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OBJECTIVES The aim of this study was to evaluate the clinical outcomes of patients undergoing off-pump robotic coronary artery bypass grafting (CABG) with either interrupted nitinol U-Clips in totally endoscopic coronary artery bypass (TECAB) or standard running suture anastomosis in robotically assisted direct coronary artery bypass (RADCAB) over a decade. METHODS From January 2007 to December 2017, 280 patients underwent robotic off-pump CABG using the da Vinci S/Si Surgical System in our centre. TECAB with interrupted nitinol U-Clips anastomosis was performed in the left internal mammary artery (LIMA) to LAD grafting in 126 patients and RADCAB (n = 154) of the LIMA to LAD was completed with standard running suture. After discharge, patients were contacted through telephone interview and were invited to attend the outpatient clinic every 6 months or 1 year. The graft patency was assessed by coronary angiography or computed tomography angiography. RESULTS All cases were completed without conversion to median sternotomy or cardiopulmonary bypass. A total of 275 single internal mammary artery (IMA) grafts (271 LIMAs, 4 right internal mammary arteries) and 5 bilateral IMA grafts were used as single graft or composite grafts. All the patients were discharged without in-hospital mortality or adverse outcomes. The average follow-up was 89.7 ± 30.4 months (range, 14–143 months). The cumulative survival rates (P = 0.53), the cumulative IMA patency rates (P = 0.83), and the rates of freedom from major adverse cerebrovascular and cardiovascular events (P = 0.41) between TECAB and RADCAB all showed no significant difference in the follow-up. CONCLUSIONS Robotic off-pump CABG using IMA grafts is safe and can provide reliable long-term outcomes. Compared with the standard hand-sewn running suture technique in RADCAB, interrupted suture with the nitinol U-Clips in TECAB showed similar long-term clinical results and graft patency in LIMA to LAD bypass grafting.

Pathological cardiac hypertrophy is one of the major predictors and inducers of heart failure, the end stage of various cardiovascular diseases. However, the molecular mechanisms underlying pathogenesis of pathological cardiac hypertrophy remain largely unknown. Here, we provided the first evidence that STEAP3 (Six-Transmembrane Epithelial Antigen of Prostate 3) is a key negative regulator of this disease. We found that the expression of STEAP3 was reduced in pressure overload-induced hypertrophic hearts and phenylephrine-induced hypertrophic cardiomyocytes. In a transverse aortic constriction-triggered mouse cardiac hypertrophy model, STEAP3 deficiency remarkably deteriorated cardiac hypertrophy and fibrosis, whereas the opposite phenotype was observed in the cardiomyocyte-specific STEAP3 overexpressing mice. Accordingly, STEAP3 significantly mitigated phenylephrine-induced cell enlargement in primary neonatal rat cardiomyocytes. Mechanistically, via RNA-seq and immunoprecipitation-mass screening, we demonstrated that STEAP3 directly bond to Rho family small GTPase 1 and suppressed the activation of downstream mitogen-activated protein kinase-extracellular signal-regulated kinase signaling cascade. Remarkably, the antihypertrophic effect of STEAP3 was largely blocked by overexpression of constitutively active mutant Rac1 (G12V). Our study indicates that STEAP3 serves as a novel negative regulator of pathological cardiac hypertrophy by blocking the activation of the Rac1-dependent signaling cascade and may contribute to exploring effective therapeutic strategies of pathological cardiac hypertrophy treatment.

Epithelial ovarian cancer has the highest mortality rate of all malignant ovarian cancer types. Great progress has been made in the treatment of ovarian cancer in recent years. However, drug resistance has led to a low level of 5-year survival rate of epithelial ovarian cancer, and the molecular mechanism of which remains unknown. The aim of the present study was to identify the role of redox status in the cisplatin (CDDP) resistance of ovarian cancer. CDDP-resistant SK-OV3 (SK-OV3/cddp) cells were prepared and their reactive oxygen species and glutathione levels were investigated. The effects of hydrogen peroxide on the CDDP sensitivity of the SK-OV3/cddp cells and their expression levels of the redox-associated protein growth arrest and DNA damage 45a (GADD45α) were also investigated. In addition, the impact of GADD45α overexpression on cell viability was evaluated in vitro and in vivo, and the levels of Ser-139 phosphorylated H2A histone family member X (γ-H2AX), which is associated with DNA damage, were detected. The results suggested that redox status affected the drug resistance of the ovarian cancer cells by increasing the expression of GADD45α. The overexpression of GADD45α reversed the CDDP resistance of the SK-OV3/cddp cells and increased the level of γ-H2AX. In conclusion, GADD45α alleviated the CDDP resistance of SK-OV3/cddp cells via the induction of redox-mediated DNA damage.

virusMED (Virus Metal binding sites, Epitopes and Drug binding sites) is a rich internet application based on a database of atomic interactions around hotspots in 7041 experimentally determined viral protein structures., Metal binding sites, antigen epitopes and drug binding sites are the hotspots in viral proteins that control how viruses interact with their hosts. virusMED (virus Metal binding sites, Epitopes and Drug binding sites) is a rich internet application based on a database of atomic interactions around hotspots in 7041 experimentally determined viral protein structures. 25306 hotspots from 805 virus strains from 75 virus families were characterized, including influenza, HIV-1 and SARS-CoV-2 viruses. Just as Google Maps organizes and annotates points of interest, virusMED presents the positions of individual hotspots on each viral protein and creates an atlas upon which newly characterized functional sites can be placed as they are being discovered. virusMED contains an extensive set of annotation tags about the virus species and strains, viral hosts, viral proteins, metal ions, specific antibodies and FDA-approved drugs, which permits rapid screening of hotspots on viral proteins tailored to a particular research problem. The virusMED portal (https://virusmed.biocloud.top) can serve as a window to a valuable resource for many areas of virus research and play a critical role in the rational design of new preventative and therapeutic agents targeting viral infections.

Current low-temperature plasma (LTP) devices essentially use a rare gas source with a short working distance (8 to 20 mm), low gas flow rate (0.12 to 0.3 m3 /h), and small effective treatment area (1-5 cm2 ), limiting the applications for which LTP can be utilised in clinical therapy. In the present study, a novel type of LTP equipment was developed, having the advantages of a free gas source (surrounding air), long working distance (8 cm), high gas flow rate (10 m3 /h), large effective treatment area (20 cm2 ), and producing an abundance of active substances (NOγ, OH, N2 , and O), effectively addressing the shortcomings of current LTP devices. Furthermore, it has been verified that the novel LTP device displays therapeutic efficacy in terms of acceleration of wound healing in normal and Type I diabetic rats, with enhanced wound kinetics, rate of condensation of wound area, and recovery ratio. Cellular and molecular analysis indicated that LTP treatment significantly reduced inflammation and enhanced re-epithelialization, fibroblast proliferation, deposition of collagen, neovascularization, and expression of TGF-β, superoxide dismutase, glutathione peroxidase, and catalase in Type I diabetic rats. In conclusion, the novel LTP device provides a convenient and efficient tool for the treatment of clinical wounds.

Fifteen chalcone derivatives 3a-3o were synthesized, and evaluated as multifunctional agents against Alzheimer's disease. In vitro studies revealed that these compounds inhibited self-induced Aβ1-42 aggregation effectively ranged from 45.9-94.5 % at 20 μM, and acted as potential antioxidants. Their structure-activity relationships were summarized. In particular, (2E)-3-[4-(dimethylamino)phenyl]-1-(pyridin-2-yl)prop-2-en-1-one (3g) exhibited an excellent inhibitory activity of 94.5 % at 20 μM, and it could disassemble the self-induced Aβ1-42 aggregation fibrils with ratio of 57.1 % at 20 μM concentration. In addition, compound 3g displayed good chelating ability for Cu2+ , and could effectively inhibit and disaggregate Cu2+ -induced Aβ aggregation. Moreover, compound 3g exerted low cytotoxicity, significantly reversed Aβ1-42 -induced SH-SY5Y cell damage. More importantly, compound 3g remarkably ameliorated scopolamine-induced memory impairment in mice. In summary, all the results revealed compound 3g was a potential multifunctional agent for AD therapy.

To develop the Chinese version of Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) and examine its psychometric properties, we investigated a sample of 689 non-clinical and 309 cli...

The administration of doxorubicin (DOX) is one of the first-line treatments of breast cancer. However, acquisition of resistance remains the major obstacle restricting the clinical application of DOX. MicroRNAs (miRNAs) are small, noncoding RNAs which play crucial role in epigenetic regulation. Recent studies have shown that miRNAs are associated with tumor chemoresistance. Here we aim to explore the role of miRNA-192-5p in resistance to DOX in breast cancer cells. Normal human breast epithelial cell line MCF-10A, breast cancer cell line Michigan Cancer Foundation-7 (MCF-7), and DOX-resistant breast cancer cell line MCF-7/ADR were used here. The expression of miR-192-5p was examined by qPCR, and the expression of peptidylprolyl isomerase A (PPIA) was examined by qPCR and Western blot. The effects of miR-192-5p overexpression on the sensitivity to DOX were confirmed by Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and Annexin-V/PI assay. Downstream molecular mechanisms, including PPIA, BAD, CASP9, Bcl-2, and c-Jun N-terminal kinase (JNK) activation, were detected by Western blot and qPCR. Luciferase reporter assay was used to validate the association between miR-192-5p and PPIA. miR-192-5p was downregulated while PPIA was upregulated in MCF-7/ADR cells. Functionally, miR-192-5p overexpression increased sensitivity to DOX by promoting cell apoptosis. Mechanistically, miR-192-5p overexpression performed its function by activating JNK, augmenting BAD and caspase9 expression, and suppressing Bcl-2 and PPIA expression. Luciferase assay validated that PPIA was a direct target of miR-192-5p. miR-192-5p sensitizes breast cancer cells to DOX by targeting PPIA, suggesting that miR-192-5p might serve as a novel target for reversing DOX resistance and controlling breast tumor growth.

Immune cells have an uncertain function during the progression of extranodal natural killer/T-cell lymphoma (ENKTL). The present study determined the distribution, phenotype, and clinical significance of B lymphocytes in ENKTL. Immunohistochemistry indicated high infiltration of CD20+ B lymphocytes in the tumour tissues of 40% of the patients, and that a high infiltration correlated with better overall survival. Moreover, B lymphocytes had an active mature phenotype in situ and suppressed the proliferation of ENKTL cells in vitro. These results suggest that tumour infiltration of CD20+ B lymphocytes may be a new prognostic indicator for patients with ENKTL.

This study aimed to investigate the hemostatic efficacy of a novel femoral artery compression device in patients undergoing an interventional procedure through femoral artery puncture.Patients enrolled in this trial were randomly assigned 1:1 to the novel femoral artery compression device (NFACD) or the manual compression (MC) group. The primary endpoints were time to hemostasis (TTH), time to ambulation (TTA), any other complications, such as the occurrence of hematoma, bleeding, pseudoaneurysm and arteriovenous fistula at the puncture site, and time to hospital discharge.A total of 617 patients were included in this study (NFACD,The novel femoral artery compression device is effective in achieving hemostasis in patients undergoing femoral artery puncture and is associated with a marked shortening of the TTH and TTA.

BACKGROUND Early interventions have been believed to have a positive influence on the neurodevelopment of infants. Our Child Health Center has carried out parenting training for parents of infants for several years to promote the neurobehavioral development of infants at an early stage. MATERIAL AND METHODS We enrolled 117 families with term infants age 0-3 months who had completed a parenting training class at the Child Health Center of the Department of Pediatrics, the Third Xiangya Hospital. Parenting training included 4 parts: nursing, intelligence, social contact, and physical ability. A nurse practitioner demonstrated procedures to parents, who then performed them at home for 1 month. The Neonatal Behavioral Neurological Assessment (NBNA) was used to evaluate infants before and 1 month after parenting training. RESULTS In the comparative analysis before and after parenting training, there was a significant increase in the NBNA scores. For the infants whose parents received parenting training, the NBNA scores in total score (33.74±0.19 before parenting training vs. 36.69±0.20 after 1 month), neonatal behavioral capacity (10.19±0.14 before parenting training vs. 11.26±0.10 after 1 month), passive muscle tension (7.28±0.07 before parenting training vs. 7.82±0.04 after 1 month), and initiative muscle tension (4.29±0.08 before the parenting training vs. 5.61±0.13 after 1 month) were significantly higher one month before (P

Flavones have the potential of being used as a dietary supplement for bone health promotion beyond calcium and vitamin D. Recent studies have showed that flavones enhanced bone formation and inhibited bone resorption by affecting osteoblast and osteoclast differentiation through various cell signaling pathways. In this study, we investigated the effects of a new flavone (2R,3S)-pinobanksin-3-cinnamate, isolated from the metabolites of the endophytic fungus Penicillium sp. FJ-1 of Acanthus ilicifolius L., Acanthaceae, on osteoblast differentiation by using MC3T3-E1 cells. It was observed that (2R,3S)-pinobanksin-3-cinnamate promoted osteoblast differentiation, as evidenced by increased mineralization process and alkaline phosphatase activity, as well as expression of genes encoding the bone differentiation. Moreover (2R,3S)-pinobanksin-3-cinnamate treatment upregulated the gene expression of wingless-type MMTV integration site family, bone morphogenetic protein and runt-related transcription factor 2, and protein expression of phosphor-Smad1/5/8, β-catenin and runt-related transcription factor 2 in MC3T3-E1 cells. The osteoblast differentiation effects induced by (2R,3S)-pinobanksin-3-cinnamate were attenuated by the bone morphogenetic protein antagonist Noggin, and wingless-type MMTV integration site family signaling pathway inhibitors Dickkopf-1. Co-treatment with adenosine 30,50-cyclic monophosphate and guanosine 30,50-cyclic monophosphate pathway inhibitors, H89 and KT5823, respectively, reversed the (2R,3S)-pinobanksin-3-cinnamate-induced activations of p-Smad1/5/8, β-catenin, and runt-related transcription factor 2. Our data demonstrated that (2R,3S)-pinobanksin-3-cinnamate promoted the osteoblast differentiation of MC3T3-E1 cells, at least partially through the adenosine 30,50-cyclic monophosphate and guanosine 30,50-cyclic monophosphate signaling pathways, providing the scientific rational to develop (2R,3S)-pinobanksin-3-cinnamate against bone loss-associated diseases. Keywords: (2R ;3S)-pinobanksin-3-cinnamate, Osteoblast differentiation, MC3T3-E1 cells, cAMP, cGMP

Background/Aims: The liver is a vital organ in vertebrates and has a wide range of functions, including glucose absorption, glycogen storage and glucose production. Fibroblast growth factor (FGF)-21 is a metabolic regulator that is primarily produced by the liver. In this paper, we studied the effect of FGF-21 on glucose metabolism in the liver. Methods: The glucose uptake of cells was detected by 2-Deoxy-d-[3H] glucose; the synergy between insulin and FGF-21 was evaluated. The mRNA expression of GLUT1-4, G6Pase and PEPCK was detected by real-time PCR. Glycogen synthesis was examined by the anthrone method. Blood samples to monitor glucose in db/db diabetic mice were obtained by tail snip. Glucose metabolism in the liver and adipose tissues was observed by fluorescence microscopy. Results: In this study, FGF-21 stimulated glucose uptake by liver cells in both a dose and time-dependent manner, and at the same time, FGF-21 specifically stimulated GLUT1 expression in the liver cells. Furthermore, FGF-21 demonstrated a synergistic effect with insulin on glucose absorption, which is in accordance with enhanced GLUT-1 and -4 expression. Treatment with FGF-21 increased glycogen storage in liver cells. Consistent with in vitro results, FGF-21 lowered the plasma glucose level and stimulated GLUT1 expression and glycogen synthesis in db/db diabetic mice. Simultaneously, FGF-21 inhibited the gene expression of G6Pase and PEPCK. Conclusion: Our results suggest that FGF-21 clears up plasma glucose by stimulating glucose absorption in the liver of diabetic animals and decreases glucose release from the liver by inhibiting gluconeogenesis. Overall, these data indicate that the liver is an important target organ of FGF-21 to regulate glucose metabolism.

The present study was planned to evaluate correlation between Helicobacter pylori (HP) infection and autoimmune liver disease (AILD). A total of 60 patients diagnosed with AILD in Affiliated Hospital of Binzhou Medical College were continuously enrolled in the present study. HP infection was detected by 13C-urea breath test. The levels of anti-myeloperoxidase were tested by ELISA. The positive rate of anti-nuclear antibody (ANA), anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (SMA) and anti-neutrophil cytoplasm antibody (ANCA) were tested by indirect immunofluorescence. The positive rates of anti-mitochondrial antibody (AMA-M2), anti-liver-kidney microsomal antibody (LKM-1), anti-liver cytoplasm antibody I (LC-1) and anti-soluble liver antigen/liver-pancreas antigen (SLA/LP) were tested by immunoblotting. Liver function indexes including alanine transaminase, aspartate transaminase, alkaline phosphatase and glutamyltransferase, were analyzed with a fully automatic biochemical analyzer. The levels of serum cytokine IFN-γ, interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) were tested by ELISA. A total of 37 patients (61.67%) were observed to be HP-positive. MPO-positive rate, positive rate of ANA, AMA, SMA and ANCA and positive rate of AMA-M2, LKM-1, LC-1 and SLA/LP in patients with positive HP infection were significantly higher than those of patients with negative HP infection. On the other hand, the levels of liver function indices did not showed any significant differences among HP-positive cases or HP-negative cases. However, the levels of IFN-γ, IL-6, IL-10 and TNF-α in patients with positive HP infection were significantly higher than those of patients with negative HP infection. In conclusion, the positive infection rate of HP infection in patients with AILD is high and is closely associated with various positive immune antibodies as well as cytokine levels.

Colorectal cancer (CRC) is the third most common cancer worldwide and its treatment remains a challenge. Effective control of cell survival and proliferation is critical in the prevention of oncogenesis and successful treatment of cancer. Long non-coding RNAs (lncRNAs) have emerged as primary regulators of carcinogenesis. Growth arrest specific 5 (GAS5), a lncRNA, is known to be aberrantly expressed in several types of cancer, however, the role of GAS5 in CRC remains unclear. In the present study, GAS5 mRNA expression was measured in CRC and adjacent normal mucosa tissue samples from 53 patients using reverse transcription-quantitative polymerase chain reaction analysis, in addition to seven CRC cell lines. GAS5 mRNA expression was observed to be markedly downregulated in human CRC tissues and cell lines. Decreased GAS5 expression was associated with an increase in tumor diameter [odds ratio (OR), 0.176 (95% CI, 0.053–0.586); P=0.003] and later tumor-node-metastasis stage [OR, 0.261 (95% CI, 0.083–0.819); P=0.019]. Patients with decreased GAS5 expression exhibited decreased overall survival rates compared with patients with increased GAS5 expression (P=0.015). The Cox proportional hazards model demonstrated that downregulated GAS5 expression was an independent prognostic factor for CRC (hazard ratio, 0.236; 95% confidence interval, 0.067–0.827; P=0.024). Functional assays demonstrated that overexpression of GAS5 inhibited cell proliferation and survival, and induced G0/G1 cell cycle arrest and apoptosis; however, knockdown of GAS5 expression enhanced cell proliferation, and reduced G0/G1 arrest and apoptosis. In conclusion, the results of the present study suggest that GAS5 is essential in the control of apoptosis and cell growth in CRC. Therefore, GAS5 may represent a novel prognostic and diagnostic marker of CRC, in addition to being a potential therapeutic target.

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of malignant pancreatic tumor. MicroRNAs (miRNAs) are a group of small, non-protein coding, endogenous RNAs that play critical roles in tumorigenesis and progression of PDAC. In the present study, we demonstrated that miR-448 expression was downregulated in PDAC tissues and cell lines. Clinical association analysis indicated that low expression of miR-448 was associated with poor prognostic features and conferred a significant reduced survival of PDAC patients. Overexpression of miR-448 suppressed PDAC cell migration and invasion, while its loss showed the opposite effects on these cellular processes. In vivo experiments revealed that miR-488 restoration prohibited liver metastasis of PDAC in nude mice. Moreover, we found that Janus kinase 1 (JAK1) was a direct target gene of miR-448 in PDAC cells. We further demonstrated that the expression of JAK1 mRNA was upregulated in PDAC tissues. Notably, the expression of JAK1 mRNA was inversely correlated with the level of miR-448 in PDAC tissues. In addition, JAK1 knockdown showed similar effects of miR-448 on the metastasis of PDAC cells. JAK1/STAT3 pathway may be involved in the function of miR-448 in PDAC cells. Taken together, these findings suggest that miR-448 functions as a tumor suppressor in the development of PDAC through targeting the JAK1/STAT3 pathway.

Pollination systems and associated floral traits generally differ between core and marginal populations of a species. However, such differences are rarely examined in plants with a mixed wind‐ and bumblebee‐pollination system, and the role of wind pollination during range expansion in ambophilous plants remains unclear. We compared floral traits and the contributions of bumblebee and wind pollination in refugium and marginal populations of the ambophilous plant Aconitum gymnandrum. We found that most floral traits differed between the two populations, and those traits associated with the shift to wind pollination were pronounced in the marginal population. Bumblebee visitation rates varied significantly, but were generally low in the marginal population. Wind pollination occurred in both populations, and the efficiency was lower than that of bumblebee pollination. Two types of pollen grains, namely round and fusiform pollen, were transported to a stigma by bumblebees and wind, but fusiform pollen contributed to wind pollination to a larger degree, especially in the marginal population. Our results suggest that wind pollination was enhanced by pollen dimorphism in the marginal population of A. gymnandrum, and wind pollination may provide reproductive assurance when bumblebee activity is unpredictable during range expansion, indicating that ambophily is stable in this species and shift in pollination system could be common when plants colonize new habitats.

The promotion of social living quality has expedited the development of leisure exercise products. However, most young people usually accomplish their tasks by sitting in front of the computers. This situation makes many people seriously deficient in exercises that may cause muscle skeleton declination. In review of current related products, most of them are primarily designed by designers’ intuition or only for a specific purpose. The objective of this research is to involve the motion analysis of physical musculoskeletal system in the integrated development process of quality function deployment for the design of lower limb leisure exercise products. A four-stage of development procedure including performance ranges of muscle-joint activities, AIO life style questionnaire, factor analysis, and quality function deployment is conducted. The implementation of quality function deployment helps to link customer requirements with product characteristics and derives design criteria for generating design alternatives. Two design alternatives based on the design criteria are generated by the computer-aided design software. It is expected that this research will provide designers with a reference or norm on designing most suitable lower limb leisure exercise products for people.

[Abstract] Objective: To investigate the influence factors of hemorrhage and stroke with retriever with Solitaire AB stent in patients with acute intracranial artery occlusion. Methods: A retrospective of 43 cases of patients with acute intracranial artery occlusion for endovascular treatment with Solitaire AB stent enrolled from March 2016 to June 2018 in our hospital, combining the characteristics of the patients of our city, through the clinical baseline data statistical analysis, complications screening of risk factors of complications. Results: There were 81.4% of patients who were dredged totally. The incidences of cerebral hemorrhage and infarction were 18.6% and 16.3%, cerebral hemorrhage group compared with control group, diabetes, blood pressure, revascularized time, NIHSS score, ASPECTS score had statistically significant differences, when infarction group compared with control group, age, opening time, ASITN_SIR score and grade of mTICI had statistically significant differences. Conclusion: Mechanical thrombectomy with Solitaire AB stent in patients with acute intracranial artery occlusion, the occurred of complications associated with various clinical factors, and the occurrence of complications seriously affect the prognosis of patients, therefore, selecting the indications strictly, and adopt individualized treatment to reduce complications.

Astrocytes are major glial cells critically in maintaining stability of the central nervous system and functional activation of astrocytes occurs rapidly in various diseased or traumatic events. We are interested in functional changes of astrocytes during the spinal cord injury, and studied expression of nerve growth factor (NGF) in activated astrocytes by mouse model of contused spinal cord injury and cell culture experiment. It revealed that the spinal cord injury resulted in apparent activation of astrocytes and microglial cells and decreased BMS scores. A larger number of astrocytes showed immunoreactivity to proNGF in the injured spinal cord areas, and proNGF expression increased and remained high level at 7 to 14dpi, which was coincided with upregulation of glial fibrillary acidic protein. The proNGF was clearly localized in both exosome-like vesicles and cytoplasm of astrocytes in culture. Electron microscopy confirmed exosome-like vesicles with proNGF-immunoreactivity in diameter sizes of 50–100 nm. Finally, cell culture with lipopolysaccharide (LPS) experiment indicated increasing expression and release of proNGF in the astrocytes with LPS exposure. This study demonstrated that reactive astrocytes increased proNGF expression after spinal cord injury, also suggesting involvement of exosome-like proNGF transport or release in triggering neuronal apoptosis and aggravating progression of spinal cord injury.

Animal-based studies have provided important insights into the structural and functional consequences of noise exposure on the cochlea. Yet, less is known about the molecular mechanisms by which noise induces cochlear damage, particularly at relatively low exposure levels. While there is ample evidence that noise exposure leads to changes in inner ear metabolism, the specific effects of noise exposure on the cochlear metabolome are poorly understood. In this study we applied liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS)-based metabolomics to analyze the effects of noise on the mouse inner ear. Mice were exposed to noise that induces temporary threshold shifts, synaptopathy and permanent hidden hearing loss. Inner ears were harvested immediately after exposure and analyzed by targeted metabolomics for the relative abundance of 220 metabolites across the major metabolic pathways in central carbon metabolism. We identified 40 metabolites differentially affected by noise. Our approach detected novel noise-modulated metabolites and pathways, as well as some already linked to noise exposure or cochlear function such as neurotransmission and oxidative stress. Furthermore, it showed that metabolic effects of noise on the inner ear depend on the intensity and duration of exposure. Collectively, our results illustrate that metabolomics provides a powerful approach for the characterization of inner ear metabolites affected by auditory trauma. This type of information could lead to the identification of drug targets and novel therapies for noise-induced hearing loss.

Age-related decline of inner ear function contributes to both hearing loss and balance disorders, which lead to impaired quality of life and falls that can result in injury and even death. The cellular mechanisms responsible for the ear's functional decline have been controversial, but hair cell loss has been considered the key cause for a long time. However, recent studies showed that in the cochlea, loss of inner hair cell (IHC) synapses precedes hair cell or neuronal loss, and this synaptopathy is an early step in the functional decline. Whether a similar process occurs in the vestibular organ, its timing and its relationship to organ dysfunction remained unknown. We compared the time course of age-related deterioration in vestibular and cochlear functions in mice as well as characterized the age-associated changes in their utricles at the histological level. We found that in the mouse, as in humans, age-related decline in vestibular evoked potentials (VsEPs) occurs later than hearing loss. As in the cochlea, deterioration of VsEPs correlates with the loss of utricular ribbon synapses but not hair cells or neuronal cell bodies. Furthermore, the age-related synaptic loss is restricted to calyceal innervations in the utricular extrastriolar region. Hence, our findings suggest that loss of extrastriolar calyceal synapses has a key role in age-related vestibular dysfunction (ARVD).

Background The feasibility and safety of robotic mitral valve repair has been proven in several studies but the mid-term to long-term outcomes are unclear. We aim to summarize our surgical experience with robotic mitral valve repair and demonstrate the follow-up results out to 7 years. Methods From 2007 to 2014, 110 consecutive patients underwent robotic mitral valve repair with da Vinci Surgical System (Intuitive Surgical, USA) in our center. The operative data were collected, and patients were echocardiographically followed regularly up to 7 years. Results The patients' average age was 45±13 (14 to 70) years with male to female ratio of 2.3:1. Mitral regurgitation (95.5%) or stenosis (4.5%) was diagnosed. The triangular or quadrangular resection was the most performed type of repair (63.3%). Nitinol U-clips (58.1%), running suture (31.1%), and Cor-Knot™ suture device (LSI Solutions, Victor, NY) (10.8%) were used to secure the annuloplasty ring. All cases were performed by the same surgeon. One case of conversion to sternotomy was noted. The mean CPB time was 121±34.3 (range, 70 to 152) minutes, and the mean cross-clamp time was 82.6±25.3 (range, 47 to 122) minutes. After surgery, one death (0.91%) and two cases of transient neurocognitive defect (1.82%) occurred. Three cases of early failure of repair that required reoperation (2.73%) were noticed. All patients were successfully followed for a median of 4.1 (range, 1 month to 7 years) years and 94.5% had freedom of re-operation. Conclusions Robotic mitral valve repair is a safe and effective procedure with excellent mid-term outcomes.

The [-2]proPSA (p2PSA) and its derivatives, the p2PSA-to-free PSA ratio (%p2PSA), and the Prostate Health Index (PHI) have greatly improved discrimination between men with and without prostate cancer (PCa) in prostate biopsies. However, little is known about their performance in cases where a digital rectal examination (DRE) and transrectal ultrasonography (TRUS) are negative. A prospective cohort of 261 consecutive patients in China with negative DRE and TRUS were recruited and underwent prostate biopsies. A serum sample had collected before the biopsy was used to measure various PSA derivatives, including total prostate-specific antigen (tPSA), free PSA, and p2PSA. For each patient, the free-to-total PSA ratio (%fPSA), PSA density (PSAD), p2PSA-to-free PSA ratio (%p2PSA), and PHI were calculated. Discriminative performance was assessed using the area under the receiver operating characteristic curve (AUC) and the biopsy rate at 91% sensitivity. The AUC scores within the entire cohort with respect to age, tPSA, %fPSA, PSAD, p2PSA, %p2PSA, and PHI were 0.598, 0.751, 0.646, 0.789, 0.814, 0.808, and 0.853, respectively. PHI was the best predictor of prostate biopsy results, especially in patients with a tPSA of 10.1-20 ng ml −1 . Compared with other markers, at a sensitivity of 91%, PHI was the most useful for determining which men did not need to undergo biopsy, thereby avoiding unnecessary procedures. The use of PHI could improve the accuracy of PCa detection by predicting prostate biopsy outcomes among men with a negative DRE and TRUS in China.

A hydrated kaolinite-methanol intercalation compound (Kaol-MeOH (hydrated)) was synthesized by utilizing kaolinite/dimethyl sulfoxide intercalation compound (Kaol-DMSO) as an intermediary, and further displacement intercalation with butyl trimethylammonium chloride (BTAC) was also carried out. The obtained samples were characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Results showed that the d001 value of the Kaol-MeOH (hydrated) could be arbitrary values between 0.86 and 1.08 nm, which could be caused by the hydrogen-bonded MeOH or water molecules between the interlayer spaces of methoxy-modified Kaol. Furthermore, this part of interlayer molecules could be removed by heating and have no obvious effect on the subsequent intercalation reaction. In addition, the time required for Kaol-MeOH (hydrated) preparation was drastically shortened to 3 days, which greatly reduces the time-consuming for the preparation of subsequent compounds.

To explore the immune reconstitution of CD4+T cells after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and its relationship with invasive fungal infection (IFI) in patients with hematological malignancies.Forty-seven patients with hematological malignancies undergoing Allo- HSCT in Binzhou Medical University Hospital from February, 2010 to October, 2014 were selected. At 1, 2 and 3 months after transplantation, the immune subpopulations and concentration of cytokines were assessed respectively using flow cytometry (FCM) and enzyme linked immunosorbent assay (ELISA). The incidence of IFI after transplantation and its correlation with immune reconstitution of CD4+T cells were investigated.The number of CD4+T cells and immune subpopulations increased progressively after transplantation as time went on, but the subpopulation cell count 3 months after transplantation was still significantly lower than in the control group (p0.01). In comparison to the control group, the levels of interleukin-6 (IL-6) and IL-10 after transplantation rose evidently (p0.01), while that of transforming growth factor-β (TGF-β) was decreased (p0.01). There was no statistically significant difference level of interferon-γ (IFN-γ) (p0.05). The incidence of IFI was 19.2% (9/47), and multivariate logistic regression revealed that IFI might be related to Th17 cell count (p0.05), instead of Th1, Th2 and Treg cell counts as well as IL-6, IL-10, TGF-β and IFN-γ levels (p0.05).After Allo-HSCT, the immune reconstitution of CD4+T cells is delayed and Th17 cell count decreases obviously, which may be related to occurrence of IFI.

Aim The aim of this study was to identify the incidence and risk factors of bacterial vaginosis among pregnant women. Material and Methods Prospective data from a cohort of 668 pregnant women were used to identify potential risk factors for bacterial vaginosis during pregnancy by Cox proportional hazards regression. Results A total of 204 incident cases of bacterial vaginosis were diagnosed in 274.8 woman-years of follow-up. The bacterial vaginosis incidence rate was 0.74 per 1 woman-year and median prevalence during follow-up was 15.6%. In the adjusted model, changing underwear nearly everyday, miscarriage history, urinary tract infection during follow-up, husbands' education level, and concurrent trichomoniasis and candidiasis remained significantly associated with bacterial vaginosis (adjusted hazard ratio and 95% confidence interval were 1.87 [1.26–2.77]; 2.96 [1.96–4.47]; 2.41 [1.05–5.49]; 0.50 [0.32–0.77]; 1.82 [1.02–3.25]; 1.88 [1.30–2.70], respectively). Conclusion Bacterial vaginosis during pregnancy can be affected by many factors, and some are indirectly acting factors. Further prospective studies that include a larger sample size and more information on the development of bacterial vaginosis are needed.

The effects of allelochemicals and aqueous extracts from different Pogostemon cablin (Blanco) Benth., Lamiaceae, parts and rhizosphere soil on growth parameters, leaf membrane peroxidation and leaf antioxidant enzymes were investigated in patchouli. P. cablin seedlings were incubated in solutions containing allelochemicals and aqueous extracts from different patchouli parts and its rhizosphere soil at several concentrations. Firstly, the growth parameters were significantly reduced by the highest concentration of leaves, roots and stems extracts (p

Photochemical degradation of typical phthalate esters, as, e.g. dimethyl phthalate (DMP), in water by the UV/H2O2 process was investigated. The degradation rate of DMP was affected by several reaction factors, including initial DMP concentration, H2O2 concentration, UV light intensity, and coexisting cations and anions. The DMP degradation rate decreased with increasing initial DMP concentration. Carbonate ions significantly reduced the reaction rate by 70.2%, while the degradation rate was improved ten-fold in the presence of ferric ions. The initial reaction mechanism and possible degradation products were investigated using density functional theory (DFT), including B3LYP and M062X hybrid functional. The addition of OH radicals (OH•) to the C4 position of the DMP ring is energetically favored for the initial reaction of DMP with OH•. Dimethyl 4-hydroxyphthalate (DMP-4OH) is one of the initial degradation intermediates. A possible reaction mechanism was also proposed based on GC/MS analysis and quantum chemical calculations. The formation of DMP-4OH has been explained by quantum chemical calculations, which indicates the advantage and promising role of this method in the degradation mechanism analysis.

AIM: This study aims to assess the prevalence of and factors associated with induced abortion among married women in rural areas of Anhui Province China. MATERIAL AND METHODS: A multistage probability sampling method was used to identify a representative sample of 53652 married women aged 18-49 years in rural areas of Anhui Province China. All women were interviewed in the form of a standardized questionnaire. RESULTS: We found that 32.0% (16800) of these women had had at least one induced abortion: 21.1% (11090) of women had had one; 7.6% (3976) of women had had two; and 4.1% (1734) of women had had at least three. The number of induced abortions per 100 pregnancies was found to be 22.0. Multivariate analysis showed that education the age of a woman at her first marriage number of total births number of total pregnancies and contraceptive methods were significant predictors for induced abortion after controlling for womens current age employment and family yearly income. CONCLUSION: The study shows that the prevalence of induced abortion is still very high among married women in rural China and highly effective methods of contraception (sterilization intrauterine device) decrease womens recourse to induced abortion.

The aim of this study was to estimate the risk factors of bacterial vaginosis (BV) among rural married women of childbearing age in Anhui Province of China. A cross-sectional study was conducted and the method of stratified cluster sampling was used to identify a sample of 53,652 married women aged 18-49 years. All women were asked to complete an interviewer-administered standardized questionnaire, covering sociodemographic characteristics, history of menstruation, marriage and procreation, sexual life, personal hygienic behaviors, and reproductive tract infections (RTIs) knowledge, followed by the gynecological examination and laboratory inspection. A total of 53,286 married women aged 18-49 years were included in this analysis. The prevalence of BV was 11.99 % (6,391/53,286). Risk factors for BV included the minority nationality, women's lower education levels, husband's elder age, over 35 days of menstrual cycle, less than 3 days of menstruation, dysmenorrhea, usage of an intrauterine device (IUD), lack of RTIs knowledge, higher frequency of washing genitals before having sex with husband and changing underwear, lower frequency of sexual intercourse per month, and suffering from other RTIs. The results suggest that BV can be affected by many factors among rural married women of reproductive age, so comprehensive, scheduled programs at healthcare educations should be provided for women in order to prevent BV.

At present, more novel smart nanomaterials offering special responses towards some environmental stimuli have been used in the design and construction of rheumatism drug delivery systems to achieve a targeted drug release, thereby improving rheumatism drug efficacy and decreasing adverse rheumatism drug reaction. The current development of the application of pH, photo, thermo, enzyme and redox-responsive smart nanomaterials in rheumatism drug delivery systems was classifiedly reviewed.

The damaged vestibular sensory epithelium of mammals has a limited capacity for spontaneous hair cell regeneration, which largely depends on the transdifferentiation of surviving supporting cells. Little is known about the response of vestibular supporting cells to a severe insult. In the present study, we evaluated the impact of a severe ototoxic insult on the histology of utricular supporting cells and the changes in innervation that ensued. We infused a high dose of streptomycin into the mouse posterior semicircular canal to induce a severe lesion in the utricle. Both scanning electron microscopy and light microscopy of plastic sections showed replacement of the normal cytoarchitecture of the epithelial layer with a flat layer of cells in most of the samples. Immunofluorescence staining showed numerous cells in the severely damaged epithelial layer that were negative for hair cell and supporting cell markers. Nerve fibers under the flat epithelium had high density at the 1 month time point but very low density by 3 months. Similarly, the number of vestibular ganglion neurons was unchanged at 1 month after the lesion, but was significantly lower at 3 months. We therefore determined that the mouse utricular epithelium turns into a flat epithelium after a severe lesion, but the degeneration of neural components is slow, suggesting that treatments to restore balance by hair cell regeneration, stem cell therapy or vestibular prosthesis implantation will likely benefit from the short term preservation of the neural substrate.

The excessive apoptosis of cells of the nucleus pulposus may plays an important role in intervertebral disc (IVD) degeneration. It has been shown that the pro-inflammatory cytokine tumour necrosis factor (TNF)-α can induce disc cell apoptosis. Insulin-like growth factor (IGF)-1 can promote nucleus pulposus cell proliferation; however, whether or not IGF-1 inhibits TNF-α-induced apoptosis in the nucleus pulposus has not yet been elucidated. In this study, our objective was to create a potentially therapeutic viral vector, which could be used to achieve the enforced expression of IGF-1 in rabbit nucleus pulposus cells. Furthermore, we investigated the ability of IGF-1 to reverse TNF-α-induced apoptosis in cells of the nucleus pulposus. Isolated nucleus pulposus cells were cultured to a confluent monolayer, digested with collagenase Ⅱ and purified using trypsin and differential adhesion methods. Nucleus pulposus cells were positively identified using type Ⅱ collagen immunohistochemistry. Following transfection with adenoviral vectors engineered to overexpress recombinant human IGF-1 (Ad-hIGF-1) or TNF-α, the cells were observed under a light microscope. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) and flow cytometry (FCM) were used to assess the rate of apoptosis. The Ad-hIGF-1 viral vector was effectively transduced into the nucleus pulposus cells and increased IGF-1 expression as confirmed by RT-PCR and western blot analysis. In the TNF-α-treated group, a large number of apoptotic cells was observed that exhibited morphological changes associated with this form of cell death. Minimal apoptosis was observed in the Ad-hIGF-1-treated group and the control group showed no obvious signs of apoptosis. TUNEL assay revealed that the rate of apoptosis in the Ad-hIGF-1 group was significantly reduced compared with the TNF-α-treated group (P

Background The Sysmex XE-5000 hematology analyzer evaluates toxic granulation and the nuclear maturity of toxic granulation neutrophils via the parameters neut-X and neut-Y. This study investigated whether neut-X and neut-Y could facilitate the auxiliary diagnosis of sepsis. Methods Blood samples were collected from 113 patients with tumors and 130 healthy individuals to detect neut-X, neut-Y, and C-reactive protein (CRP) values. Then, we created a new parameter, neut-Z, the vector sum of neut-X and neut-Y. Furthermore, we assessed procalcitonin (PCT) concentrations in patients with sepsis and compared the values with those for neut-X, neut-Y, and neut-Z. Results Neut-X, neut-Y, neut-Z, and CRP values were significantly higher in the sepsis group than in the non-sepsis and healthy groups. The ROC-AUCs for neut-X, neut-Y, neut-Z, and CRP for a diagnosis of sepsis were 0.87 (sensitivity 82%, specificity 79%), 0.87 (78 and 94%, respectively), 0.91 (82 and 88%, respectively), and 0.95 (96 and 89%, respectively), respectively. Additionally, neut-X, neut-Y, and neut-Z were correlated with CRP and PCT levels. Conclusions Neut-X and neut-Y can be used as rapid and simple auxiliary indicators in the diagnosis of sepsis in patients with tumors, and neut-Z appears to display better performance than its 2 components.

The objective of the study was to investigate the association between peptidylarginine deiminase 4 (PADI4) polymorphism and susceptibility to rheumatoid arthritis (RA). An electronic searching strategy was employed to collect relevant studies on the association between PADI4 polymorphism and susceptibility to RA. The odds ratio (OR) with the 95 % confidence interval (95 % CI) was used to evaluate the RA risk presented by PADI4 polymorphism. Fixed or random effects models were selected based on heterogeneity. Publication bias was assessed using funnel plots, Begg’s test, and Egger’s test. A total of 27 studies from 21 articles were included. Six gene loci (padi4_94, 104, 92, 90, 89, and 100) were chosen for the meta-analysis. The pooled ORs (95 % CI) for allele 2 versus 1 were 1.08 (1.05–1.12), 1.17 (1.12–1.23), 1.26 (1.18–1.36), 1.17 (1.10–1.24), 1.30 (1.17–1.44), and 1.25 (1.11–1.40), respectively. All six SNPs were significantly associated with RA in Asian populations. Three SNPs (PADI4_104, 90, 89) showed significant associations, while the other three SNPs (PADI4_94, 92, 100) exhibited no associations in the European population. A dose–response relationship between allele 2 of PADI4 and the risk of RA was also identified. In conclusion, this meta-analysis suggests that PADI4 polymorphisms represent a significant risk factor for RA, especially in Asians.

Hepatic transcatheter arterial chemoembolization (TACE), a minimally invasive procedure to block the blood supply of tumors and release of cytotoxic agents, is preferentially applied to patients with hepatocellular carcinoma (HCC) who are not able to receive radical treatments. However, the long-term effects of TACE are unsatisfactory, as the microenvironment following procedure stimulates tumor angiogenesis, which promotes recurrence and metastasis of residual tumors. Tumor associated macrophages (TAMs) have been revealed to stimulate tumor growth and angiogenesis associated with poor prognosis in HCC. The present study focused on the changes in TAMs following TACE, and explored the effects of TACE in combination with the TAM inhibitor zoledronic acid (ZA) in rat HCC models. Orthotropic HCC rats were divided into three groups: Sham TACE, TACE alone and TACE combined with ZA treatment. At 7 or 14 days following TACE, tumor growth was evaluated by magnetic resonance imaging (MRI). Infiltration of TAMs was assessed by histological analysis and flow cytometry. Tumor angiogenesis was measured as the mean vessel density, and initial slope was calculated from dynamic contrast enhancement MRI. Local and systemic levels of vascular endothelial growth factor (VEGF) were determined by western blotting or an ELISA, respectively. The results revealed that TACE inhibited tumor growth at 7 days following the procedure, but this inhibition was attenuated at 14 days following the procedure compared with the sham TACE control. If combined with ZA treatment, TACE exhibited a stable inhibition effect on tumor growth until the end of observation. Investigation of the underlying mechanisms demonstrated that TACE combined with ZA treatment inhibited infiltration of F4/80 positive TAMs and tumor angiogenesis compared with the TACE alone group at 14 days following the procedure. Additionally, the combination treatment significantly inhibited secretion of VEGF in the present models. In conclusion, ZA treatment enhanced the effects of TACE through inhibiting TAM infiltration and tumor angiogenesis in rat HCC models.

Pulmonary fibrosis (PF) is a serious progressive lung disease and it originates from inflammation-induced parenchymal injury with excessive extracellular matrix deposition to result in the destruction of the normal lung architecture. Modified Kushen Gancao Formula (mKG), derived from traditional Chinese herbal medicine, has a prominent anti-inflammatory effect. The present study is to explore the inhibitory effects of mKG on bleomycin (BLM)-induced pulmonary fibrosis in mice. mKG significantly decreased pulmonary alveolitis, fibrosis scores, and interleukin-6 (IL-6), interleukin-17 (IL-17), transforming growth factor-β (TGF-β) and hydroxyproline (HYP) levels in lung tissue of mice compared with BLM treatment. It markedly alleviated the increase of HYP content in the lung tissues and pathologic changes of pulmonary fibrosis caused by BLM instillation. In conclusion, mKG has an anti-fibrotic effect and might be employed as a therapeutic candidate agent for attenuating pulmonary fibrosis.

There is much more profit in synthesis of cordierite from high-alumina fly ash, comparing with common fly ash. In this paper, the high-alumina fly ash collected from the Jungar power plant was calcined, grinded, beneficiated with HCl, diluted and dried. Furthermore, the cordierite was conducted from the purified fly ash and talc powder mixtures by solid reaction sintering. The physical properties of the cordierite samples were measured using Archimedes’ method, and the phase of cordierite samples was analyzed by XRD and the microstructure of the cordierite samples was observed by SEM. The results show that the cordierite, based on the proportion of the treated high-alumina fly ash and talc powder designated as 1.515/1 at 1350°C or/an 1370°C for 2h or/and 3h, could meet the quality requirement of physical properties, and the major crystalline phases in the sintered samples were predominantly α-cordierite (indialite) with minor crystals of mullite, spinel and almost no glassy matter.