Normal Absolute Monocyte Count at the Time of Relapse is Associated with Improved Survival After First Salvage Therapy in Adult Patients with Early Relapsed B-Lineage Acute Lymphoblastic Leukemia.

BACKGROUND: Peripheral monocytes, a key cell type for innate immunity, have been shown to be associated with survival in various types of hematological malignancies. However, no previous studies regarding the prognostic impact of peripheral absolute monocyte count (AMC) in early relapsed B-lineage acute lymphoblastic leukemia (B-ALL) have been reported. METHODS: Forty-nine cases of early relapsed adult B-ALL were reviewed. The upper (0.80 × 109/L) and lower limits (0.12 × 109/L) of the normal value for AMC were used as cut-off points. Kaplan-Meier curves and Log rank test were used for comparison of overall survival (OS). The univariate and multivariate Cox proportional hazards models were used for investigating the factors associated with OS. RESULTS: More than half (59.2%) of all patients showed a normal AMC (0.12-0.80 × 109/L). The median follow-up was 5.3 months from the start of first salvage therapy. Univariate analysis revealed that normal AMC (versus low/high AMC) at the time of relapse was a prognostic factor for improved OS (P = 0.021). On multivariate analysis, normal AMC (versus low/high AMC) at the time of relapse remained an independent prognostic factor for improved OS (hazard ratio = 0.43, P = 0.030). CONCLUSION: AMC at the time of relapse, which can be easily derived from routine clinical laboratory testing of complete blood count, might be used as a prognostic marker for survival outcomes in adult patients with early relapsed B-ALL.

Applied anatomy of pelvic lymph nodes and its clinical significance for prostate cancer:a single-center cadaveric study.

BACKGROUND: Pelvic lymph node dissection (PLND) is one of the most important steps in radical prostatectomy (RP). Not only can PLND provide accurate clinical staging to guide treatment after prostatectomy but PLND can also improve the prognosis of patients by eradicating micro-metastases. However, reports of the number of pelvic lymph nodes have generally come from incomplete dissection during surgery, there is no anatomic study that assesses the number and variability of lymph nodes. Our objective is to assess the utility of adopting the lymph node count as a metric of surgical quality for the extent of lymph node dissection during RP for prostate cancer by conducting a dissection study of pelvic lymph nodes in adult male cadavers. METHODS: All 30 adult male cadavers underwent pelvic lymph node dissection (PLND), and the lymph nodes in each of the 9 dissection zones were enumerated and analyzed. RESULTS: A total of 1267 lymph nodes were obtained. The number of lymph nodes obtained by limited PLND was 4-22 (14.1 ± 4.5), the number obtained by standard PLND was 16-35 (25.9 ± 5.6), the number obtained by extended PLND was 17-44 (30.0 ± 7.0), and the number obtained by super-extended PLDN was 24-60 (42.2 ± 9.7). CONCLUSIONS: There are substantial inter-individual differences in the number of lymph nodes in the pelvic cavity. These results have demonstrated the rationality and feasibility of adopting lymph node count as a surrogate for evaluating the utility of PLND in radical prostatectomy, but these results need to be further explored.

Notoginseng Saponin Rg1 Prevents Cognitive Impairment through Modulating APP Processing in Aß1-42-injected Rats.

With the intensification of the aging process of the world, Alzheimer's disease (AD), which is the main type of senile dementia, has become a primary problem in the present society. Lots of strategies have been used to prevent and treat AD in animal models and clinical trials, but most of them ended in failure. Panax notoginseng saponins (PNS) contain a variety of monomer compositions which have been separated and identified. Among of the monomer compositions, notoginseng saponin Rg1 (Rg1) accounts for 20% of the cultivation of panax notoginseng roots. And now PNS have been reported to be widely used to treat cardio-cerebrovascular diseases and have neuroprotective effects to restrain the ß-amyloid peptide (Aß)25-35-mediated apoptosis. Moreover, it is reported that PNS could accelerate the growth of nerve cells, increase the length of axons and promote synaptic plasticity. Whether Rg1 can ameliorate the cognitive impairment and the underlying mechanism has not been elucidated. To study the preventive effect of Rg1 on cognitive impairment and the possible mechanism, we established the cognitive impairment model in rats through Aß1-42 (2.6 µg/µL, 5 µL) injection and then treated the rats with Rg1 (25, 50 and 100 mg/kg) administered intragastrically for 4 weeks. We observed that Aß1-42 could induce spatial learning and memory deficits in rats. Simultaneously, Aß1-42 injection also resulted in the reduced neuron number in cornuammonis 1 (CA1) and dentate gyrus (DG) of hippocampus, as well as the increased level of hyperphosphorylated ß-amyloid precursor protein (APP) at Thr668 site with up-regulation of ß-APP cleaving enzyme 1 (BACE1) and presenilin 1 (PS1) and down-regulation of a disintegrin and metalloprotease domain-containing protein 10 (ADAM10) and insulin-degrading enzyme (IDE). Administration of Rg1 effectively rescued the cognitive impairment and neuronal loss, and inhibited the ß-secretase processing of APP through reducing APP-Thr668 phosphorylation and BACE1/PS1 expression, and increasing the expression of ADAM10 and IDE. We concluded that Rg1 might have neuroprotective effects and could promote learning and memory ability, which might be a viable candidate in AD therapy probably through reducing the generation of Aß and increasing the degradation of Aß.

Chinese neurologists' perspective on intravenous thrombolysis for acute ischemic stroke.

Objectives: This study examined the neurologists' perspective toward intravenous thrombolysis for the treatment of acute ischemic stroke and the influencing factors in a Chinese Province. Methods: A cross-sectional study was conducted from 1 October 2014 to 31 January 2015. A total of 719 neurologists from 66 hospitals in Hubei Province were included. A questionnaire was designed, and multivariable logistic regression models were used to identify the factors associated with the neurologists' perspective toward intravenous thrombolysis. Results: Among the responding neurologists, 67.3% reported using intravenous thrombolysis and 32.9% believed the treatment was unsafe. Approximately 51.4% reported deficits in their knowledge of intravenous thrombolysis and 45.8% felt unconfident about their ability to employ the treatment. The majority (90.1%) supported hospitals in performing intravenous thrombolysis for eligible patients. Their safety concern was associated with hospital grade (odds ratio[OR] = 2.3; 95% confidence interval [CI], 1.4-3.7) and previous experiences with thrombolysis (OR = 3.1; 95% CI, 2.1-4.6). Their confidence was associated with their educational background (OR = 2.5; 95% CI, 1.3-4.5), knowledge mastery (OR = 10.4; 95% CI, 6.6-16.3), and previous experiences with thrombolysis (OR = 3.3; 95% CI, 2.1-5.3). Their attitudes were associated with gender (OR = 0.6; 95% CI, 0.3-1.0) and previous experiences with thrombolysis (OR = 4.9; 95% CI, 2.5-9.4). Conclusions: Most neurologists in Hubei Province, China, identified with intravenous thrombolysis for the treatment of acute ischemic stroke. However, they were weak in knowledge and lack confidence. Therefore, training, especially practical training, is needed to promote the use of thrombolysis in the region.

MicroRNA-149-5p regulates blood-brain barrier permeability after transient middle cerebral artery occlusion in rats by targeting S1PR2 of pericytes.

Blood-brain barrier (BBB) disruption caused by reperfusion injury after ischemic stroke is an intractable event conducive to further injury. Brain pericytes play a vital role in maintaining BBB integrity by interacting with other components of the BBB. In this study, we found that sphingosine-1-phosphate receptor (S1PR)2 expressed in pericytes was significantly up-regulated after ischemia in vivo and in vitro. By using a S1PR2 antagonist (JTE-013), we showed that S1PR2 plays a critical role in the induction of BBB permeability of transient middle cerebral artery occlusion (tMCAO) rats and the in vitro BBB model. Furthermore, we discovered that S1PR2 may decrease N-cadherin expression and increase pericyte migration via NF-κB p65 signal and found that S1PR2 could be regulated by miR-149-5p negatively, which was decreased in the ischemic boundary zone and cultured pericytes after ischemia. Overexpression of miR-149-5p in cultured pericytes substantially increased N-cadherin expression and decreased pericyte migration, which decreased BBB leakage in the in vitro model. Up-regulating miR-149-5p by intracerebroventricular injection of agomir-149-5p attenuated BBB permeability and improved the outcomes of tMCAO rats significantly. Thus, our data suggest that miR-149-5p may serve as a potential target for treatment of BBB disruption after ischemic stroke.-Wan, Y., Jin, H.-J., Zhu, Y.-Y., Fang, Z., Mao, L., He, Q., Xia, Y.-P., Li, M., Li, Y., Chen, X., Hu, B. MicroRNA-149-5p regulates blood-brain barrier permeability after transient middle cerebral artery occlusion in rats by targeting S1PR2 of pericytes.

MicroRNA-130a regulates cerebral ischemia-induced blood-brain barrier permeability by targeting Homeobox A5.

Blood-brain barrier (BBB) disruption plays a critical role in brain injury induced by cerebral ischemia, and preserving BBB integrity during ischemia could alleviate cerebral injury. We examined the role of miR-130a in ischemic BBB disruption by using models of rat middle cerebral artery occlusion and cell oxygen-glucose deprivation. We found that ischemia significantly increased microRNA-130a (miR-130a) level and that miR-130a was predominantly from brain microvascular endothelial cells. Antagomir-130a, an antagonist of miR-130a, could attenuate brain edema, lower BBB permeability, reduce infarct volume, and improve neurologic function. MiR-130a overexpression induced by miR-130a mimic increased monolayer permeability, and intercellular inhibition of miR-130a by a miR-130a inhibitor suppressed oxygen-glucose deprivation-induced increase in monolayer permeability. Moreover, dual luciferase reporter system showed that Homeobox A5 was the direct target of miR-130a. MiR-130a, by inhibiting Homeobox A5 expression, could down-regulate occludin, thereby increasing BBB permeability. Our results suggested that miR-130a might be implicated in ischemia-induced BBB dysfunction and serve as a target for the treatment of ischemic stroke.-Wang, Y., Wang, M.-D., Xia, Y.-P., Gao, Y., Zhu, Y.-Y., Chen, S.-C., Mao, L., He, Q.-W., Yue, Z.-Y., Hu, B. MicroRNA-130a regulates cerebral ischemia-induced blood-brain barrier permeability by targeting Homeobox A5.

MiR-150 Regulates Poststroke Cerebral Angiogenesis via Vascular Endothelial Growth Factor in Rats.

AIMS: Angiogenesis is a harmonized target for poststroke recovery. Therefore, exploring the mechanisms involved in angiogenesis after stroke is vitally significant. In this study, we are reporting a miR-150-based mechanism underlying cerebral poststroke angiogenesis. METHODS: Rat models of middle cerebral artery occlusion (MCAO) and cell models of oxygen-glucose deprivation were conducted. Capillary density, tube formation, cell proliferation, and cell migration were measured by FITC-dextran assay, matrigel assay, Ki-67 staining, and wound healing assay, respectively. The expression of miR-150 and vascular endothelial growth factor (VEGF) was, respectively, measured by RT-PCR and Western blotting. Dual-luciferase assay was conducted to confirm the binding sites between miR-150 and VEGF. RESULTS: We found that miR-150 expression in the brain and serum of rats subjected to cerebral ischemia, and in oxygen-glucose-deprived brain microvascular endothelial cells (BMVECs) and astrocytes. Upregulation of miR-150 expression could decrease vascular density of infarct border zone in rat after MCAO and decrease tube formation, proliferation, and migration of BMVECs. We also found that miR-150 could negatively regulate the expression of VEGF, and VEGF was confirmed to be a direct target of miR-150. Moreover, VEGF mediated the function of miR-150 on tube formation, proliferation, and migration of BMVECs. CONCLUSIONS: Our data suggested that miR-150 could regulate cerebral poststroke angiogenesis in rats through VEGF.

MicroRNA-150 regulates blood-brain barrier permeability via Tie-2 after permanent middle cerebral artery occlusion in rats.

The mechanism of blood-brain barrier (BBB) disruption, involved in poststroke edema and hemorrhagic transformation, is important but elusive. We investigated microRNA-150 (miR-150)-mediated mechanism in the disruption of BBB after stroke in rats. We found that up-regulation of miR-150 increased permeability of BBB as detected by MRI after permanent middle cerebral artery occlusion in vivo as well as increased permeability of brain microvascular endothelial cells after oxygen-glucose deprivation in vitro. The expression of claudin-5, a key tight junction protein, was decreased in the ischemic boundary zone after up-regulation of miR-150. We found in brain microvascular endothelial cells that overexpression of miR-150 decreased not only cell survival rate but also the expression levels of claudin-5 after oxygen-glucose deprivation. With dual-luciferase assay, we confirmed that miR-150 could directly regulate the angiopoietin receptor Tie-2. Moreover, silencing Tie-2 with lentivirus-delivered small interfering RNA reversed the effect of miR-150 on endothelial permeability, cell survival, and claudin-5 expression. Furthermore, poststroke treatment with antagomir-150, a specific miR-150 antagonist, contributed to BBB protection, infarct volume reduction, and amelioration of neurologic deficits. Collectively, our findings suggested that miR-150 could regulate claudin-5 expression and endothelial cell survival by targeting Tie-2, thus affecting the permeability of BBB after permanent middle cerebral artery occlusion in rats, and that miR-150 might be a potential alternative target for the treatment of stroke.-Fang, Z., He, Q.-W., Li, Q., Chen, X.-L., Baral, S., Jin, H.-J., Zhu, Y.-Y., Li, M., Xia, Y.-P., Mao, L., Hu, B. MicroRNA-150 regulates blood-brain barrier permeability via Tie-2 after permanent middle cerebral artery occlusion in rats.

[Study on patients with Creutzfeldt-Jakob disease in Shanghai, 2006-2012].

OBJECTIVE: To describe the epidemiological characteristics of patients with Creutzfeldt-Jakob disease (CJD) in Shanghai from 2006 to 2012. METHODS: Clinical and epidemiological information on CJD patients from Shanghai CJD Surveillance Network was analyzed. Cerebral spinal fluid (CSF)and blood specimens from patients were collected and used for detecting the 14-3-3 protein, and polymorphism of 129 amino acid and mutation of PRNP genes. Data was processed by EpiData(V3.0)and analyzed by SPSS(V17.0). RESULTS: In totally, one definite CJD patient together with 56 probable and 17 possible sporadic CJD patients were identified. One E200K genetic CJD case was diagnosed and another one was clinically diagnosed. No period- or geographic-related events were observed for these cases, but the houses of the two genetic CJD cases were close to each other. The mean age of onset of the probable CJD patients was 62 years old which was significantly older than that of those possible CJD patients. CONCLUSION: Most of the CJD patients identified in Shanghai were sporadic and the number was stable from 2006 to 2012. The mean age of onset of those probable CJD patients was older than that of the possible CJD patients.

[Epidemiologic and genetic characteristics of hepatitis E virus in Shanghai, 1997-2012].

OBJECTIVE: The aim of this study was to systemically analyze the epidemiologic, serological and genetic characteristics of hepatitis E virus (HEV) in Shanghai from 1997 to 2012. METHODS: We analyzed the data related to the epidemics of hepatitis E from China Information System for Disease Control and Prevention. We implemented serological surveillance program, based on community healthy population with enzyme-linked immunosorbent assay method and estimated the standardized sero-prevalence. We also obtained nucleotide sequences of hepatitis E patients using the nested RT-PCT assays, together with prototype sequences in the GenBank to construct a HEV genetic database in Shanghai. RESULTS: In this paper, we found that the distribution of hepatitis E patients was sporadic in the past 16 years in Shanghai. The morbidity kept declining, but with seasonal and periodical fluctuation. Morbidity in males was significantly higher than in females, with the hard hit population between 30 and 65 year-olds. In total, 3979 sera samples were collected through the serological surveillance programs in 2001, 2004, 2007 and 2012. The standardized sero-prevalence rates of the said years were 22.32%, 18.56%, 10.22% and 34.43% which all showing strong relationship with age groups and the regions where the populations were being monitored. 73 nucleotide sequences of hepatitis E patients from hospitals were identified, during 2004 and 2008. RESULTS: from phylogenetic analysis revealed that all HEV isolates belonged to genotype IV and including 4 known subtypes 4a, 4d, 4h and 4i which sharing 83.09% - 97.96%, 85.87% - 97.26% and 83.80% - 95.10% nucleotide sequence identities with the swine HEV genotype IV of GU188851, DQ450072 and EF570133. Meanwhile, 59 HEV isolates from different districts shared 99% nucleotide sequence identities with each other. CONCLUSION: Hepatitis E would still be a challenge for long time and the zoonotic questions that related to hepatitis E, need to be explored and explained in the future.

[Epidemiological characteristics of Japanese encephalitis in Shanghai].

OBJECTIVES: To understand the epidemiological characteristics of Japanese Encephalitis in Shanghai and to provide evidence for preventing JE. METHODS: Epidemic characteristics, JEV antibody in healthy population and swine infection rate in Shanghai were analyzed by methods of field survey, serology and molecular biology. RESULTS: JE incident rate in Shanghai was 0.077/100,000 in 2006; and 0.129/100,000 in 2007. Antibody positive rate before JE epidemic fastigium was 60.39%; postive rate after epidemic was 85.44%. JE IgG positive rate was 26.92% in 3-month swine and 14.86% in swine for sale; JE Gene in mosquito was analyzed for type 1. CONCLUSION: The JE prevalence rate is relatively low in Shanghai. JE antibody positive rate is high in Shanghai population. Swine as a media is infected by JE virus. The JE virus in mosquitoes belongs to genotype 1.

[Study on risk factors of sporadic hepatitis E virus cases in some districts of Shanghai].

OBJECTIVE: To study the risk factors of acute sporadic hepatitis E virus (HEV) cases and to analyze its partial sequence in some districts of Shanghai. METHODS: 30 blood samples were collected from the acute sporadic HEV cases in 2003-2004 and the RT-nPCR method was applied to obtain the sequence of HEV in these cases. Meanwhile, a 1:2 case-control study was used to identify risk factors in the process of sporadic HEV infection in these regions of Shanghai. RESULTS: Data from the sequential analysis showed that HEV of the sporadic cases belonged to HEV genotype IV. Finding from the case-control study implicated that the housing condition, outside eating history, especially seafoods (OR = 7.048) played an important role in the infection of HEV. Results from multiple logistic regression showed that eating raw seafoods appeared to be one of the risk factors of HEV infection. CONCLUSION: HEV sequences isolated from the sporadic cases of HEV in some districts of Shanghai belonged to HEV genotype IV. Foods, especially seafood, were the risk factors in the infection of HEV.