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that were not closely related to the article's theme,of poor quality,repetitive,or outdated were excluded.A total of 115 articles met the inclusion criteria.RESULTS AND CONCLUSION:(1)Functional loading is used to combine therapeutic molecules with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 observe the value of intravoxel incoherent motion(IVIM)histogram parameters for predicting perineural invasion(PNI)of rectal cancer.Methods Fifty-five patients with rectal cancer were retrospectively enrolled and divided into positive group(n=23)and negative group(n=32)according to PNI or not.Histogram parameters of apparent diffusion coefficient(ADC),perfusion fraction(f),true diffusion coefficient(D)and pseudo diffusion coefficient(D*)were obtained based on MR IVIM images,including the mean,skewness,kurtosis,entropy,as well as the 25th,50th and 75th percentiles(25th,50th,75th).The above IVIM histogram parameters were compared between groups,and those with significant difference were included in binary stepwise logistic regression analysis to screen independent factors for predicting PNI status of rectal cancer.Then a combined parameter model was established.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of IVIM histogram parameters and combined parameter model for predicting PNI of rectal cancer.Results ADCmean,ADC25th,ADC50th,ADC75th,fmean,f25th,f50th,f75th and Dentropy in positive group were all lower than those in negative group(all P＜0.05).AUC of the above parameters for predicting PNI of rectal cancer was 0.693,0.665,0.701,0.675,0.831,0.847,0.835,0.722 and 0.785,respectively.The sensitivity,specificity and AUC of combined parameter model based on f25th and Dentropy for predicting PNI of rectal cancer was 95.65％,65.63％and 0.897,respectively.Conclusion IVIM histogram parameters could be used to predict PNI of rectal cancer effectively.

Objective To observe the value of intravoxel incoherent motion(IVIM)histogram parameters for predicting perineural invasion(PNI)of rectal cancer.Methods Fifty-five patients with rectal cancer were retrospectively enrolled and divided into positive group(n=23)and negative group(n=32)according to PNI or not.Histogram parameters of apparent diffusion coefficient(ADC),perfusion fraction(f),true diffusion coefficient(D)and pseudo diffusion coefficient(D*)were obtained based on MR IVIM images,including the mean,skewness,kurtosis,entropy,as well as the 25th,50th and 75th percentiles(25th,50th,75th).The above IVIM histogram parameters were compared between groups,and those with significant difference were included in binary stepwise logistic regression analysis to screen independent factors for predicting PNI status of rectal cancer.Then a combined parameter model was established.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of IVIM histogram parameters and combined parameter model for predicting PNI of rectal cancer.Results ADCmean,ADC25th,ADC50th,ADC75th,fmean,f25th,f50th,f75th and Dentropy in positive group were all lower than those in negative group(all P＜0.05).AUC of the above parameters for predicting PNI of rectal cancer was 0.693,0.665,0.701,0.675,0.831,0.847,0.835,0.722 and 0.785,respectively.The sensitivity,specificity and AUC of combined parameter model based on f25th and Dentropy for predicting PNI of rectal cancer was 95.65％,65.63％and 0.897,respectively.Conclusion IVIM histogram parameters could be used to predict PNI of rectal cancer effectively.

Mismatch repair-deficient/microsatellite instability-high(dMMR/MSI-H)gastric cancer represents a distinct molecular subtype of tumors characterized by pronounced sensitivity to immune checkpoint inhibitors(ICIs)attributed to its unique immune microenvironment and elevated mutation burden.Various clinical studies underscore the efficacy of ICIs in treating dMMR/MSI-H gastric cancer;however,chal-lenges such as primary and acquired resistance persist.Overcoming resistance and identifying optimal ICIs for its treatment remain critical clinical issues.This review delineates the mechanisms of ICIs,recent advances in their therapeutic application for dMMR/MSI-H gastric can-cer,and ongoing challenges in combating resistance,aiming to guide clinical practice effectively.

Objective:To evaluate the clinical effect of modified posterior pharyngeal flap surgery in the treatment of velopharyngeal insufficiency.Methods:Clinical data of patients with cleft lip and palate diagnosed with velopharyngeal insufficiency and undergoing modified posterior pharyngeal flap surgery in Peking University School and Hospital of Stomatology from January 2018 to May 2022 were retrospectively analyzed. The traditional posterior pharyngeal flap surgery was improved by combining the modern concept and method of soft palate muscle reconstruction, and performed modified posterior pharyngeal flap surgery to correct velopharyngeal insufficiency. Preoperative and postoperative follow-up were performed including speech evaluation (classifying as none, mild, moderate, moderate to severe hypernasality and nasal emission), nasopharyngeal fiberscope (classifying velopharyngeal insufficiency as mild, moderate, or severe), lateral cephalometric radiographs (resting position and /i/ position), and the Nasal Obstruction Symptom Evaluation (NOSE) scale. The recovery of velopharyngeal function and nasal ventilation after the operation were statistically analyzed. The difference of resting velar length (RVL), effective working length (EWL) and angel of velar lifting (AVL) before and after the operation was compared by paired t-test to evaluate the clinical effect of surgery. P<0.05 indicates a statistically significant difference. Results:A total of 83 patients with velopharyngeal insufficiency were enrolled, including 44 males and 39 females, aged (13.04±11.31) years (4-53 years). 83 patients were followed up for 6-18 months after surgery, and all patients had primary wound healing without postoperative bleeding, perforation, or posterior pharyngeal flap detachment; 78 cases achieved complete velopharyngeal closure, the surgical success rate was 94%, three patients still had mild hypernasality and nasal emission after surgery, one patient still had moderate hypernasality and nasal emission after surgery, and one patient had severe hypernasality after surgery. The RVL was (29.27±6.01) mm before the operation and (36.88±6.51) mm after the operation.The EWL of the soft palate was (18.53±5.04) mm before the operation and (25.76±5.17) mm after the operation.The angel of velar lifting was 11.42°±11.65° before the operation and 15.91°±8.54° after operation. The differences were statistically significant ( P<0.01). 98%(81/83) patients had subjective nasal obstruction symptom in the short period after surgery (within one month), the nasal obstruction symptom evaluation (NOSE) score was 8.61±3.64. The long-term postoperative follow-up showed that the NOSE score was 3.06±2.92, and the difference was statistically significant ( P<0.01). Conclusion:Modified posterior pharyngeal flap surgery can significantly increase the resting velar length and effective working length, improve the movement ability of the soft palate, acquire functional reconstruction of velopharyngeal closure, improve speech function and achieve effectively surgical results.

To investigate the risk factors for early relapse after curative resection of Siewert type Ⅱ/Ⅲ adenocarcinoma of esophagogastric junction (AEG) and construct a visual predictive model.

Objective:To evaluate the clinical effect of modified posterior pharyngeal flap surgery in the treatment of velopharyngeal insufficiency.Methods:Clinical data of patients with cleft lip and palate diagnosed with velopharyngeal insufficiency and undergoing modified posterior pharyngeal flap surgery in Peking University School and Hospital of Stomatology from January 2018 to May 2022 were retrospectively analyzed. The traditional posterior pharyngeal flap surgery was improved by combining the modern concept and method of soft palate muscle reconstruction, and performed modified posterior pharyngeal flap surgery to correct velopharyngeal insufficiency. Preoperative and postoperative follow-up were performed including speech evaluation (classifying as none, mild, moderate, moderate to severe hypernasality and nasal emission), nasopharyngeal fiberscope (classifying velopharyngeal insufficiency as mild, moderate, or severe), lateral cephalometric radiographs (resting position and /i/ position), and the Nasal Obstruction Symptom Evaluation (NOSE) scale. The recovery of velopharyngeal function and nasal ventilation after the operation were statistically analyzed. The difference of resting velar length (RVL), effective working length (EWL) and angel of velar lifting (AVL) before and after the operation was compared by paired t-test to evaluate the clinical effect of surgery. P<0.05 indicates a statistically significant difference. Results:A total of 83 patients with velopharyngeal insufficiency were enrolled, including 44 males and 39 females, aged (13.04±11.31) years (4-53 years). 83 patients were followed up for 6-18 months after surgery, and all patients had primary wound healing without postoperative bleeding, perforation, or posterior pharyngeal flap detachment; 78 cases achieved complete velopharyngeal closure, the surgical success rate was 94%, three patients still had mild hypernasality and nasal emission after surgery, one patient still had moderate hypernasality and nasal emission after surgery, and one patient had severe hypernasality after surgery. The RVL was (29.27±6.01) mm before the operation and (36.88±6.51) mm after the operation.The EWL of the soft palate was (18.53±5.04) mm before the operation and (25.76±5.17) mm after the operation.The angel of velar lifting was 11.42°±11.65° before the operation and 15.91°±8.54° after operation. The differences were statistically significant ( P<0.01). 98%(81/83) patients had subjective nasal obstruction symptom in the short period after surgery (within one month), the nasal obstruction symptom evaluation (NOSE) score was 8.61±3.64. The long-term postoperative follow-up showed that the NOSE score was 3.06±2.92, and the difference was statistically significant ( P<0.01). Conclusion:Modified posterior pharyngeal flap surgery can significantly increase the resting velar length and effective working length, improve the movement ability of the soft palate, acquire functional reconstruction of velopharyngeal closure, improve speech function and achieve effectively surgical results.

At present, many treatment options for colorectal cancer, including chemotherapy, targeted therapy and immunotherapy, have poor efficacy due to resistance variation and patient individualization. It is urgent to find new precise and effective treatment measures at this stage. Studies have shown that the pathogenesis and progression of colorectal cancer involve multiple processes such as inflammation, immunity, and cholesterol metabolism, and there are many types of potential interactive reactions. Clarifying the regulatory mechanism of various factors is helpful to provide new ideas for colorectal cancer treatment.