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Xiaoyu Li,1,* Lin Wu,2,* Zhifang Yang,1 Yunyun Hu,1 Chun Zhou,1 Ri Ji1 1Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Geriatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chun Zhou; Ri JiDepartment of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of ChinaTel/Fax +86 021 63846590; Tel +86 18717771587Email zc40343@rjh.com.cn; jiri_1980@163.comObjective: To evaluate the foot microcirculation in type 2 diabetes mellitus (T2DM) and impaired glucose tolerance patients (IGT) with contrast-enhanced ultrasound (CEUS).Methods: The study included 37 patients with T2DM but without diabetic foot (DM group), 15 patients with impaired glucose tolerance (IGT group) and 10 elderly males with normal fasting blood glucose (FBS) and negative glucose tolerance tests (control group). Color Doppler flow imaging (CDFI) and CEUS were performed on the right foot great toes for detecting the blood perfusion performance. CEUS images were recorded and parameters of CDFI and flow time-intensity curves (TICs) were analyzed by the Student’s t-test.Results: There was no significant difference in CDFI parameters pulse index and peak systolic blood flow velocity (PSV) among the three groups (P > 0.05). Compared with control group, CEUS images of IGT and DM groups showed lower microvascular density and were pale. Peak intensity (PI) and area under time-intensity curve (AUC) in control, IGT and DM groups were decreased gradually (PI 46.36± 10.96 vs 35.26± 11.65 vs 28.15± 7.94, P = 0.001, AUC 5.12± 1.02 vs 3.25± 1.60 vs 2.81± 1.20, P = 0.001). The arrival times (AT) and time to peak (TTP) tended to be increased with the extension of DM course, but the difference was not statistically significant (AT, P = 0.260, TTP, P = 0.481).Conclusion: CEUS, as a noninvasive and valuable technique, could detect the alterations in foot microcirculation of DM and IGT patients.Keywords: type 2 diabetes mellitus, impaired glucose tolerance, contrast-enhanced ultrasound, microcirculation

BACKGROUND: Chronic hepatitis B is the most common chronic liver disease in China. For patients with chronic hepatitis B, steatosis increases the risk of cirrhosis and hepatocellular carcinoma. This study aimed to analyze and compare the clinical value of a newly developed ultrasound attenuation parameter, liver steatosis analysis (LiSA), acquired by Hepatus (Mindray, China), and controlled attenuation parameter (CAP), a widely used ultrasound attenuation parameter acquired by FibroScan (Echosens, France), for grading liver steatosis in patients with chronic hepatitis B infection. METHODS: A total of 203 patients were divided into two groups according to liver fat content validated by liver biopsy: group 1 (liver fat content 0.7) for steatosis ≥10%, and the performance of LiSA was significantly better than CAP (AUC: 0.859 vs. 0.801, P=0.048). Using optimal cut-off points, LiSA had specificity and sensitivity of 96.23% and 76.08%, respectively, for the diagnosis of steatosis ≥10%, compared to 91.53% and 72.10%, respectively, for CAP. CONCLUSIONS: LiSA and CAP are extremely efficient tools for assessing liver steatosis, even at a low grade. Both parameters are non-invasive, inexpensive, and easy to use, and can provide immediate results with high sensitivity.

Renin-angiotensin system (RAS) signaling has been implicated in the development of cancer. The new RAS ACE2/Ang-(1-7)/Mas axis antagonizes the classical ACE/Ang II/AT1R axis. Ang-(1-7) has pleiotropic roles in lung cancer including suppressing proliferation, angiogenesis, and metastasis. This research was designed to investigate the effect of Ang-(1-7) on tumor-associated angiogenesis in DDP-resistant lung cancer cell lines. We first established acquired DDP-resistant cell lines A549 (A549-DDP) and LLC (LLC-DDP). We next performed RT-qPCR, western blot, ELISA, tube formation, microvessel density detection, immunohistochemistry, and tumor formation assays. The results showed that the mRNA and protein levels of RAS components and vascular endothelial growth factor A (VEGFa) were lessened in the A549/LLC-DDP+Ang-(1-7) group compared with the A549/LLC-DDP group. This effect could be blocked by the MAS receptor antagonist A779. The data revealed that Ang-(1-7) could perform its antiangiogenic function by PI3K/AKT and MAPK pathways. Furthermore, the impact of Ang-(1-7) on tumor-associated angiogenesis has been confirmed in lung cancer xenograft model with acquired DDP resistance. These results provide a theoretical basis for designing therapeutic strategies for targeting Ang-(1-7) in the treatment of NSCLC.

To analyze the relationship between cervical vertigo and vestibular function evaluated by vestibular evoked myogenic potentials(VEMPs) and analyze the correlations between cervical vertigo and vestibular dysfunction, discuss the related factors of cervical vertigo and guide the clinical treatment of patients with cervical vertigo.A total of 75 patients with cervical vertigo as the main complaint in the outpatient clinic of the Second Hospital of Shanxi Medical University from August 2019 to July 2020 were set as the diseased group, and 60 patients without cervical and vestibular related diseases in the hospital were selected to set as non-diseased group. The age of diseased group was 12 to 70 years with an average of (46.40±10.91) years, including 25 males and 50 females;and the age of non-diseased group was 22 to 60 years with an average of(43.78±7.75) years, including 19 males and 51 females. VEMPs were performed in the two groups. The data of VEMPs were collected and the results were compared and analyzed. The patients with abnormal cervical myogenic vestibular evoked myogenic potential (cVEMP) were divided into light, moderate and severe groups. The correlation between VEMPs and cervical vertigo and its severity were analyzed by statistical method.(1)The severity of cervical vertigo in diseased group:33 cases of mild, 34 cases of moderate, 8 cases of severe; cVEMP examination:62 cases were positive and 13 cases were negative, including 13 cases of mild, 33 cases of moderate, 16 cases of severe. The cVEMP of non-diseased group:4 cases were positive and 56 cases were negative.(2) The level of cVEMP in diseased group was higher than that in non-diseased group (It is feasible to evaluate the relationship between cervical vertigo and vestibular function by VEMPs. For patients with cervical vertigo, the higher the severity, the greater the positive rate of VEMPs, which indicates that it has a greater impact on vestibular function. The treatment of patients with cervical vertigo should be the combination of cervical rehabilitation and vestibular function.

Objectives This systematic review aimed to evaluate the efficacy and safety of Tao-Hong Siwu Tang (TST) for the treatment of primary dysmenorrhea. Methods We searched four English databases (MEDLINE, EMBASE, Allied and Complementary Medicine Database, and Cochrane Central Register of Controlled Trials [CENTRAL, Cochrane Library]), three Chinese databases (China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Periodical Database), two Korean databases (Oriental Medicine Advanced Searching Integrated System and Korean traditional Knowledge Portal), and one Japanese database (Citation Information by NII). All randomized controlled trials (RCTs) using TST or modified TST (MTST) were included. Three independent reviewers extracted the data, assessed the risk of bias according to the Cochrane criteria, and performed a meta-analysis. Results A total of 85 possibly relevant articles were identified, and five trials met our inclusion criteria. The meta-analysis showed a favorable effect of MTST compared to non-steroidal anti-inflammatory drugs (NSAIDs) (n = 486, risk ratio [RR] = 1.53, 95% confidence interval [95% CI] = 1.37–1.72, I2 = 39%). Among the included trials, one RCT showed superior effects of MTST on primary dysmenorrhea recurrence rate compared to NSAIDs (n = 246, RR = 0.31, 95% CI = 0.15–0.63, P = 0.001). Another RCT revealed a beneficial impact of oral contraceptives (OCs) used in combination with TST compared to OCs alone (n = 60, RR = 1.35, 95% CI = 1.02–1.79, P = 0.04). Conclusion This systematic review and meta-analysis provides moderate quality evidence for the superiority of MTST over NSAIDs as well as that of TST plus OCs over OCs in the treatment of primary dysmenorrhea.

Limb hemiplegia is one of the common sequelae of stroke. Physical therapy-based rehabilitation training can rapidly improve limb functioning and muscle strength. This study investigated the effect of physical therapy on the recovery of upper limb motor function by employing a literature search and meta-analysis.We searched Embase, The Cochrane Central Register of Controlled Trials library, Wiley online library, PubMed, Ovid, and Clinicaltrials.org for randomized controlled trial (RCT) studies and performed an electronic search with the keyword combinations 'physical therapy/rehabilitation''stroke/post-stroke''upper extremity/upper limb'. After screening the literature for inclusion criteria and assessing the risk of bias, Revman 5.4 software was used for the analysis and to obtain forest and funnel plots.A total of 15 RCTs with 1,081 patients were included in the quantitative analysis for this study. The meta-analysis results showed that compared with conventional therapy, physical therapy improved the upper limb Fugl-Meyer Assessment for Upper Extremity (FMA) scores in convalescent stroke patients (MD =7.27, 95% CI: 4.23-10.32, Z=4.68, P0.00001), and increased the Functional Independence Measure (FIM) scores (MD =18.82, 95% CI: 6.34-31.30, Z=2.96, P=0.003), the Action Research Arm Test (ARAT) scores (MD =8.84, 95% CI: 6.53-11.15, Z=7.50, P0.00001), and the Box and Block Test (BBT) scores (MD =6.11, 95% CI: 1.18-11.04, Z=2.43, P=0.02) of patients during the rehabilitation period.The use of physical therapy-based rehabilitation training in the recovery period for stroke patients with hemiplegia can improve upper limb movement ability, increase muscle strength, reduce limb pain, and improve the quality of life.

Background We investigated whether glycemic control affects the relation between endothelial dysfunction and coronary artery disease in patients with type 2 diabetes mellitus (T2DM). Methods In 102 type 2 diabetic patients with stable angina, endothelial function was evaluated using brachial artery flow-mediated dilation (FMD) with high-resolution ultrasound, and significant stenosis of major epicardial coronary arteries (≥ 50% diameter narrowing) and degree of coronary atherosclerosis (Gensini score and SYNTAX score) were determined. The status of glycemic control was assessed by blood concentration of glycated hemoglobin (HbA1c). Results The prevalence of significant coronary artery stenosis (67.9% vs. 37.0%, P = 0.002) and degree of coronary atherosclerosis (Gensini score: 48.99 ± 48.88 vs. 15.07 ± 21.03, P 0.05). Conclusion Poor glycemic control negatively influences the association of endothelial dysfunction and coronary artery disease in T2DM patients.

Liver fibrosis is evaluated to assess the prognosis and guide the treatment of chronic hepatitis B (CHB). To compare the efficiency of 2 transient elastography techniques for grading liver fibrosis in CHB: visual transient elastography (ViTE) with real-time image guidance and FibroScan (FS) with no image guidance. All of the CHB patients in this study underwent both FS and ViTE examinations. The final diagnosis was based on the histological findings of a liver biopsy. According to the severity of liver fibrosis (based on the Scheuer criteria), the area under the receiver operating characteristic curve values for diagnostic efficiency were calculated for the 2 elastography techniques. This study enrolled 227 patients (79 [39.1%] women; mean age, 45.8 ± 16.8 years). The ViTE and FS liver elasticity measurements were highly correlated with liver fibrosis stage (r = 0.852 and r = 0.813, respectively). The area under the receiver operating characteristic curve value was larger for ViTE compared with FS, with respect to differentiating liver fibrosis stage, but not significantly (P > 0.05). The ViTE and FS can be used to detect and stage liver fibrosis. ViTE, easier and quicker to perform with superior interoperator reproducibility, is a stable and reliable elastography technique that benefits from real-time visual guidance.

Damage to the sensory hair cells and the spiral ganglion neurons of the cochlea leads to deafness. Induced pluripotent stem cells (iPSCs) are a promising tool to regenerate the cells in the inner ear that have been affected by pathology or have been lost. To facilitate the clinical application of iPSCs, the reprogramming process should minimize the risk of introducing undesired genetic alterations while conferring the cells the capacity to differentiate into the desired cell type. Currently, reprogramming induced by synthetic mRNAs is considered to be one of the safest ways of inducing pluripotency, as the transgenes are transiently delivered into the cells without integrating into the genome. In this study, we explore the ability of integration-free human-induced pluripotent cell lines that were reprogrammed by mRNAs, to differentiate into otic progenitors and, subsequently, into hair cell and neuronal lineages. hiPSC lines were induced to differentiate by culturing them in the presence of fibroblast growth factors 3 and 10 (FGF3 and FGF10). Progenitors were identified by quantitative microscopy, based on the coexpression of otic markers PAX8, PAX2, FOXG1, and SOX2. Otic epithelial progenitors (OEPs) and otic neuroprogenitors (ONPs) were purified and allowed to differentiate further into hair cell-like cells and neurons. Lineages were characterised by immunocytochemistry and electrophysiology. Neuronal cells showed inward Na+ (INa) currents and outward (Ik) and inward K+ (IK1) currents while hair cell-like cells had inward IK1 and outward delayed rectifier K+ currents, characteristic of developing hair cells. We conclude that human-induced pluripotent cell lines that have been reprogrammed using nonintegrating mRNAs are capable to differentiate into otic cell types.

Macrophage recruitment has emerged as the crucial force driving the initiation and progression of atherosclerotic lesions. Therefore, the identification of macrophages in plaques is of vital importance for identifying vulnerable plaques, and noninvasive imaging methods are particularly desirable. Some studies have reported that MRI can detect plaque macrophages through targeted nanoparticles, but it is still hard for an US to detect macrophages in atherosclerotic plaque. In this study, anti-CD68 receptor-targeted Fe-doped hollow silica nanoparticles (CD68-Fe-HSNs) were fabricated as a dual-modal US/MRI contrast agent for identifying macrophages of aorta ventralis atherosclerotic plaques in ApoE-/- mice, confirmed by immunofluorescence and bio-TEM. This system possesses biodegradable characteristics even though it is an inorganic mesoporous nanosystem, indicating its potential high biocompatibility for further in vivo research. We expect that these dual-modal US/MRI nanoparticles will play a role in assessing vulnerable plaque in future research studies.

Objective. Inorganic polyphosphates (polyP) play a multitude of roles in mammalian biology. PolyP research is hindered by the lack of a simple and sensitive quantification method. The aim of this study was to develop a robust method for quantifying the low levels of polyP in mammalian tissue such as cartilage, which is rich in macromolecules that interfere with its determination. Design. Native and in vitro formed tissues were digested with proteinase K to release sequestrated polyP. The tissue digest was loaded on to silica spin columns, followed by elution of bound polyP and various treatments were assessed to minimize non-polyP fluorescence. The eluent was then quantified for polyP content using fluorometry based on DAPI (4′,6-diamidino-2-phenylindole) fluorescence shift occurring with polyP. Results. Proteinase K pretreatment reduced the inhibitory effect of proteins on polyP recovery. The eluent was contaminated with nucleic acids and glycosaminoglycans, which cause extraneous fluorescence signals. These were then effectively eliminated by nucleases treatment and addition of concentrated Tris buffer. PolyP levels were quantified and recovery ratio determined using samples spiked with a known amount of polyP. This silica spin column method was able to recover at least 80% of initially loaded polyP, and detect as little as 10−10 mol. Conclusions. This sensitive, reproducible, easy to do method of quantifying polyP will be a useful tool for investigation of polyP biology in mammalian cells and tissues. Although the protocol was developed for mammalian tissues, this method should be able to quantify polyP in most biological sources, including fluid samples such as blood and serum.

Bone morphogenetic proteins (BMPs) are growth factors that have important functions in cell proliferation, migration and differentiation. To date, BMP pathway activation has been found in multiple human tumors and is associated with enhanced malignant tumor growth and metastasis. BMP activity is tightly regulated by a family of soluble extracellular secreted BMP modulators. Twisted gastrulation BMP signaling modulator 1 (TWSG1) is a direct BMP regulator that is required for the full signaling activity of BMPs. However, the functions and mechanisms of TWSG1 in papillary thyroid cancer (PTC) metastasis have not been reported. TWSG1 expression was detected in 44 PTC tissues with lymph node metastasis (LNM) and 56 PTC tissues without LNM using quantitative real-time polymerase chain reaction (qRT-PCR). Gain- and loss-of-function approaches were used to assess the biological function of TWSG1 in PTC cells. Matrigel assays demonstrated the effect of tumor cell-derived TWSG1 on endothelial cell function. Our results showed that TWSG1 expression was significantly enhanced in PTC with LNM compared to that in PTC without LNM. TWSG1 knockdown inhibited migration, invasion and proliferation of PTC cells. Additionally, TWSG1 suppression impaired the tumor cell-induced endothelial cell sprout formation. We found that TWSG1 signaling may be transduced by the BMP target transcription factor inhibitor of DNA binding 1 (Id1) and matrix metalloproteinases (MMPs) 2 and 9. In conclusion, TWSG1 was highly expressed in metastasized PTC; tumor growth, migration and invasion were dependent on TWSG1, and it may be a new diagnostic and therapeutic target for PTC.

Background Multimodal contrast agents with low toxicity and targeted modification have opened up new possibilities for specific imaging of breast cancer and shown broad application prospects in biomedicine and great potential for clinical transformation. In this work, a potential multifunctional imaging agent was developed by doping Fe into hollow silica nanoparticles (HS-Fe NPs), followed by modification with specific anti-HER2 antibodies, enabling the NPs to have dual-mode ultrasound (US)–magnetic resonance (MR)-specific imaging capacity with low toxicity. Methods Anti-HER2 antibodies were conjugated to silane–polyethylene glycol (PEG)–COOH-modified HS-Fe (HS-Fe-PEG) NPs to produce HER2-targeted HS-Fe-PEG (HS-Fe-PEG-HER2) NPs. The toxicity of HS-Fe-PEG-HER2 NPs on targeted cells in vitro and blood and organ tissue of mice in vivo was investigated. Distribution in vivo was also studied. Confocal laser-scanning microscopy and flow cytometry were used to evaluate the targeting ability of HS-Fe-PEG-HER2 NPs in vitro. US and MR instruments were used for imaging both in vivo and in vitro. Results The obtained HS-Fe-PEG-HER2 NPs (average diameter 234.42±48.76 nm) exhibited good physical properties and biosafety. In solution, they showed obvious enhancement of the US signal and negative contrast in T2-weighted MR imaging. The binding rate of HS-Fe-PEG-HER2 NPs to targeted cells (SKBR3) was 78.97%±4.41% in vitro. US and MR imaging in vivo confirmed that the HS-Fe-PEG-HER2 NPs were delivered passively into the tumor region of SKBR3 and bound specifically to tumor cells. Target enhancement was better than untargeted and targeted competition groups. Conclusion HS-Fe-PEG-HER2 NPs have potential as a low-cytotoxicity and dual-mode US–MR-specific imaging agent.

Xiaoyu Li,* Shujun Xia,* Wei Zhou, Ri Ji, Weiwei Zhan Ultrasound Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China *These authors contributed equally to this work Background: Multimodal contrast agents with low toxicity and targeted modification have opened up new possibilities for specific imaging of breast cancer and shown broad application prospects in biomedicine and great potential for clinical transformation. In this work, a potential multifunctional imaging agent was developed by doping Fe into hollow silica nanoparticles (HS-Fe NPs), followed by modification with specific anti-HER2 antibodies, enabling the NPs to have dual-mode ultrasound (US)–magnetic resonance (MR)-specific imaging capacity with low toxicity.Methods: Anti-HER2 antibodies were conjugated to silane–polyethylene glycol (PEG)–COOH-modified HS-Fe (HS-Fe-PEG) NPs to produce HER2-targeted HS-Fe-PEG (HS-Fe-PEG-HER2) NPs. The toxicity of HS-Fe-PEG-HER2 NPs on targeted cells invitro and blood and organ tissue of mice invivo was investigated. Distribution invivo was also studied. Confocal laser-scanning microscopy and flow cytometry were used to evaluate the targeting ability of HS-Fe-PEG-HER2 NPs invitro. US and MR instruments were used for imaging both invivo and in vitro.Results: The obtained HS-Fe-PEG-HER2 NPs (average diameter 234.42±48.76 nm) exhibited good physical properties and biosafety. In solution, they showed obvious enhancement of the US signal and negative contrast in T2-weighted MR imaging. The binding rate of HS-Fe-PEG-HER2 NPs to targeted cells (SKBR3) was 78.97%±4.41% invitro. US and MR imaging invivo confirmed that the HS-Fe-PEG-HER2 NPs were delivered passively into the tumor region of SKBR3 and bound specifically to tumor cells. Target enhancement was better than untargeted and targeted competition groups.Conclusion: HS-Fe-PEG-HER2 NPs have potential as a low-cytotoxicity and dual-mode US–MR-specific imaging agent. Keywords: dual-mode, ultrasound imaging, magnetic resonance imaging, HER2, breast cancer

An unsexed, 16-year-old blue-and-gold macaw (Ara ararauna) was presented for evaluation of rapidly growing subcutaneous masses at the left tibiotarso-tarsometatarsal joint. Results of incisional biopsy were diagnostic for an intermediate-grade soft-tissue sarcoma. A distal-femoral amputation was performed and the leg was submitted for histopathology. Histopathologic examination confirmed the biopsy diagnosis and revealed neoplastic spread into the bone marrow cavity of the tibiotarsus. Excisional margins were complete. The macaw recovered and did well until it died suddenly 32 months after surgery. At necropsy, death was attributed to acute hepatic hemorrhage. No recurrence or metastasis of the sarcoma was identified.

Background Dangguijagyag-san, also known as Dangguishaoyao-san in Chinese and Toki-shakuyakui-san in Japanese, has been frequently used to treat symptoms associated with dysmenorrhea. The purpose of this trial is to evaluate the efficacy and safety of the herbal medicine, Dangguijagyag-san, relative to those of active control, Gamisoyo-san, and a placebo control for primary dysmenorrhea. Methods This protocol details a randomized, double-blind, parallel-group, multi-center, investigator-initiated, controlled trial evaluating treatment of primary dysmenorrhea. Two hundred and forty participants will be randomly divided into one of three groups: 1) the Dangguijagyag-san experimental group (EG) (n = 105), 2) the Gamisoyo-san active control group (ACG) (n = 30), and 3) the placebo control group (PCG) (n = 105). The interventions will be administered for two menstrual cycles, and the follow-up will be carried out for the following six menstrual cycles. The primary outcomes are difference in response rates between the EG and the ACG (non-inferiority comparison) and difference in changes from baseline in average pain intensity measured by the visual analogue scale between the EG and PCG (superiority comparison). The secondary outcomes are pain scores derived from pain assessment tools (verbal multidimensional scoring system, retrospective symptom scale, and short form McGill pain questionnaire), dosage of analgesics, pattern diagnosis questionnaires, and short form 36 health survey. Adverse events and vital signs will be checked at every visit, and laboratory tests will be performed for safety evaluation. Discussion The results of this clinical trial will offer evidence for the efficacy and safety of Dangguijagyag-san for primary dysmenorrhea. Trial registration Clinical Research Information Service of Korea: KCT0003005

Development of functional theranostic platform for systemic contrast-enhanced diagnostic imaging and therapy is of great necessity in nanomedicine. However, synthesizing the biocompatible theranostic agents with enhanced merits in imaging and therapy via a facile and green way is still highly challenged. Here, we report a novel theranostic agent based on colloidal polydopamine/Au (PDA/Au) hollow spheres, which are synthesized with combined use of PDA chemistry and sacrificial template techniques. Colloidal polystyrene (PS) spheres serve as the templates with coatings of a PDA shell and Au nanoparticles in sequence, which are subsequently removed with trichloromethane, giving rise to colloidal PDA/Au hollow spheres. Colloidal PDA/Au hollow spheres exhibit excellent contrast enhancement for ultrasound imaging, and can serve as the near-infrared (NIR) photoabsorbers for the effective photothermal ablation of 4 T1 breast cancer cells in vitro with minor cytotoxicity to living cells. This method suggests a novel avenue for theranostic treatment in oncology.

Adrenomedullin (AM) is a peptide expressed in all body tissues, and its related receptors are increased in liver fibrosis. In this study, we evaluated the effect of AM deficiency on liver fibrogenesis induced by CCl 4 using AM heterozygous (HT) mice. The animals received a single injection of CCl 4 or olive oil for the acute experiment, and received CCl 4 or olive oil three times a week for 6 weeks for the chronic experiment. Fibrosis was accessed using histopathological analysis and the western blot. The AM HT mice showed mild pericentrilobular degeneration when compared to the AM wild type (WT) mice. In the acute experiment, there was no significant difference between the AM WT and AM HT mice. However, in the chronic experiment, the CCl 4 -treated AM HT mice showed more severe liver fibrosis than that of the CCl 4 -treated AM WT mice. The AST and ALT levels of the AM HT CCl 4 group were higher than those of the AM WT CCl 4 group. Additionally, the collagen deposition, α-SMA protein and TGF-β protein were increased in the AM HT CCl 4 group when compared to the AM WT CCl 4 group. The AM HT mice also exhibited severe lipid peroxidation through the GSH decrement. Taken together, our data suggest that AM deficiency increases the susceptibility to liver fibrosis induced by CCl 4 , indicating a novel therapeutic target for patients with liver fibrosis.

The comprehensive evalution of the different plant communities diversity and degradation of Prairie Meadows. The result showed that, with the increase of grassland degradation degree, the composition of communities species was single, quantity gradually decreased, the change of species important value was obvious, the communities coverage, the communities height, ground production value was obvious decreasing trend; Plant communities a:diversity index, Margalef abundance, Simpson:advantage index Shanon-wiener:diversity index and Pielou:a verage index all have obvious decreasing, communities of similarity index has increasing trend. At the basis of indicator System fuzzy comprehensive evaluation review that the rang of indicating degree respectively:vegetation communities fence:1～0.7370,light grazing areas:0.7370～0.8117,moderate grazing areas:0.8117～0.4890,heavy grazing area:0.4890～0.

Antimicrobial peptides (AMPs) are naturally produced antibiotics that play important roles in host defense mechanisms. These proteins are found in variety of animal and plant species. The antibiotic effects of AMPs are gaining attention for use in human medicine. In this study, the antimicrobial effects of coprisin, a novel AMP isolated from the dung beetle (Copris tripartitus), were evaluated. The peptide was used to treat rats with wounds infected with Staphylococcus aureus. Coprisin accelerated wound closure both grossly and microscopically compared with the untreated group. Additionally, treatment with this peptide decreased phosphorylated-Smad2/3 (p-Smad2/3) levels, a downstream factor of the transforming growth factor-β signaling pathway which is believed to inhibit reepithelization, in the nucleus and cytoplasm of regenerating cells. Moreover, increased cell populations and angiogenesis were observed in lesions treated with coprisin, suggesting that this peptide promotes wound healing via its antimicrobial activity against S. aureus. Our results demonstrated that coprisin is a potential therapeutic agent that can possibly replace traditional antibiotics and overcome microbial resistance.

The constraint relation of three-key-equipment, including coal cutter, scraper conveyor and hydraulic support, applied in the safe, high-producing and high-efficient fully mechanized mining face, was introduced; the composition principle of electro-hydraulic control system, embedded in the hydraulic support, was discussed, and the design scheme of the composition and hardware system about the electro-hydraulic control unit was presented in this paper. And finally the scheme achieved the target that we can control and monitor the working condition in near real-time, on the ground, in the crossheading and in front of the mining face.

Background The dysregulation of long noncoding RNAs (lncRNAs) has been identified in a variety of cancers. An increasing number of studies have found the critical role of lncRNAs in the regulation of cellular processes, such as proliferation, invasion and differentiation. Long noncoding RNA papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3) is a novel lncRNA that was primarily detected in papillary thyroid carcinoma. However, the biological function and molecular mechanism of lncRNA PTCSC3 in glioma are still unknown. Methods The expression level of lncRNA PTCSC3 in human microglia and glioma cell lines was examined using quantitative real-time polymerase chain reaction (qRT-PCR). The influence of lncRNA PTCSC3 on cell proliferation were studied using the cell counting kit-8, and cell cycle and apoptosis were analyzed by flow cytometry assays. The migration and invasion abilities were investigated by transwell and wound healing assays. The target genes of lncRNA PTCSC3 were explored by qRT-PCR, immunofluorescence and western blot. Results LncRNA PTCSC3 was significantly downregulated in glioma cell lines. The overexpression of lncRNA PTCSC3 suppressed proliferation and induced apoptosis in U87 and U251 cells. Additionally, the overexpression of lncRNA PTCSC3 inhibited the migration and invasion of U87 and U251 cells. Moreover, lncRNA PTCSC3 inhibited the epithelial-mesenchymal transition of U87 cells. The study also demonstrated that LRP6, as a receptor of the Wnt/β-catenin pathway, was a target of lncRNA PTCSC3. By evaluating the expression levels of Axin1, active β-catenin, c-myc, and cyclin D1, the study indicated that lncRNA PTCSC3 inhibited the activation of the Wnt/β-cateninpathway through targeting LRP6. Conclusions LncRNA PTCSC3 inhibits the proliferation and migration of glioma cells and suppresses Wnt/β-catenin signaling pathway by targeting LRP6. LncRNA PTCSC3 is a potential therapeutic target for treatment of glioma. Electronic supplementary material The online version of this article (doi:10.1186/s12883-017-0813-6) contains supplementary material, which is available to authorized users.

We observed the biphasic production of ethylene and reactive oxygen species (ROS) in susceptible tobacco (Nicotiana tabacum ‘Wisconsin 38’) plants after shoot inoculation with Phytophthora parasitica var nicotianae. The initial transient increase in ROS and ethylene at 1 and 3 h (phase I), respectively, was followed by a second massive increase at 48 and 72 h (phase II), respectively, after pathogen inoculation. This biphasic pattern of ROS production significantly differed from the hypersensitive response exhibited by cryptogein-treated wild-type tobacco plants. The biphasic increase in ROS production was mediated by both NADPH oxidase isoforms, respiratory burst oxidase homolog (Rboh) D and RbohF. Conversely, different 1-aminocyclopropane-1-carboxylic acid synthase members were involved in specific phases of ethylene production: NtACS4 in the first phase and NtACS1 in the second phase. Biphasic production of ROS was inhibited in transgenic antisense plant lines expressing 1-aminocyclopropane-1-carboxylic acid synthase/oxidase or ethylene-insensitive3 as well as in transgenic plants impaired in ROS production. All tested transgenic plants were more tolerant against P. parasitica var nicotianae infection as determined based on trypan blue staining and pathogen proliferation. Further, silencing of NtACS4 blocked the second massive increase in ROS production as well as pathogen progression. Pathogen tolerance was due to the inhibition of ROS and ethylene production, which further resulted in lower activation of ROS-detoxifying enzymes. Accordingly, the synergistic inhibition of the second phase of ROS and ethylene production had protective effects against pathogen-induced cell damage. We conclude that the levels of ethylene and ROS correlate with compatible P. parasitica proliferation in susceptible plants.

Department of Bio-engineering, College of Engineering, Hanyang University, Seoul 133-791, KoreaReceived February 7, 2011, Accepted April 26, 2011Matrix metalloproteinases (MMPs), a family of zinc-containing endopeptidases, participate in many normalprocesses such as embryonic development and wound repair, and in many pathological situations such ascancer, atherosclerosis,and arthritis. Peptidomimetic MMP inhibitors were designed and synthesized with N-formylhydroxylamine (retrohydroxamate) as a zinc-binding group and various side chains on the α, P1', andP2' positions. Using in vitro MMP assays with purified MMPs (MMP-1, MMP-2, MMP-3, MMP-9, and MMP-14) and fluorogenic peptide substrates, it was found that compounds 2d and 2g selectively inhibit gelatinases(MMP-2 and MMP-9) and interstitial collagenase (MMP-1). They also inhibited the chemo-invasion offibrosarcoma HT-1080 cells and tube formation of human umbilical vascular endothelial cells in a dose-dependent manner. Our results suggest that retrohydroxamate-based MMP inhibitors, especially compounds2d and 2g, have the potential to be used as therapeutic drugs for cancer and other MMP-related diseases. Key Words : Inhibitor, Invasion, Matrix metalloproteinase (MMP), N-Formylhydroxylamine, Retrohydrox-amateIntroductionMatrix metalloproteinases (MMPs) are endopeptidasesthat can cleave virtually any component of the extracellularmatrix. Under normal physiological conditions, the activitiesof MMPsare precisely regulated by the level of transcrip-tion, by activationof precursor zymogens, by inhibition ofendogenous inhibitors,and by interaction with specificmatrix components. Deregulation of MMP activity is involv-ed in many disastrous diseases such as tumor invasion,metastasis, atherosclerosis,aneurysms, arthritis, tissue ulcers,and fibrosis.

비생물학적 스트레스로 $H_2O_2$ 를 이용하여 산화적 스트레스와 고염분 스트레스를 처리한 후 ROS의 생성을 확인한 결과 스트레스 처리 후 30분에 일시적으로 1차 peak를 형성하였다가 거의 basal level까지 감소하고 다시 증가하여 3시간에 매우 다량의 2차 peak를 형성한 후 거의 basal level로 다시 낮아지는 biphasic 양상을 나타내게 된다. 따라서 ROS의 생성은 초기 30분 내에 일시적으로 발생한 Phase I의 ROS와 Phase II의 좀 더 장기적으로 다량의 고농도로 발생된 ROS의 생리적 역할이 다를 것으로 여겨진다. 본 논문에서는 스트레스 처리 시 생성되는 ROS를 확인한 후 ROS 생성 유전자인 RbohD와 RbohF 유전자 발현이 억제된 RbohD-AS, RbohF-AS 형질전환 식물체를 이용하여 실험을 수행하였다. 스트레스에 의해 생성되는 ROS의 생성을 억제시킴으로써 스트레스에 대한 ethylene 생성이 더 적은 것으로 나타났다. 또한, 이들 형질전환 식물체에서 ethylene 생성과 $H_2O_2$ 억제 효과를 확인하였으며 고염분 등의 스트레스에 대한 저항성은 ROS와 ethylene의 생성이 저하되어 나타난 것으로 판단된다. 산화적 스트레스와 고염분 스트레스에서 후기 ethylene이 다량으로 생성되는 시기, 즉 세포손상이 초래되는 후기에서 DNA fragmentation 분석을 통해서 ROS와 ethylene의 생성이 높은 식물체일수록 PCD가 높게 나타난 것으로 여겨지며, 이 과정에서 작용하는 유전자는 RbohD와 RbohF인 것으로 보이며, RbohD가 더 효과적으로 작용하는 것으로 생각된다. 따라서 스트레스에 반응하는 신호전달과정에서 초기에 ROS가 생성이 되고 후기에 ethylene이 다량으로 생성되어 결국 세포죽음에 이르게 하는 상호 synergism을 일으켜 반응을 나타내며, 이러한 반응 과정에서 RbohD와 RbohF 유전자 발현의 억제가 스트레스에 대한 식물체의 저항성을 높이는 것으로 사료된다. 【Although reactive oxygen species (ROS) are inevitable by-products of many redox reactions in eukaryotic cells, they play a crucial role as signaling molecules in many cellular processes for development and defense response to abiotic stresses. The biphasic ROS production which was peaked twice in a first transient phase and a second massive phase was occurred after treatment of abiotic stress such as oxidative stress, high salinity. This biphasic generation of ROS was followed by the biphasic production of stress hormone, ethylene. The mechanism of interactions between ROS and ethylene biosynthesis is studied in tobacco (Nicotiana tabaccum L.) plants under the abiotic stresses. The stress-induced ethylene production was significantly inhibited in RbohD-AS and RbohF-AS, in which antisense expression of NADPH oxidase genes was performed. The accumulation of ROS, which was determined by DAB and DCFH-DA staining, was significantly decreased after abiotic stresses in transgenic plants. The suppression of signaling with ethylene and ROS induced more tolerance in response to abiotic stress. The transgenic plants were more tolerant in MS medium supplemented with salinity stress in contrast with wild-type. Stress-induced cell damage determined by DNA fragmentation was decreased at phase II in those transgenic plants. Therefore, the first burst of ROS is more responsible for making a role as a signaling molecule during stress-induced response. These results suggested that ethylene and ROS act in a positive feedback cycle that results in mutual enhancement of ethylene and ROS production during stress-induced cell death.】

The aim of the study was to clarify the charac-teristics of fatigue status in Chinese adolescents. 1018 adolescents (490 males, 528 females) aged 12 or 15 years in Jixi city were enrolled. Between May and September 2009, fatigue status was investigated using a questionnaire devised by ourselves, which consisted of 4 physical and 4 mental fatigue items. These questions were scored from 0 to 3 based on the frequency of an item occurring, given as the average of the past one month, and the fatigue scores were calculated. Lifestyle issues such as daily sleep duration, feeling of refreshment in the morning after wake-up, extracurricular sports activity, and breakfast intake, and a physical examination such as height, weight, and waist circumference were also investigated. Physical and mental fatigue scores were significantly higher in subjects aged 15 yrs old than in those aged 12 yrs old in both genders. These scores in females were significantly higher than those in males at the age of 15 yrs. Multivariate regression analysis showed that total (physical plus mental) fatigue scores were associated with female gender and various lifestyles such as unrefreshed wake-up feeling, poor extracurricular sports activity, and more frequent skipping of breakfast. However, body mass index and waist circumference were not associated with total fatigue scores.

A 4-year-old, neutered female Cocker Spaniel was presented to the veterinary clinic for protrusion of the left third eyelid. When the third eyelids from both eyes were everted, lobulated masses were present on the bulbar surface. The left third eyelid had a larger protrusion. There was no apparent associated ocular or systemic involvement. The tumor of left third eyelid was removed and referred for histological examination. Histologically, there were proliferations of lymphoid follicles surrounded by lymphoid cells forming a marginal zone. Those lymphoid cells occasionally infiltrated into conjunctival epithelium. A few apoptotic bodies with karyopyknotic and karyorrhexic nuclei were observed in the germinal center of lymphoid follicles. Mitotic figures were rare. On immunohistochemistry, tumor cells expressed CD79a but not CD3. A diagnosis of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) of the third eyelid was established based on the histological and immunophenotypical features. At the 1-year follow-up, there was no evidence of recurrence of the mass at the area of excision of the left third eyelid and the remaining tumor of the right third eyelid was still a similar size. The dog still showed no significant findings, except those of the tumor, and no evidence of systemic involvement. To the authors' knowledge, this is the first reported case of MALT lymphoma of the third eyelid in a dog.