BACKGROUND:Extracellular vesicles have received extensive attention in the field of bone defect regeneration and repair in recent years.However,natural extracellular vesicles have deficiencies in sustained controlled release,tissue targeting,and drug loading capacity.Therefore,the introduction of engineering strategies to modify extracellular vesicles to enhance their therapeutic efficacy has become a research hotspot.OBJECTIVE:To review the role and application progress of engineered extracellular vesicles in the regeneration and repair of bone defects.METHODS:PubMed,Web of Science,CNKI,and WanFang databases were searched for relevant articles published in the past fifteen years.The search terms were"engineering,extracellular vesicles,exosomes,bone defect,bone regeneration,bone repair"in Chinese and English.After removal of poorly related,outdated,and duplicate studies by screening,93 articles were finally included for review according to inclusion criteria.RESULTS AND CONCLUSION:(1)Extracellular vesicles are primarily isolated based on their density,size,immunoaffinity,and surface charge.After isolation,extracellular vesicles are characterized using imaging techniques,size-and counting-based techniques,and flow cytometry.(2)Extracellular vesicles stimulate bone regeneration by regulating immunity,angiogenesis,and proliferation and differentiation of target cells.(3)The engineering strategies of extracellular vesicles include surface modification and cargo loading.(4)The introduction of bone morphogenetic protein 2,mutant hypoxia-inducible factor-1α,vascular endothelial growth factor,miRNA and other bioactive factors into extracellular vesicles through engineering strategies can enhance their regenerative repair ability for bone defects.

Objective:To investigate the current application status of prophylactic anti-infective drugs during the perioperative period in liver transplantation centers and provide data references for further standardizing prophylactic regimens.Methods:A questionnaire comprising 53 questions across 5 dimensions was designed and released using the WJX platform. The dimensions included basic information about medical institutions, perioperative pathogenic microorganisms, current status of empirical antibacterial prophylaxis, adjustments to prophylactic anti-infective strategies, and an overview of prophylactic measures against other pathogens. Based on the survey results, the types of common perioperative pathogens in liver transplantation, types of prophylactic antibacterial drugs, timing and duration of administration, upgraded prophylaxis strategies (such as escalation of antibiotic classes or extension of drug application duration), and prevention strategies for other pathogens were summarized.Results:A total of 13 completed questionnaires from pharmacists at liver transplantation centers were collected. The most common pathogens during the perioperative period were Gram-negative bacilli, including Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. The most frequently used prophylactic antibacterial drugs were cefoperazone/sulbactam and piperacillin/tazobactam. Regarding the timing of administration, 9 centers administered drugs 0.5 to 1.0 hour before surgery, 3 within 0.5 hour, and 1 within 1 hour preoperatively. The prophylactic duration was within 7 days postoperatively for living donor liver transplantation in 10 centers, while for cadaveric donor liver transplantation, only 6 centers adhered to the 7-day duration. When donors had infections with sensitive bacteria, 9 centers upgraded prevention strategies: 2 centers escalated the antibiotic class or adjusted regimens, 5 centers extended the duration of prophylaxis, 2 centers implemented donor-specific susceptibility-guided antibacterial treatments regardless of colonization or infection, and 5 centers administered prophylaxis only in cases of colonization based on donor susceptibility results. When donors had multi-drug resistance bacterial infections, 11 centers upgraded prevention strategies: 7 escalated the antibiotic class or adjusted regimens, 4 extended prophylaxis duration, 6 implemented susceptibility-guided treatments irrespective of colonization or infection, 1 administered prophylaxis only for colonization based on donor susceptibility results, and 2 abandoned transplantations. 7 centers routinely applied antifungal prophylactic measures, including 1 for preoperative prophylaxis and 6 for postoperative prophylaxis, using caspofungin (4 centers), fluconazole (2 centers), posaconazole (1 center), and micafungin (1 center). 6 centers initiated antifungal prophylaxis in cases with donor or recipient fungal infection history or active fungal infections detected during liver procurement. Most antifungal prophylaxis was administered within 72 hours postoperative (11 centers), with durations mostly within 14 days (12 centers). For viral infections, 6 centers adopted routine postoperative prophylactic measures. Conclusions:Currently, the perioperative prophylactic anti-infective strategies in 13 liver transplantation centers are not standardized. High-quality multicenter clinical studies are needed to compare the effectiveness of different prophylactic regimens, aiming to further standardize the types and durations of prophylactic drug use.

OBJECTIVES: To study the impact of SURF4 expression level on long-term prognosis of gastric cancer (GC) and biological behaviors of GC cells. METHODS: SURF4 expression level in GC and its association with long-term patient prognosis were analyzed using publicly available databases and in 155 GC patients with low and high SURF4 expressions detected immunohistochemically. The Cox proportional hazard model and Kaplan-Meier survival curves were used to analyze independent prognostic predictors of GC and the 5-year survival rate of the patients with different SURF4 expression levels. Informatics analyses were conducted to explore the correlation of SURF4 expression level with immune cell infiltration in GC, SURF4-related differential genes and their associated pathways. In cultured GC cell line HGC-27, the effects of SURF4 knockdown and overexpression on proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) were investigated. RESULTS: Analysis of GEPIA dataset and immunohistochemical results suggested significant SURF4 overexpression in GC (P<0.05), which was associated with shortened 5-year survival time of the patients (χ²=38.749, P<0.001). The prognosis of GC was closely related to tumor stage T3-4, N2-3, CEA≥5 μg/L and CA19-9≥37 kU/L (P<0.05). SURF4 expression level was negatively correlated with activated B cells, NK cells and CD8⁺ effector memory T cells (P<0.05) and positively correlated with CD4⁺ T cells (P<0.05). GO and KEGG enrichment analysis suggested that SUFR4 may participate in GC carcinogenesis by promoting EMT through the tight junction pathway. In HGC-27 cells, SURF4 overexpression significantly decreased E-cadherin expression, increased N-cadherin expression, inhibited ZO-1 and claudin-1 expressions, and promoted cell proliferation, migration and invasion. CONCLUSIONS SURF4 is highly expressed in GC, and its overexpression is associated with a shortened 5-year survival of the patients possibly by enhancing tumor cell proliferation, migration and invasion via inhibiting tight junction proteins and promoting EMT.
Humans ; Stomach Neoplasms/metabolism* ; Cell Proliferation ; Cell Movement ; Epithelial-Mesenchymal Transition ; Cell Line, Tumor ; Neoplasm Invasiveness ; Prognosis ; Tight Junction Proteins/metabolism* ; Membrane Proteins/metabolism* ; Female ; Male

BACKGROUND:Extracellular vesicles have received extensive attention in the field of bone defect regeneration and repair in recent years.However,natural extracellular vesicles have deficiencies in sustained controlled release,tissue targeting,and drug loading capacity.Therefore,the introduction of engineering strategies to modify extracellular vesicles to enhance their therapeutic efficacy has become a research hotspot.OBJECTIVE:To review the role and application progress of engineered extracellular vesicles in the regeneration and repair of bone defects.METHODS:PubMed,Web of Science,CNKI,and WanFang databases were searched for relevant articles published in the past fifteen years.The search terms were"engineering,extracellular vesicles,exosomes,bone defect,bone regeneration,bone repair"in Chinese and English.After removal of poorly related,outdated,and duplicate studies by screening,93 articles were finally included for review according to inclusion criteria.RESULTS AND CONCLUSION:(1)Extracellular vesicles are primarily isolated based on their density,size,immunoaffinity,and surface charge.After isolation,extracellular vesicles are characterized using imaging techniques,size-and counting-based techniques,and flow cytometry.(2)Extracellular vesicles stimulate bone regeneration by regulating immunity,angiogenesis,and proliferation and differentiation of target cells.(3)The engineering strategies of extracellular vesicles include surface modification and cargo loading.(4)The introduction of bone morphogenetic protein 2,mutant hypoxia-inducible factor-1α,vascular endothelial growth factor,miRNA and other bioactive factors into extracellular vesicles through engineering strategies can enhance their regenerative repair ability for bone defects.

Objective:To investigate the current application status of prophylactic anti-infective drugs during the perioperative period in liver transplantation centers and provide data references for further standardizing prophylactic regimens.Methods:A questionnaire comprising 53 questions across 5 dimensions was designed and released using the WJX platform. The dimensions included basic information about medical institutions, perioperative pathogenic microorganisms, current status of empirical antibacterial prophylaxis, adjustments to prophylactic anti-infective strategies, and an overview of prophylactic measures against other pathogens. Based on the survey results, the types of common perioperative pathogens in liver transplantation, types of prophylactic antibacterial drugs, timing and duration of administration, upgraded prophylaxis strategies (such as escalation of antibiotic classes or extension of drug application duration), and prevention strategies for other pathogens were summarized.Results:A total of 13 completed questionnaires from pharmacists at liver transplantation centers were collected. The most common pathogens during the perioperative period were Gram-negative bacilli, including Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. The most frequently used prophylactic antibacterial drugs were cefoperazone/sulbactam and piperacillin/tazobactam. Regarding the timing of administration, 9 centers administered drugs 0.5 to 1.0 hour before surgery, 3 within 0.5 hour, and 1 within 1 hour preoperatively. The prophylactic duration was within 7 days postoperatively for living donor liver transplantation in 10 centers, while for cadaveric donor liver transplantation, only 6 centers adhered to the 7-day duration. When donors had infections with sensitive bacteria, 9 centers upgraded prevention strategies: 2 centers escalated the antibiotic class or adjusted regimens, 5 centers extended the duration of prophylaxis, 2 centers implemented donor-specific susceptibility-guided antibacterial treatments regardless of colonization or infection, and 5 centers administered prophylaxis only in cases of colonization based on donor susceptibility results. When donors had multi-drug resistance bacterial infections, 11 centers upgraded prevention strategies: 7 escalated the antibiotic class or adjusted regimens, 4 extended prophylaxis duration, 6 implemented susceptibility-guided treatments irrespective of colonization or infection, 1 administered prophylaxis only for colonization based on donor susceptibility results, and 2 abandoned transplantations. 7 centers routinely applied antifungal prophylactic measures, including 1 for preoperative prophylaxis and 6 for postoperative prophylaxis, using caspofungin (4 centers), fluconazole (2 centers), posaconazole (1 center), and micafungin (1 center). 6 centers initiated antifungal prophylaxis in cases with donor or recipient fungal infection history or active fungal infections detected during liver procurement. Most antifungal prophylaxis was administered within 72 hours postoperative (11 centers), with durations mostly within 14 days (12 centers). For viral infections, 6 centers adopted routine postoperative prophylactic measures. Conclusions:Currently, the perioperative prophylactic anti-infective strategies in 13 liver transplantation centers are not standardized. High-quality multicenter clinical studies are needed to compare the effectiveness of different prophylactic regimens, aiming to further standardize the types and durations of prophylactic drug use.

Adolescence is defined as a population ranging from ten to nineteen years old.Permanent teeth in adolescents are of critical significance as they are actively involved in mastication,contribute to aesthetic appearance,play a role in pronunciation,and are integral to the growth and development of the stomatognathic system.Specifically,permanent teeth in adolescents comprise those with incomplete root development and those with complete root development but unstable gingival margin positions.However,the prevalence of permanent tooth defects among adolescents remains high,primarily due to their insuffi-cient awareness of oral health care and poor compliance with preventive measures.Therefore,it is very important to emphasize the necessity for timely and appropriate restoration of permanent tooth defects in adolescents.Given the distinct physiological characteristics of adolescent permanent teeth compared with mature permanent teeth,interim restoration approaches are required.The field of adolescent permanent tooth restoration is an interdisciplinary area,involving both prosthodontics and pediatric dentistry.Cur-rently,a comprehensive and standardized principle for the selection of restoration indications is lacking,which poses challenges for clinicians in making optimal treatment decisions.Therefore,this article aims to comprehensively summarize the clinical dilemmas associated with the restoration of adolescent perma-nent teeth,and propose a set of principles for the selection of restoration methods and materials,aiming to offer practical clinical guidelines for dentists when dealing with permanent tooth defects in adolescent patients.In particular,because of the different restoration dilemmas of anterior and posterior permanent teeth,a variety of interim restoration methods,their applicable conditions,advantages,and disadvanta-ges are introduced respectively.Additionally,it provides an in-depth discussion of different interim resto-ration materials,including direct restoration materials like light-cured composite resin and dual-cured temporary crown resin,as well as indirect restoration materials such as polymeric porcelain and CAD/CAM resin-matrix ceramics.The goal of this research is to provide a foundation for the development of evidence-based restoration plans in clinical practice and to contribute to the establishment of future standards in the field of adolescent permanent tooth restoration.This will enhance the quality of dental care for adolescents and promote better oral health outcomes in this population.

Accumulating evidence has demonstrated that apoptotic vesicles(apoVs)derived from mesenchymal stem cells(MSCs;MSC-apoVs)are vital for bone regeneration,and possess superior capabilities compared to MSCs and other extracellular vesicles derived from MSCs(such as exosomes).The osteoinductive effect of MSC-apoVs is attributed to their diverse contents,especially enriched proteins or microRNAs(miRNAs).To optimize their osteoinduction activity,it is necessary to determine the unique cargo profiles of MSC-apoVs.We previously established the protein landscape and identified proteins specific to MSC-apoVs.However,the features and functions of miRNAs enriched in MSC-apoVs are unclear.In this study,we compared MSCs,MSC-apoVs,and MSC-exosomes from two types of MSC.We generated a map of miRNAs specific to MSC-apoVs and identified seven miRNAs specifically enriched in MSC-apoVs compared to MSCs and MSC-exosomes,which we classified as apoV-specific miRNAs.Among these seven specific miRNAs,hsa-miR-4485-3p was the most abundant and stable.Next,we explored its function in apoV-mediated osteoinduction.Unexpectedly,hsa-miR-4485-3p enriched in MSC-apoVs inhibited osteogenesis and promoted adipogenesis by targeting the AKT pathway.Tailored apoVs with downregulated hsa-miR-4485-3p exhibited a greater effect on bone regeneration than control apoVs.Like releasing the brake,we acquired more powerful osteoinductive apoVs.In summary,we identified the miRNA cargos,including miRNAs specific to MSC-apoVs,and generated tailored apoVs with high osteoinduction activity,which is promising in apoV-based therapies for bone regeneration.

Objective To discuss the perioperative care and wound protection of xenotransplantation from genetically edited pigs to monkeys, with the goal of improving the success rate of such experimental procedures. Methods From October 2022 to October 2023, perioperative care and wound protection were performed on 7 recipient rhesus monkeys undergoing xenotransplantation of genetically edited pig tissues and organs. Customized wound protective garments were designed based on monkeys' size and surgical area to protect the wounds, alongside meticulous perioperative care. This included preoperative preparation and medication, intraoperative monitoring of physiological indicators and anesthesia management, and postoperative care comprising wound protection, observation and monitoring, and nutritional support. Results All seven monkeys successfully underwent xenotransplantation. With the aid of protective garments and detailed care, all surgical wounds healed by first intention, and postoperative recovery was satisfactory. Conclusion Proper care and wound protection during xenotransplantation from genetically edited pigs to monkeys not only promote wound healing, but also alleviate pain and harm to animals. This has significant implications for advancing experimental research in pig-monkey xenotransplantation and enhancing animal welfare.

Objective:This study aimed to evaluate the global research landscape, identify trends, and determine hotspots concerning hepatoma recurrence post-liver transplantation.Methods:We conducted a bibliometric analysis usinga systematic search was conducted in the Web of Science Core Collection database from Jan. 1992 to Oct. 2023 to identify relevant articles on hepatoma recurrence after liver transplantation. Articles were selected based on inclusion and exclusion criteria and analyzed for publication trends by country/region, journal, author, institution, citation, and keyword. Visualization tools such as Citespace, VOSviewer, and Bibliometric.com were utilized for statistical analysis, identification of emerging trends, and clustering of keyword co-occurrence.Results:Out of 4,936 articles retrieved, 1,189 were included in the final analysis. There was a notable increase in publications on hepatoma recurrence following liver transplantation from 1992 to 2021, peaking in 2021 both globally (n=103) and nationally (n=32). China has the largest number of publications in this field (n=308), maintaining significant collaboration with the United States, South Korea, Japan, Canada. 'Liver Transplantation’ journal had the highest number of publications (n=113). Zhejiang University was the leading institution (n=74), with Academician Zheng Shusen being the most prolific scholar (n=76 publications). Citation emergence detection found that Italian scholar Mazzaferro's Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis published on The Lancet Oncology in 2009 had the highest burst strength (36.98). Five bursting keywords were identified: alpha fetoprotein, model, validation, sorafenib, and risk. Cluster analysis of keyword co-occurrence revealed five primary research themes: the medication for hepatocellular carcinoma recurrence after liver transplantation, recipient selection criteria, prognostic factors, development and validation of recurrence prediction model, and local treatments for hepatocellular carcinoma.Conclusions:The study underscores rapid advancements in the research on hepatocellular carcinoma recurrence post-liver transplantation over the past three decades, with significant contributions from Chinese scholars, particularly from Zhejiang University and Academician Zheng Shusen. The evolving research hotspots have shifted from transplantation experiences and recipient selection criteria to early post-transplant recurrence risk prediction and therapeutic strategy development.

Objective To establish a fast,stable,and sensitive zebrafish model of osteoporosis(OP)using different method.Methods OP models were induced by iron overload or prednisolone(Pred),and bone formation and mortality were observed.The groups were divided into:Control group,model group(include FAC group and Pred group),and positive control group(AC group).Ammonium ferric citrate was used as the model drug in the iron-overload induction method.For the Pred induction models,the modeling time for the Pred-3 days post-fertilization(dpf)method was 3～9 dpf,the modeling time for the Pred-5 dpf method was 5～10 dpf,and Pred was administered from 3 dpf and removed from 7～9 dpf for the Pred withdrawal method.To compare the anti-osteoporosis(OP)effects of commonly used drugs such as Alfacalcidol(AC),Calcitriol(CA),and Alendronate(AL),it's important to select a stable and sensitive positive control drug and to further optimize different staining methods and conditions.Results There was no significant effect of ammonium ferric citrate 500 μg/mL on bone formation.Bone formation and the length of the first vertebra were significantly decreased in the Pred group induced by Pred-3 dpf compared with those in the control group(P＜0.01,P＜0.05),but zebrafish mortality was higher.There was no significant difference between the Pred-5 dpf method,but bone formation was significantly reduced in the Pred withdrawal group(P＜0.01),with no mortality.Alfacalcidol,calcitriol,and alendronate all had anti-OP effects,with CA having the most sensitive and stable anti-OP effect.Alizarin red staining showed that the optimal dye parameters were 0.02%concentration for dyeing 2 h,with washing in 0.5%KOH and glycerol under the conditions of a 3∶1 ratio for 3 h followed by a 1∶1 ratio for 14 h.The result of staining showed that calcein was more sensitive for staining bone nodes and ARS staining was more sensitive for staining the first vertebra.Conclusions The Pred withdrawal method can be used to establish a rapid,stable,and sensitive OP model in zebrafish as a reliable model for studying OP.