Breast cancer ranks among the most prevalent cancers worldwide,particularly affecting young and middle-aged women,who face higher recurrence rates,lower survival rates,and substantial psychological health challenges.D...Breast cancer ranks among the most prevalent cancers worldwide,particularly affecting young and middle-aged women,who face higher recurrence rates,lower survival rates,and substantial psychological health challenges.Depressive symptoms,frequently observed in breast cancer patients,significantly influence treatment outcomes and quality of life.Recent years have seen a growing focus on these symptoms,emphasizing early identification and intervention.This editorial comments on the recent study by Mao et al on a risk prediction model for de-pression in young and middle-aged breast cancer patients.Research suggests that factors such as tumor grade,monthly income,pain perception,family support,and physical activity critically influence the onset of depressive symptoms.By developing personalized risk prediction models,it becomes possible to identify high-risk patients early,allowing healthcare professionals to implement pre-ventive strategies proactively.The editorial advocates for increased attention and resources dedicated to psychological health interventions for breast cancer pa-tients,aiming to foster comprehensive care strategies that mitigate the impacts of depression and enhance overall quality of life.展开更多
Magnesium-based biomaterials(MBMs)are one of the most promising materials for tissue engineering due to their unique mechanical properties and excellent functional properties.This review describes the development,adva...Magnesium-based biomaterials(MBMs)are one of the most promising materials for tissue engineering due to their unique mechanical properties and excellent functional properties.This review describes the development,advantages,and challenges of MBMs for biomedical applications,especially for tissue repair and regeneration.The history of the use of MBMs from the beginning of the 20th century is traced,and the transformative advances in contemporary applications of MBMs in areas such as orthopedics and cardiovascular surgery are emphasized.The review also provides insight into the signaling pathways affected by MBMs,such as the PI3K/Akt and RANKL/RANK/OPG pathways,which are critical for osteogenesis and angiogenesis.The review advocates that future research should focus on optimizing alloy compositions,surface modification and exploring innovative technologies such as 3D printing to improve the efficacy of MBMs in complex tissue repair.The potential of MBMs to tissue engineering and regenerative medicine is significant,urging further exploration and interdisciplinary collaboration to maximize their therapeutic effects.展开更多
Background Observational studies highlight the association between gut microbiota(GM)composition and depression;however,evidence for the causal relationship between GM and specific depressive symptoms remains lacking....Background Observational studies highlight the association between gut microbiota(GM)composition and depression;however,evidence for the causal relationship between GM and specific depressive symptoms remains lacking.Aims We aimed to evaluate the causal relationship between GM and specific depressive symptoms as well as the mediating role of body mass index(BMI).Methods We performed a two-sample Mendelian randomisation(MR)analysis using genetic variants associated with GM and specific depressive symptoms from genome-wide association studies.The mediating role of BMI was subsequently explored using mediation analysis via two-step MR.Results MR evidence suggested the Bifidobacterium genus(β=0.03;95%CI-0.05 to-0.02;p<0.001 andβ=0.03;95%CI-0.05 to-0.02;p<0.001)and Actinobacteria phylum(β=-0.04;95%CI-0.06 to-0.02;p<0.001 andβ=-0.03;95%CI-0.05 to-0.03;p=0.001)had protective effects on both anhedonia and depressed mood.The Actinobacteria phylum also had protective effects on appetite changes(β=-0.04;95%CI-0.06 to-0.01;p=0.005),while the FamilyⅪhad an antiprotective effect(β=0.03;95%CI 0.01 to 0.04;p<0.001).The Bifidobacteriaceae family(β=-0.01;95%CI-0.02 to-0.01;p=0.001)and Actinobacteria phylum(β=-0.02;95%CI-0.03 to-0.01;p=0.001)showed protective effects against suicidality.The two-step MR analysis revealed that BMl also acted as a mediating moderator between the Actinobacteria phylum and appetite changes(mediated proportion,34.42%)and that BMI partially mediated the effect of the Bifidobacterium genus(14.14%and 8.05%)and Actinobacteria phylum(13.10%and 8.31%)on both anhedonia and depressed mood.Conclusions These findings suggest a potential therapeutic effect of Actinobacteria and Bifidobacterium on both depression and obesity.Further studies are required to translate these findings into clinical practice.展开更多
AIM To study the short term effect of Danshen ( Salvia miltiorrhiza ) on acetic acid induced chronic gastric ulcer in rats and its long term effect in preventing recurrence. METHODS Rats with acetic acid indu...AIM To study the short term effect of Danshen ( Salvia miltiorrhiza ) on acetic acid induced chronic gastric ulcer in rats and its long term effect in preventing recurrence. METHODS Rats with acetic acid induced gastric ulcer were treated with Danshen and cimetidine for 30 days. Traditional gastric mucosal auto radiography and 3H TdR incorporation into gastric mucosa in vitro were employed to study the effects of Danshen in rat acetic acid induced chronic gastric ulcer, including ulcer index (UI), ulcer inhibitory rate (IR) and label rate (LR). RESULTS On the day 5, 30 and 126 of ulcer making, the UI in the Danshen group was obviously lower than that in the cimetidine group and the control group (42 3±3 9, 3 6±1 2, 4 4±2 3; 49 1±3 6, 5 9±1 4, 9 2±1 3; 61 0±3 8, 8 9±2 5, 12 4±2 4, respectively, P <0 01), the IR (%) in the Danshen group was obviously higher than that in the cimetidine group (31, 59, 64 8; 19, 33, 26, respectively), and the LR in the Danshen group was obviously higher than that in the cimetidine group and the control group (10 0±0 5, 16 2±0 8, 15 0±0 6; 9 0±0 5, 13 9±0 6, 10 8±0 7; 6 5±0 7, 10 1±0 5, 8 0±0 7, respectively, P <0 01). There was no obvious difference in UI in the Danshen group on day 30 as compared with that on day 126. CONCLUSION Danshen is effective in promoting ulcer healing and preventing recurrence. The mechanism of action is to strengthen the gastric mucosal barrier and to promote the gastric mucosal cell proliferation along the edge of the ulcer.展开更多
BACKGROUND: Hydrophobic bile acids lead to the generation of oxygen free radicals in mitochondria. Accordingly, this study is to investigate if gene delivery of superoxide dismutase (SOD) will reduce hepatocyte injury...BACKGROUND: Hydrophobic bile acids lead to the generation of oxygen free radicals in mitochondria. Accordingly, this study is to investigate if gene delivery of superoxide dismutase (SOD) will reduce hepatocyte injury caused by experimental cholestasis. METHODS: The recombinant of pLNCX-SOD gene packaged with lipofection of AMINE was transfected into hepatocytes in vitro, which stably expressed the SOD gene. RESULTS: After transfection, hepatocytes enhanced the protective effect against injury to bile and the toxicity of serum in obstructive jaundice. The inhibition of bile at the concentration of 2% (v: v, bile: DMEM 1: 50) decreased obviously from (78.80 +/- 12.35)% to (43.35 +/- 9.69)% in 12 hours, from (82.55 +/- 11.27)% to (-26.64 +/- 7.66)% in 24 hours, and from (83.83 +/- 18.69)% to (-19.27 +/- 14.38)% in 48 hours, compared with that of the untransfected cells (P < 0.01). The inhibition of serum at the obstructive jaudice concentration of 2.5% was obviously decreased from (89.72 +/- 1.52)% to (14.68 +/- 14.33)% in 12 hours, from (92.2 +/- 11.27)% to (41.39 +/- 7.66)% in 24 hours, and from (94.25 +/- 8.96)% to (22.71 +/- 4.38)% in 48 hours (P < 0.01). CONCLUSION: Hepatocytes transfected with the pLNCX-SOD gene could obviously be resistant to the toxicity of bile and serum from rat with obstructive jaundice.展开更多
BACKGROUND: Budd-Chiari syndrome (BCS) refers to posthepatic portal vein hypertension and/or inferior vena cava hypertension syndrome caused by obstruction of the blood flow at the portal cardinal hepatic vein and/or ...BACKGROUND: Budd-Chiari syndrome (BCS) refers to posthepatic portal vein hypertension and/or inferior vena cava hypertension syndrome caused by obstruction of the blood flow at the portal cardinal hepatic vein and/or posterior hepatic inferior vena cava. The main surgical treatments of BCS include operations on pathological lesioned membrane, shunt, and combined operations. There are more than ten treatments available and reports on their therapeutic effects vary. As to operations on lesioned membrane, there are Kimura's finger rupture, balloon dilatation and membrane removal. With reference to our experience, the clinical value of membrane resection at normal temperature and under direct vision is discussed. METHODS: A total of 292 patients with BCS undergoing membrane resection at normal temperature and under direct vision from June 1996 to June 2005 were retrospectively analyzed. RESULTS: The short-term therapeutic effect in 256 patients was satisfactory and the effective rate was 87.7% (256/292). Within a week, ascitic fluid disappeared, the liver shrank and edema of the lower extremities was greatly relieved or even disappeared. Perioperative death occurred in 14 patients (4.8%). Of these, 3 had acute heart failure (one during the operation, one after 6 hours and one 7 days later). Six patients had thoracic cavity bleeding within 12 hours after the operation, 3 had acute respiratory distress syndrome (ARDS), 2 had disseminated intravascular coagulation (DIC), and I had pulmonary embolism. 158 patients were followed up for 6 months to 12 years, and 12 (7.6%) had recurrences. CONCLUSIONS: After membrane resection at normal temperature and under direct vision, hemodynamics was found to be close to normal, damage was slight, effectiveness was evident and the recurrence rate low. So this method is effective in treating BCS.展开更多
BACKGROUND: Diaphragmatic hernia of the liver is a rare clinical entity, usually found after trauma in adults. This study was undertaken to elucidate a misdiagnosis of non-traumatic diaphragmatic hernia of the liver i...BACKGROUND: Diaphragmatic hernia of the liver is a rare clinical entity, usually found after trauma in adults. This study was undertaken to elucidate a misdiagnosis of non-traumatic diaphragmatic hernia of the liver in an adult. METHOD: The clinical data of one patient with non-traumatic diaphragmatic hernia of the liver was analyzed. RESULTS: A tumor in the right lower thorax was revealed by chest X-ray and computed tomography. Non-traumatic diaphragmatic hernia of the liver was not identified until the operation. Pathological analysis confirmed the finding. The patient recovered well. CONCLUSIONS: Non-traumatic diaphragmatic hernia of the liver in an adult is a rare right-sided diaphragmatic hernia, which can move up into the chest cavity. It should be distinguished from lung cancer. The diagnosis and evaluation of non-traumatic diaphragmatic hernia of the liver can help optimize surgical management.展开更多
This study sought to investigate the clinical efficacy and safety of combined oral therapy with sildenafil and doxazosin GITS compared to sildenafil monotherapy in treating Chinese patients with erectile dysfunction ...This study sought to investigate the clinical efficacy and safety of combined oral therapy with sildenafil and doxazosin GITS compared to sildenafil monotherapy in treating Chinese patients with erectile dysfunction （ED） and lower urinary tract symptoms secondary to benign prostatic hyperplasia （BPH/LUTS）. The trial was conducted in hospitals in Beijing, Shanghai, Changsha, Wuhan and Guangzhou, five major cities in China. A total of 250 patients diagnosed with ED and BPH/LUTS aged 50-75 years, and who had International Index of Erection Function-5 （IIEF-5） scores ≤ 21 and International Prostate Symptom Score （IPSS） ≥ 10 points, were enrolled and randomly divided into Group A （168 cases; doxazosin GITS 4 mg once daily plus sildenafi125-100 mg on demand） and Group B （82 cases; sildenafi125-100 mg on demand）. Efficacies were evaluated by IIEF-5 and IPSS scores and a quality of life （QoL） questionnaire, and adverse effects were evaluated during the treatment period. There were no statistically significant differences in mean age, and IIEF-5, IPSS and QoL scores pre-treatment between the two groups. After treatment, IIEF-5, IPSS and QoL scores were significantly improved in Group A, while only IIEF-5 scores were significantly improved in Group B compared with pre-treatment. There were no significant differences in side effects between the two groups. The results indicated that combined therapy with sildenafil and doxazosin GITS for the treatment of ED and BPH/LUTS is safe and effective compared to sildenafil monotherapy.展开更多
Objective： To investigate potential prognostic factors affecting patient outcomes and to evaluate the optimal methods and effects of radiotherapy（RT） in the management of extramedullary plasmacytoma（EMP）.Methods...Objective： To investigate potential prognostic factors affecting patient outcomes and to evaluate the optimal methods and effects of radiotherapy（RT） in the management of extramedullary plasmacytoma（EMP）.Methods： Data from 55 patients with EMP between November 1999 and August 2015 were collected. The median age was 51（range, 22–77） years. The median tumor size was 3.5（range, 1.0–15.0） cm. The median applied dose was 50.0（range, 30.0–70.0） Gy. Thirty-nine patients（70.9%） presented with disease in the head or neck region. Twelve patients received RT alone, 9 received surgery（S） alone, 3 received chemotherapy（CT） alone, and 3 patients did not receive any treatment. Combination therapies were applied in 28 patients.Results：The median follow-up duration was 56 months.The 5-year local recurrence-free survival（LRFS）,multiple myeloma-free survival（MMFS）,progression-free survival（PFS）and overall survival（OS）rates were 79.8%,78.6%,65.2% and 76.0%,respectively.Univariate analysis revealed that RT was a favourable factor for all examined endpoints.Furthermore,head and neck EMPs were associated with superior LRFS,MMFS and PFS.Tumor size〈4 cm was associated with superior MMFS,PFS and OS;serum M protein negativity was associated with superior MMFS and PFS;age≥50 years and local recurrence were associated with poor MMFS.The dose≥45 Gy group exhibited superior 5-year LRFS,MMFS and PFS rates（94.7%,94.4%,90.0%,respectively）,while the corresponding values for the dose〈45 Gy group were 62.5%（P=0.008）,53.3%（P=0.036）and 41.7%（P〈0.001）.Conclusions：Involved-site RT of at least 45 Gy should be considered for EMP.Furthermore,patients with head and neck EMP,tumor size〈4 cm,age〈50 years and serum M protein negativity had better outcomes.展开更多
The robotic liver resection(RLR)has been increasingly applied in recent years and its benefits shown in some aspects owing to the technical advancement of robotic surgical system,however,controversies still exist.Base...The robotic liver resection(RLR)has been increasingly applied in recent years and its benefits shown in some aspects owing to the technical advancement of robotic surgical system,however,controversies still exist.Based on the foundation of the previous consensus statement,this new consensus document aimed to update clinical recommendations and provide guidance to improve the outcomes of RLR clinical practice.The guideline steering group and guideline expert group were formed by 29 international experts of liver surgery and evidence-based medicine(EBM).Relevant literature was reviewed and analyzed by the evidence evaluation group.According to the WHO Handbook for Guideline Development,the Guidance Principles of Development and Amendment of the Guidelines for Clinical Diagnosis and Treatment in China 2022,a total of 14 recommendations were generated.Among them were 8 recommendations formulated by the GRADE method,and the remaining 6 recommendations were formulated based on literature review and experts’opinion due to insufficient EBM results.This international experts consensus guideline offered guidance for the safe and effective clinical practice and the research direction of RLR in future.展开更多
Parathyroid carcinoma is an extremely rare malignant tumor,composed primarily of vacuolated principal cells,but may also be composed of eosinophils.The exact etiology and pathogenesis of parathyroid carcinoma is unkno...Parathyroid carcinoma is an extremely rare malignant tumor,composed primarily of vacuolated principal cells,but may also be composed of eosinophils.The exact etiology and pathogenesis of parathyroid carcinoma is unknown,and head and neck radiation exposure,chronic stimulation from renal failure,and familial syndromes can lead to the development of parathyroid carcinoma.Most parathyroid carcinoma is difficult to distinguish from benign HPT and is often diagnosed only when there is a recurrence of hypercalcemia several years later,which can manifest as weight loss,extreme fatigue,anorexia,and muscle atrophy.At present,surgical resection remains the primary treatment.In this case,the patient underwent initial surgery for primary hyperparathyroidism and was subsequently diagnosed with parathyroid carcinoma.During the 8 years of follow-up,the patient underwent 7 surgeries in combination with radiation therapy,chemotherapy and targeted medications.Although the neck tumor was cured,the patient died of complications related to hypercalcemia.We will review the literature on the combination of surgery,radiotherapy,chemotherapy,and targeted drug therapy in order to improve the diagnosis and treatment of parathyroid carcinoma.展开更多
Insulin-like growth factor 1(IGF1)is a regulator of both cellular hypertrophy and lipogenesis,which are two key processes for pathogenesis of obesity.However,the in vivo role of IGF1 in the development of obesity rema...Insulin-like growth factor 1(IGF1)is a regulator of both cellular hypertrophy and lipogenesis,which are two key processes for pathogenesis of obesity.However,the in vivo role of IGF1 in the development of obesity remains unclear.Here,we show that IGF1 expression is increased in adipose tissue in obese human patients and animal models.Elevation of IGF1 is associated with increased lipogenic gene expression and decreased energy expenditure.Genetic down-regulation of IGF1 normalizes lipogenic gene expression,restores aberrant energy metabolism and alleviates obese phenotype of a genetic mouse model with IGF1-hypersecretion.Importantly,genetic down-regulation of IGF1 exerts similar effects on development of diet-induced obesity.Furthermore,berberine that is an AMP-activated protein kinase(AMPK)activator in medicinal herbs inhibits IGF1 secretion,decreases lipogenic gene expression and alleviates diet-induced adiposity.Collectively,our findings demonstrate that hypersecretion of IGF1 is a critical factor for the development of obesity and can be targeted using AMPK activators to alleviate obesity.展开更多
The reconstruction of large osteoarticular defects caused by tumor resection or severe trauma remains a clinical challenge.Current metal prostheses exhibit a lack of osteo-chondrogenic functionality and demonstrate po...The reconstruction of large osteoarticular defects caused by tumor resection or severe trauma remains a clinical challenge.Current metal prostheses exhibit a lack of osteo-chondrogenic functionality and demonstrate poor integration with host tissues.This often results in complications such as abnormal bone absorption and prosthetic loosening,which may necessitate secondary revisions.Here,we propose a paradigm-shifting“living prosthesis”strategy that combines a customized 3D-printed hollow titanium humeral prosthesis with engineered bone marrow condensations presenting bone morphogenetic protein-2(BMP-2)and transforming growth factor-β3(TGF-β3)from encapsulated silk fibroin hydrogels.This innovative approach promotes in situ endochondral defect regeneration of the entire humeral head while simultaneously providing immediate mechanical support.In a rabbit model of total humerus resection,the designed“living prosthesis”achieved weight,macroscopic and microscopic morphologies that were comparable to those of undamaged native joints at 2 months post-implantation,with organized osteochondral tissues were regenerated both around and within the prosthesis.Notably,the“living prosthesis”displayed significantly higher osteo-integration than the blank metal prosthesis did,as evidenced by a 3-fold increase in bone ingrowth and a 2-fold increase in mechanical pull-out strength.Furthermore,the"living prosthesis"restored joint cartilage function,with rabbits exhibiting normal gait and weight-bearing capacity.The successful regeneration of fully functional humeral head tissue from a single implanted prosthesis represents technical advance in designing bioactive bone prosthesis,with promising im-plications for treating extreme-large osteochondral defects.展开更多
Introduction:Accurate contouring of thoracic organs at risk(OARs)is essential for minimizing complications in radiation treatment.Manual contouring of thoracic OARs is not only time-consuming but also prone to substan...Introduction:Accurate contouring of thoracic organs at risk(OARs)is essential for minimizing complications in radiation treatment.Manual contouring of thoracic OARs is not only time-consuming but also prone to substantial user variation.To enhance the efficiency and consistency,we developed a unified deep learning(DL)OAR contouring model,DeepOAR,that was trained using multiple partially labeled datasets for segmenting a comprehensive set of thoracic OARs following the Radiation Therapy Oncology Group(RTOG)-guided OAR atlas.This DL model supports the segmentation of six required and eight optional OARs guided by the NRG-RTOG 1106 trial,providing precise and reproducible OARs contouring that are ready to be used in radiotherapy practice.Materials and methods:Following the OAR contouring recommendation of the NRG-RTOG 1106 trial,we collected and curated three private datasets and two public datasets,comprising a total of 531 patients with partially annotated thoracic OARs.These partially annotated datasets were utilized to develop DeepOAR,which consisted of a shared encoder and 14 separate decoders,with each decoder dedicated to one specific OAR.For model training,we utilized all patients from the two public datasets and 75%of the patients from the private datasets.We reserved the remaining 25%of the private datasets for independent testing.A multi-user study involving 21 radiation oncologists was conducted on 40 randomly selected patients from the independent testing dataset to evaluate the clinical applicability of DeepOAR.The Dice coefficient score(DSC)and average surface distance(ASD)were computed to evaluate the quantitative delineation performance of the model.Results:DeepOAR outperformed nnUNet(the benchmark medical segmentation model)across all 14 OARs,achieving mean DSC and ASD values of 88.4%and 1.0 mm,respectively,in the independent testing set.Multi-user validation demonstrated that 89.7%of DeepOAR-generated OARs were clinically acceptable or required only minor revisions.A comparison using two randomly selected patients showed that the delineation variability of DeepOAR was significantly smaller than the inter-user variation among radiation oncologists.Human editing of DeepOAR’s predictions could further improve OAR delineation accuracy by an average of 3%increase in DSC and 40%reduction in ASD while significantly reducing the workload of radiation oncologists for contouring 14 thoracic OARs by an average of 77.0%.Conclusion:We developed DeepOAR,a DL-based unified contouring model trained using multiple partially labeled datasets,to delineate a comprehensive set of 14 thoracic OARs following the RTOG-guided OAR atlas.Both qualitative and quantitative results demonstrated the strong clinical applicability of DeepOAR for the OAR delineation process in thoracic cancer radiotherapy workflows,along with improved efficiency,comprehensiveness,and quality.展开更多
Although natural polymers have been widely used in constructing bone scaffolds,it still remains challenging to fabricate natural polymer-derived bone scaffolds with biomimetic mechanical properties as well as outstand...Although natural polymers have been widely used in constructing bone scaffolds,it still remains challenging to fabricate natural polymer-derived bone scaffolds with biomimetic mechanical properties as well as outstanding osteogenic properties for large-size and weight-bearing bone defects regeneration.Herein,an“organic-inorganic assembly”strategy is developed to construct silk fibroin(SF)-based bone scaffolds with the aforementioned merits.After secondary structure reshuffling,the 3.3-fold increment ofβ-sheet structures in SF hydrogel resulted in a 100-fold improvement of mineral-assembly efficacy via influencing the ion adsorption process and providing templates for mineral growth.Notably,abundant minerals were deposited within the hydrogel and also on the surface,which indicated entire mineral-assembly,which ensured the biomimetic mechanical properties of the digital light processing 3D printed SF hydrogel scaffolds with haversian-mimicking structure.In vitro experiments proved that the assembly between the mineral and SF results in rapid adhesion and enhanced osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.In vivo experiments further proved that the mineral-assembled SF hydrogel scaffold could significantly enhance integration and bone regeneration at the weight-bearing site within one month.This SF-based“organic-inorganic assembly”strategy sheds light on constructing cell-free,growth factor-free and natural polymer-derived bone scaffolds with biomimetic 3D structure,mechanical properties and excellent osteogenic properties.展开更多
Clostridioides difficile is a leading cause of healthcare-associated infections,causing billions of economic losses every year.Its symptoms range from mild diarrhea to life-threatening damage to the colon.Transmission...Clostridioides difficile is a leading cause of healthcare-associated infections,causing billions of economic losses every year.Its symptoms range from mild diarrhea to life-threatening damage to the colon.Transmission and recurrence of c.difficile infection(CDl)are mediated by the metabolically dormant spores,while the virulence of C.difficile is mainly due to the two large clostridial toxins,TcdA and TcdB.Producing toxins or forming spores are two different strategies for C.difficile to cope with harsh environmental conditions.It is of great significance to understand the molecular mechanisms for C.difficile to skew to either of the cellular processes.Here,we summarize the current understanding of the regulation and connections between toxin production and sporulation in C.difficile and further discuss the potential solutions for yet-to-be-answered questions.展开更多
Spinal cord injury(SCI)causes motor,sensory and automatic impairment due to rarely axon regeneration.Developing effective treatment for SCI in the clinic is extremely challenging because of the restrictive axonal rege...Spinal cord injury(SCI)causes motor,sensory and automatic impairment due to rarely axon regeneration.Developing effective treatment for SCI in the clinic is extremely challenging because of the restrictive axonal regenerative ability and disconnection of neural elements after injury,as well as the limited systemic drug delivery efficiency caused by blood spinal cord barrier.To develop an effective non-invasive treatment strategy for SCI in clinic,we generated an autologous plasma exosome(AP-EXO)based biological scaffold where AP-EXO was loaded with neuron targeting peptide(RVG)and growth-facilitating peptides(ILP and ISP).This scaffold can be targeted delivered to neurons in the injured area and elicit robust axon regrowth across the lesion core to the levels over 30-fold greater than naïve treatment,thus reestablish the intraspinal circuits and promote motor functional recovery after spinal cord injury in mice.More importantly,in ex vivo,human plasma exosomes(HP-EXO)loaded with combinatory peptides of RVG,ILP and ISP showed safety and no liver and kidney toxicity in the application to nude SCI mice.Combining the efficacy and safety,the AP-EXO-based personalized treatment confers functional recovery after SCI and showed immense promising in biomedical applications in treating SCI.It is helpful to expand the application of combinatory peptides and human plasma derived autologous exosomes in promoting regeneration and recovery upon SCI treatment.展开更多
基金Supported by The 2023 Government-Funded Project of the Outstanding Talents Training Program in Clinical Medicine,No.ZF2023165Key Research and Development Projects of Hebei Province,No.18277731DNatural Science Foundation of Hebei Province,No.
文摘Breast cancer ranks among the most prevalent cancers worldwide,particularly affecting young and middle-aged women,who face higher recurrence rates,lower survival rates,and substantial psychological health challenges.Depressive symptoms,frequently observed in breast cancer patients,significantly influence treatment outcomes and quality of life.Recent years have seen a growing focus on these symptoms,emphasizing early identification and intervention.This editorial comments on the recent study by Mao et al on a risk prediction model for de-pression in young and middle-aged breast cancer patients.Research suggests that factors such as tumor grade,monthly income,pain perception,family support,and physical activity critically influence the onset of depressive symptoms.By developing personalized risk prediction models,it becomes possible to identify high-risk patients early,allowing healthcare professionals to implement pre-ventive strategies proactively.The editorial advocates for increased attention and resources dedicated to psychological health interventions for breast cancer pa-tients,aiming to foster comprehensive care strategies that mitigate the impacts of depression and enhance overall quality of life.
基金supported by the National Natural Science Foundation of China(Grant No.82202672)the Key Research and Development Program of Anhui Province(No.2022e07020017)+5 种基金China Postdoctoral Science Foundation Grant(2022M723049)the National Postdoctoral Program for Innovative Talents(BX20230350)Research Funds of Centre for Leading Medicine and Advanced Technologies of IHM(No.2023IHM02007)the Foundation of National Center for Translational Medicine(Shanghai)SHU Branch(No.SUITM-202301)Anhui Provincial Research Preparation Plan(2022AH040074),Natural science fund for colleges and universities in Anhui Proxince(2023AH053289)Research Fund of Anhui Institute of translational medicine(2022zhyx-C32).
文摘Magnesium-based biomaterials(MBMs)are one of the most promising materials for tissue engineering due to their unique mechanical properties and excellent functional properties.This review describes the development,advantages,and challenges of MBMs for biomedical applications,especially for tissue repair and regeneration.The history of the use of MBMs from the beginning of the 20th century is traced,and the transformative advances in contemporary applications of MBMs in areas such as orthopedics and cardiovascular surgery are emphasized.The review also provides insight into the signaling pathways affected by MBMs,such as the PI3K/Akt and RANKL/RANK/OPG pathways,which are critical for osteogenesis and angiogenesis.The review advocates that future research should focus on optimizing alloy compositions,surface modification and exploring innovative technologies such as 3D printing to improve the efficacy of MBMs in complex tissue repair.The potential of MBMs to tissue engineering and regenerative medicine is significant,urging further exploration and interdisciplinary collaboration to maximize their therapeutic effects.
基金supported by the National Natural Science Foundation of China(grant number:81801345)Tianjin Key Medical Discipline(Specialty)Construction Project(grant number:TJYXZDXK-033A).
文摘Background Observational studies highlight the association between gut microbiota(GM)composition and depression;however,evidence for the causal relationship between GM and specific depressive symptoms remains lacking.Aims We aimed to evaluate the causal relationship between GM and specific depressive symptoms as well as the mediating role of body mass index(BMI).Methods We performed a two-sample Mendelian randomisation(MR)analysis using genetic variants associated with GM and specific depressive symptoms from genome-wide association studies.The mediating role of BMI was subsequently explored using mediation analysis via two-step MR.Results MR evidence suggested the Bifidobacterium genus(β=0.03;95%CI-0.05 to-0.02;p<0.001 andβ=0.03;95%CI-0.05 to-0.02;p<0.001)and Actinobacteria phylum(β=-0.04;95%CI-0.06 to-0.02;p<0.001 andβ=-0.03;95%CI-0.05 to-0.03;p=0.001)had protective effects on both anhedonia and depressed mood.The Actinobacteria phylum also had protective effects on appetite changes(β=-0.04;95%CI-0.06 to-0.01;p=0.005),while the FamilyⅪhad an antiprotective effect(β=0.03;95%CI 0.01 to 0.04;p<0.001).The Bifidobacteriaceae family(β=-0.01;95%CI-0.02 to-0.01;p=0.001)and Actinobacteria phylum(β=-0.02;95%CI-0.03 to-0.01;p=0.001)showed protective effects against suicidality.The two-step MR analysis revealed that BMl also acted as a mediating moderator between the Actinobacteria phylum and appetite changes(mediated proportion,34.42%)and that BMI partially mediated the effect of the Bifidobacterium genus(14.14%and 8.05%)and Actinobacteria phylum(13.10%and 8.31%)on both anhedonia and depressed mood.Conclusions These findings suggest a potential therapeutic effect of Actinobacteria and Bifidobacterium on both depression and obesity.Further studies are required to translate these findings into clinical practice.
文摘AIM To study the short term effect of Danshen ( Salvia miltiorrhiza ) on acetic acid induced chronic gastric ulcer in rats and its long term effect in preventing recurrence. METHODS Rats with acetic acid induced gastric ulcer were treated with Danshen and cimetidine for 30 days. Traditional gastric mucosal auto radiography and 3H TdR incorporation into gastric mucosa in vitro were employed to study the effects of Danshen in rat acetic acid induced chronic gastric ulcer, including ulcer index (UI), ulcer inhibitory rate (IR) and label rate (LR). RESULTS On the day 5, 30 and 126 of ulcer making, the UI in the Danshen group was obviously lower than that in the cimetidine group and the control group (42 3±3 9, 3 6±1 2, 4 4±2 3; 49 1±3 6, 5 9±1 4, 9 2±1 3; 61 0±3 8, 8 9±2 5, 12 4±2 4, respectively, P <0 01), the IR (%) in the Danshen group was obviously higher than that in the cimetidine group (31, 59, 64 8; 19, 33, 26, respectively), and the LR in the Danshen group was obviously higher than that in the cimetidine group and the control group (10 0±0 5, 16 2±0 8, 15 0±0 6; 9 0±0 5, 13 9±0 6, 10 8±0 7; 6 5±0 7, 10 1±0 5, 8 0±0 7, respectively, P <0 01). There was no obvious difference in UI in the Danshen group on day 30 as compared with that on day 126. CONCLUSION Danshen is effective in promoting ulcer healing and preventing recurrence. The mechanism of action is to strengthen the gastric mucosal barrier and to promote the gastric mucosal cell proliferation along the edge of the ulcer.
基金This study was supported by a grant from Science Foundation of Educational Department of Liaoning Province,China(No.202203257).
文摘BACKGROUND: Hydrophobic bile acids lead to the generation of oxygen free radicals in mitochondria. Accordingly, this study is to investigate if gene delivery of superoxide dismutase (SOD) will reduce hepatocyte injury caused by experimental cholestasis. METHODS: The recombinant of pLNCX-SOD gene packaged with lipofection of AMINE was transfected into hepatocytes in vitro, which stably expressed the SOD gene. RESULTS: After transfection, hepatocytes enhanced the protective effect against injury to bile and the toxicity of serum in obstructive jaundice. The inhibition of bile at the concentration of 2% (v: v, bile: DMEM 1: 50) decreased obviously from (78.80 +/- 12.35)% to (43.35 +/- 9.69)% in 12 hours, from (82.55 +/- 11.27)% to (-26.64 +/- 7.66)% in 24 hours, and from (83.83 +/- 18.69)% to (-19.27 +/- 14.38)% in 48 hours, compared with that of the untransfected cells (P < 0.01). The inhibition of serum at the obstructive jaudice concentration of 2.5% was obviously decreased from (89.72 +/- 1.52)% to (14.68 +/- 14.33)% in 12 hours, from (92.2 +/- 11.27)% to (41.39 +/- 7.66)% in 24 hours, and from (94.25 +/- 8.96)% to (22.71 +/- 4.38)% in 48 hours (P < 0.01). CONCLUSION: Hepatocytes transfected with the pLNCX-SOD gene could obviously be resistant to the toxicity of bile and serum from rat with obstructive jaundice.
文摘BACKGROUND: Budd-Chiari syndrome (BCS) refers to posthepatic portal vein hypertension and/or inferior vena cava hypertension syndrome caused by obstruction of the blood flow at the portal cardinal hepatic vein and/or posterior hepatic inferior vena cava. The main surgical treatments of BCS include operations on pathological lesioned membrane, shunt, and combined operations. There are more than ten treatments available and reports on their therapeutic effects vary. As to operations on lesioned membrane, there are Kimura's finger rupture, balloon dilatation and membrane removal. With reference to our experience, the clinical value of membrane resection at normal temperature and under direct vision is discussed. METHODS: A total of 292 patients with BCS undergoing membrane resection at normal temperature and under direct vision from June 1996 to June 2005 were retrospectively analyzed. RESULTS: The short-term therapeutic effect in 256 patients was satisfactory and the effective rate was 87.7% (256/292). Within a week, ascitic fluid disappeared, the liver shrank and edema of the lower extremities was greatly relieved or even disappeared. Perioperative death occurred in 14 patients (4.8%). Of these, 3 had acute heart failure (one during the operation, one after 6 hours and one 7 days later). Six patients had thoracic cavity bleeding within 12 hours after the operation, 3 had acute respiratory distress syndrome (ARDS), 2 had disseminated intravascular coagulation (DIC), and I had pulmonary embolism. 158 patients were followed up for 6 months to 12 years, and 12 (7.6%) had recurrences. CONCLUSIONS: After membrane resection at normal temperature and under direct vision, hemodynamics was found to be close to normal, damage was slight, effectiveness was evident and the recurrence rate low. So this method is effective in treating BCS.
文摘BACKGROUND: Diaphragmatic hernia of the liver is a rare clinical entity, usually found after trauma in adults. This study was undertaken to elucidate a misdiagnosis of non-traumatic diaphragmatic hernia of the liver in an adult. METHOD: The clinical data of one patient with non-traumatic diaphragmatic hernia of the liver was analyzed. RESULTS: A tumor in the right lower thorax was revealed by chest X-ray and computed tomography. Non-traumatic diaphragmatic hernia of the liver was not identified until the operation. Pathological analysis confirmed the finding. The patient recovered well. CONCLUSIONS: Non-traumatic diaphragmatic hernia of the liver in an adult is a rare right-sided diaphragmatic hernia, which can move up into the chest cavity. It should be distinguished from lung cancer. The diagnosis and evaluation of non-traumatic diaphragmatic hernia of the liver can help optimize surgical management.
文摘This study sought to investigate the clinical efficacy and safety of combined oral therapy with sildenafil and doxazosin GITS compared to sildenafil monotherapy in treating Chinese patients with erectile dysfunction （ED） and lower urinary tract symptoms secondary to benign prostatic hyperplasia （BPH/LUTS）. The trial was conducted in hospitals in Beijing, Shanghai, Changsha, Wuhan and Guangzhou, five major cities in China. A total of 250 patients diagnosed with ED and BPH/LUTS aged 50-75 years, and who had International Index of Erection Function-5 （IIEF-5） scores ≤ 21 and International Prostate Symptom Score （IPSS） ≥ 10 points, were enrolled and randomly divided into Group A （168 cases; doxazosin GITS 4 mg once daily plus sildenafi125-100 mg on demand） and Group B （82 cases; sildenafi125-100 mg on demand）. Efficacies were evaluated by IIEF-5 and IPSS scores and a quality of life （QoL） questionnaire, and adverse effects were evaluated during the treatment period. There were no statistically significant differences in mean age, and IIEF-5, IPSS and QoL scores pre-treatment between the two groups. After treatment, IIEF-5, IPSS and QoL scores were significantly improved in Group A, while only IIEF-5 scores were significantly improved in Group B compared with pre-treatment. There were no significant differences in side effects between the two groups. The results indicated that combined therapy with sildenafil and doxazosin GITS for the treatment of ED and BPH/LUTS is safe and effective compared to sildenafil monotherapy.
文摘Objective： To investigate potential prognostic factors affecting patient outcomes and to evaluate the optimal methods and effects of radiotherapy（RT） in the management of extramedullary plasmacytoma（EMP）.Methods： Data from 55 patients with EMP between November 1999 and August 2015 were collected. The median age was 51（range, 22–77） years. The median tumor size was 3.5（range, 1.0–15.0） cm. The median applied dose was 50.0（range, 30.0–70.0） Gy. Thirty-nine patients（70.9%） presented with disease in the head or neck region. Twelve patients received RT alone, 9 received surgery（S） alone, 3 received chemotherapy（CT） alone, and 3 patients did not receive any treatment. Combination therapies were applied in 28 patients.Results：The median follow-up duration was 56 months.The 5-year local recurrence-free survival（LRFS）,multiple myeloma-free survival（MMFS）,progression-free survival（PFS）and overall survival（OS）rates were 79.8%,78.6%,65.2% and 76.0%,respectively.Univariate analysis revealed that RT was a favourable factor for all examined endpoints.Furthermore,head and neck EMPs were associated with superior LRFS,MMFS and PFS.Tumor size〈4 cm was associated with superior MMFS,PFS and OS;serum M protein negativity was associated with superior MMFS and PFS;age≥50 years and local recurrence were associated with poor MMFS.The dose≥45 Gy group exhibited superior 5-year LRFS,MMFS and PFS rates（94.7%,94.4%,90.0%,respectively）,while the corresponding values for the dose〈45 Gy group were 62.5%（P=0.008）,53.3%（P=0.036）and 41.7%（P〈0.001）.Conclusions：Involved-site RT of at least 45 Gy should be considered for EMP.Furthermore,patients with head and neck EMP,tumor size〈4 cm,age〈50 years and serum M protein negativity had better outcomes.
文摘The robotic liver resection(RLR)has been increasingly applied in recent years and its benefits shown in some aspects owing to the technical advancement of robotic surgical system,however,controversies still exist.Based on the foundation of the previous consensus statement,this new consensus document aimed to update clinical recommendations and provide guidance to improve the outcomes of RLR clinical practice.The guideline steering group and guideline expert group were formed by 29 international experts of liver surgery and evidence-based medicine(EBM).Relevant literature was reviewed and analyzed by the evidence evaluation group.According to the WHO Handbook for Guideline Development,the Guidance Principles of Development and Amendment of the Guidelines for Clinical Diagnosis and Treatment in China 2022,a total of 14 recommendations were generated.Among them were 8 recommendations formulated by the GRADE method,and the remaining 6 recommendations were formulated based on literature review and experts’opinion due to insufficient EBM results.This international experts consensus guideline offered guidance for the safe and effective clinical practice and the research direction of RLR in future.
基金This research was funded by National Natural Science Foundation of China(Grant Number:81760142)the High-level Health Talents Project of Yunnan Provincial(Grant Number:H-2017036).
文摘Parathyroid carcinoma is an extremely rare malignant tumor,composed primarily of vacuolated principal cells,but may also be composed of eosinophils.The exact etiology and pathogenesis of parathyroid carcinoma is unknown,and head and neck radiation exposure,chronic stimulation from renal failure,and familial syndromes can lead to the development of parathyroid carcinoma.Most parathyroid carcinoma is difficult to distinguish from benign HPT and is often diagnosed only when there is a recurrence of hypercalcemia several years later,which can manifest as weight loss,extreme fatigue,anorexia,and muscle atrophy.At present,surgical resection remains the primary treatment.In this case,the patient underwent initial surgery for primary hyperparathyroidism and was subsequently diagnosed with parathyroid carcinoma.During the 8 years of follow-up,the patient underwent 7 surgeries in combination with radiation therapy,chemotherapy and targeted medications.Although the neck tumor was cured,the patient died of complications related to hypercalcemia.We will review the literature on the combination of surgery,radiotherapy,chemotherapy,and targeted drug therapy in order to improve the diagnosis and treatment of parathyroid carcinoma.
基金supported by the Ministry of Science and Technology of China(2021YFF0702100 and 2018YFA0801100 to S.C.and H.Y.W.)the National Natural Science Foundation of China(32025019 to S.C.,32400986 to P.R.)+2 种基金the Science and Technology Foundation of Jiangsu Province of China(BK20243041(Key Research Program))the Fundamental Research Funds for the Central Universities(021414380533 to S.C.)the Program A for Outstanding Ph D candidates of Nanjing University(202001A013 to P.R.)。
文摘Insulin-like growth factor 1(IGF1)is a regulator of both cellular hypertrophy and lipogenesis,which are two key processes for pathogenesis of obesity.However,the in vivo role of IGF1 in the development of obesity remains unclear.Here,we show that IGF1 expression is increased in adipose tissue in obese human patients and animal models.Elevation of IGF1 is associated with increased lipogenic gene expression and decreased energy expenditure.Genetic down-regulation of IGF1 normalizes lipogenic gene expression,restores aberrant energy metabolism and alleviates obese phenotype of a genetic mouse model with IGF1-hypersecretion.Importantly,genetic down-regulation of IGF1 exerts similar effects on development of diet-induced obesity.Furthermore,berberine that is an AMP-activated protein kinase(AMPK)activator in medicinal herbs inhibits IGF1 secretion,decreases lipogenic gene expression and alleviates diet-induced adiposity.Collectively,our findings demonstrate that hypersecretion of IGF1 is a critical factor for the development of obesity and can be targeted using AMPK activators to alleviate obesity.
基金supported by the National Key Research and Devel-opment Program of China(2023YFB3813000)the National Natural Science Foundation of China(T2121004,92268203,82301016)the Key Science and Technology Plan Projects in Jinhua City,2023-3-039.
文摘The reconstruction of large osteoarticular defects caused by tumor resection or severe trauma remains a clinical challenge.Current metal prostheses exhibit a lack of osteo-chondrogenic functionality and demonstrate poor integration with host tissues.This often results in complications such as abnormal bone absorption and prosthetic loosening,which may necessitate secondary revisions.Here,we propose a paradigm-shifting“living prosthesis”strategy that combines a customized 3D-printed hollow titanium humeral prosthesis with engineered bone marrow condensations presenting bone morphogenetic protein-2(BMP-2)and transforming growth factor-β3(TGF-β3)from encapsulated silk fibroin hydrogels.This innovative approach promotes in situ endochondral defect regeneration of the entire humeral head while simultaneously providing immediate mechanical support.In a rabbit model of total humerus resection,the designed“living prosthesis”achieved weight,macroscopic and microscopic morphologies that were comparable to those of undamaged native joints at 2 months post-implantation,with organized osteochondral tissues were regenerated both around and within the prosthesis.Notably,the“living prosthesis”displayed significantly higher osteo-integration than the blank metal prosthesis did,as evidenced by a 3-fold increase in bone ingrowth and a 2-fold increase in mechanical pull-out strength.Furthermore,the"living prosthesis"restored joint cartilage function,with rabbits exhibiting normal gait and weight-bearing capacity.The successful regeneration of fully functional humeral head tissue from a single implanted prosthesis represents technical advance in designing bioactive bone prosthesis,with promising im-plications for treating extreme-large osteochondral defects.
基金Xianghua Ye,Zhejiang Provincial Science and Technology Project,2024-KY1-001-105.This funding is intended to support the training of organ auto-segmentation models.
文摘Introduction:Accurate contouring of thoracic organs at risk(OARs)is essential for minimizing complications in radiation treatment.Manual contouring of thoracic OARs is not only time-consuming but also prone to substantial user variation.To enhance the efficiency and consistency,we developed a unified deep learning(DL)OAR contouring model,DeepOAR,that was trained using multiple partially labeled datasets for segmenting a comprehensive set of thoracic OARs following the Radiation Therapy Oncology Group(RTOG)-guided OAR atlas.This DL model supports the segmentation of six required and eight optional OARs guided by the NRG-RTOG 1106 trial,providing precise and reproducible OARs contouring that are ready to be used in radiotherapy practice.Materials and methods:Following the OAR contouring recommendation of the NRG-RTOG 1106 trial,we collected and curated three private datasets and two public datasets,comprising a total of 531 patients with partially annotated thoracic OARs.These partially annotated datasets were utilized to develop DeepOAR,which consisted of a shared encoder and 14 separate decoders,with each decoder dedicated to one specific OAR.For model training,we utilized all patients from the two public datasets and 75%of the patients from the private datasets.We reserved the remaining 25%of the private datasets for independent testing.A multi-user study involving 21 radiation oncologists was conducted on 40 randomly selected patients from the independent testing dataset to evaluate the clinical applicability of DeepOAR.The Dice coefficient score(DSC)and average surface distance(ASD)were computed to evaluate the quantitative delineation performance of the model.Results:DeepOAR outperformed nnUNet(the benchmark medical segmentation model)across all 14 OARs,achieving mean DSC and ASD values of 88.4%and 1.0 mm,respectively,in the independent testing set.Multi-user validation demonstrated that 89.7%of DeepOAR-generated OARs were clinically acceptable or required only minor revisions.A comparison using two randomly selected patients showed that the delineation variability of DeepOAR was significantly smaller than the inter-user variation among radiation oncologists.Human editing of DeepOAR’s predictions could further improve OAR delineation accuracy by an average of 3%increase in DSC and 40%reduction in ASD while significantly reducing the workload of radiation oncologists for contouring 14 thoracic OARs by an average of 77.0%.Conclusion:We developed DeepOAR,a DL-based unified contouring model trained using multiple partially labeled datasets,to delineate a comprehensive set of 14 thoracic OARs following the RTOG-guided OAR atlas.Both qualitative and quantitative results demonstrated the strong clinical applicability of DeepOAR for the OAR delineation process in thoracic cancer radiotherapy workflows,along with improved efficiency,comprehensiveness,and quality.
基金supported by the National Key Research and Development Program of China(2023YFB3813000)the National Natural Science Foundation of China(T2121004,92268203,32371411).
文摘Although natural polymers have been widely used in constructing bone scaffolds,it still remains challenging to fabricate natural polymer-derived bone scaffolds with biomimetic mechanical properties as well as outstanding osteogenic properties for large-size and weight-bearing bone defects regeneration.Herein,an“organic-inorganic assembly”strategy is developed to construct silk fibroin(SF)-based bone scaffolds with the aforementioned merits.After secondary structure reshuffling,the 3.3-fold increment ofβ-sheet structures in SF hydrogel resulted in a 100-fold improvement of mineral-assembly efficacy via influencing the ion adsorption process and providing templates for mineral growth.Notably,abundant minerals were deposited within the hydrogel and also on the surface,which indicated entire mineral-assembly,which ensured the biomimetic mechanical properties of the digital light processing 3D printed SF hydrogel scaffolds with haversian-mimicking structure.In vitro experiments proved that the assembly between the mineral and SF results in rapid adhesion and enhanced osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.In vivo experiments further proved that the mineral-assembled SF hydrogel scaffold could significantly enhance integration and bone regeneration at the weight-bearing site within one month.This SF-based“organic-inorganic assembly”strategy sheds light on constructing cell-free,growth factor-free and natural polymer-derived bone scaffolds with biomimetic 3D structure,mechanical properties and excellent osteogenic properties.
文摘Clostridioides difficile is a leading cause of healthcare-associated infections,causing billions of economic losses every year.Its symptoms range from mild diarrhea to life-threatening damage to the colon.Transmission and recurrence of c.difficile infection(CDl)are mediated by the metabolically dormant spores,while the virulence of C.difficile is mainly due to the two large clostridial toxins,TcdA and TcdB.Producing toxins or forming spores are two different strategies for C.difficile to cope with harsh environmental conditions.It is of great significance to understand the molecular mechanisms for C.difficile to skew to either of the cellular processes.Here,we summarize the current understanding of the regulation and connections between toxin production and sporulation in C.difficile and further discuss the potential solutions for yet-to-be-answered questions.
基金This work was supported by the National Key Research and Development Project of Stem Cell and Transformation Research(2019YFA0112100),ChinaNational Natural Science Foundation of China(81930070)+3 种基金National Natural Science Foundation of China(82102560)the Natural Science Foundation of Shandong Province,China(ZR2021QH097)the No.69 General Fund of China Postdoctoral Science Foundation(2021M691936)Talent project of Shandong University(22480082063100),China.
文摘Spinal cord injury(SCI)causes motor,sensory and automatic impairment due to rarely axon regeneration.Developing effective treatment for SCI in the clinic is extremely challenging because of the restrictive axonal regenerative ability and disconnection of neural elements after injury,as well as the limited systemic drug delivery efficiency caused by blood spinal cord barrier.To develop an effective non-invasive treatment strategy for SCI in clinic,we generated an autologous plasma exosome(AP-EXO)based biological scaffold where AP-EXO was loaded with neuron targeting peptide(RVG)and growth-facilitating peptides(ILP and ISP).This scaffold can be targeted delivered to neurons in the injured area and elicit robust axon regrowth across the lesion core to the levels over 30-fold greater than naïve treatment,thus reestablish the intraspinal circuits and promote motor functional recovery after spinal cord injury in mice.More importantly,in ex vivo,human plasma exosomes(HP-EXO)loaded with combinatory peptides of RVG,ILP and ISP showed safety and no liver and kidney toxicity in the application to nude SCI mice.Combining the efficacy and safety,the AP-EXO-based personalized treatment confers functional recovery after SCI and showed immense promising in biomedical applications in treating SCI.It is helpful to expand the application of combinatory peptides and human plasma derived autologous exosomes in promoting regeneration and recovery upon SCI treatment.
