OBJECTIVE To explore the effects of dexmedetomidine （DEX） increasing serpin peptidase inhibitor clade E member 1 （SERPINE1） protein on the malignant biological behavior of thyroid carcinoma （THCA） cells. METHODS THCA cells （KTC-1， TPC-1） were treated with 1， 10 and 100 nmol/L DEX， and their viabilities， clone formation rates， migration rates and invasion number were examined. Potential biological functions of DEX in THCA cells were analyzed through whole genome sequencing and gene ontology enrichment analysis. The core targets of DEX were mined through a protein-protein interaction network. The expression characteristics of DEX core targets and their relationship with patient prognosis were evaluated. The effects of DEX on mRNA and protein expressions of core targets and protein secretion in 2 types of THCA cells were detected， and the effects of this target on DEX-related effects were validated preliminarily by knocking down the core target. RESULTS Compared with the control group （0 nmol/L DEX）， DEX at 1， 10 and 100 nmol/L significantly increased the viabilities of 2 types of THCA cells （except for the KTC-1 cells in the 1 nmol/L DEX group at 24 h）， concentration-dependently elevated the rates of clone formation， migration rates （except for 2 types of THCA cells in 1 nmol/L DEX group）， and the number of invasion （P＜0.05）. A total of 287 differently expressed genes （75 up- tongxueyan180@163.com regulated and 212 down-regulated） were enriched in signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B， Wnt， and senescence-associated secretory phenotypes in the 2 kinds of DEX-treated or non-treated THCA cells. SERPINE1 was a core target of DEX for THCA， and its mRNA and protein expression in THCA tissues/cells were significantly elevated and associated with poor prognosis of the patients （P＜0.05）. Compared with the control group， mRNA and protein expression of SERPINE1 was significantly up-regulated in 2 types of cells in the 1， 10 and 100 nmol/L DEX groups， while the secretion of this protein in conditioned medium was also significantly increased， all of which showed concentration-dependence （P＜0.05）. After knocking down SERPINE1， the promoting effects of DEX on the proliferation， colony formation， migration and invasion abilities of two types of THCA cells were significantly inhibited （P＜0.05）. CONCLUSIONS DEX can promote the proliferation， migration and invasion of THCA cell， and the above effects may be associated with the expression of increased secretory SERPINE1 protein.

OBJECTIVES: To explore the relationship between the Observer's Assessment of Alertness/Sedation (OAAS) score and the bispectral index (BIS) during propofol titration for general anesthesia induction and analyze the impact of BIS monitoring delay on anesthetic depth assessment. METHODS: This study was conducted among 90 patients (ASA class I-II) undergoing elective surgery under general anesthesia. For anesthesia induction, the patients received propofol titration at the rate of 0.5 mg·kg^-1·min^-1 till OAAS scores of 4, 3, 2, and 1 were reached. After achieving an OAAS score of 1, remifentanil (2 μg·kg⁻¹) and rocuronium (0.6 mg·kg⁻¹) were administered, and tracheal intubation was performed 2 min later. BIS values, mean arterial pressure (MAP), heart rate (HR), and propofol dosage at each OAAS score were recorded, and the correlation between OAAS scores and BIS values was analyzed. The diagnostic performance of BIS values for determining when the OAAS score reaches 1 was analyzed using ROC curve. RESULTS: All the patients successfully completed tracheal intubation. BIS values of the patients at each of the OAAS scores differed significantly (P<0.01), and the mean BIS value decreased by 4.08, 8.32, 5.43 and 5.24 as the OAAS score decreased from 5 to 4, from 4 to 3, from 3 to 2, and from 2 to 1, respectively. There was a significant correlation between the OAAS score and BIS values (ρ=0.775, P<0.001). The median BIS value for an OAAS score of 1 was 76, at which point 83.33% of the patients had BIS values exceeding 60. ROC curve analysis showed that for determining an OAAS score of 1, BIS value, at the optimal cutoff value of 84, had a sensitivity of 88.9%, a specificity of 73.3%, and an area under the curve of 0.842 (0.803-0.881). CONCLUSIONS OAAS score during induction of general anesthesia is strongly correlated with BIS value and is a highly sensitive and timely indicator to compensate for the delay in BIS monitoring.
Humans ; Propofol/administration & dosage* ; Male ; Female ; Middle Aged ; Anesthesia, General/methods* ; Adult ; Consciousness Monitors ; Aged ; Young Adult ; Monitoring, Intraoperative/methods* ; Electroencephalography

Background::Risk assessment and treatment stratification for three-vessel coronary disease (TVD) remain challenging. This study aimed to investigate the prognostic value of left atrial volume index (LAVI) with the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score II, and its association with the long-term prognosis after three strategies (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], and medical therapy [MT]) in patients with TVD.Methods::This study was a post hoc analysis of a large, prospective cohort of patients with TVD in China, that aimed to determine the long-term outcomes after PCI, CABG, or optimal MT alone. A total of 8943 patients with TVD were consecutively enrolled between 2004 and 2011 at Fuwai Hospital. A total of 7818 patients with available baseline LAVI data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included all-cause death, cardiac death, MI, revascularization, and stroke. Long-term outcomes were evaluated among LAVI quartile groups. Results::During a median follow-up of 6.6 years, a higher LAVI was strongly associated with increased risk of MACCE (Q3: hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.06-1.37, P = 0.005; Q4: HR 1.85, 95%CI 1.64-2.09, P <0.001), all-cause death (Q3: HR 1.41, 95% CI 1.17-1.69, P <0.001; Q4: HR 2.54, 95%CI 2.16-3.00, P <0.001), and cardiac death (Q3: HR 1.81, 95% CI 1.39-2.37, P <0.001; Q4: HR 3.47, 95%CI 2.71-4.43, P <0.001). Moreover, LAVI significantly improved discrimination and reclassification of the SYNTAX score II. Notably, there was a significant interaction between LAVI quartiles and treatment strategies for MACCE. CABG was associated with lower risk of MACCE than MT alone, regardless of LAVI quartiles. Among patients in the fourth quartile, PCI was associated with significantly increased risk of cardiac death compared with CABG (HR: 5.25, 95% CI: 1.97-14.03, P = 0.001). Conclusions::LAVI is a potential index for risk stratification and therapeutic decision-making in patients with three-vessel coronary disease. CABG is associated with improved long-term outcomes compared with MT alone, regardless of LAVI quartiles. When LAVI is severely elevated, PCI is associated with higher risk of cardiac death than CABG.

Objective To identify factors associated with gastrointestinal heat retention in preschool children,and to provide a foundational understanding for future clinical investigations. Methods A case-control study was performed,which involved children from kindergartens in the Longgang District of Shenzhen City,Guangdong Province,from May to July 2021. Using the Children's Gastrointestinal Heat Retention Diagnostic Self-assessment Scale,subjects were allocated into a case group (children diagnosed with gastrointestinal heat retention) and a control group (children without this condition). An online survey was used to collect data on dietary behaviors,caregivers' feeding behaviors,early antibiotic use,daily routines,and birth conditions. SPSS 27.0 software was used to facilitate precise sociodemographic matching and paired logistic regression analysis to explore the association between gastrointestinal heat retention and the above factors. Results From the analysis of 51,252 matched cases,the study found that several factors contributed to an increased risk of gastrointestinal heat retention. These factors included reduced food intake compared to peers,reports of picky eating by caregivers,distractions during meals,pronounced dietary preferences,disinterest in food,meal durations ≥ 25 min,reluctance to sample new foods,consistent refusal of specific food types for over one month,irregular meal locations,coercive feeding practices,use of micronutrient supplements,allowing children too much freedom in food choice,persuading children to eat,infrequent encouragement to experiment with new foods,early antibiotic introduction,inadequate sleep,and premature birth (P<0.05). In contrast,exclusive breastfeeding in the first six months,engagement in moderate to massive physical activity,and regular napping patterns were associated with a reduced risk of gastrointestinal heat retention (P<0.05). Conclusion The suboptimal dietary habits,improper feeding practices,insufficient physical activity,inadequate sleep,and premature antibiotic exposure may be significant risk factors for gastrointestinal heat retention. Future research dedicated to unraveling the cause of gastrointestinal heat retention should prioritize these elements.

Objectives:To establish a risk prediction model for gastrointestinal bleeding after cardiopulmonary bypass heart surgery,and to verify the prediction efficacy. Methods:A total of 1 002 patients who underwent cardiopulmonary bypass heart surgery in the department of cardiac great vascular surgery of our hospital from January 2019 to November 2023 were collected by convenient sampling method.They were divided into gastrointestinal bleeding group(n=47)and non-gastrointestinal bleeding group(n=955).Logistic regression analysis was used to establish the risk prediction model,and the area under ROC curve test and Hosmer-Lemeshow χ2 test were used to compare the two groups of data Model prediction effect.Bootstrap method was used for internal validation. Results:The risk prediction model of gastrointestinal bleeding after cardiopulmonary bypass heart surgery included four predictors:time of aortic occlusion(OR=1.021,95%CI:1.012-1.030),history of digestive disease(OR=5.710,95%CI:1.697-19.212),use of intra-aortic balloon counterpulsation(OR=22.180,95%CI:5.870-83.808),and continuous kidney replacement therapy(OR=12.159,95%CI:5.066-29.181).Model formula:Logit(P)=-5.821+0.021×time of aortic occlusion+1.742×history of digestive disease+3.099×whether intra-aortic balloon counterpulsation was used+2.498×whether continuous renal replacement therapy was used.The area under ROC curve was 0.812(95%CI:0.746-0.877),sensitivity was 64.6%,specificity was 85.7%,and Youden index was 0.503.After internal validation by Bootstrap method,the consistency index after correction is 0.813. Conclusions:The risk prediction model constructed in this study cohort has a good auxiliary prediction performance for the occurrence of gastrointestinal bleeding after cardiopulmonary bypass surgery,which is helpful for risk stratification for gastrointestinal bleeding after cardiopulmonary bypass surgery and facilitate clinical decision-making in daily clinical work.

Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disability still remain high.Sonodynamic therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and sta-bilizing plaques.Promising progress has been made through cell and animal assays,as well as clinical trials.For example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been proposed.In this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDTs therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.

Objective To establish and evaluate a rapid detection method for SARS-CoV-2 based on reverse transcriptase-recombinase aided amplification(RT-RAA)combined with the clustered regularly interspaced short palindromic repeats(CRISPR)/Cas12a system.Methods RT-RAA primers and CRISPR-derived RNA(crRNA)were designed based on the nucleocapsid(N)gene of SARS-CoV-2 from NCBI database.The detection system was optimized with magnesium acetate(MgAc)concentration,RT-RAA reaction tempera-ture and time and LbCas12a reaction temperature.The sensitivity and specificity of the method were evaluated using recombinant plas-mids(100-106 copies/μL)and other respiratory pathogens.The RT-RAA-CRISPR/Cas12a method was compared with RT-PCR by tes-ting 70 clinical samples in parallel.Results The optimized RT-RAA-CRISPR/Cas12a assay could detect SARS-CoV-2 within 50 min at 37 ℃.The limit of detection was 10 copies/μL for the fluorescence-based method and 1×102 copies/μL for the lateral flow assay.The method specifically detected SARS-CoV-2 without cross-reactivity to other respiratory pathogens.The results of testing 70 clinical samples using RT-RAA-CRISPR/Cas12a showed agreement of 100％with those of RT-PCR.Conclusion The established RT-RAA-CRISPR/Cas12a assay for SARS-CoV-2 detection is rapid,cost-effective,highly sensitive and specific.It can be performed by less experienced personnel and no expensive equipment is required,thus it may provide a new approach for rapid clinical diagnosis and large-scale on-site screening of SARS-CoV-2.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.