Abstract To understand the relationship between cardiovascular disease (CVD) and adverse childhood experiences (ACEs), the present review aims to describe the burden and influencing factors of CVD, epidemiological characteristics and burden of ACEs, current research on the relationship between ACEs and CVD, and the mechanism of ACEs leading to CVD. It is proposed that further assessment of the relationship is warranted through identifying blood biomarkers, conducting prospective cohort studies and intervention studies. Such efforts would provide valuable scientific insights for primary prevention strategies for cardiovascular disease.

Objective:To compare the trueness of incisal guidance of implant-supported single crowns designed by patient-specific motion(PSM)with that designed by average-value virtual articulator(AVA).Methods:The study had recruited 12 participants with complete dentition and stable incisal guidance.An intraoral scanner was used to scan digital casts and record two types of patient-specific mo-tion(data only including protrusive movement,and data including protrusive movement and lateral pro-trusive movement).The lingual surfaces of the maxillary incisors which guided the protrusive movement was selected and elevated to create a reference cast.A maxillary central incisor of original casts was vir-tually extracted and implanted to generate a working cast.The Dental system software program was used to design implant-supported single crowns with the anatomical coping design method.The incisal guidance was designed by different methods.The incisal guidance in control group was designed by the average-value virtual articulator.The incisal guidance in experiment groups was designed by the patient-specific motion only including protrusive movement(PSM1)and with the patient-specific motion including protru-sive movement and lateral protrusive movement(PSM2).The incisal guidance of prosthesis designed by these 3 methods were compared with the original incisal guidance in Geomagic Control 2015(3DSystem,America).The measurements included:Average of positive values,ratio of positive area and maximum value reflecting supra-occlusion;average of negative values,ratio of negative area and minimum value re-flecting over-correction;and root mean square reflecting overall deviation.Results:Statistical data were collected using the median(interquartile range)method.The average of positive values,ratio of positive area and average of negative values of the PSM2 group were smaller than those of the control group[8.0(18.8)μm vs.37.5(47.5)μm;0vs.7.2％(38.1％);-109.0(63.8)μm vs.-66.5(64.5)μm],and the ratio of negative area of PSM2 group was larger than those of the control group[52.9％(47.8％)vs.17.3％(45.3％)],with significant differences(P all＜0.05).The ratio of positive area[0.1％(7.0％)]and average of negative values[-97.0(61.5)μm]of PSM1 group,were smaller than those of the control group,and the ratio of negative area[40.7％(39.2％)]of the PSM1 group was larger than that of the control group,with significant differences(P＜0.05).The average of positive values[20.0(42.0)μm]and ratio of positive area of PSM1 group was larger than that of the PSM2 group with significant differences(P＜0.05).Conclusion:To establish the incisor guidance of implant-supported single crowns,compared with the average-value virtual articulator and the patient-specific motion only including protrusive movement,the patient-specific motion including protrusive movement and lateral protrusive movement is more conducive to reducing the protrusive interference of prosthesis and improving the occlusal fit.

ObjectiveTo investigate the mechanism of neferine（Nef） in promoting vascular regeneration against cerebral ischemia through modulation of mitochondrial calcium uniporter（MCU） ion channel. MethodTaking the area of subintestinal vessels in microvascular deficiency zebrafish as an index， the vascular regenerative efficacy of Nef was evaluated， and the median effective concentration（EC₅₀） was calculated. Rats were randomly divided into a sham operation group， a model group， a positive drug group（butylphthalide， 6 mg·kg^-1）， and Nef low， medium， and high dose groups（0.125， 0.625， 3.125 μg·kg^-1）. Except for the sham operation group， the middle cerebral artery occlusion（MCAO） model was established in other groups. After modeling， the groups were administered the corresponding dose of drugs by gavage， while the sham operation and model groups received equal volumes of saline， once a day for 7 consecutive days. Neurobehavioral scores were assessed for each group of rats， and the infarct rate of ischemic brain tissue was calculated by 2，3，5-triphenyltetrazolium chloride（TTC） staining. The regional cerebral blood flow（rCBF） of each group was measured using a speckle contrast imaging. Immunofluorescence and Western blot were conducted to detect the expression of vascular endothelial growth factor（VEGF）， platelet endothelial cell adhesion molecule-1（CD31）， and hypoxia-inducible factor-1α（HIF-1α） proteins in each group. Human umbilical vein endothelial cells（HUVECs） were divided into the normal group， model group， positive drug group（astragaloside Ⅳ， 10 μmol·L^-1）， and Nef group （32 nmol·L^-1）. In the verification of mitochondrial protection of Nef and its mechanism in promoting vascular regeneration， the spermine（MCU agonist） and Nef+spermine group were added. HUVECs model of oxygen-glucose deprivation（OGD） was established in all groups except the normal group， the cell viability was assessed using 3-（4，5-dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide（MTT） assay， and cell migration ability was evaluated through scratch and tube formation assays. Fluorescent probes（Rhod-2 AM， Fluo-3 AM， JC-1， Calcein AM） and a cellular energy metabolism analyzer were used to analyze the mitochondrial protective effects of Nef. Molecular docking was performed to predict the binding ability of Nef with MCU and HIF-1α， and Western blot was used to detect the effects of Nef on the protein expressions of MCU， B-cell lymphoma-2 associated X protein（Bax）， Caspase-3 and HIF-1α in the OGD model HUVECs. ResultThe results of vascular regeneration in microvascular deficiency zebrafish showed that compared to the normal group， the area of subintestinal vessels in the model group significantly decreased（P<0.01）. Compared to the model group， different concentrations of Nef could significantly increase the area of subintestinal vessels（P<0.01）， with the maximum tolerated concentration of 10.24 μmol·L^-1 and the EC₅₀ of 0.23 μmol·L^-1. Anti-cerebral ischemia results on MCAO rats showed that compared to the sham operation group， the model group had a significant decrease in rCBF and a significant increase in infarct rate， while CD31 expression significantly decreased（P<0.01）， and VEGF and HIF-1α protein expressions significantly increased（P<0.05）. Compared to the model group， the treated groups showed significant increases in rCBF， significant reductions in infarct volume， and significant increases in CD31， VEGF， and HIF-1α protein expression（P<0.01）. Cell experiment results showed that compared to the normal group， the model group had decreased cell viability and migration ability， increased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， reduced mitochondrial permeability transition pore（MPTP） opening， and decreased mitochondrial energy metabolism capability， with increased expressions of MCU， Bax， Caspase-3 and HIF-1α proteins（P<0.05， P<0.01）. Compared to the model group， the Nef group showed increased cell viability and migration ability， decreased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， increased MPTP opening， enhanced mitochondrial energy metabolism capability， decreased expressions of MCU， Bax and Caspase-3 proteins， and increased HIF-1α protein expression（P<0.05， P<0.01）. ConclusionNef can stabilize mitochondrial membrane potential and inhibit mitochondrial apoptosis. By down-regulating the expression of MCU， it suppresses the activation of intracellular Bax and Caspase-3 while activating the HIF-1α signaling pathway， enhancing the expression of VEGF and CD31， thereby promoting vascular regeneration to treat ischemic brain injury.

In the field of dental aesthetics,digital aesthetic design plays a crucial role in helping dentists to predict treatment outcomes vis-ually,as well as in enhancing the consistency of knowledge and understanding of aesthetic goals between dentists and patients.It serves as the foundation for achieving ideal aesthetic effects.However,there is no clear standard for this digital process currently in China and abroad.Many dentists lack of systematic understanding of how to carry out digital aesthetic design for treatment.To establish standardized processes for dental aesthetic design and to improve the homogeneity of treatment outcomes,Chinese Society of Digital Dental Industry(CSD-DI)convened domestic experts in related field to compile this consensus.This article elaborates on the key aspects of digital aesthetic data collection,integration steps,and the digital aesthetic design process.It also formulates a decision tree for dental aesthetics at macro level and outlines corresponding workflows for various clinical scenarios,serving as a reference for clinicians.

BACKGROUND:In recent years,tranexamic acid has been extensively used to mitigate the substantial blood loss associated with total knee arthroplasty.However,the optimal method of topical application has not yet been established. OBJECTIVE:To evaluate the effectiveness and safety of intraoperative topical application of tranexamic acid combined with physical compression dressing in reducing perioperative blood loss in total knee arthroplasty. METHODS:A retrospective analysis was conducted on 90 patients who underwent total knee arthroplasty at the Honghui Hospital in Xi'an from January 2021 to December 2022.Based on the different topical use methods of tranexamic acid during surgery,patients were divided into three groups,with 30 cases in each group.In the compression dressing group,2 g of tranexamic acid was placed in the articular cavity,and after packing the wound with gauze and cotton pads,a bandage was used to compress the wound.In the periarticular injection group,2 g of tranexamic acid was injected into the surrounding tissue of the articular cavity.In the intra-articular injection group,2 g of tranexamic acid was injected into the articular cavity.The blood loss,operation time,coagulation indicators,inflammatory indicators,and postoperative complications of the three groups were statistically analyzed. RESULTS AND CONCLUSION:(1)In terms of total blood loss,hidden blood loss,and maximum hemoglobin drop,the periarticular injection group had the least amount,and there was no statistically significant difference between the compression dressing group and periarticular injection group(P>0.05).In terms of intraoperative blood loss,the compression dressing group had the least amount,and there were statistically significant differences compared with the periarticular injection group and intra-articular injection group(P<0.05).There was no statistically significant difference in operation time among the three groups(P>0.05).(2)There were no statistically significant differences in coagulation indicators(D-dimer and fibrinogen degradation products)and inflammation indicators(C-reactive protein and erythrocyte sedimentation rate)among the three groups preoperatively and on the first and third days after operation(P>0.05).(3)There was no statistically significant difference observed among the three groups in terms of slow blood flow in the affected limb,intramuscular venous thrombosis,soft tissue swelling,and incidence of wound complications(P>0.05).Additionally,no cases of deep vein thrombosis or pulmonary embolism were detected in any of the groups.(4)The topical application of tranexamic acid combined with compression dressing achieves the same effect as a periarticular injection in terms of simplicity of operation and reduced perioperative blood loss.This method also avoids the trauma caused by repeated punctures and does not increase the incidence of postoperative complications,making it a worthwhile option for clinical promotion.

BACKGROUND:The renin-angiotensin system plays a key role in the occurrence and development of hypertension,in which angiotensin(1-7)has antihypertensive effect and reversely regulates the adverse effects of angiotensin Ⅱ.Exercise rehabilitation therapy is an important non-pharmaceutical means to prevent and treat hypertension;however,whether angiotensin(1-7)and exercise have a synergistic effect is not yet clear. OBJECTIVE:To explore the effect of angiotensin(1-7)supplementation combined with exercise therapy on cardiac remodeling in rats with renal hypertension and to investigate the possible mechanism of angiotensin(1-7)and its receptor signal axis. METHODS:Sixty male Sprague-Dawley rats were selected,of which 12 rats were randomly selected as normotensive group and the remaining 48 rats were used to make animal models of renal hypertension using two-kidney one-clip method and were then randomly divided into hypertension control group,hypertension exercise group,angiotensin(1-7)group and combined treatment group.One week after successful modeling,different interventions were given(for a period of 6 weeks)as follows:the hypertension exercise group was subjected to a running training on an electric treadmill,the angiotensin(1-7)group was perfused with angiotensin(1-7)by implanting Alzet microosmotic pump subcutaneously on the back of the rats,and the combined treatment group was perfused with angiotensin(1-7)after running training,while the normotensive group and hypertension control group were caged quietly.At 48 hours after the last training session,the tail artery blood pressure was measured with a non-invasive sphygmomanometer;the heart structure and function were detected by echocardiography;the left ventricular myocardium was taken for histopathological observation by hematoxylin-eosin and Masson staining,and the cardiomyocyte cross-sectional area and collagen volume fraction were obtained by image analysis software as markers of myocardial hypertrophy and fibrosis,respectively;the content of angiotensin(1-7)in the heart was detected by high performance liquid chromatography;the mRNA expression of cardiac embryonic genes,atrial natriuretic peptide and β-myosin heavy chain,was detected by real-time fluorescence quantitative PCR;and the protein expression of cardiac Mas receptor,angiotensin Ⅱ type 2 receptor and endothelial nitric oxide synthase was measured by western blot assay. RESULTS AND CONCLUSION:Compared with the normotensive group,blood pressure increased(P<0.05),cardiac function had no significant changes(P>0.05),cardiomyocyte cross-sectional area and collagen volume fraction increased(P<0.05),mRNA expression of atrial natriuretic peptide and β-myosin heavy chain was upregulated(P<0.05),angiotensin(1-7)content and protein expression of Mas receptor,angiotensin Ⅱ type 2 receptor and endothelial nitric oxide synthase was downregulated(P<0.05)in the hypertension control group.Compared with the hypertension control group,blood pressure decreased(P<0.05),cardiac function improved(P<0.05),collagen volume fraction decreased(P<0.05),cardiomyocyte cross-sectional area and angiotensin(1-7)content showed no significant changes(P>0.05),mRNA expression of atrial natriuretic peptide and β-myosin heavy chain was downregulated(P<0.05),and the protein expression of Mas receptor,angiotensin Ⅱ type 2 receptor and endothelial nitric oxide synthase was upregulated(P<0.05)in the hypertension exercise group;except for an increase in myocardial angiotensin(1-7)content(P<0.05),other parameters had no statistical significance(P>0.05)in the hypertension angiotensin(1-7)group.Compared with the hypertension exercise group,blood pressure decreased(P<0.05),cardiomyocyte cross-sectional area and cardiac function had no significant changes(P>0.05),collagen volume fraction decreased(P<0.05),angiotensin(1-7)content increased(P<0.05),mRNA expression of atrial natriuretic peptide and β-myosin heavy chain was downregulated(P<0.05),and the protein expression of Mas receptor,angiotensin Ⅱ type 2 receptor and endothelial nitric oxide synthase was upregulated(P<0.05)in the combined treatment group.To conclude,supplementation of angiotensin(1-7)alone cannot improve cardiac remodeling in rats with renal hypertension,but it can enhance the efficacy of exercise.The mechanism is related to the improvement of angiotensin(1-7)receptor deficiency and restoration of its signaling pathway function.

Objective It aims to construct a quality evaluation index system for cancer multidisciplinary diagnosis and treatment(MDT)model in China from a full process perspective,providing guidance for practical application and model optimization.Methods Based on the number of MDT publications and practical situations,20 provincial-level hospitals nationwide were selected as typical cases.Rooted theory was used to extract evaluation indicators from the original text of the cases through three-level coding.A cancer MDT quality evaluation index system was constructed under the Input-Process-Output framework.Results Through three-level coding,27 initial categories,8 subcategories,and 3 main categories were sorted out,and a cancer MDT quality evaluation index system was constructed with input,process,and output as the primary evaluation indicators,and top-level design,management system,object resources,meeting preparation,meeting progress,plan implementation,patient outcomes,and hospital outcomes as the secondary evaluation indicators.Conclusion The quality evaluation index system of cancer MDT mode based on the perspective of the entire process can effectively guide practical optimization,but there is still a need for the improvement of supporting policies and information systems to assist in quality evaluation.

Objective To systematically evaluate the efficacy and safety of ciprofol for sedation and anesthesia outside the operating room.Methods Databases such as PubMed,Embase,Cochrane Library,Web of Science,CNKI,Wanfang Data,CBM,and VIP were searched for randomized controlled trials(RCTs)related to the efficacy and safety of ciprofol for sedation and anesthesia outside the operating room.The search covered all publications up to June 2023.Statistical analysis was performed using RevMan 5.4 software and Stata 15.0.Results Twelve RCTs were included,involving 2 192 patients,of which 1 154 were in the ciprofol group and 1 038 in the propofol group.Compared with the propofol group,the anesthesia induction time(MD=0.28 min,95％CI 0.08-0.47 min,P=0.006)and recovery time(MD=1.16 min,95％CI 0.44-1.87 min,P=0.001)were significantly longer in the ciprofol group,and the inci-dences of injection pain(OR=0.04,95％CI 0.02-0.06,P＜0.001),hypotension(OR=0.64,95％CI 0.49-0.83,P=0.0008),hypoxemia(OR=0.44,95％CI 0.21-0.91,P=0.03),and respirato-ry depression(OR=0.19,95％CI 0.11-0.32,P＜0.001)were significantly lower.There were no sta-tistically significant differences between the two groups in terms of sedation success rate,physician satisfac-tion,the difference in heart rate before and after anesthesia induction,incidence of body movement,brady-cardia,nausea and vomiting,and dizziness.Conclusion The anesthetic effect of cyclopofol and propofol is similar when used for anesthesia outside the operating room.Compared to propofol,ciprofol offers comparable anesthetic effects for sedation and anesthesia outside the operating room,with a lesser impact on respiratory function and more stable hemodynamics.Ciprofol also significantly lowers the incidence of adverse reactions such as injection pain,hypotension,hypoxemia,and respiratory depression.

Objective To analyze differential metabolites (DMs) in the urine of workers with occupational nickel exposure using non-targeted metabolomics, and to screen differential metabolic pathways. Methods A total of 30 nickel exposed workers were selected as the exposure group, and 30 administrative staff from the same factory were selected as the control group using the judgment sampling method. Urine samples of the individuals from the two groups were collected. The ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and non-targeted metabolomics were used to detect and identify metabolites. The differential metabolic profiles were compared between workers of the two groups, and key differential metabolic pathways and potential biomarkers were screened. The association of DMs and urinary nickel level were evaluated by Spearman correlation coefficients. The sensitivity and specificity of biomarkers were assessed by receiver operating characteristic (ROC) curve analysis. Results A total of 418 metabolites were identified in the urine of worker in the exposure and control groups. The result of principal component analysis and orthogonal partial least squares analysis showed that there were 128 DMs in the urine of workers in the exposure group compared with the control group. These DMs were mainly enriched in glutathione metabolism, carnitine synthesis, and amino acid and nucleotide metabolism pathways, including glycine and serine metabolism. The result of correlation analysis and ROC curve analysis revealed that 4-methylcatechol, 4-vinylphenol sulfate, 2-hydroxyphenylacetone sulfate, 2-dodecylbenzenesulfonic acid, and decylbenzenesulfonic acid could be the potential biomarkers for nickel exposure (all area under the ROC curve >0.800). Conclusion There were significant differences in the urinary metabolic profiles of workers with occupational nickel exposure. The five DMs including 4-methylcatechol, 4-vinylphenol sulfate, 2-hydroxyphenylacetone sulfate, 2-dodecylbenzenesulfonic acid, and decylbenzenesulfonic acid. These DMs could be potential biomarkers of occupational nickel exposure.

Biotoxins, which include bacterial, fungal, marine, plant, and animal toxins, are widespread in living and occupational environments, posing potential threats to human health. Rapid detection of biotoxins in blood is crucial for preventing health hazards and enabling timely disease diagnosis and treatment. Biosensors and immunoassay technologies have critical advantages in the rapid detection of biotoxins in blood. Common biosensors, such as surface plasmon resonance biosensors and fluorescent biosensors, enhance sensitivity and reduce detection limits through signal amplification. Common immunoassay methods, such as colloidal gold immunochromatography, fluorescence immunochromatography, and chemiluminescence immunoassay, improve detection efficacy and sensitivity through specific antibody-antigen binding and nanotechnology. However, current rapid detection technologies of bitoxins in blood face challenges such as matrix interference and insufficient specificity, and they fall short in high-throughput detection of multiple toxins simultaneously. Future developments should focus on improving sample pretreatment, innovating signal amplification methods, enhancing specificity on recognition of elements, and designing portable detection devices and high-throughput platforms for simultaneous toxin analysis. These advancements aim to improve the sensitivity and reliability of detection methods, providing more accurate and convenient solutions for biotoxin detection in blood.