Search

Pulmonary embolism remains the third leading cause of human mortality after malignant tumors and myocardial infarction. Commonly available thrombolytic therapeutic agents suffer from the limitations of very short half-life, inadequate targeting, limited clot penetration, and a propensity for severe bleeding. Inspired by the trident, we developed the armor-piercing microcapsule (MC), fucoidan-urokinase-S-nitrosoglutathione-polydopamine@MC (FUGP@MC), which exhibited a triple combination of photothermal, mechanical and pharmacological thrombolysis for the therapeutic treatment of acute pulmonary embolism (APE). Briefly, the outermost fucoidan layer was utilized for targeting to the APE area. Programmed APE treatment was triggered by near-infrared (NIR) light irradiation. Photothermal thrombolytic therapy was carried out by photothermal conversion of polydopamine. The photothermal conversion broke the S-nitroso bond in S-nitrosoglutathione (GSNO) and produced large amounts of nitric oxide (NO) for mechanical thrombolysis, which subsequently disrupted the interfacial structure of microcapsule to stimulate the release of the urokinase (UK), leading to a triple synergistic thrombolytic effect. The results demonstrated that the embolization residual rate of FUGP@MC (contained ≈ 1452.5 IU/kg UK) group was significantly lower than that of UK (10,000 IU/kg) group (6.35 % VS 16.78 %). Remarkably, FUGP@MC demonstrated a reliable in vivo biosafety proficiency. In summary, trident-inspired armor-piercing microcapsule FUGP@MC reveals a potential avenue for advancing pulmonary embolism therapeutics and promises to be a safer alternative candidate to current drug approaches., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Porcine epidemic diarrhea (PED), caused by the porcine epidemic diarrhea virus (PEDV), primarily affects the jejunum and ileum of pigs. Interferons, glycoproteins with high species specificity and potent antiviral activity, are crucial in defending against viral infections. Unlike other interferons, interferon-lambda (IFN-λ) mainly acts on mucosal epithelial cells and exhibits robust antiviral activity at mucosal surfaces. However, the high cost limits the use of naturally extracted interferons in farming. In this study, we expressed recombinant porcine interferon-lambda 1 (rpIFN-λ1) in eukaryotic cells, demonstrating effective antiviral activity against PEDV in Vero E6 and IPI-FX cells. In vivo, rpIFN-λ1 alleviated clinical symptoms and intestinal damage, enhanced antioxidant capacity, reduced inflammation, and significantly improved the survival rate of piglets following PEDV infection. Both in vitro and in vivo studies confirmed that rpIFN-λ1 upregulated interferon-stimulated genes (ISGs) via the JAK-STAT pathway, thereby exerting antiviral effects. In conclusion, rpIFN-λ1 significantly inhibited PEDV replication and alleviated clinical symptoms. The selectivity of rpIFN-λ1 for intestinal cells and its ability to reduce viral shedding suggest that this agent is a promising antiviral for enteric viruses such as PEDV. Our findings highlight rpIFN-λ1 as a cost-effective, efficient, and novel strategy for antiviral treatment of PEDV., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The PandaX-4T liquid xenon detector at the China Jinping Underground Laboratory is used to measure the solar ^{8}B neutrino flux by detecting neutrinos through coherent scattering with xenon nuclei. Data samples requiring the coincidence of scintillation and ionization signals (paired), as well as unpaired ionization-only signals (US2), are selected with energy threshold of approximately 1.1 keV (0.33 keV) nuclear recoil energy. Combining the commissioning run and the first science run of PandaX-4T, a total exposure of 1.20 and 1.04  tonne·year are collected for the paired and US2, respectively. After unblinding, 3 and 332 events are observed with an expectation of 2.8±0.5 and 251±32 background events, for the paired and US2 data, respectively. A combined analysis yields a best-fit ^{8}B neutrino signal of 3.5 (75) events from the paired (US2) data sample, with ∼37% uncertainty, and the background-only hypothesis is disfavored at 2.64σ significance. This gives a solar ^{8}B neutrino flux of (8.4±3.1)×10^{6}  cm^{-2} s^{-1}, consistent with the standard solar model prediction. It is also the first indication of solar ^{8}B neutrino "fog" in a dark matter direct detection experiment.

We report the first search for the elastic scatterings between cosmic-ray boosted sub-MeV dark matter (DM) and electrons in the PandaX-4T liquid xenon experiment. Sub-MeV DM particles can be accelerated by scattering with electrons in the cosmic rays and produce detectable electron recoil signals in the detector. Using the commissioning data from PandaX-4T of 0.63  tonne·year exposure, we set new constraints on DM-electron scattering cross sections for DM masses ranging from 10  eV/c^{2} to 3  keV/c^{2}.

Acute thrombosis and its complications are leading global causes of disability and death. Existing thrombolytic drugs, such as alteplase and urokinase (UK), carry a significant bleeding risk during clinical treatments. Thus, the development of a novel thrombolysis strategy is of utmost urgency. Based on the previous work, the hollow structure of microcapsules (MC) is fabricated. Subsequently, armor-piercing MC, known as Fucoidan/S-Nitrosoglutathione/Melanin@MC (FGM@MC) is obtained, using a layer-by-layer (LBL) self-assembly method. Utilizing near-infrared (NIR) light as a trigger, the FGM@MC demonstrated photothermal thrombolysis at the site of thrombus due to its stable and outstanding photothermal properties. Simultaneously, photothermal stimulation leads to the release of a significant amount of nitric oxide from the FGM@MC, resulting in cavitation effects for mechanical thrombolysis. In vivo experiments confirmed the stable release of nitric oxide under NIR light irradiation. Treatment of femoral vein thrombosis in rats revealed that the thrombolytic effectiveness of FGM@MC+NIR (53.71%) is comparable to that of UK (59.70%). Notably, FGM@MC does not interfere with the coagulation function of rats and exhibits a favorable safety profile. In conclusion, this study demonstrates that the drug-free armor-piercing microcapsule has significant potential in the treatment of thrombosis, offering a safe and effective alternative to traditional thrombolytic therapies., (© 2024 Wiley‐VCH GmbH.)

Background: A critical parameter of extracorporeal CO 2 removal (ECCO 2 R) applications is the CO 2 removal rate (VCO 2 ). Low-flow venovenous extracorporeal support with large-size membrane lung remains undefined. This study aimed to evaluate the VCO 2 of a low-flow ECCO 2 R with large-size membrane lung using a renal replacement therapy platform in an experimental animal model., Methods: Twelve healthy pigs were placed under mechanical ventilation and connected to an ECCO 2 R-CRRT system (surface area = 1.8 m 2 ; OMNIset®, BBraun, Germany). Respiratory settings were reduced to induce two degrees of hypercapnia. VCO 2 was recorded under different combinations of PaCO 2 (50-69 or 70-89 mm Hg), extracorporeal blood flow (ECBF; 200 or 350 mL/min), and gas flow (4, 6, or 10 L/min)., Results: VCO 2 increased with ECBF at all three gas flow rates. In severe hypercapnia, the increase in sweep gas flow from 4 to 10 L/min increased VCO 2 from 86.38 ± 7.08 to 96.50 ± 8.71 mL/min at an ECBF of 350 mL/min, whereas at ECBF of 200 mL/min, any increase was less effective. But in mild hypercapnia, the increase in sweep gas flow result in significantly increased VCO 2 at two ECBF. VCO 2 increased with PaCO 2 from 50-69 to 70-89 mm Hg at an ECBF of 350 mL/min, but not at ECBF of 200 mL/min. Post-membrane lung PCO 2 levels were similar for different levels of premembrane lung PCO 2 (p = 0.08), highlighting the gas exchange diffusion efficacy of the membrane lung in gas exchange diffusion. In severe hypercapnia, the reduction of PaCO 2 elevated from 11.5% to 19.6% with ECBF increase only at a high gas flow of 10 L/min (p < 0.05) and increase of gas flow significantly reduced PaCO 2 only at a high ECBF of 350 mL/min (p < 0.05)., Conclusions: Low-flow venovenous extracorporeal ECCO 2 R-CRRT with large-size membrane lung is more efficient with the increase of ECBF, sweep gas flow rate, and the degree of hypercapnia. The influence of sweep gas flow on VCO 2 depends on the ECBF and degree of hypercapnia. Higher ECBF and gas flow should be chosen to reverse severe hypercapnia., (© 2024 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

^{134}Xe is a candidate isotope for neutrinoless double beta decay (0νββ) search. In addition, the two-neutrino case (2νββ) allowed by the standard model of particle physics has not yet been observed. With the 656-kg natural xenon in the fiducial volume of the PandaX-4T detector, which contains 10.4% of ^{134}Xe, and its initial 94.9-day exposure, we have established the most stringent constraints on 2νββ and 0νββ of ^{134}Xe half-lives, with limits of 2.8×10^{22}  yr and 3.0×10^{23}  yr at 90% confidence level, respectively. The 2νββ (0νββ) limit surpasses the previously reported best result by a factor of 32 (2.7), highlighting the potential of large monolithic natural xenon detectors for double beta decay searches.

We report results of a search for dark-matter-nucleon interactions via a dark mediator using optimized low-energy data from the PandaX-4T liquid xenon experiment. With the ionization-signal-only data and utilizing the Migdal effect, we set the most stringent limits on the cross section for dark matter masses ranging from 30  MeV/c^{2} to 2  GeV/c^{2}. Under the assumption that the dark mediator is a dark photon that decays into scalar dark matter pairs in the early Universe, we rule out significant parameter space of such thermal relic dark-matter model.

We report a search for light dark matter produced through the cascading decay of η mesons, which are created as a result of inelastic collisions between cosmic rays and Earth's atmosphere. We introduce a new and general framework, publicly accessible, designed to address boosted dark matter specifically, with which a full and dedicated simulation including both elastic and quasielastic processes of Earth attenuation effect on the dark matter particles arriving at the detector is performed. In the PandaX-4T commissioning data of 0.63  tonne·year exposure, no significant excess over background is observed. The first constraints on the interaction between light dark matter generated in the atmosphere and nucleus through a light scalar mediator are obtained. The lowest excluded cross section is set at 5.9×10^{-37}  cm^{2} for a dark matter mass of 0.1  MeV/c^{2} and mediator mass of 300  MeV/c^{2}. The lowest upper limit of η to the dark matter decay branching ratio is 1.6×10^{-7}.

We report the search results of light dark matter through its interactions with shell electrons and nuclei, using the commissioning data from the PandaX-4T liquid xenon detector. Low energy events are selected to have an ionization-only signal between 60 to 200 photoelectrons, corresponding to a mean nuclear recoil energy from 0.77 to 2.54 keV and electronic recoil energy from 0.07 to 0.23 keV. With an effective exposure of 0.55  tonne·year, we set the most stringent limits within a mass range from 40  MeV/c^{2} to 10  GeV/c^{2} for pointlike dark matter-electron interaction, 100  MeV/c^{2} to 10  GeV/c^{2} for dark matter-electron interaction via a light mediator, and 3.2 to 4  GeV/c^{2} for dark matter-nucleon spin-independent interaction. For DM interaction with electrons, our limits are closing in on the parameter space predicted by the freeze-in and freeze-out mechanisms in the early Universe.

A search for interactions from solar ^{8}B neutrinos elastically scattering off xenon nuclei using PandaX-4T commissioning data is reported. The energy threshold of this search is further lowered compared with the previous search for dark matter, with various techniques utilized to suppress the background that emerges from data with the lowered threshold. A blind analysis is performed on the data with an effective exposure of 0.48  tonne year, and no significant excess of events is observed. Among the results obtained using the neutrino-nucleus coherent scattering, our results give the best constraint on the solar ^{8}B neutrino flux. We further provide a more stringent limit on the cross section between dark matter and nucleon in the mass range from 3 to 9  GeV/c^{2}.

Precise measurement of two-neutrino double beta decay (DBD) half-life is an important step for the searches of Majorana neutrinos with neutrinoless double beta decay. We report the measurement of DBD half-life of 136 Xe using the PandaX-4T dual-phase Time Projection Chamber (TPC) with 3.7-tonne natural xenon and the first 94.9-day physics data release. The background model in the fiducial volume is well constrained in situ by events in the outer active region. With a 136 Xe exposure of 15.5 kg-year, we establish the half-life as 2.27 ± 0.03( stat. ) ± 0.10( syst. ) × 10 21 years. This is the first DBD half-life measurement with natural xenon and demonstrates the physics capability of a large-scale liquid xenon TPC in the field of rare event searches., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2022 Lin Si et al.)

We report a search on sub-MeV fermionic dark matter absorbed by electrons with an outgoing active neutrino using the 0.63  tonne year exposure collected by the PandaX-4T liquid xenon experiment. No significant signals are observed over the expected background. The data are interpreted into limits to the effective couplings between such dark matter and the electron. For axial-vector or vector interactions, our sensitivity is competitive in comparison to existing astrophysical bounds on the decay of such a dark matter candidate into photon final states. In particular, we present the first direct detection limits for a vector (axial-vector) interaction which are the strongest in the mass range from 35 to 55 (25  to  45)  keV/c^{2} in comparison to other astrophysical and cosmological constraints.

Compared with the signature of dark matter elastic scattering off nuclei, the absorption of fermionic dark matter by nuclei opens up a new searching channel for light dark matter with a characteristic monoenergetic signal. In this Letter, we explore the 95.0-day data from the PandaX-4T commissioning run and report the first dedicated searching results of the fermionic dark matter absorption signal through a neutral current process. No significant signal was found, and the lowest limit on the dark matter-nucleon interaction cross section is set to be 1.5×10^{-50}  cm^{2} for a fermionic dark matter mass of 40  MeV/c^{2} with 90% confidence level.

Pancreatic adenocarcinoma (PDAC) is highly refractory to treatment. Standard-of-care gemcitabine (Gem) provides only modest survival benefits, and development of Gem resistance (GemR) compromises its efficacy. Highly GemR clones of Gem-sensitive MIAPaCa-2 cells were developed to investigate the molecular mechanisms of GemR and implemented global quantitative differential proteomics analysis with a comprehensive, reproducible ion-current-based MS1 workflow to quantify ∼6000 proteins in all samples. In GemR clone MIA-GR8, cellular metabolism, proliferation, migration, and 'drug response' mechanisms were the predominant biological processes altered, consistent with cell phenotypic alterations in cell cycle and motility. S100 calcium binding protein A4 was the most downregulated protein, as were proteins associated with glycolytic and oxidative energy production. Both responses would reduce tumor proliferation. Upregulation of mesenchymal markers was prominent, and cellular invasiveness increased. Key enzymes in Gem metabolism pathways were altered such that intracellular utilization of Gem would decrease. Ribonucleoside-diphosphate reductase large subunit was the most elevated Gem metabolizing protein, supporting its critical role in GemR. Lower Ribonucleoside-diphosphate reductase large subunit expression is associated with better clinical outcomes in PDAC, and its downregulation paralleled reduced MIAPaCa-2 proliferation and migration and increased Gem sensitivity. Temporal protein-level Gem responses of MIAPaCa-2 versus GemR cell lines (intrinsically GemR PANC-1 and acquired GemR MIA-GR8) implicate adaptive changes in cellular response systems for cell proliferation and drug transport and metabolism, which reduce cytotoxic Gem metabolites, in DNA repair, and additional responses, as key contributors to the complexity of GemR in PDAC. These findings additionally suggest targetable therapeutic vulnerabilities for GemR PDAC patients., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

We report a novel search for the cosmic-ray boosted dark matter using the 100  tonne·day full dataset of the PandaX-II detector located at the China Jinping Underground Laboratory. With the extra energy gained from the cosmic rays, sub-GeV dark matter particles can produce visible recoil signals in the detector. The diurnal modulations in rate and energy spectrum are utilized to further enhance the signal sensitivity. Our result excludes the dark matter-nucleon elastic scattering cross section between 10^{-31} and 10^{-28}  cm^{2} for dark matter masses from 0.1  MeV/c^{2} to 0.1  GeV/c^{2}, with a large parameter space previously unexplored by experimental collaborations.

We report the first dark matter search results using the commissioning data from PandaX-4T. Using a time projection chamber with 3.7 tonne of liquid xenon target and an exposure of 0.63  tonne·year, 1058 candidate events are identified within an approximate nuclear recoil energy window between 5 and 100 keV. No significant excess over background is observed. Our data set a stringent limit to the dark matter-nucleon spin-independent interactions, with a lowest excluded cross section (90% C.L.) of 3.8×10^{-47}  cm^{2} at a dark matter mass of 40  GeV/c^{2}.

Objective: The aims of this systematic review and meta-analysis were to summarize the current existing evidence on the outcome of critically ill patients with COVID-19 as well as to evaluate the effectiveness of clinical interventions. Data Sources: We searched MEDLINE, the Cochrane library, Web of Science, the China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Data from their inception to May 15, 2021. The search strings consisted of various search terms related to the concepts of mortality of critically ill patients and clinical interventions. Study Selection: After eliminating duplicates, two reviewers independently screened all titles and abstracts first, and then the full texts of potentially relevant articles were reviewed to identify cohort studies and case series that focus on the mortality of critically ill patients and clinical interventions. Main Outcomes and Measures: The primary outcome was the mortality of critically ill patients with COVID-19. The secondary outcomes included all sorts of supportive care. Results: There were 27 cohort studies and six case series involving 42,219 participants that met our inclusion criteria. All-cause mortality in the intensive care unit (ICU) was 35% and mortality in hospital was 32% in critically ill patients with COVID-19 for the year 2020, with very high between-study heterogeneity ( I 2 = 97%; p < 0.01). In a subgroup analysis, the mortality during ICU hospitalization in China was 39%, in Asia-except for China-it was 48%, in Europe it was 34%, in America it was 15%, and in the Middle East it was 39%. Non-surviving patients who had an older age [-8.10, 95% CI (-9.31 to -6.90)], a higher APACHE II score [-4.90, 95% CI (-6.54 to -3.27)], a higher SOFA score [-2.27, 95% CI (-2.95 to -1.59)], and a lower PaO 2 /FiO 2 ratio [34.77, 95% CI (14.68 to 54.85)] than those who survived. Among clinical interventions, invasive mechanical ventilation [risk ratio (RR) 0.49, 95% CI (0.39-0.61)], kidney replacement therapy [RR 0.34, 95% CI (0.26-0.43)], and vasopressor [RR 0.54, 95% CI (0.34-0.88)] were used more in surviving patients. Conclusions: Mortality was high in critically ill patients with COVID-19 based on low-quality evidence and regional difference that existed. The early identification of critical characteristics and the use of support care help to indicate the outcome of critically ill patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qian, Lu, Luo, Chen and Liu.)

Median survival of pancreatic ductal adenocarcinoma cancer (PDAC) is 6 months, with 9% 5-year survival. Standard-of-care gemcitabine (Gem) provides only modest survival benefits, and combination therapies integrating novel targeted agents could improve outcomes. Fibroblast growth factor (FGF) receptors (FGFRs) play important roles in PDAC growth and invasion. Therefore, FGFR inhibitors (FGFRi) merit further investigation. Efficacy of Gem combined with NVP-BGJ398, a pan-FGFRi, was investigated in multiple PDAC cell lines exposed to the drugs alone and combined. Cell cycle distribution and cell numbers were quantified over time. Two pharmacodynamic models were developed to investigate Gem/BGJ398 interactions quantitatively: a drug-mediated cell proliferation/death model, and a drug-perturbed cell cycle progression model. The models captured temporal changes in cell numbers, cell cycle progression, and cell death during drug exposure. Simultaneous fitting of all data provided reasonable parameter estimates. Therapeutic efficacy was then evaluated in a PDAC mouse model. Compared with Gem alone, combined Gem + FGFRi significantly downregulated ribonucleotide-diphosphate reductase large subunit 1 (RRM1), a gemcitabine resistance (GemR) biomarker, suggesting the FGFRi inhibited GemR emergence. The cell proliferation/death pharmacodynamic model estimated the drug interaction coefficient ψ death = 0.798, suggesting synergistic effects. The mechanism-based cell cycle progression model estimated drug interaction coefficient ψ cycle = 0.647, also suggesting synergy. Thus, FGFR inhibition appears to synergize with Gem in PDAC cells and tumors by sensitizing cells to Gem-mediated inhibition of proliferation and cell cycle progression. SIGNIFICANCE STATEMENT: An integrated approach of quantitative modeling and experimentation was employed to investigate the nature of fibroblast growth factor receptor inhibitor (FGFRi)/gemcitabine (Gem) interaction, and to identify mechanisms by which FGFRi exposure reverses Gem resistance in pancreatic cancer cells. The results show that FGFRi interacts synergistically with Gem to sensitize pancreatic cancer cells and tumors to Gem-mediated inhibition of proliferation and cell cycle progression. Thus, addition of FGFRi to standard-of-care Gem treatment could be a clinically deployable approach to enhance therapeutic benefit to pancreatic cancer patients., (Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: Position intervention has been shown to improve oxygenation, but its role in non-invasively ventilated patients with severe COVID-19 has not been assessed. The objective of this study was to investigate the efficacy of early position intervention on non-invasively ventilated patients with severe COVID-19., Methods: This was a single-center, prospective observational study in consecutive patients with severe COVID-19 managed in a provisional ICU at Renmin Hospital of Wuhan University from 31 January to 15 February 2020. Patients with chest CT showing exudation or consolidation in bilateral peripheral and posterior parts of the lungs were included. Early position intervention (prone or lateral) was commenced for > 4 hours daily for 10 days in these patients, while others received standard care., Results: The baseline parameters were comparable between the position intervention group ( n  = 17) and the standard care group ( n  = 35). Position intervention was well-tolerated and increased cumulative adjusted mean difference of SpO 2 /FiO 2 (409, 95% CI 86 to 733) and ROX index (26, 95% CI 9 to 43) with decreased Borg scale (-9, 95% CI -15 to -3) during the first 7 days. It also facilitated absorption of lung lesions and reduced the proportion of patients with high National Early Warning Score 2 (≥ 7) on days 7 and 14, with a trend toward faster clinical improvement. Virus shedding and length of hospital stay were comparable between the two groups., Conclusions: This study provides the first evidence for improved oxygenation and lung lesion absorption using early position intervention in non-invasively ventilated patients with severe COVID-19, and warrants further randomized trials., (© The Author(s) 2020. Published by Oxford University Press on behalf West China School of Medicine & West China Hospital of Sichuan University.)

Objectives: To compare and analyse the recommendations from clinical practice guidelines (CPGs) on gout worldwide, examine the consistency across CPGs, and provide suggestions to develop and update gout guidelines., Methods: We conducted systematic searches in MEDLINE, CBM, GIN, NICE, NGC, WHO, SIGN, DynaMed, UpToDate, and Best Practice databases, from their inception to August 2019 to identify and select CPGs related to gout. We used the search terms "gout", "hyperuricaemia" and "guideline". After two rounds of screening, we included the eligible CPGs of gout according to the pre-defined inclusion and exclusion criteria. Methodological quality of included guidelines was assessed with the AGREE-II instrument. The general characteristics of included guidelines and the recommendations were extracted, and the consistency of recommendations across guidelines was compared and analysed., Results: A total of 15 gout guidelines including 359 recommendations were retrieved. The main topics covered by the recommendations were diagnosis, pharmacologic treatment of gout flares, pharmacologic urate-lowering therapy (ULT) of chronic gouty arthritis, lifestyle interventions, prophylaxis, and management of asymptomatic hyperuricaemia. The results of AGREE-II appraisal showed that only two guidelines achieved high scores (≥50%) in all six domains. There was substantial discrepancy between the guidelines in recommendations covering the value of computed tomography (CT) and x-rays for diagnosis, the use of corticosteroids as a first-line treatment for flare, the use of colchicine, indications for ULT, the use of febuxostat as first-line ULT, the administration of allopurinol, and the timing of ULT initiation., Conlusions: A number of countries are devoting themselves to the development of gout guidelines, but the process of updating guidelines is slower than that suggested by the WHO. Methodological quality is not satisfactory in most guidelines, and recommendations between guidelines are not consistent.

Objective: The aim of this systematic review was to assess the diaphragmatic dysfunction (DD) as a predictor of weaning outcome., Background: Successful weaning depends on several factors: muscle strength, cardiac, respiratory and metabolic. Acquired weakness in mechanical ventilation is a growing important cause of weaning failure. With the development of ultrasonography, DD can be evaluated with ultrasound in weakness patients to predict weaning outcomes., Methods: The Cochrane Library, PubMed, Embase, Ovid Medline, WanFang Data and CNKI were systematically searched from the inception to September 2017. Ultrasound assessment of DD in adult mechanical ventilation patients was included. Two independent investigators assessed study quality in accordance with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The primary outcome was diaphragmatic thickness and excursion in the weaning success and failure group. The secondary outcome was the influence of DD on weaning outcome., Results: Eleven studies involving a total of 436 patients were included. There were eight studies comparing diaphragmatic excursion (DE), five comparing the diaphragmatic thickening fraction (DTF) and two comparing DD between groups with and without successful weaning. Overall, the DE or DTF had a pooled sensitivity of 0.85 (95% CI 0.77 to 0.91) and a pooled specificity of 0.74 (95% CI 0.66 to 0.80) for predicting weaning success. There was high heterogeneity among the included studies (I 2 =80%; p=0.0006). The rate of weaning failure was significantly increased in patients with DD (OR 8.82; 95% CI 3.51 to 22.13; p<0.00001)., Conclusions: Both DE and DTF showed good diagnostic performance to predict weaning outcomes in spite of limitations included high heterogeneity among the studies. DD was found to be a predictor of weaning failure in critically ill patients., Competing Interests: Competing interests: The authors declared no competing interests., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Large-area graphene thin films are prized in flexible and transparent devices. We report on a type of glassy graphene that is in an intermediate state between glassy carbon and graphene and that has high crystallinity but curly lattice planes. A polymer-assisted approach is introduced to grow an ultra-smooth (roughness, <0.7 nm) glassy graphene thin film at the inch scale. Owing to the advantages inherited by the glassy graphene thin film from graphene and glassy carbon, the glassy graphene thin film exhibits conductivity, transparency, and flexibility comparable to those of graphene, as well as glassy carbon-like mechanical and chemical stability. Moreover, glassy graphene-based circuits are fabricated using a laser direct writing approach. The circuits are transferred to flexible substrates and are shown to perform reliably. The glassy graphene thin film should stimulate the application of flexible transparent conductive materials in integrated circuits.

Objective: Observing and evaluating the clinical effects of panretinal photocoagulation with Argon laser for diabetic retinopathy., Methods: According to the results of fundus fluorescence angiography (FFA), panretinal photocoagulation with Argon laser were performed on 143 eyes (87 cases) of diabetic retinopathy, including 79 eyes with preproliferative diabetic retinopathy eyes with proliferative diabetic retinopathy (PPDR), 64 (PDR). Examination about FFA, visual acuity and fundus condition were carried out before laser treatment and 3 months after photocoagulation. The regular following up lasted for 6 months to 2 years., Results: Laser photocoagulation proved effective in 122 eyes (85.31%) with diabetic retinopathy, including 73 eyes (92.41%) with PPDR, 49 eyes (76.56%) with PDR. The visual acuity were improved in 32 eyes (23.38%), no changes in 87 eyes (60. 84%), decrease in 24 eyes (16.78%). No complication was found in all patients., Conclusions: Panretinal photocoagulation with Argon laser is a safe and effective method to control the condition of diabetic retinopathy.