Interventions for Postextubation Dysphagia in Critically Ill Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: This review evaluates the efficacy and safety of dysphagia interventions for patients with prolonged endotracheal intubation (⩾48 h) in critical care units. DATA SOURCES: We systematically searched PubMed, Cochrane Library, Medline, Embase, OVID, CINAHL, Wanfang (China), CNKI (China), and ProQuest Dissertations for studies published up to December 31, 2023. STUDY SELECTION: Inclusion criteria encompassed randomized controlled trials (RCTs), quasi-randomized trials, and cohort studies comparing dysphagia rehabilitation - such as swallowing stimulation, swallowing and respiratory muscle exercise, and neuromuscular electrical stimulation - with standard care or no treatment. The primary outcomes assessed were dysphagia severity, time to resume oral intake, and incidence of aspiration and aspiration pneumonia. DATA EXTRACTION: Detailed information on study design, setting, participant demographics, interventions, and outcomes was systematically extracted. DATA SYNTHESIS: Our analysis included ten studies with a total of 1031 participants. The findings demonstrate a significant reduction in dysphagia severity, time to oral intake and the risk of aspiration pneumonia, and an improvement in quality of life among patients receiving swallowing therapy. However, no substantial difference was found in nutritional status. Limited data availability necessitated a descriptive presentation of outcomes like the risk of aspiration, ICU/hospital stay duration, pharyngeal/oral residue severity, and intervention-related adverse events. CONCLUSION: The current evidence for the effectiveness of dysphagia interventions in critically ill patients with prolonged endotracheal intubation is limited. There is a pressing need for future research, particularly high-quality RCTs employing standardized outcome measures, to substantiate these findings.

The Role of Left Ventricular Pressure-strain Loop in Evaluating Myocardial Work in Patients with Type 2 Diabetes.

Objective: To quantitatively analyze the myocardial work of patients with type 2 diabetes (T2D) by use of the pressure-strain loop and to investigate the clinical factors that affect myocardial work in the left ventricle. Methods: We analyzed data from 50 control patients and 180 case patients, with 70 cases in group A (T2D only), 40 cases in group B (T2D + high blood pressure), 33 cases in group C (T2D + coronary heart disease), and 37 cases in group D (T2D + high blood pressure + coronary heart disease). Each patient received conventional ultrasonography and 2-dimensional speckle-tracking echocardiography, and the pressure-strain loop technique was applied to measure the left ventricular myocardial work parameters to compare the control and case groups. Results: Systolic blood pressure was dramatically higher in groups B and D than in the control group and in groups A and C. N-terminal pro-brain natriuretic peptide was markedly higher in group D than in the control group, and the disease duration was markedly higher in groups C and D than in group A. The left ventricular global longitudinal strain of the epicardium (LVGLSepi) was substantially lower in groups B, C, and D than in the control group. The LVGLSepi of groups C and D was significantly lower than group A, and the LVGLSepi of group D was significantly lower than group B. The LVGLS, LVGLS of the endocardium, global work index, and global constructive work progressively reduced among the control and case groups. LVGLS strongly correlated with global work index (r = -0.886; P < .001) and global constructive work (r = -0.880; P < .001). Body mass index, duration of diabetes, and glycated hemoglobin A1c independently associated with global work index (Body mass index: P = .04; duration of diabetes: P < .001; glycated hemoglobin A1c: P = .02) . In addition to the above three indicators, systolic blood pressure independently associated with global constructive work (systolic blood pressure: P = .04). Conclusion: Pressure-strain loop technology can quantitatively, accurately, and sensitively monitor the variations in left ventricular myocardial contractile function of patients with T2D and detect subclinical cardiac injury at an early disease stage.

Fear of disease in patients with epilepsy - a network analysis.

Background: Disease-related fear among patients with epilepsy has significantly impacted their quality of life. The Disease-Related Fear Scale (D-RFS), comprising three dimensions, serves as a relatively well-established tool for assessing fear in these patients. However, certain problems potentially exist within the D-RFS's attribution of items, and its internal structure is still unclear. To establish an appropriate dimensional structure and gain deeper comprehension of its internal structure-particularly its core variables-is vital for developing more effective interventions aimed at alleviating disease-related fear among patients with epilepsy. Methods: This study employed a cross-sectional survey involving 609 patients with epilepsy. All participants underwent assessment using the Chinese version of the D-RFS. We used exploratory network analysis to discover a new structure and network analysis to investigate the interrelationships among fear symptom domains. In addition to the regularized partial correlation network, we also estimated the node and bridge centrality index to identify the importance of each item within the network. Finally, it was applied to analyze the differences in network analysis outcomes among epilepsy patients with different seizure frequencies. Results: The research findings indicate that nodes within the network of disease-related fear symptoms are interconnected, and there are no isolated nodes. Nodes within groups 3 and 4 present the strongest centrality. Additionally, a tight interconnection exists among fear symptoms within each group. Moreover, the frequency of epileptic episodes does not significantly impact the network structure. Conclusion: In this study, a new 5-dimension structure was constructed for D-RFS, and the fear of disease in patients with epilepsy has been conceptualized through a network perspective. The goal is to identify potential targets for relevant interventions and gain insights for future research.

Understanding Comorbidity Between Non-Suicidal Self-Injury and Depressive Symptoms in a Clinical Sample of Adolescents: A Network Analysis.

Background: Non-suicidal self-injury (NSSI) and depression often co-occur among adolescents with more severe clinical symptoms. This study examined the network structures of NSSI and depressive symptoms in adolescents. Methods: Participants were recruited in the psychiatric outpatient clinics of three tertiary hospitals between April 10 and July 10, 2023. All participants been already found with self-injury behaviors in outpatient when enrolled. NSSI diagnostic criteria and Patient Health Questionnaire-9 (PHQ-9) were utilized to collect NSSI and depressive symptoms separately. We performed a network analysis to visualize the correlation between each symptom and to identify core and bridging symptoms in comorbidities. Results: A total of 248 patients were enrolled in the study, with a mean age of 15.48 (SD = 1.62). Based on the PHQ-9 scores and grades, our results showed that the incidence of depression in adolescents with non-suicidal self-injury behavior was relatively high (N=235, 94.76%), with the majority having severe depression. The network analysis revealed that nodes D-6 "feeling bad, failing or letting yourself or your family down", D-1 "little interest or pleasure" and D-4 "feeling tired" were the most vital and most central symptoms. The most crucial bridging symptom is the node NSSI-8 "frequent thinking about self-injury", which connects the NSSI to the depression comorbid network. Conclusion: This study offers a significant symptom-level conceptualization of the association between NSSI and depressive symptoms in a clinical sample of adolescents, which not only enhances our understanding of the comorbid but also identifies potential treatment targets to prevent and treat comorbidity between adolescent NSSI and depression.

AGIDB: a versatile database for genotype imputation and variant decoding across species.

The high cost of large-scale, high-coverage whole-genome sequencing has limited its application in genomics and genetics research. The common approach has been to impute whole-genome sequence variants obtained from a few individuals for a larger population of interest individually genotyped using SNP chip. An alternative involves low-coverage whole-genome sequencing (lcWGS) of all individuals in the larger population, followed by imputation to sequence resolution. To overcome limitations of processing lcWGS data and meeting specific genotype imputation requirements, we developed AGIDB (https://agidb.pro), a website comprising tools and database with an unprecedented sample size and comprehensive variant decoding for animals. AGIDB integrates whole-genome sequencing and chip data from 17 360 and 174 945 individuals, respectively, across 89 species to identify over one billion variants, totaling a massive 688.57 TB of processed data. AGIDB focuses on integrating multiple genotype imputation scenarios. It also provides user-friendly searching and data analysis modules that enable comprehensive annotation of genetic variants for specific populations. To meet a wide range of research requirements, AGIDB offers downloadable reference panels for each species in addition to its extensive dataset, variant decoding and utility tools. We hope that AGIDB will become a key foundational resource in genetics and breeding, providing robust support to researchers.

Validity and reliability of the Chinese version of the disease-related fear scale in patients with epilepsy.

OBJECTIVE: This study aims to test the validity and reliability of the Chinese version of the Disease-Related Fear Scale (D-RFS) in order to understand the experience of fear in patients with epilepsy (PWE). METHODS: The researchers obtained translation permission and followed international guidelines to develop a Chinese version of the D-RFS. A total of 609 PWE were recruited from a general tertiary hospital in Hangzhou, China, between January 2023 and June 2023. We evaluated the psychometric properties of the D-RFS, including content validity, reliability, test-retest reliability, internal consistency, and construct validity. RESULTS: Exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were conducted on two separate samples with a sample size of 307 and 302. The results of EFA indicated that the scale could be divided into three dimensions, which were supported by the structure in CFA. We named the three dimensions as follows: "fear of seizure consequences", "fear of poor epilepsy management", and "fear of social restrictions", respectively. The Cronbach's alpha coefficient for the entire scale was 0.960, with a coefficient of 0.907, 0.953, and 0.917 on three dimensions. CONCLUSION: The Chinese version of the D-RFS was found to be an effective and reliable tool to measure the experience of fear in adult PWE in China. The study could lay the foundation for future investigations to explore associated factors of epilepsy-related fear and establish intervention strategies to alleviate patients' fear in clinical practice.

Prediction of NH3 and HCN yield from biomass fast pyrolysis: Machine learning modeling and evaluation.

Rapid pyrolysis is a promising technique to convert biomass into fuel oil, where NOX emission remains a substantial environmental risk. NH3 and HCN are top precursors for NOX emission. In order to clarify their migration path and provide appropriate strategies for their controlling, six up-to-date machine learning (ML) models were established to predict the NH3 and HCN yield during rapid pyrolysis of 26 biomass feedstocks. Cross-validation and grid search methods were used to determine the optimal hyperparameters for these ML models. The support vector regression (SVR) model achieved optimal accuracy among them. The optimal root means square error (%), mean absolute error (%), and R2 of test set for NH3/HCN yield were 1.2901/1.1531, 1.0501/0.84712, and 0.98253/0.96152, respectively. In addition, based on the results of Pearson correlation analysis, the input variables with a weak linear correlation with the target product were eliminated, which was found capable of improving the prediction accuracy of almost all ML models except SVR. While after input variables elimination, the SVR model still showed the optimal NH3 and HCN yield prediction accuracy. It reflects SVR's great significance and potential for predicting the yield of NOX precursors during rapid biomass pyrolysis.

miR167d-ARFs Module Regulates Flower Opening and Stigma Size in Rice.

Flower opening and stigma exertion are two critical traits for cross-pollination during seed production of hybrid rice (Oryza sativa L.). In this study, we demonstrate that the miR167d-ARFs module regulates stigma size and flower opening that is associated with the elongation of stamen filaments and the cell arrangement of lodicules. The overexpression of miR167d (OX167d) resulted in failed elongation of stamen filaments, increased stigma size, and morphological alteration of lodicule, resulting in cleistogamy. Blocking miR167d by target mimicry also led to a morphological alteration of the individual floral organs, including a reduction in stigma size and alteration of lodicule cell morphology, but did not show the cleistogamous phenotype. In addition, the four target genes of miR167d, namely ARF6, ARF12, ARF17, and ARF25, have overlapping functions in flower opening and stigma size. The loss-of-function of a single ARF gene did not influence the flower opening and stigma size, but arf12 single mutant showed a reduced plant height and aborted apical spikelets. However, mutation in ARF12 together with mutation in either ARF6, ARF17, or ARF25 led to the same defective phenotypes that were observed in OX167d, including the failed elongation of stamen filaments, increased stigma size, and morphological alteration of lodicule. These findings indicate that the appropriate expression of miR167d is crucial and the miR167d-ARFs module plays important roles in the regulation of flower opening and stigma size in rice.

The relationship between nuclear factor-erythrocyte-related factor 2 and antioxidant enzymes in the placenta of patients with gestational diabetes and the metabolism of umbilical cord endothelial cells.

The paper aimed to explore the relationship between nuclear factor erythroid 2 related factor 2 (Nrf2), antioxidant enzymes and the metabolism of umbilical cord endothelial cells in the placenta of patients with gestational diabetes (GDM). A total of 200 pregnant women who underwent an obstetric examination at the Municipal Maternity and Child Health Hospital from March 2018 to December 2019 were selected, with an average age of 30.91±3.24. According to the plasma glucose level and oral glucose tolerance test (OGTT), pregnant women were divided into a control group and an observation group. Blood samples were collected from these pregnant women, serum was removed, put into a centrifuge tube and stored in the refrigerator of the laboratory at - 80 °C. Placental tissue was collected for biochemical analysis. GSH level was detected by absorbance kit, and serum MDA content was detected by spectrophotometry. The expression levels of Heme oxygenase-1(HO-1), Nrf2, and NQO1 protein in placental tissue were analyzed by gel electrophoresis. Western blot analysis was used to detect the protein expression levels of Bach1 and Keap1 in endothelial cells. PCR real-time analysis was used to detect the expression of GSH and NQO1 mRNA. Results showed that the SOD and GSH levels in the serum of the observation group were lower than those of the control group (P<0.05). The protein expression levels of HO-1, Nrf2 and NQO1 in the observation group were higher than those in the control group (P<0.05). The GSH level of the HNE+ observation group was lower than that of the HNE+ control group before stimulation (P<0.05). 1.5 hours after the stimulation, the GSH levels of the two groups of cells were decreased. After 6 hours, the GSH levels of the two groups began to increase. The GSH level of HUVEC in the HNE+ observation group was lower than that of the HNE+ control group after 48 hours. The expression level of Bach1 protein in the HNE+ observation group was lower than that in the HNE+ control group (P<0.05). The expression level of Keap1 protein in the HNE+ observation group and HNE+ control group did not change (P>0.05). The expression levels of GSH and NQO1 mRNA in the HNE+Nrf2 silence group were lower than that in the Nrf2 silence group (P<0.05). The expression levels of GSH and NQO1 mRNA in the HNE+Nrf2 overexpression observation group were higher than those of the HNE+Nrf2 silence group (P<0.05). The apoptosis of trophoblast in the placenta of GDM patients was significantly decreased. The continuous lack of redox signals in fetal endothelial cells in patients with gestational diabetes can destroy the defense ability of cells in the uterus against oxidative stress. Nrf2 antioxidant defense pathway can provide therapeutic targets for reducing oxidative stress associated with diabetes and aging.

Distribution of urinary N-acetyl-beta-D-glucosaminidase and the establishment of reference intervals in healthy adults.

BACKGROUND: Urinary N-acetyl-beta-D-glucosaminidase (NAG) plays an important role in the early diagnosis and progression of diseases related to renal tubular injury. We detected the urinary NAG concentration, assessed the preliminary statistics of its distribution, and established reference intervals for healthy adults in China using the rate method. METHODS: A total of 1,095 reference individuals (aged 20 to 79 years) met the requirements for inclusion in this study. Urinary NAG concentrations were detected using an AU5800 automatic biochemical analyzer with its matched reagents. The Kolmogorov-Smirnov test was used to analyze the normality of the data. According to the guidelines of C28-A3 and WS/T 402-2012, the reference intervals of urinary NAG were established using the nonparametric percentile method (unilateral 95th percentile). RESULTS: The urinary NAG data showed a non-normal distribution. The distribution of urinary NAG was significantly different by sex and age. Therefore, the reference intervals of urinary NAG were established using the rate method: males (aged 20-59 years) <19.4 U/L (90% CI: 18.0-20.3 U/L); males (aged 60-79 years) <22.3 U/L (90% CI: 20.2-22.6 U/L); females (aged 20-59 years) <15.7 U/L (90% CI: 15.2-16.5 U/L); and females (aged 60-79 years) <21.4 U/L (90% CI: 20.3-22.3 U/L). CONCLUSIONS: We established preliminary reference intervals of urinary NAG for healthy adults in China to provide guidance for health screening, auxiliary diagnosis, and treatment monitoring of renal tubule-related diseases.

The mitohormetic response as part of the cytoprotection mechanism of berberine : Berberine induces mitohormesis and mechanisms.

It was well-known that Berberine, a major bioactive compound extracted from natural plants Coptis chinensis, has anti-diabetic effects for decades in china. Other types of pharmacological activities, such as anti-inflammatory, antimicrobial, hypolipidemic, and anti-cancer effects, have also been examined. At cellular level, these pharmacological activities were mostly an inhibitory effect. However, the cytoprotective effect of berberine was also observed in various types of cells, such as neurons, endothelial cells, fibroblasts, and ß-cells. The paradoxical result may be closely associated with characteristics and distribution of berberine within cells, and they can be explained mechanically by mitohormesis, one particular form of hormesis. Here, we reviewed the mitohormetic response and assessed the berberine-induced effects and the possible signaling pathway involved. These findings may contribute to better clinical applications of berberine and indicate that some mitochondria-targeted conventional drugs should be considered carefully in clinical application.

The effect of asymmetric reproductive ability on the evolution of cooperation on interdependent networks.

In this paper, we consider an asymmetric reproductive ability on interdependent networks and investigate how this setting affects the evolution of cooperation. In detail, players decide to update their strategies at each step on main network (network B), while for sub network (network A), players update their strategies with a fixed probability p. Obviously, the system restores the traditional case when p = 1, where cooperation can survive by interdependent network reciprocity. And our asymmetric set-up comes into play when p < 1. Numerical simulation results show that our asymmetric coupling will hinder the overall cooperation level for small p. In detail, the introduction of asymmetric reproductive ability urges the formation of symmetry breaking and further weakens the positive impact by location synchronous effect. And the root cause is entirely distinct situation of utility differences on two networks. These observations further demonstrate a class of phenomena on interdependent networks that it would have catastrophic consequences on one network even if a unrelated change only occurs seemingly on another network.

The Preconditioning of Busulfan Promotes Efficiency of Human CD133+ Cells Engraftment in NOD Shi-SCID IL2Rγcnull (NOG) Mice via Intra-Bone Marrow Injection.

Human CD133+ stem cells were injected into the bone marrow cavity of NOG (NOD Shi-SCID IL2Rγcnull) mice with or without preconditioning of busulfan in order to assess the efficiency of human CD133+ cells engraftment. Peripheral blood from CD133+-engrafted NOG mice was analyzed by flow cytometry. The results showed that human CD19+ B lymphocytes could be detected at 4 weeks post-transplantation, and human CD4+, CD8+ subsets of T lymphocytes, CD19- CD14- HLA-DR+ DCs and CD19- CD14+ monocytes could be detected at 16 weeks post-transplantation. The survival rate of mice in busulfan-untreated group (100%) was slightly higher than that in the busulfan-pretreated group (83%) (P > 0.05). However, the differentiation efficiency of CD133+ stem cells in busulfan-pretreated group was significantly higher than that in the untreated group (P < 0.05). This data imply that CD133+ cells could be a good resource for a humanized mouse model, and the preconditioning of busulfan could be more conducive to accelerating the differentiation of human CD133+ cells in NOG mice by intra-bone marrow injection.

Combination of Berberine with Resveratrol Improves the Lipid-Lowering Efficacy.

The natural compound berberine has been reported to exhibit anti-diabetic activity and to improve disordered lipid metabolism. In our previous study, we found that such compounds upregulate expression of sirtuin 1-a key molecule in caloric restriction, it is, therefore, of great interest to examine the lipid-lowering activity of berberine in combination with a sirtuin 1 activator resveratrol. Our results showed that combination of berberine with resveratrol had enhanced hypolipidemic effects in high fat diet-induced mice and was able to decrease the lipid accumulation in adipocytes to a level significantly lower than that in monotherapies. In the high fat diet-induced hyperlipidemic mice, combination of berberine (30 mg/kg/day, oral) with resveratrol (20 mg/kg/day, oral) reduced serum total cholesterol by 27.4% ± 2.2%, and low-density lipoprotein-cholesterol by 31.6% ± 3.2%, which was more effective than that of the resveratrol (8.4% ± 2.3%, 6.6% ± 2.1%) or berberine (10.5% ± 1.95%, 9.8% ± 2.58%) monotherapy (p < 0.05 for both). In 3T3-L1 adipocytes, the treatment of 12 µmol/L or 20 µmol/L berberine combined with 25 µmol/L resveratrol showed a more significant inhibition of lipid accumulation observed by Oil red O stain compared with individual compounds. Moreover, resveratrol could increase the amount of intracellular berberine in hepatic L02 cells. In addition, the combination of berberine with resveratrol significantly increases the low-density-lipoprotein receptor expression in HepG2 cells to a level about one-fold higher in comparison to individual compound. These results implied that the enhanced effect of the combination of berberine with resveratrol on lipid-lowering may be associated with upregulation of low-density-lipoprotein receptor, and could be an effective therapy for hyperlipidemia in some obese-associated disease, such as type II diabetes and metabolic syndrome.

Molecular characterization of triosephosphate isomerase from Echinococcus granulosus.

Cystic echinococcosis (CE) is a zoonosis that can be caused by the larvae of Echinococcus granulosus; this disease occurs worldwide and is highly endemic in China. E. granulosus can produce energy by glycolysis as well as both aerobic and anaerobic respirations. Triosephosphate isomerase is a glycolytic enzyme present in a wide range of organisms and plays an important role in glycolysis. However, there has been little research on triosephosphate isomerase from E. granulosus (Eg-TIM). Here, we present a bioinformatic characterization and the experimentally determined tissue distribution characteristics of Eg-TIM. We also explored its potential value for diagnosing CE in sheep using indirect enzyme-linked immunosorbent assay (ELISA). Native Eg-TIM was located in the neck and hooks of protoscoleces (PSCs), as well as the tegument and parenchyma tissue of adult worms. The entire germinal layer was also Eg-TIM positive. Western blots showed that recombinant Eg-TIM (rEg-TIM) reacts with positive serum from sheep and had good immunogenicity. Indirect ELISA exhibited low specificity (53.6%) and low sensitivity (87.5%) and cross-reacted with both Taenia multiceps and Taenia hydatigena. Our results suggest that TIM may take part in the growth and development of E. granulosus. Furthermore, we determined that rEg-TIM is not a suitable serodiagnostic antigen for CE in sheep.

Evaluating the Effect of Repetitive Transcranial Magnetic Stimulation on Disorders of Consciousness by Using TMS-EEG.

Background: The modulation efficacy of Transcranial magnetic stimulation (TMS) on consciousness improvement of patient with disorder of consciousness (DOC) has not been definitely confirmed. Objective: This study proposes TMS-EEG to assess effects of repetitive TMS (rTMS) on brain modulation of DOC. Methods: Twenty sessions of 10 Hz rTMS were applied over the dorsolateral prefrontal cortex for a patient with DOC. Measures of Coma Recovery Scale-Revised (CRS-R) score, TMS-evoked potential (TEP), perturbation complexity index (PCI), and global mean field power (GMFP) were used to evaluate the consciousness level of the patient at three intervals: before the rTMS protocol (T0), immediately after one session rTMS (T1), and immediately after 20 sessions (T2). Results: It was found that the patient was diagnosed of a minimally conscious state minus (MCS-) by means of CRS-R at the interval of T0, however the TEP and PCI indicated the patient was vegetative state (VS). At the interval of T1, there was not any clinical behavioral improvement in CRS-R, but we could find significant changes in TEP, PCI, and GMFP. At the interval of T2 there was a significant increase of consciousness level according by CRS-R score, PCI value, TEP, and GMFP after 20 sessions of 10 Hz rTMS on the patient with DOC. Conclusions: We demonstrated that TMS-EEG might be an efficient assessment tool for evaluating rTMS protocol therapeutic efficiency in DOC.

[Significance of CD4+ CD25+ CD127(low) regulatory T cells and notch1 pathway in the pathogenesis of aplastic anemia].

OBJECTIVE: To quantify the CD4+ CD25+ CD127(low) regulatory T cell (Treg), the expression levels of forkhead/winged helix transcription factor FOXP3 and Notch1 mRNA in aplastic anemia (AA) patients before and after treatment, and explore the significance of Treg in pathogenesis of AA. METHOD: CD4+ CD25+ and CD4+ CD25+ CD127(low) T cells in peripheral blood were examined with FACS in 29 AA patients at active phase, 14 at recovery phase, 11 at unrecovery phase, and 15 normal controls. The levels of FOXP3 mRNA and Notch1 mRNA expression were detected with RT-PCR, and the correlations between Treg, FOXP3 mRNA and Notchl mRNA were analyzed. RESULTS: The percentages of peripheral activated CD4+ CD25+ T cells in AA patients at active phase (4.3 +/- 0.7)% and unrecovery phase (4.2 +/- 0.6)% were significantly higher than those in normal controls (2.4 +/- 0.8)% (P < 0.05). The proportion of these cells in AA patients at recovery phase was reduced to (2.6 +/- 0.7)% (P < 0.05), being no difference from that in control group. The number of CD4+ CD25+ CD127(low) T cells in AA patients at active phase (2.4 +/- 1.2)% and unrecovery phase (2.5 +/- 1.1)% was decreased significantly compared with those in normal controls (7.1 +/- 2.7)% (P < 0.01) and in AA patients at recovery phase (5.3 +/- 1.0)% (P < 0.01), there was no difference between the latter two groups. In active phase AA patients, the levels of FOXP3 mRNA and Notchl mRNA (0.260 +/- 0.011 and 0.018 +/- 0.005, respectively) were lower than that in control group (1.307 +/- 0.011 and 0.308 +/- 0.028, respectively) (P < 0.01 and P < 0.01). After treatment, the levels significantly increased to 1.287 +/- 0.012 and 0.281 +/- 0.013 (P < 0.01 and P < 0.01), but there was no difference with that of normal controls (P > 0.05). CD4+ CD25+ CD2(low) T cells and FOXP3 were positively related with Notchl (P < 0.01) in AA patients. CONCLUSION: The decreased number and suppressive activity of CD4 CD25+ CD127(low) Treg cells in the peripheral blood of AA patients cause over-activation of autoreactive T cells and suppression of haematopoiesis. One of the mechanisms maybe the reduced expression of Notch1 in the target cells.

[The effect of selectively inhibiting the nuclear factor kappaB activation on survivin expression in leukemic cells].

OBJECTIVE: To investigate the highly specific proteasomal inhibitor MG132-induced apoptosis and its effect on nuclear factor (NF)-kappaB activation and survivin expression in leukemic K562 cell line. METHODS: leukemic cells of the line K562 were cultured and divided into 2 groups: treatment group, undergoing co-incubation with MG132 of the concentrations of 2, 4, 6, and 8 micromol/L respectively for 24 hours, and control group without treatment of MG132. Apoptosis was detected by examination of cell morphology and flow cytometry. Survivin expression and NF-kappaB activation were analyzed by immunocytochemistry and Western blotting. RESULTS: MG132 induced apoptosis of the K562 cells dose-dependently. Both survivin and NF-kappaB were highly expressed in the K562 cells. Compared with the control group, K562 cell treated with MG132 at the concentrations of 2, 4, 6, and 8 micromol/L for 24 hours showed the decrease of NF-kappaB activation to 75.0% +/- 3.7%, 59.9% +/- 5.3%, 45.4% +/- 5.7%, and 25.0% +/- 4.2% respectively, and decrease of survivin expression to 90.9% +/- 10.1%, 66.7% +/- 5.2%, 45.4% +/- 5.7%, and 30.3% +/- 6.6% respectively. Downregulation of survivin expression was closely correlated with the inhibition of NF-kappaB activation (Pearson correlation coefficient = 0.989, P < 0.01). CONCLUSION: MG132 induces apoptosis of leukemic cells, and effectively inhibits the NF-kappaB activation accompanied by the downregulation of survivin expression.