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that were not closely related to the article's theme,of poor quality,repetitive,or outdated were excluded.A total of 115 articles met the inclusion criteria.RESULTS AND CONCLUSION:(1)Functional loading is used to combine therapeutic molecules with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.

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.

ObjectiveThis paper aims to systematically reveal the effect difference and mechanisms of Zishenwan against chronic prostatitis （CP） before and after salt-processing of Anemarrhenae rhizoma and Phellodendri chinensis cortex based on an integrated strategy of ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry （UPLC-Q-Orbitrap-MS/MS）， network pharmacology， and serum metabolomics. MethodsZishenwan samples before and after salt-processing of Anemarrhenae rhizoma and Phellodendri chinensis cortex were extracted by alcohol-water dual extraction. The chemical components of each sample were detected by UPLC-Q-Orbitrap-MS/MS， and differential components were screened by multivariate statistical analysis. Network pharmacology analysis was performed based on the identified chemical components of Zishenwan to construct a protein-protein interaction （PPI） network of "component， target， and pathway"， and the core components， targets， and pathways of Zishenwan against CP were screened. Forty-two male Sprague-Dawley （SD） rats were randomly divided into a blank group， a model group， a Qianliekang group （1.54 g·kg^-1）， low- and high-dose raw Zishenwan groups （1.8， 5.4 g·kg^-1）， and low- and high-dose salt-processed Zishenwan groups （1.8， 5.4 g·kg^-1）. The CP rat model was established by intraprostatic injection of carrageenan. After one week of recovery， the rats were administered the corresponding drugs for 21 days， while those in the blank group and model group received the same volume of normal saline. After the experiment， serum and tissue samples were collected to evaluate pharmacodynamic indicators including organ indices， histopathology， and inflammatory factors in serum. Subsequently， untargeted serum metabolomics technology was used to analyze metabolite changes and perform pathway enrichment analysis. The network pharmacology was used to construct a network of "differential metabolite， reaction， enzyme， and gene". ResultsA total of 76 components were identified in raw and salt-processed Zishenwan， and 34 differential components were screened by multivariate statistical analysis. Among them， the contents of 14 components， including berberine， berberrubine， and phellodendrine， increased after salt-processing， while the contents of 20 components， such as neomangiferin， decreased. The 28 active components and 185 potential targets were screened out by network pharmacology. The core components included berberine， phellodendrine， magnoflorine， and jatrorrhizine， and the core targets included signal transducer and activator of transcription 3 （STAT3）， protein kinase B1 （Akt1）， and transcription factor AP-1 （JUN）. These targets were significantly enriched in pro-inflammatory signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） and mitogen-activated protein kinase （MAPK）. Compared with the model group， all Zishenwan administration groups showed decreased prostate index， reduced levels of interleukin （IL）-1β， IL-18， and B-cell lymphoma-2 （Bcl-2） in serum （P<0.05， P<0.01）， as well as varying degrees of alleviation in histopathological damage. At the same dose， compared with the raw Zishenwan groups， the salt-processed Zishenwan groups showed lower prostate index， pathological scores， and IL-1β， IL-18， and Bcl-2 levels in serum， but the differences were not statistically significant. Metabolomics reveals that 38 differential metabolites were reversed after salt-processed Zishenwan administration. Both raw and salt-processed Zishenwan regulated pathways such as β-alanine metabolism and tryptophan metabolism. In addition to the common regulated pathways， the salt-processed group specifically regulated pantothenate and coenzyme A biosynthesis， pyrimidine metabolism， and arginine and proline metabolism. The intersecting pathways between network pharmacology and metabolomics were tryptophan metabolism and arginine and proline metabolism， with overlapping targets including monoamine oxidase A （MAOA） and arginase 1 （ARG1）. ConclusionThe increased contents of components such as berberine and phellodendrine in salt-processed Zishenwan may enhance its therapeutic effect on CP by inhibiting the PI3K/Akt and MAPK signaling pathways， along with multi-target regulation of tryptophan， arginine， and pantothenate metabolism pathways to comprehensively regulate inflammatory and immune responses.

Androgenic alopecia (AGA) stands as a prevalent and challenging dermatological condition in clinical practice. Its pathogenesis is complex and the condition is prone to recurrence, which seriously affects the physical and mental health of patients. This review synthesized recent advancements in understanding the multifaceted mechanisms underlying AGA progression. It delineated the intricate interplay among genetic predispositions, hormonal influences, cytokine-mediated regulations, molecular pathway activations, and alterations in the hair follicle microenvironment. By elucidating these diverse factors and their interactions, this article aimed to provide a theoretical basis and reference for new targets of action for the clinical treatment of AGA.

Objective To construct and validate the efficacy of a risk prediction model for pneumothorax after CT-guided percutaneous pulmonary puncture biopsy(CT-PCNB)based on nomograms.Methods A total of 246 patients who underwent CT-PCNB examination in the hospital from October 2020 to October 2023 were selected and divided into training set(n=144)and validation set(n=102)using a random sampling method.In the training set,univariate and multivariate logistic regression analyses were performed to identify risk factors for pneumothorax after CT-PCNB.A nomogram model was constructed based on the identified risk factors,and its accuracy was validated using the validation set.Results Multifactorial logistic regression analysis showed that age≥60 years,concomitant underlying lung disease,lesion diameter<2 cm,distance from lesion to pleura≥10 mm,puncture through interlobular pleura,and≥2 pleural punctures were the risk factors for pneumothorax after CT-PCNB in the training set(P<0.05).A nomogram model was constructed based on these six factors.The ROC curve results for the training set showed an AUC of 0.852,sensitivity of 84.50%,and specificity of 67.50%.The nomogram model was validated using the validation set,with ROC curve results showing an AUC of 0.845,sensitivity of 83.00%,and specificity of 69.50%.There was no statistically significant difference between the predicted and actual values in both the training and validation sets(χ2=1.803,1.225;P>0.05),indicating clinical validity.Conclusion The nomogram model constructed based on the risk factors for pneumothorax after CT-PCNB has high predictive efficacy and is clinically meaningful.

Objective To investigate the impact of aortic valve calcification on ascending aortic elasticity.Methods A total of 103 patients with aortic valve calcification indicated by coronary computed tomography angiography(CCTA)(calcification group),and 101 patients without aortic valve calcification(non calcification group)were selected.The calcification group was subdivided into group A,group B,and group C based on the number of calcified leaflets.The original data was automatically reconstructed at 5％R-R intervals throughout the cardiac cycle.Cross-sectional area and diameter of the ascending aorta were measured at 45 mm above the annulus,and four ascending aortic elasticity indicators aortic(％A),aortic distensibility(AD),aortic compliance(AC)and aortic stiffness index(ASI)were calculated.Agatston method was used to calculate the aortic valve calcification score.The effect of aortic valve calcification on the elasticity of the ascending aortic and its correlation were analyzed.Results The％A,AD,and AC of the calcification group were lower than those of the non calcification group,but the ASI was higher than that of the non calcification group,the difference was statistically significant(P＜0.05).The number of calcified leaflets affected ascending aortic elasticity,with comparisons between groups A and B,the difference was no statistically significant(P＞0.05),groups A and C,and groups B and C,the difference was statistically significant(P＜0.05).Calcification score was negatively correlated with％A,AD,and AC,and positively correlated with ASI.Conclusion Aortic valve calcification can affect the elasticity of the ascending aortic,and more than two calcified leaflets have more significant effects on the elasticity of the ascending aortic.

Objective To construct and validate the efficacy of a risk prediction model for pneumothorax after CT-guided percutaneous pulmonary puncture biopsy(CT-PCNB)based on nomograms.Methods A total of 246 patients who underwent CT-PCNB examination in the hospital from October 2020 to October 2023 were selected and divided into training set(n=144)and validation set(n=102)using a random sampling method.In the training set,univariate and multivariate logistic regression analyses were performed to identify risk factors for pneumothorax after CT-PCNB.A nomogram model was constructed based on the identified risk factors,and its accuracy was validated using the validation set.Results Multifactorial logistic regression analysis showed that age≥60 years,concomitant underlying lung disease,lesion diameter<2 cm,distance from lesion to pleura≥10 mm,puncture through interlobular pleura,and≥2 pleural punctures were the risk factors for pneumothorax after CT-PCNB in the training set(P<0.05).A nomogram model was constructed based on these six factors.The ROC curve results for the training set showed an AUC of 0.852,sensitivity of 84.50%,and specificity of 67.50%.The nomogram model was validated using the validation set,with ROC curve results showing an AUC of 0.845,sensitivity of 83.00%,and specificity of 69.50%.There was no statistically significant difference between the predicted and actual values in both the training and validation sets(χ2=1.803,1.225;P>0.05),indicating clinical validity.Conclusion The nomogram model constructed based on the risk factors for pneumothorax after CT-PCNB has high predictive efficacy and is clinically meaningful.

Objective To investigate the impact of aortic valve calcification on ascending aortic elasticity.Methods A total of 103 patients with aortic valve calcification indicated by coronary computed tomography angiography(CCTA)(calcification group),and 101 patients without aortic valve calcification(non calcification group)were selected.The calcification group was subdivided into group A,group B,and group C based on the number of calcified leaflets.The original data was automatically reconstructed at 5％R-R intervals throughout the cardiac cycle.Cross-sectional area and diameter of the ascending aorta were measured at 45 mm above the annulus,and four ascending aortic elasticity indicators aortic(％A),aortic distensibility(AD),aortic compliance(AC)and aortic stiffness index(ASI)were calculated.Agatston method was used to calculate the aortic valve calcification score.The effect of aortic valve calcification on the elasticity of the ascending aortic and its correlation were analyzed.Results The％A,AD,and AC of the calcification group were lower than those of the non calcification group,but the ASI was higher than that of the non calcification group,the difference was statistically significant(P＜0.05).The number of calcified leaflets affected ascending aortic elasticity,with comparisons between groups A and B,the difference was no statistically significant(P＞0.05),groups A and C,and groups B and C,the difference was statistically significant(P＜0.05).Calcification score was negatively correlated with％A,AD,and AC,and positively correlated with ASI.Conclusion Aortic valve calcification can affect the elasticity of the ascending aortic,and more than two calcified leaflets have more significant effects on the elasticity of the ascending aortic.

Androgenic alopecia (AGA) stands as a prevalent and challenging dermatological condition in clinical practice. Its pathogenesis is complex and the condition is prone to recurrence, which seriously affects the physical and mental health of patients. This review synthesized recent advancements in understanding the multifaceted mechanisms underlying AGA progression. It delineated the intricate interplay among genetic predispositions, hormonal influences, cytokine-mediated regulations, molecular pathway activations, and alterations in the hair follicle microenvironment. By elucidating these diverse factors and their interactions, this article aimed to provide a theoretical basis and reference for new targets of action for the clinical treatment of AGA.

ObjectiveTo conduct a systematic review of the health benefits of mindfulness interventions for older adults with insomnia disorders. MethodsThematic keyword search was conducted in databases including Web of Science, PubMed, Embase, EBSCO, CNKI, VIP and Wanfang data, for literature on the impact of mindfulness intervention on sleep quality in older adults with insomnia disorders, published up to August, 2023. The methodological quality of the researches was evaluated using the Physiotherapy Evidence Database (PEDro) scale. Insomnia disorders, sleep function and mindfulness interventions were coded using International Classification of Diseases 11th Revision, International Classification of Functioning, Disability and Health, and International Classification of Health Interventions Beta-3； and a systematic review was conducted following the PRISMA. ResultsNine researches from four countries were included, involving 800 participants, and all the researches were randomized controlled trials. The average score of PEDro scale was 7.1. The health-related conditions were insomnia disorders and insomnia disorders complicated with mild cognitive impairment. Mindfulness interventions used included mindfulness-based therapy for insomnia, mindfulness-based stress reduction, mindfulness-based cognitive therapy and mindfulness meditation. Interventions were implemented in institutions or health centers, care facilities, and community health service centers, varying from six to eight weeks. Health benefits of mindfulness intervention included improvements in sleep quality and psychological and behavioral health. ConclusionMindfulness interventions effectively improve sleep quality in older adults with insomnia disorders, alleviate negative emotional states such as depression, anxiety and perceived stress, and improve the quality of life.