1.Distribution of Traditional Chinese Medicine Syndromes in 2 027 Patients with Esophageal Squamous Cell Carcinoma
Jianing JIAN ; Yulong CHEN ; Ruohan LI ; Runze GUO ; Yaling ZHANG ; Yuling ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):173-181
ObjectiveTo investigate the characteristics and distribution of traditional Chinese medicine (TCM) syndromes in the patients with esophageal squamous cell carcinoma (ESCC). MethodsAn electronic questionnaire was developed to collect the general data and four examination information of ESCC patients treated in 10 areas with high incidence of esophageal cancer in China from June 2020 to March 2021. Multiple analyses including frequency analysis, factor analysis, and hierarchical cluster analysis were performed to analyze the potential syndrome elements, disease location, and common syndromes of ESCC. ResultsA total of 2 027 patients with ESCC were included. Statistical analysis was performed on 113 symptoms, physical signs, 33 tongue manifestation variables, and 23 pulse manifestation variables of the patients’ four examination information. Factor analysis was performed on 55 variables with frequency>10%, extracting 19 common factors. According to clinical experience and expert opinions, the main lesions of patients with ESCC were in the spleen and stomach, and the main syndrome elements were Qi stagnation, blood stasis, phlegm, dampness, and Qi deficiency, with the syndrome element combination of phlegm obstruction + Qi stagnation + blood stasis being the most common. The syndromes can be classified into four categories of liver-stomach disharmony + combined phlegm and Qi obstruction, kidney-spleen dysfunction + combined phlegm and stasis, spleen-kidney Yang deficiency + obstinate phlegm and blood stasis, and liver-kidney Yin deficiency + obstinate phlegm and blood stasis. The main syndrome of ESCC was liver-stomach disharmony + combined phlegm and Qi obstruction in the early stage, liver-spleen dysfunction + combined phlegm and stasis in the middle stage, and spleen-kidney Yang deficiency + obstinate phlegm and blood stasis in the late stage. ConclusionESCC mainly has main pathological features of internal deficiency and external excess and combined deficiency and excess, with the key syndrome elements being phlegm obstruction, Qi stagnation, and blood stasis. The main disease locations are in the spleen and stomach, involving the liver, kidney, chest and diaphragm, heart, and lung. The main syndrome is liver-stomach disharmony + combined phlegm and Qi obstruction. In clinical practice, it is necessary to grasp the pathogenesis dynamics of the disease and use prescriptions according to patients’ syndromes.
2.Risk factors for plastic bronchitis and pidemiological investigation of patients with mycoplasma pneumoniae pneumonia in 2020 - 2023
Tong CHENG ; Ran FU ; Yufeng WAN ; Yulong ZHENG
Journal of Public Health and Preventive Medicine 2025;36(5):76-79
Objective To investigate and analyze epidemiological characteristics of patients with mycoplasma pneumoniae pneumonia (MPP) from 2020 to 2023, and the risk factors for plastic bronchitis (PB), To provide data support for developing preventive measures. Methods The medical records of 2 257 patients with respiratory tract infection treated at Huai'an Hospital Affiliated to Xuzhou Medical University from 2020 to 2023 were collected. Count the number of MPP patients and analyze the MP detection rate. Multivariate logistic regression analysis and ROC curve was used to screen the risk factors for PB. Results A total of 858 cases were positive for MP antibodies, and the detection rate was 38.02%. There are statistically significant differences in MP detection rates among different genders, age groups, and years (P<0.05). Among the 286 patients diagnosed with MPP and undergoing bronchoscopy, 68 (23.78%) patients had PB. According to univariate and multivariate logistic regression analysis, small age, higher N%, D-D, LDH and AST levels were independent risk factors for PB (P<0.05). ROC curve analysis shows that age and combined detection are the most effective indicators for PB prediction, with areas under the curve of 0.998 and 0.961, respectively. Conclusion MP is the main pathogen of respiratory tract infections in the area from 2020 to 2023. Women and children are more susceptible to MP infection. Small age, high N%, DD, LDH and AST levels are independent risk factors for PB in patients with MPP. Targeted preventive measures should be taken for MP susceptible population, and close attention should be paid to PB related risk factors to prevent disease progression and the occurrence of PB.
3.Application of scaffold-based and scaffold-free strategy for treatment of growth plate cartilage regeneration
Ruoyi GUO ; Hanjie ZHUANG ; Xiuning CHEN ; Yulong BEN ; Minjie FAN ; Yiwei WANG ; Pengfei ZHENG
Chinese Journal of Tissue Engineering Research 2024;28(15):2437-2444
BACKGROUND:Tissue engineering is considered an ideal treatment for growth plate regeneration.However,most of the current research on regenerative tissue engineering is the traditional scaffold-based strategy.As the limitations of traditional scaffolds are gradually revealed,the research direction is gradually diversifying. OBJECTIVE:To summarize the application of scaffold-based and scaffold-free strategies in the treatment of growth plate cartilage regeneration and their respective advantages and disadvantages. METHODS:The relevant articles were searched from PubMed,Wiley,and Elsevier.The search terms were"growth plate injury,regeneration,tissue engineering,scaffold,scaffold-free,biomimetic,cartilage"in English.The time was limited from 1990 to 2023.Finally,104 articles were included for review. RESULTS AND CONCLUSION:The biomimetic strategy is to reduce the cell composition,biological signals and unique mechanical properties of each region to the greatest extent by simulating the unique organizational structure of the growth plate,so as to build a biomimetic microenvironment that can promote tissue regeneration.Therefore,the design of a biomimetic scaffold is to simulate the original growth plate as far as possible in terms of composition,structure and mechanical properties.Although some results have been achieved,there is still the problem of the unstable regeneration effect.The scaffold-free strategy believes that the limitations of scaffolds will have adverse effects on regenerative therapy.Therefore,the design of scaffold-free constructs relies as much as possible on the ability of cells to generate and maintain extracellular matrix without interfering with cell-cell signals or introducing exogenous substances.However,there are some problems,such as poor stability,low mechanical strength and greater difficulty in operation.Biomimetic strategy and scaffold-free strategy have different emphases,advantages and disadvantages,but they both have positive effects on growth plate cartilage regeneration.Therefore,subsequent studies,whether adopting a biomimetic strategy or a scaffold-free strategy,will focus on the continuous optimization of existing technologies in order to achieve effective growth plate cartilage regeneration therapy.
4.Effect of ursodeoxycholic acid on symptoms after severe acute respiratory syndrome coronavirus 2 infection in patients with primary biliary cholangitis and their family members
Gui JIA ; Chunmei YANG ; Xiufang WANG ; Juan DENG ; Ruiqing SUN ; Linhua ZHENG ; Yulong SHANG ; Ying HAN
Journal of Clinical Hepatology 2024;40(7):1370-1374
Objective To investigate the effect of ursodeoxycholic acid(UDCA)on the symptoms after severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in patients with primary biliary cholangitis(PBC)and their family member.Methods A questionnaire survey was conducted to collect related information from 171 PBC patients who attended The First Affiliated Hospital of Air Force Medical University before March 22,2023 and 128 family members,including demographic information,comorbidities,UDCA administration,SARS-CoV-2 infection,vaccination,symptoms,therapeutic medication,and the changes in liver disease-related symptoms.The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups.Results The median age was 51 years in the PBC patients and 49 years in the family members,with no significant difference between the two groups(P>0.05).Compared with the family member group,the PBC group had significantly lower body mass index(22.2±2.4 kg/m2 vs 23.3±2.9 kg/m2,P<0.001)and proportion of male individuals(10%vs 55%,P<0.001).All PBC patients received UDCA at a dose of 13—15 mg/kg,and SARS-CoV-2 infection rate was 100%in both groups.The family members had a significantly higher SARS-CoV-2 vaccination rate than the PBC patients(91%vs 57%,P<0.001).Compared with the family members,the PBC patients had significantly milder symptoms of sneezing,nasal obstruction,chest pain,and abnormal taste(P<0.05).Compared with the family members,the PBC patients had significantly lower rates of use of compound cold medicine(11%vs 20%,P<0.05)and Lianhua Qingwen capsules(12%vs 21%,P<0.05).For the PBC patients after SARS-CoV-2 infection,the liver disease-related symptoms such as fatigue,abdominal distension,dry mouth and dry eyes,pruritus,and yellow skin were aggravated by 37%,2%,27%,10%,and 3%,respectively.Conclusion Compared with the immediate family members of PBC patients who do not take UDCA,the PBC patients receiving UDCA do not show a reduction in SARS-CoV-2 infection rate,but UDCA may have a certain effect on alleviating infection-related symptoms in such patients.PBC patients may still experience the aggravation of liver disease-related symptoms after SARS-CoV-2 infection,and the long-term effect on PBC patients after SARS-CoV-2 infection should be taken seriously in clinical practice.
5.Constructing and evaluating an animal model that combines post-infection irritable bowel syndrome and the pattern of liver depression and spleen deficiency with dampness
Shumin QIN ; Yulong LI ; Yuanming YANG ; Weihuan CHEN ; Haomeng WU ; Huan ZHENG ; Shaogang HUANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(1):49-61
Objective We aimed to establish and evaluate a rat model of post-infectious irritable bowel syndrome(PI-IBS)with the pattern of liver depression and spleen deficiency coupled with dampness.Methods First,200 rats were randomly divided into the normal group,the infection group,the infection+stress group,the infection+stress+external dampness group,and the acetic acid+stress group(n=40 rats per group)for eight weeks.The rats were treated with Trichinella spiralis infection,chronic restraint stress,an artificial high-humidity climate,and/or acetic acid enema.Weight growth rate,24-hour food intake and water intake,and the fecal moisture percentage were recorded.The open field test and the sucrose consumption test were used to determine the behavioral characteristics of rats in each group.The abdominal withdrawal reflex(AWR)test was used to determine visceral sensitivity.The contents of 5-hydroxytryptamine(5-HT)and aquaporin 4(AQP4)in colon tissue were detected by ELISA.Results Compared with the normal group,the weight growth rate of rats in the infection+stress+external dampness group and the acetic acid+stress group was lower from Week 1 to Week 8 of modeling.The 24-hour food intake of rats in the infection+stress+external dampness group and the infection+stress group was lower than that in the normal group from Week 2 to Week 8 of modeling.At the end of week 2 of modeling,the 24-hour water intake of rats in the infection+stress+external dampness group,the acetic acid+stress group,and the infection+stress group was lower than that in the normal group.The fecal moisture percentage of rats in the infection+stress+external dampness group was higher than that in the normal group at the end of Week 1,6,and 8(P<0.05).At the end of Week 4 of modeling,the total distance in the open field test in the infection+stress+external dampness group and the acetic acid+stress group was shorter than that in the normal group.The sugar preference rate in the infection+stress+external dampness group was lower than that in the normal group at the end of 1,4,and 8 weeks and lower than that in the acetic acid+stress group at the end of Week 4 and 8(P<0.05).The AWR scores of rats in the infection+stress+external dampness group were higher than those in the normal group after week 1 at 60 and 80 mmHg(1 mmHg≈0.133 kPa),after Week 4 at 40,60,and 80 mmHg,and after Week 6 and 8 at 20,40,and 80 mmHg(P<0.05).At the end of Week 2 and 4,a large number of inflammatory cells were infiltrated in the colonic mucosa of the intervention groups,and the inflammation score was higher than that of the normal group(P<0.05).At the end of weeks 6 and 8,the inflammatory cell infiltration in the intestinal mucosa of the intervention groups was not obvious,and the colonic mucosa returned to normal.At the end of weeks 6 and 8,the 5-HT content was higher in the infection+stress group,the infection+stress+external dampness group,and the acetic acid+stress group than in the normal group(P<0.05).After Week 4,the AQP4 content was lower in the infection+stress+external dampness group and the acetic acid+stress group than that in the normal group(P<0.05).After week 6,compared to the normal group,the AQP4 content was lower in all groups except for the acetic acid+stress group,and the AQP4 content in the infection+stress+external dampness group was lower than that in the acetic acid+stress group.After week 8,only in the infection+stress+external dampness group the AQP4 content was lower than in the normal group(P<0.05).Conclusion The combination of Trichinella spiralis infection,chronic restraint stress,and an artificial high-humidity climate can be used to prepare a relatively stable and reliable rat model of PI-IBS with the pattern of liver depression and spleen deficiency with dampness.
6.Mid-term efficacy of single anastomosis duodenal-ileal bypass with sleeve gastrectomy in the treatment of obesity and type 2 diabetes mellitus
Minghao XIAO ; Lun WANG ; Shixing LI ; Yang LIU ; Zheng ZHANG ; Lifu HU ; Yulong CHEN ; Hui REN ; Tao JIANG
Chinese Journal of Gastrointestinal Surgery 2024;27(10):1056-1062
Objective:To evaluate the mid-term efficacy of single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) in the treatment of obesity and type 2 diabetes mellitus.Methods:The cohort of this retrospective observational study comprised 118 obese patients with body mass index (BMI) ≥40 kg/m 2 with or without other related metabolic diseases and BMI of (27.5-40.0) kg/m 2 with type 2 diabetes mellitus (T2DM) who had been treated with SADI-S. Patients who had undergone modified surgery or been followed up for less than 1 year were excluded. Clinical data of the included patients [56 men and 62 women aged (34.5±9.7) years], who had undergone SADI-S in China-Japan Union Hospital, Jilin University from October 2018 to August 2022, were collected. Their mean preoperative body mass was (125.9±25.0) kg and BMI (42.8±6.8) kg/m 2. The 60 patients with T2DM had a mean fasting blood glucose of (9.9±3.2) mmol/L and HBA1c of (8.4±1.7) % before surgery. The main outcome measures were mid-term weight loss after surgery (body mass, BMI, excess weight loss, and total weight loss) 1, 2, 3, and 4 years after surgery and efficacy regarding diabetes mellitus (fasting blood glucose, glycated hemoglobin and diabetes remission rate at 1, 2, and 3 years after surgery). Outcomes were defined as follows. Complete remission: HbA1c <6% or fasting blood glucose <6 mmol/L without hypoglycemic medication; partial remission: HBA1c <6.5% or fasting blood glucose <7 mmol/L without hypoglycemic medication; significant improvement: HBA1c <7.0%, stable decrease of at least 1% compared with preoperative HBA1c, and postoperative dose of hypoglycemic medication significantly less; ineffective: no change in HBA1c and no reduction in dosage of hypoglycemic medication. Other outcome measures included intraoperative and postoperative adverse effects and postoperative nutritional indexes. Results:SADI-S was successful in all patients. There was no significant bleeding, conversion to open surgery, or perioperative death. The operation time was (186.1±41.5) minutes, and the postoperative hospital stay 6 (5–7) days. Surgical complications occurred in four patients, comprising peritoneal effusion, internal jugular vein thrombosis, anastomotic leakage, and gastric fistula. Body weight and BMI 1, 2, 3 and 4 years were significantly lower post- than pre-operatively (all P<0.05). Excess weight loss was (81.9±16.2) %, (82.2±15.5) %, (88.3±20.1) %, and (83.2±18.1) % at 1, 2, 3, and 4 years postoperatively, respectively. Total weight loss was (39.7±8.7) %, (40.6±10.6) %, (42.2±11.5) % and (45.4±10.2) %, respectively. The mean fasting blood glucose concentrations of the 60 patients with T2DM were (5.1±1.0) mmol/L, (5.0±0.7) mmol/L, and (5.4±0.9) mmol/L 1, 2 and 3 years postoperatively, respectively. The values for glycosylated hemoglobin were (4.9±0.6) %, (4.8±0.5) %, and (5.1±0.8) %, respectively, all of which are significantly lower than preoperatively (all P<0.05). The complete remission rate of diabetes was 95.0% (38/40), 90.0% (36/40), and 9/13 1, 2, and 3 years postoperatively, respectively. Additionally, the partial remission rate and significant improvement rate were both 100%. Two years postoperatively, the incidence of anemia was 27.8% (10/36), of hypoproteinemia 11.8% (4/34), and of ferritin deficiency 25.8% (8/31), all of which were improved by conservative treatment such as blood transfusion, iron supplementation, and adjustment of diet. Conclusion:SADI-S has a significant mid-term beneficial effect on weight loss and diabetes remission status in patients with obesity and type 2 diabetes.
7.Mid-term efficacy of single anastomosis duodenal-ileal bypass with sleeve gastrectomy in the treatment of obesity and type 2 diabetes mellitus
Minghao XIAO ; Lun WANG ; Shixing LI ; Yang LIU ; Zheng ZHANG ; Lifu HU ; Yulong CHEN ; Hui REN ; Tao JIANG
Chinese Journal of Gastrointestinal Surgery 2024;27(10):1056-1062
Objective:To evaluate the mid-term efficacy of single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) in the treatment of obesity and type 2 diabetes mellitus.Methods:The cohort of this retrospective observational study comprised 118 obese patients with body mass index (BMI) ≥40 kg/m 2 with or without other related metabolic diseases and BMI of (27.5-40.0) kg/m 2 with type 2 diabetes mellitus (T2DM) who had been treated with SADI-S. Patients who had undergone modified surgery or been followed up for less than 1 year were excluded. Clinical data of the included patients [56 men and 62 women aged (34.5±9.7) years], who had undergone SADI-S in China-Japan Union Hospital, Jilin University from October 2018 to August 2022, were collected. Their mean preoperative body mass was (125.9±25.0) kg and BMI (42.8±6.8) kg/m 2. The 60 patients with T2DM had a mean fasting blood glucose of (9.9±3.2) mmol/L and HBA1c of (8.4±1.7) % before surgery. The main outcome measures were mid-term weight loss after surgery (body mass, BMI, excess weight loss, and total weight loss) 1, 2, 3, and 4 years after surgery and efficacy regarding diabetes mellitus (fasting blood glucose, glycated hemoglobin and diabetes remission rate at 1, 2, and 3 years after surgery). Outcomes were defined as follows. Complete remission: HbA1c <6% or fasting blood glucose <6 mmol/L without hypoglycemic medication; partial remission: HBA1c <6.5% or fasting blood glucose <7 mmol/L without hypoglycemic medication; significant improvement: HBA1c <7.0%, stable decrease of at least 1% compared with preoperative HBA1c, and postoperative dose of hypoglycemic medication significantly less; ineffective: no change in HBA1c and no reduction in dosage of hypoglycemic medication. Other outcome measures included intraoperative and postoperative adverse effects and postoperative nutritional indexes. Results:SADI-S was successful in all patients. There was no significant bleeding, conversion to open surgery, or perioperative death. The operation time was (186.1±41.5) minutes, and the postoperative hospital stay 6 (5–7) days. Surgical complications occurred in four patients, comprising peritoneal effusion, internal jugular vein thrombosis, anastomotic leakage, and gastric fistula. Body weight and BMI 1, 2, 3 and 4 years were significantly lower post- than pre-operatively (all P<0.05). Excess weight loss was (81.9±16.2) %, (82.2±15.5) %, (88.3±20.1) %, and (83.2±18.1) % at 1, 2, 3, and 4 years postoperatively, respectively. Total weight loss was (39.7±8.7) %, (40.6±10.6) %, (42.2±11.5) % and (45.4±10.2) %, respectively. The mean fasting blood glucose concentrations of the 60 patients with T2DM were (5.1±1.0) mmol/L, (5.0±0.7) mmol/L, and (5.4±0.9) mmol/L 1, 2 and 3 years postoperatively, respectively. The values for glycosylated hemoglobin were (4.9±0.6) %, (4.8±0.5) %, and (5.1±0.8) %, respectively, all of which are significantly lower than preoperatively (all P<0.05). The complete remission rate of diabetes was 95.0% (38/40), 90.0% (36/40), and 9/13 1, 2, and 3 years postoperatively, respectively. Additionally, the partial remission rate and significant improvement rate were both 100%. Two years postoperatively, the incidence of anemia was 27.8% (10/36), of hypoproteinemia 11.8% (4/34), and of ferritin deficiency 25.8% (8/31), all of which were improved by conservative treatment such as blood transfusion, iron supplementation, and adjustment of diet. Conclusion:SADI-S has a significant mid-term beneficial effect on weight loss and diabetes remission status in patients with obesity and type 2 diabetes.
8.Radiographic anatomical ratios between tibial plateau and distal femur and the clinical value in evaluating reduction of Schatzker Ⅳ-C tibial plateau fractures
Yulong LIU ; Rende NING ; Run FANG ; Han-Lin ZHENG ; Chengnan ZHANG ; Daobin ZHOU ; Zulong ZHOU
The Journal of Practical Medicine 2024;40(9):1257-1261
Objective To investigate the radiographic anatomical relationship between tibial plateau and distal femur and evaluate the impact of reset tibial plateau of various widths after reduction of the Schatzker Ⅳ-C tibial plateau fractures on postoperative outcomes.Methods We collected and reviewed the X-ray images of the normal knees of 207 standard neutrally-positioned adults(non-fracture group)and pre-and post-operative immediate anterior-posterior X-ray images of the knees of 60 patients with Schatzker Ⅳ-C fractures(fracture group)in our hospital from August 2012 to August 2022.We measured the proximal tibial joint width(TAW),distal femoral width(DFW),and distal femoral joint width(FAW)in both groups and calculated the TAW/DFW and TAW/FAW ratios.In the fracture group,the cases with TAW between FAW and DFW were assigned to the well-reduced group,while those with TAW outside this range between FAW and DFW to the poorly-reduced group.Both groups were assessed using the Hospital for Special Surgery knee score(HSS)one year after operation.Results In the non-fracture group,there were no significant differences in gender or affected side in terms of TAW/DFW and TAW/FAW ratios(P>0.05),while in the fracture group,there were statistically significant differences in the TAW/DFW and TAW/FAW ratios compared to the non-fracture group(P<0.05).There was a statistically signifi-cant difference in the one-year postoperative HSS scores between the well-reduced and poorly-reduced groups in the fracture group(P<0.05).Conclusion The radiographic anatomical relationship between the tibial plateau and distal femur in normal adults is relatively constant,providing a radiological reference for resetting the tibial plateau to a satisfactory width during reduction of Schatzker Ⅳ-C fractures.TAW/DFW>1 or TAW/FAW<1 indicates a poor reduction of the fracture and predicts poor postoperative recovery of knee joint function.
9.Advancements in gene therapy for pediatric rare diseases associated with skeletal conditions
Yulong BEN ; Peng LIU ; Pengfei ZHENG
Chinese Journal of Orthopaedics 2024;44(18):1246-1254
Rare diseases, also known as orphan diseases, refer to a category of illnesses characterized by low prevalence, complex disease profiles, and severe symptoms. Rare diseases often manifest early in life, with symptoms frequently appearing in childhood. Among these conditions, changes in bone structure play a crucial role, and many rare diseases of this nature have a genetic basis and lack effective treatment modalities. With advances and breakthroughs in human gene research, the etiology of many rare diseases has been gradually uncovered. This paper reviews recent advances in gene therapy for rare pediatric bone diseases and its application in treating skeletal-related rare conditions. Special attention is directed towards cases such as osteogenesis imperfecta, X-linked hypophosphatemia and achondroplasia, and related gene therapy strategies are introduced. Osteogenesis imperfecta is primarily treated with bone marrow-derived mesenchymal stem cell transplantation and gene editing techniques, with experimental data validating their efficacy and safety; X-linked hypophosphatemic rickets has focused on FGF23 monoclonal antibodies, with clinical trials showing significant improvement in patient symptoms. Achondroplasia is primarily treated with small molecule tyrosine kinase inhibitors and C-type natriuretic peptide analogs, with research indicating these methods significantly improve bone growth. Although gene therapy research is still in its early stages, it provides hope for treating these rare diseases and may become a viable future treatment option for pediatric skeletal-related rare conditions.
10.Click chemistry extracellular vesicle/peptide/chemokine nanocarriers for treating central nervous system injuries.
Huitong RUAN ; Yongfang LI ; Cheng WANG ; Yixu JIANG ; Yulong HAN ; Yiwei LI ; Dandan ZHENG ; Jing YE ; Gang CHEN ; Guo-Yuan YANG ; Lianfu DENG ; Ming GUO ; Xingcai ZHANG ; Yaohui TANG ; Wenguo CUI
Acta Pharmaceutica Sinica B 2023;13(5):2202-2218
Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.


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