[The optimal examination duration for the detection of epileptiform discharge in outpatient video-electroencephalography].

Objective: To determine the optimal examination duration by evaluating the detection rate of epileptiform discharges (EDs) with different examination duration of video-electroencephalography (EEG) in outpatients. Methods: Patients with EDs who underwent 4-hour EEG examination from Xuanwu Hospital, Capital Medical University from October 2020 to November 2021 were retrospectively enrolled, and the detection rates of EDs were calculated with examination duration of 0-0.5 h, 0-1 h, 0-2 h, 0-3 h, and 0-4 h (group A, B, C, D and E), respectively. For each patient, EDs in each hour (group H1, group H2, group H3, group H4) were counted, and the standardized amount of EDs was calculated. For each patient, EDs in wakefulness, drowsiness, non-rapid eye movement-Ⅰ (NREM-Ⅰ), NREM-Ⅱ and NREM-Ⅲ were counted, and the standardized amount of EDs in each state was calculated. Meanwhile, the sleep duration per hour of each patient was also counted (group H1', group H2', group H3', group H4'). The Wilcoxon paired test was used for intergroup comparison to determine the optimal examination duration. Results: A total of 80 patients were enrolled, and aged [M(Q1, Q3)]31 (21, 39) years (range: 5-68 years). There were 38 males and 42 females. The detection rate of EDs was 42.5% (34/80) in group A, 81.3% (65/80) in group B, and 100.0% (80/80) in group C, group D and group E, respectively. The standardized amount of EDs of H1, H2, H3 and H4 was 24.8% (7.8%, 44.2%), 41.5% (25.9%, 63.3%), 15.1% (1.3%, 27.8%) and 1.3% (0, 14.5%), respectively. The standardized amount of EDs of H2 was significantly higher than that of H1, H3 and H4 (all P<0.05). The standardized amount of EDs in wakefulness, drowsiness, NREM-Ⅰ, NREM-Ⅱ and NREM-Ⅲ were 9.6% (0, 28.2%), 3.6% (0, 16.9%), 3.3% (0, 11.8%), 47.3% (21.9%, 72.5%) and 0 (0, 11.5%), respectively. The standardized amount of EDs in NREM-Ⅱ was significantly higher than that in wakefulness, drowsiness, NREM-Ⅰ and NREM-Ⅲ (all P<0.05). The sleep duration in the group of the H1', H2', H3' and H4' was 13.6 (2.5, 23.6), 35.8 (16.5, 54.2), 14.5(0, 34.7) and 0 (0, 14.6) minutes, respectively. The sleep duration in the group of the H2' group was significantly longer than that in the group of H1', H3' and H4' (all P<0.05). Conclusion: The study recommends 2 hours video-EEG in outpatients, which not only ensures the detection rate of EDs, but also facilitates patient cooperation and optimizes the allocation of medical resources.

[Effect and safety of endobronchial placement of vaseline gauze in the treatment of patients with bronchial fistula].

Objective: To investigate the application of vaseline gauze to occlude the bronchial fistulas and its clinical effectiveness and safety in this retrospective study. Methods: This study retrospectively reviewed the clinical records of 14 patients with bronchial fistulas at Department of Respiratory and Critical Care Medicine, Shanghai Dongfang Hospital affiliated to Tongji University between June 2019 and June 2022. Seven of the 14 patients were female, and the age ranged from 16 to 74 years. We retrieved all the clinical records of all the enrolled patients during the 6 to 12 months follow-up after the operation, including the information for removal of chest drainage pipe, the failure of endobronchial blockage using vaseline gauze, as well as the complications (migration of the vaseline gauze, obstructive pneumonia, pulmonary atelectasis, et. al.) after the operation. Results: Of the 14 patients, 3 patients had fistula located in main or lobar bronchi; 10 patients had fistula located in distal airways; and 1 patient had fistula located both in main bronchi and distal airways. Ten patients were complicated with pneumonia or pleural cavity infections; Five were complicated with pneumothorax or hydropneumothorax. All of the 14 patients achieved successful airway occlusion after the placement of vaseline gauze in the responsible bronchial airways or stumps for the fistulas. Eleven of the 14 patients successfully removed the drainage tube for the residual cavity, 3 of the 14 patients successfully removed the vaseline gauze for the fistula which was healing during the follow up of 6-12 months. No one of the patients had severe complications or treatment failure. Conclusion: Bronchial placement of vaseline gauze might be a feasible and effective technique for treatment of bronchial fistulas.

[Preoperative serum creatinine as an independent prognostic biomarker in patients with early-stage cervical adenocarcinoma].

Objective: To investigate the effect of preoperative serum creatinine (Scr) level on the prognosis of patients with early cervical adenocarcinoma (ADC) and its predictive value. Methods: A retrospective review was performed on 199 patients with the International Federation of Gynecology and Obstetrics (FIGO) stage ⅠA1-ⅡA1 and pathology-proven invasive ADC from January 2005 to December 2015. Patients were followed up by phone and outpatient, with a median follow-up time 77.5 (57.0, 114.0) months, 11 cases (5.5%) were missing, 19 cases (10.1%) recurred, and 17 cases (9.0%) died. Multivariate analysis was performed by Cox regression model to analyze the related factors of the prognosis of ADC patients. The optimal cut-off point was determined by the analysis of receiver operating characteristics (ROC), and the predictive value of related factors for prognosis was evaluated by the area under the curve (AUC). Results: The median age of 199 patients was 44.0 (39.0-50.0) years. Overall, 16 patients (8.0%) were stage ⅠA1; 4 patients (2.0%) were stage ⅠA2; 147 patients (74.0%) were stage ⅠB1; 13 patients (6.5%) were stage ⅠB2; 19 patients (9.5%) were stage ⅡA1. The multivariate analysis showed that FIGO stage [4.570 (1.625-12.854)] and elevated Scr [1.065 (1.006-1.128)] were correlated with DFS in patients with early ADC, as well as correlated with OS [4.412 (1.458-13.350) and 1.076 (1.012-1.144), respectively (all P<0.05)]. The optimal cut-off point of Scr level was 75.2 µmoI/L. The AUC showed that the Scr level was a predictor of DFS (AUC=0.677, 95%CI: 0.608-0.742, P=0.006) and OS (AUC=0.677, 95%CI: 0.607-0.741, P=0.012). Conclusions: The preoperative Scr level independently predicts the prognosis of early-stage ADC; patients with Scr levels>75.2 µmoL/L might require more follow-up and adjuvant treatment, as they might have a poorer prognosis.

LncRNA ZEB2-AS1 promotes the proliferation, migration and invasion of esophageal squamous cell carcinoma cell through miR-574-3p/HMGA2 axis.

The article "LncRNA ZEB2-AS1 promotes the proliferation, migration and invasion of esophageal squamous cell carcinoma cell through miR-574-3p/HMGA2 axis, by J.-H. Xu, R.-Z. Chen, L.-Y. Liu, X.-M. Li, C.-P. Wu, Y.-T. Zhou, J.-D. Yan, Z.-Y. Zhang, published in Eur Rev Med Pharmacol Sci 2020; 24 (10): 5391-5403-DOI: 10.26355/eurrev_202005_21323-PMID: 32495874" has been withdrawn from the authors due to some technical reasons. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21323.

[The variation of serum uric acid levels among patients with myocardial infarction treated with ticagrelor and the association between serum uric acid and platelet reactivity].

Objectives: To compare the impact of ticagrelor or clopidogrel on serum uric acid levels among patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) and further evaluate the effects of variation of serum uric acid levels on platelet reactivity. Methods: STEMI patients who admitted to Fuwai Hospital from April 2017 to January 2020, and underwent primary PCI and discharged alive with aspirin and ticagrelor or clopidogrel were included in this study. Patients were divided into ticagrelor group and clopidogrel group. The baseline clinical data were collected. Serum uric acid and creatinine levels at baseline and 30 days post-PCI were measured. Light transmittance aggregometry was used to assess maximum aggregation rate induced by adenosine diphosphate and arachidonic acid. The changes of serum uric acid and creatinine were compared between the two groups. Multivariate logistic regression was performed to evaluate independent related factors for rise in the uric acid levels, and the effect of variation of serum uric acid level on platelet reactivity was analyzed. Results: A total of 967 patients were included, the age was (59.4±12.1) years, and 163 case were female. There were 550 cases in ticagrelor group (56.9%) and 417 cases in clopidogrel group (43.1%). Baseline serum uric acid and creatinine levels were similar between the 2 groups. At 30 days, the serum uric acid level [(347.2±96.5) mmol/L vs. (341.2±105.3) mmol/L, P=0.009] and absolute [46.4 (-2.4, 88.1) mmol/L vs. 25.0 (-21.9, 73.0) mmol/L, P=0.001] and percentage [13.2 (-0.01, 29.0) % vs. 7.9 (-5.7, 25.0) %, P=0.007] increase in the serum uric acid levels were significantly higher in ticagrelor group than in clopidogrel group. The level of serum creatinine at 30 days was significantly lower in ticagrelor group than in clopidogrel group [(89.7±21.3) µmol/L vs. (94.4±43.9) µmol/L, P<0.05], whereas there were no differences in absolute [8.0 (-1.4, 16.6) µmol/L vs. 7.8 (-2.0, 16.6) µmol/L] and percentage [10.5 (-1.7%, 22.6%) vs. 9.8 (-2.4%, 22.1%)] change in the serum creatinine between the 2 groups (all P>0.05). Logistic regression analysis showed that, after adjusting for confounding factors, ticagrelor therapy was an independent related factor of serum uric acid elevation (OR=1.582, 95% CI:1.023-2.447, P=0.039). The variation of the serum uric acid levels did not affect platelet aggregation and the percentage of high platelet reactivity in both groups. Conclusions: Ticagrelor use is related to a significant increase in the serum uric acid levels at 30 days post-PCI in this patient cohort. The variations in the uric acid levels do not increase the percentage of high platelet reactivity in STEMI patients treated with ticagrelor or clopidogrel.

LncRNA ZEB2-AS1 promotes the proliferation, migration and invasion of esophageal squamous cell carcinoma cell through miR-574-3p/HMGA2 axis.

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is a common malignant epithelial tumor in the elderly, and the cause is very complicated. Therefore, the study of the pathogenesis of ESCC is conducive to the effective treatment of ESCC. Many studies indicated that lncRNAs were important regulatory factors in tumor formation and disease development. However, the regulatory network of lncRNA in ESCC has not been fully explored. MATERIALS AND METHODS: The expression of miR-574-3p, ZEB2-AS1, and HMGA2 was measured using qRT-PCR. The protein expression of PCNA, Cleaved-caspase3, MMP9, and HMGA2 was detected through Western blot. Cell proliferation or apoptosis of transfected cells was calculated via CKK-8 assay or flow cytometry. Transwell assay was applied to detect cell migration and invasion of ESCC cells. Luciferase reporter assay and RNA pull-down were used to determine the relationship among miR-574-3p, ZEB2-AS1, and HMGA2 in ESCC. Moreover, the regulatory network of ZEB2-AS1 has been verified in vivo in this study. RESULTS: We found that ZEB2-AS1 was upregulated in ESCC tissues and cells. The knockdown of ZEB2-AS1 could inhibit cell proliferation, invasion, and migration, as well as promoted cell apoptosis in ESCC. Interestingly, miR-574-3p deficiency or HMGA2 promotion could reverse the effects of si-ZEB2-AS1 on ESCC cell progression. Luciferase reporter assay indicated that miR-574-3p was a target miRNA of ZEB2-AS1 and HMGA2 was a target gene of miR-574-3p in ESCC. CONCLUSIONS: In this paper, we first verified the novel regulatory mechanism of lncRNA ZEB2-AS1 in ESCC cellular process. LncRNA ZEB2-AS1 promoted the proliferation, migration, and invasion of ESCC by modulating miR-574-3p/HMGA2 axis, indicating that ZEB2-AS1 played essential roles in cell progression in ESCC and providing a new therapeutic target of ESCC.

[Associations between postprocedural D-dimer, hs-CRP, LDL-C levels and prognosis of acute myocardial infarction patients treated by percutaneous coronary intervention].

Objective: To investigate the association between postprocedural D-dimer, high sensitivity C-reactive protein(hs-CRP) and low-density lipoprotein-cholesterol(LDL-C) and outcomes of acute myocardial infarction (AMI) patients treated by percutaneous coronary intervention(PCI), in order to clarify the impacts of thrombotic, inflammatory and cholesterol risks on long-term prognosis. Methods: Patients with AMI who underwent emergency PCI from January 2010 to June 2017 in Fuwai Hospital with complete baseline data were enrolled. Patients were stratified into four groups according to quartiles of D-dimer, hs-CRP and LCL-C. Cox regression was used to analyze the relationship between these biomarkers and prognosis. Restricted cubic spline (RCS) was used to characterize the continuous association between risk of all-cause death and biomarkers. The primary outcome was all-cause death. Results: A total of 3 614 patients were included in the analysis. The age was (59.2±12.0) years old, and 2 845 (78.7%) were male and 3 161 (87.5%) patients were diagnosed as ST-segment elevation myocardial infarction. The follow-up time was 652 (414, 1 880) days. Survival analysis showed that postprocedural D-dimer and hs-CRP were significantly associated with all-cause mortality (all P<0.05). Cox regression with multiple adjustments showed that patients with D-dimer≥580 µg/L presented higher risk of all-cause death (HR=2.03, 95%CI 1.22-3.38, P=0.006), compared to patients with D-dimer<220 µg/L. RCS analysis showed that risk of all-cause death was stably high when D-dimer reached 500 µg/L. Multivariable Cox regression also showed that patients with hs-CRP<2.74 mg/L (HR=1.86, 95%CI 1.10-3.15, P=0.020)or hs-CRP≥11.99 mg/L (HR=2.14, 95%CI 1.35-3.40, P=0.001) presented higher mortality compared to patients whose hs-CRP was 2.74-7.18 mg/L. RCS analysis indicated a J-shaped relation between hs-CRP and mortality, as greater risk of death was observed when hs-CRP was lower than 2 mg/L or higher than 10 mg/L. LDL-C was not associated with outcomes (all P>0.05). Conclusions: Postprocedural D-dimer is significantly associated with long-term prognosis of AMI patients treated by PCI. Patients with extremely high or low levels of hs-CRP presents worse outcomes. Intensive and tailored antithrombotic or anti-inflammatory therapies should be considered for patients with increased thrombotic risk and those with extremely high or low inflammatory risk.

[Comparison of six-month follow-up results of primary percutaneous coronary intervention guided by optical coherence tomography or coronary angiography].

Objective: To compare the 6-month follow-up results of primary percutaneous coronary intervention (PPCI) guided by optical coherence tomography (OCT) or coronary angiography (CAG) alone in a larger ST-segment elevation myocardial infarction (STEMI) cohort. Methods: We enrolled 275 STEMI patients undergoing OCT-guided PPCI from March 2017 through December 2018. Two hundred and seventy-five propensity score matched STEMI patients undergoing CAG-guided PPCI served as control group. The 6-month clinical follow-up results were compared between the two groups. The demographic data, complications, coronary angiography and OCT characteristics were evaluated. Results: OCT evaluation showed that there were 151 patients (54.9%) with plaque prolapse and 113 patients (41.1%) with stent malposition. Proximal and/or distal dissection of stents occurred in 38 patients (13.8%), of which 3 patients (1.1%) had both proximal and distal dissection. Of the 38 patients, 2 patients received rescue stent implantation. Results of clinical follow-up at 6 months showed that there was no significant difference in cardiovascular death, repeat myocardial infarction, target vessel revascularization, stroke and hemorrhage endpoint events between OCT-guided PPCI patients and CAG-guided PPCI patients (P=0.682). Conclusion: Clinical events at 6 months are similar between OCT-guided PPCI and CAG-guided PPCI for STEMI patients.

Continued Elevation of Plasma IL-4 and IL-17 Predicts the Progression from VMC to DCM.

OBJECTIVE: To investigate plasma cytokines (interferon gamma, interleukin-4, and interleukin-17) in patients with viral myocarditis (VMC) and evaluate their predictive value in the progression from VMC to dilated cardiomyopathy (DCM). METHODS: A prospective, multicenter, observational study included 536 patients with newly diagnosed VMC admitted in cardiology departments of 24 tertiary super specialised university-affiliated hospitals in the China registry from January 2012 to June 2016. Demographics and clinical characteristics at baseline and after three months were collected, including laboratory blood tests, ECG, echocardiography, and drug treatment in each participating site. The plasma anti-viral antibodies (Abs), anti-heart autoimmune Abs, and cytokines were detected by ELISA. RESULTS: Of the 536 patients, 534 were included for analysis after two patients died in less than a month. The plasma levels of IFN-γ, IL-4, and IL-17 were continually higher in patients with incident DCM than in those without incident DCM at baseline, from the 1st month and the 3rd month; all had a P value of <0.0001. There was a positive correlation between IL-4 and LVEDd (r = 0.30, P < 0.0001) and between IL-17 and LVEDd (r = 0.11, P = 0.02). When all these covariates have entered the model simultaneously, elevated IL-4 and IL-17 were still significantly associated with DCM incidence. The RR (95% CI) of DCM incidence were 1.04 (1.02-1.06) for IL-4 and 5.24 (2.81-9.79) for IL-17. CONCLUSION: The continued elevation of plasma IL-4 and IL-17 in VMC patients were associated with a high incidence of DCM at three months, and these two cytokines were independent predictors for the progression from VMC to DCM.

The full-length genomic sequence of a novel HLA-C*07 allele, HLA-C*07:63, identified in a Chinese individual.

HLA-C*07:63 differs from HLA-C*07:04:01 by a single nonsynonymous change, resulting in an amino acid substitution.

Treatment of advanced breast cancer with chinese medicinal herbs of Fei decoction: a case report.

A 46-year-old female underwent surgery for cancer of the right breast mammary (T3N2M0) in Sep 2010. Following post surgery, adjuvant chemotherapy of CAF regimens (cyclophosphamide+adriamycin+fluorouracil) was administered. Two years later, multiple pulmonary and skeletal metastatic lesions had been found by CT (computerized tomography) and ECT (emission computed tomograph) imaging. She received the treatment of second-line chemotherapy regimens of GP (cisplatin + gemcitabine). In the meantime, we administered Chinese traditional herb drugs (Fei Decoction, mixed a variety of effective herbal components) to help her recover from the poor condition. After taking the Chinese herbs for 2 months, the tumour marker (CEA, CA15-3) dramatically decreased, resulting in the normal range. Both lung and bone metastatic sites reduced according to CT and ECT imaging, and the patient felt free from the complaint of pulmonary and cardiac discomfort. Over time, the quality of life has been greatly improved, we have managed to prolong the PFS (progression-free-survival) and TTP (time-to-progression) from the onset to date. CTM (Chinese traditional medicine) considers human body as a dynamic platform in which all organs are correlative and bind each other. Relationship between heart, liver, spleen, lung and kidney is like an interlink between mother and son, and runs in cycle as a circle. In the course of this combined treatment, we showed that Chinese herbal medicine played an important role in the therapy of breast cancer. Chinese herbs might be an additional choice with their better benefits and tolerability in the treatment of recurrent breast cancer.

In vivo study of four preparative extracts of Clematis terniflora DC. for antinociceptive activity and anti-inflammatory activity in rat model of carrageenan-induced chronic non-bacterial prostatitis.

AIM OF THE STUDY: The present study was conducted to evaluate the anti-inflammatory and antinociceptive activities of Clematis terniflora DC. extracts and fractions and to further support its traditional use as Chinese folk medicine in treatment of urinary infections, especially the disease of prostatitis. MATERIALS AND METHODS: The antinociceptive activity of its water extract (WE), 70% ethanol extract (EE), water eluted part of EE from AB-8 macroporous resin (WEPMR) and 70% ethanol eluted part of EE from AB-8 macroporous resin (EEPMR) was conducted using mice writhing test with different doses. Then the anti-inflammatory activity of the four parts was evaluated on rat models of carrageenan-induced chronic non-bacterial prostatitis (CNP). Preliminary study was taken to determine the phytochemical compositions of the four preparative extracts. RESULTS: Significant writhing inhibitory effect was found with EE at small (7.5 g/kg body wt.), moderate (15 g/kg body wt.) and large (30 g/kg body wt.) doses (doses here are presented as crude herbs) as well as EEPMR at moderate and large doses by oral administration (OA) (p≤0.01). Data from prostatic index, lecithin microsome density and white blood cell level showed that moderate dose of EE and EEPMR both had significant (p≤0.05 or p≤0.01) inhibition effect on carrageenan-induced inflammation in rat prostate. The HPLC analytical results showed that flavonoids were the main active compounds in WE, EE and EEPMR. And most flavonoids were accumulated into the part of EEPMR by AB-8 macroporous resin leaving only few compounds in WEPMR. No acute toxicity was identified in oral administration of the four parts at a dose of 100g/kg body wt. CONCLUSIONS: The results described here suggest that extracts of the aerial part of Clematis terniflora DC. might be of therapeutic interest in the treatment of prostatitis.

A submerged ceramic membrane reactor for the p-nitrophenol hydrogenation over nano-sized nickel catalysts.

The catalytic hydrogenation of p-nitrophenol to p-aminophenol over nano-sized nickel catalysts was carried out in a submerged ceramic membrane reactor. It has been demonstrated that the submerged ceramic membrane reactor is more suitable for the p-nitrophenol hydrogenation over nano-sized nickel catalysts compared with the side-stream ceramic membrane reactor, and the membrane module configuration has a great influence on the reaction rate of p-nitrophenol hydrogenation and the membrane treating capacity. The deactivation of nano-sized nickel is mainly caused by the adsorption of impurity on the surface of nickel and the increase of oxidation degree of nickel.

Effect of astragaloside on cardiomyocyte apoptosis in murine coxsackievirus B3 myocarditis.

Astragaloside is the major component of Astragalus membranaceus, one of the Chinese medical herbs, and has several pharmacological actions on cardiovascular system, including positive inotropic, anti-arrhythmia and anti-oxidant activities. We have investigated the effect of astragaloside on cardiomyocyte apoptosis and expression of apoptosis-associated genes in mice with coxsackievirus B(3) (CVB(3))-induced myocarditis, the former of which has been detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay and the latter determined by using a focused microarray. Results showed that cardiomyocyte apoptosis and expression of various apoptosis associated genes are inhibited after treatment with astragaloside. The anti-apoptotic activity of astragaloside may contribute to the improvement of clinical outcomes in treating myocarditis with pharmaceutics of Astragalus membranaceus.

Activation of p42/44 mitogen-activated protein kinase pathway in long-term potentiation induced by nicotine in hippocampal CA1 region in rats.

AIM: To investigate the relationship between activation of p42/44 mitogen-activated protein kinase (MAPK) pathway and hippocampal long term potentiation (LTP) induced by nicotine in area CA 1. METHODS: Extracellular recording of population spike (PS) was performed within the pyramidal cell layer of hippocampal area CA1 in vitro; Western blot analysis was employed to detect the active phosphorylated state and the total protein expression of p42/44 MAPK. RESULTS: PD98059 concentration-dependently (25 micromol/L, 50 micromol/L) attenuated the induction of LTP induced by nicotine 10 micromol/L; both p42 and p44 MAPK were activated with their total protein expression increasing in CA1 subregion in response to LTP induced by nicotine. CONCLUSION: Activation of p42/44 MAPK pathway is required for hippocampal LTP induced by nicotine.

Expression pattern of the Rett syndrome gene MeCP2 in primate prefrontal cortex.

Dysfunction of the prefrontal cortex may contribute to the autistic features and mental retardation of Rett syndrome, a neuropsychiatric condition caused by mutations of the gene encoding methyl-CpG-binding protein 2 (MeCP2). Because nothing is known about the expression of MeCP2 and other chromatin-associated factors in primate brain, we studied in monkey prefrontal cortex and murine cerebral cortex expression patterns of MeCP2 and of macrohistone H2A (MacroH2A), which like MeCP2 is associated with transcriptionally silent chromatin. In both species, MeCP2 and MacroH2A appeared to be ubiquitously expressed by cortical neurons, including projection neurons and GABAergic interneurons. In the adult monkey, MeCP2 expression was robust throughout all layers of the prefrontal cortex but it was limited in fetal monkeys at embryonic day 110 to the deeper cortical layers and the subplate. These results suggest that MeCP2 may be important for neuronal maintenance in the developing and in the mature primate prefrontal cortex, consistent with the previously reported phenotype of MeCP2-null mutant mice.

Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice.

Mecp2 is an X-linked gene encoding a nuclear protein that binds specifically to methylated DNA (ref. 1) and functions as a general transcriptional repressor by associating with chromatin-remodeling complexes. Mecp2 is expressed at high levels in the postnatal brain, indicating that methylation-dependent regulation of gene expression may have a crucial role in the mammalian central nervous system. Consistent with this notion is the recent demonstration that MECP2 mutations cause Rett syndrome (RTT, MIM 312750), a childhood neurological disorder that represents one of the most common causes of mental retardation in females. Here we show that Mecp2-deficient mice exhibit phenotypes that resemble some of the symptoms of RTT patients. Mecp2-null mice were normal until 5 weeks of age, when they began to develop disease, leading to death between 6 and 12 weeks. Mutant brains showed substantial reduction in both weight and neuronal cell size, but no obvious structural defects or signs of neurodegeneration. Brain-specific deletion of Mecp2 at embryonic day (E) 12 resulted in a phenotype identical to that of the null mutation, indicating that the phenotype is caused by Mecp2 deficiency in the CNS rather than in peripheral tissues. Deletion of Mecp2 in postnatal CNS neurons led to a similar neuronal phenotype, although at a later age. Our results indicate that the role of Mecp2 is not restricted to the immature brain, but becomes critical in mature neurons. Mecp2 deficiency in these neurons is sufficient to cause neuronal dysfunction with symptomatic manifestation similar to Rett syndrome.

DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals.

DNA methyltransferase I (Dnmt1), the maintenance enzyme for DNA cytosine methylation, is expressed at high levels in the CNS during embryogenesis and after birth. Because embryos deficient for Dnmt1 die at gastrulation, the role of Dnmt1 in the development and function of the nervous system could not be studied by using this mutation. We therefore used the cre/loxP system to produce conditional mutants that lack Dnmt1 in neuroblasts of embryonic day 12 embryos or in postmitotic neurons of the postnatal animal. Conditional deletion of the Dnmt1 gene resulted in rapid depletion of Dnmt1 proteins, indicating that the enzyme in postmitotic neurons turns over quickly. Dnmt1 deficiency in postmitotic neurons neither affected levels of global DNA methylation nor influenced cell survival during postnatal life. In contrast, Dnmt1 deficiency in mitotic CNS precursor cells resulted in DNA hypomethylation in daughter cells. Whereas mutant embryos carrying 95% hypomethylated cells in the brain died immediately after birth because of respiratory distress, mosaic animals with 30% hypomethylated CNS cells were viable into adulthood. However, these mutant cells were eliminated quickly from the brain within 3 weeks of postnatal life. Thus, hypomethylated CNS neurons were impaired functionally and were selected against at postnatal stages.

[Observation on collaborative treatment of dilated cardiomyopathy].

OBJECTIVE: To observe the therapeutic effect of integrated traditional Chinese and western medicine (TCM-WM) in treating dilated cardiomyopathy (DCM). METHODS: Patients of DCM were randomly divided into two groups, the 164 patients in the TCM-WM group were treated with combination therapy of traditional Chinese and western medicine, consisting of conventional western medicine, such as cardiac diuretic, vasodilative agents, taurine, coenzyme Q10, antiarrhythmics, beta blockers and Chinese herbal preparations such as Astragalus membranaceus and Shengmai injection; while the 156 cases in the control group were treated with conventional western medicine alone, including polarized liquid therapy, etc. RESULTS: The improvement of clinical symptoms and heart function in the TCM-WM group was significantly better than that in the control group. Although the total number of deceased cases in the two groups were similar, the dead number in 3-6 months in the TCM-WM group was less than that in the control group. Moreover, 1 year later, the deceased number of patients insisted with TCM-WM treatment for over 1 year was significantly less than in those treated for only 3-6 months (1 case vs 11 cases). CONCLUSION: Under the condition that there is no specific effective drugs, TCM-WM therapy can yet be regarded as an acceptable therapy for treatment of dilated cardiomyopathy.