OBJECTIVES: To investigate the role of activating transcription factor 3 (ATF3) in atherosclerotic plaques for regulating inflammatory responses during atherosclerosis (AS) progression. METHODS: Human coronary artery specimens from autopsy cases were examined for ATF3 protein expression and localization using immunofluorescence staining and Western blotting. Apolipoprotein E-deficient (ApoE^-/-) mouse models of AS induced by high-fat diet (HFD) feeding for 12 weeks were subjected to tail vein injection of adeno-associated virus serotype 9 (AAV9) to knock down ATF3 expression. After an additional 5 weeks of HFD feeding, the mice were euthanized for analyzing structural changes of the aortic plaques, and the expression levels of ATF3, inflammatory factors (CD45, CD68, IL-1β, and TNF-α), and NF-κB pathway proteins (P-IKKα/β and P-NF-κB p65) were detected. In the cell experiment, THP-1-derived foam cells were transfected with an ATF3-overexpressing plasmid or an ATF3-specific siRNA to validate the relationship between ATF3 and NF‑κB signaling. RESULTS: In human atherosclerotic plaques, ATF3 expression was significantly elevated and partially co-localized with CD68. ATF3 knockout in ApoE^-/- mice significantly increased aortic plaque volume, upregulated the inflammatory factors, enhanced phosphorylation of the NF‑κB pathway proteins, and increased the expressions of VCAM1, MMP9, and MMP2 in the plaques. In THP-1-derived foam cells, ATF3 silencing caused activation of the NF‑κB pathway, while ATF3 overexpression suppressed the activity of the NF-κB pathway. CONCLUSIONS AS promotes ATF3 expression, and ATF3 deficiency exacerbates AS progression by enhancing plaque inflammation via activating the NF-κB pathway, suggesting the potential of ATF3 as a therapeutic target for AS.
Animals ; Activating Transcription Factor 3/metabolism* ; Signal Transduction ; NF-kappa B/metabolism* ; Humans ; Mice ; Plaque, Atherosclerotic/metabolism* ; Inflammation/metabolism* ; Apolipoproteins E ; Atherosclerosis/metabolism* ; Diet, High-Fat

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Objective:To investigate the effect of serine/arginine-rich splicing factor 2 (SRSF2) on ferroptosis and its possible mechanism in glioblastoma cells.Methods:The online database of gene expression profiling interactive analysis 2 (GEPIA 2) and Chinese Glioma Genome Atlas were used to analyze the expression of SRSF2 in glioblastoma tissue and its association with patients prognosis. To validate the findings of the online databases, the pathological sections of glioblastoma and non-tumor brain tissues from Tianjin Medical University General Hospital, Tianjin, China were collected and analyzed by using immunohistochemistry. Silencing SRSF2 gene expression in glioblastoma cells by siRNA was analyzed with Western blot. The proliferation index was detected by using CCK8 assay. The rescued experiment was conducted by using expression plasmid of pcDNA3.1(+)-SRSF2. The activity of ferroptosis was assessed by using the levels of iron ions and malondialdehyde in glioblastoma cells and the changes in the ratio of glutathione to oxidized glutathione. The changes of gene expression and differential pre-mRNA alternative splicing (PMAS) induced by SRSF2 were monitored by using the third-generation sequencing technology analysis, namely Oxford nanopore technologies (ONT) sequencing analysis.Results:SRSF2 expression was higher in glioblastoma tissues than non-tumor brain tissues. Immunohistochemistry also showed a positive rate of 88.48%±4.60% in glioblastoma tissue which was much higher than the 9.97%±4.57% in non-tumor brain tissue. The expression of SRSF2 was inversely correlated with overall and disease-free disease survivals ( P<0.01). The proliferation index of glioblastoma cells was significantly reduced by silencing with SRSF2 siRNA ( P<0.01) and could be reversed with transfection of exogenous SRSF2. The levels of intracellulariron ions and malondialdehyde increased ( P<0.05), but the glutathione/oxidized glutathione ratio and the expression of key proteins in the glutathione pathway remained unchanged ( P>0.05). ONT sequencing results showed that silencing SRSF2 in glioblastoma cells could induce a significant alternative 3' splice site change on ferroptosis suppressor protein 1 (FSP1). Conclusion:SRSF2 inhibits the ferroptosis in glioblastoma cells and promotes their proliferation, which may be achieved by regulating FSP1 PMAS.

Objective To analyze the influencing factors of ovulation induction therapy in patients with polycystic ovary syndrome (PCOS), and to construct a predictive model for the efficacy of ovulation induction therapy in PCOS patients. Methods A total of 200 infertile PCOS patients suitable for ovulation induction therapy were selected as the study subjects.All patients underwent ovulation induction with letrozole or letrozole combined with urinary gonadotropins. They were divided into effective group (n=160) and ineffective group (n=40) based on the efficacy of ovulation induction. The clinical data of the two groups were retrospectively collected and analyzed. Logistic regression analysis was used to analyze the influencing factors of ovulation induction therapy in PCOS patients, and a nomogram prediction model for the efficacy of ovulation induction was constructed. The predictive performance of the nomogram model for ovulation induction therapy in PCOS patients was evaluated. Results The number of ovulations and mature follicles, proportion of ovulation patients and endometrial thickness in the effective group were significantly higher, and the androgen level in the effective group was significantly lower than that in the ineffective group (P<0.05). Logistic regression analysis showed that androgen level, ovulation count, the number of mature follicles and endometrial thickness were influencing factors for the efficacy of ovulation induction in PCOS patients (OR<1, P<0.05). Receiver operating characteristic (ROC) curve analysis revealed that the area under the curve (AUC) values for ovulation count, the number of mature follicles, endometrial thickness and androgen level in assessing the efficacy of ovulation induction therapy in PCOS patients were greater than 0.60. The verification results of the nomogram prediction model showed that the consistency index value of the calibration curve was 0.984. Conclusions Androgen level, ovulation count, the number of mature follicles and endometrial thickness areinfluencing factors for the efficacy of ovulation induction therapy in PCOS patients. The evaluation performance of the nomogram prediction model based on the above factors is good.

Background Osteoclast stimulatory transmembrane protein (OC-STAMP) is involved in silicosis fibrosis induced by silicon oxide (SiO₂) exposure. Its role in silicosis fibrosis by inducing ferroptosis of alveolar type II epithelial cells and its related mechanism remain unclear. Objective To explore the effect and possible mechanism of OC-STAMP on ferroptosis of alveolar type II epithelial cells and silicosis fibrosis in rats under SiO₂ exposure. Methods Twenty male Wistar rats of SPF grade were randomly divided into two groups: control (Sham) group and SiO₂ group, 15 rats in each group. Rats in the SiO₂ group were given 1 mL of 50 mg·L⁻¹ SiO₂ suspension at one time through the non-exposed intratracheal instillation method to establish an animal model of silicosis, and rats in the Sham group were give 1 mL of 0.9% sodium chloride solution in the same way. Rats were sacrificed after 8 weeks. Samples of lung tissue were fixed in glutaraldehyde or paraformaldehyde for observing ultrastructure of mitochondria by transmission electron microscopy; HE, Masson, VG, and Prussian blue were used to observe changes in lung tissue structure and iron deposition. The expression level of OC-STAMP and the degree of lung fibrosis were evaluated by immunohistochemistry and immunofluorescence. The expression level of OC-STAMP in rat lung tissue was detected and the transfection effect of OC-STAMP was verified by real-time fluorescence quantitative polymerase chain reaction (RT-PCR). Overexpression (OCS group) and inhibition expression (SI-OC group) models were constructed by OC-STAMP plasmid and OC-STAMP small interfering RNA (siRNA) transfection to cultured MLE-12 cells, respectively. The relative expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and other proteins in lung tissue and MLE-12 were detected by Western blotting. Results The results of HE, Masson, and VG staining showed that the silicosis modeling was successful after 8 weeks of SiO₂ exposure. The immunofluorescence results showed that OC-STAMP and ATP binding cassette subfamily A member 3 (ABCA3) co-localized in alveolar type II epithelium. The immunohistochemical results showed that the levels of OC-STAMP and collagen I in the SiO₂ group were significantly higher than those in the Sham group (P<0.01). The RT-PCR results showed that the OC-STAMP mRNA in the lung tissue of the SiO₂ group was significantly higher than that of the Sham group (P<0.01). The Prussian blue staining in the lung tissue of the SiO₂ group showed positive brownish-yellow particles. Compared with the Sham group which showed normal mitochondrial structure, the mitochondrial structure was generally swollen and the mitochondrial cristae dissolved and disappeared in the SiO₂ group by transmission electron microscope observation. The Western blotting results showed that the expression levels of SLC7A11 and GPX4 both decreased in the lung tissue of the SiO₂ group (P<0.05, P<0.01), and the expression level of Vimentin increased (P<0.01). In the transfected MLE-12 cells, compared with the Sham group, the expression levels of SLC7A11 and GPX4 in the OCS group were significantly reduced (P<0.05, P<0.01). Conclusion OC-STAMP may affect the expression of proteins related to ferroptosis, and promote lung fibrosis induced by SiO₂ exposure.

Objective:To study the epidemic characteristics of human brucellosis in Shandan County, Zhangye City, Gansu Province, and provide reference basis for formulating effective prevention and control measures.Methods:The surveillance data of brucellosis were collected from the China Disease Prevention and Control Information System and Shandan Center for Disease Control and Prevention to describe the three-compartment distribution (population, time, region distribution), and were analyzed by SPSS 19.0.Results:A total of 482 cases of brucellosis were reported with an average annual incidence of 48.99/100 000 from 2016 to 2021 in Shandan County, and farmers were the mainly occupation (84.85%, 409/482). The sex ratio of men and women was 3.16 ∶ 1.00 (366/116). The onset time was mainly concentrated in summer and autumn. Breeding cattle and sheep (feeding, cleaning pens, etc.) resulted in 107 cases of direct contact infection, accounting for 22.20% of the total cases (107/482). Incidence rate of different years was quite different (χ 2 = 121.09, P < 0.001). The average annual incidence rate of brucellosis in Laojun Township (95.72/100 000) was statistically different from that in other towns (χ 2 = 20.49, P < 0.001). Conclusions:The overall high prevalence of human brucellosis in Shandan County from 2016 to 2021. The animal husbandry department should strengthen the control of infectious sources, and the health department should increase publicity and education to curb the spread of the epidemic as soon as possible.

Objective To investigate the age-related changes of biomechanical properties for humerus, femur and tibia in male rats and their application values in age estimation. Methods According to different weeks of age, 90 healthy male SD rats were divided into 2, 4, 6, 8, 17, 26, 52, 78 and 104-week groups with 10 rats in eachgroup. After the rats were executed by excessive anesthesia, humerus, femur, and tibia were separated and the attached soft tissues were removed. The length of the above-mentioned bones and the diameter of the middle section (compression site) were measured with vernier caliper, and the three-point bending test was conducted with electronic universal material testing machine to detect the ultimate load and displacement under ultimate load. Results There were significant differences in the ultimate load of humerus, femur and tibia among male rats in different age groups (P<0. 05). With the increase of week age, the ultimate loads of the humerus, femur and tibia increased first and then decreased, and reached the peak value in 52-week age group, showing a strong positive correlation with week age before 52 weeks ( r = 0. 884,0. 933,0. 929, P<0. 05). There was no significant difference in humerus and tibia. The displacement of femur under ultimate load was weakly positively correlated with week age (R= 0. 406,P<0. 05). The age prediction accuracy for automatic linear modeling of ultimate load for humerus, femur, tibia and three above-mentioned bones in rats before 52-week age was 78. 2% , 86. 8% , 84. 1% and 88. 3% , respectively. There was a strong positive correlation between the length of humerus, femur and tibia and the ultimate load (R= 0. 904, 0. 897, 0. 814, P<0. 05). The diameters of humerus, femur and tibia were strongly positively correlated with the ultimate load (R = 0. 759, 0. 814 and 0. 745, P<0. 05). Conclusions The ultimate loads of humerus, femur and tibia in male rats increased first and then decreased with age, and were positively correlated with age before 52 weeks, which could be used for age inference. The highest accuracy of age estimation was ultimate loads of three bones, followed by femur. The length/ middle diameter of humerus, femur and tibia were strongly positively correlated with the ultimate load.

Pear is one of the main fruits with thousands of years of cultivation history in China. There are more than 2000 varieties of pear cultivars around the world, including more than 1200 varieties or cultivars in China (Legrand et al., 2016). Xinjiang Uygur Autonomous Region is an important pear production region in China with 30 of varieties or cultivars. Pyrus sinkiangensis is the most popular variety, which is mainly distributed in Xinjiang (Zhou et al., 2018). Chlorogenic acid (CGA), p-coumaric acid, and arbutin are the main polyphenols in pear fruit, and their levels show great differences among different varieties (Li et al., 2014). CGA is a potential chemo-preventive agent, which possesses many important bioactivities including antioxidant, diabetes attenuating, and anti-obesity (Wang et al., 2021). Therefore, the specific CGA content of a variety is considered the embodiment of the functional nutritional value of pears.
Chlorogenic Acid ; Fruit ; Gene Expression Profiling ; Pyrus/genetics* ; Transcriptome

Based on the characteristics of forensic pathology, this paper explains the concept, connotation and advantages of holistic medicine and integrated medicine in the teaching of forensic pathology. Then, through the introduction of the specific teaching process design and effect analysis of the death cause analysis practical cases, it clarifies the necessity and effectiveness of integrated medicine and holistic medicine in the teaching of forensic pathology, and provides new ideas for the reform of the overall teaching of forensic pathology.

Objective:To explore the application value of scenario simulation teaching combined with two-way evaluation in standardized training of pediatric nursing.Methods:A total of 34 trainees who received standardized training of pediatric nursing in The First Affiliated Hospital of Air Force Medical University from March 2018 to March 2019 were selected as the control group, and another 42 trainees from April 2019 to July 2020 were selected as the study group. The control group used traditional teaching, and the study group used scenario simulation teaching combined with two-way evaluation. Theoretical examination and scenario simulation exercise examination were used to assess the theoretical knowledge and clinical practice ability of the trainees, and questionnaire survey was used to evaluate the satisfaction of the trainees with the teaching effect. SPSS 22.0 was used for t-test. Results:The scores of theoretical examination[(95.12±6.24) vs. (91.05±5.12)] and scenario simulation exercise examination (nursing practice skill operation ability, ability to combine theory and practice, clinical thinking and judgment ability, emergency handling ability, communication ability, humanistic care and professional learning ability, and work attitude) of the trainees in the study group were higher than those in the control group, and the differences were statistically significant ( P<0.05). The satisfaction evaluation of the trainees in the study group with the teaching effect was higher than that in the control group, and the difference was statistically significant ( P<0.001). Conclusion:Scenario simulation teaching combined with two-way evaluation can improve the theoretical knowledge, clinical practice ability, and teaching satisfaction of pediatric nursing trainees.