This study aims to explore the effects and mechanisms of 4'-O-methylbavachalcone(MeBavaC), an active compound from Psoraleae Fructus, in regulating white matter neuroinflammation to improve vascular cognitive impairment. Male Sprague-Dawley(SD) rats were randomly divided into four groups: sham group, model group, high-dose MeBavaC group(14 mg·kg~(-1)), and low-dose MeBavaC group(7 mg·kg~(-1)). The rat model of chronic cerebral hypoperfusion(CCH) was established using bilateral common carotid artery occlusion. The Morris water maze test was performed to evaluate the learning and memory abilities of the rats. Luxol fast blue staining, Nissl staining, immunofluorescence, immunohistochemistry, and transmission electron microscopy were utilized to observe the morphology and ultrastructure of the white matter myelin sheaths, axon integrity, the morphology and number of hippocampal neurons, and the loss and activation of glial cells in the white matter. Transcriptome analysis was performed to explore the potential mechanisms of white matter injury induced by CCH. Western blot and quantitative real-time polymerase chain reaction(qRT-PCR) assays were conducted to measure the expression levels of NOD-like receptor protein 3(NLRP3), absent in melanoma 2(AIM2), gasdermin D(GSDMD), cysteinyl aspartate-specific proteinase-1(caspase-1), interleukin-18(IL-18), interleukin-1β(IL-1β), erythropoietin(EPO), nuclear factor erythroid 2-related factor 2(Nrf2), and heme oxygenase-1(HO-1) in the white matter of rats. The results showed that compared with the model group, MeBavaC significantly improved the learning and memory abilities of rats with CCH, improved the damage of white matter myelin sheath, maintained axonal integrity, reduced the loss of hippocampal neurons and oligodendrocytes in the white matter, inhibited the activation of microglia and the proliferation of astrocytes in the white matter, and suppressed the NLRP3/AIM2/caspase-1/GSDMD pathway. The expression levels of inflammatory cytokines IL-1β and IL-18 were significantly reduced, while EPO expression and the expression of Nrf2/HO-1 antioxidant pathway were notably elevated. In conclusion, MeBavaC can alleviate cognitive impairment in rats with CCH and suppress neuroinflammation in cerebral white matter. The mechanism of action may involve activation of EPO activity, promotion of endogenous antioxidant pathways, and inhibition of neuroinflammation in the white matter. This study suggests that MeBavaC exhibits antioxidant and anti-neuroinflammatory effects, showing potential application in improving cognitive dysfunction.
Animals ; Male ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/immunology* ; Rats ; Chalcones/administration & dosage* ; Cognitive Dysfunction/metabolism* ; Signal Transduction/drug effects* ; Neuroinflammatory Diseases/drug therapy* ; Heme Oxygenase-1/metabolism* ; Humans ; Heme Oxygenase (Decyclizing)/genetics*

OBJECTIVES: To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students. METHODS: This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia. RESULTS: The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081). CONCLUSIONS Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans ; Myopia/etiology* ; Male ; Female ; Depression/physiopathology* ; Cross-Sectional Studies ; Sleep ; Adolescent ; Students ; Child ; Time Factors ; Sleep Duration

Objective To analyze the latent categories of traditional Chinese medicine(TCM)constitution of college students,and to explore the moderating effects of latent categories of TCM constitution on the the associations between self-efficacy and depression-anxiety symptoms.Methods An investigation was carried out in two universities of Guangdong Province with 30-item TCM constitution scale,General Self-Efficacy Scale(GSES)and Kessler Psychological Distress Scale,and then a total of 1 097 valid samples were obtained.Correlation analysis,latent profile analysis,and hierarchical regression analysis were used for statistical analysis.Results(1)Four latent categories of TCM constitution were obtained in the college students:generally-balanced type(32.0%),highly-balanced type(17.4%),generally-biased type(36.9%)and highly-biased type(13.7%).There were statistically significant differences in the subscale scores of TCM constitution scale among the college students with various latent categories of TCM constitution(all P＜0.001).(2)Hierarchical regression analysis showed that the self-efficacy negatively predicted the symptoms of depression and anxiety(β value being-0.268,-0.161 respectively,P＜0.001);with the generally-balanced type as reference,the generally-biased type and the highly-biased type positively predicted the symptoms of depression and anxiety,and the highly-balanced type negatively predicted the symptoms of depression and anxiety(all P＜0.001).(3)The latent categories of TCM constitution had moderating effects on the self-efficacy and depression-anxiety symptoms:the depression-anxiety symptoms were relieved with the increase of self-efficacy in the college students with the TCM constitution being generally-biased type,highly-biased type and generally-balanced type(all P＜0.01);in the college students with highly-balanced type,the symptoms of depression(β=0.005,P=0.907)and anxiety(β=0.007,P=0.878)did not change with the increase of self-efficacy.Conclusion Obvious heterogeneity of TCM constitution is presented in the population of college students.The measures of enhancement of self-efficacy and the correction of TCM to promote the psychological health of college students should be performed with reference to the characteristics of their TCM constitution types.

Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

Objective To study the in vitro expression of three phenylalanine hydroxylase(PAH)mutants(p.R243Q,p.R241C,and p.Y356X)and determine their pathogenicity.Methods Bioinformatics techniques were used to predict the impact of PAH mutants on the structure and function of PAH protein.Corresponding mutant plasmids of PAH were constructed and expressed in HEK293T cells.Quantitative reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the three PAH mutants,and their protein levels were assessed using Western blot and enzyme-linked immunosorbent assay.Results Bioinformatics analysis predicted that all three mutants were pathogenic.The mRNA expression levels of the p.R243Q and p.R241C mutants in HEK293T cells were similar to the mRNA expression level of the wild-type control(P>0.05),while the mRNA expression level of the p.Y356X mutant significantly decreased(P<0.05).The PAH protein expression levels of all three mutants were significantly reduced compared to the wild-type control(P<0.05).The extracellular concentration of PAH protein was reduced in the p.R241C and p.Y356X mutants compared to the wild-type control(P<0.05),while there was no significant difference between the p.R243Q mutant and the wild type control(P>0.05).Conclusions p.R243Q,p.R241C and p.Y356X mutants lead to reduced expression levels of PAH protein in eukaryotic cells,with p.R241C and p.Y356X mutants also affecting the function of PAH protein.These three PAH mutants are to be pathogenic.[Chinese Journal of Contemporary Pediatrics,2024,26(2):188-193]

The purpose of this study was to investigate the epidemiological characteristics and risk factors of influenza in Hainan province,to provide evidence to support influenza prevention and control efforts.Pathogen monitoring data of influenza-like illness(ILI)in six national sentinel hospitals in Hainan province from 2013 to 2021 were analyzed in SPSS 20.0 software.A total of 50 415 ILI cases were detected during the 2013-2021 season,of which 5 581 were positive for influenza viruses,with a positivity rate of 11.07％.The dominant strains were type B,type A(H1N1)pdm09 and type A(H3N2).The positivi-ty rate of influenza virus was highest in people 5-14 years of age(17.56％)and lowest in people 0-4 years of age(7.32％).Influenza activity showed both a summer peak and a winter-spring peak in the 2014-2016,2017-2018 and 2019-2020 sea-sons,and was concentrated in April to September,with a maximum peak of 53.64％,and in November to March of the next year,with a peak of 47.30％.The 2013-2014,2016-2017 and 2018-2019 seasons showed only a winter-spring peak concen-trated between October and March of the next year,with a maximum peak of 54.17％,but no obvious summer peak.The pre-dominant influenza viruses during the eight surveillance seasons varied among H1N1,H3N2 and type B.The positive detection rate of influenza virus steeply declined during the 2020-2021 season:the positive detection rate was only 0.25％,and no obvi-ous epidemic period was observed.The intensity of influenza epidemic varied among monitoring years,and the dominant strains changed rapidly in Hainan Province.People 5-14 years of age were the key population affected.Summer,winter and spring were the key periods for influenza prevention and control.Etiological surveillance of influenza should continue to be strength-ened,the roles of health education and publicity should be emphasized,and the dual measures of influenza vaccination and non-drug intervention should be actively promoted to decrease the occurrence of influenza.

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines

Aim To clarify the anti-rheumatoid arthritis effect of Tibetan medicine Pulicaria insignis (P. insignis),sift out the active parts against rheumatoid arthritis,and investigate the mechanism. Methods Rat rheumatoid arthritis (CIA) model was established with bovine type II collagen and incomplete Freund's adjuvant. The effects of the total extract of P. insignis, macroporous resin eluted parts with different concentrations of ethanol and Tripterygium Glycosides (GTW) on the degree of foot swelling in CIA rats were observed,the levels of tumor necrosis factor (TNF-α), intd rheumaerleukin-1β (IL-1β) antoid factor (RF) in serum of rats were detected, the pathological changes of synovial tissues were investigated, and the effects on MAPK/p38/NF-κB, TLR4/NF-κB protein expressions were explored by Western blot. Results Compared with the model group, the total extract of P. insignis and the eluted part of macroporous resin 60% ethanol could significantly reduce the degree of joint swelling in CIA rats, effectively improve the pathological changes of rats synovium tissues, and significantly reduce the levels of rat tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and rheumatoid factor (RF) in serum inflammatory factors, and markedly decrease the expression of related inflammatory proteins (TLR4, NF-κB, Myd88, p-p38, p-IκBα, iNOS, etc) in synovial tissue. Conclusions (1) P. insignis can relieve the symptoms of joint inflammation in rats with rheumatoid arthritis, and the eluted part of macroporous resin 60% ethanol of P. insignis is the effective active part for anti-rheumatoid arthritis. (2) The total and partial extracts of P. insignis can relieve arthritis symptoms in CIA rats through inhibiting the MAPK/ p38/NF-κB and TLR4/NF-κB signaling pathways.

This paper aims to explore the activity of Codonopsis canescens extract against rheumatoid arthritis(RA) based on the Toll-like receptors(TLRs)/mitogen-activated protein kinases(MAPKs)/nuclear factor kappa B(NF-κB) signaling pathways and its mechanism. The ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of C. canescens extract. Forty-eight male SD rats were randomly divided into six groups, namely the normal group, the model group, the methotrexate(MTX) tablet group, and the low, medium, and high-dose C. canescens extract(ZDS-L, ZDS-M, and ZDS-H) groups, with 8 rats in each group. The model of collagen-induced arthritis in rats was induced by injection of bovine type Ⅱ collagen emulsion. MTX(2.5 mg·kg~(-1)), ZDS-L, ZDS-M, and ZDS-H(0.3 g·kg~(-1), 0.6 g·kg~(-1), and 1.2 g·kg~(-1)) were administrated by gavage. Rats in the normal group and the model group received distilled water. MTX was given once every three days for 28 days, and the rest medicines were given once daily for 28 days. Body weight, degree of foot swelling, arthritis index, immune organ index, synovial histopathological changes, and serum levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6) were observed. Protein expressions of TLR2, TLR4, NF-κB p65, p38 MAPK, and p-p38 MAPK in rats were determined by Western blot. Thirty-four main components were identified by UPLC-Q-TOF-MS, including 15 flavonoids, 7 phenylpropanoids, 4 terpenoids, 4 organic acids, 2 esters, and 2 polyalkynes. As compared with the normal group, the body weight of the model group was significantly decreased(P<0.01), and foot swelling(P<0.05, P<0.01), arthritis index(P<0.01), and the immune organ index(P<0.01) were significantly increased. The synovial histopathological injury was obviously observed in the model group. The serum levels of inflammatory factors TNF-α, IL-1β, and IL-6 were significantly increased(P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK in the synovial tissue were significantly increased(P<0.01) in the model group. As compared with the model group, the body weights of the ZDS dose groups were increased(P<0.01), and the degree of foot swelling(P<0.01) and the arthritis index were decreased(P<0.05, P<0.01). The immune organ index was decreased(P<0.01) in the ZDS dose groups, and the synovial tissue hyperplasia and inflammatory cell infiltration were alleviated. The serum levels of TNF-α, IL-1β, and IL-6 were significantly decreased(P<0.05, P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK were decreased(P<0.05, P<0.01) in the ZDS dose groups. C. canescens extract containing apigenin, tricin, chlorogenic acid, aesculin, ferulic acid, caffeic acid, and oleanolic acid has a good anti-RA effect, and the mechanism may be related to the inhibition of TLRs/MAPKs/NF-κB signaling pathways.
Animals ; Cattle ; Male ; Rats ; Arthritis, Experimental/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Body Weight ; Codonopsis/chemistry* ; Interleukin-6/blood* ; NF-kappa B/genetics* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Plant Extracts/therapeutic use* ; Rats, Sprague-Dawley ; Signal Transduction ; Toll-Like Receptor 2/metabolism* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/pharmacology*

The "student-centered" flipped classroom teaching model can improve students' academic achievement, improve cognition, and cultivate innovation ability. However, it has obvious deficiencies in the integrity and systematization of knowledge as well as education. The traditional teaching concept based on " teacher-centered" has the unique advantages of systematization of knowledge learning and education. Therefore, we integrated the merits of these two different teaching models and introduced the semi-flipped classroom teaching model into the Biochemistry teaching of 2020 stomatology, pharmacy and preventive medicine majors in Cheeloo Medical College, Shandong University, compared with the traditional teaching of 2019 same majors. The data on the improvement of students ' academic achievement and self-cognition were analyzed. The results showed that the students' achievements of the semi-flipped classroom teaching model were better than those of the traditional teaching (P<0. 01). The students' self-cognitions were significantly improved after the implementation of semi-flipped classroom teaching (P<0. 01 or P<0. 05). This study provides a reference for the related teaching and research work in medical colleges.