BACKGROUND:A large number of studies have demonstrated that stem cell exosomes play an important role in the repair of bone defects,either directly as carriers for loading other small molecules or surface modifications,or by binding to biomaterials to promote the repair and regeneration of bone tissue.OBJECTIVE:To summarize the osteogenic mechanisms of stem cell exosomes from different sources and their research progress in bone defect repair.METHODS:Chinese search terms"stem cell,exosome,bone,biomaterial,carrier,bioceramic,polymer,metal,hydrogel,engineered exosome"were used to search CNKI.English search terms"stem cell,exosome,bone defect,biomaterial,carrier,bioceramic,ploymer,metal material,hydrogel,engineering exosome"were used to search PubMed database.According to the inclusion and exclusion criteria,77 relevant articles were finally included for summary.RESULTS AND CONCLUSION:Exosomes from stem cells of different origins can promote osteoblast proliferation and differentiation,promote angiogenesis,and regulate osteoclast activity and macrophage phenotype to promote bone formation and bone mineralization.In addition,many achievements of exosomes in the field of bone defect repair were described from two aspects:biomaterial-assisted exosomes and engineered exosomes.However,the current research on stem cell exosomes in bone tissue engineering is still insufficient,and most of these studies are limited to small animal models,while the treatment of bone defects in large animals,including humans,will be more complex,which will also become a major challenge for the treatment of bone defects.This will also be a great challenge in the dissemination of exosome therapy.

BACKGROUND:A large number of studies have demonstrated that stem cell exosomes play an important role in the repair of bone defects,either directly as carriers for loading other small molecules or surface modifications,or by binding to biomaterials to promote the repair and regeneration of bone tissue.OBJECTIVE:To summarize the osteogenic mechanisms of stem cell exosomes from different sources and their research progress in bone defect repair.METHODS:Chinese search terms"stem cell,exosome,bone,biomaterial,carrier,bioceramic,polymer,metal,hydrogel,engineered exosome"were used to search CNKI.English search terms"stem cell,exosome,bone defect,biomaterial,carrier,bioceramic,ploymer,metal material,hydrogel,engineering exosome"were used to search PubMed database.According to the inclusion and exclusion criteria,77 relevant articles were finally included for summary.RESULTS AND CONCLUSION:Exosomes from stem cells of different origins can promote osteoblast proliferation and differentiation,promote angiogenesis,and regulate osteoclast activity and macrophage phenotype to promote bone formation and bone mineralization.In addition,many achievements of exosomes in the field of bone defect repair were described from two aspects:biomaterial-assisted exosomes and engineered exosomes.However,the current research on stem cell exosomes in bone tissue engineering is still insufficient,and most of these studies are limited to small animal models,while the treatment of bone defects in large animals,including humans,will be more complex,which will also become a major challenge for the treatment of bone defects.This will also be a great challenge in the dissemination of exosome therapy.

Objective To identify the indicators associated with poor prognosis by retrospectively analyzing the clinical data of 129 patients with lung adenocarcinoma (LUAD) complicated by brain metastases (BMs). Methods We retrospectively assessed the clinical data of 129 LUAD patients with BMs who met the inclusion criteria. Follow-up was conducted through electronic medical record review and telephone consultations. Univariate survival analysis was performed using the Kaplan-Meier method with corresponding survival curves. Statistically significant variables identified in the univariate analysis were subsequently incorporated into a multivariate Cox proportional hazards regression model to further identify independent adverse prognostic factors affecting the survival of LUAD patients with BMs. Results The following factors were significantly associated with patient survival prognosis (P<0.05): pathological morphology, KPS score, number of BMs, presence of genetic variations, quantity of genetic variations, type of genetic variations, EGFR mutation status, Cyfra-211, and neutrophil-to-lymphocyte ratio (NLR) at initial diagnosis. Multivariate Cox regression analysis revealed that pathological morphology, KPS score, number of BMs, NLR at initial diagnosis, and presence of genetic variations served as independent prognostic factors for LUAD patients with BMs (P<0.05). Further analysis of the survival conditions of different treatment subgroups revealed that combined therapy could significantly increase the median survival period of patients, and the difference was statistically significant (P=0.034). Conclusion Solid and complex glandular structures, KPS score <80, ≥3 BMs, elevated NLR levels at initial diagnosis, and the presence of genetic alterations are identified as independent poor prognostic factors for LUAD patients with BMs. Combination therapy can significantly prolong the survival of patients.

BackgroundModified electroconvulsive therapy （MECT） is a common front-line strategy widely used in psychiatric practice， and the optimal first stimulus dosage in MECT is usually estimated clinically based on the factors influencing the patient's initial seizure threshold （IST）. However， previous studies on the influencing factors of IST have mostly suffered from limitations such as small sample sizes and single-dimensional research perspectives. ObjectiveTo explore the factors influencing IST in MECT for patients with mental disorders， so as to provide references for stimulus dosing strategies in MECT for the patients. MethodsA retrospective study was used to include 1 446 inpatients fulfilling the diagnostic criteria for any specific mental disorder listed in the ICD-10 and receiving MECT at Shandong Daizhuang Hospital from January 1， 2021 to August 1， 2023. Their general and clinical data were collected， including IST， psychiatric diagnostic categories， gender， ethnicity， age， body weight， body mass index （BMI）， course of disease， family history of psychiatric disorders， first episode status， use of antiepileptic drugs the day before treatment， use of benzodiazepines the day before treatment， and previous MECT treatment history. Pearson correlation analysis was utilized to test the correlation of IST with age， height， body weight， BMI， and course of disease， and stepwise multivariate linear regression analysis was performed to identify the factors affecting IST. ResultsIST yielded statistical difference among patients in terms of gender， first episode status， use of antiepileptic drugs the day before treatment， and use of benzodiazepines the day before treatment （t=2.256， -3.059， -2.136， -3.006， P<0.05 or 0.01）. IST in patients of different ages and psychiatric diagnostic categories also demonstrated statistical difference （F=913.120， 6.212， P<0.01）. Within young population， IST varied significantly based on the psychiatric diagnostic categories （F=2.986， P<0.05）. Correlation analysis indicated that IST was positively correlated with age， body weight， BMI and course of disease （r=0.886， 0.055， 0.184， 0.456， P<0.05 or 0.01）， and negatively correlated with height （r=-0.183， P<0.01）. Stepwise multivariate linear regression analysis revealed that age， gender， and body weight were influencing factors of IST （β=0.888， -0.049， -0.035， P<0.01）. ConclusionsAge， gender and body weight may be factors influencing IST in MECT for patients with mental disorders. ［Funded by Key R&D Plan Projects of Jining City in 2024 (number, 2024YXNS202）］

Persistent left superior vena cava is a rare venous variant that is often combined with cardiovascular malformations. In thoracic surgery, especially mediastinal tumor resection, neglect of this variant may make the surgery difficult and risky, and careful preoperative imaging interpretation and adequate preoperative evaluation play an important role in the perioperative safety of the patient. In this paper, we reported a case of a 17-year-old female patient with a persistent left superior vena cava combined with mediastinal tumors. She was successfully discharged 5 days after thoracoscopic surgery, and after 3 years of postoperative follow-up, no tumor recurrence was observed.

ObjectiveTo investigate the value of Fried Frailty Phenotype （FFP）， liver frailty index （LFI）， and Short Physical Performance Battery （SPPB） in predicting 2-year all-cause mortality and decompensation events in patients with liver cirrhosis. MethodsA total of 277 patients with liver cirrhosis who were hospitalized in Beijing Friendship Hospital， Capital Medical University， from December 2020 to December 2021 were enrolled， and FFP， LFI， and SPPB were used to assess the state of frailty. Based on the scores of each tool， these patients were divided into frail and non-frail groups. These three tools were compared in terms of consistency and independent predictive performance. The primary endpoints were 2-year all-cause mortality rate and composite endpoints （death+decompensation events）， and the Cox regression analysis， the receiver operating characteristic （ROC） curve， net reclassification index （NRI）， and integrated discrimination improvement （IDI） index were used to analyze the predictive value of the three tools. Normally distributed continuous data were compared between two groups using the independent samples t-test， while non-normally distributed continuous data were compared using the Mann-Whitney U test. Categorical data were compared between groups using the chi-square test or Fisher’s exact test. The agreement among different frailty tools was evaluated using Cohen’s Kappa statistic. The Kaplan-Meier survival curve was plotted， and a survival analysis was performed using the log-rank test. ResultsThe prevalence rate of frailty assessed by FFP， LFI， and SPPB was 37.2%， 22.4%， and 20.2%， respectively， with a moderate consistency between FFP and LFI/SPPB （κ=0.57， 95% confidence interval ［CI］： 0.47 — 0.67； κ=0.51， 95%CI： 0.41 — 0.62） and a relatively high consistency between LFI and SPPB （κ=0.87， 95%CI： 0.80 — 0.94）. Compared with the non-frailty group， the frailty group had significantly higher all-cause mortality rate and incidence rate of composite endpoints （P0.001）. After multivariate adjustment， FFP， LFI， and SPPB had a hazard ratio of 2.42（95%CI： 1.51 — 5.11）， 2.21（95%CI： 1.11 — 4.42）， and 2.21（95%CI： 1.14 — 4.30）， respectively， in predicting all-cause mortality， as well as a hazard ratio of 2.51（95%CI： 1.61 — 3.91）， 2.40（95%CI： 1.51 — 3.80）， and 2.20（95%CI： 1.39 — 3.47）， respectively， in predicting composite endpoints. Compared with Child-Pugh score， FFP had a significantly greater area under the ROC curve （AUC） in predicting all-cause mortality （0.79 vs 0.69， P=0.032） and composite endpoints （0.75 vs 0.68， P=0.044）. Frailty assessment tools combined with Child-Pugh score significantly improved the performance in predicting all-cause mortality and composite endpoints， with an AUC of 0.81 — 0.82 and 0.77 — 0.78， respectively （P0.05）. NRI and IDI analyses further confirmed the improvement of the combined model in classification （all P0.001）. ConclusionFFP， LFI， and SPPB can independently predict adverse outcomes in patients with liver cirrhosis， among which FFP has the best predictive performance， and the combination of frailty assessment tools with Child-Pugh score can significantly enhance the accuracy of prognostic evaluation.

OBJECTIVES: To investigate the effect of in vitro cultured calculus bovis (ICCB) on cerebral ischemia/reperfusion injury (CIRI) and its mechanism. METHODS: A CIRI rat model and a cell model were induced by middle cerebral artery occlusion (MCAO) in Sprague Dawley rats and oxygen glucose deprivation/reperfusion (OGD/R) in BV2 cells, respectively. The CIRI rat model was evaluated using the modified neurological severity score (mNSS), brain water content, and cerebral infarction volume after 1.5 h of ischemia followed by 72 h of reperfusion. Histopathological changes in the cortex and hippocampal CA1 region were observed with hematoxylin and eosin staining. Microglial polarization and NOD-like receptor thermal protein domain associated protein (NLRP) 3 inflammasome expression in the cortex were examined by immunofluorescence. BV2 cell viability was measured via MTT assay after treatment with ICCB and Nigericin. The expressions of NLRP3, ASC, caspase-1 proteins and inflammatory cytokines were detected with Western blotting in OGD/R treated BV2 cells (0.5 h OGD+24 h reperfusion) and in cells pretreated with Nigericin for 24 h. RESULTS: ICCB treatment significantly improved neurological function, reduced cerebral infarct volume and brain water content, and mitigated pathological damage in the cortical and hippocampal CA1 regions of rats subjected to CIRI (all P<0.05). ICCB promoted the transition of cortical microglia from M1 to M2 phenotypes and suppressed NLRP3 activation in microglial cells (all P<0.01). ICCB significantly down-regulated the expression of NLRP3, ASC, and caspase-1 proteins, and reduced the secretion of IL-18 and IL-1β in BV2 cells of OGD/R model (all P<0.01). In addition, Nigericin significantly reversed the salvage effect of ICCB on model cells (both P<0.01) and the modulation of inflammatory cytokines (P<0.05). CONCLUSIONS ICCB exerts a protective effect against CIRI by mitigating neuroinflammation, through the reduction of M1 microglial polarization, promotion of M2 conversion, and suppression of the NLRP3/ASC/caspase-1 signaling pathway.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/prevention & control* ; Microglia/metabolism* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein ; Brain Ischemia/metabolism* ; Male

OBJECTIVE: To investigate the effect of intraoperative blood salvage autotransfusion on local recurrence and long-term metastasis of patients after carotid body tumor resection. METHODS: We retrospectively reviewed a consecutive series of 61 patients undergoing elective carotid body tumor resection from August 2009 to December 2020. Among them, 14 received intraoperative blood salvage autotransfusion (autotrasfusion group) and 47 did not (non-autotransfusion). Data of general information, surgical status and postoperative follow-up results were collected. RESULTS: The proportion of Shamblin Ⅲ in the autotransfusion group was 85.7%, which was significantly higher than 31.9% in the non-autotransfusion group (P=0.003). The average operation time of the 14 patients in the autotransfusion group was (264±84) min, intraoperative blood loss was 1 200 (700, 2 700) mL, and autologous blood transfusion was 500 (250, 700) mL. Of these, 8 patients (57%) required concomitant allogeneic blood with 400 (260, 400) mL of allogeneic blood. The average operation time of the 47 patients in the non-autotransfusion group was (153±75) min, and the intraoperative blood loss was 300 (100, 400) mL. Of these, 6 (13%) required allogeneic blood transfusion, and 520 (400, 520) mL of allogeneic blood was used. Compared with the non-autotransfusion group, the average operation time in the autologous blood transfusion group was significantly longer (P < 0.001), and the intraoperative blood transfusion volume was larger (P=0.007). Of the 14 patients undergoing autotransfusion, 8 (57%) needed allogeneic blood at the same time; while in the 47 non-autologous transfusion patients, 6 (13%) needed allogeneic blood transfusion. The proportion of autotransfusion group using allogeneic blood at the same time was even higher (P=0.002). The incidence of nerve injury within 30 days after surgery was 29.5%, and there was no significant difference between the two groups. No early deaths occurred. The average follow-up was (76±37) months. One case of local recurrence occurred in the non-autotransfusion group. There was no distant metastasis. There were no tumor-related deaths. The estimated 5-year and 10-year overall survival rates were 96.4% and 83.8%, respectively. There was no significant difference in overall survival between the two groups (P=0.506). CONCLUSION The use of intraoperative blood salvage autotransfusion increased no risk of local recurrence and distant metastasis in patients with carotid body tumor, which is safe and effective in carotid body tumor resection.
Humans ; Blood Transfusion, Autologous/methods* ; Operative Blood Salvage/methods* ; Retrospective Studies ; Male ; Female ; Carotid Body Tumor/pathology* ; Middle Aged ; Prognosis ; Neoplasm Recurrence, Local ; Blood Loss, Surgical ; Aged ; Adult ; Operative Time

Objective:To investigate the sleep characteristics and clinical features of patients with vestibular migraine（VM）, and to explore the influencing factors of sleep disorder in VM patients. Methods:A cross-sectional study method was adopted to collect VM patients from Otolaryngology department and neurology department of our hospital from June 2022 to June 2024（divided into sleep disorder group and non-sleep disorder group according to whether there is sleep disorder） as the experimental group, and recruit non-VM volunteers with clinical characteristics matching with the experimental group during the same period as the control group. The clinical data of the subjects were collected, and the sleep quality of the subjects was assessed using the Pittsburgh Sleep Quality Index（PSQI）. The influencing factors of sleep disorders in VM patients were analyzed by multivariate Logistic regression, and the correlation between sleep disorders and clinical features such as headache, vertigo and hearing in VM patients was analyzed by Spearman correlation coefficient. Results:A total of 530 individuals with VM were analyzed, including 332 with sleep disturbances（62.64%）, 198 without sleep issues（37.36%）, and 50 in the control group. The overall PSQI score and all its components were significantly higher in the VM group compared with the control group（P<0.05）. A positive correlation was observed between PSQI and VAS, DHI-T, DHI-E, DHI-F and DHI-P（r=0.797, P<0.05; r=0.834, P<0.05; r=0.794, P<0.05; r=0.771, P<0.05; r=0.877, P<0.05）, PSQI had no correlation with pure tone hearing（r=0.324, P=0.167）. Multivariate logistic regression analysis showed that female, age ≥60 years, living alone, duration of disease ≥3 months, motion sickness history, and HADS-A were independent influencing factors for comorbidification of sleep disorder in VM patients（P<0.05）. Conclusion:The prevalence of sleep disorders in patients with vestibular migraine（VM） was significantly higher compared to the control group. Moreover, the severity of sleep disorders was positively correlated with the intensity of headache and vertigo in VM patients. It is recommended that female VM patients aged 60 years or older, living alone, with a disease duration of three months or longer, a history of motion sickness, and anxiety symptoms undergo sleep assessments to determine the presence of sleep disorders. This approach provides a theoretical foundation for precise treatment and prevention strategies for VM.
Humans ; Migraine Disorders/complications* ; Sleep Wake Disorders/complications* ; Cross-Sectional Studies ; Vertigo ; Female ; Male ; Vestibular Diseases/complications* ; Sleep Quality ; Adult ; Middle Aged ; Logistic Models