Screening for metastasis-related genes in mouse melanoma cells through sequential tail vein injection.

Tumor metastasis, responsible for approximately 90% of cancer-associated mortality, remains poorly understood. Here in this study, we employed a melanoma lung metastasis model to screen for metastasis-related genes. By sequential tail vein injection of mouse melanoma B16F10 cells and the subsequently derived cells from lung metastasis into BALB/c mice, we successfully obtained highly metastatic B16F15 cells after five rounds of in vivo screening. RNA-sequencing analysis of B16F15 and B16F10 cells revealed a number of differentially expressed genes, some of these genes have previously been associated with tumor metastasis while others are novel discoveries. The identification of these metastasis-related genes not only improves our understanding of the metastasis mechanisms, but also provides potential diagnostic biomarkers and therapeutic targets for metastatic melanoma.

Accelerated Wound Healing in Diabetic Rat by miRNA-185-5p and Its Anti-Inflammatory Activity.

Aim: Addressing both inflammation and epithelialization during the treatment of diabetic foot ulcers is an important step, but current treatment options are limited. MiRNA has important prospects in the treatment of diabetic foot refractory wound ulcers. Previous studies have reported that miR-185-5p reduces hepatic glycogen production and fasting blood glucose levels. We herein hypothesized that miR-185-5p might play an important role in the field of diabetic foot wounds. Materials and Methods: MiR-185-5p in skin tissue samples from patients with diabetic ulcers and diabetic rats were measured using quantitative real-time PCR (qRT-PCR). The streptozotocin-induced diabetes rat model (male Sprague-Dawley rats) for diabetic wound healing was conducted. The therapeutic potential was observed by subcutaneous injection of miR-185-5p mimic into diabetic rat wounds. The anti-inflammation roles of miR-185-5p on human dermal fibroblast cells were analyzed. Results: We found that miR-185-5p is significantly downregulated in diabetic skin (people with DFU and diabetic rats) compared to controls. Further, in vitro upregulation of miR-185-5p decreased the inflammatory factors (IL-6, TNF-α) and intercellular adhesion molecule 1 (ICAM-1) of human skin fibroblasts under advanced glycation end products (AGEs). Meanwhile, the increase of miR-185-5p promoted cell migration. Our results also confirmed that the topical increase of miR-185-5p decreases diabetic wound p-nuclear factor-κB (p-NF-κB), ICAM-1, IL-6, TNF-α, and CD68 expression in diabetic wounds. MiR-185-5p overexpression boosted re-epithelization and expedited wound closure of diabetic rats. Conclusion: MiR-185-5p accelerated wound healing of diabetic rats, reepithelization, and inhibited the inflammation of diabetic wounds in the healing process, a potentially new and valid treatment for refractory diabetic foot ulcers.

Prognostic value of SH3PXD2B (Tks4) in human hepatocellular carcinoma: a combined multi-omics and experimental study.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and fatal cancers worldwide. HCC invasion and metastasis are crucial for its poor prognosis. SH3PXD2B is a scaffold protein and critical for intravascular and extravascular invasion and metastasis of various types of tumors. However, the role of SH3PXD2B in HCC progression remains unclear. METHODS: The levels of SH3PXD2B mRNA transcripts in the TCGA database and SH3PXD2B protein expression in the Human Protein Atlas were analyzed. Furthermore, the levels of SH3PXD2B expression in clinical samples were analyzed by quantitative RT-PCR and immunohistochemistry. The potential association of the levels of SH3PXD2B expression with clinicopathological characteristics, overall survival (OS), and recurrence-free survival (RFS) of HCC patients was analyzed. The impact of SH3PXD2B silencing by shRNA-based lentivirus transduction on the proliferation and invasion of human HCC Hep3B and Huh7 cells was determined. RESULTS: SH3PXD2B expression was up-regulated in HCC tissues in the TCGA and Human Protein Atlas as well as clinical samples, relative to that of non-tumor liver samples. The levels of SH3PXD2B expression in HCC tissues were significantly associated with higher HBV infection rate, higher HCC grades and TNM stages, higher Ki-67 expression, higher serum α-fetoprotein (AFP), a shorter OS and RFS of HCC patients. Functionally, SH3PXD2B silencing significantly inhibited the formation and function of invadopodia and the invasion of Hep3B and Huh7 cells, but did not affect their proliferation in vitro. CONCLUSIONS: Our data suggest that SH3PXD2B may promote the invasion and metastasis of HCC and be a valuable therapeutic target and biomarker for treatment and prognosis of HCC.

Taraxasterol suppresses the growth of human liver cancer by upregulating Hint1 expression.

Taraxasterol has potent anti-inflammatory and anti-tumor activity. However, the effect and potential mechanisms of Taraxasterol on the growth of human liver cancer have not been clarified. Histidine triad nucleotide-binding protein 1 (Hint1) is a tumor suppressor and its downregulated expression is associated with the development of cancer. Here, we report that Taraxasterol treatment significantly suppressed cell proliferation and induced cell cycle arrest at G0/G1 phase and apoptosis in liver cancer cells, but not in non-tumor hepatocytes. Furthermore, Taraxasterol upregulated Hint1 and Bax, but downregulated Bcl2 and cyclin D1 expression, accompanied by promoting the demethylation in the Hint1 promoter region in liver cancer cells. The effects of Taraxasterol were abrogated by Hint1 silencing and partially mitigated by Bax silencing, Bcl2 or cyclin D1 over-expression in HepG2 cells. Moreover, oral administration with Taraxasterol did not affect body weight, urinary protein levels, and the heart, liver, and kidney morphology in BALB/c mice but effectively inhibited the growth of implanted SK-Hep1 tumor in vivo. Collectively, we demonstrate that Taraxasterol inhibits the growth of liver cancer at least partially by enhancing Hint1 expression to regulate Bax, Bcl2, and cyclin D1 expression. Taraxasterol may be a drug candidate for the treatment of human liver cancer. KEY MESSAGES: Taraxasterol inhibits growth and induces apoptosis in human liver cancer cells. Taraxasterol enhances Hint1 expression by promoting demethylation in Hint1 promoter. Taraxasterol increases Hint1 levels to regulate Bax, Bcl2, and cyclinD1 expression. The effects of Taraxasterol are abrogated by Hint1 silencing in liver cancer cells. Taraxasterol inhibits the growth of subcutaneously implanted liver cancers in mice.

MicroRNA profile analysis of host cells before and after wild human rotavirus infection.

Rotavirus infection is an important cause of acute gastroenteritis in children, but the interaction between rotavirus and host cells is not completely understood. We isolated a wildtype (wt) rotavirus strain, ZTR-68(P [8] G1), which is derived from an infant with diarrhea in southwest China in 2010. In this study, we investigated host cellular miRNA expression profiles changes in response to ZTR-68 in early stage of infection to investigate the role of miRNAs upon rotavirus infection. Differentially expressed miRNAs were identified by deep sequencing and qRT-PCR and the function of their targets predicted by Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. A total of 36 candidate miRNAs were identified. Comparative analysis indicated that 29 miRNAs were significantly down-regulated and 7 were up-regulated after infection. The data were provided contrasting the types of microRNAs in two different permissive cell lines (HT29 and MA104). The target assays results showed that mml-miR-7 and mml-miR-125a are involved in anti-rotavirus and virus-host interaction in host cells. These results offer clues for identifying potential candidates in vector-based antiviral strategies. J. Med. Virol. 88:1497-1510, 2016. © 2016 Wiley Periodicals, Inc.

AMP-activated protein kinase-dependent autophagy mediated the protective effect of sonic hedgehog pathway on oxygen glucose deprivation-induced injury of cardiomyocytes.

Sonic hedgehog (Shh) pathway has been reported to protect cardiomyocytes in myocardial infarction (MI), but the underlying mechanism is not clear. Here, we provide evidence that Shh pathway induces cardiomyocytes survival through AMP-activated protein kinase-dependent autophagy. Shh pathway agonist SAG increased the expression of LC3-II, and induced the formation of autophagosomes in cultured H9c2 cardiomyocytes under oxygen glucose deprivation (OGD) 1 h and 4 h. Moreover, SAG induced a profound AMP-activated protein kinase (AMPK) activation, and then directly phosphorylated and activated the downstream autophagy initiator Ulk1, independent of the autophagy suppressor mammalian target of rapamycin (mTOR) complex 1. Taken together, our results have shown that Shh activates AMPK-dependent autophagy in cardiomyocytes under OGD, suggesting a role of autophagy in Shh-induced cellular protection.

Value of combined three dimensional constructive interference in steady state with phase-contrast MR in diagnosis of hydrocephalus children / 中华放射学杂志

Objective To investigate the value of combined 3D-constructive interference in steady state(3D-CISS) with phase-contrast MR(PC-MR) in diagnosis of hydrocephalus children.Methods We collected retrospectively 28 children with hydrocephalus who caused by obstructive membranes.They all underwent MR imaging examination with a 1.5 T consisting of 3D-CISS, conventional sequences and PC-MR.With the result of surgery and CT cisternography as gold standard,we analysised different sequence in the diagnosis of membranous obstruction.The results of obstructive were analysed by x2 test between 3D-CISS combined with PC-MR and conventional sequences.Results The study included 28 children, of whom 16 showed obstructive membranes in CSF pathways of ventricle and 12 displayed obstructive membranes in CSF pathways of cistern.Conventional sequences diagnosed obstructive membranes of 15 children, and obstructive membranes of 11 children were consistent with gold standard, and 4 cases were false positive.The 3D-CISS diagnosed obstructive membranes of 40, and 12 cases were false positive.There were significant difference between 3D-CISS combined with PC-MR and conventional sequence about obstructive membranes diagnosis of CSF pathways(x2=24.410, P=0.001).Conclusions Making use of jointing 3D-CISS sequence and PC-MR sequence successively, and we can diagnose the position of obstructive membrane for hydrocephalus, which can be helpful to select a perfect surgical approach.

Expression and biological significance of human kallikrein 6 in gastric cancer tissues.

AIM OF THE STUDY: This study aims to investigate the expression of human kallikrein 6 (hK6) in gastric cancer, gastric ulcer and normal gastric mucosa tissues and its biological significance. MATERIAL AND METHODS: The expression of hK6 in 15 normal gastric mucosa (NGM) tissues, 15 gastric ulcer (GU) tissues and 55 gastric carcinoma (GC) tissues was respectively detected by immunohistochemistry. The correlations between the expression of hK6 and the clinical pathological parameters of gastric cancer were also analyzed. RESULTS: Human kallikrein 6 was mainly expressed in cytoplasm. The positive rate of hK6 was significantly higher in gastric cancer tissues than that in gastric ulcer or normal gastric mucosa tissues (70.9%, 40% and 20%, respectively, p < 0.01). With the increase of the invasion depth of gastric cancer cells, aggravation of TNM stage and development of lymph node metastasis, the expression of hK6 increased significantly (p < 0.05 and p < 0.01). There was no obvious correlation between the expression of hK6 and sex, age, tumor diameter, histodifferentiation degree or primary pathological location of gastric cancer (p > 0.05). CONCLUSIONS: The overexpression of hK6 is related to the depth of invasion, lymph node metastasis and clinical stage of gastric carcinoma, which suggests that hK6 may act as a new marker of gastric cancer biological behavior.

Quantifying the amplitude of microvolt T wave alternans with sparse principal component analysis / 生物医学工程学杂志

T wave alternans in ECG is an important prediction factor for a sudden death. It is crucial in clinic to quantify the amplitude of T wave alternans. However, T wave alternans are highly non-stationary, which makes accurate quantification very difficult. In this study, we proposed a new method to improve the amplitude quantification. We identified T wave alternans by principal component analysis (PCA) with statistical test, and processed the principal components with T wave alternans further by imposing sparse constraint. We evaluated and compared our method against other 4 popular solutions on an international benchmark database. The results including rank correlation coefficient and relative error indicate that this sparse principal component (SPC) based method is better than others.

Study on motion artifact reduction based on periodic component analysis using ECG as a case / 生物医学工程学杂志

Motion artifacts are a main interference source of ambulatory physiology signals. The interference in wearable detection systems is more serious because of using dry electrodes. On account of the instantaneity in motion artifacts and periodicity in physiological signal, we presented a new method based on periodic component analysis for motion artifact reduction. The single channel signal is transformed into multi-channel signal with multi resolution analysis, and then periodic component analysis can help us to separate the normal physiological signal from motion artifacts. A case study in electrocardiogram (ECG) demonstrates that periodic component analysis is better than the empirical mode decomposition and adaptive filtering methods. Periodic component analysis as a time domain method can discriminate the signal with frequency aliasing, and recover the ECG waveform feature corrupted. This method can be easily extended to other physiological signal processing.

The expression, purification, and immunogenicity of a new chimeric virus-like particle.

Virus-like particles (VLPs) are highly immunogenic. In this study, gene fragments encoding hepatitis A virus (HAV) vp1 (aa 24-171), a hepatitis E virus (HEV) ORF2 gene fragment encoding aa 431-615, and gene fragments encoding a nine-peptide linker were spliced together. The spliced gene fragments were then inserted into the expression vector pBV220, resulting in the recombinant plasmid pBV-EA342, which expressed a 342-amino acid fusion protein. The fusion protein was expressed in Escherichia coli and specifically reacted to human hepatitis A- and E-positive sera. VLPs were formed during the renaturation of the EA342 fusion protein. The chimeric HAV and HEV VLPs were able to immunize KM mice, and they induced strong anti-HAV and anti-HEV humoral immune responses. These results are promising for future studies.

[Epidemiological study of high risk human papillomavirus infection in 25 to 54 years old married women in Beijing.].

OBJECTIVE: To investigate high risk human papillomavirus (HR-HPV) prevalence among married women in Beijing and to study the high risk factors. METHODS: During March 2007 to September 2008, a total of 6185 married women sampled from 137 communities in 12 districts were screened by HR-HPV DNA test and cytological test. The interview was carried out with unified questionnaires. The database was set up and twice entered in EpiData 3.0. After checked up, the data were analyzed in SPSS 15.0. RESULTS: (1) The HR-HPV infection rate was 9.89%. The HR-HPV infection rate of the city zone, the suburb and the exurb were 9.34%, 10.51% and 9.51% (P > 0.05). The HR-HPV infection rate of the native and the outlander were 9.53%, 11.30% (P < 0.05). (2) The age distribution of HR-HPV infection was that the rate was around 10% among 25 to 44 age groups, which was the highest (11.21%) in 30 to 34 age group; then the rate was descended as the age raising, the rate of 50 to 54 age group was the lowest (7.78%). (3) Multiple logistic regression showed that the related risk factors of HR-HPV infection mainly included 1000 RMB and above of family income per person per month, possessing more than 1 sexual partner of her husband, outlander and high levels of education. (4) The prevalence of cervical intraepithelial neoplasia (CIN) in HR-HPV positive group was significantly higher than that in HR-HPV negative group (29.76% vs 3.32%, P < 0.01). CONCLUSIONS: (1) The HR-HPV infection rate among aged 25 to 54 years was 9.9% and there was no significant difference in area distribution. (2) The high risk population which should strengthen screening was the married bearing-age women with high level of family income, outlander, high levels of education and her husband possessing more than 1 sexual partner. (3) HR-HPV infection is the main risk factor for CIN and cervical cancer, while does not provide a causal relationship with them. The high risk population should be checked regularly to understand the development of HR-HPV infection and CIN incidence.

Results of preservative free sodium hyaluronate and basic fibroblast growth factor eye drops in the treatment of dry eyes after ophthalmic surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the results of preservative free sodium hyaluronate and basic fibroblast growth factor(bFGF) eye drops in the treatment of dry eyes after eye operation.·METHODS: One hundred and thirty two patients of dryeyes underwent 149 different eye surgeries. The Schirmer test Ⅰ and tear break up time (BUT) were performed prior to surgery and post operatively after 2 weeks and after 4 weeks when the patients were using Oflaxacine, Tobramycin-dexamethasone eye drops. In addition, preservative free sodium hyaluronate and bFGF eye drops were given post operatively. The antibiotic-cortisone eye drops were stopped after the requirted period depending on the type of eye surgery done, and preservative free sodium hyaluronate and bFGF eye drops were stopped after 4 weeks.Then, after 5 weeks Schirmer test Ⅰ and BUT were done.·RESULTS: The Schirmer test Ⅰ and BUT results prior to surgery and after eye surgery showed a statistically significant improvement of the dry eye condition.·CONCLUSION: Usage of preservative free sodium hysluronate and bFGF eye drops help definitely in the management of dry eye after ophthalmic surgery.

Research on Precise Location Algorithm for QRS in ECG / 航天医学与医学工程

Objective To research the precise location algorithm of onset and end of one wave for QRS in ECG. Methods During monitoring the ambulatory electrocardiograph (AECG),it was necessary to design new automatic analysis algorithms. The windows formed by filtering and integrating process could be considered as the fiducially mark. From the window,the apex of Q wave and S wave could be recognized. Results Introducing an auxiliary line from the apex,we could judge the boundary of the Q and S wave with the distance from ECG curve to the line. Conclusion Many cases studies inelicate that the algorithm is of low level locating error,about one sample point,and the accuracy of judgement of S wave boundary is raised obviously compared with the same kind of software in the world.

Study Progress of Effect of Curcuma on Anti-Helicobacter Pylori / 实用儿科临床杂志

Helicobacter pylori(Hp) is an important pathogenic factor in chronic gastritis,peptic ulcer and gastric cancer.With the extensive use of broad-spectrum atibiotics in recent years,the antibiotic resistence of Hp was increasing,together with many side effets and low patient compliance,so the study of new anti-Hp drugs became a research hotspot.Domestic and foreign scholars had extracted active anti-Hp ingredients from the traditional Chinese drug curcuma,they hope to open a new way for the treatment of Hp infection.This paper was to make a brief overview on the study progress of effect of curcuma on anti-Hp.