Objective:To compare the efficacy of intranasal nebulized remimazolam versus esketamine for preoperative sedation in pediatric patients.Methods:In this randomized double-blind controlled trial, 90 pediatric patients scheduled for elective surgery with general anesthesia at Fuyang People′s Hospital between October 2024 and January 2025, were divided into 3 groups ( n=30 each) using a simple randomization: remimazolam group (group R), esketamine group (group S) and normal saline group (group C). Group R received intranasal nebulization of remimazolam 1.5 mg/kg, group S received intranasal nebulization of esketamine 1 mg/kg, and group C received intranasal nebulization of normal saline 0.05 ml/kg. Primary outcome: The preoperative anxiety was assessed using the modified Yale Preoperative Anxiety Scale before intranasal drug administration (baseline), at 10 and 20 min after administration, and before anesthesia induction. Secondary outcomes included sedation level (Ramsay Sedation Scale score), satisfaction with intranasal administration acceptance, parental separation anxiety and mask acceptance, development of emergence agitation, emergence time, time of recovery from anesthesia, and nausea and vomiting and increased secretions. Results:Compared to group C, the incidence of anxiety was significantly decreased at 10 and 20 min after intranasal nebulization and before anesthesia induction, the level of sedation was deepened (to light sedation), and the satisfaction with intranasal administration acceptance was decreased in group R ( P<0.017), the incidence of anxiety was significantly decreased before anesthesia induction, the level of sedation was deepened (to deep sedation), and the satisfaction with intranasal administration acceptance was increased in group S ( P<0.017), and the satisfaction with parental separation anxiety and mask acceptance and anesthesiologists′ satisfaction were significantly increased in R and S groups( P<0.017). Compared to group R, the incidence of anxiety was significantly increased at 10 min after intranasal nebulization (7 cases [23%] versus 20 cases [67%]), the level of sedation was lighter at 10 min after intranasal nebulization, the level of sedation was deeper, and the satisfaction with intranasal administration acceptance was increased in group S ( P<0.017). Compared to groups C and R, the emergence time and time of recovery from anesthesia were significantly prolonged in group S ( P<0.017). There was no significant difference in the incidence of emergence agitation, nausea and vomiting and increased secretions or in parental satisfaction among three groups ( P>0.05). Conclusions:Both intranasal nebulized remimazolam and esketamine can produce good preoperative sedation in pediatric patients. Compared to esketamine, remimazolam provides a more appropriate level of sedation with a faster onset and does not prolong the recovery from anesthesia, making it more suitable for preoperative sedation in minor procedures.

Objective:To compare the efficacy of intranasal nebulized remimazolam versus esketamine for preoperative sedation in pediatric patients.Methods:In this randomized double-blind controlled trial, 90 pediatric patients scheduled for elective surgery with general anesthesia at Fuyang People′s Hospital between October 2024 and January 2025, were divided into 3 groups ( n=30 each) using a simple randomization: remimazolam group (group R), esketamine group (group S) and normal saline group (group C). Group R received intranasal nebulization of remimazolam 1.5 mg/kg, group S received intranasal nebulization of esketamine 1 mg/kg, and group C received intranasal nebulization of normal saline 0.05 ml/kg. Primary outcome: The preoperative anxiety was assessed using the modified Yale Preoperative Anxiety Scale before intranasal drug administration (baseline), at 10 and 20 min after administration, and before anesthesia induction. Secondary outcomes included sedation level (Ramsay Sedation Scale score), satisfaction with intranasal administration acceptance, parental separation anxiety and mask acceptance, development of emergence agitation, emergence time, time of recovery from anesthesia, and nausea and vomiting and increased secretions. Results:Compared to group C, the incidence of anxiety was significantly decreased at 10 and 20 min after intranasal nebulization and before anesthesia induction, the level of sedation was deepened (to light sedation), and the satisfaction with intranasal administration acceptance was decreased in group R ( P<0.017), the incidence of anxiety was significantly decreased before anesthesia induction, the level of sedation was deepened (to deep sedation), and the satisfaction with intranasal administration acceptance was increased in group S ( P<0.017), and the satisfaction with parental separation anxiety and mask acceptance and anesthesiologists′ satisfaction were significantly increased in R and S groups( P<0.017). Compared to group R, the incidence of anxiety was significantly increased at 10 min after intranasal nebulization (7 cases [23%] versus 20 cases [67%]), the level of sedation was lighter at 10 min after intranasal nebulization, the level of sedation was deeper, and the satisfaction with intranasal administration acceptance was increased in group S ( P<0.017). Compared to groups C and R, the emergence time and time of recovery from anesthesia were significantly prolonged in group S ( P<0.017). There was no significant difference in the incidence of emergence agitation, nausea and vomiting and increased secretions or in parental satisfaction among three groups ( P>0.05). Conclusions:Both intranasal nebulized remimazolam and esketamine can produce good preoperative sedation in pediatric patients. Compared to esketamine, remimazolam provides a more appropriate level of sedation with a faster onset and does not prolong the recovery from anesthesia, making it more suitable for preoperative sedation in minor procedures.

BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

Autophagy is a cellular self-degradation process that maintains homeostasis and has been shown to promote tumor progression in advanced stages.Pancreatic cancer cells and the surrounding stromal cells exhibit high levels of autophagy.Therefore,targeting au-tophagy has emerged as a promising therapeutic strategy for pancreatic cancer.This review focuses on research targeting autophagy in pancreatic cancer treatment,elaborating on the roles and underlying mechanisms of autophagy in pancreatic cancer cell proliferation,metas-tasis,modulation of the tumor immune microenvironment,and drug resistance.Additional-ly,we summarize preclinical and clinical studies investigating autophagy-targeted therapies both as monotherapy and in combination with other treatments,aiming to provide new theo-retical rationale and therapeutic strategies for pancreatic cancer management.

Autophagy is a cellular self-degradation process that maintains homeostasis and has been shown to promote tumor progression in advanced stages.Pancreatic cancer cells and the surrounding stromal cells exhibit high levels of autophagy.Therefore,targeting au-tophagy has emerged as a promising therapeutic strategy for pancreatic cancer.This review focuses on research targeting autophagy in pancreatic cancer treatment,elaborating on the roles and underlying mechanisms of autophagy in pancreatic cancer cell proliferation,metas-tasis,modulation of the tumor immune microenvironment,and drug resistance.Additional-ly,we summarize preclinical and clinical studies investigating autophagy-targeted therapies both as monotherapy and in combination with other treatments,aiming to provide new theo-retical rationale and therapeutic strategies for pancreatic cancer management.

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with al-terations in synaptic currents and mitochondrial dynamics.However,the specific associations between these pathological changes remain unclear.In this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models.The investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,trans-mission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assess-ment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular docking.The results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD models.Remarkably,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic transmission.The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular cortex.DZSM intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and length.Moreover,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial morphology.In conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.

Objectives:This study aims to investigate the association between cumulative fasting blood glucose(FBG)and presence of coronary artery calcification(CAC). Methods:A total of 1 113 participants were recruited from the Beijing Community-based Cohort of Atherosclerosis.Anthropometric measurements and laboratory examinations including FBG were performed in 1998,2008-2009 and 2013-2014 respectively,and coronary CT scan was performed in 2013-2014.Participants were classified into 4 groups according to the level of cumulative FBG(10-year weighted cumulative value of at least 2 FBGs):<50.0 mmol/L group(n=495),50.0-55.9 mmol/L group(n=345),56.0-69.9 mmol/L group(n=176),and≥70.0 mmol/L group(n=97).CAC score>0 was defined as presence of CAC.Multivariable logistic regression model was applied to analyze the impact of cumulative FBG exposure on the risk of CAC,and subgroup analyses were conducted according to factors such as sex and age. Results:The mean age of enrolled participants was(59.7±6.4)years,523(47.0%)were male and 478(42.9%)had CAC.The proportion of subjects with CAC increased with the increment of cumulative FBG.Compared with the<50.0 mmol/L group,the multivariable-adjusted OR(95%CI)for CAC in the 50.0-55.9 mmol/L group,56.0-69.9 mmol/L group,and≥70.0 mmol/L group were 1.43(1.04-1.98),1.92(1.24-2.99)and 2.79(1.35-5.77),respectively(Ptrend<0.05).The risk for CAC increased by 34%per 10 mmol/L increase in cumulative FBG,with OR(95%CI)of 1.34(1.12-1.59).There was no statistically significant difference in the risk of CAC presence for each 10 mmol/L increase in cumulative FBG level between the subgroups(all P≥0.05). Conclusions:Elevated cumulative FBG is a risk factor for the prevalence of CAC,indicating the importance of maintaining healthy FBG in preventing the occurrence of CAC.

Background::Familial hypercholesterolemia (FH) is underrecognized, and its association with coronary artery disease (CAD) remains limited, especially in China. We aimed to investigate the prevalence of FH and its relationship with CAD in a large Chinese cohort.Methods::FH was defined using the Make Early Diagnosis to Prevent Early Death (MEDPED) criteria. The crude and age-sex standardized prevalence of FH were calculated based on surveys of the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project during 2007-2008. The associations of FH with incident CAD and its major subtypes were estimated with the cohort-stratified multivariate Cox proportional hazard models based on the data from the baseline to the last follow-up (2018-2020).Results::Among 98,885 included participants, 190 participants were defined as FH. Crude and age-sex standardized prevalence and 95% confidence interval (CI) of FH were 0.19% (0.17%–0.22%) and 0.13% (0.10%–0.16%), respectively. The prevalence varied across age groups and peaked in the group of 60–<70 years (0.28%), and the peak prevalence (0.18%) in males was earlier, yet lower than the peak crude prevalence in females (0.41%). During a mean follow-up of 10.7 years, 2493 cases of incident CAD were identified. After multivariate adjustment, FH patients had a 2.03-fold greater risk of developing CAD compared to non-FH participants.Conclusions::The prevalence of FH was estimated to be 0.19% in the participants, and it was associated with an elevated risk of incident CAD. Our study suggests that early screening of FH has certain public health significance for the prevention of CAD.

Background::Population-based epidemiological evidence regarding the association between fruit and vegetable intake and the incidence of hypertension is inconsistent. This prospective cohort study aimed to investigate the association between fruit and vegetable intake and the risk of new-onset hypertension.Methods::Based on the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR), 58,981 Chinese adults without hypertension at baseline were included. Information on fruit and vegetable intake was collected using a food-frequency questionnaire. Cox proportional hazards models were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension.Results::During 640,795 person-years of follow-up, 21,008 new cases of hypertension were recorded. Compared with participants in the lowest quintile (Q1) of total fruit and vegetable (TFV) intake, the HRs (95% CIs) of incident hypertension were 0.90 (0.86-0.95), 0.85 (0.81-0.90), 0.82 (0.78-0.86), and 0.83 (0.78-0.88) for the Q2 to Q5 group ( ptrend < 0.001), respectively. In further analyses categorizing participants according to the recommended intake level (500 g/day), we found that increasing the intake of TFV, even though it was still insufficient for the recommendation, also had a protective effect against the incident hypertension. When considering the intake of fruit or vegetable separately, we found similar trends as the TFV intake. Conclusion::These results suggest that a higher intake of fruit and vegetable is beneficial for preventing hypertension in Chinese adults.