CircNFIB inhibits tumor growth and metastasis through suppressing MEK1/ERK signaling in intrahepatic cholangiocarcinoma.

BACKGROUND: Considerable evidence shows that circular RNAs (circRNAs) play an important role in tumor development. However, their function in intrahepatic cholangiocarcinoma (ICC) metastasis and the underlying mechanisms are incompletely understood. METHODS: circNFIB (hsa_circ_0086376, termed as cNFIB hereafter) was identified in human ICC tissues through circRNAs sequencing. The biological role of cNFIB was determined in vitro and in vivo by gain or loss of functional experiments. Fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down assays were conducted to analyze the interaction of cNFIB with dual specificity mitogen-activated protein kinase kinase1 (MEK1). Duolink in situ proximity ligation assay (PLA) and coimmunoprecipitation (co-IP) assay were used to investigate the effects of cNFIB on the interaction between MEK1 and mitogen-activated protein kinase 2 (ERK2). Finally, a series of in vitro and in vivo experiments were performed to explore the influences of cNFIB on the anti-tumor activity of trametinib (a MEK inhibitor). RESULTS: cNFIB was significantly down-regulated in human ICC tissues with postoperative metastases. The loss of cNFIB was highly associated with aggressive characteristics and predicted unfavorable prognosis in ICC patients. Functional studies revealed that cNFIB inhibited the proliferation and metastasis of ICC cells in vitro and in vivo. Mechanistically, cNFIB competitively interacted with MEK1, which induced the dissociation between MEK1 and ERK2, thereby resulting in the suppression of ERK signaling and tumor metastasis. Moreover, we found that ICC cells with high levels of cNFIB held the potential to delay the trametinib resistance. Consistently, in vivo and in vitro studies demonstrated that cotreatment with trametinib and lentivirus vector encoding cNFIB showed greater inhibitory effect than isolated trametinib treatment. CONCLUSIONS: Our findings identified that cNFIB played a key role in ICC growth and metastasis by regulating MEK1/ERK signaling. Given the efficacy of cNFIB modulation on ICC suppression and trametinib sensitivity, cNFIB appears to be a potential therapeutic molecule for ICC treatment.

The role and mechanism of noncoding RNAs in regulation of metabolic reprogramming in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Metabolic reprogramming is considered to be an important hallmark of cancer. Emerging studies have demonstrated that noncoding RNAs (ncRNAs) are closely associated with metabolic reprogramming of HCC. NcRNAs can directly regulate the expressions or functions of metabolic enzymes or indirectly regulate the metabolism of HCC cells through some vital signaling pathways. Until now, the mechanisms of HCC development and progression remain largely unclear, and understanding the regulatory mechanism of ncRNAs on metabolic reprogramming of HCC may provide an important basis for breakthrough progress in the treatment of HCC. In this review, we summarize the ncRNAs involved in regulating metabolic reprogramming of HCC. Specifically, the regulatory roles of ncRNAs in glucose, lipid and amino acid metabolism are elaborated. In addition, we discuss the molecular mechanism of ncRNAs in regulation of metabolic reprogramming and possible therapeutic strategies that target the metabolism of cancer cells by modulating the expressions of specific ncRNAs.

Robotic versus laparoscopic distal gastrectomy for gastric cancer: A systematic review and meta-analysis.

Distal gastrectomy (DG) with lymph node dissection for gastric cancer is routinely performed. In this meta-analysis, we present an updated overview of the perioperative and oncological outcomes of laparoscopic DG (LDG) and robotic DG (RDG) to compare their safety and overall outcomes in patients undergoing DG. An extensive search was conducted using the MEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials from the establishment of the database to June 2023 for randomized clinical trials comparing RDG and LDG. The primary outcome was operative results, postoperative recovery, complications, adequacy of resection, and long-term survival. We identified twenty studies, evaluating 5,447 patients (1,968 and 3,479 patients treated with RDG and LDG, respectively). We observed no significant differences between the two groups in terms of the proximal resection margin, number of dissected lymph nodes, major complications, anastomosis site leakage, time to first flatus, and length of hospital stay. The RDG group had a longer operative time (P < 0.00001), lesser bleeding (P = 0.0001), longer distal resection margin (P = 0.02), earlier time to oral intake (P = 0.02), fewer overall complications (P = 0.004), and higher costs (P < 0.0001) than the LDG group. RDG is a promising approach for improving LDG owing to acceptable complications and the possibility of radical resection. Longer operative times and higher costs should not prevent researchers from exploring new applications of robotic surgery.

Research progress on cuproptosis in cancer.

Cuproptosis is a recently discovered form of cell death that is mediated by copper (Cu) and is a non-apoptotic form of cell death related to oligomerization of lipoylated proteins and loss of Fe-S protein clusters. Since its discovery, cuproptosis has been extensively studied by researchers for its mechanism and potential applications in the treatment of cancer. Therefore, this article reviews the specific mechanism of cuproptosis currently studied, as well as its principles and strategies for use in anti-cancer treatment, with the aim of providing a reference for cuproptosis-based cancer therapy.

Robotic versus laparoscopic gastrectomy for gastric cancer in patients with obesity: systematic review and meta-analysis.

Introduction: The number of overweight patients with gastric cancer (GC) is increasing, and no previous study has compared laparoscopic gastrectomy (LG) and robotic gastrectomy (RG) in obese patients with GC. To investigate the perioperative and oncologic outcomes of RG and LG in obese GC patients, we performed a meta-analysis of propensity matched scores and retrospective studies to compare the perioperative parameters, oncologic findings, and short-term postoperative outcomes between the two groups. Methods: This study was performed according to the PRISMA guidelines. A search was performed on PubMed, Web of Science, EMBASE, and Cochrane Central Register to identify eligible propensity matched scores and retrospective studies conducted and published before December 2022. Data on perioperative and oncological outcomes were included in the meta-analysis. Results: Overall, we identified 1 propensity score match study and 5 randomized control trials of RG and LG, enrolling a total of 718 patients (197 and 521 patients received RG and LG, respectively). No significant differences were observed between the two groups in terms of complications, bleeding, or lymph node dissection. Of note, RG had a longer procedure time (P = 0.03), earlier oral intake (P = 0.0010), shorter hospital stay (P = 0.0002), and shorter time to defecation (P < 0.00001). Conclusions: This meta-analysis concluded that patients in the RG group had shorter hospital stays, earlier postoperative feeding, and earlier postoperative ventilation; however, no differences were found in blood loss, number of lymph nodes removed, or overall complications. RG is an effective, safe, and promising treatment for obese patients with GC, compensating for the shortcomings of laparoscopy and allowing for less trauma and faster recovery. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022298967.

Circular RNAs in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is the most common primary biliary malignancy with an adverse prognosis. Although its incidence is relatively low, early diagnosis is difficult due to the lack of specific symptoms. Current treatment options for CCA are limited, resulting in a low curative rate. Circular RNAs (circRNAs) have become a new research hotspot in recent years, and they are frequently dysregulated in CCA and may become therapeutic targets and prognostic biomarkers of CCA. Accumulating evidence has demonstrated that numerous dysregulated circRNAs are vital players in the etiopathogenesis of CCA. Aberrant expression of specific circRNAs was correlated with unfavourable clinical characteristics in CCA. Many studies have found that circRNAs are involved in the progression and development of CCA through various mechanisms, including competitive inhibition of miRNAs via the competing endogenous RNA (ceRNA) network, interaction with RNA-binding proteins (RBPs), activation of cancer-related signalling pathways, and regulation of proteins and peptides. Additionally, some circRNAs are involved in the inflammatory microenvironment of CCA and play a crucial role in chemotherapy drug resistance. Thus, they are essential for the early diagnosis and prediction of CCA, and more attention should be given to the roles and mechanisms of circRNAs in CCA. In this review, we summarize the abnormal expression of circRNAs in CCA and the specific inflammatory microenvironment involved, as well as the roles and mechanisms of circRNAs in the occurrence and development of CCA. We also review the latest knowle dge on circRNAs in CCA and discuss the challenges associated with the introduction of circRNAs into clinical practice and their potential clinical value.

Integrated printed BDNF-stimulated HUCMSCs-derived exosomes/collagen/chitosan biological scaffolds with 3D printing technology promoted the remodelling of neural networks after traumatic brain injury.

The restoration of nerve dysfunction after traumatic brain injury (TBI) faces huge challenges due to the limited self-regenerative abilities of nerve tissues. In situ inductive recovery can be achieved utilizing biological scaffolds combined with endogenous human umbilical cord mesenchymal stem cells (HUCMSCs)-derived exosomes (MExos). In this study, brain-derived neurotrophic factor-stimulated HUCMSCs-derived exosomes (BMExos) were composited with collagen/chitosan by 3D printing technology. 3D-printed collagen/chitosan/BMExos (3D-CC-BMExos) scaffolds have excellent mechanical properties and biocompatibility. Subsequently, in vivo experiments showed that 3D-CC-BMExos therapy could improve the recovery of neuromotor function and cognitive function in a TBI model in rats. Consistent with the behavioural recovery, the results of histomorphological tests showed that 3D-CC-BMExos therapy could facilitate the remodelling of neural networks, such as improving the regeneration of nerve fibres, synaptic connections and myelin sheaths, in lesions after TBI.

CircZNF215 promotes tumor growth and metastasis through inactivation of the PTEN/AKT pathway in intrahepatic cholangiocarcinoma.

BACKGROUND: Increasing evidence shows that circular RNAs (circRNAs), a novel class of noncoding RNAs, play a crucial role in the development of cancers, including intrahepatic cholangiocarcinoma (iCCA). Nevertheless, their functions and exact mechanisms in iCCA progression and metastasis are still unclear. Ipatasertib is a highly selective inhibitor of AKT that inhibits tumor growth by blocking the PI3K/AKT pathway. In addition, phosphatase and tensin homolog (PTEN) can also inhibit the activation of the PI3K/AKT pathway, but it is not clear whether the cZNF215-PRDX-PTEN axis plays a role in the antitumor activity of ipatasertib. METHODS: We identified a new circRNA (circZNF215, termed cZNF215) through high-throughput circRNA sequencing (circRNA-seq). In addition, RT‒qPCR, immunoblot assay, RNA pull-down assay, RNA immunoprecipitation (RIP) assay, and fluorescence in situ hybridization assay (FISH) were used to investigate the interaction of cZNF215 with peroxiredoxin 1 (PRDX1). Coimmunoprecipitation (Co-IP) assays and duolink in situ proximity ligation assays (PLAs) were conducted to analyze the effects of cZNF215 on the interaction between PRDX1 and PTEN. Finally, we tested the potential effects of cZNF215 on the antitumor activity of ipatasertib with in vivo experiments. RESULTS: We found that cZNF215 expression was obviously upregulated in iCCA tissues with postoperative metastases and was correlated with iCCA metastasis and poor outcome in patients with iCCA. We further revealed that overexpression of cZNF215 promoted iCCA cell growth and metastasis in vitro and in vivo, while cZNF215 knockdown had the opposite effect. Mechanistic studies suggested that cZNF215 competitively interacted with PRDX1, which blocked the association between PRDX1 and PTEN, subsequently leading to oxidation-induced inactivation of the PTEN/AKT pathway and finally contributing to iCCA progression and metastasis. Additionally, we also revealed that silencing cZNF215 in iCCA cells had the potential to enhance the antitumor effect of ipatasertib. CONCLUSIONS: Our study demonstrates that cZNF215 facilitates iCCA progression and metastasis by regulating the PTEN/AKT pathway and may serve as a novel prognostic predictor in patients with iCCA.

Low-temperature 3D-printed collagen/chitosan scaffolds loaded with exosomes derived from neural stem cells pretreated with insulin growth factor-1 enhance neural regeneration after traumatic brain injury.

There are various clinical treatments for traumatic brain injury, including surgery, drug therapy, and rehabilitation therapy; however, the therapeutic effects are limited. Scaffolds combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain injury. In this study, we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (3D-CC-INExos) to improve traumatic brain injury repair and functional recovery after traumatic brain injury in rats. Composite scaffolds comprising collagen, chitosan, and exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (INExos) continuously released exosomes for 2 weeks. Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model, as assessed by the Morris water maze test and modified neurological severity scores. In addition, immunofluorescence staining and transmission electron microscopy showed that 3D-CC-INExos implantation significantly improved the recovery of damaged nerve tissue in the injured area. In conclusion, this study suggests that transplanted 3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.

Carpal tunnel syndrome caused by tophi deposited under the epineurium of the median nerve: A case report.

Introduction: Usually caused by compression of the wrist's median nerve, carpal tunnel syndrome (CTS) is one of the most common types of peripheral neuropathy. Tophi deposited under the epineurium of the median nerve compress the median nerve, leading to CTS, which is very rare. Case presentation: We report a 64-year-old man with a history of tophaceous gout who presented with typical CTS symptoms and was admitted to our hospital. A physical examination revealed swelling over the right volar aspect of the carpal region, and he was unable to flex due to subcutaneous rigidity. Tinel's sign and Phalen's maneuver were positive. Electrophysiological studies confirmed the diagnosis of CTS. A carpal tunnel release and surgery to remove the gouty tophus of the right wrist were performed when serum uric acid levels were within normal limits (5.8 mg/dl). During the operation, tophi deposited under the epineurium of the median nerve were found, and the tophi were completely removed. Operative findings confirmed the diagnosis of CTS due to gout. The patient recovered uneventfully without signs of recurrence of gout and CTS symptoms during a 1-year follow-up period. Conclusion: A gouty tophus is an uncommon cause of CTS, and CTS may be caused by gouty tophi if there is evidence of extrinsic compression of the median nerve or symptoms emanating from the carpal tunnel.

An ingested metallic wire migrating from stomach to pancreas treated by laparoscopic surgery: A case report.

Introduction: Foreign bodies inside the pancreas are rare and usually occur after the ingestion of sharp objects such as a fish bone, a sewing needle, or a toothpick. Furthermore, an ingested metallic wire migrating from stomach to pancreas is very rare. Case Presentation: We report a 36-year-old woman who was admitted to our hospital with "3-day history of dull progressive epigastric pain." Computed tomography of the abdomen revealed a linear, high-density body between the stomach wall and the pancreas. During the operation, a linear, hard, metallic wire was found in the adhesive tissue between the gastric antrum and the pancreatic body. The operation was uneventful, and the patient recovered well. Conclusion: The case of a foreign body inside the pancreas caused by a metallic wire is very rare. Radiological examinations play a vital role in the diagnosis of metallic wire ingestion. Metallic wire ingestion can be treated with laparoscopic surgery, both technically and safely.

Updated Evaluation of Robotic- and Video-Assisted Thoracoscopic Lobectomy or Segmentectomy for Lung Cancer: A Systematic Review and Meta-Analysis.

Objectives: Robot-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS) are the two principal minimally invasive surgical approaches for patients with lung cancer. This study aimed at comparing the long-term and short-term outcomes of RATS and VATS for lung cancer. Methods: A comprehensive search for studies that compared RATS versus VATS for lung cancer published until November 31, 2021, was conducted. Data on perioperative outcomes and oncologic outcomes were subjected to meta-analysis. PubMed, Web of Science, and EMBASE were searched based on a defined search strategy to identify eligible studies before November 2021. Results: Twenty-six studies comparing 45,733 patients (14,271 and 31,462 patients who underwent RATS and VATS, respectively) were included. The present meta-analysis showed that there were no significant differences in operative time, any complications, tumor size, chest drain duration, R0 resection rate, lymph station, 5-year overall survival, and recurrence rate. However, compared with the VATS group, the RATS group had less blood loss, a lower conversion rate to open, a shorter length of hospital stay, more lymph node dissection, and better 5-year disease-free survival. Conclusions: RATS is a safe and feasible alternative to VATS for patients with lung cancer.

Cardiac Doppler Parameters and Progress in Clinical Manifestation of Primary Lower Extremity Varicose Veins: A Prospective Study in China.

Objective: To investigate the features of cardiac Doppler parameters in patients with primary lower extremity varicose veins in China. Materials and Methods: We performed a prospective statistical analysis of cardiac Doppler parameters between 129 Chinese patients with varicose veins and normal controls. Furthermore, we evaluated the relationship between cardiac Doppler and the progress or severity of lower extremity varicose veins. Results: Compared with normal controls, patients with primary varicose veins had significantly lower early mitral and tricuspid diastolic inflow and annular velocities (E- and e'-waves), significantly higher late mitral and tricuspid diastolic inflow and annular velocities (A- and a'-waves), significantly higher mitral systolic annular velocities (s'-wave), and significantly lower mitral and tricuspid E/A ratio. There was no significant association between deep venous reflux (DVR) of the lower extremities and cardiac Doppler parameters. The relationship between Clinical Etiological Anatomical Pathophysiological (CEAP) clinical class and cardiac Doppler parameters showed on that: In comparison with normal control, all cardiac Doppler parameters of C2 clinical class patients were basically unchanged, but the cardiac Doppler parameters of the C3 or higher CEAP class patients changed. Hence, we found a potential CEAP grade cut-off value (C3) linked to statistical changes in cardiac Doppler parameters. Conclusion: Cardiac Doppler parameters in patients with primary varicose veins could indeed be different from those of normal people, especially for C3 class or higher CEAP clinical class patients. Therefore, for those patients, pre-operative echocardiography can be used to evaluate cardiac hemodynamic changes, but large-scale clinical promotion requires further large sample studies.

Case report: Adrenal myelolipoma resected by laparoscopic surgery.

Introduction: Adrenal myelolipomas are benign tumors composed mainly of lipomatous elements with myeloid cells. With the development of medical imaging technology, the detection rate has gradually increased. We report a case of adrenal myelolipoma successfully excised through the laparoscope and reviewed existing literature in recent ten years to summarize the feasibility of the laparoscopic approach for this tumor. Case presentation: Herein, we described a case of adrenal myelolipoma resected by laparoscope in a 63-year-old male patient. He did not have any other symptoms except the incidental finding of a left adrenal mass. An abdominal CT examination revealed a mixed-density lesion containing some amount of adipose tissue. In conjunction with the patient's willingness, we performed a laparoscopic operation to remove the lump. The definite diagnosis was confirmed as an adrenal myelolipoma according to the pathology. The patient recovered well postoperatively and without signs of recurrence at a 5-month follow-up. Conclusion: Adrenal myelolipoma is commonly benign, asymptomatic, and hormonal inactivity. A surgical strategy is suggested for high-complication-risk patients. The laparoscopic approach is safe and effective with an obvious advantage over open procedures.

Case report: The safety of laparoscopic surgery for the retroperitoneal bronchogenic cyst.

Introduction: Bronchogenic cyst is a congenital aberration of bronchopulmonary malformation with bronchial-type, pseudostratified cylindrical epithelium. They are usually discovered in the mediastinum and intrapulmonary but are rarely encountered in retroperitoneum. We report a case of the retroperitoneal bronchogenic cyst and perform a literature review to summarize the safety of laparoscopic resection for this rare disease. Case presentation: We report a 57-year-old woman who was admitted to our hospital with no clinical symptoms and was found by chance to have masses in the adrenal gland area during a routine physical examination. An abdominal CT examination revealed a cystic lesion was found in the left suprarenal region. Afterward, the patient underwent a laparoscopic exploration. Histopathological findings confirmed the diagnosis of a retroperitoneal bronchogenic cyst. The patient recovered uneventfully without signs of recurrence during a 1-year follow-up period. Conclusion: Bronchogenic cyst is rare in the retroperitoneal region. It should be considered as one of the differential diagnoses of a retroperitoneal neoplasm, especially in the left retroperitoneal region. Laparoscopic surgery is technically feasible and safe for the treatment of patients with a retroperitoneal bronchogenic cyst.

Uncommon Cause of Right Upper Quadrant Pain Treated by Laparoscopic Surgery: A Case Report.

Introduction: Right upper quadrant pain is a very common symptom of cholecystitis. Right upper quadrant pain caused by fish bone perforation of the stomach wall is rare. Case Presentation: We report a 42-year-old woman who was admitted to our hospital with "1-month history of dull progressive right upper quadrant pain radiating to the back." Computed tomography of the abdomen revealed a linear, high-density body between the stomach wall and the liver. On history, the patient stated she had eaten a bony fish a month prior but did not note any significant pain at the time. Laparoscopy revealed a fish bone 2 cm in length half on the surface of the caudate lobe of the liver, and no perforation of the gastrointestinal tract was found. The postoperative course was uncomplicated, and the patient was discharged home on day 3 after surgery. Conclusion: The case of right upper quadrant pain caused by the fish bone is very rare. Radiological examinations play a significant role in the diagnosis of fish bone ingestion. Laparoscopic surgery is technically feasible and safe for the treatment of patients with fish bone ingestion.

Robotic Versus Laparoscopic Pancreaticoduodenectomy: An Up-To-Date System Review and Meta-Analysis.

Background: Although minimally invasive pancreaticoduodenectomy has gained worldwide interest, there are limited comparative studies between two minimally invasive pancreaticoduodenectomy techniques. This meta-analysis aimed to compare the safety and efficacy of robotic and laparoscopic pancreaticoduodenectomy (LPD), especially the difference in the perioperative and short-term oncological outcomes. Methods: PubMed, China National Knowledge Infrastructure (CNKI), Wanfang Data, Web of Science, and EMBASE were searched based on a defined search strategy to identify eligible studies before July 2021. Data on operative times, blood loss, overall morbidity, major complications, vascular resection, blood transfusion, postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), conversion rate, reoperation, length of hospital stay (LOS), and lymph node dissection were subjected to meta-analysis. Results: Overall, the final analysis included 9 retrospective studies comprising 3,732 patients; 1,149 (30.79%) underwent robotic pancreaticoduodenectomy (RPD), and 2,583 (69.21%) underwent LPD. The present meta-analysis revealed nonsignificant differences in operative times, overall morbidity, major complications, blood transfusion, POPF, DGE, reoperation, and LOS. Alternatively, compared with LPD, RPD was associated with less blood loss (p = 0.002), less conversion rate (p < 0.00001), less vascular resection (p = 0.0006), and more retrieved lymph nodes (p = 0.01). Conclusion: RPD is at least equivalent to LPD with respect to the incidence of complication, incidence and severity of DGE, and reoperation and length of hospital stay. Compared with LPD, RPD seems to be associated with less blood loss, lower conversion rate, less vascular resection, and more retrieved lymph nodes. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD2021274057.

Hypoxia-pretreated mesenchymal stem cell-derived exosomes-loaded low-temperature extrusion 3D-printed implants for neural regeneration after traumatic brain injury in canines.

Regenerating brain defects after traumatic brain injury (TBI) still remains a significant difficulty, which has motivated interest in 3D printing to design superior replacements for brain implantation. Collagen has been applied to deliver cells or certain neurotrophic factors for neuroregeneration. However, its fast degradation rate and poor mechanical strength prevent it from being an excellent implant material after TBI. In the present study, we prepared 3D-printed collagen/silk fibroin/hypoxia-pretreated human umbilical cord mesenchymal stem cells (HUCMSCs)-derived exosomes scaffolds (3D-CS-HMExos), which possessed favorable physical properties suitable biocompatibility and biodegradability and were attractive candidates for TBI treatment. Furthermore, inspired by exosomal alterations resulting from cells in different external microenvironments, exosomes were engineered through hypoxia stimulation of mesenchymal stem cells and were proposed as an alternative therapy for promoting neuroregeneration after TBI. We designed hypoxia-preconditioned (Hypo) exosomes derived from HUCMSCs (Hypo-MExos) and proposed them as a selective therapy to promote neuroregeneration after TBI. For the current study, 3D-CS-HMExos were prepared for implantation into the injured brains of beagle dogs. The addition of hypoxia-induced exosomes further exhibited better biocompatibility and neuroregeneration ability. Our results revealed that 3D-CS-HMExos could significantly promote neuroregeneration and angiogenesis due to the doping of hypoxia-induced exosomes. In addition, the 3D-CS-HMExos further inhibited nerve cell apoptosis and proinflammatory factor (TNF-α and IL-6) expression and promoted the expression of an anti-inflammatory factor (IL-10), ultimately enhancing the motor functional recovery of TBI. We proposed that the 3D-CS-loaded encapsulated hypoxia-induced exosomes allowed an adaptable environment for neuroregeneration, inhibition of inflammatory factors and promotion of motor function recovery in TBI beagle dogs. These beneficial effects implied that 3D-CS-HMExos implants could serve as a favorable strategy for defect cavity repair after TBI.