Objective:To clarify the potential correlation between biological changes of meninges in periodontitis mice and cognitive impairment by analyzing the biological changes of meninges in periodontitis mice using single-cell RNA sequencing.Methods:Thirty C57BL/6 mice were divided into two groups by using random number table method (15 mice in each group). Mice in the control group were locally administered 2% carboxyl methyl cellulose (CMC) without Porphyromonas gingivalis (Pg) on both buccal sides. A mixture of Pg W83 and 2% CMC was applied on both buccal sides in the experimental group mice three times a week, lasting for 16 weeks in total. The absorption of alveolar bone, locomotor activity and cognitive function, the activation of microglia and astrocytes in the cortex were observed and assessed. The mRNA expression levels of Occludin in meninges and brain were detected in two groups. Single-cell RNA sequencing data of meninges were processed by uniform manifold approximation and projection (UMAP). Differential genes expressions of endothelial cells were processed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In addition, real-time fluorescence quantitative PCR (RT-qPCR) was used to verify the expressions of transcription activating factor 3 (Atf3) and apolpoprotein L domain-containing 1 (Apold 1). Results:Methylene blue staining found the distances of buccal and palatal cement-enamel junction-alveolar bone crest in experimental mice [(185.60±17.60), (206.90±13.37) μm] increased significantly compared with the control group [(135.33±9.57), (163.05±14.98) μm] ( t=5.02, P=0.002; t=4.37, P=0.005). Open field experiment showed the total distance and average speed of mice in the experimental group [(971.88±164.57) cm, (3.25±0.55) cm/s] were not statistically significant compared with the control group [(914.24±278.81) cm, (3.05±0.93) cm/s] ( t=0.65, P=0.525; t=0.65, P=0.520). The recognition index of the experimental group [(48.02±16.92) %] was lower than the control group [(66.27±17.90) %] ( t=2.40, P=0.027) by novel object recognition tests. Compared with the control group [(63.56±11.88) %], the alternation of experimental group [(50.99±14.17) %] was significantly decreased in Y maze tests ( t=2.33, P=0.030). Immunohistochemistry results showed microglia and astrocytes were activated in the cortex of experimental mice. Compared with the control group (1.02±0.25, 1.04±0.31), the relative mRNA expressions of Occludin decreased significantly in the meninges and brain of periodontitis mice, respectively (0.61±0.10, 0.64±0.20) ( t=3.47, P=0.010; t=2.66, P=0.024). By single-cell RNA sequencing, meninges cells were divided into 11 types, such as endothelial cells, fibroblasts, immune cells and so on. Endothelial cells were the main cell types in meninges [the control group: 26.47% (1 589/6 004), the experimental group: 26.26% (807/3 073)]. Compared with the control group [5.56% (334/6 004)], the percentage of granulocytes increased in the periodontitis mice [11.65% (358/3 073)]. Using clustering analysis to further focus on endothelial cells, GO enrichment analysis revealed differential genes were mainly related to angiogenesis, cell adhesion, apoptosis and so on. KEGG enrichment analysis revealed that differential genes were related to signaling pathways of interleukin-17, relaxin and so on. The relative mRNA expressions of Atf3 and Apold1 in meninges of periodontitis mice (0.42±0.24, 0.54±0.27) were significantly lower than the control group (1.03±0.26, 1.02±0.23) ( t=3.88, P=0.005; t=3.02, P=0.017). Conclusions:The mice chronically infected with Pg W83 occurred memory impairment, neuroinflammation and changes of barrier function. In the meninges of periodontitis mice, there were infiltration of immune cells and down-regulation expressions of Atf3 and Apold1 by single-cell RNA sequencing. Meningeal immunity and changes of barrier function may play an important role in the cognitive impairment caused by periodontitis.

Objective:To explore the effects of the scaffolding-based flipped classroom approach in the teaching of Infectious Disease Nursing. Methods:We assigned 152 students of nursing and midwifery majors of grade 2018 (experimental group) to be taught using the scaffolding-based flipped classroom approach and 182 students of grade 2017 (control group) to be taught using the traditional lecture method. Teaching effects were evaluated through students' exam performance and a questionnaire survey. Numerical data were analyzed using the χ2 test and t test with the use of SPSS 18.0, and text data were processed using NVivo 11 for thematic analysis. Results:The experimental group and control group showed significant differences in the interim exam score (83.19±7.96 vs. 79.62±3.14, P<0.001) and final exam score (78.47±6.92 vs. 73.16±8.24, P<0.001). The students of grade 2018 had a high level of participation in online learning. The questionnaire results showed that the scaffolding-based flipped classroom was well recognized in terms of students' overall perception, perceived course quality, perceived value of learning, and satisfaction and the open-ended question, with low scores for learner complaints and loyalty. Conclusions:The scaffolding-based flipped classroom is feasible in the teaching of Infectious Disease Nursing, which can improve students' academic performance and overall competence.

Objective:To investigate the clinicopathological characteristics of giant cell tumor of bone (GCTB) in children.Methods:A total of 35 cases of GCTB diagnosed at Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiaotong University School from 2016 to 2023 were collected, and a retrospective analysis of clinicopathological features and imaging findings was conducted.Results:Pediatric GCTB accounted for approximately 4.6% of total GCTB cases during the study period. There were 11 males and 24 females. The onset age ranged from 9 to 18 years (mean age 15 years, median age 16 years), with 8 cases (8/35, 22.9%) experiencing postoperative recurrence. Twenty-eight cases (28/35, 80%) primarily affected long bones, while 7 cases involved small or irregular bones. Imaging revealed osteolytic changes as the predominant feature, with 3 cases exhibited open physis, one of which had the tumor primarily at the diaphysis without crossing the physis. Histologically, pediatric GCTB resembled adult cases, characterized by mononuclear cells and osteoclast-like giant cells. Seven cases with denosumab treatment demonstrated degrees of giant cell disappearance, increased fibrous tissue and reactive bone proliferation in the stroma. One case was diagnosed as pediatric multicentric GCTB, and three cases as pediatric primary malignant GCTB, with malignant transformation into osteosarcoma. In all 35 cases, mutations in the H3F3A gene were identified, comprising 32 cases with H3.3 p.G34W mutations, one case with H3.3 p.G34V mutation, and 2 cases with H3.3 p.G34L mutations. Notably, the former two categories were successfully validated at the protein level through immunohistochemical staining, utilizing highly specific antibodies tailored for these mutation types: H3.3 p.G34W antibody and H3.3 p.G34V antibody. However, immunohistochemical staining was not available for the last category.Conclusions:Pediatric GCTB predominantly affects females and occurs primarily in long bones, mainly around the knee joint, the majority of tumors predominantly arise in the epiphysis and extend into the metaphysis; however, in cases where the epiphyseal plates are still unclosed, the tumors may be restricted to the metaphysis. Detection of H3F3A gene mutation is crucial for the diagnosis and differential diagnosis of pediatric GCTB.

Purpose To investigate the diagnostic value of postsystolic shortening in ischemia with non-obstructive coronary arteries(INOCA).Materials and Methods A total of 85 INOCA patients admitted to People's Hospital of Liaoning Province from May 2020 to December 2022 were selected and divided into two groups according to the ratio of distal diastolic average blood velocity of left anterior descending branch before and after treatment obtained by thymosidine load echocardiography(coronary flow velocity reserve,CFVR):CFVR<2.0 was in the coronary microvascular dysfunction(CMD)group(n=40),and CFVR≥2.0 was in the control group(n=45).Conventional echocardiographic parameters of all enrolled subjects were measured:left ventricular end-diastolic diameter index(LVEDDI),left ventricular end-diastolic volume index(LVEDVI),left ventricular end-systolic volume index(LVESVI),left ventricular ejection fraction(LVEF),early and late mitral valve diastolic blood flow velocity(E,A),E/A,average velocity of mitral valve annulus and interventricular septum in early diastolic(e')and E/e'on the wall and septal side were measured.The global longitudinal strain(GLS)and the post systolic index(PSI)of the left ventricle were measured by two-dimensional speckle tracking automated functional imaging.The differences of echocardiographic parameters,GLS and PSI between CMD group and control group were observed.The relationship between CFVR and PSI in CMD group was analyzed.Results There were no significant differences in LVEDDI,LVEDVI,LVESVI,LVEF,E,A,E/A,e',E/e'and GLS between control group and CMD group(t=-0.577-1.472,P>0.05).There was a statistically significant difference in PSI increase between CMD group and control group(t=-5.370,P<0.05).There was a good correlation between CFVR and PSI in CMD group(r=-0.486,P<0.05).The receiver operator characteristic curve showed that the area under the curve predicted by PSI for CMD was 0.786,the sensitivity was 68.0%,and the specificity was 77.8%.Conclusion PSI has good application value in evaluating left ventricular systolic function in INOCA patients,and can detect left ventricular systolic function injury in such patients at an early stage.

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment

Background Long-term occupational polycyclic aromatic hydrocarbons (PAHs) exposure is an important risk factor for cognitive impairment. At the same time, it can also cause a decrease of brain-derived neurotrophic factor (BDNF). However, it is not clear whether BDNF plays a key role in the cognitive impairment of workers caused by occupational PAHs exposure. Objective To analyze the correlation between the levels of PAHs in the plasma of coke oven workers and cognitive impairment, and to explore the possible mediating effect of plasma BDNF level on the relationship between PAHs and cognitive impairment. Methods A cross-sectional survey was carried out to select 138 pairs of workers from a coking plant (exposure group) and an energy plant (control group) in a large enterprise in Taiyuan, and the matching variables included age, education level and smoking status. The basic data of the workers were collected by questionnaire. The cognitive function of the workers was assessed by the Montreal Cognitive Assessment (MoCA) scale. Fasting elbow venous blood was collected, the plasma concentrations of 16 PAHs were determined by high performance gas chromatography-mass spectrometry (GC-MS), and the plasma concentration of BDNF was detected by enzyme-linked immunosorbent assay (ELISA). Multiple linear regression model was used to analyze the relationship between 12 PAHs levels in plasma and MoCA scores, and Bootstrap method was used to analyze the mediating effect of BDNF in the relationship between these two indicators. Results The average (\begin{document}$\bar x \pm s $\end{document}) age of workers in the two groups was (48.46±5.04) years, the length of service was (21.45±9.78) years, and 58.7% of the participants reported their education level at secondary vocational school, high school, and above. The median level (25th and 75th percentiles) [M(P₂₅, P₇₅)] of plasma Σ₁₂PAHs concentration of workers in the exposure group [20.937 (9.454, 38.387) μg·L⁻¹] was significantly higher than that of the control group [9.997 (4.952, 23.770)μg·L⁻¹] and the MoCA score (22.82±2.38) of the exposure group was significantly lower than that of the control group (24.60±5.67) (P<0.05). The plasma BDNF showed no significant difference between the exposure group [(29.99±9.80) μg·L⁻¹] and the control group [(31.48±9.09) μg·L⁻¹](P>0.05). Taking plasma PAHs as independent variable and MoCA score as dependent variable, after adjusting selected covariates, the results of multiple linear regression model showed that the MoCA score changed by −0.020 (95%CI: −0.035 - −0.005) for every 1 μg·L⁻¹ increase of plasma Σ₁₂PAHs. Low (<P₃₃), medium ( P₃₃~P₆₆) and high (>P₆₆) dummy variables were set according to the intertertile boundaries (8.31, 23.76) μg·L⁻¹ of the plasma level of Σ₁₂PAH of the workers. The change of MoCA score in the high concentration group versus the low concentration group was −1.167 (95%CI: −1.866 - −0.467). The MoCA score changed by 0.066 (95%CI: 0.012 - 0.119) for each 1 μg·L⁻¹ increase in plasma BDNF level. The results of dichotomous logistic regression analysis showed that the risk of cognitive impairment in the high concentration group was 2.635 (95% CI: 1.085 - 6.398) times higher than that in the low concentration group. The results of mediating effect analysis showed that plasma BDNF level was an intermediate variable between PAHs and cognitive impairment, and 45.50% of PAHs-induced cognitive impairment risk was mediated by reduced BDNF level. Conclusion The level of plasma PAHs in coke oven workers is negatively correlated with MoCA score, and PAHs may mediate cognitive impairment by reducing plasma BDNF level.

Background Although transforming growth factor-β (TGF-β)/Smad signaling pathway is important in regulating the occurrence and development of pulmonary fibrosis, the pathogenesis of pulmonary fibrosis remains elusive. Objective To explore the functions of genes associated with TGF-β/Smad signaling pathway in the progression of pulmonary fibrosis. Methods A NIH-3T3 fibroblast model induced by TGF-β1 was established. The experiment samples were divided into a control group and a TGF-β1 treatment group. The control group was exposed to normal saline, while the TGF-β1 treatment group was exposed to 10 ng·mL⁻¹ TGF-β1 for 12 h. The RNAs of the two groups were extracted, sequenced, and analyzed by bioinformatics methods to identify seven key genes in TGF-β pathway, including Dcn, Smad3, Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3. The gene expression levels of five markers [Collagen1α1, Collagen1α2, α-smooth muscle actin (α-SMA), TGF-β1, and TGF-β3] and the seven key genes were detected by quantitative real-time PCR (qRT-PCR). The proteins of the two groups were extracted. The important marker protein expression levels of Smad3, the phosphorylation of Smad3 (P-Smad3), and α-SMA were detected by Western blotting. At the same time, 30 healthy SPF-grade C57BL/6 mice were randomly divided into three groups, with 10 mice in each group: a control group, a SiO₂ inhalation exposure group for 28 d (10 mice), and a SiO₂ inhalation exposure group for 56 d (10 mice). The mice in the two treatment groups were exposed to a natural SiO₂ environment for 4 h per day with a 10-min pause for breathing fresh air at 2 h intervals. The lung tissues of the mice were taken after execution. The changes of pulmonary fibrosis were detected by Masson staining, and mRNAs and proteins were extracted to detect the expression of the above key genes and proteins. Results The expression levels of the five marker genes Collagen1α1, Collagen1α2, α-SMA, TGF-β1, and TGF-β3 were significantly increased in the TGF-β1-induced NIH-3T3 fibroblasts than those in the control group (P < 0.01); the expression levels of P-Smad3 and α-SMA proteins increased significantly (P < 0.01); the expression results of the seven key genes screened in the TGF pathway were that Dcn and Smad3 were obviously down-regulated (P < 0.01), and Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3 were obviously up-regulated (P < 0.01). The changes in gene expression levels of the transcriptome sequencing showed the same trend. The results of Masson staining showed that the content of collagen fibers in the lung tissues also increased in the SiO₂ inhalation exposure groups over time. In the mouse experiment, five marker genes were obviously up-regulated compared with the control group (P < 0.01); no obvious change was found in the expression of Smad3 protein, and the expression levels of P-Smad3 and α-SMA were obviously higher in the SiO₂ exposure groups than those in the control group (P < 0.01); the expression levels of Dcn and Smad3 showed a down-regulated trend, while the expression levels of Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3 showed an up-regulated trend with the increase of SiO₂ inhalation exposure days (P < 0.01). The expression levels of the above five marker genes, three important marker proteins, and seven key genes were consistent with the expression trends of TGF-β1-induced NIH-3T3 fibroblasts. Conclusion The expression levels of pulmonary fibrosis-related marker genes and proteins change significantly in TGF-β1-induced fibroblast cells, and the lung tissues of mice under natural SiO₂ inhalation exposure has obvious fibrosis characteristics. Seven genes (Dcn, Smad3, Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3) may be involved in the regulation of pulmonary fibrosis by the TGF-β/Smad signaling pathway.

This paper discusses from two aspects of case writing and PBL implementation experience. PBL cases should be based on professional requirements and reflect professional characteristics. Health inspection and quarantine cases targeted at application-oriented talent cultivation can be integrated into relevant experimental skills items. At the same time, the forms of case writing are expanded according to the differences of theme forms, which are designed as parallel cases and serial cases, so as to be applicable to the curriculum integration in different areas. In the implementation of PBL teaching, students' learning status is the key to the efficiency of classroom discussion, which determines whether the implementation of PBL is completely autonomous learning or embedded instruction. Teachers should establish cooperative learning atmosphere to improve the efficiency of classroom discussion

Transport monitoring is an important link in the transport process of radioactive materials, involving the whole process, that is, before departure, during transportation and after arrival. To do well in transport monitoring, radiation monitoring organizations need to actively participate in the work, and also need to do a good job in the supervision of radioactive materials transport monitoring. Beijing is one of the radioactive materials distribution centers in China, the monitoring workload is large, the number of monitoring reports is large, the number of packages by air transportation is relatively large, and the transportation and monitoring for medical use is dominant. Through the introduction of radioactive materials transportation monitoring work, and analysis of 2006—2020 radioactive materials transportation monitoring situation, this paper discusses the problems that need to be paid attention to in the monitoring work and the ways to deal with them, so as to provide ideas for radiation monitoring organizations to carry out monitoring work and manage the transport of radioactive materials well.

Objective:To investigate the changes of dynamic functional connectivity between the default mode network (DMN) and executive control network (ECN) in the resting state in patients with alcohol use disorder (AUD).Methods:From September 2018 to June 2019, 23 cases of AUD group and 24 cases of healthy control (HC) group matched with age, gender, education level and handedness were collected at Renmin Hospital of Wuhan University. Mini-mental state examination (MMSE) and Michigan alcoholism screening test (MAST) were performed in all subjects for cognition and alcohol dependence score. All the subjects underwent T 1WI-3D structural imaging and resting state functional MRI (rs-fMRI) examination. Group spatial independent component analysis (ICA) was used to select the independent components of DMN and ECN. Then dynamic changes in the functional connectivity between the DMN and the DMN were obtained by sliding window approach and clustering method. Finally, the independent sample t test was used to compare the difference of general clinical data between the two groups, the linear correlation analysis was conducted in the parameter value and MMSE and MAST scores. Results:Compared with the HC group, the static functional connectivity analysis showed that the precuneus and posterior cingulate gyrus of the DMN were enhanced in the AUD group ( P=0.016, t=2.496). The DMN and ECN functional connectivity showed four different brain activity states, the proportion of state1 increased by 6.81% and state2 decreased by 6.83% in the AUD group, state3 and state4 were relatively stable. In state1, the internal functional connectivity of the DMN in the AUD group was enhanced, while the functional connectivity between DMN and ECN was mainly enhanced. In state2, the internal functional connectivity of the ECN was enhanced, and the connectivity between the DMN and ECN was mainly weakened. The mean dwell of state2 in the AUD group was negatively correlated with the MAST score ( r=-0.433, P=0.039). Conclusions:Dynamic functional connectivity patterns between DMN and ECN have been changed in patients with AUD. Dynamic functional connectivity can reveal transient changes in brain activity, which can provide certain imaging evidence for finding changes in AUD deep brain activity.