1.The Nucleus Accumbens CRH-CRHR1 System Mediates Early-Life Stress-Induced Sleep Disturbance and Dendritic Atrophy in the Adult Mouse.
Ting WANG ; Yu-Nu MA ; Chen-Chen ZHANG ; Xiao LIU ; Ya-Xin SUN ; Hong-Li WANG ; Han WANG ; Yu-Heng ZHONG ; Yun-Ai SU ; Ji-Tao LI ; Tian-Mei SI
Neuroscience Bulletin 2023;39(1):41-56
Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood, one of which is sleep disturbance. As the corticotropin-releasing hormone (CRH)-corticotropin-releasing hormone receptor 1 (CRHR1) system and nucleus accumbens (NAc) play important roles in both stress responses and sleep-wake regulation, in this study we investigated whether the NAc CRH-CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice. Using the limited nesting and bedding material paradigm from postnatal days 2 to 9, we found that early-life stress disrupted sleep-wake behaviors during adulthood, including increased wakefulness and decreased non-rapid eye movement (NREM) sleep time during the dark period and increased rapid eye movement (REM) sleep time during the light period. The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure. Importantly, Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology, whereas NAc Crhr1 knockdown reversed these effects (including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy). Together, our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc, and highlight the critical role of the NAc CRH-CRHR1 system in modulating these negative outcomes evoked by early-life stress.
Animals
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Mice
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Corticotropin-Releasing Hormone/metabolism*
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Nucleus Accumbens/metabolism*
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Receptors, Corticotropin-Releasing Hormone/metabolism*
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Sleep
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Sleep Wake Disorders
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Stress, Psychological/complications*
2.Therapeutic effect of anti-IL-12/IL-23 p40 on experimental autoimmune uveitis and its mechanism
Xuexue CUI ; Zhihui ZHANG ; Lingzi WU ; Yongtao LI ; Shuang CHEN ; Nu CHEN ; Xiaomin ZHANG
Chinese Journal of Experimental Ophthalmology 2022;40(8):707-715
Objective:To explore the therapeutic effect of anti-interleukin (IL)-12/IL-23 p40 antibody on experimental autoimmune uveitis (EAU) and its mechanism.Methods:Sixty-six SPF female C57BL/6N mice aged 6-8 weeks were selected.EAU model was established in 24 mice through immunization with the interphotoreceptor retinoid-binding protein (IRBP) 651-670.The 24 mice were sacrificed before immunization, and on the 3rd, 12th, and 18th day after immunization, with 6 at each time point.Flow cytometry was used to detect the proportion of IL-17A + interferon-γ (IFN-γ) + CD4 + T cells in the spleen, lymph nodes and eyeballs.Another 6 mice were selected to establish EAU model, and fundus images of the mice were taken with a small animal imaging instrument and optical coherence tomography (OCT) 18 days after immunization.The 6 mice were sacrificed after OCT examination and the eyeballs were collected.Hematoxylin-eosin staining was used to observe the retinal inflammation and morphological changes in tissue structure.Flow cytometry was employed to detect the proportion of IL-17A + IFN-γ + CD4 + T cells in lymph nodes.The 6 mice were divided into IL-17A + IFN-γ + highly expressed group and IL-17A + IFN-γ + lowly expressed group according to flow cytometry results, and the retinal injury was compared between the two groups.EAU model was established in another 36 mice, which were divided into anti-IL-12/IL-23 p40 group and IgG group by random number table method, with 18 mice in each group.Anti-IL-12/IL-23 p40 or IgG was injected by tail vein at a 3-day inteval according to grouping.On the 12th and 18th day after immunization, 6 mice were selected from each group to collect lymph nodes and eyeballs, and the proportion of T cell subsets was detected by flow cytometry.Eyeballs of 6 mice in each group were extracted on the 24th day after immunization and retinal damage was observed by hematoxylin-eosin staining.The induced differentiation of CD4 + T cells in vitro was assayed by flow cytometry.The expressions of IL-17 and IFN-γ were detected by enzyme-linked immunosorbent assay (ELISA) after induced differentiation of IL-17A + IFN-γ + CD4 + T cells.The relative expression levels of Th1 transcription factor T-bet and Th17 transcription factor retinoid acid-related orphan nuclear receptor γt (ROR-γt) after induced differentiation of IL-17A + IFN-γ + CD4 + T cells were detected by real-time quantitative PCR.The use and care of animals followed the ARVO statement and this study protocol was approved by an Ethics Committee of Experimental Animals of Tianjin Medical University Eye Hospital (No.TJYY2019111019). Results:There were significant differences in the proportion of IL-17A + IFN-γ + CD4 + T cells in lymph nodes, spleen and eyeballs between wild-type mice and EAU mice at the 3rd, 12th and 18th day after immunization ( H=9.642, 16.531, 10.385; all at P<0.05). Compared with before immunization, the proportion of IL-17A + IFN-γ + CD4 + T cells was significantly increased in lymph nodes of EAU mice on the 12th day following immunization and was significantly increased in spleen and lymph nodes on day 18 after immunization (all at P<0.05). Severe retinal exudation, retinal detachment, severe inflammatory cell infiltration and extensive retinal folds were detected in IL-17A + IFN-γ + highly expressed mice.Mild retinal edema, focal inflammatory cell infiltration and mild retinal folds were found in IL-17A + IFN-γ + lowly expressed mice.The proportion of CD3 and IL-17A + IFN-γ + CD4 + T cells in the eyeballs of anti-IL-12/IL-23 p40 group was lower than that in IgG group at the 18th day after immunization, and the differences were statistically significant ( t=15.304, 8.080; both at P<0.05). On day 12 after immunization, the percentage of IL-17A + IFN-γ + CD4 + T cells in anti-IL-12/IL-23 p40 group was (0.33±0.18)%, which was significantly lower than (4.83±0.45)% in IgG group ( t=15.974, P<0.001). Compared with IgG group, the percentage of Th1, Th17, IL-17A + IFN-γ + CD4 + T cells and the expression levels of IL-17, IFN-γ, T-bet, ROR-γt in anti-IL-12/IL-23 p40 group were significantly decreased, with statistical significances (all at P<0.05). Conclusions:Anti-IL-12/IL-23 p40 has a therapeutic effect on EAU by inhibiting IL-17A + IFN-γ + CD4 + T cells.
3.The distribution of sleep duration in mid-pregnancy and its association with prehypertension
Xiao-tong WANG ; Nu TANG ; Wei-jia WU ; Wen-ting PAN ; Ya-jie LV ; Dan-yu CHEN ; Xiao-wei DAI ; Ya-jun CHEN ; Jin JING ; Li CAI
Chinese Journal of Disease Control & Prevention 2020;24(3):335-340
Objective To study the distribution of sleep duration in mid-pregnancy women and examine its association with prehypertension ( PHT) . Methods In the baseline survey of a prospective cohort study,943 women in mid-pregnancy were recruited in Guangzhou,China in 2017-2018. A standardized questionnaire was used to assess demographic characteristics,sleep duration and other lifestyles. We obtained maternal blood pressure values,weights,heights,and medical histories from medical records. Multivariate logistic regression was conducted to examine the association between sleep duration and PHT. Results The average daily sleep duration of women in mid -pregnancy was ( 10. 41 ± 1. 67 ) hours,and it was negatively related to age and educational level. Overall,98. 33% of pregnant women had a daily sleep duration ≥ 7 h and the distribution was related to passive smoking. The average night time sleep duration was ( 9. 48±1. 21 ) hours,and it was negatively related to age and educational level. The daytime sleep duration was ( 0. 93 ± 0. 69 ) hours,and it was positively associated with physical activity. The average bedtime was( 22 ∶ 42 ± 1.24) ,and it was positively associated with passive smoking. The prevalence of PHT was 9. 61%. We did not observe any significant association between sleep duration and PHT. Conclusions The mid-pregnancy women in Guangzhou had relatively long sleep duration, and it differed by maternal age,educational level,physical activity,and passive smoking. There was no significant association between sleep duration and PHT.
4.Comparison and reflections on the training of rehabilitation physicians in Taiwan and Mainland China
Mi CHEN ; Chao LI ; Baolan WANG ; Yi-Nan LIAN ; Yanling XI ; Yu REN ; Nu BA ; Haixia HUANG
Chinese Journal of Medical Education Research 2019;18(4):371-376
Rehabilitation physician training is an important part of the development of rehabilitation medicine.Rehabilitation physician education in Taiwan has a complete and standardized training system,and rehabilitation physician training in mainland China is mainly achieved through standardized residency training.This article compares the differences in training processes for rehabilitation physicians in education in medical colleges and universities,residency training,and specialist training between Taiwan and mainland China.The results show that rehabilitation physician training in Taiwan is rigorous and orderly,with reasonable contents,clear objectives,strong specialty,and standardized assessment,while in mainland China,rehabilitation physicians in mainland China have insufficient training time,and there is a lack of detailed training plan and unified assessment standards.Rehabilitation physician training in mainland China needs to learn from advanced experience,further reform the training process,improve the operability of the overall education program,and perfect the training system of rehabilitation physicians.
5.The effect of maternal food consumption during pregnancy on infantile eczema: a cohort study
Pei-qi YE ; Wei-jia WU ; Nian-qing WAN ; Min-yi TAN ; Nu TANG ; Yu-ming CHEN ; Ya-jun CHEN ; Jin JING ; Li CAI
Chinese Journal of Disease Control & Prevention 2019;23(10):1213-1218
Objective To investigate the association between maternal food group intakes during pregnancy and the risk of infantile eczema in a Chinese population. Methods A prospective birth cohort study was conducted and 523 women were recruited at 20-28 weeks of pregnancy in Guangzhou from 2017 to 2018. A validated 81-item quantitative food frequency questionnaire was used to assess maternal dietary intakes during the past month. Food items were divided into ten food groups according to the Chinese Dietary Guidelines. Offspring were followed up at 6 months by the symptom questionnaire of eczema. Multivariate Logistic regression model was conducted to evaluate the association between maternal food group intakes during pregnancy and the risk of infantile eczema. Results The cumulative incidence of eczema at 6 months was 51.8%. Maternal consumption of poultry was higher in the eczema group (27.62±25.20 g/d) than the control group (22.03±22.63 g/d, P=0.022). Comparing to the lowest quantile (Q1), higher maternal intake of poultry (Q4) and fish (Q3) were significantly associated with an increased risk of infantile eczema (OR=2.71, 95% CI=1.24-4.81; OR=2.38, 95% CI=1.23-4.59, respectively) after multivariate adjustment. Conclusion Higher intakes of poultry or fish during pregnancy were associated with an increased risk of infantile eczema in Chinese population.
6. Differential expression and bioinformation analysis of retinal proteins in mice with experimental autoimmune uveitis
Shuang CHEN ; Xianfeng SHAO ; Zhihui ZHANG ; Nu CHEN ; Lingzi WU ; Xuexue CUI ; Xiaorong LI ; Xiaomin ZHANG
Chinese Journal of Experimental Ophthalmology 2019;37(12):949-955
Objective:
To observe the expression of retinal proteins in experimental autoimmune uveitis (EAU) mice and to explore the possible molecular mechanism of autoimmune uveitis.
Methods:
Twelve female C57BL/6J mice were randomly divided into model group and normal control group, 6 mice in each group.In the model group, the EAU model was established by subcutaneous injection of human interphotoreceptor retinoid-binding protein (IRBP) 651-670.The fundal change of EAV mice was assessed by direct ophthalmoscope, OCT and histopathological staining.At 18 days after immunization, the retinas of the two groups were taken for retinal protein extraction, protein restriction enzyme digestion, mass spectrometry detection, data analysis, and bioinformatics analysis.This study was approved by the experimental animal Ethics Committee of Tianjin Medical University Eye Hospital (TJYY2018070113). The feeding and use of experimental animals follow the ARVO statement.
Results:
The EAU mouse model was successfully established.At 10 days after immunitation, the retina of EAV mouse was damaged.At 18 days after immunization, retinal edema and infiltration of inflammatory cells into vitreous were observed.Proteomic results showed that a total of 4 458 proteins were identified in this study, of which 522 were differentially-expressed proteins (fold change>1.5,
7.The comparison of hypertension prevalence among children based on different references of hypertension
Nu TANG ; Ya-jun CHEN ; Wei-qing TAN ; Lu DENG ; Shao-min LU ; Min-yi TAN ; Xia ZENG ; Li CAI
Chinese Journal of Disease Control & Prevention 2019;23(2):162-167
Objective To compare the differences in the hypertension prevalence among children aged 7-12 in Guangzhou based on different references of hypertension. Methods A total of 7698 children aged 7-12 years old in Guangzhou were recruited by stratified cluster random sampling method. Demographic information such as gender and age was collected by questionnaire. Children’s height, weight, and blood pressure were objectively measured. There were five references for diagnosing children’s hypertension: Mi 2010, Mi 2017, Ma 2017, America 2004, and America 2017 reference. Results Based on the references above, the prevalence of hypertension for children aged 7-12 in Guangzhou reached a very high level. The prevalence of hypertension, high systolic blood pressure (SBP) and high diastolic blood pressure (DBP) based on Mi 2017 reference were all higher than those based on Mi 2010 reference, but both of them were distinctly higher than Ma 2017 reference. Compared with Mi 2010 reference, the agreement of diagnosis of high SBP and high DBP were both higher for Mi 2017 than those for Ma 2017. The agreement of high SBP was higher between Mi 2017 and America 2017 than that between Ma 2017 and America 2017 (Kappa: 0.846 vs. 0.727). Conclusion The prevalence of hypertension in children aged 7-12 in Guangzhou reachs a very high level. The prevalence of hypertension based on Mi 2017 reference is the highest and follows with America 2017 reference, and the agreement between them is excellent. Compared with Mi 2010 or America 2017 reference, the agreement for Ma 2017 is lower than that for Mi 2017 reference, respectively.
8.Factors contributing to myasthenic crisis after thymectomy-a multivariate analysis study
Jinshan MA ; Xiaolei WANG ; Kang CHEN ; Erlan NU ; Xianfeng LI ; Kaiti XIAO ; Yongwei YANG ; Chengyü JIN ; Rui GUO
Chinese Journal of Thoracic and Cardiovascular Surgery 2011;27(1):27-29
Objective To evaluate the risk factors of myasthenic crisis(MC) after thymectomy for myasthenia gravis (MG) Methods A retrospective study was conducted in 84 patients with MG from July 1995 to December 2009. The following factors were evaluated: sex, age, history of preoperative myasthenic crisis, Osssrmen classification, use steroid hormones and anticholinesterase drugs before operation, operation methods, operation time, thymoma, pathology, transfusion, course of disease, postopertive lung infection,etc. Multivariate logistic regrossion analysis was used to find the predictors of postoperative myasthenic crisis. Results Twenty-four patients(28.6%) developed myasthenic crisis after thymectomy. Statistics showed that history of preoperative myasthenic crisis, Ossermen classification, operation methods, operation time were related to postoperative myasthenic crisis. Conclusion Preoperative myastheric crisis, Ossermen classification≥I b, traditional operation methods, long opertion time are the independent risk factors for myasthenic crisis after thymectomy.
9.Epidemical survey of glaucoma among Uigur peasants aged 40 years or above in Kuche rural
Ting-yu, XIE ; Liang, GAO ; Ke, AI ; Jing, FU ; Bao, GUO ; Mei-li-ba-nu SUFU, YU ; Xue-yi, CHEN
Chinese Journal of Experimental Ophthalmology 2011;29(2):169-173
Background Glaucoma is one of the leading causes of blindness worldwide;while the different types of glaucoma is vary from different region. Objective Present study was to survey the prevalence and types of glaucoma among peasants of Uigur adults in Kuche county and offer the basis for the prevent and treatment of glaucoma in Uigur nationanlity. Methods 4191 Uigur peasants aged 40 years or above were collected in Kuche county for the survey of prevalence and types of glaucoma by randomized cluster sampling in March and April of 2009. The subjects were grouped into 40-,50-,60- and ≥70 years groups according to the distribution of age. The disease history of glaucoma, regular eye examination, funds examination and measurement of the anterior chamber depth, gonioscope were performed in the all subjects. Darkroom prone test and mydriasis test were carried out in suspicious glaucomous patients. The depth of periphery anterior chamber was assessed based on van Herick' s criteria, and the width of chamber angle was graded based on Scheie' s method. The standardized training was performed. This survey approved by Xinjiang Medical Ethics Committee, all subjects signed the informed consent before the examination. Results 4191 of 4873 subjects finished all the examinations with the response rate 86%. All the subjects showed a good compliance. The prevalence of glaucoma was 3. 79% , and the prevalence of primary angle-closed glaucoma(PACG) .primary angle-open glaucoma (PAOG) and secondary glaucoma was 2.22% ,0.26% and 1. 31% respectively, showing a significant difference among the different types of glaucoma( P<0. 05). The prevalence of glaucoma was elevated with aging (χ2 - 116. 69 ,P<0. 05) and presented a high rate in male subjects compared with female ones(χ2 = 7. 34, P<0. 05 ). Bilateral blindness was found in 19.75% glaucoma peasants, in which 25.3% glaucoma peasants received anti-glaucoma surgery. The distribution of visual acuity of patients was of significant difference among different age groups(χ2 = 37. 69 ,P<0. 05 ) . Conclusions The prevalence of the glaucoma among Uigur peasants in Kuche county was higher than most area no matter inland or overseas. PACG still is the common type in those people.
10.Role of Ommaya reservoir in the management of neonates with post-hemorrhagic hydrocephalus.
Zhen-lang LIN ; Bo YU ; Zhi-qiang LIANG ; Xian-wei CHEN ; Jiang-qin LIU ; Shang-qin CHEN ; Zi-ying ZHANG ; Nu ZHANG
Chinese Journal of Pediatrics 2009;47(2):140-145
OBJECTIVEIntra-ventricular hemorrhage (IVH) is one of the most serious complications of preterm infants. Significant numbers of the surviving infants with severe IVH go on to develop post-hemorrhagic hydrocephalus (PHH). The management of PHH remains a very challenging problem for both neonatologists and pediatric neurosurgeons. This study aimed to evaluate the efficacy and safety of the use of Ommaya reservoirs and serial cerebrospinal fluid (CSF) drainage in the management of a series of neonates with PHH.
METHODBetween January 1, 2003 and December 30, 2005, 15 consecutive newborn infants with IVH grades III to IV, complicated with progressive ventricular dilatation, underwent placement of an Ommaya reservoir. CSF was intermittently aspirated percutaneously from the reservoir. The amount and frequency of CSF aspiration were based on the clinical presentation and the follow-up results of serial cranial ultrasonograms or CT scans. The changes of CSF cell counts and chemistries were also followed. Patients whose progressive ventricular dilatation persisted despite serial CSF aspiration through Ommaya reservoir eventually had ventriculo-peritoneal shunts (V-P shunt) placed. All the patients were followed up in the outpatient clinic after discharge from the hospital and the neurodevelopmental outcomes were evaluated through 18-36 months of age.
RESULTA total of 15 infants were included in this series. Of them, 11 were preterm infants who were at gestational ages of 29 to 34 weeks and 4 infants were full-term. All of the 4 full term infants presented with progressive ventricular dilatation after suffering from the intra-cranial hemorrhage (3 infants were due to vitamin K deficiency and 1 was due to birth trauma). Thirteen infants had grade III IVH, and 2 had grade IV IVH based on initial cranial ultrasonographic and CT scans. The mean age when IVH was diagnosed was (9 +/- 1) days in preterm infants and (22 +/- 7) days in full-term infants; the mean age when Ommaya reservoir was placed was (18 +/- 11) days in preterm infants and (31 +/- 7) days in full-term infants. All the infants tolerated the surgical procedure well. The Ommaya reservoir was tapped for an average of (21.5 +/- 4.6) times per patient. The mean CSF volume per tap was (10.2 +/- 1.3) ml/kg. The values of CSF protein, glucose and cell counts slowly reached normal levels at approximately 3 - 5 weeks after the placement of the reservoir. The velocity of head circumference increase per week was less than 1 cm in 13 patients in 1 - 4 weeks after the placement of the reservoir and the size of ventricles decreased gradually. By 12 - 18 months, 12 infants had normal size ventricles, and 1 patient still had mild ventricular dilation at 36 months. Two infants developed progressive hydrocephalus after serial CSF aspiration through Ommaya reservoir. One infant had a V-P shunt placed at 2 months of age and another infant died at 3 months of age at home after parents refused further therapy. Complications consisted of reservoir leaking and CSF infection at 16th day of placement in one patient after repeated tapping. By the end of 18 - 36 months of follow-up, 11 of 14 infants were considered normal, two patients had mild impairment in neurodevelopmental outcome (both had spastic bilateral lower limbs paresis, and one of whom also had amblyopia) and the other had seizure disorder.
CONCLUSIONThe results from this series indicate that the placement of an Ommaya reservoir is relatively safe in newborn infants and is useful in the initial management of neonates with PHH and may be beneficial in improving their neurodevelopmental outcomes. A multicenter randomized trial may be needed to further validate the results of this report.
Cerebral Hemorrhage ; complications ; therapy ; Cerebral Ventricles ; Drainage ; methods ; Female ; Humans ; Hydrocephalus ; etiology ; therapy ; Infant, Newborn ; Male ; Subdural Effusion ; etiology ; therapy

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