COLEC10 Induces Endoplasmic Reticulum Stress by Occupying GRP78 and Inhibits Hepatocellular Carcinoma.

Collectin subfamily member 10 (COLEC10), a C-type lectin mainly expressed in the liver, is involved in the development of hepatocellular carcinoma (HCC). However, its underlying molecular mechanism in HCC progression remains unknown. In this study, reduced COLEC10 expression in tumor tissues was validated using various HCC cohorts and was associated with poor patient prognosis. COLEC10 overexpression attenuated HCC cell growth and migration abilities in vitro and in vivo. We identified that COLEC10 was a novel interactor of 78-kDa glucose-regulated protein (GRP78), a master modulator of the unfolded protein response in the endoplasmic reticulum (ER). COLEC10 overexpression potentiated ER stress in HCC cells, as demonstrated by elevated expression levels of phosphorylated protein kinase RNA-like ER kinase, phosphorylated inositol-requiring protein 1α, activating transcription factor 4, DNA damage-inducible transcript 3, and X-box-binding protein 1s. The ER in COLEC10-overexpressing cells also showed a dilated and fragmented pattern. Mechanistically, COLEC10 overexpression increases GRP78 occupancy through direct binding by the C-terminal carbohydrate recognition domain in the ER, which released and activated the ER stress transducers protein kinase RNA-like ER kinase and phosphorylated inositol-requiring protein 1α, triggering the unfolded protein response activity. COLEC10-overexpressing HCC cells generated a relatively high reactive oxygen species level and switched to apoptotic cell death under sorafenib-treated conditions. Our study provides the first novel view that COLEC10 inhibits HCC progression by regulating GRP78-mediated ER stress signaling and may serve as a promising therapeutic and prognostic biomarker.

Transforming growth factor-ß: An early predictor of a functional cure in chronic hepatitis B treated with interferon.

BACKGROUND: The relationship between the serum transforming growth factor (TGF)-ß level and HBsAg loss has not been clearly elaborated in patients with chronic hepatitis B (CHB). METHODS: Two cohorts of patients with CHB were studied. Cohort A: A total of 207 hepatitis B e antigen (HBeAg)-negative CHB patients who finished ≥1 year nucleos(t)ide analogue monotherapy and sequentially received PEGylated interferon treatment for less than 96 weeks were included. Cohort B: Forty HBeAg-positive patients who initially received entecavir therapy for at least 96 weeks were included. Their viral markers and serum TGF-ß levels were measured at different time points during therapy. RESULTS: The levels of serum TGF-ß and HBsAg (0-24 W) were significantly lower in the patients who had HBsAg< 0.05 IU/mL at 48 weeks than in patients who did not in cohort A. We got the same results when we further divided the patients into subgroups according to the initial HBsAg cut-off values (1000 IU/mL, 100 IU/mL, 50 IU/mL) in cohort A. However, HBeAg seroconversion did not lead to the downregulation of TGF-ß levels. The levels of serum TGF-ß were significantly correlated with HBsAg quantitation in cohort A (12-24 W) but not in cohort B (0-48 W). The levels of TGF-ß at week 12 could be used as an early index to predict a functional cure (AUC=0.818) as well as the levels of HBsAg itself (AUC=0.882) in HBeAg-negative chronic hepatitis B patients treated with PEGylated interferon. CONCLUSIONS: The levels of serum TGF-ß were significantly associated with HBsAg loss but not with HBeAg seroconversion and could be used as an early index to predict a functional cure in CHB patients treated with PEGylated interferon.

GTSE1 promotes SNAIL1 degradation by facilitating its nuclear export in hepatocellular carcin oma cells.

Snail family transcriptional repressor 1 (SNAIL1) is a master inducer of the epithelial­to­mesenchymal transition (EMT) process, contributing to tumor metastasis and recurrence. Our previous study reported that G2 and S phase­expressed­1 (GTSE1) served a role in regulating SNAIL1 expression in hepatocellular carcinoma (HCC). However, the underlying mechanism remains unknown. Therefore, the present study aimed to reveal the regulatory mechanism of GTSE1 on SNAIL1 expression using in vitro assays performed in HCC cell models. It was demonstrated that endogenous SNAIL1 expression was downregulated and upregulated by GTSE1 overexpression or small interfering RNA­mediated knockdown, respectively. Via cycloheximide chase experiments, it was identified that GTSE1 overexpression increased the protein turnover of SNAIL1, while knockdown of GTSE1 reduced its degradation rate. Furthermore, it was demonstrated that GTSE1 overexpression induced the cytoplasmic expression of SNAIL1 using immunofluorescence and subcellular fractionation methods. The nuclear export inhibitor leptomycin B was able to decrease the cytoplasmic retention of SNAIL1 caused by GTSE1 overexpression. In addition, TGF­ßI treatment increased both the mRNA and protein expression levels of GTSE1, and decreased the protein expression level of SNAIL1 without affecting its mRNA transcription in Huh7 cells. It was also found that TGF­ß signaling could upregulate the transcription of GTSE1 expression by transactivating the Smad binding elements in the GTSE1 promoter. Moreover, the TGF­ßI­induced decrease in SNAIL1 protein expression was GTSE1­dependent in Huh7 cells. In conclusion, the current study provides a novel mechanism via which GTSE1 affects the stability of SNAIL1 by regulating its subcellular localization in HCC cells.

Distinct T-cell receptor profiles associated with hepatitis B e antigen seroconversion during entecavir treatment.

BACKGROUND & AIMS: T-cell receptor (TCR) repertoire is ambiguously changed in chronic hepatitis B (CHB) patients during antivirus therapy. We tried to assess TCR repertoire dynamics and its clinical significance upon HBeAg seroconversion in CHB patients. METHODS: Twenty CHB patients undergoing 1-year entecavir (ETV) treatment were enrolled, including 10 complete response (CR) vs 10 non-complete response (NCR) patients based on HBeAg seroconversion at week 48. The TCRß complementarity-determining region 3 (CDR3) of peripheral CD4+ and CD8+ T cells at weeks 0, 12 and 48 was analyzed by unbiased high-throughput sequencing. The TCR repertoire profiles and their correlations with serological parameters were analyzed. RESULTS: The diversity of TCRß repertoires was decreasing in CR patients but increasing in NCR patients. The distribution pattern of TCR repertoires stratified according to clonotype frequencies changed in the opposite direction between CR and NCR patients. Narrow amounts of newly appearing clonotypes in CR patients experienced a more intensive and robust expansion and this phenomenon could occur as early as week 12 for the CD4+ subset but later at week 48 for the CD8+ subset. There existed some CR-exclusive clonotypes with a relatively low but increasing frequency at week 48. The number of unique TCRß clonotypes was positively correlated with the ALT or HBV DNA level in CR patients but showed no or negative correlation in NCR patients. CONCLUSION: Distinct TCR profiles contribute to predicting HBeAg seroconversion in CHB patients during ETV treatment and certain TCRß CDR3 motif may be utilized for CHB immunotherapy in the future.

Overexpressing PLOD family genes predict poor prognosis in gastric cancer.

Procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLODs) are a set of enzymes involved in the hydroxylation of lysine and stabilization of collagen by crosslinks. Previous studies have highlighted that overexpressing PLOD genes were related to the progression, migration and progression of different human cancers. However, the diverse expression patterns and prognostic values of PLOD genes remain to be elucidated in gastric cancer (GC). In this study, we mined the expression and survival data in GC patients through ONCOMINE, UALCAN and Kaplan-Meier Plotter database. STRING portal couple with DAVID was used to establish a functional protein interaction network of PLOD family genes and analyze the GO and KEGG enriched pathways. Differential gene expression correlated with PLOD family genes was identified with LinkedOmics. We found that PLOD1, 2 and 3 were up-regulated in GC patients compared with normal tissues. High expression levels of PLOD1 and PLOD3 were associated with shorter overall survival (OS), first progression (FP) and post progression survival (PPS) while high expression level of PLOD2 was only associated with shorter FP in all GC patients. Specifically, only high PLOD2 expression had significant correlation with shorter OS, FP and PPS in the diffuse type GC patients. Furthermore, combinatorial use of expressions of all PLOD genes was a superior prognostic indicator for GC patients. Pathway analysis confirmed that PLOD family genes mainly participate in regulating the collagen metabolism and extracellular matrix constitution, and the cellular adaptor protein SHC1, which helps to transduce an extracellular signal into an intracellular signal, could be the regulatory module mediating PLOD's effect on GC. Therefore, we propose that individual PLOD genes or PLOD family genes as a whole could be potential prognostic biomarkers for GC.

CACYBP Enhances Cytoplasmic Retention of P27Kip1 to Promote Hepatocellular Carcinoma Progression in the Absence of RNF41 Mediated Degradation.

Calcyclin-binding protein (CACYBP) is a multi-ligand protein implicated in the progression of various human cancers. However, its function in hepatocellular carcinoma (HCC) remains unknown. Methods: The expression of CACYBP and RNF41 (RING finger protein 41) in HCC cancer and adjacent non-tumor tissues was detected by immunohistochemistry. CCK-8 assays, colony formation assays, flow cytometry detection and xenograft models were used to evaluate the impact of CACYBP expression on HCC cell growth, apoptosis and cell cycle regulation. Immunoprecipitation and ubiquitination assays were performed to determine how RNF41 regulates CACYBP. The regulatory mechanism of RNF41-CACYBP signaling axis on P27Kip1 was investigated by western blotting and immunofluorescence. Results: CACYBP was highly expressed and associated with poor prognosis in HCC. CACYBP expression was required for HCC cell growth in vitro and in vivo. Moreover, we identified RNF41 as a specific binding partner of CACYBP at exogenous and endogenous levels. RNF41 recruited CACYBP by its C-terminal substrate binding domain, subsequently ubiquitinating CACYBP and promoting its degradation in both proteasome- and lysosome-dependent pathways. In HCC tissues, RNF41 expression was reduced and conferred a negative correlation with CACYBP expression. Mechanistically, CACYBP overexpression stimulated the Ser10, Thr157 and Thr198 phosphorylation of P27Kip1 and its cytoplasmic retention, and RNF41 co-expression attenuated this phenomenon. CACYBP depletion led to decreased levels of cyclin D1, cyclin A2, CDK2 and CDK4, causing a typical cell cycle arrest at G1/S phase and increasing apoptosis in HCC cells. P27Kip1-S10D but not P27Kip1-S10A reconstitution rescued partially the cell cycle function and apoptotic feature after CACYBP depletion. Conclusion: Our findings provide novel insights into the functional role and regulatory mechanism of CACYBP in HCC.

[Investigation of preoperative anxiety and postoperative quality of life in patients with periodontal mucogingival surgery].

PURPOSE: To evaluate preoperative anxiety and postoperative quality of life in patients with periodontal mucogingival surgery, and provide a theoretical basis for preventing preoperative anxiety and improving postoperative quality of life in mucogingival surgery. METHODS: According to the inclusion and exclusion criteria, 26 patients with mucogingival surgery were randomly selected, including 13 cases undergoing free gingival graft and 13 cases undergoing subepithelial connective tissue graft. All patients were asked to answer the following questionnaires which included self-rating anxiety scale (SAS), modified dental anxiety scale (MDAS), pain evaluation using visual pain scale (VAS), clinical performance evaluation (swelling, bleeding, nausea, oral odor), and oral function evaluation (chewing, speaking, sleeping, working). Data analysis was performed using SPSS 18.0 software package. RESULTS: The preoperative SAS score was 44.33±11.99, 4 patients had anxiety, accounting for 15.38%. The preoperative MDSA score was 9.85±2.41, 4 patients had anxiety, accounting for 15.38%. The VAS values at 1 day, 3 days, 5 days, 7 days, and 10 days after surgery were moderate pain (4.54±1.32), mild pain (3.31±1.31), mild pain (2.00±1.14), and painless( 0.70±0.72), painless (0.08±0.27). The VAS values at 1 day, 3 days, and 5 days after FGG were greater than those after CTG (P<0.05).The most common discomforts after mucogingival surgery were swelling, bleeding, disturbance in chewing and speech. Swelling, disturbance in chewing and speech persisted until 7 days after surgery, and bleeding continued until 5 days after surgery. The postoperative discomfort of FGG was significantly higher than that of CTG. CONCLUSIONS: Four had preoperative anxiety prior to mucogingival surgery. The main clinical symptoms after surgery were moderate to mild pain, swelling, bleeding, disturbance in chewing and speech within 1-7 days after surgery. The effect of CTG on the quality of life of patients was significantly less than that of FGG.

Promising diagnostic and prognostic value of E2Fs in human hepatocellular carcinoma.

BACKGROUND: A growing body of evidence suggests that E2Fs, by regulating gene expression related to cell cycle progression and other cellular processes, play a pivotal role in human cancer. However, the distinct roles of each E2F in the development and treatment of hepatocellular carcinoma (HCC) remain unknown. In the present study, the mRNA expression and prognostic value of different E2Fs in HCC are analyzed. MATERIALS AND METHODS: Transcriptional and survival data related to E2F expression in patients with HCC were obtained through ONCOMINE and UALCAN databases. Survival analysis plots were drawn with Kaplan-Meier Plotter. The sequence alteration data for E2Fs were obtained from The Cancer Genome Atlas and c-BioPortal. Gene functional enrichment analyses were performed in Database for Annotation, Visualization and Integrated Discovery. RESULTS: The mRNA expression levels of E2F1-E2F8 were all significantly upregulated in HCC patients, and high expression of each E2F was obviously related to poor prognosis. Similarly, the expression of E2Fs showed prognostic prediction value in HCC patients with different cancer stages and pathological grades. Moreover, the mutation rate of E2Fs was relatively high in HCC patients, and the DNA sequence alterations primarily occurred in E2F5, E2F3, and E2F6, which were associated with worse overall survival and disease-free survival in HCC patients. Network analysis confirmed that the expression levels of cell cycle-related genes were mostly affected by E2F mutations. CONCLUSION: High expression of individual E2Fs was associated with poor prognosis in all liver cancer patients. E2Fs may be exploited as good prognostic targets for comprehensive management of HCC patients, but this notion should be further evaluated in clinical studies.

Birth prevalence of orofacial clefts among perinatal infants: A register-based study in Bao'an district, Shenzhen, China.

BACKGROUND: The birth prevalence of orofacial clefts (OFCs) has been widely studied, but results are considerable varied, and epidemiological studies in southern China are few in numbers. To address this gap, we carried out a register-based study to estimate the birth prevalence of OFCs in Bao'an district, Shenzhen, China. METHODS: Data of perinatal infants born between 2003 and 2017 were extracted from Shenzhen Maternal and Child Health Management System. The overall OFCs birth prevalence with 95% confidence interval (CI) as well as subgroup analysis based on selected demographic factors was conducted. Cochran-Armitage trend tests were applied to evaluate the time trend by 5-year intervals. RESULTS: The overall birth prevalence of OFCs, cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO) was 1.30 (95% CI 1.21-1.39), 1.00 (95% CI 0.92-1.08), and 0.30 (95% CI 0.25-0.34) per 1,000 births, respectively. An overall declining tendency was observed in the OFCs (from 1.83 to 1.04 per 1,000 births), specifically CL/P (from 1.53 to 0.69 per 1,000 births) birth prevalence over 5-year intervals, with statistical significance (p < 0.01). Subgroup analysis revealed that the CL/P and CPO birth prevalence was differed by infant gender, household registration, maternal age, and parity. CONCLUSION: Our findings had firstly reported the birth prevalence of OFCs in Bao'an district, and might help other researchers to plan more comprehensive public health strategies to reduce the occurrence of OFCs in further generation.

Successful treatment of an adult with Kasabach-Merritt syndrome using thalidomide, vincristine, and prednisone.

OBJECTIVE: Kasabach-Merritt syndrome is a rare disease that mainly occurs in infants and adolescents. It usually manifests as disseminated intravascular coagulation and severe bleeding, and is associated with high mortality. However, its low incidence and clinical rarity in adults mean that there is currently no well-verified treatment regimen for this disease. We report on an effective novel therapeutic regimen in a patient with Kasabach-Merritt syndrome. METHODS: A woman with Kasabach-Merritt syndrome presented with a recurrent subcutaneous mass and disseminated intravascular coagulation, and was treated with prednisone, vincristine and thalidomide. RESULTS: This treatment regimen successfully resolved the patient's symptoms, with tumor regression. The patient remained disease-free after 6 years of follow-up. CONCLUSIONS: Prednisone combined with vincristine and thalidomide may be an effective treatment for Kasabach-Merritt syndrome, but further studies are needed to verify the use of this regimen.

Up-regulated and interrelated expressions of GINS subunits predict poor prognosis in hepatocellular carcinoma.

The GINS complex is one of the core components of the eukaryotic replicative helicase CMG (Cdc45-MCM helicase-GINS) complex that serves as the replicative helicase unwinding duplex DNA ahead of moving replication fork during chromosome duplication. Many studies have highlighted the important functions amongst GINS subunits in various cancers. Nevertheless, the functions and prognostic roles of distinct GINS subunits in hepatocellular carcinoma (HCC) were largely unexplored. In the present study, we reported the prognostic values of GINS subunits in HCC patients through analysis of several databases, including Oncomine, (TCGA), and Kaplan-Meier Plotter (KMPlotter). We found that mRNA expressions of all GINS subunits were significantly up-regulated in HCC tumor than in non-tumor liver tissues. Survival analysis revealed that elevated expression of individual GINS subunit predicts a poor overall survival (OS) in all HCC patients. When sorting the patients by gender, the correlation between elevated expression of individual GINS subunit and poor OS remains significant in male patient subgroup, but not in female patient subgroup. Additionally, we found that co-overexpression of all GINS subunits was significantly associated with a higher hazard ratio, suggesting the GINS complex may co-operate to promote HCC progression. Indeed, their expressions were highly correlated with each other in the same cohort and TRANSFAC analysis revealed that four transcription factors including C/EBPα, Oct-1, Sp1, and USF may serve as common transcription factors binding to the promoters of all four GINS subunits. Therefore, we propose that individual GINS subunit or GINS complex as a whole could be potential prognostic biomarkers for HCC.

Anillin is required for tumor growth and regulated by miR-15a/miR-16-1 in HBV-related hepatocellular carcinoma.

Anillin (ANLN) is an actin-binding protein essential for assembly of cleavage furrow during cytokinesis. Although reportedly overexpressed in various human cancers, its role in hepatocellular carcinoma (HCC) is unclear. To address this issue, we confirmed that in 436 liver samples obtained from surgically removed HCC tissues, higher ANLN expression was detected in tumor tissues than in adjacent non-tumor tissues of HCC as measured by immunohistochemistry, quantitative real-time PCR and western blotting. Correlation and Kaplan-Meier analysis revealed that patients with higher ANLN expression were associated with worse clinical outcomes and a shorter survival time, respectively. Moreover, ANLN inhibition resulted in growth restraint, reduced colony formation, and a lower sphere number in suspension culture. Mechanistically, ANLN deficiency induced an increasing number of multinucleated cells along with the activation of apoptosis signaling and DNA damage checkpoints. Furthermore, HBV infection increased ANLN expression by inhibiting the expression of microRNA (miR)-15a and miR-16-1, both of which were identified as ANLN upstream repressors by targeting its 3' untranslated region. Thus, we conclude that ANLN promotes tumor growth by ways of decreased apoptosis and DNA damage. Expression level of ANLN significantly influences the survival probability of HCC patients and may represent a promising prognostic biomarker.

[CD200/CD200R Expression Levels and Its Significance after Allogeneic Hematopoietic Stem Cell Transplantation].

BACKGROUND: CD200 and its receptor CD200R are both type-1 membrane glycoproteins, which are members of the immunoglobulin superfamily (IgSF). Besides the inhibitory effect on macrophages, CD200/CD200R also play an important role in regulating the regulatory T cells, allergicreaction, autoimmune diseases, allograft, neurological diseases and other autoimmune-related diseases, etc. OBJECTIVE: To investigate the role of CD200 and its receptor in the graft versus host disease (GVHD). METHODS: Experimental samples were divided into aGVHD group, non-aGVHD group, cGVHD group and non-cGVHD group, the healthy persons were used as normal controls. Firstly, the expression levels of CD200 and CD200R on CD19+ cell, CD3+ cell and dendritic cell (CD19- CD14- CD1c+) surfaces in each group were detected by using flow cytometry, so as to determine whether there were expression differences among each groups. Then, the mRNA levels of each groups were tested by using real-time quantitative polymerase chain reaction for finding the differences of mRNA expression level among each group. Finally, the peripheral blood mononuclear cells of the patients and healthy controls were co-cultured with anti-CD200R1 antibody for 48 hours, and the interleukin-10 level in the co-culture system was tested by using enzyme linked immunosorbent assay for verifying the function of CD200/CD200R. RESULTS: The CD200 expression level on CD19+ cell surface in the aGVHD group and non-aGVHD group was both lower than that in healthy control group; that in the non-aGVHD group was higher than that in the aGVHD group. The CD200 expression level on CD19+ CD200+ cells in the non-cGVHD group were higher than that in the cGVHD group and healthy control group. There were no significant differences of CD200 and CD200R expression levels on CD3 cells and dendritic cells among all groups. The CD200 mRNA expression levels in the aGVHD group and cGVHD group were both lower than the healthy control group. The CD200 mRNA expression level was lower in the aGVHD group than in the non-aGVHD group, and was lower in the cGVHD group than in the non-cGVHD group. There was no significant difference of the CD200R mRNA expression level among all groups. After the peripheral blood mononuclear cells of the patients and healthy controls were co-cultured with anti-CD200R1 antibody for 48 hours, the interleukin-10 concentration decreased with the increasing of anti-CD200R1 antibody concentrations in the co-culture system. CONCLUSION: The CD200/CD200R may play a role in the pathogenesis of GVHD after allo-HSCT.

TACC3 promotes stemness and is a potential therapeutic target in hepatocellular carcinoma.

Transforming acidic coiled-coil protein 3 (TACC3) is essential for cell mitosis and transcriptional functions. In the present study, we first demonstrated that both TACC3 protein and mRNA levels were elevated in HCC tissue samples compared with non-cancerous tissue biopsies according to western blot analyses, immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) assays. Moreover, high TACC3 expression was positively correlated with poor overall survival (OS) and disease-free survival (DFS) (p < 0.001). Using HCC cell lines, we then demonstrated that either TACC3 knockdown or treatment with the potential TACC3 inhibitor KHS101 suppressed cell growth and sphere formation as well as the expression of stem cell transcription factors, including Bmi1, c-Myc and Nanog. Silencing TACC3 may suppress the Wnt/ß-catenin and PI3K/AKT signaling pathways, which regulate cancer stem cell-like characteristics. Taken together, these data suggest that TACC3 is enriched in HCC and that TACC3 down-regulation inhibits the proliferation, clonogenicity, and cancer stem cell-like phenotype of HCC cells. KHS101, a TACC3 inhibitor, may serve as a novel therapeutic agent for HCC patients with tumors characterized by high TACC3 expression.

Residual amount of HBV DNA in serum is related to relapse in chronic hepatitis B patients after cessation of nucleos(t)ide analogs.

OBJECTIVE: To investigate the relationship between relapse and the levels of the residual amount of HBV DNA in serum at cessation in chronic hepatitis B patients meeting 2008 Asian Pacific Association for the Study of the Liver (APASL) nucleos(t)ide analogs (NAs) cessation criteria. METHODS: A total of 72 chronic hepatitis B patients who took NAs and had reached 2008 APASL cessation criteria entered the study. Patients were followed up for 6 months or longer after antiviral therapy was stopped. Serum HBV DNA level at cessation was detected by a highly sensitive polymerase chain reaction assay with detection limitation of 2 IU/mL. RESULTS: Of all the 72 patients, 42 patients (65.3%) relapsed after NA cessation. The detectable rate of the trace amount of HBV DNA at cessation was 41.7% by highly sensitive polymerase chain reaction reagents. The detectable rate of patients with consolidation treatment duration of <18 months was higher than that with consolidation duration of ≥18 months (47.5% vs. 15.4%, P=0.034), and the detectable rate of patients with HBeAg seroconversion within 6 months of treatment was lower than that of ≥6 months (25.0% vs. 61.5%, P=0.036). The residual amount of HBV DNA and detectable rate at cessation showed significant differences between relapsed and nonrelapsed patients (130.4±420.90 vs 44.6±155.16 IU/mL, P=0.004; 55.3% vs. 16.0%, P=0.001). The cutoff value predicting relapse was 2.24 IU/mL, with a sensitivity of 0.553 and specificity of 0.840. CONCLUSIONS: Residual amount of HBV DNA in serum at NA cessation is associated with HBV relapse. The cutoff value predicting relapse was 2.24 IU/mL, with a sensitivity of 0.553 and specificity of 0.840.

A network of epigenetic regulators guides developmental haematopoiesis in vivo.

The initiation of cellular programs is orchestrated by key transcription factors and chromatin regulators that activate or inhibit target gene expression. To generate a compendium of chromatin factors that establish the epigenetic code during developmental haematopoiesis, a large-scale reverse genetic screen was conducted targeting orthologues of 425 human chromatin factors in zebrafish. A set of chromatin regulators was identified that target different stages of primitive and definitive blood formation, including factors not previously implicated in haematopoiesis. We identified 15 factors that regulate development of primitive erythroid progenitors and 29 factors that regulate development of definitive haematopoietic stem and progenitor cells. These chromatin factors are associated with SWI/SNF and ISWI chromatin remodelling, SET1 methyltransferase, CBP-p300-HBO1-NuA4 acetyltransferase, HDAC-NuRD deacetylase, and Polycomb repressive complexes. Our work provides a comprehensive view of how specific chromatin factors and their associated complexes play a major role in the establishment of haematopoietic cells in vivo.

[Diversity and niche of soil moniliaceous hyphomycetes in Taibai Mountain].

Sixteen genera of soil moniliaceous hyphomycetes were isolated from 40 soil samples collected from the southern and northern slopes of Taibai Mountain, and the indices Shannon-Wiener diversity index, evenness, niche breadth, and niche overlap were used to analyze the community structure and niche of soil moniliaceous hyphomycetes in different forest types on the southern and northern slopes of Taibai Mountain. The results showed that the distribution of soil moniliaceous hyphomycetes on the study area had an obvious environmental gradient pattern. Altitude and forest type were the main determinants of the fungal community distribution. The species richness and diversity index of soil moniliaceous hyphomycetes decreased significantly with increasing altitude, but the community evenness represented an increasing trend. Among the genera of soil moniliaceous hyphomycetes, Penicillium, Aspergillus, Verticillium, Paecilomyces and Acremonium had larger niche width and greater niche overlap with other genera, suggeting that these genera had wide distribution on the southern and northern slopes of Taibai Mountain. As for Trichothecium, Gliocladium and Metarhizium, their niche width was narrower, and their niche overlap with other genera was smaller, indicating that the distribution of these genera was more affected by altitude and vegetation, with the occurrence only in special forest types.

[Influencing factors on the death of infants born to HIV infected mothers].

OBJECTIVE: To understand the influencing factors on the death of infants born to HIV infected mothers in areas with high prevalence of HIV/AIDS in China. METHODS: Based on the follow-up cohort study targeting at HIV/AIDS infected pregnant women and their babies initiated in 2004, a survey on the death status and influencing factors on the infants born to HIV/AIDS infected mothers enrolled in this cohort from Jan.2004 to Nov.2007 was carried out during Aug.to Nov.2008 in seven counties of four provinces in China. A total of 498 pairs of HIV-infected mothers and their infants were enrolled and their related information was collected. Single factor and multiple factors Cox model methods were adopted for data analysis. RESULTS: The total observed person-years of 498 infants was 406.22, among which, 45 infants died, and the mortality density was 110.78 per 1000 child-year. A single factor Cox model showed, the pregnancy in pre-period of HIV/AIDS and HIV/AIDS period (RR = 1.971, 95%CI: 1.143 - 3.396), living status of the pregnancy (RR = 3.062, 95%CI: 1.097 - 8.550), multipara women (RR = 0.517, 95%CI: 0.278 - 0.961), natural childbirth (RR = 0.561, 95%CI: 0.345 - 0.910), premature labor (RR = 5.302, 95%CI: 2.944 - 9.547), low birth weight (RR = 4.920, 95%CI: 2.691 - 8.994), mother-child pairs taking antiretroviral drugs (RR = 0.227, 95%CI: 0.121 - 0.428) and infants infected HIV (RR = 5.870, 95%CI: 3.232 - 10.660) could affect the infants death. The death of HIV-exposed infants was influenced by various factors. The death risk of infants born to HIV infected mothers who were in the danger of pre-period of HIV/AIDS and HIV/AIDS period was greater than the infants delivered by HIV infected mothers who were in preclinical period of HIV/AIDS (RR = 6.99, 95%CI: 1.92 - 25.64). The death risks were greater in the group that the women whose CD4(+)TLC count number lower than 200 cells/microl (RR = 2.05, 95%CI: 1.01 - 4.15). The infants whose mothers had no ARV treatment had higher possibility to die than the others (RR = 6.17, 95%CI: 1.62 - 23.26). The death risk of premature delivered infants was 2.87 times of mature delivered infants (95%CI: 1.12 - 7.35). The death risk of HIV/AIDS infected infants was 9.87 times of the HIV/AIDS uninfected infants (95%CI: 3.81 - 25.62). CONCLUSION: Some measurements including improving HIV-infected pregnant women's immunity, reducing mother to child transmission of HIV and premature birth, low birth weight are beneficial to reducing infant mortality.

[Analysis of clinical features and virological characteristics in patients infected with three different HBV subgenotypes].

OBJECTIVE: To investigate the clinical characteristics and the pattern of precore and core promoter mutations of hepatitis B virus (HBV) subgenotypes Ba, C1 and C2. METHODS: A cohort of 151 patients with chronic HBV infection in Guangdong province of China was enrolled in this study. HBV subgenotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Precore and core promoter mutations were analysed using nucleotide sequencing. RESULTS: Of the 151 patients, 80, 51 and 20 were infected with subgenotypes Ba, C1 and C2 respectively. No significant differences were found in HBeAg positivity and liver functional indexes among these three subgenotypes when age and sex were matched. Virologically, HBV/Ba showed the highest frequency of A1896 mutation but the lowest frequency of T1762/A1764 mutation. HBV/C1 was associated with the highest tendency to develop T1762/A1764 mutation, but the lowest prevalence of A1896 mutation. HBV/C2 was associated with an intermediate tendency to develop A1896 and T1762/A1764 mutations. CONCLUSION: Different mutation patterns in precore and core promoter regions are responsible for HBeAg-negative HBV infections among different subgenotypes.