Objective

To assess the prevalence of HIV infection and characteristically risk of factors which associated with HIV infection among MSM in Harbin, China.

Methods

A face-to-face questionnaire interview was conducted among 463 Men Who Have Sex with Men (MSM) who were recruited by the snowball sampling in Harbin from April, 2011 to July, 2011. The questionnaire mainly included demographics, AIDS knowledge, homosexual behavior and the status of intervention in MSM. Blood specimens were obtained and tested for the diagnoses of HIV, syphilis and hepatitis C virus (HCV). Associations between above exposed factors and HIV infection were analyzed using a univariate analysis and forward stepwise logistic regression.

Results

The prevalence of HIV and syphilis was 9.5 and 14.3%. The awareness rate of AIDS was 86.8%. The rate of unprotected sexual behavior was 57.6% of MSM during the past 6 months. The univariate analysis identified that the age (age≥35 years old), cohabitation, more than 10 years of homosexual behavior and more than 10 homosexual partners were risk factors which associated with the HIV infection, and that protected sex during the past 6 months was a protective factor for the HIV infection. The multivariate analysis identified that the duration of homosexual behavior and commercial sexual behavior were independent risk factors which associated with the HIV infection, and the protected sex during the past 6 months was a protective factor for the HIV infection.

Conclusion

The prevalence of HIV among MSM in Harbin has been rapidly increasing in the past few years. Targeted, tailored, and comprehensive interventions are urgently needed to prevent the HIV infection from MSM.

There is a strong need to assess early tumor response to chemotherapy in order to avoid adverse effects from unnecessary chemotherapy and allow early transition to second-line therapy. This study was to quantify tumor perfusion changes with dynamic contrast-enhanced ultrasound (CEUS) in the evaluation of early tumor response to cytotoxic chemotherapy. Sixty nude mice bearing with MCF-7 breast cancer were administrated with either adriamycin or sterile saline. CEUS was performed on days 0, 2, 4 and 6 of the treatment, in which time-signal intensity (SI) curves were obtained from the intratumoral and depth-matched liver parenchyma. Four perfusion parameters including peak enhancement (PE), area under the curve of wash-in (WiAUC), wash-in rate (WiR) and wash-in perfusion index (WiPI) were calculated from perfusion curves and normalized with respect to perfusion of adjacent liver parenchyma. Histopathological analysis was conducted to evaluate tumor perfusion, tumor cell density, microvascular density (MVD) and proliferating cell density. Significant decreases of tumor normalized perfusion parameters (i.e., nPE, nWiAUC, nWiR and nWiPI) were noticed between adriamycin-treated and control groups (P<0.01) 2 days after therapy. There were significant differences of tumor volumes between control and treated groups on day 6 (P<0.001) while there were no significant differences in tumor volume on days 0, 2 and 4 (P>0.05). Significant decreases of tumor perfusion, tumor cell density, MVD and proliferating cell density were seen in adrianycin-treated group 2 days after therapy when compared to control group (P<0.001). Dynamic CEUS for quantification of tumor perfusion could be used for early detection of cancer response to cytotoxic chemotherapy prior to notable tumor shrinkage.

Objective: Side population (SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer. Many kinds of cell lines and tissues have demonstrated the presence of SP cells, including several gastric cancer cell lines. This study is aimed to identify the cancer stem-like cells in the SP of gastric cancer cell line MKN-45. Methods: We used fluorescence activated cell sorting (FACS) to sort SP cells in the human gastric carcinoma cell line MKN-45 (cells labeled with Hoechst 33342) and then characterized the cancer stem-like properties of SP cells. Results: This study found that the SP cells had higher clone formation efficiency than major population (MP) cells. Five stemness-related gene expression profiles, including OCT-4, SOX-2, NANOG, CD44, and adenosine triphosphate (ATP)-binding cassette transporters gene ABCG2, were tested in SP and MP cells using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Western blot was used to show the difference of protein expression between SP and MP cells. Both results show that there was significantly higher protein expression in SP cells than in MP cells. When inoculated into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, SP cells show higher tumorigenesis tendency than MP cells. Conclusions: These results indicate that SP cells possess cancer stem cell properties and prove that SP cells from MKN-45 are gastric cancer stem-like cells.

Basic helix–loop–helix (bHLH) transcription factors control developmental decisions for a wide range of embryonic cell types. Hand1 and Hand2 are closely related bHLH proteins that control cardiac, craniofacial, and limb development. Within the developing heart, Hand1 expression becomes restricted predominantly to the left ventricle, whereas Hand2 becomes restricted predominantly to the left ventricle, for which findings have shown each Hand factor to be necessary for normal chamber formation. Forced overexpression of Hand1 throughout the early developing heart induces abnormal interventricular septal development, with resulting pathogenesis of congenital heart defects. To investigate the potential transcriptional mechanisms involved in heart morphogenesis by Hand2, this study used a replacement targeting approach to knock Hand2 into the Hand1 locus and ectopically express one copy of Hand2 within the endogenous Hand1 expression domain in the developing hearts of transgenic mice. The findings show that high-percentage Hand1Hand2 chimeras die at birth and exhibit a range of congenital heart defects. These findings suggest that Hand factors may act via unique transcriptional mechanisms mediated by bHLH factor partner choice, supporting the notion that alterations of Hand factor stoichiometry may be as deleterious to normal heart morphogenesis as Hand factor loss of function.

Analysis of patient tumors suggests multiple MAP3kinases (MAP3Ks) are critical for growth and metastasis of cancer cells. MAP3Ks selectively control the activation of ERK1/2, JNK, p38 and ERK5 in response to receptor tyrosine kinases and GTPases. We used MDA-MB-231 cells because of their ability to metastasize from the breast fat pad to distant lymph nodes for an orthotopic xenograft model to screen the function of seven MAP3Ks in controlling tumor growth and metastasis. Stable shRNA knockdown was used to inhibit the expression of each of the seven MAP3Ks, which were selected for their differential regulation of the MAPK network. The screen identified two MAP3Ks, MEKK2 and MLK3, whose shRNA knockdown caused significant inhibition of both tumor growth and metastasis. Neither MEKK2 nor MLK3 have been previously shown to regulate tumor growth and metastasis in vivo. These results demonstrated that MAP3Ks, which differentially activate JNK, p38 and ERK5 are necessary for xenograft tumor growth and metastasis of MDA-MB-231 tumors. The requirement for MAP3Ks signaling through multiple MAPK pathways explains why several members of the MAPK network are activated in cancer. MEKK2 was required for EGF receptor and Her2/Neu activation of ERK5, with ERK5 being required for metastasis. Loss of MLK3 expression increased mitotic infidelity and apoptosis in vitro. Knockdown of MEKK2 and MLK3 resulted in increased apoptosis in orthotopic xenografts relative to control tumors in mice, inhibiting both tumor growth and metastasis; MEKK2 and MLK3 represent untargeted kinases in tumor biology for potential therapeutic development.

Summary

EPAC proteins are the guanine nucleotide exchange factors that act as the intracellular receptors for cyclic AMP. Two variants of EPAC genes including EPAC1 and EPAC2 are cloned and are widely expressed throughout the brain. But, their functions in the brain remain unknown. Here, we genetically delete EPAC1 (EPAC1-/-), or EPAC2 (EPAC2-/-) or both EPAC1 and EPAC2 genes (EPAC-/-) in the forebrain of mice. We show that EPAC null mutation impairs long-term potentiation (LTP) and that this impairment is paralleled with the severe deficits in spatial learning and social interactions and is mediated in a direct manner by miR-124 transcription and Zif268 translation. Knockdown of miR-124 restores Zif268 and hence reverses all aspects of the EPAC-/- phenotypes, whereas expression of miR-124 or knockdown of Zif268 reproduces the effects of EPAC null mutation. Thus, EPAC proteins control miR-124 transcription in the brain for processing spatial learning and social interactions.

SYNOPSIS

Upon ras activation, ornithine decarboxylase (ODC) is markedly induced, and numerous studies suggest that ODC expression is controlled by Ras effector pathways. ODC is therefore a potential target in the treatment and prevention of Ras-driven tumors. We compared ODC mRNA translation profiles and stability in normal and Ras12V-transformed rat intestinal epithelial (RIE-1) cells. While translation initiation of ODC increased modestly in Ras12V cells, ODC RNA was stabilized 8-fold. Treatment with the specific mTORC1 inhibitor rapamycin or siRNA knockdown of mTOR destabilized the ODC message, but rapamycin had only a minor effect on ODC translation initiation. Inhibition of mTORC1 also reduced the association of the mRNA binding protein HuR with the ODC transcript. We have shown previously that HuR binding to the ODC 3′UTR results in significant stabilization of the ODC mRNA, which contains several AU-rich regions within its 3′UTR that may act as regulatory sequences. Analysis of ODC 3′UTR deletion constructs suggests that cis-acting elements between bases 1969 and 2141 of the ODC mRNA act to stabilize the ODC transcript. These experiments thus define a novel mechanism of ODC synthesis control. Regulation of ODC mRNA decay could be an important means of limiting polyamine accumulation and subsequent tumor development.

Background

This study aimed to evaluate the feasibility of intraarterial (IA) delivery and in vivo MR imaging of superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs) in a canine stroke model.

Methodology

MSCs harvested from beagles’ bone marrow were labeled with home-synthesized SPIO. Adult beagle dogs (n = 12) were subjected to left proximal middle cerebral artery (MCA) occlusion by autologous thrombus, followed by two-hour left internal carotid artery (ICA) occlusion with 5 French vertebral catheter. One week later, dogs were classified as three groups before transplantation: group A: complete MCA recanalization, group B: incomplete MCA recanalization, group C: no MCA recanalization. 3×106 labeled-MSCs were delivered through left ICA. Series in vivo MRI images were obtained before cell grafting, one and 24 hours after transplantation and weekly thereafter until four weeks. MRI findings were compared with histological studies at the time point of 24 hours and four weeks.

Principal Findings

Home-synthesized SPIO was useful to label MSCs without cell viability compromise. MSCs scattered widely in the left cerebral hemisphere in group A, while fewer grafted cells were observed in group B and no cell was detected in group C at one hour after transplantation. A larger infarction on the day of cell transplantation was associated with more grafted cells in the brain. Grafted MSCs could be tracked effectively by MRI within four weeks and were found in peri-infarction area by Prussian blue staining.

Conclusion

It is feasible of IA MSCs transplantation in a canine stroke model. Both the ipsilateral MCA condition and infarction volume before transplantation may affect the amount of grafted cells in target brain. In vivo MR imaging is useful for tracking IA delivered MSCs after SPIO labeling.

Hantaviruses are among the most important zoonotic pathogens of humans and the subject of heightened global attention. Despite the importance of hantaviruses for public health, there is no consensus on their evolutionary history and especially the frequency of virus-host co-divergence versus cross-species virus transmission. Documenting the extent of hantavirus biodiversity, and particularly their range of mammalian hosts, is critical to resolving this issue. Here, we describe four novel hantaviruses (Huangpi virus, Lianghe virus, Longquan virus, and Yakeshi virus) sampled from bats and shrews in China, and which are distinct from other known hantaviruses. Huangpi virus was found in Pipistrellus abramus, Lianghe virus in Anourosorex squamipes, Longquan virus in Rhinolophus affinis, Rhinolophus sinicus, and Rhinolophus monoceros, and Yakeshi virus in Sorex isodon, respectively. A phylogenetic analysis of the available diversity of hantaviruses reveals the existence of four phylogroups that infect a range of mammalian hosts, as well as the occurrence of ancient reassortment events between the phylogroups. Notably, the phylogenetic histories of the viruses are not always congruent with those of their hosts, suggesting that cross-species transmission has played a major role during hantavirus evolution and at all taxonomic levels, although we also noted some evidence for virus-host co-divergence. Our phylogenetic analysis also suggests that hantaviruses might have first appeared in Chiroptera (bats) or Soricomorpha (moles and shrews), before emerging in rodent species. Overall, these data indicate that bats are likely to be important natural reservoir hosts of hantaviruses.

Author Summary

Hantaviruses are important human pathogens, occasionally emerging from animal reservoirs. However, both the biodiversity of hantaviruses in nature, as well as the frequency with which they have jumped species barriers in the past, are unclear. Here, we describe four novel hantaviruses (Huangpi virus, Lianghe virus, Longquan virus, and Yakeshi virus) that were sampled from bats and shrews in China. These viruses are different from known hantaviruses, with each representing a novel species. An evolutionary analysis of all known hantaviruses including the novel viruses described here reveals the existence of four distinct phylogenetic groups of viruses that infect a range of mammalian hosts, and which have sometimes exchanged genes through segment reassortment. Our analysis also suggests that hantaviruses might have first appeared in bats or insectivores, before spreading to rodents, even though rodents are currently the best documented hosts of hantaviruses. Because the phylogenetic trees of the hantaviruses do not always match those of their mammalian hosts, we conclude that both host-jumping and co-divergence have played important roles in hantavirus evolution. Overall, our study shows that bats are likely to be important natural reservoir hosts of hantaviruses from which novel hantaviruses may emerge in the future.

How the surface state (SS) develops and how the spin transport in a curved cylindrical topological insulator nanowire have attracted theoretical attention recently. However, experimental confirmation for the SS in such a real modeling system still remains insufficient. Here we carried out a systematic comparative study on the cylindrical single-crystal Bi2Te3 nanowires of various diameters, and report unambiguously dual evidence for the Dirac SS. Both the predicted anomalous Aharonov-Bohm (AB) quantum oscillations with a period of h/e in H// and the 1/2-shifted Shubnikov-de Haas (SdH) oscillations (i.e., γ = −1/2) in H⊥ were indentified below 1.4 K. In addition, Altshuler-Aronov-Spivak (AAS)-like oscillations with a period of h/2e and ordinary SdH oscillations with γ = 0 were also resolved. These data provide clear evidence of coexistence of the nontrivial topological Dirac state and trivial electron state on the surface of topological insulator nanowire.

Objective

Earlier studies have suggested that a common genetic architecture underlies the clinically heterogeneous polygenic Fredrickson hyperlipoproteinemia (HLP) phenotypes defined by hypertriglyceridemia (HTG). Here, we comprehensively analyzed 504 HLP-HTG patients and 1213 normotriglyceridemic controls and confirmed that a spectrum of common and rare lipid-associated variants underlies this heterogeneity.

Methods and Results

First, we demonstrated that genetic determinants of plasma lipids and lipoproteins, including common variants associated with plasma triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) from the Global Lipids Genetics Consortium were associated with multiple HLP-HTG phenotypes. Second, we demonstrated that weighted risk scores composed of common TG-associated variants were distinctly increased across all HLP-HTG phenotypes compared with controls; weighted HDL-C and LDL-C risk scores were also increased, although to a less pronounced degree with some HLP-HTG phenotypes. Interestingly, decomposition of HDL-C and LDL-C risk scores revealed that pleiotropic variants (those jointly associated with TG) accounted for the greatest difference in HDL-C and LDL-C risk scores. The APOE E2/E2 genotype was significantly overrepresented in HLP type 3 versus other phenotypes. Finally, rare variants in 4 genes accumulated equally across HLP-HTG phenotypes.

Conclusion

HTG susceptibility and phenotypic heterogeneity are both influenced by accumulation of common and rare TG-associated variants.

Introduction

In general, bony injuries heal well with immobilization when the fractured segments are well apposed in the cases of stable atlas fracture. Osseous nonunion of the displaced anterior arch fracture of the atlas has been reported in the literature. However, there have been no reports published on the treatment of nonunion of the atlas fractures.

Objective

The objective of this study is to describe a new technique for direct repair of the displaced anterior arch fracture of the atlas in a minimally invasive manner.

Methods

Seven patients with the atlas fracture were treated by a minimally invasive approach. Reduction of anterior arch fractures was not performed by skull traction and the displacement of fractures was more than 5 mm. Direct autograft was performed under microendoscope to improve union of the anterior arch fractures. Radiographic and CT evaluation of the atlas fractures were performed at 3, 6 and 12 months postoperatively.

Results

Seven cases of the atlas fractures (one old and six new fractures) underwent the surgical procedure smoothly without major complications. Total average displacement of the anterior arch fracture was 5.7 mm (range 5–8 mm) before surgery. Of the seven patients, bony union of the fracture developed in six. At latest follow-up, two patients had neck pain associated with movement and limited range of rotational motion.

Conclusion

Direct repair under microendoscope is a new technique that improves bony union of displaced anterior arch of the atlas fractures.

Purpose

Drug-resistant tuberculosis is a major public-health concern globally and can be difficult to manage clinically. Spinal tuberculosis is the most common manifestation of extrapulmonary tuberculosis. However, there have been few reports on the topic of drug-resistant spinal tuberculosis. The aim of this study was to investigate the clinical characteristics and drug susceptibility patterns and the outcomes of management with a combination of surgery and individualised chemotherapy, for drug-resistant spinal tuberculosis.

Methods

We retrospectively analysed 35 patients with drug-resistant tuberculous spondylitis. After surgery, individualised chemotherapy was tailored for each patient according to the drug-resistance profile and previous history of chemotherapy. The patients were followed up clinically and radiologically for an average period of 35.8 months.

Results

Among 35 drug-resistant spinal tuberculosis cases, 13 were retreatment cases. Twelve were multi-drug resistant tuberculosis (MDR-TB), and 23 were non-MDR-TB. The patients with MDR-TB and non-MDR-TB had undergone previous chemotherapy for an average of 14.50 ± 2.00 (0–60) months and 4.56 ± 1.54 (0–74) months, respectively. A total of 32 cases underwent open operations, and the other three had percutaneous drainage and local chemotherapy. Patients received individualised chemotherapy for an average of 23.6 months postoperatively. Local recurrence was observed in six patients. Thirty-three patients had been cured at the final follow-up, and the other two were still receiving chemotherapy.

Conclusions

Drug-resistant tuberculous spondylitis is mainly acquired through previous irregular chemotherapy and the spreading of drug-resistant strains. Management with a combination of surgery and individualised chemotherapy is feasible in the treatment of severe complications and the prevention of acquired drug resistance.

Background

Rare variant accumulation studies can implicate genes in disease susceptibility when a significant burden is observed in patients versus controls. Such analyses might be particularly useful for candidate genes that are selected based on experiments other than genome-wide association studies (GWAS). We sought to determine whether rare variants in non-GWAS candidate genes identified from mouse models and human Mendelian syndromes of hypertriglyceridemia (HTG) accumulate in patients with polygenic adult-onset HTG.

Methods and Results

We resequenced protein coding regions of 3 genes with established roles (APOC2, GPIHBP1, LMF1) and 2 genes recently implicated (CREB3L3 and ZHX3) in TG metabolism. We identified 41 distinct heterozygous rare variants, including 29 singleton variants, in the combined sample; in total, we observed 47 rare variants in 413 HTG patients versus 16 in 324 controls (OR=2.3; P=0.0050). Post hoc assessment of genetic burden in individual genes using three different tests suggested that the genetic burden was most prominent in the established genes LMF1 and APOC2, and also in the recently identified CREB3L3 gene.

Conclusions

These extensive resequencing studies show a significant accumulation of rare genetic variants in non-GWAS candidate genes among patients with polygenic HTG, and indicate the importance of testing specific hypotheses in large-scale resequencing studies.

A cotton germplasm collection with data for 20 quantitative traits was used to investigate the effect of the scale of quantitative trait data on the representativeness of plant sub-core collections. The relationship between the representativeness of a sub-core collection and two influencing factors, the number of traits and the sampling percentage, was studied. A mixed linear model approach was used to eliminate environmental errors and predict genotypic values of accessions. Sub-core collections were constructed using a least distance stepwise sampling (LDSS) method combining standardized Euclidean distance and an unweighted pair-group method with arithmetic means (UPGMA) cluster method. The mean difference percentage (MD), variance difference percentage (VD), coincidence rate of range (CR), and variable rate of coefficient of variation (VR) served as evaluation parameters. Monte Carlo simulation was conducted to study the relationship among the number of traits, the sampling percentage, and the four evaluation parameters. The results showed that the representativeness of a sub-core collection was affected greatly by the number of traits and the sampling percentage, and that these two influencing factors were closely connected. Increasing the number of traits improved the representativeness of a sub-core collection when the data of genotypic values were used. The change in the genetic diversity of sub-core collections with different sampling percentages showed a linear tendency when the number of traits was small, and a logarithmic tendency when the number of traits was large. However, the change in the genetic diversity of sub-core collections with different numbers of traits always showed a strong logarithmic tendency when the sampling percentage was changing. A CR threshold method based on Monte Carlo simulation is proposed to determine the rational number of traits for a relevant sampling percentage of a sub-core collection.

Zinc ions highly concentrate in hippocampus and play a key role in modulating spatial learning and memory. At a time when dietary fortification and supplementation of zinc have increased the zinc consuming level especially in the youth, the toxicity of zinc overdose on brain function was underestimated. In the present study, weaning ICR mice were given water supplemented with 15 ppm Zn (low dose), 60 ppm Zn (high dose) or normal lab water for 3 months, the behavior and brain zinc homeostasis were tested. Mice fed high dose of zinc showed hippocampus-dependent memory impairment. Unexpectedly, zinc deficiency, but not zinc overload was observed in hippocampus, especially in the mossy fiber-CA3 pyramid synapse. The expression levels of learning and memory related receptors and synaptic proteins such as NMDA-NR2A, NR2B, AMPA-GluR1, PSD-93 and PSD-95 were significantly decreased in hippocampus, with significant loss of dendritic spines. In keeping with these findings, high dose intake of zinc resulted in decreased hippocampal BDNF level and TrkB neurotrophic signaling. At last, increasing the brain zinc level directly by brain zinc injection induced BDNF expression, which was reversed by zinc chelating in vivo. These results indicate that zinc plays an important role in hippocampus-dependent learning and memory and BDNF expression, high dose supplementation of zinc induces specific zinc deficiency in hippocampus, which further impair learning and memory due to decreased availability of synaptic zinc and BDNF deficit.

Background/Objectives

Portal hypertension (PH) is a clinical sequelae of liver cirrhosis, and bleeding from esophageal varices (EV) is a serious complication of PH with significant morbidity and mortality. The aims of this study were to assess the ability of 2D multislice breath-hold susceptibility weighted imaging (SWI) to detect Gamna-Gandy bodies (GGBs) in the spleens of patients with PH and to evaluate the potential role of GGB number as a non-invasive marker of PH and EV.

Materials and Methods

T1-, T2- and T2*- weighted imaging and SWI were performed on 135 patients with PH and on 37 control individuals. Platelet counts were collected from all PH patients. Two radiologists analyzed all magnetic resonance imaging (MRI) data, and measured the portal vein diameter, splenic index (SI), and platelet count/spleen diameter ratio. The numbers of patients with GGBs in the spleen were determined, and the numbers of GGB were counted in the four MRI sequences in GGB-positive patients. The portal vein diameter, SI, platelet count, and platelet count/spleen diameter ratio of control individuals were compared with those of GGB-negative and GGB-positive patients on SWI images. The correlations among GGB numbers, the portal vein diameter, the SI, the platelet count, and the platelet count/spleen diameter ratio were analyzed.

Results

The GGB detection rate and the detected GGB number by using SWI were significantly greater than those by using T1-, T2-, and T2*- weighted images. The number of GGBs in the SWI images correlated positively with the portal vein diameter and SI and correlated negatively with the platelet count and platelet count/spleen diameter ratio.

Conclusion

SWI provided more accurate information of GGBs in patients with PH. The number of GGB may be a non-invasive predictor of improving the selection for endoscopic screening of PH patients at risk of EV.

Background

Although the expenses of liver cirrhosis are covered by a critical illness fund under the current health insurance program in China, the economic burden associated with hepatitis B virus (HBV) related diseases is not well addressed. In order to provide evidence to address the economic disease burden of HBV, we conducted a survey to investigate the direct economic burden of acute and chronic hepatitis B, cirrhosis and liver cancer caused by HBV-related disease.

Methods

From April 2010 to November 2010, we conducted a survey of inpatients with HBV-related diseases and who were hospitalized for seven or more days in one of the seven tertiary and six secondary hospitals in Shandong, China. Patients were recorded consecutively within a three-to-five month time period from each sampled hospital; an in-person survey was conducted to collect demographic and socio-economic information, as well as direct medical and nonmedical expenses during the last month and last year prior to the current hospitalization. Direct medical costs included total outpatient, inpatient, and self-treatment expenditures; direct nonmedical costs included spending on nutritional supplements, transportation, and nursing. Direct medical costs during the current hospitalization were also obtained from the hospital financial database. The direct economic cost was calculated as the sum of direct medical and nonmedical costs. Our results call for the importance of implementing clinical guideline, improving system accountability, and helping secondary and smaller hospitals to improve efficiency. This has important policy implication for the on-going hospital reform in China.

Results

Our data based on inpatients with HBV-related diseases suggested that the direct cost in US dollars for acute hepatitis B, severe hepatitis B, chronic hepatitis B, compensated cirrhosis, decompensated cirrhosis and primary liver cancer was $2954, $10834, $4552, $7400.28, $6936 and $10635, respectively. These costs ranged from 30.72% (for acute hepatitis B) to 297.85% (for primary liver cancer) of the average annual household income in our sample. Even for patients with health insurance, direct out-of-pocket cost of all HBV-related diseases except acute hepatitis B exceeded 40.00% of the patient’s disposable household income, making it a catastrophic expenditure for the household.

Conclusion

Hepatitis B imposes considerable economic burden on a family. Our findings will help health policy makers’ understanding of the magnitude of the economic burden of HBV-related diseases in China. Evidence from our study also contributes to our understanding of potential benefits to society from allocating more resources to preventing and treating HBV infection, as well as increasing insurance coverage in China. These findings have important policy implications for health care reform efforts currently underway in China focusing on how to reduce the burden of catastrophic disease for its citizens.

Type III secretion system (T3SS) of the plague bacterium Y. pestis encodes a syringe-like structure consisting of more than 20 proteins, which can inject virulence effectors into host cells to modulate the cellular functions. Here in this report, interactions among the possible components in T3SS of Yersinia pestis were identified using yeast mating technique. A total of 57 genes, including all the pCD1-encoded genes except those involved in plasmid replication and partition, pseudogenes, and the putative transposase genes, were subjected to yeast mating analysis. 21 pairs of interaction proteins were identified, among which 9 pairs had been previously reported and 12 novel pairs were identified in this study. Six of them were tested by GST pull down assay, and interaction pairs of YscG-SycD, YscG-TyeA, YscI-YscF, and YopN-YpCD1.09c were successfully validated, suggesting that these interactions might play potential roles in function of Yersinia T3SS. Several potential new interactions among T3SS components could help to understand the assembly and regulation of Yersinia T3SS.

The research on self-healing polymers has been a hot topic. The encapsulated-monomer/catalyst, supramolecular self-assembly, and reversible or dynamic covalent bond formation are the prevailingly adopted strategies. The alternative of irreversible covalent bond formation is, however, to be further developed. In this contribution, self-healing hyperbranched poly(aroyltriazole)s of PI and PII sharing such mechanism were developed. The polymers were synthesized by our developed metal-free click polymerizations of bis(aroylacetylene)s and triazide. They are processible and have excellent film-forming ability. High quality homogeneous films and sticks free from defects could be obtained by casting. The scratched films could be self-repaired upon general heating. The cut films and sticks could be healed by stacking or pressing the halves together at elevated temperature. Thus, these hyperbranched polymers could find broad applications in diverse areas, and our design concept for self-healing materials should be generally applicable to other hyperbranched polymers with reactive groups on their peripheries.

Depression has been associated with reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. Genetic association studies of the BDNF Val66Met polymorphism (rs6265) in geriatric depression have produced inconsistent results. A meta-analysis of studies was conducted to compare the frequency of the BDNF Val66Met variant between cases with geriatric depression and age-matched controls. A total of five studies involving 523 cases with geriatric depression and 1,220 psychiatrically healthy controls was included. Met allele carriers had an increased risk for geriatric depression when compared to Val/Val homozygotes (P =0.004, OR =1.48, 95% CI =1.13–1.93). Our findings suggest the BDNF Met allele may confer increased risk for depression as individual age.

Plant autophagy plays an important role in delaying senescence, nutrient recycling, and stress responses. Functional analysis of plant autophagy has almost exclusively focused on the proteins required for the core process of autophagosome assembly, but little is known about the proteins involved in other important processes of autophagy, including autophagy cargo recognition and sequestration. In this study, we report functional genetic analysis of Arabidopsis NBR1, a homolog of mammalian autophagy cargo adaptors P62 and NBR1. We isolated two nbr1 knockout mutants and discovered that they displayed some but not all of the phenotypes of autophagy-deficient atg5 and atg7 mutants. Like ATG5 and ATG7, NBR1 is important for plant tolerance to heat, oxidative, salt, and drought stresses. The role of NBR1 in plant tolerance to these abiotic stresses is dependent on its interaction with ATG8. Unlike ATG5 and ATG7, however, NBR1 is dispensable in age- and darkness-induced senescence and in resistance to a necrotrophic pathogen. A selective role of NBR1 in plant responses to specific abiotic stresses suggest that plant autophagy in diverse biological processes operates through multiple cargo recognition and delivery systems. The compromised heat tolerance of atg5, atg7, and nbr1 mutants was associated with increased accumulation of insoluble, detergent-resistant proteins that were highly ubiquitinated under heat stress. NBR1, which contains an ubiquitin-binding domain, also accumulated to high levels with an increasing enrichment in the insoluble protein fraction in the autophagy-deficient mutants under heat stress. These results suggest that NBR1-mediated autophagy targets ubiquitinated protein aggregates most likely derived from denatured or otherwise damaged nonnative proteins generated under stress conditions.

Author Summary

Autophagy is an evolutionarily conserved process that sequestrates and delivers cytoplasmic macromolecules and organelles to the vacuoles or lysosomes for degradation. In plants, autophagy is involved in supplying internal nutrients during starvation and in promoting cell survival during senescence and during biotic and abiotic stresses. Arabidopsis NBR1 is a homolog of mammalian autophagy cargo adaptors P62 and NBR1. Disruption of Arabidopsis NBR1 caused increased sensitivity to a spectrum of abiotic stresses but had no significant effect on plant senescence, responses to carbon starvation, or resistance to a necrotrophic pathogen. NBR1 contains an ubiquitin-binding domain, and the compromised stress tolerance of autophagy mutants was associated with increased accumulation of NBR1 and ubiquitin-positive cellular protein aggregates in the insoluble protein fraction under stress conditions. Based on these results, we propose that NBR1 targets ubiquitinated protein aggregates most likely derived from denatured and otherwise damaged nonnative proteins for autophagic clearance under stress conditions.

Herein we developed a new “smart” Gd-based MR contrast agent (i.e., 1) which is susceptive to furin, a protease overexpressed in tumor. Under the action of furin, 1 condenses to form dimers (1-Ds) and the latter self-assemble into gadolinium nanparticles (Gd-NPs). Relaxivity of 1-D is more than 2 folds of those of 1 and magnevist at 1.5 T, and 1.4 folds of that of 1 at 3 T. Intracellular condensation of 1 in furin-overexpressed MDA-MB-468 cells was proven with direct two-photon laser microscopy (TPLM) fluorescence imaging of the cells incubated with the europium analog of 1 (i.e., 2). Intracellular Gd-NPs of 1 were uncovered and characterized for the first time. MRI of MDA-MB-468 tumors showed that 1 has enhanced MR contrast within the tumors than that of its scrambled control 1-Scr.

Previous studies have indicated that 2,2′-dipyridyl, a lipid-soluble ferrous iron chelator, can reduce brain injury after cerebral ischemia and reduce cerebral vasospasm after subarachnoid hemorrhage. In this study, we examined the efficacy of 2,2′-dipyridyl after intracerebral hemorrhage (ICH) in 12-month-old mice. ICH was modeled by intrastriatal injection of collagenase or autologous whole blood. 2,2′-Dipyridyl or vehicle was administered intraperitoneally 2 h before ICH (pretreatment) or 6 h after ICH (post-treatment) and then once daily for up to 3 days. Mice in the pretreatment group were sacrificed 1 or 3 days after ICH and examined for iron deposition, neuronal death, oxidative stress, microglial/astrocyte activation, neutrophil infiltration, and white matter damage. Mice in the post-treatment group were examined for brain lesion volume and edema on day 3 and for neurologic deficits on days 1, 3, and 28 after ICH. Pretreatment with 2,2′-dipyridyl decreased iron accumulation and neuronal death, attenuated production of reactive oxygen species, reduced microglial activation without affecting astrocytes or neutrophil infiltration, and attenuated white matter damage. Post-treatment reduced brain lesion volume and edema and improved neurologic function. These results indicate that the lipid-soluble ferrous iron chelator 2,2′-dipyridyl can reduce brain injury and improve functional outcome after ICH.