BACKGROUND:Exosomes are nanoscale extracellular vesicles secreted by various types of cells,with advantages such as high bioavailability,low toxicity,low immunogenicity,and good biocompatibility.However,natural exosomes have certain limitations in clinical therapy.By using bioengineering techniques to modify and engineer exosomes,the engineered exosomes not only improve their original therapeutic effects but also exhibit excellent biostability and targeting specificity,showing great potential for application in the field of tissue repair.OBJECTIVE:To summarize the various strategies for engineering exosomes,including functional loading and surface modification,outline the research progress of engineered exosomes in different tissue repairs,and explore the therapeutic potential of engineered exosomes in tissue repair.METHODS:PubMed database was searched for relevant literature published between 2010 and 2024 using the search terms"engineered exosomes,tissue repair,biomaterials,tissue engineering,wound healing,parenchyma,bone regeneration,cartilage,neural,myocardial,hepatic."Studies that were not closely related to the article's theme,of poor quality,repetitive,or outdated were excluded.A total of 115 articles met the inclusion criteria.RESULTS AND CONCLUSION:(1)Functional loading is used to combine therapeutic molecules with exosomes to obtain additional properties or to enhance the original physiological function of the exosome,among which ultrasonication and extrusion are simple to operate and can obtain higher drug loading capacity at the same time.(2)Surface modification can make exosomes express desired proteins or enhance their targeting,including genetic engineering and chemical modification.Genetic engineering is complicated,poorly reproducible,and the end product is poorly controllable.Chemical modification,on the other hand,is relatively simple and versatile,and is more suitable for designing highly targeted and functionally specific engineered exosomes.(3)Among the techniques for pre-treating cells to obtain engineered exosomes,hypoxic pre-treatment is more widely used because of its simplicity and clearer mechanism,which can activate glycolysis to promote cell proliferation,and regulate the vascular endothelial growth factor receptor signaling pathway through the generation of hypoxia-inducible factors to promote angiogenesis.(4)The function of exosomes is affected by various factors such as cell source,cell state,synthesis process,and extracellular environment.If the engineering strategy is complicated,it is more difficult to ensure the functional consistency of the final engineered exosomes,so the relatively simple and reliable engineering strategy is more suitable for its clinical application.(5)Engineered exosomes combined with biomaterials or scaffolds can be used to treat complex wounds of skin soft tissue,such as infected wounds and diabetic ulcers.This approach enhances exosome delivery and controls their release,promotes tissue repair,controls infection,and regulates the local microenvironment of the wound.(6)A single mechanism of engineered exosomes is often ineffective due to the specificity of the bone tissue fracture,so dual or even multi-functional engineered exosomes are needed to promote fracture repair while anti-inflammatory or remodeling the vascular system.(7)The source of exosomes has a significant impact on neural tissue repair.Exosomes derived from different neural cells promote neural repair through different effects.In addition,the combination of stents and engineered exosomes for traumatic brain injury has obvious advantages,the stent itself provides hemostasis and support,combined with the engineered exosomes itself to promote the repair effect,can obtain better therapeutic effect.(8)In cardiac and hepatic tissue repair,it is needed to develop anti-fibrotic engineered exosomes to resist the abnormal repair of cardiac and hepatic tissues themselves,which will require further research in the future.

Patients with Takayasu arteritis combined with aortic valve disease often have a poor prognosis following surgical valve replacement, frequently encountering complications such as perivalvular leakage, valve detachment, and anastomotic aneurysm. This article presents a high-risk case wherein severe aortic valve insufficiency associated with Takayasu arteritis was successfully managed through transcatheter aortic valve implantation via the transapical approach. The patient had satisfactory valve function with no complications observed during the six-month postoperative follow-up. This case provides a minimally invasive and feasible alternative for the clinical management of such high-risk patients.

Objective: To investigate the prevalence of undernutrition and its associated factors among left behind and non left behind primary and secondary school students in the Nutrition Improvement Program for Rural Compulsory Education Students (NIPRCES) areas of central and western China, so as to provide evidence for improving the nutritional status of children and adolescents. Methods: A survey was conducted among 123 782 students selected by random cluster sampling method in grades 3-9 from NIPRCES in central (Hebei, Shanxi, Heilongjiang, Jilin, Anhui, Jiangxi, Henan, Hunan, Hubei, and Hainan) and western (Gansu, Guangxi, Inner Mongolia, Ningxia, Tibet, Shaanxi, Guizhou, Sichuan, Xinjiang, the Xinjiang Production and Construction Corps, Yunnan, Qinghai, and Chongqing) China in 2023. Anthropometric measurements and questionnaires were used to assess nutritional and dietary status. The prevalence of undernutrition was compared between left behind and non left behind students by Chi square test, and associated factors were analyzed by three level Logistic mixed effects model. Results: The prevalence of undernutrition was 8.5% (4 326) in left behind students and 8.1% (5 905) in non left behind students. Three level Logistic mixed effect model analysis showed that whether left behind or non left behind, the undernutrition rates of primary and secondary students in western regions were higher than those of students in central regions [ OR (95% CI )=1.72(1.57-1.87),2.25(2.07- 2.43 )]; the undernutrition risk was lower for those whose fathers had a cultural level of high school or above [ OR (95% CI )=0.69(0.62-0.77),0.90(0.82-0.98)] or junior high school [ OR (95% CI )=0.72(0.66-0.79),0.92(0.85-0.99)] compared to those with primary school or below; picky eating or selective eating increased the risk of undernutrition [ OR (95% CI )=2.36(2.07-2.68),2.28(2.04-2.55)], and primary and secondary school students without nutritional content in health education classes had higher rates of undernutrition [ OR (95% CI )=1.12(1.03-1.23),1.09(1.01-1.17)](all P <0.05). Conclusion The prevalence of undernutrition is slightly higher in left behind primary and secondary students than in non left behind primary and secondary students in central and western NIPRCES areas, with variations across different characteristics.

Objective: To analyze the trends of the frequency of meat, egg, and milk consumption among rural primary and junior high school students in central and western China covered by the Nutrition Improvement Program for Rural Compulsory Education Students (NIPRCES) from 2015 to 2023, so as to provide basis for formulating more targeted nutrition intervention policies and health education strategies. Methods: Using data from six rounds of monitoring and evaluation (2015-2021 and 2023), the study included 323 870 students from grade 3 to 9 across 22 provinces (autonomous regions and municipalities) in central and western China. The consumption frequencies of meat, egg, and milk over the past week were collected via questionnaires. The Cochran-Armitage trend test was used to analyze temporal trends, and multivariable Logistic regression models were employed to analyze factors associated with the frequency of meat, egg and milk consumption and to test for interaction effects between the year and gender, region, and grade level. Results: From 2015 to 2023, the proportion of students consuming meat, egg, and milk ≥1 time/day increased from 23.20 %, 10.71%, and 0.74% to 35.53%, 22.09%, and 26.63%, respectively. Trend tests indicated a significant upward trend for the daily intake of all three food categories for meat, egg and milk over the years ( Z =67.18, 64.90, 93.14, all P <0.01). Multivariable Logistic regression analysis showed that the daily meat intake was lower in the central region than in the western region ( OR=0.77, 95%CI =0.76-0.78), whereas the daily intake of eggs ( OR=1.19, 95%CI =1.17-1.22) and milk ( OR= 1.27 , 95%CI =1.24-1.29) was higher in the central region (all P <0.05). Compared with grade 3-4 students, junior high school students had lower daily intake of meat, eggs, and milk≥1 time/day ( OR =0.95, 0.77, 0.77, all P <0.05), with a declining trend as grade increased. Girls also had lower daily intake of meat, eggs, and milk ≥1 time/day than boys ( OR =0.95，0.93，0.91, all P < 0.05). Significant interactions were observed between year and region, as well as between year and grade (all P <0.05). Conclusion From 2015 to 2023, the NIPRCES improved the intake level of among rural students, but the situation of relatively insufficient intake of egg and milk among females, junior high school students and those in the western region still exists.

BACKGROUND:Exosomes are nanoscale extracellular vesicles secreted by various types of cells,with advantages such as high bioavailability,low toxicity,low immunogenicity,and good biocompatibility.However,natural exosomes have certain limitations in clinical therapy.By using bioengineering techniques to modify and engineer exosomes,the engineered exosomes not only improve their original therapeutic effects but also exhibit excellent biostability and targeting specificity,showing great potential for application in the field of tissue repair.OBJECTIVE:To summarize the various strategies for engineering exosomes,including functional loading and surface modification,outline the research progress of engineered exosomes in different tissue repairs,and explore the therapeutic potential of engineered exosomes in tissue repair.METHODS:PubMed database was searched for relevant literature published between 2010 and 2024 using the search terms"engineered exosomes,tissue repair,biomaterials,tissue engineering,wound healing,parenchyma,bone regeneration,cartilage,neural,myocardial,hepatic."Studies that were not closely related to the article's theme,of poor quality,repetitive,or outdated were excluded.A total of 115 articles met the inclusion criteria.RESULTS AND CONCLUSION:(1)Functional loading is used to combine therapeutic molecules with exosomes to obtain additional properties or to enhance the original physiological function of the exosome,among which ultrasonication and extrusion are simple to operate and can obtain higher drug loading capacity at the same time.(2)Surface modification can make exosomes express desired proteins or enhance their targeting,including genetic engineering and chemical modification.Genetic engineering is complicated,poorly reproducible,and the end product is poorly controllable.Chemical modification,on the other hand,is relatively simple and versatile,and is more suitable for designing highly targeted and functionally specific engineered exosomes.(3)Among the techniques for pre-treating cells to obtain engineered exosomes,hypoxic pre-treatment is more widely used because of its simplicity and clearer mechanism,which can activate glycolysis to promote cell proliferation,and regulate the vascular endothelial growth factor receptor signaling pathway through the generation of hypoxia-inducible factors to promote angiogenesis.(4)The function of exosomes is affected by various factors such as cell source,cell state,synthesis process,and extracellular environment.If the engineering strategy is complicated,it is more difficult to ensure the functional consistency of the final engineered exosomes,so the relatively simple and reliable engineering strategy is more suitable for its clinical application.(5)Engineered exosomes combined with biomaterials or scaffolds can be used to treat complex wounds of skin soft tissue,such as infected wounds and diabetic ulcers.This approach enhances exosome delivery and controls their release,promotes tissue repair,controls infection,and regulates the local microenvironment of the wound.(6)A single mechanism of engineered exosomes is often ineffective due to the specificity of the bone tissue fracture,so dual or even multi-functional engineered exosomes are needed to promote fracture repair while anti-inflammatory or remodeling the vascular system.(7)The source of exosomes has a significant impact on neural tissue repair.Exosomes derived from different neural cells promote neural repair through different effects.In addition,the combination of stents and engineered exosomes for traumatic brain injury has obvious advantages,the stent itself provides hemostasis and support,combined with the engineered exosomes itself to promote the repair effect,can obtain better therapeutic effect.(8)In cardiac and hepatic tissue repair,it is needed to develop anti-fibrotic engineered exosomes to resist the abnormal repair of cardiac and hepatic tissues themselves,which will require further research in the future.

Objective:To investigate the expression levels and clinical significance of miR-627 and miR-448 in colorectal cancer tissues.Methods:Ninety-eight patients with colorectal cancer admitted to Xi’an Jiaotong University Affiliated Red Cross Hospital from Apr. 2019 to Apr. 2021 were gathered. Colorectal cancer tissue and adjacent tissues were collected during surgery, and the expression levels of miR-627 and miR-448 were detected by qRT-PCR. According to postoperative follow-up, patients were separated into a good prognosis group and a poor prognosis group. Kaplan-Meier survival curve was applied to analyze the relationship between miR-627, miR-448 and the prognosis of colorectal cancer patients. ROC curve was plotted to analyze the predictive value of miR-627 and miR-448 for poor prognosis in colorectal cancer. The prognostic factors of colorectal cancer patients were analyzed using COX regression.Results:There was a difference in the expression levels of miR-627 and miR-448 between colorectal cancer tissue and adjacent tissues ( P<0.05). The expression of miR-627 and miR-448 in colorectal cancer tissue was related to clinical features (TNM stage, differentiation degree, lymph node metastasis, and depth of infiltration) ( P<0.05). The survival rate of patients with high expression of miR-627 was higher than that of patients with low expression ( χ2=10.050, P<0.05); the survival rate of patients with high expression of miR-448 was higher than that of patients with low expression ( χ2=9.033, P<0.05). The expression levels of miR-627 and miR-448 in the poor prognosis group were greatly lower than those in the good prognosis group ( P<0.05). According to the ROC curve, the AUC of miR-627 in predicting poor prognosis of colorectal cancer was 0.811, the AUC of miR-448 in predicting poor prognosis of colorectal cancer was 0.772, and the AUC of combination of the two in predicting poor prognosis of colorectal cancer was 0.859. The combination of the two was better than their individual predictions (Z combination vs. miR-627=2.538, Z combination vs. miR-448=2.572, P<0.05). Multivariate COX regression found that miR-627, miR-448, and clinical features (TNM stage, degree of differentiation, lymph node metastasis, and depth of infiltration) were risk factors affecting the prognosis of colorectal cancer patients ( P<0.05) . Conclusion:The expression levels of miR-627 and miR-448 in colorectal cancer tissues were greatly reduced. The combination of the two is related to the clinical characteristics and prognosis of patients, and can greatly improve the predictive value for prognosis of colorectal cancer patients.

Objective To establish two osteoarthritis models of destabilization of the medial meniscus(DMM)and chronic ankle instability(CAI)in mice,and compare the effects of knee osteoarthritis with varus deformity on ipsilateral ankle cartilage degeneration.Methods Thirty 6-week-old C57BL/6J male mice were randomly divided into a control group and two surgical groups(DMM group and CAI group),respectively.The progression of ankle joint degeneration was quantitatively evaluated through behavioral observation,imaging techniques and histopathology analysis in each group of mice over a 12-week period.Results A decline in gait stability and balance was observed in two surgical groups.Compared to the control group,the time required to cross the balance beam was increased by 23.20％,and the number of slips was increased by 43.26％at 12th week postoperatively in the DMM group.The bone volume fraction and bone mineral density of ankle joints also increased.Meanwhile,wear and tear of the ankle cartilage were found,with the formation of osteophytes,and OARSI score was increased by 88.89％.These changes in ankle joint were more pronounced in the CAI group.Conclusions This mouse model-based study revealed a coupling relationship between the knee and ankle motion.Knee osteoarthritis with varus deformity could lead to a significant ankle joint degeneration,while the damage was less severe than that observed in CAI.

To analyze all-cause mortality among hepatitis C cases aged ≥18 years in Yuxi City from 2005 to 2023 and explore the interactions of factors influencing survival time. Baseline and follow-up data for hepatitis C cases reported during this period were extracted from the Chinese National Notifiable Disease Reporting System. Survival time and related factors were assessed using the Cox proportional hazards model. Kaplan-Meier cumulative mortality risk curves were generated for treated and untreated hepatitis C cases, and interactions among subgroups of various influencing factors were examined. A total of 5 110 hepatitis C cases aged ≥18 years were reported from 2005 to 2023, encompassing 35 349.25 person-years of observation with the follow-up time duration M ( Q1, Q3) was 6.17 (2.33, 11.08) person-years. There were 763 all-cause deaths, corresponding to a mortality density of 2.16 per 100 person-years. Survival analysis showed a statistically significant difference in cumulative mortality between the treated and untreated groups (Log-rank χ2=122.033, P<0.001), with a lower risk of death observed among treated patients. Additive model analysis showed that there was a synergistic interaction between treatment status and age group, with relative excess of interaction, attributable proportions of interaction, and synergy index of 6.16 (95 %CI: 2.70-9.61), 1.83 (95 %CI: 1.46-2.30), and 0.42 (95 %CI: 0.31-0.53), respectively; and between treatment status and gender. There was a synergistic interaction between treatment status and sex, with relative excess of interaction, attributable proportions of interaction, and synergy index of 2.63 (95 %CI: 1.14-4.13), 1.56 (95 %CI: 1.19-2.06), and 0.32 (95 %CI: 0.17-0.46), respectively. The cause of death composition were 38.53% (249 cases) attributed to hepatitis C-related causes.The leading non-hepatitis C-related causes of death were cardiovascular and cerebrovascular diseases, pulmonary diseases, malignancies, drug overdose, and injuries. In conclusion, hepatitis C cases ≥18 years of age in Yuxi City had a lower cumulative mortality rate when treated than when untreated. Treatment status interacted with age and gender on patient survival, respectively. Changes in patients with concomitant cardiovascular diseases, pulmonary diseases and malignancies should be focused.

Objective:To investigate the expression levels and clinical significance of miR-627 and miR-448 in colorectal cancer tissues.Methods:Ninety-eight patients with colorectal cancer admitted to Xi’an Jiaotong University Affiliated Red Cross Hospital from Apr. 2019 to Apr. 2021 were gathered. Colorectal cancer tissue and adjacent tissues were collected during surgery, and the expression levels of miR-627 and miR-448 were detected by qRT-PCR. According to postoperative follow-up, patients were separated into a good prognosis group and a poor prognosis group. Kaplan-Meier survival curve was applied to analyze the relationship between miR-627, miR-448 and the prognosis of colorectal cancer patients. ROC curve was plotted to analyze the predictive value of miR-627 and miR-448 for poor prognosis in colorectal cancer. The prognostic factors of colorectal cancer patients were analyzed using COX regression.Results:There was a difference in the expression levels of miR-627 and miR-448 between colorectal cancer tissue and adjacent tissues ( P<0.05). The expression of miR-627 and miR-448 in colorectal cancer tissue was related to clinical features (TNM stage, differentiation degree, lymph node metastasis, and depth of infiltration) ( P<0.05). The survival rate of patients with high expression of miR-627 was higher than that of patients with low expression ( χ2=10.050, P<0.05); the survival rate of patients with high expression of miR-448 was higher than that of patients with low expression ( χ2=9.033, P<0.05). The expression levels of miR-627 and miR-448 in the poor prognosis group were greatly lower than those in the good prognosis group ( P<0.05). According to the ROC curve, the AUC of miR-627 in predicting poor prognosis of colorectal cancer was 0.811, the AUC of miR-448 in predicting poor prognosis of colorectal cancer was 0.772, and the AUC of combination of the two in predicting poor prognosis of colorectal cancer was 0.859. The combination of the two was better than their individual predictions (Z combination vs. miR-627=2.538, Z combination vs. miR-448=2.572, P<0.05). Multivariate COX regression found that miR-627, miR-448, and clinical features (TNM stage, degree of differentiation, lymph node metastasis, and depth of infiltration) were risk factors affecting the prognosis of colorectal cancer patients ( P<0.05) . Conclusion:The expression levels of miR-627 and miR-448 in colorectal cancer tissues were greatly reduced. The combination of the two is related to the clinical characteristics and prognosis of patients, and can greatly improve the predictive value for prognosis of colorectal cancer patients.

Purpose To explore the value of tumor intratumoral and peritumoral radiomics models based on dynamic contrast-enhanced MRI in predicting benign and malignant breast tumors.Materials and Methods This retrospective study analyzed clinical data and MRI imaging features from 309 patients with pathologically confirmed solitary breast tumors at the Second Affiliated Hospital of Xiamen Medical College from August 2018 to December 2022.The cohort was randomly divided into training(n=248)and testing(n=61)cohorts in an 8∶2 ratio.Using second-phase dynamic contrast-enhanced MRI images,five distinct peritumoral regions were segmented through 3D-Slicer software:intratumoral region,peritumoral 2 mm region,peritumoral 4 mm region,intratumoral combined with peritumoral 2 mm region and intratumoral combined with peritumoral 4 mm region.Radiomic features were extracted from these regions of interest.Machine learning algorithms integrated with Logistic regression analysis were employed for feature selection,with cross-validation techniques determining the optimal radiomic signature combination.Results Of 309 patients,150 were benign tumors and 159 were malignant tumors.The age,maximum diameter and enhancement type of benign and malignant breast tumors were statistically significant(Z/χ2=-7.695,-5.775,30.248;all P<0.001).For the region of interest of intratumoral combined with peritumoral 4 mm region,the area under curve,sensitivity,specificity,accuracy and F1 scores of the training and validation were 0.893,89.1%,75.0%,82.3%,0.838 and 0.881,74.2%,86.7%,80.3%,0.793,respectively.In the training set,the area under curve of intratumoral combined with peritumoral 4 mm region was significantly higher than that of intratumoral,peritumoral 2 mm,peritumoral 4 mm and intratumoral combined with peritumoral 2 mm regional imaging models(Z=2.506,2.982,3.392,2.157;all P<0.05).The Hosmer-Lemeshow test showed that the calibration curve of the model combined with region of interest of intratumoral combined with peritumoral 4 mm region was highly consistent with the ideal curve(training P=0.381,validation P=0.159).The decision curve indicated that the net benefit of the radiomics model in the region of interest of intratumoral combined with peritumoral 4 mm region was the highest when the risk threshold was between 0 and 1.0.Conclusion The radiomics model has good predictive performance in predicting benign or malignant breast tumors,among them the combined region of interest of intratumoral combined with peritumoral 4 mm region provides the best performance and highest benefit.The technology clinical application will provide a non-invasive predictive method for the differential diagnosis of benign and malignant breast tumors.