Haploidentical donor transplant is associated with secondary poor graft function after allogeneic stem cell transplantation: A single-center retrospective study.

BACKGROUND: Secondary poor graft function (sPGF) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) related to poor outcome. We aimed to retrospectively evaluate the morbidity and hazard elements of sPGF after allo-HSCT. METHODS: Eight hundred and sixty-three patients who achieved initial engraftment of both neutrophils and platelets were retrospectively reviewed in this study. RESULTS: Fifty-two patients developed sPGF within 180 days post-transplants, with the median onset time was 62 days (range, 34-121 days) post-transplants. The overall cumulative incidence of sPGF within 180 days post-transplantation was 6.0%, with 3.4%, 3.4%, and 10.1%, respectively, in matched sibling donor (MSD), matched unrelated donor (MUD), and haploidentical donor (HID) transplant (p < 0.0001). Multivariable analysis showed that HID (HID vs. MSD: hazard ratio [HR] 2.525, p = 0.004; HID vs. MUD: [HR] 3.531, p = 0.017), acute graft versus host disease (aGVHD) within +30 days ([HR] 2.323, p = 0.003), and cytomegalovirus (CMV) reactivation ([HR] 8.915, p < 0.0001) within +30 days post-transplants were hazard elements of sPGF. The patients with sPGF had poorer survival than good graft function (51.7±8.1% vs. 62.9±1.9%, p < 0.0001). Our results also showed that only CMV reactivation was the hazard element for the development of PGF in HID transplant ([HR] 12.521 p < 0.0001). CONCLUSION: HID transplant is also an independent hazard element of sPGF except for aGVHD and CMV reactivation.

Allogeneic hematopoietic stem cell transplantation overcomes the poor prognosis in MLL-rearranged solid tumor therapy related-acute myeloid leukemia.

MLL rearrangement is very common in solid tumor therapy-related acute myeloid leukemia (t-AML). To investigated the prognosis of solid tumor MLL t-AML, 157 patients were divided into 3 groups: non-MLL t-AML (n=41), MLL t-AML (n=18) and MLL de novo AML (n=98). Of the 150 patients underwent anti-leukemia therapy, the complete remission (CR) was similar in MLL t-AML, non-MLL t-AML and MLL de novo AML (P=0.251). 3-years overall survival (OS) was 37.5%, 21.5% and 20.4% (P=0.046), and leukemia-free survival (LFS) was 28.0%, 32.2% and 22.7% (P=0.031), and the incidence of relapse was 30.0%, 50.4% and 53.5% (P=0.382), respectively, in the three groups. Multivariate analysis revealed that MLL t-AML was a risk factor while allo-HSCT was a protective factor for OS, LFS, and relapse (P<0.001, P<0.001 and P=0.005) (P=0.002, P<0.001 and P<0.001, respectively). The 3-years OS was 0%, 17.9% and 2.3% (P=0.038), and LFS was 0%, 23.1% and 3.3% (P=0.017), and relapse was 100%, 53.1% and 74.4% (P=0.001), respectively, among three groups in patients undergoing chemotherapy alone, while OS was 64.3%, 52.7% and 40.7% (P=0.713), LFS was 60.0%, 48.8% and 37.0% (P=0.934), and relapse was 25.0%, 47.4% and 47.5% (P=0.872), respectively, among these groups in patients undergoing allo-HSCT. Intriguingly, MLL t-AML was no longer risk factor for relapse and LFS (P=0.882 and P=0.484, respectively), and it became a favorable factor for OS (P=0.011) in patients undergoing allo-HSCT. In conclusion, MLL t-AML had poor prognosis compared with non-MLL t-AML and MLL de novo AML, but allo-HSCT might overcome the poor prognosis of MLL t-AML.

[Spatial-temporal Distribution of Suspended Solids and Its Sedimentation Flux and Nutrients Effects in Xin'anjiang Reservoir, China].

To analyze the spatial-temporal distribution and sedimentation characteristics of suspended solids in reservoirs, high-frequency monitoring of a sediment trap and buoy, combined with three-dimensional water sampling, was conducted and analyzed in Xin'anjiang Reservoir for a year. The results showed that the turbidity data of the buoy has significant correlation with rainfall, inflow, and suspended solids (SS), particularly for SS (P<0.01, R2=0.86). There is an obvious spatial difference in SS between spring and summer, when the rainfall season occurs (river area > transition area > lake area). However, there is little difference in SS concentration between autumn and winter. There is a spatial trend of river area > transition area > lake area (with rates of 27.82, 4.34, and 0.26 g·(m2·d)-1, respectively), and a temporal trend of spring and summer > autumn and winter. The sedimentation flux of the whole lake is 2.57×106 t·a-1 combined with the investigation of the four-season SS at 60 points across the whole lake, and the settlement flux in spring and summer is higher than that in autumn and winter. The contents of particulate nitrogen (PN) in JK, XJS, and DB were 6812, 15886, and 21986 mg·kg-1, and the particulate phosphorus (PP) contents were 2545, 3269, and 3077 mg·kg-1, respectively. Statistical analysis shows that there is a good exponential relationship between moderate rainfall and turbidity growth rate in the river area of the reservoir (R2=0.81). Moreover, the continuous heavy rainfall affects turbidity in river area, but has little effect on the transition area. The concentration of SS has a good exponential decay with distance from the river to the dam (R2=0.84), especially in spring and summer. Research shows that the average annual deposition rate in Xin'anjiang Reservoir is 0.07%, lower than other large reservoirs in the country; however, there are certain risks in front of the dam because the nutrient sediments are high. The results suggest that reservoir managers should pay attention to water and soil conservation in the watershed to reduce the impact of rainfall on reservoir water quality. Meanwhile, the potential nutrient internal release risk in the downstream area before the dam should be considered.

[Occurrence and Influencing Factors of Odorous Compounds in Reservoirs Used as Drinking Water Resources in Jiangsu Province].

In order to recognize the risk of odorous compounds and its driving mechanisms in water source reservoirs, the water quality, plankton, and odorous compounds of 17 provincial water source reservoirs in Jiangsu Province were investigated during a high-risk period of odorous compounds. A high eutrophication status, such as high algal biomass and low transparency, were widely observed in our study reservoirs. In addition, 2-methylisoborneol (MIB) exceeded the standard in some water layers of one-third of the reservoirs, of which the average concentration was (13.7±20.7) ng·L-1. Geosmin (GSM) was also detected in several reservoirs, although the maximum concentration of 4.6 ng·L-1 did not exceed the drinking water quality standard. With respect to the relationships between odorous compounds and environmental conditions, significant correlation (P<0.05) was noted between the MIB concentration and eutrophication indicators, including chlorophyll-a, Secchi depth, suspended solids, and comprehensive nutrition state index (TLI), particularly for chlorophyll-a and TLI (P<0.01). These results indicate that the risk of odorous compounds in water source reservoirs depend largely on the eutrophic status. Therefore, nutrient reduction, improvement in vegetation coverage of the reservoir basin, reasonable fishing practices are considered as effective strategies to avoid the risk of the odorous compounds in reservoirs.

[Applicability of Bioavailable Phosphorus in Sediments to Indicating Trophic Levels of Lakes and Reservoirs].

Twelve lakes and reservoirs with different water depths and different water residence times were studied to identify the applicability of bioavailable phosphorus of sediments in indicating trophic levels. Water and sediment samples were collected in these 12 lakes and reservoirs to analyze the relationship of nutrient levels between the sediment and the water column. Sodium hydroxide extracted phosphorus (NaOH-P) determined using the SMT classification method is defined as the bioavailable phosphorus of sediment. The results showed that total phosphorus levels in sediments in different lakes and reservoirs ranged from 225 to 760 mg·kg-1 (mean value 502 mg·kg-1); the NaOH-P levels in sediments ranged from 86 to 584 mg·kg-1 (mean value 263 mg·kg-1); the total phosphorus concentrations in the water was 0.02-0.35 mg·L-1 (mean value 0.11 mg·L-1), and the chlorophyll a concentrations in the water were 3-349 µg·L-1 (mean value 51 µg·L-1). It was found that NaOH-P was more effective than total phosphorus in indicating the trophic status of the lakes and reservoirs. However, the NaOH-P levels were significantly related to the phosphorus concentrations in the water column only in shallow water with a long residence time. It was revealed that water residence time and water depth are two key factors that affect the relationship of the phosphorus content between the sediment and the water column. In deep waters or waters with short residence time, the NaOH-P content in the sediment hardly influenced the phosphorus concentration in the water columns, even at high levels. However, in shallow waters with long residence time, the sediment acted as both sources and sinks and frequently exchanged nutrients with the overlying water, especially during bloom periods in summer. Thus NaOH-P could be a potential risk of eutrophication in such waters.

Characterization and fungal community of antler dermophytosis in Jilin and Liaoning provinces / 中国人兽共患病学报

Dermophytosis is a common fungal disease that affects fast-growing antlers of sika deer (Cervus nippon)and red deer (Cervus elaphus),causing the so-called 'white-skin antlers'and 'crusted antlers'.Here we described the features of dermophytosis in deer antler observed from 20 affected deer from 8 farms in Jilin and Liaoning province by clinical findings,he-matology,pathological examination and fungal species distribution.The fungal infection in the antlers as indicated by HE stai-ning,affected only epidermis and the dermis layers,with the main lesion of necrosis of the dermis tissue and inflammatory in-filtrate.Hematologic profile suggested the insignificant cell count change of lymphocyte,neutrophil,white blood cell between dermophytosis and healthy deer(n=10).A total of 68 fungi isolates were then recovered from the antlers with dermophytosis, of which 64.7% (44/68)were identified as members within Deuteromycotina,the rest 35.3% (24/68)belonged to the Saccha-romycotina.Notably,the well-known opportunistic pathogen,including species within Trichophyton,Epidermophyton as well as Candida albican,might account for the dermophytosis of deer antler.In conclusion,'white-skin antlers'and 'crusted antlers'are high likely caused by opportunistic fungi.

Detection of Multi-drug Resistant Acinetobacter Lwoffii Isolated from Soil of Mink Farm / 生物医学与环境科学（英文）

There were 4 Acinetobacter lwoffii obtained from soil samples. The antimicrobial susceptibility of the strains to 16 antimicrobial agents was investigated using K-B method. Three isolates showed the multi-drug resistance. The presence of resistance genes and integrons was determined using PCR. The aadA1, aac(3')-IIc, aph(3')-VII, aac(6')-Ib, sul2, cat2, floR, and tet(K) genes were detected, respectively. Three class 1 integrons were obtained. The arr-3-aacA4 and blaPSE-1 gene cassette, which cause resistance to aminoglycoside and beta-lactamase antibiotics. Our results reported the detection of multi-drug resistant and carried resistant genes Acinetobacter lwoffii from soil. The findings suggested that we should pay close attention to the prevalence of multi-drug resistant bacterial species of environment.

Serine Proteases of Parasitic Helminths

Serine proteases form one of the most important families of enzymes and perform significant functions in a broad range of biological processes, such as intra- and extracellular protein metabolism, digestion, blood coagulation, regulation of development, and fertilization. A number of serine proteases have been identified in parasitic helminths that have putative roles in parasite development and nutrition, host tissues and cell invasion, anticoagulation, and immune evasion. In this review, we described the serine proteases that have been identified in parasitic helminths, including nematodes (Trichinella spiralis, T. pseudospiralis, Trichuris muris, Anisakis simplex, Ascaris suum, Onchocerca volvulus, O. lienalis, Brugia malayi, Ancylostoma caninum, and Steinernema carpocapsae), cestodes (Spirometra mansoni, Echinococcus granulosus, and Schistocephalus solidus), and trematodes (Fasciola hepatica, F. gigantica, and Schistosoma mansoni). Moreover, the possible biological functions of these serine proteases in the endogenous biological phenomena of these parasites and in the host-parasite interaction were also discussed.

4-Hydroxynonenal promotes growth and angiogenesis of breast cancer cells through HIF-1α stabilization.

4-Hydroxynonenal (4-HNE) is a stable end product of lipid peroxidation, which has been shown to play an important role in cell signal transduction, while increasing cell growth and differentiation. 4-HNE could inhibit phosphatase and tensin homolog (PTEN) activity in hepatocytes and increased levels have been found in human invasive breast cancer. Here we report that 4-HNE increased the cell growth of breast cancer cells as revealed by colony formation assay. Moreover, vascular endothelial growth factor (VEGF) expression was elevated, while protein levels of hypoxia inducible factor 1 alpha (HIF-1α) were up-regulated. Sirtuin-3 (SIRT3), a major mitochondria NAD+-dependent deacetylase, is reported to destabilize HIF-1α. Here, 4-HNE could inhibit the deacetylase activity of SIRT3 by thiol-specific modification. We further demonstrated that the regulation by 4-HNE of levels of HIF-1α and VEGF depends on SIRT3. Consistent with this, 4-HNE could not increase the cell growth in SIRT3 knockdown breast cancer cells. Additionally, 4-HNE promoted angiogenesis and invasion of breast cancer cells in a SIRT3-dependent manner. In conclusion, we propose that 4-HNE promotes growth, invasion and angiogenesis of breast cancer cells through the SIRT3-HIF-1α-VEGF axis.

Regulation of integrin αV subunit expression by sulfatide in hepatocellular carcinoma cells.

Integrin is important in migration and metastasis of tumor cells. Changes of integrin expression and distribution will cause an alteration of cellular adhesion and migration behaviors. In this study, we investigated sulfatide regulation of the integrin αV subunit expression in hepatoma cells and observed that either exogenous or endogenous sulfatide elicited a robust upregulation of integrin αV subunit mRNA and protein expression in hepatoma cells. This regulatory effect occurred with a corresponding phosphorylation (T739) of the transcription factor Sp1. Based on the electrophoretic mobility shift assay, sulfatide enhanced the integrin αV promoter activity and strengthened the Sp1 complex super-shift. The results of chromatin immunoprecipitation analysis also indicated that sulfatide enhanced Sp1 binding to the integrin αV promoter in vivo. Silence of Sp1 diminished the stimulation of integrin αV expression by sulfatide. In the early stage of sulfatide stimulation, phosphorylation of Erk as well as c-Src was noted, and inhibition of Erk activation with either U0126 or PD98059 significantly suppressed Sp1 phosphorylation and integrin αV expression. We demonstrated that sulfatide regulated integrin αV expression and cell adhesion, which was associated with Erk activation.

Identification and characterization of two novel germ line p53 mutations in the non-LFS/non-LFL breast cancer families in Chinese population.

Germ line mutations in the tumor suppressor gene, p53, are known to cause Li-Fraumeni syndrome (LFS) or Li-Fraumeni-like syndrome (LFL). We sought to identify p53 germ line mutations in potential hereditary breast cancer patients without LFS/LFL phenotype, which will help us establish the genetic testing strategy for p53 in Chinese high-risk breast cancer families. We screened all coding exons and intron-exon boundaries of p53 in 240 women with early-onset breast cancer or affected relatives from four breast disease clinical centers in China by utilizing PCR-DHPLC and DNA sequencing analysis. Additionally, three cell lines (H1299, MCF-7, and MDA-MB-231) were transfected with pEGFP-N1-only or pEGFP-N1 vectors expressing either wild-type or two novel identified mutant p53. And then we performed flow cytometry analysis in the transfected cells to determine the status of cell apoptosis, and real-time PCR as well as western blot analysis to ascertain the expression of p53, p21, and p27. Two novel germ line mutations (563T > C and 643_660del18) were detected in two independent families. Neither of them, however, was present in the 768 normal controls. Functional assays revealed that the ability to trigger cell apoptosis and transcriptional activation of target gene under similar expression of p53 were lower in two mutants versus wild-type p53. Deleterious mutations of p53 seemed to be responsible for approximately 1% of non-BRCA1/BRCA2 hereditary breast cancer in Chinese population, and our findings suggested that p53 should be included in genetic testing of Chinese non-LFS/non-LFL high-risk breast cancer families.

Genetic variation analysis of canine parvovirus VP2 gene in China / 病毒学报

To recognize the molecular biology character, phylogenetic relationship and the state quo prevalent of Canine parvovirus (CPV), Faecal samnples from pet dogs with acute enteritis in the cities of Beijing, Wuhan, and Nanjing were collected and tested for CPV by PCR and other assay between 2006 and 2008. There was no CPV to FPV (MEV) variation by PCR-RFLP analysis in all samples. The complete ORFs of VP2 genes were obtained by PCR from 15 clinical CPVs and 2 CPV vaccine strains. All amplicons were cloned and sequenced. Analysis of the VP2 sequences showed that clinical CPVs both belong to CPV-2a subtype, and could be classified into a new cluster by amino acids contrasting which contains Tyr-->Ile (324) mutation. Besides the 2 CPV vaccine strains belong to CPV-2 subtype, and both of them have scattered variation in amino acids residues of VP2 protein. Construction of the phylogenetic tree based on CPV VP2 sequence showed these 15 CPV clinical strains were in close relationship with Korea strain K001 than CPV-2a isolates in other countries at early time, It is indicated that the canine parvovirus genetic variation was associated with location and time in some degree. The survey of CPV capsid protein VP2 gene provided the useful information for the identification of CPV types and understanding of their genetic relationship.