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The quality safety risks and quality management issues of traditional fermented meat products were analyzed. This paper put forward suggestions on increasing research and development efforts, accelerating the knowledge benefit transformation process, standardizing the standard system, refining supervision standards, standardizing workshop production, optimizing product markets, strengthening the awareness of social participation, and promoting social co-governance, in order to improve the overall quality and safety level of the traditional fermented meat products industry.

The production of vertebrate retinal projection neurons, retinal ganglion cells (RGCs), is regulated by cell-intrinsic determinants and cell-to-cell signaling events. The basic-helix-loop-helix (bHLH) protein Atoh7 is a key neurogenic transcription factor required for RGC development. Here, we investigate whether manipulating human ATOH7 expression among uncommitted progenitors can promote RGC fate specification and thus be used as a strategy to enhance RGC genesis. Using the chicken retina as a model, we show that cell autonomous expression of ATOH7 is sufficient to induce precocious RGC formation and expansion of the neurogenic territory. ATOH7 overexpression among neurogenic progenitors significantly enhances RGC production at the expense of reducing the progenitor pool. Furthermore, forced expression of ATOH7 leads to a minor increase of cone photoreceptors. We provide evidence that elevating ATOH7 levels accelerates cell cycle progression from S to M phase and promotes cell cycle exit. We also show that ATOH7-induced ectopic RGCs often exhibit aberrant axonal projection patterns and are correlated with increased cell death during the period of retinotectal connections. These results demonstrate the high potency of human ATOH7 in promoting early retinogenesis and specifying the RGC differentiation program, thus providing insight for manipulating RGC production from stem cell-derived retinal organoids.

HLA‐B*15:02:15 differs from HLA‐B*15:02:01:01 by one nucleotide in exon 2. [ABSTRACT FROM AUTHOR]

The anterior segment of the vertebrate eye consists of highly organized and specialized ocular tissues critical for normal vision. The periocular mesenchyme, originating from the neural crest, contributes extensively to the anterior segment. During chick eye morphogenesis, the homeobox gene Six3 is expressed in a subset of periocular mesenchymal cells and in differentiating anterior segment tissues. Retrovirus-mediated misexpression of Six3 causes eye anterior segment malformation, including corneal protrusion and opacification, ciliary body and iris hypoplasia, and trabecular meshwork dysgenesis. Histological and molecular marker analyses demonstrate that Six3 misexpression disrupts the integrity of the corneal endothelium and the expression of extracellular matrix components critical for corneal transparency. Six3 misexpression also leads to a reduction of the periocular mesenchymal cell population expressing Lmx1b, Pitx2, and Pax6, transcription factors critical for eye anterior segment morphogenesis. Moreover, elevated levels of Six3 attenuate proliferation of periocular mesenchymal cells in vitro and differentiating anterior segment tissues in vivo. These results suggest that, in addition to its function in eye primordium determination, Six3 plays a role in regulating the development of the vertebrate eye anterior segment. Keywords: eye; development; anterior segment; mesenchyme; Six3; misexpression; chick.

Objective To determine the expression level of SLC7A11 gene (solute carrier family 7 member 11) in liver cancer and its adjacent tissues, and to understand the relationship between SLC7A11 gene and the clinical characteristics of liver cancer patients. Methods The expression level of SLC7A11 gene in 102 liver cancer tissues and their adjacent tissues was determined by semi-quantitative PCR and real-time PCR, and the relationship between SLC7A11 gene and age, sex, tumor size, HBV infection, lymph node metastasis, survival time and histological grade of liver cancer patients was analyzed. Results Semi-quantitative PCR of SLC7A11 gene in 85.0% (17/20) liver cancer tissues was significantly up-regulated compared with that in paracancerous tissues. Real-time PCR was used to detect SLC7A11 mRNA expression in 102 liver cancer and paracancerous tissues, and SLC7A11 mRNA expression was significantly up-regulated in 72.5% (74/102) liver cancer tissues (P<0.01). The average survival time of the SLC7A11 mRNA high expression group (64 cases) was 16 months, the average survival time of the low expression group was 22 months, and the survival time of the SLC7A11 mRNA high expression group was shorter (P<0.01). SLC7A11 mRNA expression was significantly up-regulated in liver cancer patients with tumors larger than 3 cm, SLC7A11 gene expression level was positively correlated with tumor size (P<0.05), but not with age, sex, HBV infection, lymph node metastasis or histological grade (all P>0.05). Conclusion SLC7A11 expression is up-regulated in hepatocellular carcinoma, which affects tumor proliferation and survival of patients, suggesting that SLC7A11 plays an important role in the occurrence and development of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Background: High expression of leucine-rich alpha-2-glycoprotein 1 (LRG1) is closely related to angiogenesis, which may play an important role in promoting invasion and metastasis. However, the current literature has yet to clarify the clinical significance of LRG1 in breast cancer. Objectives: The purpose of this work was to validate the correlation between LRG1 expression and prognosis in early breast cancer. Methods: We utilized an LRG1 detection agent in 330 cases of early breast cancer. The correlation of LRG1 expression with clinicopathological features, patient recurrence, and survival was investigated. Results: Compared with adjacent tissue samples, an elevated expression of LRG1 was observed in breast cancer samples. Moreover, LRG1 expression is associated with the number of lymphatic metastases and TNM pathological stage (p = 0.000, p = 0.000, respectively). For disease-free survival (DFS), the Kaplan-Meier curve indicated a poorer prognosis for the group with high LRG1 levels compared with the low LRG1 group (p = 0.000). A similar result was found for overall survival (OS; p = 0.000). The multivariate Cox regression indicated that LRG1 was still associated with DFS (HR 2.090, 95% CI 1.205–3.625, p = 0.009) and OS (HR 2.112, 95% CI 1.167–3.822, p = 0.013). The histological grade, TNM pathological stage, and molecular subtype were identified as independent risk factors affecting OS. Conclusion: In the malignant progression of breast cancer, high LRG1 levels are associated with lymphatic metastasis, histological grade, poor DFS, and poor OS. This study validates the use of LRG1 as a potential prognosis biomarker for early breast cancer. [ABSTRACT FROM AUTHOR]

Proper dorsal-ventral pattern formation of the optic cup is essential for vertebrate eye morphogenesis and retinotectal topographic mapping. Previous studies have suggested that midline tissue-derived Sonic hedgehog (Shh) molecules play critical roles in establishing the bilateral eye fields and in determining the proximal-distal axis of the eye primordium. Here, we have examined the temporal requirements for Shh during the optic vesicle to optic cup transition and after early optic cup formation in chick embryos. Both misexpressing Shh by virus and blocking Shh activity by antibodies resulted in disruption of ventral ocular tissues. Decreasing endogenous Shh signals unexpectedly revealed a sharp morphological boundary subdividing dorsal and ventral portions of the optic cup. In addition, Shh signals differentially influenced expression patterns of genes involved in ocular tissue specification (Pax6, Pax2, and Otx2) and dorsal-ventral patterning (cVax) within the ventral but not dorsal optic cup. Ectopic Shh suppressed expression of Bone Morphogenetic Protein 4 (BMP4) in the dorsal retina, whereas reducing endogenous Sonic hedgehog activity resulted in a ventral expansion of BMP4 territory. These results demonstrate that temporal requirements for Shh signals persist after the formation of the optic cup and suggest that the early vertebrate optic primordium may be subdivided into dorsal and ventral compartments. We propose a model in which ventrally derived Shh signals and dorsally restricted BMP4 signals act antagonistically to regulate the growth and specification of the optic primordium. [C] 2001 Academic Press Key Words: eye; chick; dorsal-ventral; Sonic hedgehog; BMP4; Vax; Pax6; Pax2; Otx2.

Based on the studies of the vascular tree's simulation and combined with the mixed bio-heat transfer model, the traditional Pennes bio-heat transfer equation was improved by using the blood perfusion considering the local heat transfer between the blood and the tissue. COMSOL Multiphysics was used to simulate, and the results of Pennes equation improved before and after were compared. The results showed that the improved Pennes equation could reflect the local influence of the vascular tree on organization's regional temperature distribution, while the traditional Pennes equation only described the homogeneous form of tissue temperature distribution. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression of STAT3 gene in patients with acute myeloid leukemia and its correlation with clinical characteristics., Methods: The real-time quantitative RT-PCR was used to detect the level of STAT3 mRNA in bone marrow samples from 38 newly diagnosed patients with acute myeloid leukemia(AML), and its relevance with clinical characteristics and prognosis were statistically analyzed. Western blot was employed to detect the STAT3 protein level in AML patients. The bone marrow cells from 15 healthy subjects were used as control., Results: At the mRNA level, the expression level of STAT3 in the AML group was significantly higher than that in control group (P<0.05). The level of STAT3 in AML group correlated positively with the risk factors of patients (P<0.01，r=0.592）. The STAT3 expression level in the high-risk group was statistically higher than that in the standard-risk group and the control group (P<0.01，P<0.01). Furthermor, there was no statistical difference between the sub-groups of AML (P>0.05). The median survival time of patients in STAT3 low expression group was logner than that in high expression group, but the difference was not statistically significant (P>0.005). The level of STAT3 protein in AML patients was significantly higher than that in control group (P<0.05）., Conclusion: The STAT3 gene is highly expressed in AML patients, which may be used as a predictor for high-risk of AML.

Objective: To investigate whether Artesunate(ART) can inhibit the proliferation of THP-1 cells and to explore the potential mechanism of its anti-leukemia effect., Methods: THP-1 cells were treated with 5 concentrations of Artesunate for 24 h, 48 h or 72 h. The viability of cells was detected with CCK-8 assay, apoptosis was assessed by using flow cytometry, and the STAT3, Caspase3 and Caspase8 protein levels were measured with Western blot ., Results: Compared with the control group, ART significantly inhibited the proliferation of THP-1 cells in a dose-dependent manner (r=0.9829, P<0.05). ART also increased the apoptosis of THP-1 cells. The results of Western blot showed that after treated with ART, the STAT3 protein expression in THP-1 cells was significantly down-regulated (P<0.01), and the expressions of Caspase3, cleaved Caspase3 and Caspase8 proteins were up-regulated(P<0.01)., Conclusion: Artesunate can inhibit the proliferation of THP-1 cells, which may relate with the down-regulation of STAT3 expression and the activation of Capase3 and Caspase8.

Aim: To comprehensively understand the underlying molecular events accounting for aberrant Wnt signaling activation in hepatocellular carcinoma (HCC)., Methods: This study was retrospective. The HCC tissue specimens used in this research were obtained from patients who underwent liver surgery. The Catalogue of Somatic Mutations in Cancer (COSMIC) database was searched for the mutation statuses of CTNNB1, TP53, and protein degradation regulator genes of CTNNB1. Dual-luciferase reporter assay was performed with TOP/FOP reporters to detect whether TP53 gain-of-function (GOF) mutations could enhance the transcriptional activity of Wnt signaling. Methylation sensitive restriction enzyme-quantitative PCR was used to explore the methylation status of CpG islands located in the promoters of APC, SFRP1, and SFRP5 in HCCs with different risk factors. Finally, nested-reverse transcription PCR was performed to examine the integration of HBx in front of LINE1 element and the existence of HBx-LINE1 chimeric transcript in Hepatitis B virus-related HCC. All results in this article were analyzed with the software SPSS version 19.0 for Windows, and different groups were compared by χ(2) test as appropriate., Results: Based on the data from COSMIC database, compared with other solid tumors, mutation frequency of CTNNB1 was significantly higher in HCC (P < 0.01). The rate of CTNNB1 mutation was significantly less frequent in Hepatitis B virus-related HCC than in other etiologies (P < 0.01). Dual-luciferase reporter system and TOP/FOP reporter assays confirmed that TP53 GOF mutants were able to enhance the transcriptional ability of Wnt signaling. An exclusive relationship between the status of TP53 and CTNNB1 mutations was observed. However, according to the COSMIC database, TP53 GOF mutation is rare in HCC, which indicates that TP53 GOF mutation is not a reason for the aberrant activation of Wnt signaling in HCC. APC and AXIN1 were mutated in HCC. By using methylation sensitive restriction enzyme-quantitative PCR, hypermethylation of APC was detected in HCC with different risk factors, whereas SFRP1 and SFRP5 were not hypermethylated in any of the HCC etiologies, which indicates that the mutation of APC and AXIN1, together with the methylation of APC could take part in the overactivation of Wnt signaling. Nested-reverse transcription PCR failed to detect the integration of HBx before the LINE1 element, or the existence of an HBx-LINE1 chimeric transcript, suggesting that integration could not play a role in the aberrant activation of Wnt signaling in HCC., Conclusion: In HCC, genetic/epigenetic aberration of CTNNB1 and its protein degradation regulators are the major cause of Wnt signaling overactivation.

A new sesquiterpenoid, 8α-hydroxy-6β-methoxy-1-oxoeremophila-7 (11), 9 (10) -diene-12, 8-olide (1) and five known compounds, petasin (2), caffeic acid (3), hepta-cosanol (4), β-sitosterol (5) and β-daucosterol (6) have been isolated from the roots of Ligularia intermedia. The compounds were isolated by column chromatography on silica gel and Sephadex LH-20, and identified based on spectral analyses (MS, 1H-NMR, 13C-NMR).

Mesenchymal stem cells (MSCs) possess multipotent capacity and exhibit immunoregulatory properties. In particular, MSCs can be easily isolated from various organs, can differentiate into various types of cells and generate regulatory T cells. Using human MSC derived from bone marrow and adipose tissue, we have clarified the following novel findings in vitro. 1) MSCs differentiated into osteoblasts or osteocytes under osteoblast-conditioned medium including the inflammatory stimuli such as IL-1. 2) The combination of IL-6 and soluble IL-6 receptor induced differentiation of MSCs to chondrocyte, whereas IL-17 inhibited their differentiation. 3) MSCs highly produced osteoprotegerin and inhibited osteoclastogenesis. Furthermore, we developed a local delivery system of MSCs by using nano-fiber scaffold. MSCs seeded on nano-fiber scaffold suppressed arthritis and bone destruction due to inhibition of systemic inflammatory reaction and immune response by suppressing T cell proliferation and reducing anti-type II collagen antibody production in vivo. Thus, our data may serve as a new strategy for MSC-based therapy in inflammatory diseases and an alternative delivery method for the treatment of destruction of bone and joints.

A new eremophilane derivative, (3aR,4R,5S,7S,7aS)-2-acetyl-7,7a-dihydroxy-3a,4-dimethyl-3a,4,5,6,7,7a-hexahydro-3H-inden-5-yl acetate (1) and three known compounds, 10beta-hydroxy-eremophil-7 (11)-en-12,8alpha-olide(2), beta-sitosterol (3) and beta-daucosterol(4) have been isolated from Ligularia intermedia. The compounds were isolated by column chromatography on silica gel and Sephadex LH-20,and identified on the basis of spectral analyses (MS, 1H-NMR, 13C-NMR).

This study is designed to investigate the effects of chinfloxacin hydrochloride (CFX) on the kinetics of HERG K+ channel. Whole cell patch clamp technique was used to record HERG K+ currents from HEK293 cells transiently transfected with cgi-HERG-GFP plasmids and channel kinetics were assessed in the absence and presence of CFX and moxifloxacin hydrochloride (MOX). Results demonstrated that the open state of HERG K+ channel was inhibited by CFX in a concentration- and time-dependent manner, with an IC50 of 162.1 +/- 14.2 micromol x L(-1), two folds higher than its positive control MOX. But there were no significant effects on channel kinetics. In addition, the inhibitory effect of CFX on HERG was enhanced when cells were subjected to altered extracellular K+ concentration.

Objective: To explore biological aspects of Tiam1 gene expression in nasopharyngeal carcinoma cells., Methods: Tiam1/C1199HA expression plasmids were transfected into nasopharyngeal carcinoma cells of C666-1 and CNE1 by lipofectamine2000. RT-PCR, real-time PCR and Western blot Analyses were performed to evaluate the expression of Tiam1 mRNA and protein levels, respectively. In vitro cell adhesion, wound healing and matrigel invasion assays were used to study the biological impact of Tiam1 on cell adhesion, mobility and invasion., Results: Tiam1 over expression significantly increased the abilities of adhesion, migratory and invasion of C666-1 and CNE1 cells, comparing with that of the control untransfected cells (P < 0.05)., Conclusion: Tiam1 expression correlates with the invasion and metastasis of nasopharyngeal carcinoma cells.

Objective: To investigate the relationship between the protein expression of T-lymphoma invasion and metastasis gene 1 (Tiam-1) and the biological behaviors of nasopharyngeal carcinoma (NPC)., Methods: Immunohistochemistry was performed to detect the expressions of Tiam-1 protein in 60 specimens of NPC tissue, 20 specimens of chronic nasopharyngitis (CN) tissue, and 6 tumor tissues from nude mice inoculated with metastatic human NPC cells., Results: The positivity rate and average score for Tiam-1 expression were significantly higher in NPC tissues than in CN tissue (63.33% vs 36.67%, 2.9167 +/- 1.3057 vs 0.7000 +/- 0.9234; chi(2)=20.429, P=0.001; t=7.0162, P=0.0000, respectively). No difference was found in Tiam-1 expression among NPC patients in different T stages (F=2.36, P=0.0811), while the expression differed significantly between the patients with lymph node metastasis and those without metastasis, and also between patients with organ metastasis and those without (P=0.0001). High Tiam-1 expressions were found in the tumor tissues in nude mice inoculated with metastatic NPC cells., Conclusion: Tiam-1 expression is closely associated with the invasiveness and metastasis of NPC, indicating that Tiam-1 is an important factor that promotes the invasion and metastasis of NPC.

Objective: To investigate the possible mechanism by which adiponectin influences the osteoclastogenesis., Methods: Human osteoblasts were cultured in vitro and adiponectin of the concentrations 0, 3, 10, and 30 microg/ml were added for 48 hours to investigate the dose-dependent effect on the mRNA and protein expression of osteoprotegerin (OPG) in osteoblasts, and adiponectin of the concentrations 0 or 30 microg/ml was added for 0-48 hours to investigate the time-dependent effect. Fluorescent quantitation PCR and ELISA were used to detect the expression of OPG and receptor activator of nuclear factor-kappaB ligand (RANKL). Other human osteoblasts were cultured with CD14 + peripheral blood mononuclear cells (PBMCs), and incubated together with adiponectin of the concentration of 30 microg/ml for 14 days, and then stained by antitartaric acid phosphatase, a marker enzyme of osteoclast., Results: The expression levels of mRNA and protein of OPG in osteoblasts were 100% +/- 9%, 68% +/- 7%, 47% +/- 8%, and 30% +/- 5%, and (9.2 +/- 0.3), (6.6 +/- 0.4), (4.1 +/- 0.4), and (2.6 +/- 0.4) ng/ml respectively after incubation with adiponectin of the concentrations of 0, 3, 10, and 30 microg/ml for 48 hours. The mRNA and protein expression levels of RANKL were 100% +/- 5%, 165% +/- 8%, 213% +/- 6%, and 316% +/- 10%, and (1.3 +/- 0.2), (2.1 +/- 0.1), (2.3 +/- 0.2), and (2.8 +/- 0.1) ng/ml respectively. Adiponectin inhibited the osteoblast OPG expression and promoted the osteoblast RANKL expression dose- and time-dependently (P < 0.05). Adiponectin induced the osteoclast formation in the coculture systems of osteoblast and PBMCs systems., Conclusion: Adiponectin increases osteoclast formation via stimulating RANKL and inhibiting OPG production in the osteoblasts, which may be one of the mechanisms adiponectin influences the osteoclastogenesis thereby.

Objective: To investigate the clinical significance of the determination of glycosylated hemoglobin (HbAlc) in gestational abnormal glucose metabolism., Methods: The level of fasting plasma glucose (FPG) and HbAlc in 540 normal gravida and 387 pregnant women with abnormal glucose metabolism was determined. Glucose challenge test (GCT) with 50 g glucose was done to those whose level of FPG was normal and 75 g glucose tolerance test (OGTT) was done to those whose GCT was abnormal. The levels of HbAlc of all subjects were assessed. And all subjects were divided into some groups according to the levels of HbA1c, to investigate the relationship between the complication and the levels of HbAlc., Results: The positive rate of HbAlc in abnormal glucose metabolism pregnant women was 20.9%. It was not sensitive if diagnosed only by this sign. Diagnosis by both FPG and this sign could solve this problem. The incidence of complication was increasing with the rise of HbA1c titre in the study group., Conclusion: The determination of HbAlc is important in the screening, diagnosing and assessing the prognoses of the gestational abnormal glucose metabolism.