1.Epidemiological characteristics and influencing factors of severe fever with thrombocytopenia syndrome in Zhejiang Province
LÜ ; Jing ; XU Xinying ; QIAO Yingyi ; SHI Xinglong ; YUE Fang ; LIU Ying ; CHENG Chuanlong ; ZHANG Yuqi ; SUN Jimin ; LI Xiujun
Journal of Preventive Medicine 2026;38(1):10-14
Objective:
To analyze the epidemiological characteristics and influencing factors of severe fever with thrombocytopenia syndrome (SFTS) in Zhejiang Province from 2019 to 2023, so as to provide the reference for strengthening SFTS prevention and control.
Methods:
Data on laboratory-confirmed SFTS cases in Zhejiang Province from 2019 to 2023 were collected through the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System. Meteorological data, geographic environment and socioeconomic factors during the same period were collected from the fifth-generation European Centre for Medium-Range Weather Forecasts, Geospatial Data Cloud, and Zhejiang Statistical Yearbook, respectively. Descriptive epidemiological methods were used to analyze the epidemiological characteristics of SFTS from 2019 to 2023, and a Bayesian spatio-temporal model was constructed to analyze the influencing factors of SFTS incidence.
Results:
A total of 578 SFTS cases were reported in Zhejiang Province from 2019 to 2023, with an annual average incidence of 0.23/105. The peak period was from May to July, accounting for 52.60%. There were 309 males and 269 females, with a male-to-female ratio of 1.15∶1. The cases were mainly aged 50-<80 years, farmers, and in rural areas, accounting for 82.53%, 77.34%, and 75.43%, respectively. Taizhou City and Shaoxing City reported more SFTS cases, while Shaoxing City and Zhoushan City had higher annual average incidences of SFTS. The Bayesian spatio-temporal interaction model showed good goodness of fit. The results showed that mean temperature (RR=1.626, 95%CI: 1.111-2.378) and mean wind speed (RR=1.814, 95%CI: 1.321-2.492) were positively correlated with SFTS risk, while altitude (RR=0.432, 95%CI: 0.230-0.829) and population density (RR=0.443, 95%CI: 0.207-0.964) were negatively correlated with SFTS risk.
Conclusions
SFTS in Zhejiang Province peaks from May to July. Middle-aged and elderly people and farmers are high-risk populations. Taizhou City, Shaoxing City, and Zhoushan City are high-incidence areas. Mean temperature, mean wind speed, altitude, and population density can all affect the risk of SFTS incidence.
2.Consistent Detection of Aquaporin-4 Antibodies:A Comparative Analysis Between Fixed and Live Cell-Based Assays
Jing WANG ; Linge WANG ; Xiaolin YANG ; Zhizhong LI ; Jinyu JIANG ; Qiao XU ; Siyuan HUANG ; Qing FU ; Yang YANG ; Rongrong ZHANG ; Lin YANG ; Ai CHEN ; Xiaopeng ZENG ; Ke XU ; Peng ZHENG ; Xinyue QIN ; Jinzhou FENG
Journal of Clinical Neurology 2026;22(2):212-220
Background:
and Purpose Live cell-based assays (LCBA) are increasingly used for serological antibody detection due to their ability to preserve antigen conformation, offering moderately higher sensitivity than fixed cell-based assays. However, the clinical necessity of prioritizing LCBA for the detection of aquaporin-4 immunoglobulin G (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) remains unclear, especially when compared to its established role in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease.
Methods:
We compared the performance of live cell-based assays using immunofluorescence (LCBA-IF) and fixed cell-based assays using immunofluorescence (FCBA-IF) in detecting AQP4-IgG in 90 cases of NMOSD meeting 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, alongside 40 controls. Additionally, we further investigated the relationship between AQP4-IgG titers as measured by LCBA-IF and FCBA-IF and clinical parameters in NMOSD patients.
Results:
Results showed 96.9% agreement between LCBA-IF and FCBA-IF (Cohen’s κ=0.935), with a strong Spearman correlation (0.977, p<0.001). Both methods demonstrated 100% specificity, with LCBA-IF showing slightly higher sensitivity compared to FCBA-IF. Within LCBAIF-tested groups, statistically significant differences in annualized relapse rates were observed across all pairwise comparisons (low-titer vs. moderate-titer, low-titer vs. high-titer, and moderate-titer vs. high-titer; all p<0.050). However, this association reached statistical significance in some FCBA-IF-tested groups.
Conclusions
Overall, there is a strong concordance between LCBA-IF and FCBA-IF in detecting AQP4-IgG, where LCBA-IF shows slightly higher sensitivity. Furthermore, there is a potential link between elevated AQP4-IgG titers and an increased risk of relapse, and this correlation may appear more pronounced when using LCBA-IF.
3.Expert consensus on the application of artificial intelligence in lung cancer screening, diagnosis, and treatment (2026 edition)
Wenzhao ZHONG ; Haibo WANG ; Yi HU ; Hao ZHANG ; Jigang DAI ; Junqiang FAN ; Guibin QIAO ; Fan YANG ; Jian HU ; Fengwei TAN ; Xuening YANG ; Qiang PU ; Zihao CHEN ; Hongxia TIAN ; Lunxu LIU ; Hecheng LI ; Xiaolong YAN ; Zongyang YU ; Zhenbin QIU ; Yihua SUN ; Jing HU ; Yuhang SHI ; Zhifei GUO ; Peng ZHANG ; Kezhong CHEN ; Shugeng GAO ; Yilong WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(06):848-856
With the continuous deepening of the concept of precision diagnosis and treatment for lung cancer, how to achieve higher efficiency and accuracy in the screening, diagnosis, and treatment pathways in clinical practice has become an important issue that urgently needs to be overcome. The current clinical difficulty lies in the fact that despite continuous advancements in imaging and molecular diagnostic technologies, there are still limitations in manual efficiency and subjective experience when it comes to massive data analysis and multi-scale feature extraction. Artificial intelligence (AI), especially algorithm systems based on deep learning, is an innovative technology capable of deeply empowering medical big data. This method utilizes algorithms such as convolutional neural networks, combined with radiomics, pathomics, and multi-modal data fusion analysis, demonstrating immense potential in early precise detection and benign-malignant differentiation of pulmonary nodules, digital pathological subtype recognition and non-invasive prediction of driver genes, precise 3D surgical planning and automatic delineation of radiotherapy target volumes, as well as dynamic risk warning during follow-up. This innovative technology provides a brand-new solution for realizing intelligent and individualized lung cancer diagnosis and treatment models. This consensus, based on the latest evidence from evidence-based medicine and combined with the development trends in the AI field and real-world clinical needs, was ultimately formed by gathering the consensus opinions of multidisciplinary experts in radiology, pathology, thoracic surgery, and other fields. The main content covers the application specifications of AI in the three core scenarios of lung cancer screening, diagnosis, and treatment, the technical standards for data collection and algorithm validation, as well as the ethical and regulatory challenges faced at the current stage. It aims to clarify the applicable boundaries of AI as a clinical auxiliary decision support tool, providing scientific guidance and standardized exploration directions for peers currently engaged in or planning to carry out AI-assisted clinical diagnosis, treatment, and translation of lung cancer.
4.Research progress on the application of virtual reality technology in amblyopia visual training
Kang WANG ; Qiao WANG ; Pengfei LI ; Yunfan ZHANG ; Zifan QIN ; Jing LI
International Eye Science 2026;26(8):1411-1416
The therapeutic concept of amblyopia has gradually shifted from improving the visual acuity of the amblyopic eye to restoring binocular visual function.Conventional occlusion therapy and routine visual training have issues such as long treatment cycles, insufficient entertainment value and poor patient compliance, which limits the stability of therapeutic effects. Virtual reality(VR)technology, characterized by immersion, interactivity, and adjustable stimulus parameters, has been increasingly applied to visual training for amblyopia.Current evidence suggests that VR-based training can improve visual acuity and binocular visual function in amblyopia patients to a certain extent.Moreover, its gamified interactions and feedback-driven design may also enhance patient motivation and treatment adherence. This review begins with the mechanisms and theoretical basis of VR training for amblyopia, proceeds to summarizeits advantages over conventional methods, current systems, training modes, clinical efficacy, commonly used outcome measures, as well as safety and acceptability, aiming to provide a reference for its standardization, clinical translation, and widespread adoption.
5.Risk factors for therapeutic plasma exchange-related adverse events in patients undergoing allogeneic hematopoietic stem cell transplantation
Jingyuan QIN ; Jing LONG ; Lili YUAN ; Yuemei ZHANG ; Jiali QIAO ; Xuelian YANG ; Qingxue YIN ; Juan CHEN
Chinese Journal of Blood Transfusion 2026;39(9):1254-1261
Objective: To investigate the incidence and independent risk factors of adverse events (AEs) associated with therapeutic plasma exchange (TPE) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to provide evidence to support the safe use of TPE in clinical practice. Methods: This retrospective study included 167 allo-HSCT recipients who underwent a total of 385 TPE procedures between March 2022 and December 2023. Patients were divided into two groups according to the occurrence of TPE-related AEs. Baseline characteristics, plasma exchange parameters, and clinical features were collected. Univariate analysis and multivariable Firth logistic regression were performed to identify independent risk factors for AEs. Results: A total of 385 TPE procedures were performed in 167 allo-HSCT patients, and 33 patients (19.8%) experienced TPE-related AEs. Among the 33 patients who experienced AEs, allergic reactions were the most common (n=18, 54.5%), followed by blood pressure fluctuations (n=11, 33.3%) and hypocalcemia (n=4, 12.1%). Most AEs were classified as grade II (n=23, 69.7%), and no grade IV (fatal) events were observed. Univariate analysis demonstrated a significant difference in the incidence of AEs among different hematocrit (HCT) categories (<20%, 20%-30%, and>30%) (Fisher's exact test, P=0.022). Although the overall difference was statistically significant, none of the pairwise comparisons remained significant after Bonferroni correction (adjusted P>0.0167). Multivariable Firth logistic regression identified higher HCT levels, analyzed as a continuous variable (OR=1.07, 95% CI: 1.01-1.13, P=0.020), and TPE performed for cytokine release syndrome (CRS) (OR=9.21, 95% CI: 1.25-78.00, P=0.030) as potential independent risk factors for TPE-related AEs. Receiver operating characteristic (ROC) curve analysis showed that HCT had an AUC of 0.67 (95% CI: 0.57-0.77) for predicting AEs, with an optimal cutoff value of 24.5%, a sensitivity of 60.6%, and a specificity of 75.4%. Using this cutoff, the AEs rate was significantly higher in patients with HCT≥24.5% than in those with HCT<24.5% (37.7% vs 11.4%, P<0.001). Conclusion: A-mong allo-HSCT patients receiving TPE, allergic reactions were the predominant AEs. Higher HCT levels and TPE performed for CRS may be associated with an increased risk of AEs. HCT≥24.5% may help identify patients requiring intensified monitoring, although its discriminatory ability is moderate (AUC=0.67) and it should not be used as a standalone criterion for clinical decision-making. Findings regarding the CRS subgroup require validation in larger cohorts. Optimizing extracorporeal circuit priming and strengthening peri-procedural monitoring may help improve the safety of TPE.
6.Brain-heart Axis in Neurodegenerative and Cardiovascular Comorbidity: Oxidative Stress, Inflammation, and Biomarkers
Xu-Lin LIU ; Ying-Ao XIE ; Yun-Fei WANG ; Jing CHENG ; Qiao-Qiao LI
Progress in Biochemistry and Biophysics 2026;53(10):2558-2582
Neurodegenerative diseases (NDs), particularly Alzheimer’s disease (AD) and Parkinson’s disease (PD), and cardiovascular diseases (CVDs), including heart failure (HF) and coronary artery disease (CAD), are major chronic disorders associated with population aging. Their frequent coexistence in clinical practice suggests that they may not progress independently, but may instead be linked through bidirectional pathological communication within the brain-heart axis. Epidemiological evidence underscores this clinical burden: systematic reviews and meta-analyses have reported pooled relative risks for dementia of approximately 1.27 among individuals with a history of CAD and 1.60 among those with HF, while the pooled prevalence of cognitive impairment and dementia in patients with HF has been estimated at approximately 41.42% and 19.79%, respectively. This review synthesizes current evidence on the mechanistic links, disease-state manifestations, biomarkers, and potential therapeutic strategies involved in the comorbidity between NDs and CVDs from the perspective of the brain-heart axis. The brain and heart communicate through autonomic, neuroendocrine, neuroimmune, vascular, and humoral pathways. Sympathetic activation, parasympathetic withdrawal, vagal dysfunction, cerebral hypoperfusion, endothelial injury, blood-brain barrier (BBB) alterations, peripheral immune activation, and circulating inflammatory mediators may jointly contribute to cross-organ pathological signaling. Oxidative stress and inflammatory response are not specific to the brain-heart axis; rather, they may act as candidate amplifying processes within this network. Mitochondrial dysfunction and NADPH oxidase activation can increase the generation of reactive oxygen species and reactive nitrogen species, which may activate nuclear factor-κB, the NLRP3 inflammasome, and mitogen-activated protein kinase/c-Jun N-terminal kinase signaling. These pathways can promote the release of interleukin-1β, interleukin-6, tumor necrosis factor‑α, and other inflammatory mediators, which may in turn aggravate mitochondrial injury, endothelial dysfunction, immune cell activation, and further oxidant generation. Cytokines, chemokines, oxidized lipids, mitochondrial DNA, damage-associated molecular patterns, and extracellular vesicles may transmit these signals between the cardiovascular and central nervous systems, whereas autonomic reflexes provide an additional route for bidirectional amplification. Distinct disease states illustrate different manifestations of this network. The association between AD and CVDs may involve vascular risk factors, impaired amyloid-β clearance, abnormal cholesterol homeostasis, cerebral microvascular injury, neuroinflammation, and endothelial dysfunction. HF-related cognitive impairment may be linked to reduced cardiac output, recurrent cerebral hypoperfusion, hypoxia-related signaling, BBB dysfunction, circulating inflammation, and impaired autonomic feedback. In PD, cardiovascular autonomic dysfunction and abnormalities in heart rate and blood pressure regulation may interact with vascular injury, reduced cerebral perfusion, inflammation, and oxidative stress. However, the relationship between PD and CAD remains heterogeneous and may be modified by age, ethnicity, medication use, metabolic factors, and coexisting diseases. Biomarker evaluation should therefore move beyond isolated indicators. Traditional markers, including malondialdehyde, superoxide dismutase, glutathione, C-reactive protein, and interleukin-6, reflect systemic oxidative or inflammatory burden but lack sufficient specificity to distinguish primary neurodegeneration, cardiovascular injury, or a comorbid state involving both. Greater clinical value may be obtained from cross-system panels that combine oxidative stress and inflammatory markers with cardiac stress or injury biomarkers, such as N-terminal pro-B-type natriuretic peptide; glial or neuronal biomarkers, such as glial fibrillary acidic protein and neurofilament light chain; BBB- or endothelial injury-related biomarkers; and omics-derived candidates, including microRNAs, long non-coding RNAs, DNA methylation signatures, metabolites, and proteins. Multi-omics integration and artificial intelligence-assisted analysis may support risk stratification, disease monitoring, and prediction of treatment response. However, these approaches require standardized analytical platforms, validation in independent cohorts, and careful distinction between associative findings and causal mechanisms. Potential interventions include antioxidant, anti-inflammatory, mitochondria-targeted, and multi-target combination strategies, together with emerging approaches such as nanodelivery, CRISPR/Cas9- or CRISPR/dCas9-based regulation, mesenchymal stem cell-mediated mitochondrial transfer, and ergothioneine supplementation. Nevertheless, most available evidence is indirect, preclinical, or derived from other disease indications, and no single drug or technology can currently be regarded as specific to brain-heart axis comorbidity. The clinical relevance of these strategies will depend on whether they can be matched to dominant pathological phenotypes and improve both neurological and cardiovascular outcomes. Overall, comorbidity between NDs and CVDs is more appropriately understood as a heterogeneous cross-organ regulatory network than as a disorder driven by a single pathway. Future research should prioritize multicenter longitudinal cohorts, standardized clinical phenotyping, validation of cross-system biomarker panels, and mechanism-guided interventions in clearly defined patient subgroups, with integrated assessment of cognitive function, cardiovascular events, quality of life, long-term safety, and treatment response.
7.Influencing factors for hand, foot, and mouth disease in Binzhou City based on a Bayesian spatio-temporal model
XU Xinying ; YAN Wei ; SHI Xinglong ; LÜ ; Jing ; YUE Fang ; QIAO Yingyi ; LIU Guanxiang ; LI Xiujun
Journal of Preventive Medicine 2026;38(2):161-165
Objective:
To investigate the epidemiological characteristics and influencing factors for hand, foot, and mouth disease (HFMD) incidence in Binzhou City, Shandong Province, so as to provide the evidence for developing HFMD prevention and control strategies.
Methods:
Data on HFMD cases in Binzhou City from 2017 to 2023 were collected through the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System. Meteorological data during the same period were collected from the fifth-generation European Centre for Medium-Range Weather Forecasts. The incidence of HFMD was calculated, and the temporal, population, and regional distribution characteristics of HFMD were analyzed descriptively. Bayesian spatiotemporal model was used to analyze the influencing factors for HFMD incidence
Results:
From 2017 to 2023, a total of 17 314 HFMD cases were reported in Binzhou City, with an annual average reported incidence of 62.57/105. The incidence peak was from June to September, and a secondary peak appeared from October to November in some years. The annual average reported incidences were higher in Bincheng District and Yangxin County, which were 107.41/105 and 72.95/105, respectively. There were 10 461 males and 6 853 females, with a male-to-female ratio of 1.53∶1. The age was mainly 1-3 years, with 11 713 cases accounting for 67.65%. Bayesian spatiotemporal model analysis showed that the risk of HFMD incidence had obvious seasonality and regionality. From 2017 to 2019 and in 2021, the peaks occurred in weeks 24-27 and 44-47 each year, with RR values of 1.771-6.747. From 2022 to 2023, it showed a single peak distribution. The RR values were all >1 in Bincheng District, Yangxin County, and Huimin County. Average temperature (RR=1.092, 95%CI: 1.080-1.105) and average relative humidity (RR=1.015, 95%CI: 1.008-1.022) were positively correlated with the risk of HFMD incidence, while average wind speed (RR=0.749, 95%CI: 0.655-0.856) was negatively correlated with the risk of HFMD incidence.
Conclusions
HFMD in Binzhou City mainly occurs in summer and in central areas. Males and children aged 1-3 years are high-risk populations. The risk of HFMD incidence increases with the increase of average temperature and average relative humidity, and decreases with the increase of average wind speed.
8.Effect of Rhei Radix et Rhizoma Before and After Steaming with Wine on Intestinal Flora and Immune Environment in Constipation Model Mice
Yaya BAI ; Rui TIAN ; Yajun SHI ; Chongbo ZHAO ; Jing SUN ; Li ZHANG ; Yonggang YAN ; Yuping TANG ; Qiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):192-199
ObjectiveTo study on the different therapeutic effects and potential mechanisms of Rhei Radix et Rhizoma(RH) before and after steaming with wine on constipation model mice. MethodsFifty-four male ICR mice were randomly divided into control group, model group, lactulose group(1.5 mg·kg-1), high, medium and low dose groups of RH and RH steaming with wine(PRH)(8, 4, 1 g·kg-1). Except for the control group, the constipation model was replicated by gavage of loperamide hydrochloride(6 mg·kg-1) in the other groups. After 2 weeks of modeling, each administration group was gavaged with the corresponding dose of drug solution, and the control and model groups were given an equal volume of normal saline, 1 time/d for 2 consecutive weeks. After administration, the feces were collected for 16S rRNA sequencing, the levels of gastrin(GAS), motilin(MTL), interleukin-6(IL-6), γ-interferon(IFN-γ) in the colonic tissue were detected by enzyme-linked immunosorbent assay(ELISA), the histopathological changes of colon were observed by hematoxylin-eosin(HE) staining, flow cytometry was used to detect the proportion changes of CD4+, CD8+ and regulatory T cell(Treg) in peripheral blood. ResultsCompared with the control group, the model group showed significantly decrease in fecal number in 24 h, fecal quality and fecal water rate(P<0.01), the colon was seen to have necrotic shedding of mucosal epithelium, localized intestinal glands in the lamina propria were degenerated, necrotic and atrophied, a few lymphocytes were seen to infiltrate in the necrotic area in a scattered manner, the contents of GAS and MTL, the proportions of CD4+, CD8+ and Treg were significantly reduced(P<0.01), the contents of IL-6 and IFN-γ were significantly elevated(P<0.05, P<0.01). Compared with the model group, the fecal number in 24 h, fecal quality and fecal water rate of high-dose groups of RH and PRH were significantly increased(P<0.05, P<0.01), the pathological damage of the colon was alleviated to varying degrees, the contents of GAS, MTL, IL-6 and IFN-γ were significantly regressed(P<0.05, P<0.01), and the proportions of CD4+ and CD8+ were significantly increased(P<0.01), although the proportion of Treg showed an upward trend, there was no significant difference. In addition, the results of intestinal flora showed that the number of amplicon sequence variant(ASV) and Alpha diversity were decreased in the model group compared with the control group, and there was a significant difference in Beta diversity, with a decrease in the relative abundance of Lactobacillus and an increase in the relative abundances of Bacillus and Helicobacter. Compared with the model group, the ASV number and Alpha diversity were increased in the high-dose groups of RH and PRH, and there was a trend of regression of Beta diversity to the control group, the relative abundance of Lactobacillus increased, and the relative abundances of Bacillus and Helicobacter decreased. ConclusionRH and PRH can improve dysbacteriosis, promote immune system activation, inhibit the release of inflammatory factors for enhancing the gastrointestinal function, which may be one of the potential mechanisms of their therapeutic effect on constipation.
9.Analysis on the recovery of stereoscopic vision and its influencing factors in children with intermittent exotropia after binocular vision training
Jing CHEN ; Shanli QIAO ; Jianfei ZHANG ; Guangmei DONG ; Changfeng SUN
International Eye Science 2025;25(8):1377-1380
AIM: To analyze the recovery of stereopsis and its influencing factors in children with intermittent exotropia(IXT)after binocular vision training.METHODS: A total of 166 cases of IXT children who were treated in our hospital from October 2021 to October 2023(2 cases lost their follow-up, and 164 cases were finally included)were included as the research object, taking 36 cases with no stereopsis after binocular vision training in eye position correction surgery as no stereopsis group, and other 128 cases as stereopsis group. All the children underwent eye position correction surgery under general anesthesia, and all received binocular vision training for 6 mo after surgery. The recovery of stereoscopic vision of IXT children after binocular vision training was counted, and the influencing factors of stereoscopic vision recovery of IXT children after binocular vision training were analyzed by single factor and multi-factor Logistic regression analysis.RESULTS: The incidence of postoperative no stereopsis was 22.0%. The proportion of children with an age ≥9 years old, course of disease ≥1 a and anisometropia in the group without stereoscopic vision after operation was larger than the group with stereoscopic vision(all P<0.05). Multivariate Logistic regression analysis showed that the course of disease ≥1 a, age ≥9 years old and anisometropia were independent influencing factors for the recovery of stereoscopic vision in IXT children after binocular vision training(OR=1.470, 1.626, 1.539, all P<0.05).CONCLUSION: Age ≥9 years old, course of disease ≥1 a, and anisometropia are the independent influencing factors of stereopsis recovery of IXT children after binocular vision training. Therefore, targeted intervention measures can be given to high-risk children to improve the stereopsis recovery of IXT children after binocular vision training.
10.Effects of Xiaozhong Zhitong Mixture (消肿止痛合剂) on Angiogenesis and the Dll4/Notch1 Signaling Pathway in Wound Tissue of Diabetic Foot Ulcer Model Rats
Xiao HAN ; Tao LIU ; Yuan SONG ; Jie CHEN ; Jiaxuan SHEN ; Jing QIAO ; Hengjie WANG ; Lewen WU ; Yazhou ZHAO
Journal of Traditional Chinese Medicine 2025;66(16):1695-1703
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.


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