Lin Liu

Patients with hepatitis C virus (HCV) infection with psychiatric disorders and/or substance abuse face significant barriers to antiviral treatment. New strategies might be needed to improve treatment rates and outcomes. We investigated whether an integrated care (IC) protocol, which includes multi-disciplinary care coordination and patient case management, could increase the proportion of patients with chronic HCV infection who receive antiviral treatment (a combination of interferon-based and direct acting antiviral agents) and achieve a sustained virologic response (SVR). We performed a prospective, randomized trial at 3 medical centers in the US. Participants (n=363 patients attending HCV clinics) had been screened and tested positive for depression, post-traumatic stress disorder, and/or substance use; they were randomly assigned (1:1) to groups that received IC or usual care (controls) from March 2009 through February 2011. A mid-level mental health practitioner was placed in e...

As an essential element of plant nutrition, phosphorus plays an important role in the agricultural sustainable development and ecosystem balance. Adopting appropriate soil phosphorus fractionation scheme to study the forms, transformation, and availability of soil phosphorous is critical for understanding soil phosphorus supply and its losses. This paper reviewed the recent researches about the forms of soil inorganic and organic phosphorous, as well as their fractionation schemes and limitations. Hedley method, a widely used soil phosphorous fractionation scheme, gives attention to both organic and inorganic phosphorous forms, being available to understand the bioavailability and dynamics of soil phosphorus. The process of Hedley method and its application scope were described. A detailed discussion of its modification, the Tiessen method, was also presented.

The decomposition of yak dung and its effect on soil nutrition of grassland in northwestern Sichuan,China were investigated.Soil samples were taken around(10 cm and 30 cm radius from center) dung piles on five occasions over a period of 84 days in summer.The samples were analyzed for NO3--N,NH4+-N,available K,inorganic P,total organic C(TOC),total N(TN) and total P(TP).The result showed that yak dung supplied the ecosystem there with substantial nutrients.It was estimated that the N contribution from dung was approximately 699～932 kg hm-2 and P about 110～147 kg hm-2.The total quantities of NO3--N,NH4+-N,available K and inorganic P from the initial dung largely decreased to almost none after 84 days.In the initial days(1～9 d),NO3--N,NH4+-N,available K and inorganic P in siol under the dung piles were found with a significant increase,and after two months the content of NO3--N was 8.4 times larger than that in the initial days.The contents of NH4+-N,available K and inorganic P at place 10 cm from the edge of dung piles increased signifi cantly(P0.05),but no significant increase was found(P0.05) at 30 cm.Differing from the common belief,no obvious increases in TOC,TN and TP were observed in the whole experiment process.Fig 4,Tab 1,Ref 31

We assessed remission rates and toxicity in 24 consecutive elderly (age>or=60) patients with untreated Acute myeloid leukemia (AML) who received the anthracycline-free combination of fludarabine, cytosine arabinoside and G-CSF (FLAG) as initial induction chemotherapy at our center. CR was achieved following one cycle of FLAG in 14 patients (58%). Another four patients cleared blasts from their bone marrow by day 30 without complete platelet recovery. Three patients died from infections prior to neutrophil recovery (12%). No other grade 3/4 toxicities and no clinically significant mucositis were seen. No significant association was found between age, WBC and cytogenetic risk group with likelihood of achieving CR. Fifteen patients proceeded to consolidation therapy and seven patients received a stem cell transplant (six autologous, one allogeneic). Primary induction with FLAG in elderly AML patients achieves a high remission rate without prohibitive mucosal or cardiac toxicity and may thus be considered as an alternative to standard anthracycline-based regimens in this setting.

Improved data transmission technologies have facilitated data collected from positive airway pressure (PAP) devices in the home environment. Although clinicians’ treatment decisions increasingly rely on autoscoring of respiratory events by the PAP device, few studies have specifically examined the accuracy of autoscored respiratory events in the home environment in ongoing PAP use. “PAP efficacy” studies were conducted in which participants wore PAP simultaneously with an Embletta sleep system (Embla, Inc., Broomfield, CO), which was directly connected to the ResMed AutoSet S8 (ResMed, Inc., San Diego, CA) via a specialized cable. Mean PAP-scored Apnea-Hypopnea Index (AHI) was 14.2 ± 11.8 (median: 11.7; range: 3.9–46.3) and mean manual-scored AHI was 9.4 ± 10.2 (median: 7.7; range: 1.2–39.3). Ratios between the mean indices were calculated. PAP-scored HI was 2.0 times higher than the manual-scored HI. PAP-scored AHI was 1.5 times higher than the manual-scored AHI, and PAP-scored AI ...

Interpatient variability in the kinetics of peripheral blood progenitor cell (PBPC) mobilization is commonly seen with conventional chemotherapy-based mobilization regimens. This necessitates the availability of leukapheresis (LP) facilities 7 days a week. The efficacy of an approach where LP was invariably commenced on Day 11 after intermediate-dose cyclophosphamide followed by sequential administration of granulocyte-macrophage-colony-stimulating factor (CSF) and granulocyte-CSF (Cy/GM/G) was retrospectively analyzed in 225 consecutive, unselected patients undergoing autologous hematopoietic stem cell transplantation for all diagnoses other than acute leukemia at our center. Cy/GM/G was scheduled to avoid weekend LP. After Cy/GM/G, a CD34+ cell yield of at least 2.0x10(6) per kg was achieved in 90.7 percent of patients. Optimal yield (OY; >or=5x10(6) or 10x10(6) CD34+ cells/kg depending on diagnosis) was achieved in 67.6 percent of patients. Only three patients (1.3%) required LP on Saturday or Sunday. Febrile neutropenia (FN) was encountered in 5.3 percent. PBPC yield was highest on Day 1 of LP (p<0.001). In multivariate analyses, platelet (PLT) count on Day 1 of LP (PLT-D1LP) was positively associated with achievement of OY (p<0.001). PLT-D1LP and diagnosis of myeloma were associated with a shorter time to achieve a CD34+ cell yield of at least 5x10(6) per kg (p<0.001 and p=0.002, respectively). Cy/GM/G with scheduled LP commencement on Day 11 enables optimal CD34+ cell yields in most patients undergoing autologous transplantation, despite a low risk of FN and avoidance of weekend LP.

Rats with streptozotocin (STZ)-induced diabetes were studied in order to identify abnormal microRNA (miRNA) expression profiles in diabetic retinopathy (DR) and to ascertain miRNAs associated with DR. Histopathologically, we observed characteristic features of DR in rats at 10 weeks after STZ injection. Investigation of miRNA expression profiles in the retinas of control and diabetic rats using miRNA microarrays revealed that many miRNAs were abnormally expressed in DR. On the basis of their fold changes and probability values, a total of 37 miRNAs were selected for further validation by real-time PCR analysis. The results showed that 11 miRNAs were significantly upregulated and 6 miRNAs were notably downregulated in DR. Furthermore, these changes in retinal miRNA expression levels paralleled the course of DR. Levels of miR-182, miR-96, miR-183, miR-211, miR-204, and miR-124 were significantly increased during the progress of DR, whereas miR-10b, miR-10a, miR-219-2-3p, miR-144, miR-...

ABSTRACTHepatitis C virus (HCV) research is hampered by the use of arbitrary representative isolates in cell culture and immunology. The most replicative isolatein vitrois a subtype 2a virus (JFH-1); however, genotype 1 is more prevalent worldwide and represents about 70% of infections in the United States, and genotypes differ from one another by 31% to 33% at the nucleotide level. For phylogenetic and immunologic analyses, viruses H77 and HCV-1 (both subtype 1a) are commonly used based on their historic importance. In an effort to rationally design a representative subtype 1a virus (Bole1a), we used Bayesian phylogenetics, ancestral sequence reconstruction, and covariance analysis on a curated set of 390 full-length human HCV 1a sequences from GenBank. By design, Bole1a contains variations present in widely circulating strains and matches more epitope-sized peptides in a full-genome comparison to subtype 1a isolates than any other sequence studied. Parallel analyses confirm that s...

During the transition from acute to chronic infection in individuals persistently infected with hepatitis C virus (HCV), cellular responses initiate within the first 6 months of primary infection and collapse thereafter, whereas humoral responses activate later during the chronic phase. Whether and how this deviation of immune responses specifically influences HCV evolution are unknown. To determine the pattern of HCV evolution during this critical period, we conducted extensive sequence analysis on annual clonal hemigenomic sequences for up to 3 years in six well-characterized subjects, using statistical methods that accounted for repeated measures. Significantly different evolutionary rates were observed in envelope versus nonenvelope genes, with an increasing rate of nonsynonymous change ( dN ) in envelope genes and a stable dN in nonenvelope genes ( P = 0.006). The ratio of the envelope to nonenvelope nonsynonymous rate increased from 2 in year 1 to 5 in years 2 and 3. Centripet...

Increased rigidity of the extracellular matrix (ECM) is commonly associated with hepatocellular carcinoma (HCC). The purpose of this study was to quantitate the mechanical stiffness of various hepatic tissues, evaluate integrin β1 expression, and investigate the correlation between these two factors in the development of HCC. Twenty-three normal specimens, 152 cases of cirrhosis, and 105 cases of HCC were included in this study. The mechanical stiffness of the ECM of each specimen was detected using atomic force microscopy to calculate elastic modulus (E) values. Integrin β1 expression was also evaluated using semi-quantitative RT-PCR, western blot, and immunohistochemistry. Expression of integrin β1 in HepG2 cells plated on substrates with different mechanical stiffnesses was also evaluated. A positive correlation between ECM mechanical stiffness and integrin β1 expression was detected. Expression of integrin β1 also correlated with Edmondson pathologic grade, encapsulation, metastasis, and HBV infection (P < 0.01). In vitro, expression of integrin β1 by HepG2 cells was also significantly higher when the cells were plated on stiffer substrates. Expression of integrin β1 is regulated by the mechanical stiffness of the ECM, and correlates with the invasion and metastasis events of HCC in patients with cirrhosis.

In this study we tested the hypothesis that hyperbaric oxygen preconditioning (HBO-PC) reduces retinal neuronal death due to optic nerve crush (ONC). Adult male Sprague-Dawley rats were subjected to ONC accompanied by a contralateral sham operation. HBO-PC was conducted four times by giving 100% oxygen at 2.5 atmospheres absolute (ATA) for 1 h every 12 h for 2 days prior to ONC. The rats were euthanized at 1 or 2 weeks after ONC. Retinal ganglion cell (RGC) density was counted by hematoxylin and eosin (H&E) staining of the retina and retrograde labeling with FluoroGold application to the superior colliculus. Visual function was assessed by flash visual evoked potentials (FVEP). TUNEL straining and caspase-3 and caspase-9 activity in the retinas were assessed. The RGC density in the retinas of ONC HBO-PC-treated rats was significantly higher than that of the corresponding ONC-only rats (the survival rate was 67.2% versus 49.7% by H&E staining, and 60.3% versus 28.9% by retrograde labeling with FluoroGold, respectively; p < 0.01) at 2 weeks after ONC. FVEP measurements indicated a significantly better preserved latency and amplitude of the P1 wave in the ONC HBO-PC-treated rats than the ONC-only rats (92 +/- 7 msec, 21 +/- 3 microv in the sham-operated group, 117 +/- 12 msec, 14 +/- 2 microv in the HBO-PC-treated group, and 169 +/- 15 msec, 7 +/- 1 microv in the corresponding ONC group; p < 0.01). TUNEL assays showed fewer apoptotic cells in the HBO-PC-treated group, accompanied by the suppression of caspase-3 and caspase-9 activity. These results demonstrate that HBO-PC appears to be neuroprotective against ONC insult via inhibition of neuronal apoptosis pathways.

Hepatitis C virus (HCV) is an important human pathogen that represents a model for chronic infection given that the majority of infected individuals fail to clear the infection despite generation of virus-specific T cell responses during the period of acute infection. Although viral sequence evolution at targeted MHC class I-restricted epitopes represents one mechanism for immune escape in HCV, many targeted epitopes remain intact under circumstances of viral persistence. To explore alternative mechanisms of HCV immune evasion, we analyzed patterns of expression of a major inhibitory receptor on T cells, programmed death-1 (PD-1), from the time of initial infection and correlated these with HCV RNA levels, outcome of infection, and sequence escape within the targeted epitope. We show that the level of PD-1 expression in early HCV infection is significantly higher on HCV-specific T cells from subjects who progress to chronic HCV infection than from those who clear infection. This cor...

Vaccines designed to prevent or to treat hepatitis C viral infection must achieve maximum cross-reactivity against widely divergent circulating strains. Rational approaches for sequence selection to maximize immunogenicity and minimize genetic distance across circulating strains may enhance vaccine induction of optimal cytotoxic T cell responses. We assessed T cell recognition of potential hepatitis C virus (HCV) vaccine sequences generated using three rational approaches: combining epitopes with predicted tight binding to the MHC, consensus sequence (most common amino acid at each position), and representative ancestral sequence that had been derived using Bayesian phylogenetic tools. No correlation was seen between peptide–MHC binding affinity and frequency of recognition, as measured by an IFN-γ T cell response in HLA-matched HCV-infected individuals. Peptides encoding representative, consensus, and natural variant sequences were then tested for the capacity to expand CD8 T cell ...

ABSTRACT: Soil phosphorus (P) availabili ty and fractions are influenced to a large extent by land use and cover changes. Inorganic P (IP) and organic P (OP) fractions in surface soils (0–20 cm) under typical vegetation types, including subalpine coniferous forests, alpine ...

As the first and largest user of next-generation Illumina HiSeq 2000 (HiSeq) sequencers in the world, Beijing Genomics Institute (BGI) has extensive experience utilizing HiSeq, covering almost all sequencing areas, including human, animal, plant and microbe, and almost all sequencing types, including de novo sequencing, resequencing, metagenome sequencing, RNA-Seq, Digital Gene Express. BGI has managed to convert the full sequencing