Prevalence and Risk Factors of Frailty in Stroke Patients: A Meta-Analysis and Systematic Review.

OBJECTIVES: Summarize the existing evidence regarding the prevalence and risk factors of frailty in stroke patients. DESIGN: A meta-analysis and systematic review. PARTICIPANTS: Stroke patients in hospitals or communities. METHODS: We undertook a systematic review and meta-analysis using articles available in 8 databases, including PubMed, The Cochrane Library, Web of Science, Embase, Chinese Biomedical Database (CBM), China National Knowledge Infrastructure Database (CNKI), Wanfang Database, and Weipu Database (VIP) from January 1990 to April 2022. Studies were quality rated using the Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality tool. RESULTS: A total of 24 studies involving 30,423 participants were identified. The prevalence of frailty and pre-frailty in stroke patients was 27% (95%CI: 0.23-0.31) and 47.9% (95%CI: 0.43-0.53). Female gender (OR = 1.76, 95%CI: 1.63-1.91), advanced age (MD = 6.73, 95%CI: 3.55-9.91), diabetes (OR = 1.34, 95%CI: 1.06-1.69), hyperlipidemia (OR = 1.46, 95%CI: 1.04-2.04), atrial fibrillation (OR = 1.36, 95%CI: 1.01-1.82), National Institutes of Stroke Scale (NIHSS) admission scores (MD = 2.27, 95%CI: 1.72-2.81) were risk factors of frailty in stroke patients. CONCLUSIONS: Frailty was more prevalent in stroke patients. Female gender, advanced age, diabetes, hyperlipidemia, atrial fibrillation, and National Institutes of Stroke Scale (NIHSS) admission scores were identified as risk factors for frailty in stroke patients. In the future, medical staff should pay attention to the early screening of frailty in high-risk groups and provide information on its prevention.

[Evaluation of carotid atherosclerotic plaques by vascular plaque quantification (VPQ) technology of three-dimensional ultrasonography].

OBJECTIVE: To analyze the feasibility of using vascular plaque quantification (VPQ) to evaluate carotid atherosclerotic plaques and to observe the effect of statins on carotid atherosclerotic plaques. METHODS: Patients with carotid plaques from January 2016 to September 2018 in Peking University First Hospital Neurology Department were recruited and underwent three-dimonsional ultrasound (3DUS). Their gray scale median (GSM) and other parameters of carotid plaques were measured with VPQ. The patients were divided into low GSM group (GSM < 40) and high GSM group (GSM≥40). The clinical characteristics and plaque characteristics of the patients in the two groups were compared to analyze the stability of plaques. According to whether taking statins or not, the patients were further divided into statin group and non-statin group, plaque GSM and other parameters of their carotid plaques were measured and the changes of carotid plaques at the end of 3 months and 2 years were observed. RESULTS: A total of 120 patients were enrolled, including 79 males and 41 females, with an average age of (65.39±9.11) years. The patients were divided into low GSM group (31 cases) (GSM < 40) and high GSM group (89 cases) (GSM≥40). The stenosis of the lumen in the low GSM group was more severe (the area stenosis rate was 41.32%±21.37% vs. 29.79%±17.16%, P < 0.05). The nor-malized wall index (NWI) of plaque in low GSM group was significantly higher than that in high GSM group (0.61 ±0.14 vs. 0.52±0.12, P < 0.01). A total of 77 patients, including 51 males and 26 females, aged (64.96±9.58) years, were enrolled to observe the statin effects on carotid plaque. They were divided into statin group (n=56) and non-statin group (n=21) according to whether taking statins or not. At the baseline and 3-month follow-up, there were no significant differences in carotid plaque volume, area, degree of luminal stenosis and GSM between the two groups (P>0.05). At the end of the 2-year follow-up, GSM increased in the statin group [median 10.00 (2.00, 28.00)] but decreased in the non-statin group [median －7.00 (－11.00, 5.50)], with a statistically significant difference between the two groups (P < 0.01). There was no significant increase in carotid plaque volume in the statin group, while there was a slight increase in the non-statin group, but there was no significant difference between the two groups [median increase in plaque volume was 0.00 (－30.00, 40.00) mm3 in the statin group and 30.00 (10.00, 70.00) mm3 in the non-statin group, P>0.05]. CONCLUSION: The VPQ technology of 3DUS can be used to evaluate carotid atherosclerotic plaques. Patients with low GSM (GSM < 40) have more severe vascular stenosis and higher normalized wall index. VPQ technology can also be used to observe the effect of statins on carotid plaque, the GSM of plaques increase in patients who are taking moderate-intensity statin treatment for two years.

[Effects of cinepazide maleate injection on blood pressure in patients with acute ischemic stroke and hypertension].

Objective: To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection. Methods: This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes. Results: This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%,P>0.05) between cinepazide maleate group and control group. Conclusion: Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

[Susceptibility vessel sign in subacute stroke patients with large vessel occlusion].

OBJECTIVE: To investigate the presentation of susceptibility vessel sign (SVS) in subacute stroke patients with large vessel occlusion. METHODS: We collected consecutive stroke patients who were admitted to Peking University First Hospital from December 2017 to August 2019 retrospectively. Those who had intracranial large vessel occlusion and received sensitivity weighted imaging (SWI) within 3 to 14 days after stroke onset were included in our analysis. The diagnosis of large vessel occlusion was based on magnetic resonance angiography (MRA), CT angiography (CTA) or digital subtraction angiography (DSA). The demographic information, clinical characteristics and imaging results were obtained from medical record. The occurrence rates of SVS sign were compared between stroke patients with cardioembolism (CE) and large artery atherosclerosis (LAA). In the sensitivity analysis, we performed a subgroup analysis in those patients who received SWI within 7 to 14 days after stroke onset. We also compared the occurrence rate of SVS sign between the patients with and without atrial fibrillation. RESULTS: A total of 51 patients, 19 females and 32 males, with an average age of (63.04±11.23) years were analyzed in this study. Compared with LAA group, the patients in CE group were older and more likely to have an atrial fibrillation (P < 0.05). There were no significant differences between the CE group and LAA group in gender, hypertension, diabetes, coronary heart disease, hyperlipidemia, smoking, or National Institute of Health stroke scale(NIHSS) score at admission. SVS sign was found in 30 patients. Of whom, 3 were in CE group and 27 in LAA group. The occurrence rate of SVS sign was higher in the LAA group than in the CE group significantly (65.9% vs. 30.0%, P=0.039). The subgroup analysis showed that, in the patients who received SWI examination within 7 to 14 days after stroke onset, the differences between the two groups were still statistically significant (0 vs. 72.7%, P=0.006). Another sensitivity analysis showed that, the rate of SVS in the patients with atrial fibrillation was significantly lower than those patients without atrial fibrillation (25% vs. 65.1%, P=0.043). CONCLUSION: In subacute stroke patients, the occurrence rate of SVS sign in CE group was lower than that of LAA group. The significance of SVS sign in the differentiation of stroke subtype needs further validation.

A case of GNE myopathy mimicking hereditary motor neuropathy.

A 36-year-old woman who presented with upper limb distal weakness since the age of 15 years, with gradual progression to the lower limbs, is reported. Hereditary motor neuropathy was initially suspected based on distal weakness and hyporeflexia; however, whole exome sequencing accidentally revealed a compound heterozygous variant in the GNE gene, and ultrasound revealed increased homogeneous echogenicity in the involved muscles, which is characteristic of myopathic changes. Muscle magnetic resonance imaging revealed fatty infiltration in all limb muscles, sparing the triceps brachii, vastus lateralis and vastus medialis. Muscle biopsy revealed intracytoplasmic rimmed vacuole, supporting the diagnosis of GNE myopathy.

[Prediction of syncope with nonlinear dynamic analysis during head-up tilt in vasovagal syncope patients].

OBJECTIVE: To quantify the relationship between cerebral blood flow velocity and peripheral blood pressure during hypotension period, aiming to predict the brain hypotension before symptomatic occurrence. METHODS: Twenty vasovagal syncope (VVS) patients who had a previous clinical history were selected in groups and 20 pair-matched control subjects underwent 70° tilt-up test. The subjects remained supine for 30 minutes before recordings when Doppler probes, electrodes and Finapres device were prepared. After continuous baseline recordings for 10 min, the subjects underwent head up tilt (HUT) test (70°), and were standing upright for 30 minutes or until syncope was imminent. For ethical reasons, the subjects were turned back to supine position immediately after SBP dropped to ≥20 mmHg, when their consciousness persisted. The point of syncope was synchronized for all the subjects by the point SBP reached the minima. Their beat-to-beat blood pressures (BP) were recorded continuously and bilateral middle cerebral artery (MCA) flow velocities were obtained with two 2 MHz Doppler probes from a transcranial Doppler ultrasonography (TCD) system. A nonlinear dynamic method--multimodal pressure flow (MMPF) analysis was introduced to access cerebral autoregulation during different time intervals. We introduced a new indicator--syncope index (SI), which was extracted from blood flow velocity (BFV) signal to evaluate the variation of cerebral vascular tension, and could reflect the deepness of dicrotic notch in BFV signal. RESULTS: Compared with the syncope index of the baseline value at the beginning of the tilt test, SI in VVS group showed significantly lower when the VVS occurred (0.16±0.10 vs.0.27±0.10,P<0.01),while there was no significant difference in syncope index between the control group at the end of the tilt test and the baseline value at the beginning of the tilt test. For those VVS patients, pulse index and resistance index had no significant change. Syncope index decreased significantly 3 minutes before the point of syncope (0.23±0.07 vs.0.29±0.07,P<0.01). CONCLUSION: Dynamic regulation is exhausted when vasovagal syncope occurred. Tension decrease of small vessels could have some relationship with loss of the cerebral autoregulation capability. The proposed syncope index could be a useful parameter in predicting syncope of VVS patients since it decreased significantly up to 3 minutes earlier from the point of syncope.

[Correlation between DCE-MRI quantitative perfusion histogram parameters, apparent diffusion coefficient and Ki-67 in different pathological types of lung cancer].

Objective: To explore the efficacy of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) histogram molecular imaging index, apparent diffusion coefficient (ADC) in different types of lung cancer and explore their correlation with Ki-67. Methods: A total of 33 cases of lung cancer patients confirmed by pathology in Shaoxing People's Hospital from March 2017 to March 2018 were collected, 28 males and 5 females aged 50-85 years old, including 15 cases of squamous cell carcinoma, 12 cases of adenocarcinoma, and 6 cases of small cell carcinoma. All patients performed DCE-MRI and DWI imaging within one week before surgery or puncture. ADC values, DCE-MRI quantitative perfusion parameters by histogram metrics analysis (mean value, skewness, kurtosis, uniformity, entropy, energy, quantile) of K(trans), K(ep), V(e), and V(p) were then collected. Ki-67 expression in lung cancer tissue was detected by immunohistochemical method. One-way analysis of variance and least significant difference were used to compare the differences among the parameters of the three groups which were normal distribution and equal variances, while Kruskal-Walls test and Mann-Whitney U test were used to compare the parameters that did not conform to normal distribution or variance. Pearson correlation analysis was used to compare the correlations between quantitative perfusion histogram parameters, ADC values and immunohistochemical scores of Ki-67. Results: The Ki-67 count in small cell lung cancer(458±82, P=0.011) and squamous cell carcinoma(355±277, P=0.034)were significantly higher than that in adenocarcinoma (168±164). The correlation analysis showed that there was a significant negative correlation between ADC values and Ki-67 (P=0.018, r=-0.416). And V(e) (Q5, Q10) was negatively related to Ki-67 (P=0.017, r=-0.420; P=0.040, r=-0.366). In squamous cell carcinoma patients, V(e) (homogeneity) was significantly negatively correlated with the expression of Ki-67 (P=0.033, r=-0.570). K(trans)(homogeneity) and V(e) (homogeneity, Q5, Q10, Q25) were significantly positively correlated with ADC values (P value from 0.001 to 0.035, r value from 0.545 to 0.765). Conclusion: DCE-MRI quantitative perfusion histogram parameters, ADC value can evaluate the lung cancer cell proliferation activity in different pathological types.

[The correlation between the cell density of local advanced lung cancer tumor and the ADC value of 3.0 T MRI diffusion weighted imaging].

Objective: To investigate the correlation between tumorous cellular density (TCD) and apparent diffusion coefficient (ADC) of 3.0 T magnetic resonance diffusion weighted imaging (DWI) in local advanced lung cancer. Methods: From January 2015 to December 2017, a total of 59 patients with locally advanced lung cancer confirmed by pathology in Shaoxing People's Hospital who underwent DWI by 3.0 T magnetic resonance imaging were included.The ADC and TCD values of tumor were measured. The difference and correlation between ADC value and TCD in lung cancer were analyzed. Results: Among 59 lung cancer cases who were examined with DWI, 45 cases of TCD were obtained. Statistical analysis showed that the ADC value of small cell lung cancer (SCLC) was significantly higher than that of squamous cell carcinoma (P=0.011)and adenocarcinoma (P=0.004). TCD of small cell carcinoma was significantly higher than that of squamous cell carcinoma (P=0.007) and adenocarcinoma (P<0.01). There was no statistical difference in ADC value and TCD between squamous cell carcinoma and adenocarcinoma (all P>0.05). There was negative correlation between the ADC value and TCD in lung cancer (P=0.001, r=-0.534). Conclusions: DWI is not only beneficial to distinguish SCLC from squamous cell carcinoma and adenocarcinoma, but also can indirectly reflect the tumorous cellular density.It can provide a basis for monitoring the therapeutic effect of clinical lung cancer.

Analysis of specific serum markers of colon carcinoma using a Bhattacharyya-based support vector machine.

We aimed to evaluate the specificity of 12 tumor markers related to colon carcinoma and identify the most sensitive index. Bhattacharyya distance was used to evaluate the index. Then, different index combinations were used to establish a support vector machine (SVM) diagnosis model of malignant colon carcinoma. The accuracy of the model was checked. High accuracy was assumed to indicate the high specificity of the index. The Bhattacharyya distances of carcinoembryonic antigen, neuron-specific enolase, alpha-feto protein, and CA724 were the largest, and those of CYFRA21-І, CA125, and UGT1A83 were the second largest. The specificity of the combination of the above seven indexes was higher than that of other combinations, and the accuracy of the established SVM identification model was high. Using Bhattacharyya distance detection and establishing an SVM model based on different serum marker combinations can increase diagnostic accuracy, providing a theoretical basis for application of mathematical models in cancer diagnosis.

Comparisons of different myosin heavy chain types, AMPK, and PGC-1α gene expression in the longissimus dorsi muscles in Bama Xiang and Landrace pigs.

Bama Xiang and Landrace pigs are the local fatty and lean breeds, respectively, in China. We compared differences in carcass traits, meat quality traits, and myosin heavy chain (MyHC) types in the longissimus dorsi muscles between Bama Xiang and Landrace pigs. This was done in pigs of the same age, using real-time PCR, to investigate the relationship between MyHC fiber types and carcass characteristics, meat quality traits, and the key factors regulating muscle fiber type. Bama Xiang pigs exhibited smaller size and slower growth than Landrace pigs (P < 0.01). We found that the superior meat quality, especially the high intramuscular fat (IMF) content in Bama Xiang pig, was related to elevated type I oxidative muscle fiber content (P < 0.01). In contrast, Landrace pig muscle had a higher glycolytic type IIb muscle fiber content (P < 0.01). MyHC I gene expression was significantly positively correlated with backfat thickness and IMF content (P < 0.01). MyHC IIb was significantly negatively correlated with IMF content (P < 0.05), and positively correlated with carcass yield (P < 0.05). AMP-activated protein kinase and peroxisome proliferator-activated receptor-g coactivator-1a are suggested to be the two key factors regulating muscle fiber type in pigs. Our results indicate that muscle fiber composition is one of the key differences leading to the differences of meat quality between Bama Xiang and Landrace pigs. These results may provide a theoretical basis for further studies of the molecular mechanism underlying the excellent meat quality of the Bama Xiang pig.

The curative effect comparison of two kinds of therapeutic regimens on decreasing the relative intensity of microembolic signal in CLAIR trial.

BACKGROUND: Microembolic signals (MESs) are direct markers of unstable large artery atherosclerotic plaques. In a previous study, we found that the number of MESs is associated with stroke recurrence and that clopidogrel plus aspirin more effectively reduce the number of MESs than does aspirin alone. Stroke recurrence is associated with not only the number of MESs but also the size of the MES, which can theoretically be estimated by monitoring the MES intensity via transcranial doppler (TCD). Thus, we compared the effects of clopidogrel and aspirin with aspirin alone on MES intensity using TCD. METHODS: We recruited 100 patients who experienced acute ischemic stroke or transient ischemic attack (TIA) within 7days of symptom onset. All patients also had large artery stenosis in the cerebral or carotid arteries and the presence of MES as revealed by TCD. The patients were randomized to receive either aspirin or clopidogrel and aspirin for 7days. MES monitoring was performed on days 2 and 7. RESULTS: Intent-to-treat (ITT) analysis (46 patients in the dual therapy group, 52 patients in the monotherapy group) and per-protocol (PP) analysis (25 patients in the dual therapy group, 31 patients in the monotherapy group) were performed on 98 patients. The primary finding was that the MES intensity was dramatically reduced in the dual therapy group. ITT analysis of the dual therapy group revealed that the MES intensity was 8.04 (0-16) dB before treatment, 0.00 (0-17) dB on day 2, and 0.00 (0-12) dB on day 7 (P=0.000). In the monotherapy group, the MES intensity was 9.00 (0-20) dB before treatment, 8.25 (0-17) dB on day 2, and 7.0 (0-18) dB on day 7 (P=0.577). PP analysis revealed similar results. No severe hemorrhagic complications were detected. The two patients in this study who experienced stroke recurrence were in the monotherapy group. CONCLUSIONS: Clopidogrel and aspirin more effectively decrease the MES intensity than aspirin alone in patients with large artery stenotic minor stroke or TIA.

Gene expression and enzyme activity of lipoprotein lipase correlate with intramuscular fat content in Guangxi san-huang and Arbor Acres chickens.

Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism. This study investigated LPL gene expression, LPL enzyme activity, and the correlation of each with intramuscular fat (IMF) in Chinese Guangxi san-huang (GXSH) and Arbor Acres (AA) chickens. The results showed that age and breed had significant effects on LPL expression and enzyme activity. Correlation analyses showed significant positive correlations between LPL expression levels and IMF contents in the breast and thigh tissues of both GXSH (r = 0.712, P = 0.001; r = 0.792, P < 0.001, respectively) and AA (r = 0.644, P < 0.001; r = 0.545, P < 0.001, respectively) chickens. The results also indicated a significant positive correlation between LPL enzyme activity and IMF contents in the breast and thigh tissues of both GXSH (r = 0.615, P = 0.001; r = 0.685, P < 0.001, respectively) and AA (r = 0.600, P = 0.001; r = 0.528, P = 0.003, respectively) chickens. The results indicated that the LPL gene was significantly correlated with IMF in these two breeds. The results presented here could contribute to knowledge of LPL mRNA developmental expression patterns and enzyme activity, and it could facilitate further research on the molecular mechanisms underlying IMF deposition in chickens.

Complete mitochondrial genome of the Cyclemys dentata and phylogenetic analysis of the major family Geoemydidae.

In the present study, the complete mitochondrial (mt) genome of Cyclemys dentata was determined using PCR reactions. The structural organization and gene order of C. dentata were equivalent to those of most other vertebrates. The mt genome was 16,489 bp in length, has rich A+T content, consisting of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a control region (D-loop). All protein-coding genes started with ATG, many genes have complete stop codons, except ND2, COX3, ND3, and cyt-b genes had incomplete stop codons of T. The light-strand replication origin (OL) of C. dentata might fold into a stable stem-loop secondary structure, and its loop had 2 nt less than that of the Cyclemys atripons OL sequence. The D-Loop of C. dentata contained a central domain (CD), 2 extended termination associated sequences (ETAS1, ETAS2) and 3 conserved sequence blocks (CSB1, CSB2, CSB3). The average length of 20 turtles' mt genomes was 16,692.5 bp, including 34.1% A, 27.0% T, 26.0% C and 12.9% G. The C. dentata mitochondrial genome could provide useful data for further studies on phylogenetics and conservation genetics of this species. The phylogenetic relationships of the family Geoemydidae were analyzed by maximum-likelihood (ML) and neighbor-joining (NJ) based on concatenated sequences of 13 protein-coding genes from 20 turtle species. The ML and NJ trees had homologous topologies. The results support the existing classification of the genera of Geoemydidae, that C. dentata was a sister species of C. atripons, Pyxidea nested in Cuora, and Chinemys was synonymous with Mauremys.

Identification of a novel HLA-DRB1 allele, HLA-DRB1*12:51, in a Chinese Cord Blood Donor.

HLA-DRB1*12:51 has a single nucleotide difference to DRB1*12:02:01 at position 208, G > T.

¹H NMR-based metabonomics in brain nucleus accumbens and striatum following repeated cocaine treatment in rats.

Studies have shown a few cerebral metabolites modified by cocaine in brain regions; however, endogenous metabolic profiling has been lacking. Ex vivo (1)H NMR (hydrogen-1 nuclear magnetic resonance) spectroscopy-based metabonomic approach coupled with partial least squares was applied to investigate the changes of cerebral metabolites in nucleus accumbens (NAc) and striatum of rats subjected to cocaine treatment. Our results showed that both single and repeated cocaine treatment can induce significant changes in a couple of cerebral metabolites. The increase of neurotransmitters glutamate and gamma-amino butyric acid (GABA) were observed in NAc and striatum from the rats repeatedly treated with cocaine. Creatine and taurine increased in NAc whereas taurine increased and creatine decreased in striatum after repeated cocaine treatment. Elevation of N-acetylaspartate in NAc and striatum and decrease of lactate in striatum were observed, which may reflect the mitochondria dysregulation caused by cocaine; moreover, alterations of choline, phosphocholine and glycerol in NAc and striatum could be related to membrane disruption. Moreover, groups of rats with and without conditioned place preference (CPP) apparatus are presenting difference in metabolites. Collectively, our results provide the first evidence of metabonomic profiling of NAc and striatum in response to cocaine, exhibiting a regionally-specific alteration patterns. We find that repeated cocaine administration leads to significant metabolite alterations, which are involved in neurotransmitter disturbance, oxidative stress, mitochondria dysregulation and membrane disruption in brain.

Sensitive measurement of quantity dynamics of FLT3 internal tandem duplication at early time points provides prognostic information.

BACKGROUND: The level of minimal residual disease (MRD) in acute myeloid leukemia (AML) at early time points (TPs) may be an important prognostic factor. Although internal tandem duplication of FLT3 (FLT3-ITD) as an MRD marker has been questioned for its instability based on semi-quantitative methods, we hypothesized that FLT3-ITD dynamics measured by sensitive quantitative real-time PCR at early TPs before appearance of instability may provide prognostic information. PATIENTS AND METHODS: We measured mutant quantity in 493 serial samples from 55 patients with a median follow-up time of 64.8 months. The FLT3-ITD quantities after induction (TP1) and after the first post-induction chemotherapy (TP2) were analyzed. RESULTS: We found that lower FLT3-ITD levels at TP2 predicted longer overall survival (OS) and disease-free survival (DFS) regardless of cytogenetic risk. Multivariate analysis showed that ≥3 log reduction of FLT3-ITD at TP2 independently predicted better DFS and a trend toward better OS. FLT3-ITD disappeared at relapse in 16.7% of patients and none in those harboring mutant NPM1 compared with 29.4% in those with wild-type NPM1 (P = 0.032). CONCLUSIONS: Though the mutation may disappear at relapse in a few patients, FLT3-ITD levels at early TPs after chemotherapy provide prognostic information. FLT3-ITD is significantly more stable in those with mutant NPM1.

Salicylate, an aspirin metabolite, specifically inhibits the current mediated by glycine receptors containing alpha1-subunits.

BACKGROUND AND PURPOSE: Aspirin or its metabolite sodium salicylate is widely prescribed and has many side effects. Previous studies suggest that targeting neuronal receptors/ion channels is one of the pathways by which salicylate causes side effects in the nervous system. The present study aimed to investigate the functional action of salicylate on glycine receptors at a molecular level. EXPERIMENTAL APPROACH: Whole-cell patch-clamp and site-directed mutagenesis were deployed to examine the effects of salicylate on the currents mediated by native glycine receptors in cultured neurones of rat inferior colliculus and by glycine receptors expressed in HEK293T cells. KEY RESULTS: Salicylate effectively inhibited the maximal current mediated by native glycine receptors without altering the EC(50) and the Hill coefficient, demonstrating a non-competitive action of salicylate. Only when applied simultaneously with glycine and extracellularly, could salicylate produce this antagonism. In HEK293T cells transfected with either alpha1-, alpha2-, alpha3-, alpha1beta-, alpha2beta- or alpha3beta-glycine receptors, salicylate only inhibited the current mediated by those receptors that contained the alpha1-subunit. A single site mutation of I240V in the alpha1-subunit abolished inhibition by salicylate. CONCLUSIONS AND IMPLICATIONS: Salicylate is a non-competitive antagonist specifically on glycine receptors containing alpha1-subunits. This action critically involves the isoleucine-240 in the first transmembrane segment of the alpha1-subunit. Our findings may increase our understanding of the receptors involved in the side effects of salicylate on the central nervous system, such as seizures and tinnitus.

Acute myeloid leukemia bearing t(7;11)(p15;p15) is a distinct cytogenetic entity with poor outcome and a distinct mutation profile: comparative analysis of 493 adult patients.

Acute myeloid leukemia (AML) with t(7;11)(p15;p15), which results in a NUP98-HOXA9 fusion, is a distinct entity, but this subtype has not been characterized in detail. In a comprehensive study comparing 11 such patients with another 482 adult patients, we found that those with t(7;11) were younger (P=0.0076) and female (P=0.0111), with almost all having the M2-subtype of AML (P<0.0001). Even when those with low-risk karyotypes were excluded, patients with t(7;11) had poorer overall survival than the other AML group (median 13.5 and 20 months, respectively, P=0.045) and poorer relapse-free survival (median 6 and 12 months, respectively, P=0.003). The NUP98-HOXA9 fusion was strongly associated with KRAS and WT1 mutations (P=0.015 and P=0.0018, respectively). We characterized four varieties of this fusion, among which NUP98 exon 12/HOXA9 exon 1b was present in all 11 patients. We developed a highly sensitive and specific assay to quantify the abundance of leukemic cells, and found that the fusion remained detectable in morphological complete remission, even after allogeneic stem cell transplantation, suggesting that this disease was highly refractory to very intensive treatment. AML with NUP98-HOXA9 fusion therefore appears to have a distinct clinical and biological profile, and should be regarded as a poor prognostic group.

A door-to-door survey of intracranial atherosclerosis in Liangbei County, China.

We studied 590 asymptomatic villagers aged > or =40 years in Liangbei County in central rural China and found 41 subjects (prevalence 6.9%) with intracranial atherosclerosis. In a multivariate analysis, the significant risk factors for intracranial stenosis were hypertension (OR 2.53; 95% CI 1.12 to 5.72), glycosuria (OR 3; 1.19 to 7.97), heart disease (OR 4; 1.39 to 11.6), and family history of stroke (OR 5.2; 1.38 to 20). Intracranial atherosclerosis is not uncommon among asymptomatic Chinese subjects.

Indiscernible benefit of high-resolution HLA typing in improving long-term clinical outcome of unrelated umbilical cord blood transplant.

The success of allogeneic hematopoietic stem cell transplantation depends in part on the accuracy of human leukocyte antigen (HLA) matching between the donor-recipient pair. The higher the number of matching HLA alleles, the smaller the chance that the transplant recipient will develop complications. Umbilical cord blood (UCB) transplantation was noted to result in a remarkably low frequency and severity of graft-versus-host disease (GvHD) and graft rejection compared to that in unrelated bone marrow transplant recipients. At present most banks match UCB donors for respective recipients by HLA-A, -B low-resolution typing and -DRB1 high-resolution typing. We retrospectively conducted high-resolution sequence-based HLA typing on DNA samples available from 65 Chinese UCB-recipient pairs typed previously by using low-resolution sequence-specific oligonucleotide probes and sequence-specific primers, and evaluated the clinical outcome. High-resolution typing revealed imperceptible HLA alleles that were hardly identified in low-resolution typing. Univariate analyses demonstrated no significant correlation between the extents of high-resolution HLA disparity with engraftment, graft failure, acute GvHD, transplant-related mortality and long-term 6-year overall survival. Data from the study suggest that high-resolution typing for HLA-A, -B and -DRB1 contributed no substantial improvement to UCB transplant outcome. Low-resolution typing appears to be amenable to matching UCB-recipient pairs without compromising the quality of transplant.