1.Molecular Crosstalk Mechanisms of Shoutai Wan and Juyuan Jian on Maternal-fetal Interface Subcellular Clusters in CBA/J×DBA/2 Recurrent Pregnancy Loss Model
Jingxin GAO ; Qiuping CHEN ; Xiaoyan ZHENG ; Pengfei ZENG ; Rui ZHOU ; Yancai TANG ; Qian ZENG ; Wenli GUO ; Jinzhu HUANG ; Weijun DING ; Linwen DENG ; Hang ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):70-87
ObjectiveTo systematically compare the differential regulation of the maternal-fetal interface cell lineages and communication networks in the CBA/J×DBA/2 mouse model of recurrent pregnancy loss (RPL) by the two classic therapeutic methods-tonifying the kidney to stabilize the fetus and invigorating the spleen to stabilize the fetus (Shoutai Wan, Juyuan Jian)-of traditional Chinese medicine (TCM) at the single-cell resolution and clarify their modern scientific connotations. MethodsFemale non-pregnant CBA/J mice were caged with male BALB/c (blank group) and DBA/2 (modeling group) mice separately. Pregnant mice in the modeling group were randomly grouped as follows: high/low-dose Shoutai Wan, high/low-dose Juyuan Jian, model (RPL), and positive control (dydrogesterone), with 10 mice in each group. Starting from the day after the detection of the vaginal plug, mice were administrated with drugs or an equal volume of normal saline by gavage for 10 consecutive days. After the intervention, the following indicators were measured. ① Macroscopic evaluation: general conditions, uterine wet weight, embryo loss rate, four coagulation parameters [prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and thrombin time (TT)], and peripheral blood estradiol (E2) and progesterone (Pg) levels. The decidua with embryos was stained with hematoxylin-eosin (HE) and evaluated by transmission electron microscopy (TEM). The expression of B-cell lymphoma-2 (Bcl-2), vascular endothelial growth factor (VEGF), angiotensin Ⅱ (AngⅡ), matrix metalloproteinase-2 (MMP-2), interleukin-6 (IL-6), leukemia inhibitory factor (LIF), CXC chemokine ligand 12 (CXCL12), and microtubule-associated protein 1 light chain 3 homolog (LC3)Ⅰ/Ⅱ was quantified by Western blot. ② Mechanism analysis at the single-cell level: The decidua with embryos from the blank, model, high-dose Shoutai Wan, and high-dose Juyuan Jian groups (6 mice per group, with 3 single-cell samples per group, totaling 24 mice) were analyzed by the BD Rhapsody™ platform, and the whole-cell atlas was drawn by uniform manifold approximation and projection (UMAP) dimensionality reduction clustering combined with the single-cell mouse cell atlas (scMCA). The differentially expressed genes (DEGs) and cell interaction networks were analyzed via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and CellChat, and the protein-protein interaction (PPI) map of subtype cells was constructed. The CytoTRACE pseudo-temporal analysis was performed to explore the developmental trajectories of core immune cells (natural killer cells, NK cells) from maternal and fetal sources. Results① Pathological and Western blot results indicated that compared with the blank group, the RPL group showed an increase in the embryo loss rate (P<0.01), down-regulated expression of Bcl-2, LIF, MMP-2, and Vegf in the decidua with embryos (P<0.05), up-regulated protein levels of CXCL-12, AngⅡ, and IL-6 (P<0.05), blocked angiogenesis, apoptosis-inflammation imbalance, and coagulation dysfunction. Both prescriptions dose-dependently reduced the abortion rate and restored the angiogenesis-inflammation balance, and Shoutai pill showed superior performance in restoring the E2 level to the Pg level (P<0.05). ② Single-cell transcriptome analysis indicated that compared with the blank group, the RPL group showed differences in multiple key cell populations such as decidual cells, trophoblast cells, endothelial cells, erythroblasts, NK cells, and macrophages at the maternal-fetal interface. Immunity and angiogenesis were the key links in RPL. Compared with the RPL group, high-dose Shoutai Wan reversed the changes of NK cells in the embryonic layer (upregulating the mRNA levels of 17 genes and downregulating the mRNA levels of 29 genes) and macrophages (upregulating the mRNA levels of 117 genes and downregulating the mRNA levels of 53 genes) through the regulation of gene expression. High-dose Shoutai pill regulated the immune cells to affect unfolded proteins, cell adhesion, and programmed cell death, thereby promoting decidualization and angiogenesis and modulating embryo-membrane development. High-dose Juyuan Jian regulated the key subgroups of NK cells (up-regulating the mRNA levels of 9 genes and down-regulating the mRNA levels of 17 genes) and macrophages (up-regulating the mRNA levels of 110 genes and down-regulating the mRNA levels of 81 genes), which affected decidual inflammation and apoptosis and intervened in glycolysis. ③ The pseudo-temporal analysis and communication network indicated that the communication frequency of the RPL group decreased. High-dose Shoutai Wan restored maternal-fetal tolerance through pathways such as NKG2D, CDH5, GDF, and FASLG. High-dose Juyuan Jian enhanced the IL-6/LIFR/JAK/signal transducer and activator of transcription 3 (STAT3) and desmosome/SEMA6/tumor necrosis factor-like weak inducer of apoptosis (TWEAK) signaling to improve endometrial receptivity. The RPL group showed an increased proportion of toxic dNK7, a decreased proportion of reparative dNK4, and blocked embryo fNK1. High-dose Shoutai Wan down-regulated dNK7 and up-regulated dNK4. High-dose Juyuan Jian inhibited the terminal differentiation of dNK7 and up-regulated LILRB1, thus restoring the balance of cytotoxicity and repair. ConclusionBoth the kidney-tonifying and spleen-invigorating methods are effective in treating RPL. NK and macrophages are the key immune cells in the interaction between the embryo and the membrane. The kidney-tonifying method (Shoutai Wan) has an advantage in regulating the phenotypes of unfolded protein, cell adhesion, and programmed cell death, and shows expression characteristics closer to the physiological state in the regulation of NKG2D and CDH5 signals. The spleen-invigorating method (Juyuan Jian) has an advantage in regulating epithelial-mesenchymal transition (EMT), angiogenesis, and glycolysis and shows higher communication intensity in the IL-6 and LIFR pathways.
2.Association Between Vitamin D Status and Insulin Resistance in Adolescents: A Cross-sectional Observational Study
Xiaoyuan GUO ; Yutong WANG ; Zhibo ZHOU ; Shi CHEN ; Mei ZHANG ; Bo BAN ; Ping LI ; Xinran ZHANG ; Qiuping ZHANG ; Kai YANG ; Hongbo YANG ; Hanze DU ; Hui PAN
Medical Journal of Peking Union Medical College Hospital 2025;16(3):577-583
To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents. This cross-sectional observational study employed convenience sampling to recruit 2021-grade(8th grade) students from Jining No.7 Middle School in Shandong Province on June 5, 2023. Data collection included questionnaires, physical examinations, and imaging assessments to obtain general information, secondary sexual characteristics development, and bone age. Venous blood samples were collected to measure fasting blood glucose(FBG), fasting insulin(FINS), homeostasis model assessment of insulin resistance(HOMA-IR), and 25-hydroxyvitamin D[25(OH)D] levels. Spearman correlation analysis and multivariate linear regression models were used to examine the associations between serum vitamin D levels and FBG, FINS, and HOMA-IR. The study included 168 pubertal adolescents[69 females(41.1%), 99 males(58.9%); mean age(13.27±0.46) years]. All participants had entered puberty based on sexual development assessment. Vitamin D deficiency was observed in 41 participants(24.4%), insufficiency in 109(64.9%), and sufficiency in 18(10.7%). The median HOMA-IR was 3.49(2.57, 5.14).Significant differences were found across vitamin D status groups for HOMA-IR [4.45(2.54, 6.62) Vitamin D deficiency/insufficiency is prevalent among pubertal adolescents, and serum vitamin D levels show a significant inverse association with insulin resistance. These findings suggest the potential importance of vitamin D status in metabolic health during puberty.
3.Exploration of the "Wisdom-Transmission-Modeling-Linkage" Intelligent Inheritance Model for the Academic Thoughts and Clinical Experience of Famous Chinese Medicine Practitioners
Qiuping CHEN ; Hang ZHOU ; Ju CHEN ; Chongcheng XI ; Baixue LI ; Quansheng FENG
Journal of Traditional Chinese Medicine 2025;66(14):1419-1423
As traditional Chinese medicine (TCM) culture evolves, the academic thoughts of these practitioners, being a core component of TCM inheritance, are gradually shifting from traditional models to digital and intelligent approaches. However, this process faces challenges, including insufficient standardization of data collection and processing, low inheritance efficiency, and the risk of inheritance alienation. To address these issues, this paper proposed the construction of an intelligent platform following the "intelligence-transmission-modeling-linkage" path. "Intelligence" involves using smart perception technologies to accurately collect and classify diagnostic and therapeutic information from famous TCM practitioners, laying the foundation for digital inheritance; "transmission" focuses on leveraging artificial intelligence to mine and inherit the clinical experience of famous TCM practitioners, thereby establishing a "regional academic schools+group commonality" dynamic inheritance system; "modeling" integrates the academic thoughts and advantageous diseases of multiple schools to develop intelligent diagnostic and therapeutic models of famous TCM practitioners, resulting in personalized treatment plans; "linkage" involves constructing a clinical decision support system of famous TCM practitioners by integrating blockchain and generative intelligence, creating an AI digital avatar of TCM diagnostic and therapeutic knowledge. The "intelligence-transmission-modeling-linkage" intelligent inheritance model not only provides new ideas for the digital inheritance of TCM academic schools, but also offers strong support for the modernization and internationalization of TCM.
4.Research on the anti-inflammatory effects of a novel sleep-aid decoction on elderly insomnia patients across traditional Chinese medicine constitutional types.
Zhen WU ; Zhuoqiong BIAN ; Ailin CHEN ; Qiuping ZHANG ; Jie LI ; Hui ZHOU ; Hongying ZHU
Chinese Journal of Cellular and Molecular Immunology 2025;41(11):1007-1012
Objective To evaluate the clinical efficacy of a novel sleep-aid decoction in treating elderly insomnia patients with different traditional Chinese medicine (TCM) constitutional types, and its effects on neurotransmitter and inflammatory factor levels. Methods A total of 200 patients with four different TCM constitutions-peaceful, Qi-deficient, Yin-deficient, and Yang-deficient-were recruited. Peripheral blood neurotransmitter and inflammatory factor levels were measured for variations among insomnia patients across different constitutions. These patients were treated using the novel sleep-aid decoction, the effects of which were evaluated based on changes in neurotransmitters and inflammatory factors. Results Compared to the peaceful constitution group, insomnia patients with Qi-deficient, Yin-deficient, and Yang-deficient constitutions exhibited significantly elevated baseline levels of neurotransmitters (5-HT, GABA) and inflammatory factors (IL-6, TNF-α, IL-1β, CRP). Following the treatment, the Qi-deficient and Yin-deficient groups showed a marked increase in 5-HT levels, restored balance of Glu, GABA, and melatonin, and significant reductions in IL-6 and TNF-α levels. The overall effective rate was 83.5%, with optimal efficacy observed in the Qi-deficient (97.72%) and Yin-deficient (95.34%) groups. Conclusion The novel sleep-aid decoction is effective in treating insomnia in elderly patients, with the best results observed in the Qi-deficient and Yin-deficient constitution groups.
Humans
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Sleep Initiation and Maintenance Disorders/blood*
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Aged
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Male
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Female
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Drugs, Chinese Herbal/therapeutic use*
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Medicine, Chinese Traditional
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Middle Aged
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Tumor Necrosis Factor-alpha/blood*
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Sleep Aids, Pharmaceutical/therapeutic use*
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Anti-Inflammatory Agents/therapeutic use*
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Interleukin-6/blood*
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Interleukin-1beta/blood*
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Neurotransmitter Agents/blood*
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Aged, 80 and over
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C-Reactive Protein/metabolism*
5.Comparison of initiation of antihypertensive therapy strategies for primary preven-tion of cardiovascular diseases in Chinese population:A decision-analytic Markov modelling study
Tianjing ZHOU ; Qiuping LIU ; Minglu ZHANG ; Xiaofei LIU ; Jiali KANG ; Peng SHEN ; Hongbo LIN ; Xun TANG ; Pei GAO
Journal of Peking University(Health Sciences) 2024;56(3):441-447
Objective:To evaluate the health benefits and intervention efficiency of different strategies of initiating antihypertensive therapy for the primary prevention of cardiovascular diseases in a community-based Chinese population from the Chinese electronic health records research in Yinzhou(CHERRY)study.Methods:A decision-analytic Markov model was used to simulate and compare different antihy-pertensive initiation strategies,including:Strategy 1,initiation of antihypertensive therapy for Chinese adults with systolic blood pressure(SBP)≥140 mmHg(2020 Chinese guideline on the primary preven-tion of cardiovascular diseases);Strategy 2,initiation of antihypertensive therapy for Chinese adults with SBP≥130 mmHg;Strategy 3,initiation of antihypertensive therapy for Chinese adults with SBP ≥140 mmHg,or with SBP between 130 and 140 mmHg and at high risk of cardiovascular diseases(2017 American College of Cardiology/American Heart Association guideline for the prevention,detection,evaluation,and management of high blood pressure in adults);Strategy 4,initiation of antihypertensive therapy for Chinese adults with SBP≥ 160 mmHg,or with SBP between 140 and 160 mmHg and at high risk of car-diovascular diseases(2019 United Kingdom National Institute for Health and Care Excellence guideline for the hypertension in adults:Diagnosis and management).The high 10-year cardiovascular risk was de-fined as the predicted risk over 10%based on the 2019 World Health Organization cardiovascular disease risk charts.Different strategies were simulated by the Markov model for ten years(cycles),with parame-ters mainly from the CHERRY study or published literature.After ten cycles of simulation,the numbers of quality-adjusted life years(QALY),cardiovascular events and all-cause deaths were calculated to evaluate the health benefits of each strategy,and the numbers needed to treat(NNT)for each cardiovas-cular event or all-cause death could be prevented were calculated to assess the intervention efficiency.One-way sensitivity analysis on the uncertainty of incidence rates of cardiovascular disease and probabilis-tic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted.Results:A to-tal of 213 987 Chinese adults aged 35-79 years without cardiovascular diseases were included.Com-pared with strategy 1,the number of cardiovascular events that could be prevented in strategy 2 increased by 666(95%UI:334-975),while the NNT per cardiovascular event prevented increased by 10(95%UI:7-20).In contrast to strategy 1,the number of cardiovascular events that could be prevented in strategy 3 increased by 388(95%UI:194-569),and the NNT per cardiovascular event prevented decreased by 6(95%UI:4-12),suggesting that strategy 3 had better health benefits and intervention efficiency.Compared to strategy 1,although the number of cardiovascular events that could be prevented decreased by 193(95%UI:98-281)in strategy 4,the NNT per cardiovascular event prevented decreased by 18(95%UI:13-37)with better efficiency.The results were consistent in the sensitivity analyses.Conclusion:When initiating antihypertensive therapy in an economically developed area of China,the strategy combined with cardiovascular risk assessment is more efficient than those purely based on the SBP threshold.The cardiovascular risk assessment strategy with different SBP thresholds is suggested to balance health benefits and intervention efficiency in diverse populations.
6.Automatic assessment of root numbers of vertical mandibular third molar using a deep learning model based on attention mechanism
Chunsheng SUN ; Xiubin DAI ; Manting ZHOU ; Qiuping JING ; Chi ZHANG ; Shengjun YANG ; Dongmiao WANG
STOMATOLOGY 2024;44(11):831-836
Objective To develop a deep learning network based on attention mechanism to identify the number of the vertical man-dibular third molar(MTM)roots(single or double)on panoramic radiographs in an automatic way.Methods The sample consisted of 1 045 patients with 1 642 MTMs on paired panoramic radiographs and Cone-beam computed tomography(CBCT)and were randomly grouped into the training(80%),the validation(10%),and the test(10%).The evaluation of CBCT was defined as the ground truth.A deep learning network based on attention mechanism,which was named as RN-MTMnet,was trained to judge if the MTM on pano-ramic radiographs had one or two roots.Diagnostic performance was evaluated by accuracy,sensitivity,specificity,and positive predict value(PPV),and the receiver operating characteristic(ROC)curve with the area under the ROC curve(AUC).Its diagnostic perform-ance was compared with dentists'diagnosis,Faster-RCNN,CenterNet,and SSD using evaluation metrics.Results On CBCT images,single-rooted MTM was observed on 336(20.46%)sides,while two-rooted MTM was 1 306(79.54%).The RN-MTMnet achieved an accuracy of 0.888,a sensitivity of 0.885,a specificity of 0.903,a PPV of 0.976,and the AUC value of 0.90.Conclusion RN-MTM-net is developed as a novel,robust and accurate method for detecting the numberof MTM roots on panoramic radiographs.
7.Neonatal leukemoid reaction: clinical analysis of 36 cases
Zhenhui ZHOU ; Qiuping LI ; Li DONG ; Shaodong HUA
Chinese Journal of Neonatology 2023;38(4):230-233
Objective:To study the clinical characteristics of neonatal leukemoid reaction (NLR).Methods:The newborns with NLR admitted to the neonatal intensive care unit of the Seventh Medical Center of PLA General Hospital from September 2010 to January 2022 were selected as the observation group, and the newborns without NLR, who were admitted to the Hospital at the same time and matched with gestational age and birth weight of the NLR newborns were selected as the control group at a ratio of 1∶2. The gestational age, birth weight, maternal complications, maximum leukocyte count, percentage of neutrophils, C-reactive protein, hemoglobin, platelet count, disease diagnosis and other relevant information of the newborns were recorded, and SPSS 21.0 statistical software was applied to compare the data of the two groups of newborns.Results:A total of 36 cases were in the observation group and 72 cases in the control group. Naive granulocytes were found in the peripheral blood of all patients in the observation group, and leukocyte count was higher than that of the control group [61.7 (54.2, 90.6)×10 9/L vs. 19.6 (14.2,27.3)×10 9/L], the difference was statistically significant ( P<0.001), but there was no statistically significant difference in the percentage of neutrophils, hemoglobin, platelets, and C-reactive protein between the two groups ( P>0.05). The proportion of vaginal delivery, meconium-stained amniotic fluid, and neonatal sepsis in the observation group were higher than that in the control group [69.4% (25/36) vs. 38.9% (28/72), 19.4% (7/36) vs. 5.6% (4/72), 47.2% (17/36) vs. 8.3% (6/72)], and the proportion of gestational diabetes mellitus, gestational hypertension and prenatal use of glucocorticoid was lower than that in the control group, with statistical significance ( P<0.05). There was no significant difference in the incidence of premature rupture of membranes, neonatal asphyxia, intracranial hemorrhage, pulmonary hemorrhage, bacterial meningitis, and bronchopulmonary dysplasia between the two groups ( P>0.05). Conclusions:Newborns with NLR are frequently complicated with sepsis. Early prevention and treatment of maternal comorbidities and active control of infection are important for the prevention and treatment of NLR.
8.Correlation between hemodynamic characteristics or dynamic cerebral autoregulation and postoperative hyperperfusion in patients undergoing carotid endarterectomy
Na LI ; Fubo ZHOU ; Xia LU ; Qiuping LI ; Hongxiu CHEN ; Yue ZHAO ; Yingqi XING
Chinese Journal of Ultrasonography 2023;32(2):105-110
Objective:To investigate the hemodynamic characteristics and dynamic cerebral autoregulation(dCA) of patients with severe carotid stenosis before carotid endarterectomy(CEA), and to analyze their correlations with hyperperfusion after CEA.Methods:A total of 63 patients with unilateral severe carotid artery atherosclerotic stenosis who underwent CEA were consecutively recruited prospectively in Xuanwu Hospital, Capital Medical University from January 2021 to August 2021. According to postoperative hyperperfusion, patients were divided into hyperperfusion group (13 cases) and non-hyperperfusion group (50 cases). The general clinical data and hemodynamic parameters were compared between the two groups. The dCA was evaluated by the transfer function analysis that measured the fluctuation amplitude of mean cerebral blood flow velocity(CBFV) with blood pressure change, the time difference of phase with blood pressure change, and the correlation between mean CBFV and blood pressure change. The value of dCA for predicting postoperative hyperperfusion was analyzed through the ROC curve and the area under the curve(AUC).Results:①The proportion of hypertension in hyperperfusion group was higher than that in non-hyperperfusion group ( P<0.05). ②The peak systolic velocity (PSV) at the stenosis lesion of the internal carotid artery, the end-diastolic velocity (EDV) at the stenosis lesion of the internal carotid artery and the ratio of PSV at the stenosis lesion of the internal carotid artery to the distal internal carotid artery in the hyperperfusion group were higher than the non-hyperperfusion group.And the PSV of the ipsilateral middle cerebral artery in the hyperperfusion group was lower than the non-hyperperfusion group (all P<0.05). ③In the very low-frequency and low-frequency region, the phase in the hyperperfusion group was lower than that in the non-hyperperfusion group (all P<0.05), while there was no significant difference in the high-frequency regions( P>0.05). In the three regions of very low-frequency, low-frequency and high-frequency, there were no significant differences in the gain and coherence between the two groups(all P>0.05). ④The best cutoff value of phase in the very low-frequency was 33.28 for predicting hyperperfusion after CEA (AUC=0.766, 95% CI=0.629-0.904, P=0.03), with the specificity of 0.700, and sensitivity of 0.846. Conclusions:There are differences in hemodynamics and dCA between the hyperperfusion group and the non-hyperperfusion group after CEA. The impaired preoperative dynamic cerebral autoregulation is an independent predictor of postoperative hyperperfusion.
9.Intake of liquid dairy products among the fourth grade studentsin Nanjing City
Chenchen WANG ; Aihua FU ; Qiuping JIA ; Hairong ZHOU ; Weiwei WANG ; Xin HONG
Journal of Preventive Medicine 2022;34(2):142-146
Objective:
To investigate the intake of liquid dairy products and identify its influencing factors among the fourth grade students in Nanjing City.
Methods:
The fourth grade students were selected as the study subjects in Nanjing City using a multi-stage random cluster sampling method in September 2020. Their general information, frequency of liquid dairy product intake one week prior to survey and mean intake amount per time were collected. According to the 2016 Dietary Guidelines for Chinese Residents, weekly intake of liquid dairy products of 2 100 g and greater was defined eligible. Factors affecting the frequency and amount of liquid dairy product intake were identified using multivariable logistic regression analysis.
Results:
A total of 2 268 questionnaires were allocated and 2 216 valid questionnaires were recovered, with an effective recovery rate of 97.71%. The respondents included 1 199 boys ( 54.11% ) and 1 017 girls ( 45.89% ). The frequency of liquid dairy product intake was (6.41±4.86) times per week, and the median intake amount was 1 250.00 g per week (interquartile range, 1 750.00 g per week). There were 607 students ( 27.39% ) consuming liquid dairy products of 2 100 g and greater a week, and 1 016 students ( 45.85% ) consumed liquid dairy products for 7 times and more a week. Multivariable logistic regression analysis showed that living in urban areas ( OR=1.204, 95%CI: 1.005-1.443 ), knowing nutrition labels ( OR=1.221, 95%CI: 1.021-1.460 ), periodical measurement of body weight (OR=1.486, 95%CI: 1.098-2.011) and restricted intake of sugar-containing drinks ( OR=1.264, 95%CI: 1.005-1.590 ) facilitated the intake of liquid dairy products for 7 times and more a week, and students with periodical measurement of body weight were more likely to consume liquid dairy products for 2 100 g and greater a week ( OR=1.821, 95%CI: 1.240-2.676 ).
Conclusions
Inadequate intake of liquid dairy products is found among the fourth grade students in Nanjing City. Residence, awareness of nutrition labels, periodical measurement of body weight, and parental restriction of sugar-containing drink intake affect the intake of liquid dairy products.
10.Melatonin inhibits astrocyte activation in periventricular white matter via NF-κB pathway
Shuqi JIANG ; Qiuping ZHOU ; Huifang WANG ; Qian LI ; Nan LIU ; Yiyu DENG
Chinese Journal of Emergency Medicine 2021;30(2):173-178
Objective:To investigate the effect of melatonin (MEL) influence on lipopolysaccharide (LPS)-induced long-term anxiety-like behavior and activation of astrocytes in septic neonatal rats.Methods:Sprague-Dawley rats were randomly(random number) assigned to the control group, LPS group and LPS+MEL group. Sepsis model was intraperitoneally injected with LPS (1 mg/kg), and neonatal rats in the MEL group were administered with MEL (10 mg/kg) 30 min after LPS injection. At different time points after injection, rats in each group were divided into three subgroups: 3 d, 7 d and 28 d. The expression of GFAP and TNF-α in the corpus callosum was detected by immunofluorescence staining and Western blot. Open-field test was applied to observe anxiety-like behaviors. In vitro, cultured neonatal SD rat astrocytes were divided into the control group, LPS group, LPS+MEL group, and LPS+MEL+luzindole group. Immunofluorescence staining was used to observe the expression of GFAP and TNF-α. Expression of GFAP, TNF-α, p-NF-κBp65, NF-κBp65 protein in astrocytes were assessed by Western blot. RT-qPCR was used to investigate the mRNA expression of GDNF and BDNF. One-way ANOVA and two-way ANOVA were used for comparison of multiple groups of variables. A P<0.05 was considered statistically significant. Results:LPS reduced the duration of movement in the central area and distance in the central area/total distance in open-field test, while melatonin evidently reversed the LPS-induced anxiety-like behavior. Compared with the LPS group, the expressions of GFAP and TNF-α were significantly decreased in the corpus callosum at 3 d and 7 d in the MEL group ( P< 0.05). Compared with the LPS group, MEL could significantly decrease the expression of GFAP, TNF-α and p-NF-κBp65 in astrocytes ( P< 0.05), which could be blocked by Luzindole. In addition, compared with the LPS group, MEL pretreatment could reverse the down regulation of GDNF and BDNF induced by LPS ( P<0.05). Conclusions:MEL can relieve LPS-induced long-term anxiety-like behavior in septic neonatal rats. The mechanism may be related to the inhibition of astrocyte activation and inflammatory reaction through NF - κ B pathway.


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