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that were not closely related to the article's theme,of poor quality,repetitive,or outdated were excluded.A total of 115 articles met the inclusion criteria.RESULTS AND CONCLUSION:(1)Functional loading is used to combine therapeutic molecules with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 Based on the visualization graph analysis of the research hotspots of Angelica sinensis, predict the future research trends, and provide references for the next step of Angelica sinensis research. Methods Chinese and English literatures on Angelica sinensis collected from CNKI, WanFang, VIP and Web of Science from 2012 to 2022 were retrieved. CiteSpace 6.1.R6 software was used to perform visualization econometrics analysis on the number of publications, authors, institutions, journals, keywords and other topics. Results 3490 Chinese literatures and 409 English literatures were included. Visual knowledge map analysis showed that Gansu University of Chinese Medicine and Nanjing University of Chinese Medicine were the research institutions with the largest number of literature publications in Chinese and English respectively. Journals published mainly include Shizhen Traditional Chinese Medicine and Materia medica, Evidence-based Complementary and Alternative Medicine. Current research hotspots include the effects of Angelica sinensis polysaccharides, volatile oils, and ferulic acid on the hematopoietic system, chronic diseases, and cognitive impairment, as well as clinical efficacy evaluations of classic prescriptions containing Angelica sinensis and their modified formulations. The research trend was characterized by a focus on the pharmacological study of Danggui Buxue Tang,employing various experimental approaches such as network pharmacology, serum pharmacology, and metabolomics to elucidate the mechanisms of Angelica sinensis. Conclusion The pharmacological effects of Angelica sinensis and its compound were extensive, which should be further researched.

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.

The inflammatory microenvironment is closely associated with the initiation and progression of osteoarthritis （OA）， specifically manifesting as macrophage activation， dysregulation of inflammatory cytokines， and redox imbalance. Following an overview of the pathological characteristics of the OA inflammatory microenvironment， this paper reviews the research progress on the mechanism of traditional Chinese medicine （TCM） intervening in OA by modulating the inflammatory microenvironment. It has been found that TCM monomers/active ingredients （such as total alkaloids from Strychnos nux-vomica ， quercetin， triptolide， etc.）， herb pairs （e.g. Angelica pubescens - Gentiana macrophylla ， Carthami Flos-Lycopodii Herba）， and TCM formulas （such as Zhuanggu jianxi formula， Duhuo jisheng decoction and Rongjin niantong formula， etc.） can inhibit macrophage activation， reduce the release of proinflammatory cytokines and the generation of reactive oxygen species by inhibiting multiple signaling pathways， including nuclear factor-κB， Wnt/ β -catenin， and mitogen-activated protein kinase， thereby alleviating the articular inflammatory microenvironment， restoring local joint homeostasis， and slowing the progression of OA.

OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

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 assess the echogenicity of the ultrasound-guided catheter and its associated delivery system. Methods The study consisted of in vitro characterization experiments and animal studies. In the in vitro phase, the acoustic and mechanical properties of the ultrasound-guided catheter were compared with those of the traditional MPA2 catheter, including parameters such as echo intensity, recognizability, and angle dependence. In the animal experiments, a ventricular septal defect (VSD) model was established in miniature pigs to compare the procedural performance of the ultrasound-guided delivery system versus the conventional system. Evaluation indicators included the time required for the system to cross the VSD, the detection rate of the system within the right ventricle, and the occurrence of intraoperative complications. Results The ultrasound-guided catheter demonstrated a significantly higher mean echo intensity than the MPA2 catheter [(237.3±1.8) dB vs. (190.9±13.1) dB, P<0.001] and a markedly improved recognizability rate (82.3%±5.6% vs. 26.7%±3.2%, P<0.001), along with better angle independence and image quality. In animal experiments, the ultrasound-guided delivery system significantly reduced the time required to cross the VSD [(18.5±5.7) min vs. (30.3±4.5) min, P<0.001] and substantially increased the detection rate within the right ventricle (100.0% vs. 30.0%). No severe complications occurred in any experimental animal. Conclusion The ultrasound-guided catheter and its corresponding delivery system exhibite superior ultrasound visibility and operational performance in both in vitro and animal experiments, indicating strong potential for clinical application.

Objective: o analyze the epidemic characteristics of five sexually transmitted diseases (STDs), including syphilis, gonorrhea, condyloma acuminatum, genital herpes and genital Chlamydia trachomatis infection in Yangzhou City, Jiangsu Province from 2019 to 2023, so as to provide the reference for the prevention and control strategies of STDs. Methods: Data of the onset time and diagnostic types of STDs cases in Yangzhou City from 2019 to 2023 were collected from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. The temporal, regional and population characteristics of five types of STDs was analyzed using the descriptive epidemiological method. Results: A total of 10 895 cases of STDs were reported in Yangzhou City from 2019 to 2023, with an average annual reported incidence rate of 47.83/105. The average annual reported incidence rates of syphilis, gonorrhea, condyloma acuminatum, genital herpes and genital Chlamydia trachomatis infections were 41.11/105, 2.83/105, 2.59/105, 0.43/105 and 0.85/105, respectively. The reported incidence rate of STDs showed a decreasing trend from 2019 to 2023 (P<0.05), with an average annual growth rate of -3.44%. The reported incidence rates of syphilis and gonorrhea showed a decreasing trend (both P<0.05), with average annual growth rates of -4.26% and -6.47%, respectively. The reported incidence rate of genital Chlamydia trachomatis infection showed an increasing trend (P<0.05), with an average annual growth rate of 22.32%. Baoying County, Guangling District and Hanjiang District had the top three reported incidence rates of STDs, at 56.61/105, 55.61/105 and 46.50/105, respectively. The average annual reported incidence rate of STDs among males was higher than that among females (53.19/105 vs. 42.54/105, P<0.05). The STD cases were primarily people aged 50 years and above, with 6 641 cases accounting for 60.95%. The occupations of STD cases were mainly farmers, housekeepers and unemployed, with 4 670 and 3 273 cases accounting for 42.86% and 30.04%, respectively. Conclusions The overall reported incidence of STDs in Yangzhou City from 2019 to 2023 showed a downward trend, while the reported incidence of genital Chlamydia trachomatis infection showed an upward trend. The individuals aged 50 years and above, farmers, housekeepers and the unemployed were identified as high-risk groups for STDs.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Objective To establish and evaluate an integrated disease-syndrome rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Methods Thirty male Wistar rats were allocated randomly into three groups(n=10 per group):sham operation(sham),2-vessel occlusion(2-VO)group,and sleep deprivation combined with 2-VO(SD+2-VO)group.We comprehensively assessed Qi deficiency and blood stasis syndrome manifestations in the rats using a dual evaluation approach,combining exhaustive swimming tests with quantitative tongue chroma analysis.Cognitive function was evaluated using the Barnes maze,and cerebral blood flow was compared using laser speckle contrast imaging.The histopathology of the hippocampal cytoarchitecture and white matter were examined using hematoxylin-eosin(HE)and Luxol fast blue(LFB)staining,respectively,and ultrastructural alterations of neurons in the hippocampal CA1 region were observed by transmission electron microscopy(TEM).Protein expression levels of NeuN,vascular endothelial growth factor A(VEGFA)and CD31 were detected by Western Blot and immunofluorescence.Results Cerebral blood flow was significantly reduced in rats in the 2-VO group compared with the sham group,but they failed to recapitulate the key clinical hallmarks of Qi deficiency and blood stasis syndrome.In contrast,rats in the SD+2-VO group exhibited significantly reduced locomotor activity,exacerbated cerebral hypoperfusion,shortened swimming duration,and darkened tongue color compared with 2-VO rats.Rats in the SD+2-VO group demonstrated significantly impaired learning and memory abilities in the Barnes maze test.Consistent with these observations,HE staining,TEM,and LFB staining revealed substantial neuronal and white matter damage in the SD+2-VO group.NeuN expression was decreased and VEGFA and CD31 expression levels were increased in the 2-VO and SD+2-VO groups,as shown by Western Blot.Taken together,these findings indicated that the SD+2-VO model effectively recapitulated the clinical features of chronic cerebral ischemia with Qi deficiency and blood stasis pattern.Conclusions The combination of sleep deprivation and bilateral carotid artery occlusion successfully established a rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Compared with the 2-VO model,SD+2-VO model demonstrates more pronounced syndrome manifestations and better clinical relevance,thus providing a valuable animal model for traditional Chinese medicine research on chronic cerebral ischemia.