[Clinical and genetic characteristics of young patients with myeloproliferative neoplasms].

Objectives: To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN). Methods: In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients. Results: 1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion: Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.

[Health-related quality of life and its associated variables in Chinese patients with Philadelphia-negative myeloproliferative neoplasms].

Objectives: To explore health-related quality of life (HRQoL) and identify its associated variables in Chinese patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) . Methods: In this cross-sectional study, anonymous questionnaires were distributed to adult patients with MPNs to assess symptom burden measured by MPN-10 and HRQoL measured by Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) . Results: The data from 1405 respondents with MPNs, including 645 (45.9%) with essential thrombocythemia (ET) , 297 (21.1%) with polycythemia vera (PV) , and 463 (33.0%) with myelofibrosis (MF) , were analyzed. 646 (46.0%) respondents were male. The median age was 56 (range, 18-99) years. The mean MPN-10 scores were 13.0±12.7, 15.0±14.7, and 21.0±16.6 (P<0.001) , and the physical component summary (PCS) and mental component summary (MCS) scores were 48.0±8.5, 47.0±9.0, and 42.0±10.0 (P<0.001) and 51.0±11.0, 50.0±10.8, and 49.0±11.1 (P=0.002) for respondents with ET, PV, and MF, respectively. Respondents with MF reported the lowest score of physical functioning, role functioning, emotional functioning, cognitive functioning, social function, and global health status (all P<0.01) and the highest score of fatigue, pain, dyspnea, appetite loss, diarrhea, and financial problems (all P<0.05) in EORTC QLQ-C30. Multivariate analyses revealed that higher MPN-10 scores were significantly associated with lower PCS (-0.220 to -0.277, P<0.001) and MCS (-0.244 to -0.329, P<0.001) scores; increasing age (-1.923 to -4.869; all P<0.05) , lower PCS score. Additionally, comorbidity (ies) , symptom at diagnosis, splenomegaly, anemia, unknown driver gene, and higher annual out-of-pocket cost were significantly associated with lower PCS and/or MCS scores. However, age ≥ 60 years, urban household registration, concomitant medication, and receiving ruxolitinib therapy in respondents with MF were associated with higher MCS scores. Weak correlations were found between MPN-10 score (except the subscale of appetite loss and constipation) and EORTC QLQ-C30 score in majority of subscales in respondents with ET (|r| = 0.193-0.457, all P<0.001) , PV (|r| = 0.192-0.529, all P<0.01) , and MF (|r| = 0.180-0.488, all P<0.001) , respectively. Conclusions: HRQoL in patients with MPN was significantly reduced, especially in patients with MF. Sociodemographic and clinical variables were significantly associated with the HRQoL in patients with MPNs.

[Efficacy tubular paraspinal approach and conventional semi-laminar approach in treating lumbar stenosis].

Objective: To analysis of the efficacy of tubular paraspinal approach and conventional semi-laminar approach in treating lumbar stenosis. Methods: Retrospective research of clinical data of 56 lumbar stenosis cases who were operated in neurosurgery department of first center of PLA general hospital from May 2015 to June 2018. Collecting the information of sex, age, operating time, intraoperative blood loss, postoperative duration in bed, as well as length of hospital stay of those patients. The 2 groups of cases, tubular paraspinal approach group (n=35)and semi-laminal approachgroup (n=21), compared by Japanese orthopedic association (JOA) score and visual analogue scale to assess the functional situation of the patients before operation, 1 week after operation, 1 month after operation, 6 months after operation, and the last follow up. Results: The operating time(83.1±7.3 vs 86.1±9.6 min), intraoperative blood loss(18.2±3.9 vs 40.5±13.3 ml), postoperative duration in bed(37.4±7.8 vs 63.7±15.8 h), as well as length of hospital stay (3.8±1.1 vs 6.5±2.0 d)were all obviously better in tubular paraspinal approach group than in traditional semi-laminar approach group(P<0.05). The postoperative 1 week, 1month, and 6 months JOA score (21.8±3.4, 23.6±2.4, 24.2±2.4 vs 19.9±3.7, 21.6±2.8, 22.4±2.1)and VAS (2.2±1.0, 2.0±1.1, 0.4±0.1 vs 3.1±1.2, 2.6±1.3, 0.5±0.1) were better in tubular paraspinal approach group than semi-laminar approach group (P<0.05). While at the last follow up, the JOA score and VAS were similar in the 2 groups (P>0.05) . Conclusions: In non-fusion techniques for treating lumbar stenosis, tubular paraspinal approach demonstrated less blood loss, shorter stay in bed as well as in hospital, and better symptom relief in early postoperative period than traditional semi-laminal approach. While at long term follow up, both approaches achieved satisfactory outcome.

[Prognostic significance of proteins expression by immunohistochemical method in diffuse large B cell lymphoma].

Objective: To analyze the prognostic significance of TP53, Bcl-2, Bcl-6, Myc proteins expression by immunohistochemical method (IHC) in diffuse large B cell Lymphoma (DLBCL) . Methods: Clinical and pathologic data of 223 patients with DLBCL hospitalized in Zhejiang First Hospital from March 2009 to June 2015 were retrospectively analyzed. Results: The 223 cases, a median age of 56 years old with a male predominance, had shown a 39.0% of TP53 positive expression, 38.6% of Myc, 69.1% of Bcl-2, 56.5% of Bcl-6, and 22.7% of Myc/Bcl-2 double expression. According to Hans' classification, 27.4% were GCB and 72.6% were non-GCB. With a median follow-up of 38 (2-97) months, the 3 and 5 years survival rates were 70% and 66% , respectively. By multivariate analysis, TP53 over-expression and Myc/Bcl-2 double expression were independently associated with poor outcomes. 3-year and 5-year overall survival were 59% and 57% for patients with TP53 positive, 77% and 71% for patients with TP53 negative expression. Patients with non-GCB subtype receiving chemotherapy combined with rituximab had a higher OS than those without rituximab. But rituximab did not improve the prognosis of patients with TP53 positive. Conclusion: Myc/Bcl-2 double expression and TP53 over-expression are poor prognosis for DLBCL patients. Patients with Myc/Bcl-2 double expression have shorter OS. Patients with non-GCB subtype who received chemotherapy combined with rituximab have a better OS than those without rituximab. But rituximab does not improve the prognosis of patients with TP53 positive.

[A preliminary study on the outcome of lower-risk myelodysplastic syndrome by low-dose decitabine].

Objective: To assess the efficiency and safety of low-dose decitabine in patients with lower-risk myelodysplastic syndrome (MDS) to couple with the clinical significance of MDS-related gene mutations. Methods: This study was done in 4 institutions in Zhejiang Province. A total of 62 newly diagnosed patients with lower-risk MDS were assigned to two groups of decitabine (12 mg·m(-2)·d(-1) for 5 consecutive days) and best supportive care (BSC) . Their bone marrow samples were subject to examinations of MDS-related 15 gene mutations. The primary endpoints were the proportion of patients who achieved overall response (ORR) after at least two cycles and progression-free survival (PFS) , and their relevances to the gene mutations. Results: Of 62 enrolled patients, and 51 cases were included in the final analysis. 16 of 24 patients (66.7%) in decitabine group achieved ORR versus 8 of 27 (29.6%) in BSC group (χ(2)=6.996, P=0.008) ; PFS prolongation of decitabine versus BSC was statistically significant (not reached vs 13.7 months, P=0.037) . Among 51 patients, at least one gene mutation was identified in 20 patients (39.2%) , including 4 single SF3B1 mutation. PFS in cases with gene mutations (not including single SF3B1 mutation) was significantly shorter than of no gene mutation (9.2 months vs 18.5 months, P=0.008) , but not for ORR (37.5% vs 58.1%, P=0.181) . Among 16 patients with mutated genes, ORR in decitabine and BSC groups were 75% (6/8) and 0 (0/8) , respectively. The most adverse events in decitabine group were grade 3 to 4 neutropenia (45.8%) and grade 3 to 4 infections (33.3%) . Conclusion: This preliminary study showed that low-dose decitabine produced promising results with an acceptable safety in lower-risk MDS patients, especially for those with mutated genes. Further study targeting poor prognostic lower-risk MDS patients should be warranted.

Large Positive Thermal Expansion and Small Band Gap in Double-ReO3-Type Compound NaSbF6.

Double-ReO3-type structure compound NaSbF6 undergoes a low-temperature rhombohedral to high-temperature cubic phase between 303 and 323 K, as revealed by temperature-dependent X-ray diffractions. Although many double-ReO3-type fluorides exhibit either low thermal expansion or negative thermal expansion (NTE), NaSbF6 exhibits positive thermal expansion (PTE) with a large volumetric coefficient of thermal expansion, αv = 62 ppm/K, in its cubic phase. Raman spectroscopy reveals that the low-frequency transverse vibration of fluorine atoms is stiffened in NaSbF6, compared with the typical NTE compound CaZrF6 with the same structure. The related weak contraction associated with the polyhedral rocking would be overcome by the notable elongation of the Na-F bond length on heating, thus leading to the large volumetric PTE. Unlike ScF3 and CaZrF6 which are insulators with a wide band gap, a relative small band gap of 3.76 eV was observed in NaSbF6. The small band gap can be attributed to the hybridization between the Sb 5s and F 2p orbitals.

[Efficacy and safety analysis of different dose idarubicin plus cytarabine regimen as induction chemotherapy for young patients with de-novo acute myeloid leukemia].

OBJECTIVE: To compare the efficacy, safety and long-term prognosis between different dose idarubicin (IDA) combined with cytarabine (IA) as induction chemotherapy in newly diagnosed young patients of acute myeloid leukemia (AML). METHODS: A total of 149 newly diagnosed young AML patients (APL excluded) between January 2009 to July 2014 was enrolled. According to the dose of IDA, the patients were divided into three groups, high standard- dose IA group (10- 12 mg · m (- 2) · d(- 1)), low standard-dose IA group (8-9 mg·m(-2)·d(-1)) and low-dose IA group (<8 mg·m(-2)·d(-1)). The efficacy, adverse effects and long- term prognosis among the three groups were compared. RESULTS: Of them, 34 patients were in high standard-dose IA group, 53 in low standard-dose IA group and 62 in low-dose IA group. After one cycle of induction chemotherapy, the complete remission (CR) rate was 79.4%, 75.5% and 46.8%, the overall response (OR) rate was 97.1%, 94.3% and 64.5%, and the overall CR rate was 85.3%, 81.1% and 54.8%, respectively. Compared with low- dose IA group, high standard- dose IA group and low standard-dose IA group had significantly better result (P<0.05), but there was no significant difference between the latter two groups (P>0.05). Multivariate analysis also showed that standard-dose IA was favorable factor for induction chemotherapy (P<0.05). The adverse effects were similar in the three group, other than the lowest count of WBC (P=0.002). Low standard-dose IA can improve the OS compared to the low-dose IA (P=0.003), but EFS, RFS was similar in the three groups. CONCLUSIONS: For the newly diagnosed young(<55) AML patients, the standard-dose IA has better CR rate. The adverse effects were similar in the three groups. High-dose IA may improve the OS compared to the low-dose IA.

Two cases of overlap severe cutaneous adverse reactions to benznidazole treatment for asymptomatic Chagas disease in a nonendemic country.

Chagas disease is a parasitosis endemic to South America. It is normally treated with benznidazole as first choice, which has been associated with numerous cutaneous reactions. However, very few benznidazole-associated severe cutaneous adverse reactions have been reported to date. The rise of Chagas disease in nonendemic countries represents a growing public health challenge. We report two patients who met the criteria for drug reaction with eosinophilia and systemic symptoms syndrome and Stevens-Johnson syndrome/toxic epidermal necrolysis according to the RegiSCAR scoring systems. They were thus deemed overlapping cases, with a lymphocyte transformation test positive for benznidazole. Both required intensive care unit admission and both survived. Considering the rising application of this drug for trypanosomiasis in immigrant populations, clinicians should be aware of this newly reported, potentially life-threatening risk.

Development of emission factors and emission inventories for motorcycles and light duty vehicles in the urban region in Vietnam.

This paper reports on a 2-year emissions monitoring program launched by the Centre for Environmental Monitoring of the Vietnam Environment Administration which aimed at determining emission factors and emission inventories for two typical types of vehicle in Hanoi, Vietnam. The program involves four major activities. A database for motorcycles and light duty vehicles (LDV) in Hanoi was first compiled through a questionnaire survey. Then, two typical driving cycles were developed for the first time for motorcycles and LDVs in Hanoi. Based on this database and the developed driving cycles for Hanoi, a sample of 12 representative test vehicles were selected to determine vehicle specific fuel consumption and emission factors (CO, HC, NOx and CO(2)). This set of emission factors were developed for the first time in Hanoi with due considerations of local driving characteristics. In particular, it was found that the emission factors derived from Economic Commission for Europe (ECE) driving cycles and adopted in some previous studies were generally overestimated. Eventually, emission inventories for motorcycles and LDVs were derived by combining the vehicle population data, the developed vehicle specific emission factors and vehicle kilometre travelled (VKT) information from the survey. The inventory suggested that motorcycles contributed most to CO, HC and NOx emissions while LDVs appeared to be more fuel consuming.

Homoharringtonine in combination with cytarabine and aclarubicin resulted in high complete remission rate after the first induction therapy in patients with de novo acute myeloid leukemia.

To assess the efficacy and toxicity of HAA regimen (homoharritonine 4 mg/m2/day, days 1-3; cytarabine 150 mg/m2/day, days 1-7; aclarubicin 12 mg/m2/day, days 1-7) as an induction therapy in the treatment of de novo acute myeloid leukemia (AML), 48 patients with newly diagnosed AML, aged 35 (14-57) years, were entered into this clinical study. The median follow-up was 26 months. Eighty-three percent of patients achieved complete remission (CR), and the first single course of induction HAA regimen resulted in CR rate of 79%. The CR rate of 100, 82 and 33% were achieved in patients with favorable, intermediate and unfavorable cytogenetics, respectively. For all patients who achieved CR, the median time from the initiation of the induction therapy to the evaluation of the remission status was 32 days. For all patients, the estimated 3 years overall survival (OS) rate was 53%, whereas for patients with M5, the estimated OS rate at 3 years was 75%. The toxicities associated with HAA regimen were acceptable, and the most common toxicity was infection. This study suggested that HAA regimen might be a well-tolerable, effective induction regimen in young adult patients with AML.

Antisense expression of a cell wall-associated protein kinase, WAK4, inhibits cell elongation and alters morphology.

The Arabidopsis cell wall-associated receptor-like kinase (WAK) gene family contains five highly related members whose products are suited for exchanging signals between the intracellular and extracellular compartments. WAK members are expressed in specific organs and regulated differentially by various biotic and abiotic factors. To gain further insight into how WAKs function during development, we used a glucocorticoid-inducible system to express ectopically the WAK4 antisense gene. The induced expression of the WAK4 antisense gene resulted in a significant decrease of WAK proteins. Ninety-six hours after the induction of WAK4 antisense expression, WAK proteins became undetectable. Cell elongation was impaired, and lateral root development was blocked. The level of WAK protein could be controlled by the concentration of the applied inducer, dexamethasone, and was correlated with the severity of the cell elongation inhibition phenotype. These results suggest that the WAKs serve a vital role in cell elongation and are required for plant development.

The role of visual and body movement information in infant search.

Three experiments investigated the use of visual input and body movement input arising from movement through the world on spatial orientation. Infants between 9 1/2 and 18 months participated in a search task in which they searched for a toy hidden in 1 of 2 containers. Prior to beginning search, either the infants or the containers were rotated 180 degrees; these rotations occurred in a lit or dark environment. These experiments were distinguished by the environmental cues for object location; Experiment 1 used a position cue, Experiment 2 a color cue, and Experiment 3 both position and color cues. Accuracy was better in Experiments 2 and 3 than in Experiment 1. All studies found that search was best after infant movement in the light; all other conditions led to equivalently worse performance. These results are discussed relative to a theoretical characterization of spatial coding focusing on the uses of spatial information.

On-road motor vehicle emissions and fuel consumption in urban driving conditions.

This paper reports on the analysis of on-road vehicle speed, emission, and fuel consumption data collected by four instrumented vehicles. Time-, distance-, and fuel-based average fuel consumption, as well as CO, HC, NOx, and soot emission factors, were derived. The influences of instantaneous vehicle speed on emissions and fuel consumption were studied. It was found that the fuel-based emission factors varied much less than the time- and distance-based emission factors as instantaneous speed changed. The trends are similar to the results obtained from laboratory tests. The low driving speed contributed to a significant portion of the total emissions over a trip. Furthermore, the on-road data were analyzed using the modal approach. The four standard driving modes are acceleration, cruising, deceleration, and idling. It was found that the transient driving modes (i.e., acceleration and deceleration) were more polluting than the steady-speed driving modes (i.e., cruising and idling) in terms of g/km and g/sec. These results indicated that the on-road emission measurement is feasible in deriving vehicle emissions and fuel consumption factors in urban driving conditions.

Monobromopolychlorodibenzo-p-dioxins and dibenzofurans in municipal waste incinerator flyash.

Capillary column gas chromatography/high-resolution mass spectrometry was used in two different selected-ion monitoring modes to analyze trace levels of monobromopolychlorodibenzo-p-dioxins and dibenzofurans (BPCDD/Fs) in municipal waste incinerator (MWI) flyash. The mass profile monitoring mode is well-suited for identification of unknown compounds in uncharacterized matrices because it has superior diagnostic capability. Owing to its high sensitivity, conventional peak top monitoring was used to quantify, on the basis of polychlorodibenzo-p-dioxin and dibenzofuran (PCDD/F) standards, the BPCDD/Fs in the sample. The results were compared with those obtained by using two commercial BPCDDs as standards, and the latter results are 4 times greater, indicating the need for appropriate standards. The high certainty and sensitivity obtained from these two mass spectrometric techniques combined with the resolving power of capillary gas chromatography enabled us to compare for the first time the isomer distribution patterns between BPCDD/Fs and their PCDD/F analogues at a high confidence level. The comparison indicates BPCDD/Fs and PCDD/Fs found in MWI flyash are closely related and that many BPCDD/Fs with a 2,3,7,8-substitution configuration may be present in MWI flyash.

Mass profile monitoring in trace analysis by gas chromatography/mass spectrometry.

The advantages of gas chromatography/mass spectrometry (GC/MS) selected-ion monitoring (SIM) in the mass profile (MP) mode at medium mass resolving power were investigated for analyses requiring detection of low-picogram quantities of analytes in complex mixtures. The mass profile monitoring provides a certainty at least 10 times greater than that achieved by conventional GC/MS-SIM in the peak-top monitoring mode, and it can be operated at lower mass resolving power to compensate for the loss of sensitivity in the MP mode. The examination of mass profile peak shape, central mass shift, and sequential changes during GC elution not only reveals the presence of interfering compounds but also results in accurate mass measurement for those interferences. The latter feature takes the MP mode beyond the target mass analysis that GC/MS-SIM was originally designed for. This additional dimension of information is particularly useful for those complex and incompletely characterized matrices that are frequently encountered in environmental and biological sample analyses.

Effects of 2,4,5-trichlorophenoxyacetic acid, pentachlorophenol, methylprednisolone, and Freund's adjuvant on 2-hydroxyethylnitrosourea carcinogenesis in MRC-Wistar rats.

A link was proposed between human non-Hodgkin's lymphoma and exposure to 2,4,5-trichlorophenoxyacetic acid (245T) and pentachlorophenol (PCP). To test this view and the hypothesis that immune suppression or stimulation could affect B-cell lymphoma (BCL) induction, we administered chronically to MRC-Wistar (MRC-W) rats of both sexes 98% pure 245T (600 mg/kg diet), 86% pure PCP (500 mg/kg diet), methylprednisolone (20 mg/kg ip weekly), and Freund's adjuvant (0.5 ml im every 3-6 wk) for 40 wk, together with 75 mg 2-hydroxyethylnitrosourea (HENU)/l drinking water, a system known to induce B-cell lymphoma. The 245T was shown to contain only 1-4 micrograms/kg each of 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and 2,3,7,8-tetrachlorodibenzofuran (TCDF), but the PCP contained 25 micrograms TCDD and 670 micrograms TCDF/kg. HENU given alone induced B-cell lymphoma and osteosarcoma as before, with higher incidences of both tumors in males than in females. The B-cell lymphoma diagnosis was confirmed by immunologic typing of cell-surface markers and by probes for gene rearrangements. Coadministration with HENU of three of the four test agents did not affect tumor incidence, but PCP acted synergistically with HENU to induce acute myelocytic leukemia. PCP given alone or with HENU induced a 40-67% incidence of liver cell adenomas in the female rats. These effects were probably not due to TCDD in the PCP. HENU induced acute myelocytic leukemia and lung tumors in Wistar rats and n-butylnitrosourea induced acute myelocytic leukemia in MRC-Wistar rats, indicating that B-cell lymphoma induction was specific to the HENU-MRC-Wistar rat model.