HUVEC injury model,and the cell sur-vival rate was measured by CCK-8 assay.EDU method was used to detect cell proliferation.Western blot was used to detect the protein levels of Ki-67,Bcl-2,cleaved Caspase-3,Bax,endothelial nitric oxide synthase(eNOS),intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule 1(VCAM-1)and epidermal growth factor receptor(EGFR)in HUVEC.RT-qPCR was used to detect the mRNA expression levels of interleukin-6(IL-6)and tumor necro-sis factor-α(TNF-α)in HUVEC.Using Swiss targets,GeneCards databases,gene ontology(GO)and Kyoto encyclope-dia of genes and genomes(KEGG),protein-protein interaction(PPI)network analysis,and ClickDocking(https://mcule.com/apps/1-click-docking/)to predict the target of empagliflozin.Results CCK-8 results showed that 0.025 μmol/L empagliflozin significantly alleviated ox-LDL-induced HUVEC injury(P＜0.01).EDU results showed that ox-LDL treatment for 24 h significantly inhibited the proliferation of HUVEC(P＜0.01),while empagliflozin treatment sig-nificantly alleviated the inhibition of cell proliferation(P＜0.01).The results of Western blot showed ox-LDL treatment significantly decreased the protein expression levels of Ki-67,Bcl-2,and eNOS,and increased the protein expression levels ofcleaved Caspase-3,Bax,ICAM-1,and VCAM-1 in HUVEC(all P＜0.05).However,empagliflozin treatment reversed these changes(all P＜0.05).RT-qPCR results showed that ox-LDL treatment increased the mRNA expression levels of IL-6 and TNF-α in HUVEC(P＜0.01),while empagliflozin treatment decreased their expression levels(P＜0.05).However,after adding EGFR agonist NSC 228155,the protective effect of empagliflozin against ox-LDL-mediated HUVEC injury was significantly reversed(P＜0.05).Conclusion Empagliflozin can significantly reduce ox-LDL-in-duced HUVEC injury,which may be related to EGFR signaling pathway.

Objective:To investigate the differences in acute intestinal injury and regulatory mechanisms in mice following carbon ion FLASH radiotherapy (FLASH-RT) and conventional dose rate radiotherapy (CONV-RT).Methods:Healthy C57BL/6J mice were randomly divided into three groups: control group, FLASH-RT group (100 Gy/s), and CONV-RT group (0.1 Gy/s), with 9 mice in each group. All mice received carbon ion whole abdominal radiotherapy. DNA double-strand breaks (DSB) and cell proliferation were evaluated by measuring the expression of phosphorylated histone H2AX (γ-H2AX) and nuclear-associated antigen 67 (Ki67) using immunohistochemistry; apoptosis was analyzed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL); transcriptome sequencing was used to analyze the differences in molecular pathways between FLASH-RT and CONV-RT.Results:Compared with the CONV-RT group, the FLASH-RT group showed significantly reduced intestinal γ-H2AX signal at 3 h after radiotherapy ( t=3.80, P<0.01), significantly increased expression of Ki67 at the base of intestinal crypts at 6 h after radiotherapy ( t=4.30, P<0.001), and a significantly decreased number of TUNEL-positive cells at 12 h after radiotherapy ( t=3.08, P<0.01). Transcriptome sequencing analysis showed that FLASH-RT specifically activated the insulin-like growth factor (IGF) pathway, avoiding the excessive activation of CONV-RT-induced nuclear factor-κB and B cell receptor inflammatory pathways as well as the inhibition of energy metabolism. Conclusions:Compared with CONV-RT, carbon ion FLASH-RT can reduce DSB damage, preserve the proliferative activity of intestinal stem cells, activate the IGF pathway, and regulate inflammatory, immune, and metabolic pathways, thereby significantly alleviating acute intestinal epithelial injury. Specifically, the regulation of repair pathways mediated by reduced DSB and the inhibition of inflammatory pathways are potential protective mechanisms for normal tissues.

Objectives:To evaluate the safety and feasibility of endovascular aortic repair without contrast agent under branch artery guidewire marking(FLARE technique).Methods:The clinical data of 7 patients who underwent contrast-free endovascular aortic repair with branch artery guidewire marking in Fuwai Hospital from 2024 to 2025 were retrospectively analyzed.The criteria for patient selection included renal insufficiency,history of contrast agent allergy,high risk of high-pressure angiography due to extensive calcification of the aortic arch,and patients'strong personal wishes,all patients merited with anatomically friendly and anchored area criteria.The patients were evaluated by preoperative computed tomography or color Doppler ultrasound,and the occlusive stent anchor point was located by branch artery guidewire marking combined with bone marking during surgery.The primary endpoints were early stage of postoperative renal function changes(comparison of preoperative and postoperative serum creatinine)and surgical technique success rate,and the secondary endpoints included the incidence of internal leakage,re-intervention rates,and incidence of aneurysm and kidney-related adverse events during follow-up.Results:Among the seven patients who underwent endovascular aortic repair without contrast using a branch artery guidewire,four were male,with an average age of(72.0±5.9)years.Six of these patients had infrarenal abdominal aortic aneurysms,two of them with bilateral renal artery severe stenosis and renal insufficiency underwent renal artery stenting combined with endovascular aortic repair,one patient had isolated chronic renal insufficiency,one had a history of iodine contrast skin allergy,and the remaining two cases wished this surgery option.The seventh patient had a penetrating ulcer in the aortic arch and descending aorta,along with extensive thrombosis and calcification in the ascending aorta,aortic arch and descending aorta.All the patients achieved surgical technique success.No iodine contrast agent was used during the procedure for endovascular aortic repair.In patients with chronic renal insufficiency and renal artery stenosis before surgery,serum creatinine levels were significantly improved after surgery.All patients did not need hemodialysis,there was no allergic reaction,and no graft-related or perioperative complications.The average follow-up was(5.8±3.0)months,all patients recovered well without re-intervention or complications.The creatinine levels did not fluctuate significantly after surgery.Conclusions:Branch artery guidewire marked contrast-free aortic endovascular repair may be a safe and feasible treatment option in selected patients,especially in patients with contraindications to contrast agents.