[MiR-340 mediates the involvement of high mobility group box 1 in the pathogenesis of liver fibrosis].

Objective: To explore the pathogenic mechanism of the miR-340/high mobility group box 1 (HMGB1) axis in the formation of liver fibrosis. Methods: A rat liver fibrosis model was established by injecting CCl(4) intraperitoneally. miRNAs targeting and validating HMGB1 were selected with gene microarrays after screening the differentially expressed miRNAs in rats with normal and hepatic fibrosis. The effect of miRNA expressional changes on HMGB1 levels was detected by qPCR. Dual luciferase gene reporter assays (LUC) was used to verify the targeting relationship between miR-340 and HMGB1. The proliferative activity of the hepatic stellate cell line HSC-T6 was detected by thiazolyl blue tetrazolium bromide (MTT) assay after co-transfection of miRNA mimics and HMGB1 overexpression vector, and the expression of extracellular matrix (ECM) proteins type I collagen and α-smooth muscle actin (SMA) was detected by western blot. Statistical analysis was performed by analysis of variance and the LSD-t test. Results: Hematoxylin-eosin and Masson staining results showed that the rat model of liver fibrosis was successfully established. Gene microarray analysis and bioinformatics prediction had detected eight miRNAs possibly targeting HMGB1, and animal model validation had detected miR-340. qPCR detection results showed that miR-340 had inhibited the expression of HMGB1, and a luciferase complementation assay suggested that miR-340 had targeted HMGB1. Functional experiments results showed that HMGB1 overexpression had enhanced cell proliferation activity and the expression of type I collagen and α-SMA, while miR-340 mimics had not only inhibited cell proliferation activity and the expression of HMGB1, type I collagen, and α-SMA, but also partially reversed the promoting effect of HMGB1 on cell proliferation and ECM synthesis. Conclusion: miR-340 targets HMGB1 to inhibit the proliferation and ECM deposition in hepatic stellate cells and plays a protective role during the process of liver fibrosis.

[Research Progress on the Effect of Synthetic Cathinones on Animal Behavior].

ABSTRACT: Synthetic cathinones are a class of new psychoactive substances with a structure similar to amphetamine drugs, which can produce excitatory effects similar to drugs such as amphetamine and cocaine after being taken. In recent years, the abuse of synthetic cathinones worldwide has become increasingly serious, posing a serious threat to social security and public health. This article focuses on several common synthetic cathinones, collects their research results in animal autonomous activity experiments and drug dependence model experiments and summarizes their relevant experimental conclusions in animal body temperature regulation, learning and memory, and anxiety, in order to provide data reference and method guidance for the domestic development of related drug research.

Final kissing balloon inflation for coronary bifurcation lesions treated with single-stent technique : A meta-analysis.

BACKGROUND: The efficacy of final kissing balloon (FKB) inflation in one-stent techniques for bifurcation lesions is controversial. The goal of the present study was to investigate the impact of FKB on long-term clinical outcomes in one-stent strategies. METHODS: A literature search of the PubMed, Embase, and Cochrane Library databases was undertaken through August 2017. The primary outcome was major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction, and target lesion revascularization. Overall hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random-effects model. RESULTS: Ten studies comprising 7364 patients treated with a one-stent technique were included in the analysis. Overall, FKB did not demonstrate a significant reduction in MACE compared with non-FKB in both randomized trials (HR: 1.13; 95% CI: 0.65-1.98) and observational studies (HR: 0.86; 95% CI: 0.61-1.20). The risk of cardiac death (HR: 0.89; 95% CI: 0.53-1.49), myocardial infarction (HR: 0.76; 95% CI: 0.53-1.09), and target lesion revascularization (HR: 0.96; 95% CI: 0.74-1.23) was also similar in both groups. CONCLUSION: FKB may not be mandatory and a selective FKB strategy might be more justified in one-stent techniques for bifurcation lesions.

Polymorphisms of the prolactin gene and their association with egg production traits in two Chinese domestic ducks.

1. Prolactin (PRL) as a polypeptide hormone which plays a crucial role in egg production traits. 2. Polymorphisms of the PRL gene were analysed with DNA sequencing and polymerase chain reaction-single-strand conformation polymorphism methods in two Chinese domestic laying duck breeds (Jinding, n = 400, Youxian, n = 400, respectively). 3. The results showed that one polymorphism was detected (A-412G) in intron 1 of the PRL gene, with three genotypes: AA, AG and GG. Association analysis showed that the ducks with the GG genotype had significantly greater egg production and egg weight than those with AG and AA genotype (p < 0.05). Hence, the 412A > G polymorphism of the PRL gene in intron 1 is a potentially valuable genetic marker for laying duck breeding programmes.

The distribution of different virulence grass carp reovirus strains in some neglected tissues.

Grass carp reovirus (GCRV) is the causative agent of hemorrhagic disease in infected grass carp. During an outbreak, a mortality rate of up to 85% can be experienced, thus leading to substantial economic losses. The current understanding of disease pathogenesis is limited, with the distribution and dynamics of replication amongst different GCRV strains in vivo largely unknown. We determined distribution of different GCRV strains in infected grass carp, especially in some neglected tissues, such as the gill, brain, blood and so on. The results showed elevated viral RNA copy numbers in the blood, with some tissues such as the kidney, heart, brain, and bladder exhibiting even higher viral loads following infection with the virulent GCRV-CL strain. Even more interesting is that the brain exhibited the highest viral load, with a copy number of 800,000 following GCRV-CL infection. Overall, this study provides further insight into GCRV viral load distributions following infection and potentially identified some new viral tropism sites to provide a foundation for further studies aimed at characterizing GCRV viral pathogenesis.

Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials.

UNLABELLED: To identify the role of vitamin K2 for the prevention and treatment of osteoporosis in postmenopausal women, we conducted this meta-analysis of 19 randomized controlled trials. Our results showed that vitamin K2 might play a role in maintaining the bone mineral density and in reducing the incidence of fractures for postmenopausal women with osteoporosis. INTRODUCTION: Vitamin K2 has been revealed to be effective in the prevention and treatment of osteoporosis in Japan, which was not confirmed in western countries. Thus, we conduct this meta-analysis to verify the hypothesis that vitamin K2 plays a role in the prevention and treatment of osteoporosis for postmenopausal women. METHODS: We searched the Cochrane Library, Pub Med, EMBASE, and ISI web of knowledge (until December 1, 2013) and reference lists of eligible articles. A meta-analysis of all-including randomized controlled trials was then performed. RESULTS: Nineteen randomized controlled trials encompassing 6759 participants have met the inclusion criteria. Subgroup analysis of postmenopausal women with osteoporosis revealed a significant improvement of vertebral BMD for both medium-term and long-term results favoring vitamin K2 group (p < 0.00001 and p = 0.0005). However, no significant difference in BMD changes was revealed for the non-osteoporosis subgroup analysis. As for the incidence of fractures, pooled analysis of the seven related studies demonstrated no significant difference in the incidence of fractures favoring vitamin K2 (RR = 0.63, p = 0.08). However, sensitivity analysis by rejecting the study inducing heterogeneity demonstrated a significant difference in the incidence of fractures favoring vitamin K2 (RR = 0.50, p = 0.0005). Significant differences were found in undercarboxylated osteocalcin reduction and osteocalcin increment. The result of adverse reaction analysis showed that vitamin K2 group seemed to have a higher adverse reaction rate (RR = 1.22, p = 0.06). CONCLUSIONS: This meta-analysis seemed to support the hypothesis that vitamin K2 plays kind of a role in the maintenance and improvement of vertebral BMD and the prevention of fractures in postmenopausal women with osteoporosis. The reduction of undercarboxylated osteocalcin and increment of osteocalcin may have some relation to the process of bone mineralization. However, the effect of vitamin K2 for postmenopausal women without osteoporosis had not been identified. Further high-quality RCTs with large sample size are needed to confirm the role of vitamin K2 in osteoporosis for postmenopausal women.

Cloning, expression, and polymorphism at the 5'-flanking region of the GnRH gene and their association with laying traits in Muscovy duck (Cairina moschata).

Gonadotropin-releasing hormone (GnRH), a neuropeptide, plays a vital role in the hypothalamus-pituitary-gonadal (HPG) axis. In vertebrates, GnRH is crucial for the onset of sexual development and the entire reproductive process. The purpose of this study was to identify genetic factors associated with egg-laying traits of Muscovy ducks. The full-length cDNA (474 bp) of Muscovy duck GnRH was obtained and characterised. It encodes 92 amino acids containing a 1-amino acid signal peptide cleavage site. Phylogenetic analysis revealed that Muscovy duck GnRH has a close relationship with Anas platyrhynchos GnRH. GnRH showed significantly different expression profiles between 4 developmental periods in the hypothalamus, pituitary, and ovary. The expression of GnRH in the laying period (36 weeks) was higher than at other periods in the three tissues. GnRH was widely expressed in 12 examined tissues of nesting and laying Muscovy ducks. In the hypothalamus, pituitary and gonads, the expression of GnRH was higher than in other tissues. In laying Muscovy ducks, the expression of GnRH in the hypothalamus, pituitary, ovary, muscular stomach, pancreas, heart, duodenum and spleen was significantly higher than in nesting dusks. Differences were detected in the liver and glandular stomach between laying ducks and nesting ducks. Differences between the kidney and lung were not significant. In the pituitary, the GnRH and GnRH receptor (GnRHR) genes shared the same expression profiles during 4 time points. Both genes had the highest expression at 36 weeks of age. A mutation (g.206G > A) in the 5'-flanking region was associated with egg-laying performance. Individuals with genotype GG had better egg-laying performance than the individuals with genotype AA. GnRH may be used as a marker gene for laying performance in the Muscovy duck.

Uniform detection of HIV-1 in alveolar macrophages of pediatric but not adult AIDS patients.

Manifestations of pulmonary disease in pediatric AIDS patients differ from those in adults. To evaluate whether differences in the frequency of alveolar macrophage (AM) infection with human immunodeficiency virus type 1 (HIV-1) could account for these clinical distinctions, we undertook a comparative analysis of HIV-1 DNA in AMs from pediatric and adult AIDS patients by enzymatic amplification. A higher frequency of viral DNA detection in pediatric cases (100%) compared with adults (67%) was observed. The sensitivity of detection was 1 viral DNA copy per 4000 AMs; matched peripheral blood mononuclear cells from six of seven pediatric and eight of nine adult patients tested HIV-1 DNA positive. Adult but not pediatric patients exhibited a marked alveolar lymphocytosis, 32% mean lymphocyte count compared with 7.0%, respectively. These results suggest that the burden of HIV-1 in the lungs of pediatric AIDS patients is greater than that in adults.

Effect of corticosteroids on IL1 beta and TNF alpha release by alveolar macrophages from patients with AIDS and Pneumocystis carinii pneumonia.

The mechanisms by which corticosteroids (CCs) improve the outcome of AIDS patients with severe Pneumocystis carinii pneumonia (PCP) are unclear. We studied IL1 beta and TNF alpha release from alveolar macrophages (AMs) of patients receiving CCs for the treatment of PCP and also the effect of in vitro hydrocortisone on this release. Cytokine release from AMs of AIDS patients with pulmonary complications not receiving CCs (group 1) was compared with that from AM of those receiving CCs for PCP (group 2). The AMs of HIV-negative normal subjects (group 3) served as controls. All participants were nonsmokers or exsmokers. We found that lipopolysaccharide-stimulated AM from group 2 released significantly less interleukin-1 beta (IL1 beta) and tumor necrosis factor alpha (TNF alpha) than AM from group 1 and was similar to that from group 3. There was a significant positive correlation between the amount of TNF alpha and IL1 beta released. The presence of HC in the culture medium reduced in vitro IL1 beta and TNF alpha release from stimulated AM of the three groups. Thus, stimulated AMs from AIDS patients who receive CCs for treatment of PCP release significantly less IL1 beta and TNF alpha than AM from patients not receiving CCs. These findings suggest a mechanism by which CCs improve the outcome of AIDS patients with PCP.

Effect of bronchoalveolar lavage fluid from patients with sarcoidosis or AIDS on interleukin 1 beta release from alveolar macrophages.

We studied the effect of concentrated surfactant-depleted BALF from 8 normal subjects, 13 patients with sarcoidosis, and 13 patients with AIDS on IL1 beta release by human AM. Adherent target AM were exposed to concentrated BALF in the presence or absence of LPS (1 microgram/ml) for two hours. Control AM were unexposed to BALF. After an additional 24-hour incubation, AM supernatants were collected and measured for IL1 beta by ELISA. No spontaneous IL1 beta release occurred from unstimulated AM. One of the sarcoid-BALF and three of the AIDS-BALF samples induced a small amount of IL1 beta release from unstimulated AM. In LPS-stimulated AM, exposure to normal BALF did not significantly alter IL1 beta release compared to unexposed AM. Exposure to sarcoid-BALF significantly increased the release of IL1 beta, while exposure to AIDS-BALF significantly reduced the IL1 beta level in the AM supernatants. The latter effect was related to the higher mortality induced by AIDS-BALF in AM. These data show that release of IL1 beta from LPS-stimulated AM is modified by a short exposure to a sample of alveolar fluid from patients with lung disease.

Correlation of bronchoalveolar lavage findings to severity of Pneumocystis carinii pneumonia in AIDS. Evidence for the development of high-permeability pulmonary edema.

We correlated bronchoalveolar lavage findings with the clinical course and outcome of Pneumocystis pneumonia. Forty-eight patients with AIDS and a confirmed diagnosis of P carinii pneumonia were studied. Patients with additional pulmonary infections were excluded. On the basis of BAL findings, they were divided into those with a low neutrophil count (less than 5 percent) and those with a high neutrophil count (greater than or equal to 5 percent). Sixteen patients with AIDS but without PCP served as a control group. All BAL fluid samples from the control group showed a low neutrophil count. The group with PCP and a high neutrophil count had more severe respiratory compromise and greater morbidity than the group with PCP and a low neutrophil count. Mortality rate was not different. The group showing a high BALF neutrophil count also showed a higher BALF protein concentration, a higher ratio of BALF protein concentration to plasma protein concentration, and the presence of alpha 2-globulins compared with other groups. These findings suggest that increased alveolar-capillary permeability occurs during severe PCP.

Nutrition and hydration in terminally ill patients: an update.

Many health care professionals lack knowledge about artificial nutrition and hydration at the end of life or may hold different attitudes about artificial nutrition and hydration compared with other treatments. Consequently, they may convey inaccurate or misleading information to patients or their surrogate decision makers. An updated understanding about artificial nutrition and hydration in light of prevailing medical evidence is presented.

[Genetic analysis of 35 microsatellite loci in 5 lineages of xishuangbanna miniature pig inbred line].

The polymorphism of 35 microsatellites in 5 lineages of Xishuangbanna small-ear miniature pig inbred line (XMI) was analysed. Nmuber of alleles of each lineage was counted, and rates of homozygote for 35 microsatellite loci in 5 lineages were calculated. According to gene frequencies of 35 microsatellites polymorphism information content (PIC) and mean heterozygosity were calculated for each lineage, and genetic distances between these lineage were estimated. The dendrograms were obtained based on genetic distances. The results suggest that rates of homozygote in these lineage are all high, and that is the highest in lineage 151. The results also suggest that polymorphism information content and mean heterozygosity in all the lineages are low. Composition of alleles of each lineage was quite different and the genetic relationship between lineages accorded with the process of inbred line. So it is suggested that the inbreeding degree of 5 lineages of XMI are all high, and the richness of genetic diversity is lower than general commercial pig breeds. It also shows each lineage has been different groups with individual genes.

Superconducting gap in the hubbard model and the two-gap energy scales of high-T{c} cuprate superconductors.

Recent experiments (angle-resolved photoemission spectroscopy and Raman) suggest the presence of two distinct energy gaps in high-temperature superconductors (HTSC), exhibiting different doping dependences. The results of a variational cluster approach to the superconducting state of the two-dimensional Hubbard model are presented which show that this model qualitatively describes this gap dichotomy. The antinodal gap increases with less doping, a behavior long considered as reflecting the general gap behavior of the HTSC. On the other hand, the near-nodal gap does even slightly decrease with underdoping. An explanation of this unexpected behavior is given which emphasizes the crucial role of spin fluctuations in the pairing mechanism.

Infection of macrophages with lymphotropic human immunodeficiency virus type 1 can be arrested after viral DNA synthesis.

Lymphotropic strains of human immunodeficiency virus type 1 (HIV-1), including HTLV-IIIB, replicate poorly in macrophages. We have shown previously that lymphotropic HIV-1 fuses equally well with T lymphocytes and macrophages (M. J. Potash, M. Zeira, Z.-B. Huang, T. Pearce, E. Eden, H. Gendelman, and D. J. Volsky, Virology 188:864-868, 1992), suggesting that events in the virus life cycle following virus-cell fusion limit virus replication. We report here that HIV-1 DNA is synthesized efficiently in either ADA or HTLV-IIIB infected alveolar macrophages or monocyte-derived macrophages within 24 h of virus infection, as observed by polymerase chain reaction for amplification of viral DNA sequences from the gag gene. Infection by a cloned lymphotropic HIV-1 strain, N1T-A, also leads to viral DNA synthesis. However, circular viral DNA was detected during strain ADA infection but not during HTLV-IIIB or N1T-A infection of monocyte-derived macrophages. These findings indicate that during replication of lymphotropic HIV-1 in macrophages, all steps of the virus life cycle up to and including reverse transcription take place and that defects in later events, including DNA migration to the nucleus, may account for the limited production of viral proteins.

Virus-cell membrane fusion does not predict efficient infection of alveolar macrophages by human immunodeficiency virus type 1 (HIV-1).

Alveolar macrophages (AM) are the principal target cells for HIV-1 in lung tissue. To investigate the mechanisms of HIV-1 infection and efficient replication in these cells we isolated AM from 14 HIV-1 negative donors and exposed them to two virus isolates, either N1T, which replicates well in T lymphocytic and monocytic cell lines, or ADA, a monocytotropic virus. Membrane fluorescence dequenching assays demonstrated that HIV-1/N1T fuses efficiently with AM plasma membranes at neutral pH and that this interaction requires cellular CD4. Despite efficient fusion, AM from eight of 14 donors were not susceptible to productive infection with N1T. In contrast, ADA replicated in all AM populations tested. Soluble CD4 blocked infection of AM by either N1T or ADA, indicating that, like membrane fusion, entry of infectious virus requires an interaction with cellular CD4. Analysis of HIV-1 DNA accumulation in infected cells by enzymatic amplification revealed that productive infection by ADA correlated with a high HIV-1 DNA copy number and abortive infection by N1T was characterized by little or no stable cDNA. These studies suggest that the differences between the two HIV-1 strains studied in their ability to replicate in AM reside in phases of the virus life cycle that follow virus-cell fusion.