Maternal death after postpartum onset of citrullinemia type Ⅰ: a case report / 中华围产医学杂志

This paper reports a woman diagnosed with citrullinemia type I (CTLNⅠ) in puerperium who was unfortunately died later. The 28-year-old patient (G1P1) delivered a live girl at 39 +2 gestational weeks and was transferred from a local hospital to Henan Provincial People's Hospital on January 11, 2020, due to "a 3-day paroxysmal confusion accompanied by dizziness 4 days after delivery". Intermittent confusion, elevated blood ammonia, and citrulline concentration, and encephaledema were presented 10 h after delivery, and the patient eventually died of cerebral hernia on the day of self-discharge. Two pathogenic mutations of the ASS1 gene were found by genetic testing, including c.422t>G (p.val141gl; HET) and c.431c>G (p.pro144arg; HET) and confirmed the diagnosis of CTLNⅠ. CTLNⅠ is a life-threatening disease that could be easily overlooked and misdiagnosed and was difficult to treat. It most often occurs in newborns and infants, whilst it is rare during pregnancy and postpartum. The possibility of this disease should be considered in patients with neurological system symptoms and elevated blood ammonia during pregnancy or puerperium.

Expression and significance of long noncoding RNA nuclear-enriched abundant transcript 1 (lncRNA NEAT1) in pregnant women with systemic lupus erythematosus / 中华微生物学和免疫学杂志

Objective:To investigate the function and mechanism of long noncoding RNA nuclear-enriched abundant transcript 1 (lncRNA NEAT1)-mediated epigenetic regulation of Th2 cell differentiation and development in pregnant women with systemic lupus erythematosus (SLE).Methods:This study involved 11 women with normal singleton pregnancy (control group) and 15 pregnant women with SLE who delivered in the Henan Provincial People′s Hospital from July 1, 2014 to July 1, 2019. Peripheral blood mononuclear cells (PBMCs) were collected and analyzed by qPCR to detect the expression of NEAT1 at mRNA level. ELISA and flow cytometry were used to detect the expression of IFN-γ and IL-4 at protein level. Na?ve CD4 + T cells were sorted out by flow cytometry. RNA binding protein immunoprecipitation (RIP) was performed to detect the binding of EZH2 to NEAT1. After knockdown of NEAT1 expression, Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the expression of itchy E3 ubiguitin protein ligase(ITCH) at mRNA and protein levels. Chromatin immunoprecipitation (ChIP) was used to detect the abundance of EZH2 at ITCH promoter in pregnant patients with SLE. ELISA was used to detect IL-4 level after overexpression of NEAT1 and ITCH. Statistical data analysis was performed with t test. Results:The expression of NEAT1 at mRNA level in peripheral blood of pregnant women with SLE was significantly higher than that in controls. IFN-γ levels were significantly reduced, while IL-4 levels were significantly increased in pregnant women with SLE than in controls. RIP analysis revealed that there was a great enrichment of NEAT1 in the na?ve CD4 + T cells using anti-EZH2 compared to the control group. After knocking down the expression of NEAT1, the mRNA and protein levels of ITCH were significantly increased. ChIP assay demonstrated that EZH2 was recruited to the promoter of ITCH in pregnant women with SLE. ITCH significantly inhibited the production of IL-4 by na?ve CD4 + T cells, while overexpression of NEAT1 upregulated the expression of IL-4 at protein level. Conclusions:LncRNA NEAT1 was significantly up-regulated in pregnant women with SLE. It recruited EZH2 to the promoter of ITCH and promoted the differentiation of na?ve CD4 + T cells to Th2 cells, resulting Th1/Th2 imbalance and affecting disease progression.

Effect of pregnancy on endothelial progenitor cells in patients with rheumatoid arthritis and its mechanism / 中华风湿病学杂志

Objective:To investigate the effect of pregnancy on endothelial progenitor cells (EPCs) in patients with rheumatoid arthritis (RA) and its mechanism.Methods:The newly treated RA patients in our hospital from January 2016 to June 2018, were included in this study. According to pregnancy or not, patients were divided into simple RA group and RA pregnancy group. They were all female patients, 30 in each group. Immunohistochemical staining was used to detect the number of lymphocyte common antigen (LCA) + lymphocytes and CD68 + macrophages in synovial tissue, flow cytometry was used to detect the proportion of EPC and endothelial cells, and enzyme-linked immunosorbent assay(ELISA) was used to detect the concentrations of vascular endothelial growth factor (VEGF), stromal cell derived factor (SDF-1), interleukin (IL)-6 and IL-10 in EPC supernatant. T-test was used for the comprarison between the two groups, and single factor analysis of variancewas used for the comparison between multiple groups. Results:Immunohistoche-mical results showed that the number of CD68 + macrophages and LCA + lymphocytes in synovium of RA with pregnancy group was significantly lower than that of non-pregnant RA group. The results of ELISA showed that the concentration of human leucocyte antigen-G (HLA-G) in peripheral blood was (8.9±1.7) pg/ml in non- pregnant RA group and (396.7±89.6) pg/ml in RA pregnancy group, the difference beween the two groups was statistically significant ( t=4.329, P<0.01). The results of flow cytometry showed that the proportion of EPC in lymphocytes was (0.13±0.03)% in non-pregnant RA group and (0.76±0.09)% in RA with pregnancy group, the difference beween the two groups was statisti-cally significant ( t=6.671, P<0.01). The results of correlation analysis showed that the proportion of EPC in peripheral blood was positively correlated with HLA-G concentration ( r=0.886 1, P<0.01). In vitro experiments showed that HLA-G could promote the recovery of EPC paracrine and differentiation function in RA patients. Conclusion:Pregnancy can improve the number and biological function of EPC in patients with RA. HLA-G may play an important role in this process.

Signaling pathways and neural circuits of alcohol reward memory / 中华行为医学与脑科学杂志

A key symptom of alcohol dependence is the strong desire to consume alcohol,which of-ten leads individuals to relapse despite negative social,interpersonal and health consequences. Core of crav-ing is repeatedly drinking alcohol and relevant cues can form pathological reward memory,which is the root cause of craving and relapse. Therefore,the extinction of the alcohol related reward memory is important for reducing relapse. The establishment of alcohol reward memories is associated with reward,motivation and memory circuits in the brain. Dysregulation of alcohol reward memory pathways is a key factor in the devel-opment of alcohol dependence, and the nature of these pathways varies depending on the brain region in which they are located. So systematic review that what reward memory pathways are involved in the develop-ment of alcohol dependence,and what brain regions are involved in these pathways,combined with animal ex-periments and alcohol dependent magnetic resonance imaging data,explain how alcohol reward memory signa-ling pathways regulate alcohol reward memory and how these pathways interact with neural circuits,plays a key role in the early recognition,prevention and treatment of alcohol dependence.

Research status of sleep disorders in children / 中华实用儿科临床杂志

Good sleep plays a key role in children's physical growth,mental development and personality matu-rity.Sleep disorders are common and most easily neglected problems in children.Early sleep problems of children can sustain from childhood to adulthood,not only have relevance to the children's physical,cognitive and behavioral development,but also to be the high risk factors of the adult obesity,hypertension,depression,anxiety and other chronic diseases.A deep study of sleep disorders in children is very important for the protection of children's physical and men-tal health.This article reviews the etiology,classification,diagnosis and treatment of sleep disorders in children.

Correlation Study Between the Syndrome of Stagnation of Liver Qi and Spleen Deficiency and Intestinal Flora / 世界科学技术-中医药现代化

In recent years, the relationship between TCM (traditional Chinese medicine) syndrome and intestinal flora has attracted wide attention from the medical community. The syndrome of stagnation of liver qi and spleen deficiency is a common clinical syndrome of multiple diseases, involving multiple system pathological change. And the disorganized intestinal flora also cause a multisystem pathological change. The development of molecular biology and metagenomic technology provides strong support for the study of syndrome diseases and intestinal flora. In this paper, it reviewes the correlation of syndrome of stagnation of liver qi and spleen deficiency and intestinal flora in nerve, digestive, endocrine, metabolic system.

Discussion on Modern Biological Basis of Liver-qi Stagnation and Spleen Deficiency Syndrome / 世界科学技术-中医药现代化

Liver-qi stagnation and spleen deficiency syndrome can be seen in a variety of clinical diseases,such as chronic hepatitis,liver cirrhosis,chronic gastritis,peptic ulcer,irritable bowel syndrome (IBS),p.sychosis and so on.Disease characteristics determine the symptom characteristic and criterion of syndrome differentiation and treatment.Therefore,different diseases with liver-qistagnation and spleen deficiency syndrome have different clinical manifestation and diagnostic criteria.This paper summarized the modern biological basis of liver-qistagnation and spleen deficiency syndrome from the nervous system,endocrine system,digestive system,circulatory system,immune system and metabolic system,in order to provide reference for researches on modern biology basis of liver-qistagnation and spleen deficiency syndrome.

The effects of sodium butyrate on ethanol-seeking behavior and H3K9 acetylation in NMDA receptor 2B subunit promotor region in the hippocampus of rats / 中华行为医学与脑科学杂志

Objective To investigate the effects of sodium butyrate on ethanol-seeking behavior and H3K9 acetylation levels in NMDA receptor 2B subunit(NR2B) promoter region in the hippocampus of Wistar rats.To explore the epigenetic mechanism underlying ethanol-seeking behavior.Methods According to random number table,48 male Wistar rats were divided into saline group,sodium butyrate group,ethanol group and sodium butyrate + ethanol group,with 12 rats in each group and administered by intraperitioneal injection respectively.Conditioned place preference (CPP)was used to evaluate the ethanol-seeking behavior.Using Western-blot,real-time PCR and chromatin immunoprecipitation assays,the expression of NR2B protein,NR2BmRNA and the relative level acetylated H3K9 in NR2B promoter region in the hippocampus were determined respectively.Results The CPP test and the CPP score in each group were different (P＜ 0.05).Compared with the CPP test(261.1 ± 102.2) and the CPP score(48.5±94.6) of saline group,the CPP test ((406.8±109.2),(502.7±72.89)) and the CPP score((198.2± 119.4),(277.5±76.2)) of ethanol group and sodium butyrate + ethanol group were significantly higher(P＜0.05),the CPP test(193.4±93.8) and the CPP score (9.7±94.0)of sodium butyrate group were not significantly different(P＞0.05).Compared with the ethanol group,CPP test of sodium butyrate + ethanol group was significantly higher(P＜0.05).The expression of NR2B protein,NR2BmRNA and acetylated level H3K9 in NR2B promoter region in the hippocampus in each group were different (P＜ 0.05).Compared with the expression of NR2B protein (1.00 ± 0.28),NR2BmRNA(1.00±0.14) and H3K9 acetylation in NR2B promoter region(1.00±0.25)in the hippocampus of saline group the expression of NR2B protein((1.40±0.34),(1.79±0.30)),NR2BmRNA((1.26±0.16),(1.50±0.08)) and aeetylated level H3K9 in NR2B promoter region ((1.68±0.16),(2.35±0.45)) of ethanol group and sodium butyrate ± ethanol group were significantly higher(P＜0.05).The expression of NR2B protein(0.85±0.24),NR2BmRNA(1.05±0.13) and acetylated level H3K9 in NR2B promoter region(0.96±0.41) of sodium butyrate group were not significantly different(P＞0.05).Compared with the ethanol group,the expression of NR2B protein,NR2BmRNA and acetylated level H3K9 in NR2B promoter region in the hippocampus of ethanol group,these of sodium butyrate + ethanol group were significantly higher (P＜0.05).The CPP score were positively correlated with the expression of NR2B protein (r=0.474,P＜0.05).The expression of NR2B protein were positively correlated with the expression of NR2BmRNA (r=0.468,P＜0.05).The expression of NR2BmRNA were positively correlated with the expression of H3K9 acetylation in NR2B promoter region(r=0.596,P＜0.05),and the CPP score were positively correlated with the expression of H3K9 acetylation in NR2B promoter region (r=0.542,P＜0.05).Conclusion The increasing acetylation level of H3K9 in NR2B promoter region in the hippocampus may be one of the epigenetic mechanisms of promoting ethanolseeking behavior,and H3K9 deacetylation in NR2B promoter region in the hippocampus is likely to be a new target for controlling ethanol dependence.

The changes of NR2B expression in the striatum of rats with chronic alcohol exposured at different withdrawal time / 中华行为医学与脑科学杂志

Objective To observe the changes of N-methyl-D-aspartate (NMDA) receptor 2B subunit (NR2B) expression in the striatum of chronic alcohol exposured rats at different withdrawal time.Methods 72 male Wistar rats were randomly divided into withdrawal 2h group,withdrawal 6h group,withdrawal 12h group,withdrawal 1d group,withdrawal 3d group and control group,and 12 rats in each group.In the 5 withdrawal groups,ethanol was administered in drinking water at the concentration of 6％ (V/V) for 16 weeks,and rats in control group were maintained with water.After 16 weeks ethanol was removed and ethanol withdrawal syndromes were evaluated.The expression of NR2B protein in the striatum was measured by immunofluorescence and western blot and the expression of NR2B mRNA in the striatum was measured by realtime PCR.Results Compared with withdrawal scores of control group((1.50±0.80)),scores of withdrawal 2h,6h,12h,1d,3d groups ((10.42±2.50),(15.42± 1.93),(9.25±2.01),(7.67± 1.92),(2.25±0.87) respectively) were higher,and the withdrawal scores of withdrawal 6h group were the highest.Compared with the expression of NR2B fluorescence intensity (2210.00± 178.20),the expression of NR2B protein(0.150±0.009) and the expression of NR2B mRNA(0.006±0.001) in the striatum of control group,the expression of NR2B fluorescence intensity (2710.56 ± 194.21),(5035.16 ± 234.41),(3326.23 ± 378.16),(2570.64 ±177.88),the expression of NR2B protein (0.192±0.008),(1.649±0.205),(0.783±0.109),(0.180±0.009) and the expression of NR2B mRNA (0.026±0.002),(0.351±0.034),(0.248± 0.023),(0.024±0.003) of withdrawal 2h,6h,12h,ld groups were significantly higher (P＜0.05),and with the extension of the withdrawal time,the expression was gradually increased.The expression of withdrawal 6h group was the highest,then began to decline,and returned to baseline levels at withdrawal 3 d(P＞0.05).Withdrawal scores were positively correlated with the expression of NR2B protein(r=0.719,P＜0.01),the expression of NR2B protein was positively correlated with the expression of NR2B mRNA(r=0.937,P＜0.01),and the expression of NR2B mRNA was positively correlated with withdrawal scores(r=0.673,P＜0.01).Conclusion The expression of NR2B was up-regulated in the striatum of chronic alcohol exposured rats at different withdrawl time.NR2B protein and NR2B mRNA expression is positively correlated with the withdrawal scores,suggesting that regulating the expression of NR2B may be a new target for the treatment of ethanol withdrawal symptoms.

Relationship between memory impairment and N-methyl-D-aspartate receptor 2B expression in alcohol dependence patients / 中华行为医学与脑科学杂志

Objective To explore the characteristic of memory impairment and its relationship with Nmethyl-D-aspartate receptor 2B (NR2B) expression in alcohol dependence patients,in order to provide an unprecedented view of alcohol-associated memory impairment therapy.Methods Participants (n=67) included 35 alcohol dependence patients and 32 matched healthy controls.Wechsler memory scale (WMS) was used to access the memory.The expression levels of NR2B were detected with quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Results Compared with the memory quotient(MQ) of controls(69.45±8.96),that of alcohol dependence patients(50.59±8.64) significantly decreased (t=-6.08,P＜0.01).Compared with the NR2B expression level of controls (1.00-0.00),that of alcohol dependence patients (3.52 ± 1.17) significantly increased (t =9.67,P＜0.01).MQ was negatively correlated with the levels of NR2B expression (r=-0.44,P＜0.05).Conclusion Alcohol dependence patients suffer memory impairment detected by WMS,and modulate NR2B expression may improve the memory.

Effects of nicotine exposure and ethanol-preferring behavior on mRNA expression of some nAChR subunits in the rat VTA / 中华行为医学与脑科学杂志

ObjectiveTo investigate the effects of nicotine exposure and ethanol-preferring behavior on mRNA expression of some nAChR subunits in the rat ventral tegmental area(VTA) and to explore possible mechanisms of dependence on tobacco and alcohol.Methods39 male Wistar rats,35-day-old,were randomly divided into an experimental group (group N,n=20) and a control group (group C,n=19).Rats in group N were treated with nicotine ( 1.0 mg · kg -1 · d -1 ) by subcutaneous injection while in group C with saline both for 10 days,after which 6 rats (respectively group NE,n =6,group CE,n =6 )were drawn randomly from each group and killed by cutting off the head.mRNA was extracted from the VTA tissue,and the expression of nAChR subunits,including α4,α5,α7 and β2,were examined by Real Time-PCR.Other rats both in groups N and C ( respectively group NA,n=14,group CA,n=13) were induced for 69 days to establish two-bottle free choice alcohol-preferring behavior model by Samson sucrose fading program from 60-day-old on.The same indexes mentioned above were detected by the same methods in the VTA tissue.Results① The factor analysis showed that both the two factors,nicotine and alcohol-preferring behavior,showed regulating effects on the expression of nAChR subunits α4 and α5 ( respectively F was 6.13,5.407,5.186,7.132,P ＜ 0.05 ),and the factor,alcohol-preferring behavior,on subunit β2 (F =5.896,P＜0.05) ; the two factors exhibited strong interaction on the expression of subunit α7 (F=13.894,P＜0.001 ),and some interaction on subunits α5 and β2 (respectively F was 6.149,4.222,P＜0.05 ).② The mRNA expression of nAChR subunits α4,α5,α7,and β2 were significantly up-regulated by different degrees in group NA compared to group CA ( respectively Fwas 7.941,13.517,17.438,9.272,respectively P ＜ 0.05,P ＜ 0.05,P ＜ 0.01,P ＜ 0.01 ),the expression level of subunits α4,α5,α7 and β2 were significantly higher in different degrees in group NA than in group NE( respectively F was 5.293,8.500,6.149,4.837,P ＜0.05) ; while subunit α7 was significantly down-regulated in group CA compared to group CE (F =12.750,P ＜0.01 ).ConclusionNicotine and ethanol co-affect on the nAChR subtype comprised of subunits α4,α5,α7 and β2.