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.

Objective:To compare the efficacy of low-dose febuxostat and low-dose benzbromarone in lowering serum uric acid and their impact on liver function in male patients with renal underexcretion gout.Methods:This prospective cohort study enrolled 303 patients with renal underexcretion gout and normal baseline liver function. Participants were assigned to either the low-dose febuxostat group(20 mg qd) or the low-dose benzbromarone group(25 mg qd). A linear mixed-effects model was used to compare the uric acid target achievement rate(<360 μmol/L) and changes in liver enzyme levels between the two groups.Results:At week 4, the proportion of patients achieving the serum uric acid target(<360 μmol/L) was significantly higher in the benzbromarone group than that in the febuxostat group(64.2% vs 42.3%, P<0.001), with a trend toward greater efficacy at weeks 8 and 12. The incidence of alanine aminotransferase(ALT) or aspartate aminotransferase(AST) elevation above the upper limit was significantly higher in the febuxostat group compared to the benzbromarone group(35.2% vs 13.85%, P<0.001). After adjusting for baseline liver enzyme levels in the mixed-effects model, mean ALT and AST levels remained significantly higher in the febuxostat group than those in the benzbromarone group at weeks 4, 8, and 12( P<0.05). In the febuxostat group, ALT and AST levels significantly increased over time during weeks 0-4 and 4-8 ( P<0.001), peaking at week 8 followed by a decreasing trend. By week 12, the levels were not significantly different from baseline ( P>0.05). Whereas there was no significant difference at each follow-up time point in the benzbromarone group( P>0.05). Conclusions:In male patients with renal underexcretion gout, low-dose benzbromarone demonstrated superior urate-lowering efficacy and better hepatic safety compared to low-dose febuxostat.

Objective:To investigate the correlation of neutrophil-to-albumin ratio (NAR) and glucose-to-lymphocyte ratio (GLR) with in-hospital death in patients with acute myocardial infarction (AMI).Methods:The clinical data of 2 657 patients with AMI from January 2017 to December 2022 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. Using receiver operating characteristic (ROC) curve to determine the optimal cutoff values of GLR and NAR (6.02 and 0.25) for predicting in-hospital mortality in patients with AMI, the patients were divided into high GLR group (GLR≥6.02, 768 cases) and low GLR group (GLR<6.02, 1 889 cases), high NAR group (NAR≥0.25, 547 cases) and low NAR group (NAR<0.25, 2 110 cases) according the optimal cutoff values. The baseline characteristics and occurrence of in-hospital major adverse cardiovascular events (MACE) were recorded. Multivariate Logistic regression was used to analyze the independent risk factors for in-hospital death in patients with AMI.Results:Among the 2 657 patients with AMI, 265 patients had in-hospital MACE (10.0%), and 50 patients (1.9%) died. The age, proportion of Killip≥ 2 grade, proportion of diabetes, proportion of myocardial infarction, proportion of cerebral infarction history, proportion of ST-elevation myocardial infarction (STEMI), thrombolysis in myocardial infarction clinical trial score (TIMI score), global registry of acute coronary event score (GRACE score), fibrinogen, fasting blood glucose, glycated hemoglobin, high-density lipoprotein cholesterol (HDL-C), cardiac troponin I (cTnI) peak, N-terminal B-type natriuretic peptide (NT-proBNP), hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), NAR, GLR, neutrophil count, left ventricular end-diastolic diameter (LVEDD) in high GLR group were significantly higher than those in low GLR group, the proportion of males, body mass index (BMI), proportion of smoking history, proportion of non-ST elevation myocardial infarction (NSTEMI), albumin, estimated glomerular filtration rate (eGFR), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), lymphocyte count, monocyte count and left ventricular ejection fraction (LVEF) were significantly lower than those in low GLR group, and there were statistical differences ( P<0.01 or <0.05). The proportion of Killip≥2 grade, proportion of STEMI, TIMI score, GRACE score, fibrinogen, fasting blood glucose, TC, LDL-C, cTnI peak, hs-CRP, IL-6, NAR, GLR, white blood cell count, neutrophil count and monocyte count in high NAR group were significantly higher than those in low NAR group, the age, proportion of myocardial infarction history, proportion of NSTEMI, albumin, lymphocyte count, left atrial diameter (LAD) and LVEF were significantly lower than those in low NAR group, and there were statistical differences ( P<0.01 or <0.05). The incidences of in-hospital MACE, death, ventricular fibrillation or pulseless ventricular tachycardia, atrial fibrillation, cardiac arrest and bleeding in high GLR group were significant higher than those in low GLR group: 15.2% (117/768) vs. 7.8% (148/1 889), 4.6% (35/768) vs. 0.8% (15/1 889), 5.3% (41/768) vs. 2.9% (54/1 889), 6.9% (53/768) vs. 4.0% (75/1 889), 4.7% (36/768) vs. 1.4% (26/1 889) and 2.3% (18/768) vs. 0.7% (13/1 889), and there were statistical differences ( P<0.01); there was no statistical difference in the incidence of heart rupture between two groups ( P>0.05). The incidence of in-hospital MACE, death, ventricular fibrillation or pulseless ventricular tachycardia, cardiac arrest, cardiac rupture and bleeding in high NAR group were significantly higher than those in low NAR group: 16.6% (91/547) vs. 8.2% (174/2 110), 5.9% (32/547) vs. 0.9% (18/2 110), 8.0% (44/547) vs. 2.4% (51/2 110), 5.9% (32/547) vs. 1.4% (30/2 110), 1.6% (9/547) vs. 0.4% (9/2 110) and 2.4% (13/547) vs. 0.9% (18/2 110), and there were statistical differences ( P<0.01); there was no statistical difference in the incidence of atrial fibrillation between two groups ( P>0.05). Multivariate Logistic regression analysis result showed that the Killip 3 and 4 grades, high NAR, high GRACE score, high fasting glucose and low LVEF were independent risk factors for in-hospital death in patients with AMI ( OR = 3.827, 4.660, 3.779, 1.020, 1.095 and 0.962; 95% CI 1.158 to 12.649, 1.184 to 18.344, 1.856 to 7.649, 1.009 to 1.032, 1.027 to 1.167 and 0.932 to 0.993; P<0.05 or <0.01). Conclusions:The NAR can independently predict the risk of in-hospital death in patients with AMI.

Pregnancy is a complex biological process of human body,involving the growth and development of the embryo and the formation of the placenta and other stages.Placental-derived exosome(PdE)is secreted by various placental cells and is rich in various RNA,DNA,protein and lipids.PdE,as active carriers of molecular biomarkers and mediators of cell-to-cell communication,regulate the physiological functions of the mother and maintain the normal development of the fetus,and participate in the pathological process of pregnancy.This review examines the roles of placental microRNAs,long-chain non-coding RNAs,circular RNAs in gestational diabetes mellitus,focusing on their molecular mechanisms and potential as biomarkers for early diagnosis and therapeutic targets.

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 study the relationship between the levels of multiple elements in urine and the risk of arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region (Inner Mongolia).Methods:From April 2023 to January 2024, a case-control study method was used to select 128 individuals with a residence time of ≥10 years in drinking water arsenic exposed areas in Inner Mongolia as study subjects. Eighty-one individuals diagnosed with arsenic poisoning were selected as the case group, and 47 healthy individuals were selected as the control group for urine sample collection and questionnaire survey. Inductively coupled plasma mass spectrometry was employed to determine the levels of 10 elements (chromium, manganese, cobalt, nickel, copper, zinc, arsenic, molybdenum, cadmium and lead) in urine. The levels of each element in urine were divided into four groups ( Q1, Q2, Q3, and Q4 groups) based on quartiles. The associations between the levels of various elements in urine and the risk of arsenic poisoning were studied using binary logistic regression model and restricted cubic spline (RCS). Results:The age of the control group and the case group [ M ( Q1, Q3)] were 61 (53, 69) and 61 (56, 67) years old, respectively. There were 19 and 43 males, and 28 and 38 females, respectively. There was no statistically significant differences in age and and gender composition between the two groups ( Z = - 0.39, P = 0.700; χ 2 = 1.91, P = 0.167). The levels of urinary copper and cadmium of the case group were higher than those of the control group, and the differences were statistically significant ( Z = - 2.66, - 2.16, P < 0.05). The results of univariate logistic regression analysis showed that urinary copper was an influencing factor for arsenic poisoning ( P = 0.017). The results of multivariate logistic regression analysis revealed that after adjusting for covariates, urinary copper and arsenic were independent influencing factors of arsenic poisoning ( P < 0.05). Taking Q1 group as a reference, urinary copper in Q3 group [ OR (95% CI) = 8.23 (1.81, 37.39), P = 0.006] increased the risk of arsenic poisoning, while urinary arsenic in Q2, Q3, and Q4 groups [ OR (95% CI) = 0.24 (0.06, 0.92), 0.12 (0.03, 0.53), 0.15 (0.04, 0.63), P < 0.05] decreased the risk of arsenic poisoning. After adjusting for covariates, RCS did not show a dose-response relationship between urinary copper, urinary arsenic, and arsenic poisoning ( P > 0.05). Conclusion:Urinary arsenic and copper are associated with the risk of arsenic poisoning in the drinking water arsenic exposed areas of Inner Mongolia, copper exposure may contribute significantly to arsenic poisoning.

Objective:To analyze and discuss the current status, hotspots and development dynamics of self-management in chronic heart failure (CHF) patients at home and abroad based on China National Knowledge Infrastructure and Web of Science databases.Methods:Literature on self-management of CHF patients was searched in China National Knowledge Infrastructure and Web of Science. The search period was from January 1, 2014 to May 31, 2024. Keyword cluster analysis was performed using Cite Space 6.3.R1 software.Results:A total of 411 articles in Chinese and 878 articles in English were included. In the past ten years, the annual publication volume of English literature was generally even, and the distribution trend of annual publication volume of Chinese literature showed an upward and then a downward trend. The hotspots of self-management of CHF patients in the Chinese literature mainly focused on health education, self-efficacy, and disease prognosis, and the hotspots of self-management of CHF patients in the English literature mainly focused on quality of life, disease management, and self-care.Conclusions:Analyzing the current status, hotspots and developmental dynamics of self-management in CHF patients can provide a reference for how to effectively promote self-management in CHF patients and conduct related research in the future.

Pregnancy is a complex biological process of human body,involving the growth and development of the embryo and the formation of the placenta and other stages.Placental-derived exosome(PdE)is secreted by various placental cells and is rich in various RNA,DNA,protein and lipids.PdE,as active carriers of molecular biomarkers and mediators of cell-to-cell communication,regulate the physiological functions of the mother and maintain the normal development of the fetus,and participate in the pathological process of pregnancy.This review examines the roles of placental microRNAs,long-chain non-coding RNAs,circular RNAs in gestational diabetes mellitus,focusing on their molecular mechanisms and potential as biomarkers for early diagnosis and therapeutic targets.

Objective:To investigate the correlation of neutrophil-to-albumin ratio (NAR) and glucose-to-lymphocyte ratio (GLR) with in-hospital death in patients with acute myocardial infarction (AMI).Methods:The clinical data of 2 657 patients with AMI from January 2017 to December 2022 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. Using receiver operating characteristic (ROC) curve to determine the optimal cutoff values of GLR and NAR (6.02 and 0.25) for predicting in-hospital mortality in patients with AMI, the patients were divided into high GLR group (GLR≥6.02, 768 cases) and low GLR group (GLR<6.02, 1 889 cases), high NAR group (NAR≥0.25, 547 cases) and low NAR group (NAR<0.25, 2 110 cases) according the optimal cutoff values. The baseline characteristics and occurrence of in-hospital major adverse cardiovascular events (MACE) were recorded. Multivariate Logistic regression was used to analyze the independent risk factors for in-hospital death in patients with AMI.Results:Among the 2 657 patients with AMI, 265 patients had in-hospital MACE (10.0%), and 50 patients (1.9%) died. The age, proportion of Killip≥ 2 grade, proportion of diabetes, proportion of myocardial infarction, proportion of cerebral infarction history, proportion of ST-elevation myocardial infarction (STEMI), thrombolysis in myocardial infarction clinical trial score (TIMI score), global registry of acute coronary event score (GRACE score), fibrinogen, fasting blood glucose, glycated hemoglobin, high-density lipoprotein cholesterol (HDL-C), cardiac troponin I (cTnI) peak, N-terminal B-type natriuretic peptide (NT-proBNP), hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), NAR, GLR, neutrophil count, left ventricular end-diastolic diameter (LVEDD) in high GLR group were significantly higher than those in low GLR group, the proportion of males, body mass index (BMI), proportion of smoking history, proportion of non-ST elevation myocardial infarction (NSTEMI), albumin, estimated glomerular filtration rate (eGFR), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), lymphocyte count, monocyte count and left ventricular ejection fraction (LVEF) were significantly lower than those in low GLR group, and there were statistical differences ( P<0.01 or <0.05). The proportion of Killip≥2 grade, proportion of STEMI, TIMI score, GRACE score, fibrinogen, fasting blood glucose, TC, LDL-C, cTnI peak, hs-CRP, IL-6, NAR, GLR, white blood cell count, neutrophil count and monocyte count in high NAR group were significantly higher than those in low NAR group, the age, proportion of myocardial infarction history, proportion of NSTEMI, albumin, lymphocyte count, left atrial diameter (LAD) and LVEF were significantly lower than those in low NAR group, and there were statistical differences ( P<0.01 or <0.05). The incidences of in-hospital MACE, death, ventricular fibrillation or pulseless ventricular tachycardia, atrial fibrillation, cardiac arrest and bleeding in high GLR group were significant higher than those in low GLR group: 15.2% (117/768) vs. 7.8% (148/1 889), 4.6% (35/768) vs. 0.8% (15/1 889), 5.3% (41/768) vs. 2.9% (54/1 889), 6.9% (53/768) vs. 4.0% (75/1 889), 4.7% (36/768) vs. 1.4% (26/1 889) and 2.3% (18/768) vs. 0.7% (13/1 889), and there were statistical differences ( P<0.01); there was no statistical difference in the incidence of heart rupture between two groups ( P>0.05). The incidence of in-hospital MACE, death, ventricular fibrillation or pulseless ventricular tachycardia, cardiac arrest, cardiac rupture and bleeding in high NAR group were significantly higher than those in low NAR group: 16.6% (91/547) vs. 8.2% (174/2 110), 5.9% (32/547) vs. 0.9% (18/2 110), 8.0% (44/547) vs. 2.4% (51/2 110), 5.9% (32/547) vs. 1.4% (30/2 110), 1.6% (9/547) vs. 0.4% (9/2 110) and 2.4% (13/547) vs. 0.9% (18/2 110), and there were statistical differences ( P<0.01); there was no statistical difference in the incidence of atrial fibrillation between two groups ( P>0.05). Multivariate Logistic regression analysis result showed that the Killip 3 and 4 grades, high NAR, high GRACE score, high fasting glucose and low LVEF were independent risk factors for in-hospital death in patients with AMI ( OR = 3.827, 4.660, 3.779, 1.020, 1.095 and 0.962; 95% CI 1.158 to 12.649, 1.184 to 18.344, 1.856 to 7.649, 1.009 to 1.032, 1.027 to 1.167 and 0.932 to 0.993; P<0.05 or <0.01). Conclusions:The NAR can independently predict the risk of in-hospital death in patients with AMI.