[Effects of surface treatment on the phase and fracture strength of yttria- and magnesia-stabilized zirconia implants].

OBJECTIVE: To evaluate the effects of surface treatment on the phase and fracture strength of yttria-and magnesia-stabilized and its mechanisms. METHODS: One-piece cylindrical screw-type implants were fabricated with yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) and magnesia partially stabilized zirconia (Mg-PSZ) using computer aided design (CAD)/computer aided manufacture (CAM) technique.They were divided into three groups: (1) placed in water for 1 h after final sintering (control group), (2) sandblasting using 110 µm Al2O3 particles, (3) sandblasting plus etching with hydrofluoric acid for 1 h.The surface morphology and roughness of the implants were evaluated.Tetragonal to monoclinic transformation was measured on the surface by X-ray diffraction.Static tests of the zirconia implants were carried out at room temperature following the International Standards Organization (ISO)14801:2014 Standard. RESULTS: Both sandblasting alone and sandblasting plus acid etching significantly increased surface roughness (Ra) of Mg-PSZ and Y-TZP implants (P < 0.01), with sandblasting plus acid etching exhibited the highest surface roughness.No monoclinic band was detected in Mg-PSZ surface.Compared with the control group, the surface monoclinic content of Mg-PSZ had no obvious change after surface treatments.However, strong monoclinic bands appeared in surface modified Y-TZP.Monoclinic content of Y-TZP was higher than that of control group (1.55%) after both sandblasting alone (16.44%) and sandblasting plus acid etching (7.68%).For Mg-PSZ implants, fracture strengths of sandblasting group and sandblasting plus acid etching group were (294.1±3.3) N and (331.3±26.4) N respectively, which were lower than that of control group (458.4±48.7) N with significant differences (P < 0.01).For Y-TZP implants, fracture strength of control group was (827.3±101.6) N.Compared with control group, sandblasting group showed significantly higher fracture strength (P=0.03), which was (1 162.9±116.5) N.While sandblasting plus acid etching group had a fracture strength of (867.2±171.0) N, with no significant difference with control group (P>0.99). CONCLUSION: Sandblasting improved the fracture strength of Y-TZP implants.For the Mg-PSZ implants manufactured in this study, surface treatments with sandblasting and sandblasting plus acid etching resulted in a decrease of fracture strength.

Infection risk in psoriatic patients receiving tumour necrosis factor inhibitors: a 20-year systematic review and meta-analysis of randomized controlled trials.

Tumour necrosis factor inhibitors (TNFis) are commonly used for treating psoriatic diseases; however, the risk of infection while receiving TNFis remains uncertain. The aim of this study was to investigate the infection risk in patients with psoriatic disease receiving TNFis. A prospectively registered systematic literature search was conducted in Medline (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and the ClinicalTrials.gov databases from inception to December 31, 2021. We included double-blind randomized controlled trials that compared TNFis or other biologics with placebo in adults with psoriasis or psoriatic arthritis. The primary outcomes included overall and serious infection risks, and secondary outcomes included upper respiratory infections and nasopharyngitis risks. The risk ratio of the dichotomous outcome was calculated using the Mantel-Haenszel method with random effects, and heterogeneity was assessed using Cochran's Q statistic and quantified using the I-squared statistic. A total of 48 studies with 15 464 patients with psoriatic diseases were included. The meta-analysis demonstrated a slightly increased overall infection risk (risk ratio = 1.09; 95% confidence interval, 1.02-1.15) but not serious infection risk (risk ratio = 0.95; 95% confidence interval, 0.61-1.49) among patients receiving TNFis. There were also no increased risks of upper respiratory infections (risk ratio = 1.10; 95% confidence interval, 0.94-1.28) or nasopharyngitis (risk ratio = 1.14; 95% confidence interval, 1.00-1.30). In subgroup analyses using the fixed effects model, only etanercept and certolizumab pegol were, respectively, associated with an increased risk of overall infection (RR = 1.14, 95% CI, 1.03-1.27) and upper respiratory infections (RR = 1.42, 95% CI, 1.02-1.98). In conclusion, evidence to date suggests an increased overall infection risk that is generally tolerable in patients with psoriatic diseases receiving TNFis. There are no increased risks of serious infections, upper respiratory infections or nasopharyngitis.

[Cardiovascular biomarkers improve precise risk assessment for cardiovascular diseases].

Cardiovascular diseases (CVD) is an urgent threat to Chinese. It is of primary importance to assess risk for cardiovascular diseases. However, there are some limitations about traditional tools for CVD risk assessment. Recently, numbers of clinical trials demonstrated that CVD risk assessments based on cardiovascular biomarkers would significantly improve sensitivity and specificity of prediction. The comment review the limitations of traditional tools for CVD risk assessment, the application value of novel tools and advances of cardiovascular biomarkers in CVD prediction. It is benefit for precise stratification and management of general population during risk stage. Archieving the strategic goal of"Healthy China"would be promising soon.

Gamma-Ray Observation of the Cygnus Region in the 100-TeV Energy Region.

We report observations of gamma-ray emissions with energies in the 100-TeV energy region from the Cygnus region in our Galaxy. Two sources are significantly detected in the directions of the Cygnus OB1 and OB2 associations. Based on their positional coincidences, we associate one with a pulsar PSR J2032+4127 and the other mainly with a pulsar wind nebula PWN G75.2+0.1, with the pulsar moving away from its original birthplace situated around the centroid of the observed gamma-ray emission. This work would stimulate further studies of particle acceleration mechanisms at these gamma-ray sources.

First Detection of sub-PeV Diffuse Gamma Rays from the Galactic Disk: Evidence for Ubiquitous Galactic Cosmic Rays beyond PeV Energies.

We report, for the first time, the long-awaited detection of diffuse gamma rays with energies between 100 TeV and 1 PeV in the Galactic disk. Particularly, all gamma rays above 398 TeV are observed apart from known TeV gamma-ray sources and compatible with expectations from the hadronic emission scenario in which gamma rays originate from the decay of π^{0}'s produced through the interaction of protons with the interstellar medium in the Galaxy. This is strong evidence that cosmic rays are accelerated beyond PeV energies in our Galaxy and spread over the Galactic disk.

First Detection of Photons with Energy beyond 100 TeV from an Astrophysical Source.

We report on the highest energy photons from the Crab Nebula observed by the Tibet air shower array with the underground water-Cherenkov-type muon detector array. Based on the criterion of a muon number measured in an air shower, we successfully suppress 99.92% of the cosmic-ray background events with energies E>100 TeV. As a result, we observed 24 photonlike events with E>100 TeV against 5.5 background events, which corresponds to a 5.6σ statistical significance. This is the first detection of photons with E>100 TeV from an astrophysical source.

Photoinduced antibacterial activity of NRC03 peptide-conjugated dopamine/nano-reduced graphene oxide against Staphylococcus aureus.

In recent years, several drugs have become relatively easy to obtain with the rapid development of the economy and improvement in people's living standards. However, pathogenic bacteria have evolved strains that are resistant to certain drugs, such as antibiotics. Peptides are generally considered to be safe, have high tolerance to drugs, and are easy to manufacture. However, peptides are easily decomposed in complex biological environments. To solve this problem, many studies have modified peptides on the surface of nanomaterials to increase their functionality, biocompatibility, and stability. Meanwhile, nanomaterials have exhibited good absorption of near-infrared (NIR) light. When the NIR laser is focused on nanomaterials, photons are absorbed and the energy of the photons is converted into heat. Low-toxicity NRC03 peptide-conjugated dopamine/nano-reduced-graphene oxide (NRC03-DA/nRGO) nanomaterials are synthesized in this study for antibacterial testing using photothermal technology. The strains used in this study were Gram-positive Staphylococcus aureus (S. aureus). Our results indicated that the synthesized NRC03-DA/nRGO exhibits good absorption of NIR light and high photothermal conversion efficiency. Moreover, the synthesized NRC03-DA/nRGO inhibits the growth and survival of S. aureus. When the NRC03 peptide is modified on the surface of DA/nRGO, its biological stability is improved and the photothermal effect generated by NIR light produces additive effects, thereby indicating potential antibacterial applications.

Understanding the Early Biological Effects of Isoprene-Derived Particulate Matter Enhanced by Anthropogenic Pollutants.

INTRODUCTION: Airborne fine particulate matter (PM2.5; particulate matter ≤ 2.5 µm in aerodynamic diameter) plays a key role in air quality, climate, and public health. Globally, the largest mass fraction of PM2.5 is organic, dominated by secondary organic aerosol (SOA) formed from atmospheric oxidation of volatile organic compounds (VOCs). Isoprene from vegetation is the most abundant nonmethane VOC emitted into Earth's atmosphere. Isoprene has been recently recognized as one of the major sources of global SOA production that is enhanced by the presence of anthropogenic pollutants, such as acidic sulfate derived from sulfur dioxide (SO2), through multiphase chemistry of its oxidation products. Considering the abundance of isoprene-derived SOA in the atmosphere, understanding mechanisms of adverse health effects through inhalation exposure is critical to mitigating its potential impact on public health. Although previous studies have examined the toxicological effects of certain isoprene-derived gas-phase oxidation products, to date, no systematic studies have examined the potential toxicological effects of isoprene-derived SOA, its constituents, or its SOA precursors on human lung cells. SPECIFIC AIMS: The overall objective of this study was to investigate the early biological effects of isoprene-derived SOA and its subtypes on BEAS-2B cells (a human bronchial epithelial cell line), with a particular focus on the alteration of oxidative stress- and inflammation-related genes. To achieve this objective, there were two specific aims.1. Examine toxicity and early biological effects of SOA derived from the photochemical oxidation of isoprene, considering both urban and downwind-urban types of chemistry.2. Examine toxicity and early biological effects of SOA derived directly from downstream oxidation products of isoprene (i.e., epoxides and hydroperoxides). METHODS: Isoprene-derived SOA was first generated by photooxidation of isoprene under natural sunlight in the presence of nitric oxide (NO) and acidified sulfate aerosols. Experiments were conducted in a 120-m3 outdoor Teflon-film chamber located on the roof of the Gillings School of Global Public Health, University of North Carolina at Chapel Hill (UNC-Chapel Hill). BEAS-2B cells were exposed to chamber- generated isoprene-derived SOA using the Electrostatic Aerosol in Vitro Exposure System (EAVES). This approach allowed us to generate atmospherically relevant compositions of isoprene-derived SOA and to examine its toxicity through in vitro exposures at an air-liquid interface, providing a more biologically relevant exposure model. Isoprene-derived SOA samples were also collected, concurrently with EAVES sampling, onto Teflon membrane filters for in vitro resuspension exposures and for analysis of aerosol chemical composition by gas chromatography/electron ionization-quadrupole mass spectrometry (GC/EI-MS) with prior trimethylsilylation and ultra-performance liquid-chromatography coupled to high-resolution quadrupole time-of-flight mass spectrometry equipped with electrospray ionization (UPLC/ESI-HR-QTOFMS). Isoprene-derived SOA samples were also analyzed by the dithiothreitol (DTT) assay in order to characterize their reactive oxygen species (ROS)-generation potential.Organic synthesis of known isoprene-derived SOA precursors, which included isoprene epoxydiols (IEPOX), methacrylic acid epoxide (MAE), and isoprene-derived hydroxyhydroperoxides (ISOPOOH), was conducted in order to isolate major isoprene-derived SOA formation pathways from each other and to determine which of these pathways (or SOA types) is potentially more toxic. Since IEPOX and MAE produce SOA through multiphase chemistry onto acidic sulfate aerosol, dark reactive uptake experiments of IEPOX and MAE in the presence of acidic sulfate aerosol were performed in a 10-m3 flexible Teflon indoor chamber at UNC-Chapel Hill. Since the generation of SOA from ISOPOOH (through a non-IEPOX route) requires a hydroxyl radical (•OH)-initiated oxidation, ozonolysis of tetramethylethylene (TME) was used to form the needed •OH radicals in the indoor chamber. The resultant low-volatility multifunctional hydroperoxides condensed onto nonacidified sulfate aerosol, yielding the ISOPOOH-derived SOA needed for exposures. Similar to the outdoor chamber SOAs, IEPOX, MAE- and ISOPOOH-derived SOAs were collected onto Teflon membrane filters and were subsequently chemically characterized by GC/EI-MS and UPLC/ESI-HR-QTOFMS as well as for ROS-generation potential using the DTT assay. These filters were also used for resuspension in vitro exposures.By conducting gene expression profiling, we provided mechanistic insights into the potential health effects of isoprene-derived SOA. First, gene expression profiling of 84 oxidative stress- and 249 inflammation-associated human genes was performed for cells exposed to isoprene-derived SOA generated in our outdoor chamber experiments in EAVES or by resuspension. Two pathway-focused panels were utilized for this purpose: (1) nCounter GX Human Inflammation Kit comprised of 249 human genes (NanoString), and (2) Human Oxidative Stress Plus RT2 Profiler PCR Array (Qiagen) comprised of 84 oxidative stress-associated genes. We compared the gene expression levels in cells exposed to SOA generated in an outdoor chamber from photochemical oxidation of isoprene in the presence of NO and acidified sulfate seed aerosol to cells exposed to a dark control mixture of isoprene, NO, and acidified sulfate seed aerosol to isolate the effects of the isoprene-derived SOA on the cells using the EAVES and resuspension exposure methods. Pathway-based analysis was performed for significantly altered genes using the ConsensusPathDB database, which is a database system for the integration of human gene functional interactions to provide biological pathway information for a gene set of interest. Pathway annotation was performed to provide biological pathway information for each gene set. The gene-gene interaction networks were constructed and visualized using the GeneMANIA Cytoscape app (version 3.4.1) to predict the putative function of altered genes. Lastly, isoprene-derived SOA collected onto filters was used in resuspension exposures to measure select inflammatory biomarkers, including interleukin 8 (IL-8) and prostaglandin-endoperoxide synthase 2 (PTGS2) genes, in BEAS-2B cells to ensure that effects observed from EAVES exposures were attributable to particle-phase organic products. Since EAVES and resuspension exposures compared well, gene expression profiling for IEPOX-, MAE- and ISOPOOH-derived SOA were conducted using only resuspension exposures. RESULTS AND CONCLUSIONS: Chemical characterization coupled with biological analyses show that atmospherically relevant compositions of isoprene-derived SOA alter the levels of 41 oxidative stress-related genes. Of the different composition types of isoprene-derived SOA, MAE- and ISOPOOH-derived SOA altered the greatest number of genes, suggesting that carbonyl and hydroperoxide functional groups are oxidative stress promoters. Taken together, the different composition types accounted for 34 of the genes altered by the total isoprene-derived SOA mixture, while 7 remained unique to the total mixture exposures, indicating that there is either a synergistic effect of the different isoprene-derived SOA components or an unaccounted component in the mixture.The high-oxides of nitrogen (NOx) regime, which yielded MAE- and methacrolein (MACR)-derived SOA, had a higher ROS-generation potential (as measured by the DTT assay) than the low- NOx regime, which included IEPOX- and isoprene-derived SOA. However, ISOPOOH-derived SOA, which also formed in the low- NOx regime, had the highest ROS-generation potential, similar to 1,4-naphthoquinone (1,4-NQ). This suggests that aerosol-phase organic peroxides contribute significantly to particulate matter (PM) oxidative potential. MAE- and MACR- derived SOA showed equal or greater ROS-generation potential than was reported in prior UNC-Chapel Hill studies on diesel exhaust PM, highlighting the importance of a comprehensive investigation of the toxicity of isoprene-derived SOA. Notably, ISOPOOH-derived SOA was one order of magnitude higher in ROS-generation potential than diesel exhaust particles previously examined at UNC-Chapel Hill. As an acellular assay, the DTT assay may not be predictive of oxidative stress; therefore, we also focused on the gene expression results from the cellular exposures.We have demonstrated that the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and the redox-sensitive activation protein-1 (AP-1) transcription factor networks have been significantly altered upon exposure to isoprene-derived SOA. The identification of Nrf2 pathway in cells exposed to isoprene-derived SOA is in accordance with our findings using the DTT assay, which measures the thiol reactivity of PM samples as a surrogate for their ROS-generation potential. Specifically, our results point to the cysteine-thiol modifications within cells that lead to activation of Nrf2-related gene expression.However, based on our gene expression results showing no clear relationship between DTT activity and the number of altered oxidative stress-related genes, the DTT activity of isoprene-derived SOA may not be directly indicative of toxicity relative to other SOA types. While activation of Nrf2-associated genes has been identified with responses to oxidative stress and linked to traffic related air pollution exposure in both toxicological and epidemiological studies, their implicit involvement in this study suggests that activation of Nrf2-related gene expression may occur with exposures to all sorts of PM types.By controlling the exposure time, method, and dose we demonstrated that among the SOA derived from previously identified individual precursors of isoprene-derived SOA, ISOPOOH-derived SOA alters moreoxidative stress related genes than does IEPOX-derived SOA, but fewer than MAE-derived SOA. This suggests that the composition of MAE-derived SOA may be the greatest contributor to alterations of oxidative stress-related gene expression observed due to isoprene-derived SOA exposure. Further study on induced levels of protein expression and specific toxicological endpoints is necessary to determine if the observed gene expression changes lead to adverse health effects. In addition, such studies have implications for pollution-control strategies because NOx and SO2 are controllable pollutants that can alter the composition of SOA, and in turn alter its effects on gene expression. The mass fraction of different components of atmospheric isoprene derived SOA should be considered, but altering the fraction of high- NOx isoprene-derived SOA (e.g., MAE derived SOA) may yield greater changes in gene expression than altering the fraction of low- NOx isoprene derived SOA types (ISOPOOH- or IEPOX-derived SOA). Finally, this study confirms that total isoprene-derived SOA alters the expression of a greater number of genes than does SOA derived from the tested precursors. This warrants further work to determine the underlying explanation for this observation, which may be uncharacterized components of isoprene-derived SOA or the potential for synergism between the studied components.

[Prospective controlled observation ofeffect of adjuvant chemotherapy onsurvival and prognosis ofhigh-risk upper tract urothelial carcinoma patients underwent radical nephroureterectomy].

Objective: To assess the oncologic outcomes of radical nephroureterectomy (RNU) combined with adjuvant chemotherapy (ACT) in patients with high risk upper tract urothelial carcinoma (UTUC). Methods: From January 2014, all high-risk UTUC patients after RNU surgery were enrolled in this prospective comparative trial. And these patients were randomized to ACT group (Gemcitabine+Cisplatin three weeks regimen) and observing group. Cox proportional hazard modeling and Kaplan-Meier analysis were used to determine overall survival (OS), cancer specific survival (CSS) and disease-free survival (PFS) in the cohort. Results: The median follow-up duration was36 months (range: 6-54) in the ACT group (n=94) and 30 months (range: 6-54) in the observing group (n=82). Oncologic outcomes of RNU treated high-risk UTUC patients were improved much significantly by ACT: OS [P=0.0397, HR: 1.39(0.91-1.75)], CSS [P=0.0255, HR: 1.26(1.07-1.45)] and PFS [P=0.0033, HR: 3.78(3.13-4.55)]. The further analysis in lymph node positive cohort displayed that median times of oncologic events were prolonged in the ACT group compared with the observing group: OS (26.8mon vs 36.3mon, P=0.0255), CSS (28.2mon vs39.3mon, P=0.0197) and PFS (11.4mon vs 31.9mon, P=0.0018). Additionally in T3/4 cohort, the significant growth in the median times of OS (20.6mon vs 32.2mon, P=0.0183), CSS (21.9mon vs 38.4mon, P=0.0226) and PFS (13.9mon vs 36.3mon, P=0.0217) were observed in ACT group. Conclusion: ACT could play the important synergistic role in improving the OS, CSS and PFS of high-risk UTUC patients after RNU.

[Derepression of CXCR7 indicates resistance to enzalutamide in castration resistant prostate cancer].

Objective: To investigate the effect of the derepression of chemokine receptor-7 (CXCR7) in prostatic tissues from patients with Castration Resistant Prostate Cancer (CRPC) on the resistance to enzalutamide (Enza). Methods: During the period of January 2015 to December 2017 all CRPC cases who underwent radical radiotherapy or androgen deprivation therapy (ADT) were evaluated. After prostatic puncture biopsy, the tissues were treated for immunostaining with CXCR7. Cox proportional hazard modeling and Kaplan-Meier analysis were used to determine PSA Progression-Free Survival (PSAP-FS) and Clinical or Radiographic Progression-Free Survival (CRP-FS) in the cohort. At last, PSA response rates and progression outcomes in CXCR7 negative cases and CXCR7 positive cases were analyzed. Results: Total 39 CRPC patients were enrolled in this study. And 23 cases derepress CXCR7, 16 cases negatively express CXCR7. The median follow-up duration was 12 months (range: 6-18) in the cohort. Chi-square analysis confirmed that PSA response rates after Enza treatment were significantly associated with CXCR7 derepression (χ(2)=22.129, P=0.000 06). Compared with CXCR7 positive expression group, CXCR7 negative expression group displayed improved median PSAP-FS (4.4 mon vs 11.7 mon, P=0.040 8) and CRP-FS (5.2 mon vs 13.1 mon, P=0.036 2) after Enza treatment. Conclusion: Derepression of CXCR7 in CRPC patients may be associated with resistance to enzalutamide. This protein may be novel target for treatment of CRPC.

[Oncologic outcomes of high-risk upper tract urothelial carcinoma patients undergoing radical nephroureterectomy combined with adjuvant chemotherapy].

Objective: To assess the oncologic outcomes of radical nephroureterectomy (RUN) combined with adjuvant chemotherapy (ACT) in patients with high risk upper tract urothelial carcinoma (UTUC). Methods: One-hundred-thirty-four individuals with high-risk UTUC who underwent RUN with or without ACT were evaluated. Cox proportional hazard model and Kaplan-Meier analysis were used to determine overall and cancer specific survival in the cohort. Results: The median follow-up duration was 24 months (range: 6-36) in the RUN group (n=61) and 18 months (range: 6-36) in the RUN+ACT group (n=73). Median time of overall survival (OS) and cancer specific survival (CSS) showed much better in RUN+ACT group than in RUN group, but the differences were not reached the significant standard. The further analysis in lymph node positive cohort displayed that median times of oncologic events were prolonged in the RUN+ACT group compared with the RUN group: OS (30.1 mon vs 18.0 mon, P=0.083) and CSS (29.2 mon vs 18.6 mon, P=0.047). Additionally in T3/T4 cohort, the significant growth in the median times of OS (25.2 mon vs 12.6 mon, P=0.038) and CSS (31.3 mon vs 18.9 mon, P=0.044) were observed in combination treatment group. Conclusion: ACT could play the important synergistic role in improving the OS and CSS of RUN treated UTUC patients with lymph node-positive or stage of T3/T4.

[Correlation between interleukin-6 single nucleotide polymorphism and the occurrence and prognosis of hepatitis B virus-associated acute-on-chronic liver failure].

Objective: To investigate the correlation between interleukin-6 (IL-6) single nucleotide polymorphism (SNP) and the occurrence and prognosis of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Methods: Patients with chronic hepatic diseases diagnosed as HBV infection in the Hepatology Center of the First Affiliated Hospital of Fujian Medical University from July 2012 to March 2018 were divided into HBV-ACLF and non-ACLF group. SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) was determined by the improved multi-temperature ligase detection reaction (imLDRTM) technique. Simultaneously, case data were reviewed with the 3-months followed up survival condition of the ACLF group. Normally distributed data were expressed as arithmetic means and SDs, and t-test was adopted. Data with skewed distribution were expressed as medians with interquartile range, and were measured by non-parametric test. Multivariate logistic regression analysis was used to analyze the relative risk of genetic polymorphism and HBV-ACLF as well as the relationship between IL-6 SNPs with the occurrence and prognosis of HBV-ACLF. Results: Four hundred patients were included in the study, with 122 (30.5%) in the HBV-ACLF and 278 (69.5%) in the non-ACLF group. There were significant differences in total bilirubin, albumin, and white blood cell count, percentage of neutrophils, platelet count, alanine aminotransferase, aspartate aminotransferase, prothrombin time and international standardized ratio, creatinine and the model for end-stage liver disease score between the two groups (P < 0.001). The genotype of IL-6 genes (rs1800795, rs1800797, rs2069827, and rs2069830) of all subjects showed no mutation or the mutation rate under 1%. There was no significant difference in the genotype of IL-6 (rs1524107, rs2069837, rs2069840 and rs2069845) between the two groups (P > 0.05). Multivariate logistic regression analysis showed that the SNPs in the above four loci of IL-6 gene was not associated with HBV-ACLF risk, nor had significant correlation with the 3-months prognosis. Conclusion: The SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) is unrelated to the occurrence and short-term prognosis of HBV-ACLF.

[Activation of HIF-1α/ß-catenin signal pathway leads to radioresistance of prostate cancer cells].

Objective: To investigate the role of hypoxia-inducible factor-1α (HIF-1α) and ß-catenin in radioresistance of prostate cancer (PCa) cells. Method: Two PCa cell lines, LNCaP and C4-2B, were grouped as: negative control (no treatment), HIF-1α overexpression group (transfected with HIF-1α plasmids), and ß-catenin silencing group (transfected with HIF-1α plasmids and ß-catenin-shRNA). Cell proliferation, cycle, invasion, and radiosensitivity were measured under normal or hypoxic condition. Radiosensitivity was tested in two mice PCa models (the LNCaP orthotopic BALB/c-nu mice model and the C4-2B subcutaneous SCID mice model). Results: In both LNCaP and C4-2B cells, HIF-1α transfection led to an enhanced ß-catenin nuclear translocation, while ß-catenin silencing inhibited the ß-catenin nuclear translocation. Enhanced ß-catenin nuclear translocation caused by HIF-1α overexpression resulted in enhanced cell proliferation and invasion, altered cell cycle distribution, reduced apoptosis, and improved non-homologous-end-joining (NHEJ) repair under irradiation condition. In vivo imaging of orthotopic models showed that HIF-1α overexpression LNCaP cells produced tumors with 3-fold volume (P=0.003 1) and 2-fold wet weight (P=0.039 4) than those by negative control cells at day 21, and ß-catenin silencing cells aberrantly reduced both tumor volume (P=0.000 3) and wet weight (P=0.017 5) than HIF-1α overexpression cells. In addition, C4-2B subcutaneous models showed similar tumor promotion effects induced by HIF-1α overexpression (tumor volume: P=0.000 1 and wet weight: P=0.047 3) and suppressive effects by ß-catenin silencing (tumor volume: P<0.000 1 and wet weight: P=0.022 1) as LNCaP orthotopic xenograft with regard to tumor volume and wet weight. Conclusions: HIF-1α overexpression enhanced ß-catenin nuclear translocation, which led to the activation of the ß-catenin/NHEJ signaling pathway and increased cell proliferation, invasion, and DNA repair. These results suggest that HIF-1α overexpression led to radioresistance of PCa cells.

[The relationship between smoking and hyperuricemia in Chinese residents].

Objective: To explore the relationship between smoking and hyperuricemia in Chinese residents. Methods: Based on data from the China Health and Nutrition Survey (CHNS), residents with blood samples provided in the 2009 round (including information of socio-demographic factors, lifestyle behaviors, medical history, and laboratory examinations etc.) were selected as the participants in the current analysis. Unconditional logistic regression models were utilized to compute the ORs and corresponding 95%CIs for assessing the relationship between smoking and hyperuricemia. Results: Among the 8 785 subjects, 1 435 had hyperuricemia with a prevalence rate of 16.3%, consisting of 886 men and 549 women with prevalence rates of 21.6% (886/4 110) and 11.7% (549/4 675) , respectively. Compared with never smokers, the adjusted OR (95%CI) for hyperuricemia was 0.83 (0.70-0.98) among current smokers, 0.77 (0.63-0.94) among current smokers with 20-39 years of smoking, and 0.79 (0.65-0.97) among current smokers with 11-20 cigarettes per day. When stratified by gender and compared with non-smoker, the adjusted OR (95%CI) for hyperuricemia among current smokers compared with never smokers was 0.83 (0.70-0.98) among men, while no significant association was found in female current smokers (OR=0.73, 95%CI: 0.42-1.26, P=0.260). Conclusion: In Chinese residents, there is an inverse association between smoking and hyperuricemia prevalence, and this association may be related to duration and intensity of smoking among current smokers. The findings need to be validated in large prospective cohort studies.

Effect of a high-concentrate diet on milk components and mammary health in Holstein dairy cows.

In order to evaluate the milk yield, milk quality, and health of dairy cows fed a high-concentrate (HC) diet, eight lactating Holstein dairy cattle were randomly assigned to HC or low-concentrate (LC) diet groups and fed for 50 days, and the auto-control studying before and after treatment with the two diets was used. During the experiment, plasma and milk samples were collected and measured. With regard to milk component, HC feeding led to higher milk production (P < 0.05), but significantly lower milk protein percentage (P < 0.05), milk protein yield (P < 0.05), and milk fat percentage (P < 0.05) throughout the five periods than LC feeding. Milk somatic cell count and N-acetyl-D-glucosaminidase activity (P < 0.01) were higher than those observed under LC feeding. mRNA expression levels of interleukin-8 (IL-8), C-C motif chemokine ligand (CCL5), and lactalbumin alpha (α-LA) were investigated by qPCR and found to be significantly lower (P < 0.01) in cattle fed the HC diet. The amino acid content was analyzed by high performance liquid chromatography (HPLC), and the content of Asp (P < 0.01), Gln (P < 0.01), Ala (P < 0.05), Leu (P < 0.05), Lys (P < 0.05), and Ile (P < 0.01) was significantly lower in the HC group, whereas the content of Arg (P < 0.05) and Phe (P < 0.01) was significantly higher. These results suggest that the HC diet might have an important influence on mammary health. The amino acid content was lower, suggesting that depletion of amino acids, resulting in depleted milk protein, affects milk quality.

[Amphioxus ortholog of ECSIT, an evolutionarily conserved adaptor in the Toll and BMP signaling pathways].

In vertebrates, evolutionarily conserved signaling intermediate in the Toll pathway (ECSIT) interacts with the TNF-receptor associated factor 6 (TRAF6) to regulate the processing of MEKK1, activate NF-κB, and also control BMP target genes. However, the role of ECSIT in invertebrates remains largely unexplored. We performed comparative investigations of the expression, gene structure, and phylogeny of ECSIT, Toll-like receptor (TLR), and Smad4 in the cephalochordate Branchiostoma belcheri. Phylogenetic analysis indicated that, in amphioxus, ECSIT, TLR, and Smad4 form independent clusters at the base of Chordate   clusters. Interestingly, overall gene structures were comparable to those in vertebrate orthologs. Transcripts of AmphiECSIT were detectable at the mid-neural stage, and continued to be expressed in the epithelium of the pharyngeal region at later stages. In adult animals, strong expression was observed in the nerve cord, endostyle, epithelial cells of the gut and wheel organ, genital membrane of the testis, and coelom and lymphoid cavities, what is highly similar to AmphiTLR and AmphiSmad4 expression patterns during development and in adult organisms. Our data suggests that ECSIT is evolutionarily conserved. Its amphioxus ortholog functions during embryonic development and as part of the innate immune system and may be involved in TLR/BMP signaling.

[Long-term oncologic outcomes of localized high-risk prostate cancer undergoing brachytherapy combined with external-beam radiation therapy and maximal androgen blockade].

Objective: To investigate the oncologic outcome and PSA kinetics of localized high-risk prostate cancer (PCa) patients treated with combination strategy of radiation therapy (RT) and maximal androgen blockade (MAB). Methods: We retrospectively reviewed the clinical data of 320 localized PCa patients undergoing RT+ MAB from 2001 to 2015. And radiation treatment protocol consisted of permanent prostate brachytherapy (PPB) at 110 Gy and EBRT at 45 Gy/23 fractions. Results: The median follow-up time was 90 (range: 12-186) months. And 117 (36.6%) cases underwent MAB + external-beam radiotherapy (EBRT), and other 203 (63.4%) cases received MAB+ EBRT+ PPB. Multivariate Cox regression analyses showed that PSA kinetics were positive indicators of oncologic outcomes. Furthermore, PSA kinetics were aberrantly improved by supplemental PPB to MAB+ EBRT as following, PSA nadir (1.3±0.7)µg/L vs(0.11±0.06)µg/L, time of PSA decrease to nadir (7.5±1.8)months vs (3.2±2.1)months, PSA doubling time (15.6±4.2)months vs (22.6±6.1)months, PSA decreasing amplitude (84.6±6.2)%vs(95.8±3.4)%. Additionally, the median time of several important oncologic events in MAB+ EBRT+ PPB group were also prolonged than that in MAB+ EBRT group as following, overall survival (12.3 years vs 9.1 years, P<0.001), biochemical recurrence-free survival (9.8 years vs 6.5 years, P<0.001), skeletal-related event (10.4years vs 8.2 years, P<0.001), and cytotoxic chemotherapy (11.6 years vs 8.8 years, P=0.007). Conclusion: MAB+ EBRT+ PPB is extremely effective combination strategy for localized high-risk PCa patients, and PPB plays the important synergistic role in improving PSA kinetics, which are independent predictor for oncologic outcomes.

A myosin activator improves actin assembly and sarcomere function of human-induced pluripotent stem cell-derived cardiomyocytes with a troponin T point mutation.

We have investigated cardiac myocytes derived from human-induced pluripotent stem cells (iPSC-CMs) from two normal control and two family members expressing a mutant cardiac troponin T (cTnT-R173W) linked to dilated cardiomyopathy (DCM). cTnT is a regulatory protein of the sarcomeric thin filament. The loss of this basic charge, which is strategically located to control tension, has consequences leading to progressive DCM. iPSC-CMs serve as a valuable platform for understanding clinically relevant mutations in sarcomeric proteins; however, there are important questions to be addressed with regard to myocyte adaptation that we model here by plating iPSC-CMs on softer substrates (100 kPa) to create a more physiologic environment during recovery and maturation of iPSC-CMs after thawing from cryopreservation. During the first week of culture of the iPSC-CMs, we have determined structural and functional characteristics as well as actin assembly dynamics. Shortening, actin content, and actin assembly dynamics were depressed in CMs from the severely affected mutant at 1 wk of culture, but by 2 wk differences were less apparent. Sarcomeric troponin and myosin isoform composition were fetal/neonatal. Furthermore, the troponin complex, reconstituted with wild-type cTnT or recombinant cTnT-R173W, depressed the entry of cross-bridges into the force-generating state, which can be reversed by the myosin activator omecamtiv mecarbil. Therapeutic doses of this drug increased both contractility and the content of F-actin in the mutant iPSC-CMs. Collectively, our data suggest the use of a myosin activation reagent to restore function within patient-specific iPSC-CMs may aid in understanding and treating this familial DCM.

N-cadherin-functionalized polymer-tethered multi-bilayer: a cell surface-mimicking substrate to probe cellular mechanosensitivity.

Fate and function of anchorage-dependent cells depend on a variety of environmental cues, including those of mechanical nature. Previous progress in the understanding of cellular mechanosensitivity has been closely linked to the availability of artificial cell substrates of adjustable viscoelasticity, allowing for a direct correlation between substrate stiffness and cell response. Exemplary, polymeric gel substrates with polymer-conjugated cell-substrate linkers provided valuable insight into the role of mechanical signals during cell migration in an extracellular matrix environment. In contrast, less is known about the role of external mechanical signals across cell-cell interfaces, in part, due to the limitations of traditional polymeric substrates to mimic the remarkable dynamics of cell-cell linkages. To overcome this shortcoming, we introduce a cell surface-mimicking cell substrate of adjustable stiffness, which is comprised of a polymer-tethered lipid multi-bilayer stack with N-cadherin linkers. Unlike traditional polymeric cell substrates with polymer-conjugated linkers, this novel artificial cell substrate is able to replicate the dynamic assembly/disassembly of cadherin linkers into linker clusters and the long-range movements of cadherin-based cell-substrate linkages observed at cell-cell interfaces. Moreover, substrate stiffness can be changed by adjusting the number of bilayers in the multi-bilayer stack, thus enabling the analysis of cellular mechanosensitivity in the presence of artificial cell-cell linkages. The presented biomembrane-mimicking cell substrate provides a valuable tool to explore the functional role of mechanical cues from neighboring cells.

Effects of pelvic floor muscle exercise on faecal incontinence in rectal cancer patients after stoma closure.

The purpose of this study was to examine the effects of pelvic floor muscle exercise (PFME) on the faecal incontinence (FI) of rectal cancer patients following stoma closure. Participants were randomly distributed into an exercise group (n = 27) and non-exercise group (n = 26). An experimental design and longitudinal approach were implemented for data collection. Baseline data were collected at 1 day before discharge, and then PFME was taught before the patients were discharged from the hospital. We collected data and followed up with the patients at their pre-discharge visit and at 1, 2, 3, 6 and 9 months after discharge. The Cleveland Clinic Faecal Incontinence (CCI) score was used to measure patient outcome. PFME proved to effectively decrease the degree of FI in stoma closure recipients. The FI score of the exercise group significantly decreased from 8.37 to 2.27 after PFME compared with that of the non-exercise group (from 8.54 to 2.58). The generalised estimation equation tests showed that both group and time were significantly different. The tests also indicated that although PFME appeared to hasten the decline of incontinence, this effect was no longer detectable at 9 months; thus, it may be an effective intervention for FI when implemented up to half a year after discharge.