BACKGROUND:Previous studies have demonstrated that the cannabinoid type Ⅰ receptor can enhance the proliferation and neural differentiation of neural stem cells and mesenchymal stem cells.Moreover,cannabinoid type Ⅰ also governs the proliferation and mineralization capacity of human apical papilla stem cells.However,there are relatively few investigations concerning the impact of cannabinoid type Ⅰ overexpression on the neural differentiation of human apical papilla stem cells.OBJECTIVE:To investigate the effect of cannabinoid type Ⅰ on neural differentiation of human apical papilla stem cells in vitro.METHODS:Healthy third molars with immature root tips that need to be removed for orthodontic treatment were collected,and human apical papilla stem cells were isolated and cultured by tissue block method combined with enzyme digestion method.Cannabinoid type Ⅰ gene was introduced into human apical papilla stem cells by lentivirus-mediated transfection technique.A blank control group,a negative control group,and cannabinoid type Ⅰ overexpression group were set up.The transfection effect of overexpression of cannabinoid type Ⅰ lentivirus on human apical papilla stem cells was verified by Western Blot.The control group,negative control group,cannabinoid type Ⅰ overexpression group and cannabinoid type Ⅰ overexpression+AM251(cannabinoid type Ⅰ receptor antagonist)group were set up.Cell proliferation was detected by CCK-8 assay at 1,5,and 10 days after neural induction.On day 10 of neural induction,the expression levels of TH,NeuroD-1,and NCAM1 genes were detected by qRT-PCR,and the protein expression levels of Nestin and TUBB3 were detected by immunofluorescence.RESULTS AND CONCLUSION:(1)Compared with the blank control group and the negative control group,the expression of cannabinoid receptor Ⅰ protein in the cannabinoid receptor Ⅰ overexpression group was significantly increased,and the difference was significant(P＜0.05).(2)Compared with the blank control group and the negative control group,the proliferation ability of human apical papilla stem cells in the cannabinoid type Ⅰ overexpression group was the strongest at 5 and 10 days after neural induction(P＜0.05).(3)Compared with the blank control group and the negative control group,the mRNA expression of NeuroD-1,NCAM1,and TH in the stem cells of the human apical papilla in the cannabinoid type Ⅰ overexpression group was significantly increased,and the fluorescence intensity of Nestin and TUBB3 was significantly enhanced(P＜0.05).(4)Compared with the cannabinoid type Ⅰ overexpression group,the proliferation ability,mRNA expression level of NeuroD-1,NCAM1,and TH,as well as the fluorescence intensity of Nestin and TUBB3,were significantly decreased in the cannabinoid type Ⅰ overexpression+AM251 group(P＜0.05).These findings conclude that overexpression of cannabinoid type Ⅰ promoted the proliferation and neural differentiation of human apical dentin papilla stem cells.

BACKGROUND:Previous studies have demonstrated that the cannabinoid type Ⅰ receptor can enhance the proliferation and neural differentiation of neural stem cells and mesenchymal stem cells.Moreover,cannabinoid type Ⅰ also governs the proliferation and mineralization capacity of human apical papilla stem cells.However,there are relatively few investigations concerning the impact of cannabinoid type Ⅰ overexpression on the neural differentiation of human apical papilla stem cells.OBJECTIVE:To investigate the effect of cannabinoid type Ⅰ on neural differentiation of human apical papilla stem cells in vitro.METHODS:Healthy third molars with immature root tips that need to be removed for orthodontic treatment were collected,and human apical papilla stem cells were isolated and cultured by tissue block method combined with enzyme digestion method.Cannabinoid type Ⅰ gene was introduced into human apical papilla stem cells by lentivirus-mediated transfection technique.A blank control group,a negative control group,and cannabinoid type Ⅰ overexpression group were set up.The transfection effect of overexpression of cannabinoid type Ⅰ lentivirus on human apical papilla stem cells was verified by Western Blot.The control group,negative control group,cannabinoid type Ⅰ overexpression group and cannabinoid type Ⅰ overexpression+AM251(cannabinoid type Ⅰ receptor antagonist)group were set up.Cell proliferation was detected by CCK-8 assay at 1,5,and 10 days after neural induction.On day 10 of neural induction,the expression levels of TH,NeuroD-1,and NCAM1 genes were detected by qRT-PCR,and the protein expression levels of Nestin and TUBB3 were detected by immunofluorescence.RESULTS AND CONCLUSION:(1)Compared with the blank control group and the negative control group,the expression of cannabinoid receptor Ⅰ protein in the cannabinoid receptor Ⅰ overexpression group was significantly increased,and the difference was significant(P＜0.05).(2)Compared with the blank control group and the negative control group,the proliferation ability of human apical papilla stem cells in the cannabinoid type Ⅰ overexpression group was the strongest at 5 and 10 days after neural induction(P＜0.05).(3)Compared with the blank control group and the negative control group,the mRNA expression of NeuroD-1,NCAM1,and TH in the stem cells of the human apical papilla in the cannabinoid type Ⅰ overexpression group was significantly increased,and the fluorescence intensity of Nestin and TUBB3 was significantly enhanced(P＜0.05).(4)Compared with the cannabinoid type Ⅰ overexpression group,the proliferation ability,mRNA expression level of NeuroD-1,NCAM1,and TH,as well as the fluorescence intensity of Nestin and TUBB3,were significantly decreased in the cannabinoid type Ⅰ overexpression+AM251 group(P＜0.05).These findings conclude that overexpression of cannabinoid type Ⅰ promoted the proliferation and neural differentiation of human apical dentin papilla stem cells.

The investigator-initiated trials （IIT）， as a widely existing form of clinical research both domestically and internationally， have attracted the attention of governments around the world due to the potential legal risks and issues they may cause， and the trend of legal supervision has gradually strengthened. The legal regulation of IIT in China is still in its early stages， with numerous legal issues that need to be clarified and sorted out. Based on the domestic and international legal reviews of IIT， this paper systematically sorted out the current situation of legal supervision of IIT in China and examined the existing issues， including weak legislative rules， incomplete regulatory systems， imperfect protection rules for research participants and informed consent systems， inadequate regulation of conflicts of interest management， and lax legal supervision of ethical review. Furthermore， this paper proposed suggestions for legal regulation of IIT from three perspectives， including strengthening legislation and emphasizing regulation， improving the mechanism for protecting research participants’ rights and interests， and balancing the legalization of IIT and the scientific development of clinical research， with a view to providing references for legal regulatory paths of IIT in China.

Objective To explore the efficiency of operating room(OR)and its influencing factors from a phenomeno-logical perspective,proposing corresponding improvement strategies.Methods A phenomenological method was adopted,invol-ving in-depth interviews with 13 surgical team members from a tertiary Traditional Chinese Medicine(TCM)orthopedic hospital in Henan Province,to collect and analyze their multifaceted understanding of OR efficiency.Results The study demonstrated eight interpretative ways of efficiency among team members.The overall framework was largely organization-oriented,with addi-tional human-centered considerations regarding the factors influencing efficiency.Conclusion A unified understanding is crucial for improving both efficiency and quality.This study suggests strategies to optimize OR processes through lean management and human-centered team development to enhance operating room efficiency.Additionally,it highlights the need for future research to incorporate more patient views.

Objective To explore the efficiency of operating room(OR)and its influencing factors from a phenomeno-logical perspective,proposing corresponding improvement strategies.Methods A phenomenological method was adopted,invol-ving in-depth interviews with 13 surgical team members from a tertiary Traditional Chinese Medicine(TCM)orthopedic hospital in Henan Province,to collect and analyze their multifaceted understanding of OR efficiency.Results The study demonstrated eight interpretative ways of efficiency among team members.The overall framework was largely organization-oriented,with addi-tional human-centered considerations regarding the factors influencing efficiency.Conclusion A unified understanding is crucial for improving both efficiency and quality.This study suggests strategies to optimize OR processes through lean management and human-centered team development to enhance operating room efficiency.Additionally,it highlights the need for future research to incorporate more patient views.

Objective:To investigate the control status of out-of-hospital blood glucose and blood lipids in patients with acute myocardial infarction (AMI) complicated with diabetes mellitus and its correlation with prognosis.Methods:The clinical data of 406 patients with AMI complicated with diabetes mellitus from January 2017 to December 2022 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The demographic and out-of-hospital clinical information of patients were recorded, and the control level of out-of-hospital risk factors and the occurrence of major adverse cardiovascular event (MACCE) were also recorded. The patients were grouped according to the levels of glycosylated hemoglobin (HbA 1c) and low-density lipoprotein cholesterol (LDL-C). HbA 1c<6.0% was the low HbA 1c group, HbA 1c 6.0% to 7.0% was the medium HbA 1c group, and HbA 1c>7.0% was the high HbA 1c group; LDL-C<1.4 mmol/L was low LDL-C group, LDL-C 1.4 to 1.8 mmol/L was medium LDL-C group, and LDL-C>1.8 mmol/L was high LDL-C group. Multivariate Cox regression analysis was used to analyze the independent risk factors for out-of-hospital MACCE in patients with AMI complicated with diabetes mellitus. Results:The HbA 1c data of 249 patients were recorded in detail, and only 51.0% (127/249) of patients with HbA 1c≤7%. There were statistical differences in the history of cerebral infarction, out-of-hospital fasting blood glucose, out-of-hospital total cholesterol (TC) and out-of-hospital LDL-C among the low HbA 1c group (24 cases), medium HbA 1c group (103 cases) and high HbA 1c group (122 cases) ( P<0.05). The incidences of out-of-hospital MACCE in low HbA 1c group, medium HbA 1c group and high HbA 1c group were 20.8%(5/24), 12.6%(13/103) and 32.0%(39/122), respectively. The incidence of out-of-hospital MACCE in high HbA 1c group was significantly higher than that in medium HbA 1c group, and there was statistical difference ( P<0.05); there was no statistical difference between low HbA 1c group and high HbA 1c group ( P>0.05). Among the 406 patients, 53.4%(217/406) had LDL-C≤1.8 mmol/L, and only 20.0%(81/406) had LDL-C<1.4 mmol/L. There were statistical differences in hyperlipidemia, out-of-hospital HbA 1c, out-of-hospital fasting blood glucose, out-of-hospital alanine aminotransferase (ALT), out-of-hospital TC and out-of-hospital triglyceride (TG) among low LDL-C group (81 cases), medium LDL-C group (136 cases) and high LDL-C group (189 cases) ( P<0.05). The incidences of MACCE in low LDL-C group, medium LDL-C group and high LDL-C group were 18.5% (15/81), 25.7% (35/136) and 36.5% (69/189), respectively. The incidence of MACCE in high LDL-C group was significantly higher than that in low LDL-C group, and there was statistical difference ( P<0.05); there was no statistical difference between low LDL-C group and medium LDL-C group ( P>0.05). In the different HbA 1c groups, multivariate Cox regression analysis result showed that HbA 1c>7% and high out-of-hospital fasting blood glucose were independent risk factors for out-of-hospital MACCE in patients with AMI complicated with diabetes mellitus ( OR = 2.575 and 1.064, 95% CI 1.345 to 4.927 and 1.005 to 1.128, P<0.01 and <0.05). In different LDL-C groups, multivariate Cox regression analysis result showed that high out-of-hospital HbA 1c was an independent risk factor for out-of-hospital MACCE in patients with AMI complicated with diabetes mellitus ( OR = 1.303, 95% CI 1.144 to 1.485, P<0.01). Conclusions:The control rates of out-of-hospital blood glucose and blood lipids are low in patients with AMI complicated with diabetes mellitus, and HbA 1c level can independently predict the risk of out-of-hospital MACCE in patients with AMI complicated with diabetes mellitus.

Objective To observe the efficacy and safety of mechanical thrombectomy in acute ischemic stroke patients after vertebral-basilar artery stent implantation.Methods From May 2018 to October 2022,patients with acute vertebral basilar artery occlusion who underwent mechanical thrombectomy were retrospectively analyzed.The patients were divided into two groups:stent occlusion group and acute atherosclerotic stenosis occlusion(ICAS)group.The baseline characteristics of the two groups were balanced by propensity score matching method.The successful recanalization rate,90-day good outcome rate,90-day mortality rate,and symptomatic intracranial hemorrhage rate were compared.Results We enrolled 107 patients,with 14 cases in stent occlusion group and 93 cases in ICAS group.We analyzed 14 pairs by propensity score matching,including 14 cases in stent occlusion group and 27 cases in ICAS group.The successful recanalization rate and 90-day good outcome rate was lower in stent occlusion group than in ICAS group[(78.6％(11/14)vs.100％(27/27),P=0.062,28.6％(4/14)vs.44.4％(12/27),X2=0.976,P=0.323],but there was no statistical difference.The 90-day mortality rate in the stent occlusion group was significantly higher than that in the ICAS group[57.1％(8/14)vs.25.9％(7/27),x2=3.873,P=0.049].The incidence of symptomatic intracranial hemorrhage was higher in the stent occlusion group than in the ICAS group,with no statistical difference[35.7％(5/14)vs.14.8％(4/27),x2=1.289,P=0.256].Conclusion The successful recanalization rate,90-day good outcome rate,and incidence of symptomatic intracranial hemorrhage in stent occlusion group did not significantly differ from those in ICAS group,but the 90-day mortality rate was significantly higher in the former group.

Objective:To investigate the molecular markers involved in death related to acute myocardial infarction (AMI) and provide new targets for early intervention.Methods:Consecutive patients who hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from January 2017 to December 2021 and diagnosed with AMI were enrolled. The clinical factors and markers associated with in-hospital death after AMI were analyzed. In addition, patients diagnosed with AMI hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from September 2022 to April 2023 were enrolled. We prospectively analyzed the plasma protein of death related to AMI via Olink Precision Proteomics based on proximity extension assay (PEA) technology.Results:In the retrospective study, 2 325 patients with AMI were analyzed, including 75 patients in the in-hospital death group and 2 250 subjects in the survival group. The overall mortality rate during hospitalization was 3.23% (75/2325). The patients in the death group were older: 72 (64, 80) years vs. 63 (55, 71) years. And Interleukin-6 (IL-6), hypersensitive C-reactive protein (Hs-CRP), leukocyte counts and neutrophil counts were markedly higher in the death group than those in the survival group: 69.0 (26.7, 136.6) ng/L vs. 18.2 (9.4, 36.5) ng/L, 45.7 (28.7, 50.5) mg/L vs. 5.5 (2.0, 17.2) mg/L, 12.0 (9.8, 14.1) ×10 9/L vs. 8.9 (7.2, 11.2) × 10 9/L, 9.8 (7.8, 12.1) ×10 9/L vs. 6.5(4.7, 8.8) ×10 9/L ( P<0.01). In this prospective study, 86 patients with AMI were analyzed. 61 proteins including Insulin-like growth factor-binding protein 1, 2 (IGFBP-1, IGFBP-2), Chitotriosidase-1 (CHIT1), Complement component C1q receptor (CD93) were independently associated with in-hospital death related to AMI ( P<0.05). The differential proteins were mainly enriched in inflammatory response, cell adhesion, cytokine signaling pathway and apoptosis. Moreover, 22 proteins including Urokinase plasminogen activator surface receptor (U-PAR), Trefoil factor 3 (TFF3), Perlecan (PLC), Growth differentiation factor 15 (GDF-15), Junctional adhesion molecule A (JAM-A) were plotted according to a logistic regression model, and the area under the curve (AUC) was more than 0.9, showing the high accuracy in predicting in-hospital death after AMI. Conclusions:Molecular markers of the inflammatory response, cell adhesion, cell growth and apoptosis might be involved in death related to AMI, which provides new targets for early intervention.

Objective To observe the efficacy and safety of mechanical thrombectomy in acute ischemic stroke patients after vertebral-basilar artery stent implantation.Methods From May 2018 to October 2022,patients with acute vertebral basilar artery occlusion who underwent mechanical thrombectomy were retrospectively analyzed.The patients were divided into two groups:stent occlusion group and acute atherosclerotic stenosis occlusion(ICAS)group.The baseline characteristics of the two groups were balanced by propensity score matching method.The successful recanalization rate,90-day good outcome rate,90-day mortality rate,and symptomatic intracranial hemorrhage rate were compared.Results We enrolled 107 patients,with 14 cases in stent occlusion group and 93 cases in ICAS group.We analyzed 14 pairs by propensity score matching,including 14 cases in stent occlusion group and 27 cases in ICAS group.The successful recanalization rate and 90-day good outcome rate was lower in stent occlusion group than in ICAS group[(78.6％(11/14)vs.100％(27/27),P=0.062,28.6％(4/14)vs.44.4％(12/27),X2=0.976,P=0.323],but there was no statistical difference.The 90-day mortality rate in the stent occlusion group was significantly higher than that in the ICAS group[57.1％(8/14)vs.25.9％(7/27),x2=3.873,P=0.049].The incidence of symptomatic intracranial hemorrhage was higher in the stent occlusion group than in the ICAS group,with no statistical difference[35.7％(5/14)vs.14.8％(4/27),x2=1.289,P=0.256].Conclusion The successful recanalization rate,90-day good outcome rate,and incidence of symptomatic intracranial hemorrhage in stent occlusion group did not significantly differ from those in ICAS group,but the 90-day mortality rate was significantly higher in the former group.

Objective:To investigate the molecular markers involved in death related to acute myocardial infarction (AMI) and provide new targets for early intervention.Methods:Consecutive patients who hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from January 2017 to December 2021 and diagnosed with AMI were enrolled. The clinical factors and markers associated with in-hospital death after AMI were analyzed. In addition, patients diagnosed with AMI hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from September 2022 to April 2023 were enrolled. We prospectively analyzed the plasma protein of death related to AMI via Olink Precision Proteomics based on proximity extension assay (PEA) technology.Results:In the retrospective study, 2 325 patients with AMI were analyzed, including 75 patients in the in-hospital death group and 2 250 subjects in the survival group. The overall mortality rate during hospitalization was 3.23% (75/2325). The patients in the death group were older: 72 (64, 80) years vs. 63 (55, 71) years. And Interleukin-6 (IL-6), hypersensitive C-reactive protein (Hs-CRP), leukocyte counts and neutrophil counts were markedly higher in the death group than those in the survival group: 69.0 (26.7, 136.6) ng/L vs. 18.2 (9.4, 36.5) ng/L, 45.7 (28.7, 50.5) mg/L vs. 5.5 (2.0, 17.2) mg/L, 12.0 (9.8, 14.1) ×10 9/L vs. 8.9 (7.2, 11.2) × 10 9/L, 9.8 (7.8, 12.1) ×10 9/L vs. 6.5(4.7, 8.8) ×10 9/L ( P<0.01). In this prospective study, 86 patients with AMI were analyzed. 61 proteins including Insulin-like growth factor-binding protein 1, 2 (IGFBP-1, IGFBP-2), Chitotriosidase-1 (CHIT1), Complement component C1q receptor (CD93) were independently associated with in-hospital death related to AMI ( P<0.05). The differential proteins were mainly enriched in inflammatory response, cell adhesion, cytokine signaling pathway and apoptosis. Moreover, 22 proteins including Urokinase plasminogen activator surface receptor (U-PAR), Trefoil factor 3 (TFF3), Perlecan (PLC), Growth differentiation factor 15 (GDF-15), Junctional adhesion molecule A (JAM-A) were plotted according to a logistic regression model, and the area under the curve (AUC) was more than 0.9, showing the high accuracy in predicting in-hospital death after AMI. Conclusions:Molecular markers of the inflammatory response, cell adhesion, cell growth and apoptosis might be involved in death related to AMI, which provides new targets for early intervention.