Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

Objective:To construct 68Ga-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-CD44 as a novel atherosclerosis tracer targeting hyaluronic acid (HA), and evaluate its biological property and molecular imaging features. Methods:Low molecular weight (LMW) recombinant human CD44 protein was selected, and the C-terminal of the protein was modified by sulfonation and coupled to the bifunctional ligand NOTA to synthesize a novel molecular probe 68Ga-NOTA-CD44 targeting HA. The biological properties of the probe, such as labeling rate and in vitro stability, were studied. Three atherosclerotic plaque model mice and three normal C57BL/6 mice were studied by 68Ga-NOTA-CD44 microPET/CT imaging and pathological examination. Results:68Ga-NOTA-CD44 tracer was synthesized and purified with the radiochemical purity above 99%, and the specific activity was up to 62.22 MBq/nmol. lts stability was good in PBS, and the radiochemical purity was over 90% after incubation for 3 h. After intravenous injection, the probe was metabolized mainly by the kidneys, and its metabolic level decreased successively in the liver, lungs and blood. MicroPET/CT imaging results of atherosclerotic model mice suggested that the uptake in the plaque of abdominal aorta was higher at 60 min after injection, with SUV max and target/background ratio (TBR) max of 1.14±0.02 and 4.95±0.93, and the probe had certain atherosclerotic plaque eroded targeting, which was consistent with the pathological result. Conclusions:As a novel probe, 68Ga-NOTA-CD44 is simple to prepare and has a high labeling rate. It has good physicochemical properties and in vivo biological properties, and can display atherosclerotic eroded plaques sensitively. 68Ga-NOTA-CD44 has a promising prospect to be a new molecular probe for early noninvasive recognition of atherosclerotic eroded plaques.

Objective Scutellaria baicalensis stems and leaves glucuronic hydrolase(sbsl GUS)was used to enzymatically hydrolyze scutellarin in Erigeron breviscapus(Vant.)Hand.Mazz.to prepare scutellarein,and the high-purity scutellarein was obtained through separation and purification.Methods Orthogonal experiments were used to optimize the process parameters for the extraction of Erigeron breviscapus(Vant.)Hand.Mazz..Using the rate of enzymatic hydrolysis conversion of scutellarin as the index,the amount of enzyme,pH,temperature,time and antioxidant were investigated,and the preparation process parameters of scutellarein were optimized.Ethanol extraction,activated carbon decolorization,and fractional crystallization were used to purify the crude extract.Results The extraction process was determined to be:segments of Erigeron breviscapus were decocted twice with 10 times water for 1 hour each time.The preparation process of scutellarein was as follows:the amount of sbsl GUS extract and Erigeron breviscapus decoction was 1∶10 based on crude drugs,0.5%sodium metabisulfite was added,pH value was about 6.0,the temperature was about 45℃,and the time was 20 hours.The crude extract of scutellarein with the content more than 60%was obtained.The crude extract was purified by fractional crystallization,refluxed with 80%ethanol,decolorized with activated carbon,concentrated and crystallized,and the scutellarein extract with content more than 85%was obtained.Conclusion sbsl GUS enzymatic hydrolysis technology,which was used to prepare scutellarein,is simple and feasible.This study provides a new way for the manufacture of scutellarein.

Objective To investigate the changes in interleukin-34 (IL-34)levels in serum and bronchoalveolar lavage fluid (BALF) of patients with severe pneumonia and their prognostic value. Methods A total of 66 patients with severe pneumonia (severe pneumonia group), 35 patients with non-severe pneumonia (non-severe pneumonia group), and 27 healthy adults (control group) were enrolled. The severe pneumonia group was further divided into survival group of 38 patients and non-survival group of 28 patients based on 28-day survival. Clinical data of all subjects were analyzed. Receiver operating characteristic (ROC) curves were plotted to assess the predictive power of serum IL-34 and relative IL-34 gene expression in BALF for 28-day mortality in patients with severe pneumonia, as well as the predictive power of serum IL-34 for severe pneumonia. Kaplan-Meier survival curves were plotted, and the Log-rank test was used to compare cumulative survival rates. Cox regression analysis was conducted to explore risk factors for 28-day mortality in patients with severe pneumonia. Pearson correlation analysis was used to assess the correlation between serum IL-34 levels and relative IL-34 gene expression in BALF of patients with severe pneumonia. Results Serum IL-34 levels were higher in the severe pneumonia group than those in the non-severe pneumonia group, and were higher in the non-severe pneumonia group than in the control group (P < 0.05). Serum IL-34 levels and relative IL-34 gene expression in BALF were higher in the non-survival group than in the survival group (P < 0.05). ROC curve analysis showed that the areas under the curve for predicting 28-day mortality in patients with severe pneumonia were 0.908 for serum IL-34 levels and 0.878 for relative IL-34 gene expression in BALF. The optimal cutoff value for serum IL-34 levels in predicting severe pneumonia was 129.9 pg/mL. Multivariate Cox regression analysis showed that increased serum IL-34 levels and increased relative IL-34 gene expression in BALF were independent risk factors for 28-day mortality in patients with severe pneumonia (P < 0.05). The Kaplan-Meier survival analysis results indicate that, with a cutoff value of 129.9 pg/mL, patients with severe pneumonia who had high serum levels of IL-34 exhibited a lower cumulative survival rate compared to those with low IL-34 level(Log-rank P < 0.001). Conclusion Serum IL-34 levels are significantly increased in patients with severe pneumonia, and relative IL-34 gene expression in BALF is positively correlated with serum IL-34 levels. Both can be used as indicators for predicting the prognosis of 28-day mortality in patients with severe pneumonia.

Objective To observe the value of quality control system based on artificial intelligence(AI)for improving imaging quality of chest CT.Methods Totally 1 726 CT images obtained from 415 patients were retrospectively collected,among which 1 414 images were used for convolutional neural network(CNN)training and the rest 312 images were used for validation.Precision,Recall,F1-Score,mean average precision(mAP)and intersection over union(IOU)of quality control system based on AI for chest CT scanning were calculated.Meanwhile,21 patients with unsatisfactory chest CT who would undergo re-examination were prospectively enrolled,and chest CT scanning with quality control system based on AI were performed.The results of 2 examinations were compared.Results Precision,Recall,F1-Score,mAP and IOU of quality control system based on AI for chest CT were all good.All 21 cases were diagnosed correctly with re-examination CT based on quality control system.Among 21 cases,the first CT misdiagnosed 19 cases,the displaying of the area,volume and display quality of pulmonary nodules were not significantly different,but the morphology,boundaries,spiny protrusions,vacuolar signs,inflatable bronchial signs of nodules as well as the thickened and twisted blood vessels were obviously different between 2 times examination.The first CT missed 1 case while correctly diagnosed 1 case.Conclusion The quality control system based on AI was helpful for improving imaging quality of chest CT and increasing diagnostic efficacy.

Objective:To investigate the clinical value of left ventricular shape index (SI) and eccentricity index (EI) in evaluating left ventricular remodeling.Methods:A retrospective analysis was performed on 324 patients (264 males, 60 females, age (62.5±11.8) years) diagnosed with myocardial infarction (MI) and 113 healthy controls (HC; 47 males, 66 females, age (57.8±10.7) years) who received gated myocardial perfusion imaging (GMPI) in First Hospital of Shanxi Medical University from January 2016 to September 2020. SI (end-diastolic SI (EDSI), end-systolic SI (ESSI)), EI and left ventricular function parameters (end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular ejection fraction (LVEF), summed motion score (SMS), summed thickening score (STS), peak ejection rate (PER) and peak filling rate (PFR)) were obtained by quantitative gated SPECT (QGS) software. Propensity score (PS) inverse probability of treatment weighting (IPTW) was used to balance the intergroup covariates. The differences and correlations of EDSI, ESSI, EI and left ventricular function parameters between patients in MI group and HC group were analyzed. ROC curve analysis was used to evaluate the values of EDV, EDSI, ESSI and EI alone and in combination in the assessment of left ventricular systolic function impairment. Data were analyzed by independent-sample t test, Pearson correlation and Spearman rank correlation analyses, and Delong test. Results:After IPTW, EDSI and ESSI in MI group ( n=319) were higher than those in HC group ( n=133; EDSI: 0.66±0.09 vs 0.60±0.06; ESSI: 0.59±0.11 vs 0.47±0.07; t values: 8.05, 14.67, both P<0.001), and EI was lower than that in HC group (0.81±0.06 vs 0.85±0.03; t=-8.93, P<0.001). In both groups, there were significant correlations between EDSI and ESSI ( r values: 0.928, 0.873), between EDSI, ESSI and EI ( r values: from -0.831 to -0.641), between EDSI, ESSI and LVEF ( r values: from -0.627 to -0.201), between ESSI and EDV, ESV and SMS ( rs values: 0.336-0.584), between ESSI and -PER, PFR ( rs values: from -0.406 to -0.402, r values: from -0.352 to -0.325) (all P<0.01). ROC curve analysis showed that EDV (AUC: 0.895) and ESSI (AUC: 0.839) had the highest efficacy in evaluating left ventricular systolic function impairment in MI group and HC group, respectively. EDV-EDSI-ESSI-(1-EI) had higher efficacy in the assessment of impaired left ventricular systolic function in MI group (AUC: 0.956), which was higher than that of EDV or EDV-EDSI or EDV-ESSI or EDV-(1-EI) ( z values: from -2.64 to -2.18, P values: 0.008-0.029); EDV-EDSI-ESSI-(1-EI) also had high efficacy in HC group (AUC: 0.911), which was higher than that of EDV or EDV-EDSI or EDV-(1-EI) ( z values: from -2.60 to -2.43, P values: 0.009-0.015). Conclusions:In MI patients, the increase of SI and the decrease of EI indicate the increase of left ventricular sphericity and the aggravation of left ventricular remodeling. SI and EI have certain clinical application values in evaluating left ventricular morphology, predicting left ventricular remodeling and left ventricular systolic function impairment.

Objective:To establish an ICP-MS method for the determination of 10 elemental impurities in meglu-mine(APIs).Methods:The samples were processed by closed high-pressure microwave digestion,and the con-tents of the Class 1 elemental impurities arsenic(As),cadmium(Cd),mercury(Hg)and lead(Pb),the Class 2 A elemental impurities cobalt(Co),nickel(Ni)and vanadium(V),and the Class 3 elemental impurities lithium(Li),antimony(Sb)and copper(Cu)were detected by ICP-MS with total quantification.Results:The linear correlation coefficients(r)of each elemental impurity were greater than 0.997.The recoveries of the spiked samples ranged from 93.6％to 116.8％with RSD values of the recoveries lower than 7.4％.RSD values of the precision were lower than 5.4％.The content of nickel in 11 batches of the samples was lower than the permissible daily exposure(PDE)of the impurities of the elements of category 2A in the elemental guideline of ICH Q3D(R2)for oral use but higher than that of PDE of the impurities of category 2A for injection.Conclusion:The method is sensitive and precise enough to accurately determine the levels of Class 1,2A and 3 elemental impurities in meglumine.Nine batches of meglumine were found to have a high risk of nickel residue.

Objective: To investigate the relationship between health literacy and sports injuries among high school students with athletic specialization, so as to provide theoretical basis for the intervention of sports injury occurrence of sports special students. Methods: A total of 443 high school students with athletic specialization aged 16-18 years old from 21 urban and rural areas in Shangrao City, Ganzhou City and Nanchang City of Jiangxi Province were selected by convenient sampling method from March to April 2023, and the health literacy and sports injury incidence were investigated. The assessment of sports injury was based on the Monitoring Method of Child and Adolescent Injury, and the assessment of health literacy level was conducted using the Interactive Health Literacy Questionnaire of Chinese Adolescents. χ 2 test was used to compare the reported rate of sports injuries among the demographic and sports training groups and the correlation between health literacy and sports injuries. Binary Logistic regression analysis was used to infer the correlation between the health literacy level of high school students with athletic specialization and the occurrence of sports injuries. Results: The prevalence of sports injury was 49.4% in high school students with athletic specialization. Binary Logistic regression analysis showed that the risk of sports injury of high school students with athletic specialization with medium and low level of health literacy was significantly increased compared with high level (medium level: OR = 1.98,95% CI =1.12-3.51; low level: OR =2.08, 95% CI =1.18-3.68), high school students with athletic specialization in low level of health awareness of sports injury risk was higher than other dimensions of health literacy level (middle level: OR =2.77, 95% CI =1.48-5.19; low level: OR =2.01, 95% CI =1.04-3.88)( P <0.05). The results of stratified analysis showed that among male students with athletic specialization and students with track and field, students with moderate/low overall health literacy had a higher risk of sports injuries compared to high level students (male students: low level, OR =2.46, 95% CI =1.15-5.28; track and field: intermediate level, OR =2.17, 95% CI =1.06-4.43, low level, OR =2.09, 95% CI =1.02-4.30; P <0.05). Conclusions There is a correlation between the health literacy level of high school students with athletic specialization and the occurrence of sports injuries. Students health awareness should be improved to reduce the risk of sports injuries.

Abstract: Objective To investigate the prevalence of dissociative tendency and its influencing factors among middle school students, so as to provide insights into prevention and early interventions of adolescent dissociative tendency. Methods: Students at ages of 13 to 18 years that studied in 9 high schools were sampled using a multistage, stratified, cluster sampling method from 3 counties (districts) of Hangzhou City from January, 2021 and March, 2022. Participants' demographics and social, school, family environment and psychological factors were collected using self-designed questionnaires and standardized scales. The dissociative tendency was initially screened using the Adolescent Dissociative Experience Scale (A-DES), and the diagnosed by three psychiatrists according to Diagnostic and Statistical Manual of Mental Disorders (5th Edition). Factors affecting ADT were identified using a multivariable logistic regression model. Results: Totally 3 240 students were recruited, and 2 841 students were qualified, with a response rate of 87.69%. The respondents included 1 389 men (48.89%) and 1 452 women (51.11%), and had a mean age of (15.69±1.58) years. The prevalence of dissociative tendency was 24.04%, and the detection of dissociative tendency was higher among men than among women (29.23% vs. 19.08%; χ2=24.529, P<0.001). Multivariable logistic regression analysis identified negative teacher-student relationship (OR=1.055, 95%CI: 1.010-1.103), family emotional expressiveness (OR=0.872, 95%CI: 0.777-0.978), family conflict (OR=1.152, 95%CI: 1.045-1.271), family organization (OR=0.880, 95%CI: 0.780-0.992) and family cohesion (OR=0.871, 95%CI: 0.766-0.987) as factors affecting dissociative tendency among men, and somatization (OR=1.041, 95%CI: 1.002-1.082) and paranoid ideation (OR=1.094, 95%CI: 1.006-1.190) as factors affecting dissociative tendency among women. Conclusions The prevalence of dissociative tendency was 24.04% among middle school students. Negative teacher-student relationship, family emotional expressiveness, family conflict, family organization, and family cohesion may affect dissociative tendency among men, while somatization and paranoid ideation may affect dissociative tendency among women.

Objective:To prepare nanoprobes by using polydopamine (PDA) as a carrier which is modified with the sonosensitizer protoporphyrin Ⅸ (PpⅨ) and labeled with 131I, 99Tc m or 177Lu, and to explore the value of these new nanoprobes in diagnosis and combination therapy of breast cancer. Methods:PDA particles were synthesized by aqueous oxidation, and a layer of polyethylene glycol (PEG) and PpⅨ were modified on the surface to product PDA-PEG-PpⅨ. Then the nuclides 131I, 99Tc m and 177Lu were labeled on PDA, respectively, and the labeling yield and stability were determined. The cytotoxicity test was conducted by comparing the viabilities of 4T1 tumor cells in free 131I group and 131I-PDA-PEG-PpⅨ group. The 4T1 cells were divided into 7 groups according to different treatment methods: PDA-PEG-PpⅨ group, PDA-PEG-PpⅨ+ photothermal therapy (PTT) group, PDA-PEG-PpⅨ+ sonodynamic therapy (SDT) group, 131I-PDA-PEG-PpⅨ+ PTT group, 131I-PDA-PEG-PpⅨ+ SDT group, 131I-PDA-PEG-PpⅨ+ PTT+ SDT group (100 μg/ml PDA-PEG-PpⅨ, 925 kBq/ml 131I), and the control group (DMEM culture medium). The cell viabilities of those groups were compared to evaluate the therapeutic effect. 4T1 tumor bearing mouse models were established, then 99Tc m-PDA-PEG-PpⅨ was injected through the tail vein (29.6 MBq) or intratumorally (14.8 MBq) to perform gamma imaging. The independent-sample t test and one-way analysis of variance were used for data analysis. Results:The PDA particles were uniform in size, with a particle size of (160.0±1.5) nm. They had a good photothermal conversion effect. A characteristic peak consistent with PpⅨ (400 nm) appeared in the UV-Vis absorption spectrum of PDA-PEG-PpIX. In the cytotoxicity test, when the radioactivity was 1.850 or 3.700 or 7.400 MBq/ml, the cell viabilities of free 131I group and 131I-PDA-PEG-PpⅨ group were significantly different ((72.18±6.57)% vs (86.07±5.17)%, (59.31±9.06)% vs (80.85±4.21)%, (42.90±1.30)% vs (72.99±5.73)%; t values: 3.71, 4.82, 11.46, P values: 0.006, 0.001, <0.001). The 131I-PDA-PEG-PpⅨ+ PTT+ SDT combination therapy had a better killing effect on 4T1 tumor cells than the combination of 131I-PDA-PEG-PpⅨ+ PTT and 131I-PDA-PEG-PpⅨ+ SDT (cell viabilities: (10.09±2.50)% vs (16.04±2.63)%, (28.65±4.72)%; F=351.66, P<0.001). In vivo imaging showed that 99Tc m-PDA-PEG-PpⅨ was stable in mouse models and could be effectively enriched in tumors. Conclusions:A multifunctional nanoprobe based on PDA is successfully prepared. The radionuclide labeling method is simple and effective, with a good stability. 131I-PDA-PEG-PpⅨ can kill 4T1 cells efficiently. 99Tc m-PDA-PEG-PpⅨ has an obvious tumor concentration effect in mouse models.