A deep learning framework for predicting disease-gene associations with functional modules and graph augmentation.

BACKGROUND: The exploration of gene-disease associations is crucial for understanding the mechanisms underlying disease onset and progression, with significant implications for prevention and treatment strategies. Advances in high-throughput biotechnology have generated a wealth of data linking diseases to specific genes. While graph representation learning has recently introduced groundbreaking approaches for predicting novel associations, existing studies always overlooked the cumulative impact of functional modules such as protein complexes and the incompletion of some important data such as protein interactions, which limits the detection performance. RESULTS: Addressing these limitations, here we introduce a deep learning framework called ModulePred for predicting disease-gene associations. ModulePred performs graph augmentation on the protein interaction network using L3 link prediction algorithms. It builds a heterogeneous module network by integrating disease-gene associations, protein complexes and augmented protein interactions, and develops a novel graph embedding for the heterogeneous module network. Subsequently, a graph neural network is constructed to learn node representations by collectively aggregating information from topological structure, and gene prioritization is carried out by the disease and gene embeddings obtained from the graph neural network. Experimental results underscore the superiority of ModulePred, showcasing the effectiveness of incorporating functional modules and graph augmentation in predicting disease-gene associations. This research introduces innovative ideas and directions, enhancing the understanding and prediction of gene-disease relationships.

Induction of oxidative stress and cardiac developmental toxicity in zebrafish embryos by arsenate at environmentally relevant concentrations.

The contamination of water by arsenic (As) has emerged as a significant environmental concern due to its well-documented toxicity. Environmentally relevant concentrations of As have been reported to pose a considerable threat to fish. However, previous studies mainly focused on the impacts of As at environmentally relevant concentrations on adult fish, and limited information is available regarding its impacts on fish at early life stage. In this study, zebrafish embryos were employed to evaluate the environmental risks following exposure to different concentrations (0, 25, 50, 75 and 150 µg/L) of pentavalent arsenate (AsV) for 120 hours post fertilization. Our findings indicated that concentrations ≤ 150 µg/L AsV did not exert significant effects on survival or aberration; however, it conspicuously inhibited heart rate of zebrafish larvae. Furthermore, exposure to AsV significantly disrupted mRNA transcription of genes associated with cardiac development, and elongated the distance between the sinus venosus and bulbus arteriosus at 75 µg/L and 150 µg/L treatments. Additionally, AsV exposure enhanced superoxide dismutase (SOD) activity at 50, 75 and 150 µg/L treatments, and increased mRNA transcriptional levels of Cu/ZnSOD and MnSOD at 75 and 150 µg/L treatments. Concurrently, AsV suppressed metallothionein1 (MT1) and MT2 mRNA transcriptions while elevating heat shock protein70 mRNA transcription levels in zebrafish larvae resulting in elevated malondialdehyde (MDA) levels. These findings provide novel insights into the toxic effects exerted by low concentrations of AsV on fish at early life stage, thereby contributing to an exploration into the environmental risks associated with environmentally relevant concentrations.

Dihalogenated nitrophenols exposure induces developmental neurotoxicity in zebrafish embryo.

2,6-Dihalogenated nitrophenols (2,6-DHNPs) are emerging halogenated nitroaromatic pollutants that have been detected in various water environments. However, there is currently limited research available regarding their potential impacts on locomotion behavior and neurotoxicity. Therefore, this study utilized zebrafish embryos to investigate the potential neurotoxic effects of 2,6-DHNPs by examining their impact on the nervous system at a concentration defined as 10% of the median lethal concentration. Our findings demonstrated that exposure to 2,6-DHNPs resulted in a significant 30 % decrease in the total swimming distance of zebrafish larvae, accompanied by notable impairments in motor neuron development and central nervous system. These effects were evidenced by a substantial 25% decrease in axonal growth, as well as disruptions in synapse formation and neuronal differentiation. Additionally, neurotransmitter analysis revealed marked decreases of 40%, 35%, and 30% in dopamine, 5-hydroxytryptamine, and acetylcholine levels respectively, highlighting disturbances in their synthesis, transport, and degradation mechanisms. These results emphasize the considerable neurotoxicity of 2,6-DHNPs at concentrations previously considered safe; thus necessitating a re-evaluation of environmental risk assessments and regulatory standards for such emerging contaminants.

Hydrochemical characterization and comprehensive water quality assessment of groundwater within the main stream area of Yishu River.

To gain a comprehensive understanding of the hydrochemical characteristics, controlling factors, and water quality of groundwater in the main stream area of Yishu River (MSYR), a study was conducted using water quality data collected during both the dry and wet seasons. Through statistical analysis, hydrochemical methods, fuzzy comprehensive evaluation, and health risk evaluation modeling, the water chemical characteristics of the main stream area of Yishu River were studied, and the water quality of the area was comprehensively evaluated. The findings indicate that HCO3- and Ca2+ are the predominant anions and cations in the MSYR during the dry and wet seasons, respectively. Moreover, anion concentration in groundwater follows HCO3- > SO42- > NO3- > Cl-, while cations are ranked as Ca2+ > Na+ > Mg2+ > K+. Overall, the groundwater manifests as weakly alkaline and is predominantly classified as hard-fresh water. During the wet season, there is greater groundwater leaching and filtration, with rock and soil materials more readily transferred to groundwater, and the concentrations of main chemical components in groundwater are higher than those during the dry season, and the hydrochemical types are primarily characterized as HCO3-Ca·Mg and SO4·Cl-Ca·Mg types. These results also suggest that the chemical composition of the groundwater in the MSYR is influenced mainly by water-rock interaction. The primary ions originate from the dissolution of silicate rock and carbonate rock minerals, while cation exchange plays a critical role in the hydrogeochemical process. Groundwater in the MSYR is classified mostly as class II water, indicating that it is generally of good quality. However, areas with high levels of class IV and V water are present locally, and NO3- concentration is a crucial factor affecting groundwater quality. In the wet season, more groundwater and stronger mobility lead to greater mobility of NO3- and wider diffusion. Therefore, the risk evaluation model shows that nitrate health risk index is higher in the wet season than it is in the dry season, with children being more vulnerable to health risks than adults. To study groundwater in this area, its hydrochemical characteristics, water quality, and health risk assessment are of great practical significance for ensuring water safety for residents and stable development of social economy.

Molecular insights of 2,6-dichlorobenzoquinone-induced cytotoxicity in zebrafish embryo: Activation of ROS-mediated cell cycle arrest and apoptosis.

2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), as an emerging disinfection by-product, has been frequently detected in waters, posing potential health risk on public health. Although some studies have pointed out that 2,6-DCBQ exposure can induce cytotoxicity, limited information is available for underlying mechanism for 2,6-DCBQ-induced cytotoxicity. To explore this mechanism, we assessed the levels of reactive oxygen species (ROS), acridine orange (AO) staining, and the mRNA transcriptions of genes (Chk2, Cdk2, Ccna, Ccnb and Ccne) involved in cell-cycle and genes (p53, bax, bcl-2 and caspase 3) involved in apoptosis in zebrafish embryo, after exposed to different concentrations (10, 30, 60, 90 and 120 µg/L) of 2,6-DCBQ for 72 h. Our results indicated that 2,6-DCBQ exposure induced ROS generation and cell apoptosis, and disturbed the mRNA transcription of genes related to cell cycle and apoptosis in zebrafish embryo. Moreover, we also found that 30 ~ 60 µg/L 2,6-DCBQ is the important transition from cell-cycle arrest to cell apoptosis. These results provided novel insight into 2,6-DCBQ-induced cytotoxicity.

Metal/metalloid levels in hair of Shenzhen residents and the associated influencing factors.

129 Shenzhen residents' hair samples were collected and the metal/metalloid concentrations of Hg, As, Pb, Cd, Cr, Cu, Mn, Zn, Fe and Ni were detected. Meanwhile, the relationships between metal/metalloid contents in human hair and gender, age, seafood diet habit, smoking habit, as well as the housing type (dwelling environment) were analyzed. Results showed that the average content of Hg, As, Pb, Cd, Cr, Cu, Mn, Zn, Fe and Ni in human hair of Shenzhen residents was 0.76 ± 0.96, 0.10 ± 0.04, 5.25 ± 4.88, 0.25 ± 0.33, 0.60 ± 0.31, 13.84 ± 3.67, 2.82 ± 2.01, 196.90 ± 145.01, 12.20 ± 5.10 and 0.34 ± 0.32 µg/g, respectively. Compared with other regions at home and abroad, most metal/metalloids in Shenzhen residents were at a moderate level, and the highly toxic elements (i.e. Pb, Cd, As and Hg) didn't exceed the upper limit of normal values in China. Statistical analysis showed that the young male people contained significantly higher (p < 0.05) level of Pb (in age group of 20-30 years old) and Fe (in age group of 20-40 years old) in hair than the female people. Smokers had significantly (p < 0.05) higher level of Cd (0.35 µg/g) but lower level of Zn (101.24 µg/g) than non-smokers (Cd: 0.17 µg/g; Zn: 252.63 µg/g). Hg and Pb contents in hair of Shenzhen people were positively related with the frequencies of seafood consumption and the age, respectively. Moreover, residents lived in private buildings (well decorated house) accumulated significantly higher (p < 0.05) levels of Pb, Cr, Fe and Ni as compared with those lived in public rental house and village house (no decoration or simple decoration), suggesting that decoration material was also an important way for human exposure to heavy metals.

Cyclophosphamide induced physiological and biochemical changes in mice with an emphasis on sensitivity analysis.

The widespread use of cyclophosphamide (CP) in medical treatment had caused ubiquitous contamination in the environment. To data, many studies have been carried out on the toxic effect of CP. However, among these toxic effects of CP, which are the most sensitive remains unclear. Present study aimed to investigate the toxicity of CP on mice and evaluate the sensitivity of physiological-biochemical parameters upon exposure of mice to CP. Results showed that as compared with the control group, CP caused significant reduction in body weight (p < 0.01), spleen coefficient (p < 0.01), leukocyte density (p < 0.01) and alanine transaminase (ALT) in kidney (p < 0.01); However superoxide dismutase (SOD), malondialdehyde (MDA), ALT in liver and creatinine (Cr) in kidney significantly (p < 0.05) increased. Among the suppressed physiological and biochemical parameters, the sensitivity to CP toxicity was generally ranked as body weight > leukocyte density > ALT in kidney > spleen coefficient; while among the stimulated parameters, the sensitivity was ranked as MDA (liver) > Cr (kidney) > ALT (liver). Overall, the most sensitive parameters to CP toxicity may be associated with growth, immune system and the normal function of liver and kidney.

Environmentally relevant concentrations of arsenic induces apoptosis in the early life stage of zebrafish.

Arsenic (As) in the aquatic environment is a considerable environmental issue, previous studies have reported the toxic effects of low concentrations (≤ 150 µg/L) of As on fish. However, limited information is available regarding the impact of low levels of As on apoptosis. To evaluate this, zebrafish embryos were exposed to different concentrations (0, 25, 50, 75, and 150 µg/L) of As (arsenite [AsIII] and arsenate [AsV]) for 120 h. Our results indicated that low concentrations of AsIII exposure significantly inhibited the survival of zebrafish larvae, and significantly increased the transcription of Caspase-9 and Caspase-3, the ratio of Bax/Bcl-2 transcription, and protein levels of Caspase-3. In contrast, AsV decreased the ratios of Bax/Bcl-2 transcription and protein levels, as well as protein levels of Caspase-3. Our data demonstrated that AsIII and AsV exert different toxic effects, AsIII induced apoptosis via the mitochondrial pathway and the extrinsic pathway, while AsV induced apoptosis only via the mitochondrial pathway.

Pesticides in human milk collected from Jinhua, China: Levels, influencing factors and health risk assessment.

In China, many studies have been carried out on pesticide residues in human milk, yet all of them are on organochlorine pesticides (OCPs) and mostly focused on large, economically developed cities. In this study, 27 pesticides including OCPs, pyrethroid pesticides (PYRs) and organophosphate pesticides (OPPs) in human milk were investigated in Jinhua, an inland and medium sized city in China. Method based on QuEChERS extraction and gas chromatography-mass spectrometer (GC-MS) determination was adopted to analyze the above pesticide residues. The influencing factors as well as the health risks were also evaluated. Results show that PYRs and OPPs in human milk samples were both undetectable. Regarding OCPs, the detection rate of hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ß-HCH) and p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE) were 83.6%, 36.4% and 58.2%, respectively, and their mean value were 29.4, 32.0 and 85.2 ng/g lipid, respectively. p,p'-DDE levels in human milk was significantly (p < 0.05) related to maternal age, but no association was detected between OCPs residues and other factors (living environment, dietary habit, living style, etc.), suggesting that OCPs in human milk in Jinhua were originated from nonspecific source. All estimated daily intake of pesticides (EDIpesticides) by infants were under the guideline suggested by Food and Agriculture Organization (FAO) and China Ministry of Health (CMH). Yet 9% of EDIsHCB and 16% of EDIsHCHs exceeded the guideline recommended by Health Canada. The associations between DDE residues and the delivery way as well as HCBs residues and the birth weight were seemly significant, yet the significance disappeared when consider age or gestational age as a cofounder, indicating that OCPs residue in mother's body in Jinhua has no obvious influence on fetus development and the delivery way.

Antioxidant responses and pathological changes in the gill of zebrafish (Danio rerio) after chronic exposure to arsenite at its reference dose.

Gill, as the organ of fish to contact most directly with xenobiotics, suffered more threat. To evaluate the impact of arsenite (AsIII) on the gill of fish, we measured the antioxidative responses (superoxide dismutase (SOD) and catalase (CAT) activities) and oxidative damage (malondialdehyde (MDA) content), histological changes and mRNA transcriptional responses of zebrafish gill, after exposure to AsIII (0, 10, 50, 100, and 150 µg L-1) solutions for 28 days. We found that AsIII increased the activities of CAT by 46%-87%, decreased the activities of SOD and the contents of MDA by 19% and 21%-32%. Furthermore, CuZnSOD and MnSOD mRNA transcription levels were also inhibited, decreasing by 62%-82% and 70%-77%. Besides, ≥ 100 µg L-1 AsIII also caused histological changes (a loss of mucus and desquamation in the surface of the epithelial cells) on zebrafish gill. These results showed that low concentrations of AsIII influenced biochemical and physiological performances of fish gill, which probably aggravates the toxic effect of AsIII on fish.

Chronic exposure to dichloroacetamide induces biochemical and histopathological changes in the gills of zebrafish.

To evaluate the impact of DCAcAm on zebrafish gill, we measure the responses of antioxidant enzyme (superoxide dismutase, SOD), lipid peroxidation (malondialdehyde, MDA), ATPase (Na+ /K+ -ATPase and Ca2+ /Mg2+ -ATP) and histopathological changes of gill in adult zebrafish, after exposed to different concentrations of DCAcAm (0, 1, 10, 100, and 1000 µg L-1 ) for 30 days. Results indicated that DCAcAm first increased and then decreased SOD activity, and DCAcAm also lowered the activities of Na+ /K+ -ATPase and Ca2+ /Mg2+ -ATPase. These results indicated that high affinity of DCAcAm probably be a main factor, which can damage the structures of enzymes, thereby inhibiting the SOD and ATPase activities. Besides, histopathological investigation results also manifested that chronic exposure to DCAcAm can damage the gill tissues, disrupting the normal function of gills. We conclude that chronic exposure to DCAcAm was harmful to organisms, not only influence gill function, but also further cause damage on the gill tissues.

Genetic polymorphisms, forensic efficiency and phylogenetic analysis of 17 autosomal STR loci in the Han population of Wuxi, Eastern China.

The autosomal short tandem repeat (STR) plays a unique role in population comparisons, phylogenetic reconstruction and migration history tracing. This study investigated the frequencies of 17 autosomal STR loci in the Han population from Wuxi, Eastern China, with the aim of expanding the available population information in human genetic databases and for forensic DNA analysis. The genetic polymorphisms of 17 STR loci were analysed in 5358 individuals of the Han population from Wuxi, Eastern China. Population comparisons including genetic distances, the neighbour-joining tree and multidimensional scaling plot were carried out between the Wuxi Han population and different ethnic groups. A total of 777 alleles at 17 autosomal STR loci were observed, with the corresponding allelic frequencies ranging from 0.0001-0.5210. The combined power of discrimination and exclusion for the 17 autosomal STR loci were 0.0000 and 0.000, respectively. Moreover, the phylogenetic analysis was performed between the Wuxi Han population and other relevant populations. The neighbour-joining tree and multidimensional scaling plot were generated based on Nei's standard genetic distance. Population comparisons indicated that the Wuxi Han population had the closest genetic relationship with the Hubei Han population, relative to the other populations, which mirrors the historical and geographical background of the populations compared.

Soybean processing wastewater supported the removal of propyzamide and biochemical accumulation from wastewater by Rhodopseudomonas capsulata.

Simultaneous (SPW and propyzamide) wastewater treatment and the production of biochemicals by Rhodopseudomonas capsulata (R. capsulata) were investigated with supplement of soybean processing wastewater (SPW). Compared to control group, propyzamide was removed and biochemicals production were enhanced with the supplement of SPW. Propyzamide induced camH gene expression through activating MAPKKKs gene in MAPK signal transduction pathway. The induction of camH gene and CamH occurs after 1 day for R. capsulata. However, lack of organics in original wastewater did not maintain R. capsulata growth for over 1 day. The supplement of SPW provided sufficient carbon source for R. capsulata under three addition dosages. This new method resulted in the mixed (SPW and propyzamide) wastewater treatment and improvement of biochemicals simultaneously, as well as the realization of reutilization of wastewater and R. capsulata as sludge. Meanwhile, high-order nonlinear mathematical model of the relationship between propyzamide removal rate, Xt and Xt/r, was established.

Regression models evaluating THMs, HAAs and HANs formation upon chloramination of source water collected from Yangtze River Delta Region, China.

Present study aimed to generate multiple regression models to estimate the formation of trihalomethanes (THMs), haloacetonitriles (HANs) and haloacetic acids (HAAs) during chloramination of source water obtained from Yangtze River Delta Region, China. The results showed that the regression models for trichloromethane (TCM), dichloroacetonitrile (DCAN), dichloroacetic acid (DCAA), dihaloacetic acids (DHAAs), 5 HAAs species regulated by U.S. EPA (HAA5) and total haloacetic acids (HAA9) have good evaluation ability (prediction accuracy reached 81-94%), while the models for total haloacetonitriles (HAN4), trichloroacetic acid (TCAA), trihaloacetic acids (THAAs) and total trihalomethanes (THM4), they appeared relative low prediction accuracy (58-72%). For THMs, dissolved organic nitrogen (DON) was their key organic precursor, yet for HAN, DHAAs and THAAs, UVA254 played the dominant role. The other key factors influencing DBP formation included the bromide (THM4, DHAAs and HAA9), reaction time (DCAN, HAN4), chloramine dose (TCM, DCAA, TCAA, HAA5 and THAAs). These results provided important information for water works to optimize the water treatment process to control DBPs, and give an evaluating method for DBPs levels when estimating the health risks related with DBP exposure during chloramination.

Arsenic Relative Bioavailability in Rice Using a Mouse Arsenic Urinary Excretion Bioassay and Its Application to Assess Human Health Risk.

A steady-state mouse model was developed to determine arsenic (As) relative bioavailability (RBA) in rice to refine As exposure in humans. Fifty-five rice samples from 15 provinces of China were analyzed for total As, with 11 cooked for As speciation and bioavailability assessment. Arsenic concentrations were 38-335 µg kg-1, averaging 133 µg kg-1, with AsIII being dominant (36-79%), followed by DMAV (18-58%) and AsV (0.5-16%). Following oral doses of individual As species to mice at low As exposure (2.5-15 µg As per mouse) over a 7-d period, strong linear correlations (R2 = 0.99) were observed between As urinary excretion and cumulative As intake, suggesting the suitability and sensitivity of the mouse bioassay to measure As-RBA in rice. Urinary excretion factor for DMAV (0.46) was less than inorganic As (0.63-0.69). As-RBA in cooked rice ranged from 13.2 ± 2.2% to 53.6 ± 11.1% (averaging 27.0 ± 12.2%) for DMAV and 26.2 ± 7.0% to 49.5 ± 4.7% (averaging 39.9 ± 8.3%) for inorganic As. Calculation of inorganic As intake based on total inorganic As in rice overestimated As exposure by 2.0-3.7 fold compared to that based on bioavailable inorganic As. For accurate assessment of the health risk associated with rice consumption, it is important to consider As bioavailability especially inorganic As in rice.

Effects of novel brominated flame retardant TBPH and its metabolite TBMEHP on human vascular endothelial cells: Implication for human health risks.

As a replacement for polybrominated diphenyl ethers, bis-(2-ethylhexyl) tetrabromophthalate (TBPH) is widely used as a novel flame retardant and has been detected in many environmental matrix including human blood. TBPH can be metabolized into mono-(2-ethyhexyl) tetrabromophthalate (TBMEHP) by carboxylesterase. However, their adverse effects on human vascular endothelium and their potential impacts on human cardiovascular disease are unknown. In this study, their adverse effects and associated molecular mechanisms on human vascular endothelial cells (HUVECs) were investigated. A concentration-dependent inhibition on HUVECs' viability and growth was observed for TBMEHP but not for TBPH. TBMEHP induced a marked G0/G1 cell cycle arrest and robust cell apoptosis at 1µg/mL by inducing expression of p53, GADD45α and cyclin dependent kinase (CDK) inhibitors (p21and p27) while suppressing the expression of cyclin D1, CDK2, CDK6, and Bcl-2. Unlike TBMEHP, TBPH caused early apoptosis after G2/M phase arrest only at 10µg/mL via up-regulation of p21 and down-regulation of CDK2 and CDK4. TBMEHP decreased mitochondrial membrane potential and increased caspase-3 activity at 1µg/mL, suggesting that activation of p53 and mitochondrial pathway were involved in the cell apoptosis. The data showed that TBPH and TBMEHP induced different cell cycle arrest and apoptosis through different molecular mechanisms with much higher toxicity for TBMEHP. Our study implies that the metabolites of TBPH, possibly other novel brominated flame retardants, may be of potential concern for human cardiovascular disease.

Predicting the Relative Bioavailability of DDT and Its Metabolites in Historically Contaminated Soils Using a Tenax-Improved Physiologically Based Extraction Test (TI-PBET).

Due to their static nature, physiologically based in vitro assays often fail to provide sufficient sorption capacity for hydrophobic organic contaminants (HOCs). The addition of a sorption sink to in vitro intestinal solution has the potential to mimic dynamic intestinal uptake for HOCs, thereby increasing their desorption from soil. However, the effectiveness of sorption sinks for improving in vitro assays needs to be compared with in vivo data. In this study, Tenax was added as a sorption sink into the physiologically based extraction test (PBET), while DDT and its metabolites (DDTr) were investigated as typical HOCs. Tenax added at 0.01-0.2 g to the PBET intestinal solution sorbed ∼100% of DDTr in 6.3-19 min, indicating its ability as an effective sorption sink. DDTr bioaccessibility in six contaminated soils using Tenax-improved PBET (TI-PBET; 27-56%) was 3.4-22 fold greater than results using the PBET (1.2-15%). In vivo DDTr relative bioavailability (RBA) was measured using a mouse adipose model with values of 17.9-65.4%. The inclusion of Tenax into PBET improved the in vivo-in vitro correlation from r(2) = 0.36 (slope = 2.1 for PBET) to r(2) = 0.62 (slope = 1.2 for TI-PBET), illustrating that the inclusion of Tenax as a sorption sink improved the in vitro prediction of DDTr RBA in contaminated soils.

Arsenic Relative Bioavailability in Contaminated Soils: Comparison of Animal Models, Dosing Schemes, and Biological End Points.

Different animals and biomarkers have been used to measure the relative bioavailability of arsenic (As-RBA) in contaminated soils. However, there is a lack of As-RBA comparison based on different animals (i.e., swine and mouse) and biomarkers [area under blood As concentration curve (AUC) after a single gavaged dose vs steady-state As urinary excretion (SSUE) and As accumulation in liver or kidney after multiple doses via diet]. In this study, As-RBA in 12 As-contaminated soils with known As-RBA via swine blood AUC model were measured by mouse blood AUC, SSUE, and liver and kidney analyses. As-RBA ranges for the four mouse assays were 2.8-61%, 3.6-64%, 3.9-74%, and 3.4-61%. Compared to swine blood AUC assay (7.0-81%), though well correlated (R(2) = 0.83), the mouse blood AUC assay yielded lower values (2.8-61%). Similarly, strong correlations of As-RBA were observed between mouse blood AUC and mouse SSUE (R(2) = 0.86) and between urine, liver, and kidney (R(2) = 0.75-0.89), suggesting As-RBA was congruent among different animals and end points. Different animals and biomarkers had little impact on the outcome of in vivo assays to validate in vitro assays. On the basis of its simplicity, mouse liver or kidney assay following repeated doses of soil-amended diet is recommended for future As-RBA studies.

Assessment of immune cells and function of the residual spleen after subtotal splenectomy due to splenomegaly in cirrhotic patients.

BACKGROUND: The spleen is thought to be central in regulating the immune system, a metabolic asset involved in endocrine function. Overwhelming postsplenectomy infection leads to a mortality rate of up to 50%. However, there is still controversy on performing subtotal splenectomy as treatment of splenomegaly due to portal hypertension in cirrhotic patients. In the present study, immunocytes and the indexes of splenic size, hemodynamics, hematology and immunology in the residual spleen were analyzed to support subtotal splenectomy due to splenomegaly. RESULTS: In residual spleen, T lymphocytes mainly were focal aggregation in the periarterial lymphatic sheath. While B lymphocytes densely distributed in splenic corpuscle. In red pulp, macrophages were equally distributed in the xsplenic cord and adhered to the wall of splenic sinus with high density. The number of unit area T and B lymphocytes of splenic corpuscle and marginal zone as well as macrophages of red pulp were obviously increased in the residual spleen, while the number of macrophages didn't be changed among the three groups in white pulp. While there were some beneficial changes (i.e., Counts of platelet and leucocyte as well as serum proportion of CD3+ T cells, CD4+ T cells, CD8+ T cells were increased markedly; serum levels of M-CSF and GM-CSF were decreased significantly; The proportion of granulocyte, erythrocyte, megakaryocyte in bone marrow were changed obviously; But serum IgA, IgM, IgG, Tuftsin level, there was no significant difference; splenic artery flow volume, portal venous diameter and portal venous flow volume, a significant difference was observed in residual spleen) in the clinical indices. CONCLUSION: After subtotal splenectomy with splenomegaly due to portal hypertension in cirrhotic patients, the number of unit area T and B lymphocytes, and MØ in red pulp of residual spleen increased significantly. However, whether increase of T, B lymphocytes and MØs in residual splenic tissue can enhance the immune function of the spleen, still need further research to confirm.