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that were not closely related to the article's theme,of poor quality,repetitive,or outdated were excluded.A total of 115 articles met the inclusion criteria.RESULTS AND CONCLUSION:(1)Functional loading is used to combine therapeutic molecules with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

Objective To investigate the efficacy and safety of conventional open Latarjet surgery,arthroscopic Latarjet surgery,arthroscopic Bankart repair combined with Remplissage surgery in the treatment of recurrent anterior shoulder dislocation(RASD)with scapula glenoid bone defect>15%and meshing Hill-Sachs lesion.Methods The clinical data of 65 patients with RASD with 15%～25%scapula glenoid bone defect and meshing Hill-Sachs lesion admitted to our hospital from January 2022 to December 2024 were retrospectively analyzed.They were divided into group A,group B,and group C according to different surgical methods.Among them,group A underwent conventional open Latarjet surgery(n=18),group B underwent arthroscopic Latarjet surgery(n=21),and group C underwent arthroscopic Bankart repair combined with Remplissage surgery(n=26).The surgical conditions,preoperative and postoperative scores of related scales[visual analogue scale(VAS),Constant-Murley shoulder score,the University of California Los Angeles(UCLA)shoulder score],shoulder range of motion,postoperative complications and recurrence were compared among the three groups.Results Operation time:group B was longer than group A and group C(P<0.05),and group A was longer than group C(P<0.05).Intraoperative blood loss and hospital stay:group A was more or longer than group B and group C(P<0.05),group B was more or longer than group C(P<0.05).The VAS scores of the three groups at 1,6 and 12 months after operation were lower than those before operation(P<0.05).Pain VAS score at 1 and 6 months after operation:group A was higher than group B and group C(P<0.05).Pain VAS score at 1 month after operation:group B was higher than group C.Pain VAS score at 12 months after operation:there was no significant difference among the three groups(P>0.05).The UCLA shoulder scores of group A at 6 and 12 months after operation and group B and group C at 1,6 and 12 months after operation were higher than those before operation(P<0.05).UCLA score at 1 month after operation:group A0.05).The Constant-Murley scores of group A at 6 and 12 months after operation and group B and group C at 1,6 and 12 months after operation were higher than those before operation(P<0.05).Constant-Murley score at 1 month after operation:group A was lower than group B and group C(P<0.05).Constant-Murley score at 6 and 12 months after operation:three groups were equivalent(P>0.05).Forward flexion and lifting range of motion in the three groups:at 12 months after operation>before operation(P<0.05).Forward flexion and lifting range of motion was evaluated at 12 months after operation:there was no significant difference among the three groups(P>0.05).The range of motion of external rotation at body side and external rotation at 90° abduction before operation and at 12 months after operation:there was no significant difference between group A and group B(P>0.05).External rotation at body side and external rotation at 90° abduction of group C:at 12 months after operation of it was less than that before operation(P<0.05).The range of motion of external rotation at body side and external rotation at 90° abduction was obtained at 12 months after operation:group A and group B were greater than group C(P<0.05).Postoperative complication rate and recurrence rate:three groups were equivalent(P>0.05).Conclusion Conventional open Latarjet surgery,arthroscopic Latarjet surgery,arthroscopic Bankart repair combined with Remplissage surgery can effectively improve shoulder joint function and relieve pain in the treatment of RASD with 15%～25%scapula glenoid bone defect and meshing Hill-Sachs lesion.However,the two shoulder arthroscopic procedures are less traumatic and have faster postoperative recovery.

Objective To investigate the efficacy and safety of conventional open Latarjet surgery,arthroscopic Latarjet surgery,arthroscopic Bankart repair combined with Remplissage surgery in the treatment of recurrent anterior shoulder dislocation(RASD)with scapula glenoid bone defect>15%and meshing Hill-Sachs lesion.Methods The clinical data of 65 patients with RASD with 15%～25%scapula glenoid bone defect and meshing Hill-Sachs lesion admitted to our hospital from January 2022 to December 2024 were retrospectively analyzed.They were divided into group A,group B,and group C according to different surgical methods.Among them,group A underwent conventional open Latarjet surgery(n=18),group B underwent arthroscopic Latarjet surgery(n=21),and group C underwent arthroscopic Bankart repair combined with Remplissage surgery(n=26).The surgical conditions,preoperative and postoperative scores of related scales[visual analogue scale(VAS),Constant-Murley shoulder score,the University of California Los Angeles(UCLA)shoulder score],shoulder range of motion,postoperative complications and recurrence were compared among the three groups.Results Operation time:group B was longer than group A and group C(P<0.05),and group A was longer than group C(P<0.05).Intraoperative blood loss and hospital stay:group A was more or longer than group B and group C(P<0.05),group B was more or longer than group C(P<0.05).The VAS scores of the three groups at 1,6 and 12 months after operation were lower than those before operation(P<0.05).Pain VAS score at 1 and 6 months after operation:group A was higher than group B and group C(P<0.05).Pain VAS score at 1 month after operation:group B was higher than group C.Pain VAS score at 12 months after operation:there was no significant difference among the three groups(P>0.05).The UCLA shoulder scores of group A at 6 and 12 months after operation and group B and group C at 1,6 and 12 months after operation were higher than those before operation(P<0.05).UCLA score at 1 month after operation:group A0.05).The Constant-Murley scores of group A at 6 and 12 months after operation and group B and group C at 1,6 and 12 months after operation were higher than those before operation(P<0.05).Constant-Murley score at 1 month after operation:group A was lower than group B and group C(P<0.05).Constant-Murley score at 6 and 12 months after operation:three groups were equivalent(P>0.05).Forward flexion and lifting range of motion in the three groups:at 12 months after operation>before operation(P<0.05).Forward flexion and lifting range of motion was evaluated at 12 months after operation:there was no significant difference among the three groups(P>0.05).The range of motion of external rotation at body side and external rotation at 90° abduction before operation and at 12 months after operation:there was no significant difference between group A and group B(P>0.05).External rotation at body side and external rotation at 90° abduction of group C:at 12 months after operation of it was less than that before operation(P<0.05).The range of motion of external rotation at body side and external rotation at 90° abduction was obtained at 12 months after operation:group A and group B were greater than group C(P<0.05).Postoperative complication rate and recurrence rate:three groups were equivalent(P>0.05).Conclusion Conventional open Latarjet surgery,arthroscopic Latarjet surgery,arthroscopic Bankart repair combined with Remplissage surgery can effectively improve shoulder joint function and relieve pain in the treatment of RASD with 15%～25%scapula glenoid bone defect and meshing Hill-Sachs lesion.However,the two shoulder arthroscopic procedures are less traumatic and have faster postoperative recovery.

Objective Based on U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,the signal mining of tizanidine adverse drug events(ADEs)was conducted to explore the occurrence characteristics of ADE,hoping to provide references for the safe clinical application of tizanidine.Methods The reporting odds ratio(ROR)and medicines and healthcare products regulatory agency methods(MHRA)were used to analyse the ADE of tizanidine using FAERS registration data from the first quarter of 2004 to the second quarter of 2022.After valid signals were obtained,the MedDRA was used for translation and system organ classification.Results A total of 7 135 reports of tizanidine ADE were obtained,including 1 732 patients,1 304 ADE types were involved.According to the results of 2 ADE signal mining methods,at the preferred term(PT)level,177 signals were detected.There were 32 PT signals not included in the drug instructions,including potassium wasting nephropathy,cardio-respiratory arrest,and foetal growth restriction etc.In 1 732 patients,the number of ADE cases of female was 2.37 times that in male(1 057 vs.446),and the age group between 40 and 64 accounted for a large proportion(36.03％).The highest proportion(32.79％)reported by consumers.The system organ class involved mainly included various neurological diseases and psychosis.The median time to onset of tizanidine-related ADEs was 75 d(interquartile range:28-223 d),but it was necessary to be vigilant that ADE may still occur 1 year after starting the drug(13.38％).Conclusion This study aims to suggest that clinical application of tizanidin-related ADE should be paid full attention to the occurrence of ADE such as potassium-wasting nephropathy and suicidally completed,as well as key populations such as women and patients of 40-64 years old.

BACKGROUND: How to locate pulmonary ground-glass nodules in thoracoscopic surgery is an important clinical topic in minimally invasive thoracic surgery. There is no unified localization method at present. This study intends to investigate the accuracy and security of body surface theodolitic puncture localization method in video-assisted thoracoscopic surgery for pulmonary ground-glass nodules. METHODS: The clinical data of 41 patients from August 2018 to December 2019 were analyzed retrospectively, including 28 males and 13 females. After anesthesia, the patient was located by body surface theodolitic puncture, and then partial lobectomy was performed under video-assisted thoracoscopy. The distance from the nodule to the marked suture and the distance from the nodule to the incisal margin were measured, and the accuracy of localization, the rate of complication and the success rate of surgical resection were calculated. RESULTS: A total of 51 nodules in 41 patients were located by body surface theodolitic puncture localization method. The accuracy rate was 96.1%, and the average location time was 8.3 min. Puncture bleeding occurred in 5 cases (12.2%), all of which were successfully stopped by video-assisted thoracoscopy, and there were no other complications. All patients underwent thoracoscopic partial lobectomy, including 33 cases of anatomical segmentectomy and 8 cases of wedge lobectomy. All the patients in operation process smoothly. The distance between nodule and incisal margin was measured, and all specimens were more than 2 cm, reaching a safe distance. The success rate of surgical resection was 100.0%. CONCLUSIONS In video-assisted thoracoscopic surgery for ground glass nodules of lung, the body surface theodolitic puncture localization method can be accurate, safe and simple.

Vision formation is classically based on projections from retinal ganglion cells (RGC) to the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). Neurons in the mouse V1 are tuned to light stimuli. Although the cellular information of the retina and the LGN has been widely studied, the transcriptome profiles of single light-stimulated neuron in V1 remain unknown. In our study, in vivo calcium imaging and whole-cell electrophysiological patch-clamp recording were utilized to identify 53 individual cells from layer 2/3 of V1 as light-sensitive (LS) or non-light-sensitive (NS) by single-cell light-evoked calcium evaluation and action potential spiking. The contents of each cell after functional tests were aspirated in vivo through a patch-clamp pipette for mRNA sequencing. Moreover, the three-dimensional (3-D) morphological characterizations of the neurons were reconstructed in a live mouse after the whole-cell recordings. Our sequencing results indicated that V1 neurons with a high expression of genes related to transmission regulation, such as Rtn4r and Rgs7, and genes involved in membrane transport, such as Na/K ATPase and NMDA-type glutamatergic receptors, preferentially responded to light stimulation. Furthermore, an antagonist that blocks Rtn4r signals could inactivate the neuronal responses to light stimulation in live mice. In conclusion, our findings of the vivo-seq analysis indicate the key role of the strength of synaptic transmission possesses neurons in V1 of light sensory.

OBJECTIVE： To investigate the effects of adiponectin （APN） on the expression of myocardial AMPK in myocardial insulin resistance （IR） model dogs during cardiopulmonary bypass （CPB）. METHODS： Totally 24 dogs were randomly divided into control group， model group， APN group （36 μg/kg）， AMPK inhibition group （APN 36 μg/kg+AMPK inhibitor compound C 0.5 mg/kg）， with 6 dogs in each group. All dogs underwent CPB； except for control group without medicine， CPB myocardial IR model were established in other groups， and perfused with St.Thomas cardiac cardioplegia lipid no medicine or containing relevant drugs after main artery block. Coronary sinus blood and carotid artery blood samples were collected before bypass and after 15， 90 min reperfusion following 60 min myocardial ischemia. Left ventricular apical tissue was taken， and the uptake rate of myocardial glucose and insulin resistance index （IRI） were determined and calculated； the changes of myocardial injury indexes （cTnT concentration） and cardiac function indexes （LVSP， +dp/dtmax） were monitored. The level of p-AMPK was detected. RESULTS： There was no statistical significance in above indexes of dogs before bypass （P＞0.05）. Compared with control group， the rate of myocardial glucose uptake， the levels of LVSP， +dp/dtmax and p-AMPK in model group were decreased significantly after 15， 90 min reperfusion （P＜0.05）， and the concentrations of IRI and cTnT were increased significantly （P＜0.05）. Compared with model group， the rate of myocardial glucose uptake， LVSP， +dp/dtmax and p-AMPK were increased significantly in APN group and AMPK inhibitor group （P＜0.05）， while the concentrations of IRI and cTnT were decreased significantly （P＜0.05）； moreover， the effect of APN group was better than that of AMPK inhibitor group （P＜0.05）. CONCLUSIONS： APN can promote myocardial glucose uptake and metabolism， and contribute the recovery of cardiac function， the mechanism of which may be associated with increasing the activity of AMPK.

Objective To study the clinical value of anti-oxidative stress biomarkers for diagnosing in-stent restenosis and in-reocclusion after coronary stent implantation in aged patients.Methods A total of 72 advanced-aged patients with in-stent restenosis and in-stent reocclusion after coronary stent implantation were successively recruited in this retrospective study from February 2010 to November 2017.Changes in serum superoxide dismutase 3(SOD3),nitric oxide(NO),endothelial cell nitric oxide synthase(eNOS)and malondialdehyde(MDA)levels were measured.Results Serum 1evels of SOD3,NO and eNOS decreased and serum MDA levels were elevated in advanced-aged patients with in-stent restenosis.There were significant differences in serum levels of SOD3,NO,eNOS and MDA between the advanced-aged patients without in-stent restenosis and the advanced-aged patients with multivessel in-stent restenosis or reocclusion[(20.0±3.2) × 103U/L vs.(10.9±3.9) ×103U/L,(61.2±14.2)μmol/L vs.(28.3±17.2)μmol/L,(75.9±24.7)ng/L vs.(33.0±119.6)ng/L,(2.2±1.4)nmol/L vs.(11.7±3.1)nmol/L,respectively,P＜0.01].Patients with 50-69％ restenosis had higher serum levels of SOD3,NO and eNOS and lower levels of MDA than patients with 100％ restenosis[(21.3 ± 2.9) × 103 U/L vs.(10.3 ± 4.0) × 103 U/L,(59.7 ± 16.7) μmol/L vs.(38.3 ±16.3)μmol/L,(74.5±21.1)ng/L vs.(41.9±26.8)ng/L,(2.6±3.9 nmol/L)vs.(10.1±3.1)nmol/L,respectively,P ＜ 0.01].Patients with left ventricular ejection fraction (LVEF) ≥ 55 ％ had higher serum levels of SOD3,NO and eNOS and lower levels of MDA than patients with LVEF＜30％ [(21.0±4.1) × 103 U/L vs.(5.3±1.9) × 103 U/L,(60.1 ± 14.2)μmol/L vs.(29.0± 13.2)μmol/L,(74.7±25.1)ng/L vs.(39.3 ± 20.3) ng/L,(2.3 ± 1.5) nmol/L vs.(10.0 ± 3.9) nmol/L,respectively,P ＜0.01].Serum levels of SOD3,NO and eNOS were higher and MDA levels were lower in patients with New York Heart Association(NYHA)Class Ⅰ than in patients with NYHA Class Ⅳ[(22.1±3.5)×103U/L vs.(9.7±2.9) × 103 U/L,(62.9± 13.9)μmol/L vs.(24.9± 13.3)μmol/L,(76.7±26.7) ng/L vs.(41.9±21.5)ng/L,(2.7± 1.9)nmol/L vs.(8.7±3.8)nmol/L,respectively,P＜0.01].Conclusions Serum level changes of anti-oxidative stress biomarkers such as SOD3,NO and eNOS may have clinical value in diagnosing in-stent restenosis and in-reocclusion after coronary stent implantation in aged patients.

Objective To investigate risk factors for in-stent restenosis and reocclusion after coronary stent implantation in aged patients.Methods 131 patients diagnosed with chronic total occlusion and old myocardial infarction due to coronary stenosis were recruited in this retrospective study from Mar 2004 to May 2015.Patients were divided into 50 to 59 years old group (n=51),60 to 69 years old group (n=43),and 70 to 80 years old group (n=37) to study coronary lesion characteristics.In-stent restenosis and reocclusion were detected at 6,12,18,and 24 months after coronary stent implantation.Results Before coronary stent implantation,the incidence rate of type 2 diabetes was significantly increased with three increasing age groups:9.8％ at ages 50-59 group (n=5),18.6％ at ages 60-69 group (n=8),and 27.0％ at ages 70-80 group (n=10) (all-P＜0.01).The incidence rates of multiple coronary artery disease,long coronary lesions (＞20 mm),eccentric coronary lesions,serious angle of coronary lesions,irregular coronary lesions,proximal coronary curvature,moderate to severe calcified coronary lesions,coronary restenosis (90％-99％ or 100％),and complex bifurcation lesions were significantly elevated with three increasing age groups (P ＜0.01 or P ＜0.05).The ratios of patients with in-stent restenosis at 24 months after coronary stent implantation were significantly elevated with three increasing age groups:at 9.8％ (n=5),18.6％ (n=8),and 27.0％(n=10) for 90％ 99％ restenosis sub-group,and at 5.9％ (n=3),14.0％ (n=6) and 24.3％ (n=9) for 100％ restenosis sub-group,respectively (all P＜0.05 or P＜0.01)Conclusions Type 2 diabetes is an independent risk factor for complex coronary lesions in aged patients Complex coronary lesions,three or more stents,and long coronary stents may lead to ir-stent restenosis and reocclusion after coronary stent implantation in aged patients.