A novel de novo synonymous variant in GREB1L impacts the mRNA splicing associated with aplasia of the urogenital system.

GREB1-like retinoic acid receptor coactivator (GREB1L) gene is associated with autosomal dominant renal hypodysplasia/aplasia 3 (RHDA3) and deafness, autosomal dominant 80 (DFNA80). Among the GREB1L variants reported, most of them are missense or frameshift, while no pathogenic synonymous variants have been recorded. Classical theory paid little attention to synonymous variants and classified it as nonpathogenic; however, recent studies suggest that the variants might be equally important. Here, we report a 7-year-old girl with new symptoms of clitoromegaly, uterovaginal, and ovarian agenesis as well as right kidney missing. A novel de novo GREB1L synonymous variant (NM_001142966: c.4731C>T, p.G1577=) was identified via whole exome sequencing. The variant was predicted to be disease-causing through in silico analysis and was classified as likely pathogenic. Minigene splicing assays confirmed a 6 bp deletion in mutant cDNA comparing with the wild type, leading to two amino acids lost in GREB1L protein. Secondary and tertiary structure modeling showed alterations in protein structure. Our finding reveals a novel GREB1L variant with a new phenotype of urogenital system and is the first to report a pathogenic synonymous variant in GREB1L which affects mRNA splicing, suggesting synonymous variants cannot be ignored in prenatal diagnosis and genetic counseling.

Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene polymorphisms and five related serum molecular levels in 2587 patients: Associated differentially with adverse pregnancy.

BACKGROUND: The aim of the study is to investigate the relationship between Methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR) polymorphisms, 5 serum related molecular levels and the risk of adverse pregnancies in different genders. METHODS: Patients aged from 22 to 38 with a history of adverse pregnancy treated in our genetic eugenics clinic of Henan Provincial People's Hospital are selected. The controls aged from 20 to 34 undergoing eugenics examinations in our genetic eugenics clinic that had no history of adverse pregnancy and at least one healthy child are selected. Sanger sequencing and Chemiluminescence Microparticle Immuno Assay (CMIA) are used for detecting the mutations of MTHFR and MTRR and the 5 serum molecular serum levels. RESULTS: In the female group, MTHFR 677 C > T is associated with Recurrent spontaneous abortion (RSA) (P = 0.0017), Chromosomal abnormality (CA) (P = 0.0053), Cleft lip and palate (CLP) (P = 0.0326) and Brain dysplasia (BD) (P = 0.0072); MTHFR 1298 A > C is associated with Infertility (P = 0.0026) and BD (P = 0.0382); MTRR 66 A > G is associated with CLP (P = 0.0131). In the male group, MTHFR 677 C > T is associated with RSA (P = 0.0003), Infertility (P = 0.0013), CA (P = 0.0027) and BD (P = 0.0293). In the female group, the genotype of MTHFR 677 C > T is associated with RSA (P = 0.0017), CA (P = 0.0014) and BD (P = 0.0021); MTHFR 1298 A > C is associated with Infertility (P = 0.0081) and MTRR 66 A > G is associated with Infertility (P = 0.0309). In the male group, the genotype of MTHFR 677 C > T is associated with RSA (P = 0.0008), Infertility (P = 0.0096) and CA (P = 0.0165) and MTRR 66 A > G is associated with Infertility (P = 0.0158) and congenital heart disease (CHD) (P = 0.0218). In the male group, there is statistically significant difference of the serum Homocysteine (Hcy) levels (P < 0.0001) between adverse pregnancy group and controls. In the female group, there is statistically significant difference of the serum vitamin D levels (P = 0.0015) between adverse pregnancy group and controls. CONCLUSIONS: Polymorphic variants in MTHFR and MTRR, serum Folic acid (FA), Hcy and B12 levels in the male group and vitamin D levels in the female group are associated differentially with adverse pregnancy.

Correlation between maternal serum biomarkers and the risk of fetal chromosome copy number variants: a single-center retrospective study.

OBJECTIVE: To explore the association between the concentration of maternal serum biomarkers and the risk of fetal carrying chromosome copy number variants (CNVs). METHODS: Pregnant women identified as high risk in the second-trimester serological triple screening and underwent traditional amniotic fluid karyotype analysis, along with comparative genomic hybridization array (aCGH)/copy number variation sequencing (CNV-seq), were included in the study. We divided the concentration of serum biomarkers, free beta-human chorionic gonadotropin (fß-hCG), alpha fetoprotein (AFP) and unconjugated estriol (uE3), into three levels: abnormally low, normal and abnormally high. The prevalence of abnormally low, normal and abnormally high serum fß-hCG, AFP and uE3 levels in pregnant women with aberrant aCGH/CNV-seq results and normal controls was calculated. RESULTS: Among the 2877 cases with high risk in the second-trimester serological triple screening, there were 98 chromosome abnormalities revealed by karyotype analysis, while 209 abnormalities were detected by aCGH/CNVseq (P＜0.001) . The carrying rate of aberrant CNVs increased significantly when the maternal serum uE3 level was less than 0.4 multiple of median (MoM) of corresponding gestational weeks compared to normal controls, while the carrying rate of aberrant CNVs decreased significantly when the maternal serum fß-hCG level was greater than 2.5 MoM compared to normal controls. No significant difference was found in the AFP group. CONCLUSION: Low serum uE3 level (<0.4 MoM) was associated with an increased risk of aberrant CNVs.

[Clinical features and genetic analysis of 17 Chinese pedigrees affected with X-linked intellectual disability].

OBJECTIVE: To analyze the clinical features and genetic etiology of 17 Chinese pedigrees affected with X-linked intellectual disability (XLID). METHODS: Seventeen pedigrees affected with unexplained intellectual disability which had presented at Henan Provincial People's Hospital from May 2021 to May 2023 were selected as the study subjects. Clinical data of the probands and their pedigree members were collected. Trio-whole exome sequencing (Trio-WES), Sanger sequencing and X chromosome inactivation (XCI) analysis were carried out. Pathogenicity of candidate variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics and co-segregation analysis. RESULTS: The 17 probands, including 9 males and 8 females with an age ranging from 0.6 to 8 years old, had all shown mental retardation and developmental delay. Fourteen variants were detected by genetic testing, which included 4 pathogenic variants (MECP2: c.502C>T, MECP2: c.916C>T/c.806delG, IQSEC2: c.1417G>T), 4 likely pathogenic variants (MECP2: c.1157_1197del/c.925C>T, KDM5C: c.2128A>T, SLC6A8: c.1631C>T) and 6 variants of uncertain significance (KLHL15: c.26G>C, PAK3: c.970A>G/c.1520G>A, GRIA3: c.2153C>G, TAF1: c.2233T>G, HUWE1: c.10301T>A). The PAK3: c.970A>G, GRIA3: c.2153C>G and TAF1: c.2233T>G variants were considered as the genetic etiology for pedigrees 12, 14 and 15 by co-segregation analysis, respectively. The proband of pedigree 13 was found to have non-random XCI (81:19). Therefore, the PAK3: c.1520G>A variant may underlie its pathogenesis. CONCLUSION: Trio-WES has attained genetic diagnosis for the 17 XLID pedigrees. Sanger sequencing and XCI assay can provide auxiliary tests for the diagnosis of XLID.

Assessment of heavy metal concentrations in roadside soils and plants around the Dexing copper mine: implications for environmental management and remediation.

While land transportation is crucial for social development, it also introduces various pollutants, including heavy metals, which pose risks to both the environment and human health. This issue is particularly acute in mining areas, yet research focusing on heavy metal accumulation in soils and plants along transportation routes in these areas has been limited. Addressing this gap, this study investigates soil contamination levels and heavy metal concentrations in dominant plants along a highway and railway in the vicinity of the Dexing Copper Mine, the largest open-pit copper mine in China, located in Jiangxi Province. These transportation routes are heavily utilized for ore transportation, making them critical areas for environmental monitoring. Results reveal that the primary heavy metal contaminants in the soil were Cu (84.9 to 2554.3 mg/kg), Pb (38.3 to 2013.4 mg/kg), Cd (0.1 to 46.6 mg/kg), Zn (81.3 to 875.8 mg/kg), and As (11.8 to 2985.2 mg/kg), with significantly higher concentrations found in soils adjacent to the railway compared to the highway. Specifically, for plants along the highway, Cyperus rotundus showed a significant enrichment in Cd and demonstrated a notable capacity to translocate heavy metals from its roots to aerial parts. This is evidenced by the elevated concentration of Cd in the plant's aboveground tissues (0.87 mg/kg). Notably, both the bioconcentration factor (BCF) and translocation factor (TF) values exceeded 1, ranging from 1.07 to 3.62. Contrastingly, despite the elevated heavy metal concentrations in soils adjacent to the railway, plants in these areas did not exhibit hyperaccumulation characteristics. The unique behavior of Cyperus rotundus in accumulating and translocating Cd underscores its potential role in phytoremediation, particularly in the context of environmental management for areas impacted by mining activities, such as those surrounding China's largest copper mine.

Clinical and Virological Characteristics of Ebola Virus Disease Patients Treated With Favipiravir (T-705)-Sierra Leone, 2014.

BACKGROUND: During 2014-2015, an outbreak of Ebola virus disease (EVD) swept across parts of West Africa. No approved antiviral drugs are available for Ebola treatment currently. METHODS: A retrospective clinical case series was performed for EVD patients in Sierra Leone-China Friendship Hospital. Patients with confirmed EVD were sequentially enrolled and treated with either World Health Organization (WHO)-recommended supportive therapy (control group) from 10 to 30 October, or treated with WHO-recommended therapy plus favipiravir (T-705) from 1 to 10 November 2014. Survival and virological characteristics were observed for 85 patients in the control group and 39 in the T-705 treatment group. RESULTS: The overall survival rate in the T-705 treatment group was higher than that of the control group (56.4% [22/39] vs 35.3% [30/85]; P = .027). Among the 35 patients who finished all designed endpoint observations, the survival rate in the T-705 treatment group (64.8% [11/17]) was higher than that of the control group (27.8% [5/18]). Furthermore, the average survival time of the treatment group (46.9 ± 5.6 days) was longer than that of the control group (28.9 ± 4.7 days). Most symptoms of patients in the treatment group improved significantly. Additionally, 52.9% of patients who received T-705 had a >100-fold viral load reduction, compared with only 16.7% of patients in the control group. CONCLUSIONS: Treatment of EVD with T-705 was associated with prolonged survival and markedly reduced viral load, which makes a compelling case for further randomized controlled trials of T-705 for treating EVD.

Thermal, water, and land cover factors led to contrasting urban and rural vegetation resilience to extreme hot months.

With continuing global warming and urbanization, it is increasingly important to understand the resilience of urban vegetation to extreme high temperatures, but few studies have examined urban vegetation at large scale or both concurrent and delayed responses. In this study, we performed an urban-rural comparison using the Enhanced Vegetation Index and months that exceed the historical 90th percentile in mean temperature (referred to as "hot months") across 85 major cities in the contiguous United States. We found that hot months initially enhanced vegetation greenness but could cause a decline afterwards, especially for persistent (≥4 months) and intense (≥+2 °C) episodes in summer. The urban responses were more positive than rural in the western United States or in winter, but more negative during spring-autumn in the eastern United States. The east-west difference can be attributed to the higher optimal growth temperatures and lower water stress levels of the western urban vegetation than the rural. The urban responses also had smaller magnitudes than the rural responses, especially in deciduous forest biomes, and least in evergreen forest biomes. Within each biome, analysis at 1 km pixel level showed that impervious fraction and vegetation cover, local urban heat island intensity, and water stress were the key drivers of urban-rural differences. These findings advance our understanding of how prolonged exposure to warm extremes, particularly within urban environments, affects vegetation greenness and vitality. Urban planners and ecosystem managers should prioritize the long and intense events and the key drivers in fostering urban vegetation resilience to heat waves.

Heavy Metal Contamination and Ecological Risk Assessments in Urban Mangrove Sediments in Zhanjiang Bay, South China.

With the acceleration of industrialization and urbanization, increasing attention has been paid to the problem of heavy metal pollution in mangroves and its ecological restoration. Urban mangroves can be used to measure the impact of human activities on the urban ecological environment because mangroves are sensitive to human activities. However, studies on the evaluation of heavy metal elements in urban mangroves are still limited. Consequently, this study selected the urban mangroves in a central commercial area of Zhanjiang Bay as a case study to investigate the content and distribution of the heavy metals (Co, V, Cu, Pb, Ni, As, Cd, and Hg) in mangrove surface sediments. Risk levels and possible sources of heavy metals were evaluated based on multivariate statistical analysis methods and pollution indices. The results showed that the average concentrations of heavy metals for Co, V, Cu, Pb, Ni, As, Cd, and Hg were 2.91, 29.96, 18.24, 20.07, 7.86, 5.0, 0.20, and 0.09 mg/kg, respectively. Cd, Cu, and Hg were most prominent within the Zhanjiang Bay mangrove sediments, whereas other metals showed a low contamination factor of therm. Cd displayed a high potential ecological risk followed by Hg and Cu. The sampling site, the sewage outlet sampling site, exhibited the highest pollution degree followed by the surrounding area of the sewage outlet sampling site. Those polluted heavy metals could arise from anthropogenic sources, including domestic sewage and automobile exhaust emission. Correlation analysis between the heavy metals and physicochemical properties indicated that fine particles and organic matter play a key role in controlling heavy metal enrichment.

Machine learning-based observation-constrained projections reveal elevated global socioeconomic risks from wildfire.

Reliable projections of wildfire and associated socioeconomic risks are crucial for the development of efficient and effective adaptation and mitigation strategies. The lack of or limited observational constraints for modeling outputs impairs the credibility of wildfire projections. Here, we present a machine learning framework to constrain the future fire carbon emissions simulated by 13 Earth system models from the Coupled Model Intercomparison Project phase 6 (CMIP6), using historical, observed joint states of fire-relevant variables. During the twenty-first century, the observation-constrained ensemble indicates a weaker increase in global fire carbon emissions but higher increase in global wildfire exposure in population, gross domestic production, and agricultural area, compared with the default ensemble. Such elevated socioeconomic risks are primarily caused by the compound regional enhancement of future wildfire activity and socioeconomic development in the western and central African countries, necessitating an emergent strategic preparedness to wildfires in these countries.

Quantification of human contribution to soil moisture-based terrestrial aridity.

Current knowledge of the spatiotemporal patterns of changes in soil moisture-based terrestrial aridity has considerable uncertainty. Using Standardized Soil Moisture Index (SSI) calculated from multi-source merged data sets, we find widespread drying in the global midlatitudes, and wetting in the northern subtropics and in spring between 45°N-65°N, during 1971-2016. Formal detection and attribution analysis shows that human forcings, especially greenhouse gases, contribute significantly to the changes in 0-10 cm SSI during August-November, and 0-100 cm during September-April. We further develop and apply an emergent constraint method on the future SSI's signal-to-noise (S/N) ratios and trends under the Shared Socioeconomic Pathway 5-8.5. The results show continued significant presence of human forcings and more rapid drying in 0-10 cm than 0-100 cm. Our findings highlight the predominant human contributions to spatiotemporally heterogenous terrestrial aridification, providing a basis for drought and flood risk management.

Analysis of the change of clinical nursing pathway in health education among patients with ovarian carcinoma.

OBJECTIVE: To investigate the effect of health education via clinical nursing pathway (CNP) on self-care agency, quality of life, negative emotions and nursing satisfaction among patients with ovarian carcinoma. METHODS: The clinical data of 61 patients with ovarian carcinoma admitted to the Oncology Department of our hospital from January 2019 to January 2020 were analyzed retrospectively. According to the different nursing methods, the patients were divided into a control group (n=31) and an observation group (n=30). The postoperative complications, the scores of self-care agency and quality of life before and after intervention, sleep quality and negative emotions were compared and analyzed between the two groups. RESULTS: Patients in the observation group had higher mastery of health knowledge and lower incidence of postoperative complications than those in the control group. The scores of SDS, SAS and PSQI were significantly decreased in both groups after intervention compared with those before intervention (P<0.05), and the scores in the observation group were significantly lower than those in the control group (P<0.05). After intervention, both groups showed higher scores of self-care agency and quality of life than before intervention (P<0.05), and patients in the observation group showed higher scores than those in the control group (P<0.05). The overall nursing satisfaction of patient was relatively high. CONCLUSION: Health education via CNP can help patients better understand the diseases, reduce their psychological burden and improve sleep quality. Informing patients of the methods of postoperative restorative exercise through health education is able to reduce complications incidence and improve self-care agency and quality of life of patients.

Composition and Distribution of Aliphatic Hydrocarbon Compounds and Biomarkers in Seafloor Sediments from Offshore of the Leizhou Peninsula (South China).

The offshore of Leizhou Peninsula (LP, China), which contains unique ecosystems such as mangroves, seagrass beds, and coral reefs, is an environmentally sensitive area. For this reason, the levels of aliphatic hydrocarbon including biomarkers (hopanes, steranes) in the offshore seafloor sediments were analyzed in terms of their composition, distribution, and input sources and aimed to evaluate the extent of possible petroleum hydrocarbon contamination in the sediments of coastal areas. The total aliphatic hydrocarbons (TAH) fraction, the content of total n-alkanes (nC14-nC37) (∑n-alkanes), and content of hopane + sterane are in the range of 13.76-99.53, 1.22-8.33, and 0.02-0.23 µg/g dw, respectively. The presence of unresolved complex mixture (UCM) hydrocarbons hump and petrogenic steranes and hopanes in these seafloor sediments suggest that petrogenic sourced hydrocarbon inputs were present. The stations on the peninsula's southwest side had the lowest values of UCM/resolved aliphatic compounds (UCM/R) and UCM/n-alkanes. These findings suggest that seafloor sediments from the southwest offshore of the peninsula were likely contaminated by recently inputted petroleum hydrocarbons. The presence of relatively high ∑n-alkanes content in seafloor sediments from southwest offshore of the LP, combined with relatively low natural n-alkane ratios (NARs), indicates an increased influence of petrogenic hydrocarbons. The elevated levels of recent petrogenic hydrocarbon contamination in the sediments from the LP's southwestern offshore were likely related to petroleum exploitation in the Beibu Gulf's Maichen and Wushi sags.

Outcome of Chinese children with unrelated donor hematopoietic stem cell transplantation.

BACKGROUND: To evaluate the prognostic factors and outcomes in Chinese children undergoing unrelated donor hematopoietic stem cell transplantation (UDT). METHODS: Retrospective analysis of clinical data from 53 consecutive children who received UDT from November 2002 to December 2007 in our center. RESULTS: The median recipient age was 8.4 years (range 1.5-21). With a median follow-up of 36 months (range 18-80), the probability of 3-year overall survival (OS) was 71.5%. Treatment-related mortality (TRM) was 19.0%, and 9.5% died after post-transplant leukemia relapse. Incidence of grades I-II, III-IV acute and chronic graft versus host disease (GVHD) was 63%, 29%, and 46%. There was significant difference in OS between patients older or younger than 10 years (50.0% vs. 84.8%, P = 0.003), patients with different underlying diseases (ALL, AML, CML, and non-malignant disease: 36.4%, 80.0%, 61.5%, and 100%, P = 0.001) and patients receiving either HLA 0-1 versus 2-3 loci high-resolution mismatched UDT (83.3% vs. 53.3%, P = 0.034). The OS was not affected by the stem cell source (peripheral stem cell 70.3%, bone marrow 87.5% vs. cord blood 62.5%, P = 0.542) or the severity of acute GVHD (grade 0-II 77.8% vs. grade III-IV 60.0%, P = 0.140). CONCLUSIONS: The important prognostic factors for OS after UDT were the degree of HLA match, the age of patient and the type of underlying disease. Patients < 10-year with non-malignant disease receiving 0-1 locus high-resolution mismatched UDT had the most favorable outcomes.

Geochemical Signatures and Controlling Factors of Rearranged Hopanes in Source Rocks and Oils from Representative Basins of China.

The origin and geochemical significance of the rearranged hopanes in hydrocarbon source rocks or crude oil have attracted extensive attention. Despite numerous studies, there is not yet a proper conclusion. Therefore, this paper discusses the formation conditions of such compounds and points out their geochemical significance in more detail using a remarkably broad range of source rocks and crude oils from four basins in China. Varying content of rearranged hopanes was found in a total of 19 source rocks and oils from the Ordos, Sichuan, and Tarim basins and the North China Block. Gas chromatography-mass spectrometry (GC-MS) in combination with X-ray diffraction (XRD) and conventional geochemical parameters was used for Pearson correlation analysis to reveal the enrichment mechanisms of rearranged hopanes in the studied rock and oil samples. The GC-MS and XRD results showed that the studied source rocks with high rearranged hopane contents are closely associated with the high abundance of quartz rather than that of clay. Furthermore, the present study reveals that anoxic lacustrine conditions are the primary controlling factors of relatively high abundance of rearranged hopanes in the studied rocks and oils, whereas thermal maturity and terrigenous organic matter input are the secondary factors.

Quantifying the drivers and predictability of seasonal changes in African fire.

Africa contains some of the most vulnerable ecosystems to fires. Successful seasonal prediction of fire activity over these fire-prone regions remains a challenge and relies heavily on in-depth understanding of various driving mechanisms underlying fire evolution. Here, we assess the seasonal environmental drivers and predictability of African fire using the analytical framework of Stepwise Generalized Equilibrium Feedback Assessment (SGEFA) and machine learning techniques (MLTs). The impacts of sea-surface temperature, soil moisture, and leaf area index are quantified and found to dominate the fire seasonal variability by regulating regional burning condition and fuel supply. Compared with previously-identified atmospheric and socioeconomic predictors, these slowly evolving oceanic and terrestrial predictors are further identified to determine the seasonal predictability of fire activity in Africa. Our combined SGEFA-MLT approach achieves skillful prediction of African fire one month in advance and can be generalized to provide seasonal estimates of regional and global fire risk.

The benefit of ATG in immunosuppressive therapy of children with moderate aplastic anemia.

BACKGROUND: Previous studies specifically focused on the immunosuppressive therapy (IST) of children with moderate aplastic anemia (MAA) are rare. The aim of this study was to evaluate the advantage of using antithymocyte globulin (ATG) in the IST and its outcome of children with MAA. METHODS: Forty-two children diagnosed with moderate aplastic anemia from 1993 to 2006 were retrospectively reviewed. Eighteen patients treated with ATG, cyclosporin A (CSA), and androgen are defined as the ATG group, the other 24 patients treated with CSA and androgen are defined as the non-ATG group. Survival and hematological response of the two groups were studied. RESULTS: Response rate and transfusion-independent survival of the ATG group were both significantly higher than those of the non-ATG group (83.33 vs. 41.7%, p = .006; and 83.33 vs. 50%, p = .043, respectively). Compared with non-ATG group, fewer patients in ATG group progress to severe aplastic anemia (p = .03). CONCLUSION: Immunosuppressive therapy including ATG benefits children with moderate aplastic anemia.

[Relationship between immunological characteristics and prognosis in children with acute myeloid leukemia].

OBJECTIVE: The prognostic significance of immunophenotyping in acute myeloid leukemia (AML) has been controversial. This study investigated the relationship of immunophenotypes with French-American-British (FAB) subtypes and chromosomal abnormalities and assessed the prognostic value of immunophenotyping in children with AML. METHODS: From January 1998 to May 2003, 75 children with newly diagnosed AML were enrolled on protocol AML-XH-99. Immunophenotypes were measured with the flow cytometry. According to the McAbs used, the patients were classified into five groups: panmyeloid antigens (CD13, CD33, and MPO), myeloid-lineage associated antigens (CD14, CD15), lineage-specific antigens (CD41, GlyA), progenitor-associated antigens (CD34, HLA-DR) and lymphoid-associated antigens (CD19, CD7). The probability of event-free survival (EFS) was estimated by Kaplan-Meier analysis. The distributions of EFS were compared using the log-rank test. Chi-square analysis or Fisher exact test was used to compare the differences in the distribution of biologic presenting features. A Cox proportional hazards model was used to identify independent prognostic factors. RESULTS: At least one of panmyeloid antigens CD13, CD33 and MPO was expressed in 72 patents (97.3%). Two or more panmyeloid antigens were expressed in 45 patients (60.8%). The proportion of children with AML expressing one or more of the lymphoid-associated antigens was 24.3%. Lymphoid-associated antigen CD19 was expressed by blast cells in most of FAB M2 patients. The patients with acute promyelocytic leukemia were characterized by the absence of HLA-DR and lymphoid-associated antigens CD19 and CD7. Monovariate analysis showed immunophenotypes were not related to the complete remission rate after the first induction course and the 5-year-EFS. Multivariate analysis suggested immunophenotyping had no independent prognostic value in AML. CONCLUSIONS: Immunophenotyping can not be used independently in the evaluation of risk classification in children with AML. However, it is useful in the reorganization of special types of AML.

[Tandem application of flow cytometry and polymerase chain reaction for choice targets of minimal residual disease in childhood acute lymphoblastic leukemia].

OBJECTIVE: Minimal residual disease (MRD) is one of the most important prognostic factors in childhood acute lymphoblastic leukemia (ALL). Flow cytometry and PCR are two common techniques for examining MRD in ALL. This study aimed to identify MRD targets by tandem application of both techniques in children with ALL. METHODS: From September 2001 to October 2003, 126 children with newly diagnosed ALL were enrolled on the treatment protocol ALL-XH-99. Tandem application of flow cytometry and PCR was performed to identify MRD targets in these patients. RESULTS: 1. Using sets of combined antibodies, immunophenotypic expression of leukemia cells was observed in 95 of 106 B-lineage ALL cases (89.6%). Only one aberrant immunophenotype was observed in 11 cases (11.6%) and most patients with B-lineage ALL (88.4%) expressed at least two suitable targets. 2. Using PCR technique, T-cell receptor (TCR) or immunoglobulin gene rearrangements were identified in 26 of 27 patients (96.3%). Two or more monoclonal/ bi-allelic gene rearrangements were identified in 17 cases (65.4%). The majority (70%) of T-lineage ALL cases contained TCRVgammaI-Jgamma1.3/2.3. Cross-lineage TCR rearrangements were found in 57.1% of cases with B-lineage ALL. 3. Suitable MRD targets of immunophenotypic abnormalities or antigen receptor gene rearrangements were detected in 121 patients (96.0%). CONCLUSIONS: MRD targets were identified using tandem application of flow cytometry and PCR in almost of children with ALL. Cross-lineage TCR rearrangements and bi-allelic gene rearrangements were observed in many patients.

Increasing nitrogen export to sea: A scenario analysis for the Indus River.

The Indus River Basin faces severe water quality degradation because of nutrient enrichment from human activities. Excessive nutrients in tributaries are transported to the river mouth, causing coastal eutrophication. This situation may worsen in the future because of population growth, economic development, and climate change. This study aims at a better understanding of the magnitude and sources of current (2010) and future (2050) river export of total dissolved nitrogen (TDN) by the Indus River at the sub-basin scale. To do this, we implemented the MARINA 1.0 model (Model to Assess River Inputs of Nutrients to seAs). The model inputs for human activities (e.g., agriculture, land use) were mainly from the GLOBIOM (Global Biosphere Management Model) and EPIC (Environmental Policy Integrated Model) models. Model inputs for hydrology were from the Community WATer Model (CWATM). For 2050, three scenarios combining Shared Socio-economic Pathways (SSPs 1, 2 and 3) and Representative Concentration Pathways (RCPs 2.6 and 6.0) were selected. A novelty of this study is the sub-basin analysis of future N export by the Indus River for SSPs and RCPs. Result shows that river export of TDN by the Indus River will increase by a factor of 1.6-2 between 2010 and 2050 under the three scenarios. >90% of the dissolved N exported by the Indus River is from midstream sub-basins. Human waste is expected to be the major source, and contributes by 66-70% to river export of TDN in 2050 depending on the scenarios. Another important source is agriculture, which contributes by 21-29% to dissolved inorganic N export in 2050. Thus a combined reduction in both diffuse and point sources in the midstream sub-basins can be effective to reduce coastal water pollution by nutrients at the river mouth of Indus.

[Treatment of 2 children with mucopolysaccharidosis by allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: Mucopolysaccharidosis(MPS) is a congenital hereditary disease. Only a few patients with this disease can be controlled by enzyme replacement therapy. Most of them are short of effective interference. To exploit the effect of treatment with allogenic hematopoietic stem cell transplantation, two children were treated with the transplantation. METHODS: The two patients included a 23 month MPS-IH and an 18 month old MPS-VI at the time of transplantation. Busulfan of 20 mg/kg plus 200 mg of Cyclophosphamide were used as the conditioning regimen. Peripheral stem cells were collected from a 9/10 high resolution matched unrelated donor and a matched sibling carrier donor, respectively. The heart and lung were affected in the patient with MPS-IH. Medium obstructed pulmonary impairment was found by pulmonary function test at the time of transplantation. Medium mitral valve countercurrent and patent ductus arteriosis(PDA) were found by Doppla examination. RESULTS: The number of hematopoietic stem cells was comparative between the two donors with total nucleated cells and CD34+ cells of 11 x 10(8)/kg and 17 x 10(8)/kg, and 7.6 x 10(6)/kg and 7.2x 10(6)/kg respectively. Neutrophil engrafted at day 11. The process of transplantation in the MPS-VI patient went smoothly with grade II graft versus host disease(GVHD) briefly and only 1 U RBC and 2 U platelet were transfused. For the MPS-IH patient, the process of transplantation was tough with platelet reaching to 20 x 10(9)/L till day 40 and 5 U RBC and 7 U platelet were transfused during transplantation. Grade III GVHD was resolved by steroid, mycophenolate mofetil (MMF) and CD25 antibody. Pneumonia recurred 3 times with 2 times rescued by trachea intubation and mechanical ventilation because of accompanying acute heart failure. At day 14 the lymphocytes in both patients were 100% from donors as evidenced by short tandem repeat-PCR(STR-PCR). MPS associated enzyme activity was increased to 70 nmol/h.mg and 66 nmol/h.mg at 3 month and still remained 50.9 nmol/h.mg and 44.5 nmol/h.mg at 2 years post transplantation. Till now the 2 patients have been followed up for 25 months and 28 months with good general condition. The cardiac and pulmonary functions have improved obviously in the MPS-IH patient. The cornea became clear in this patient. CONCLUSION: Allogeneic hematopoietic stem cell transplantation is an effective measure to treat patient with MPS-IH and MPS-VI. Transplantation at earlier stage of age can decrease transplant related complications. It requires longer time follow up for observing the clinical effects for these patients.