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Jingjing Hao, Jingyuan Liu, Lin Pu, Chuansheng Li, Ningning Yin, Ang Li Department of Critical Care Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Ang Li, Email liang@ccmu.edu.cnBackground: Respiratory failure in acquired immunodeficiency syndrome (AIDS) patients was the leading cause of intensive care unit (ICU) admission in our center. We aimed to describe the pulmonary infections and outcomes for respiratory failure in AIDS patients.Methods: A retrospective study was conducted on AIDS adult patients with respiratory failure who were admitted to the ICU in Beijing Ditan hospital, China, from January 2012 to December 2021. We investigated pulmonary infections complicated by respiratory failure in AIDS patients. The primary outcome was ICU mortality, and a comparison between survivors and nonsurvivors was performed. Multiple logistic regression analysis was used to identify predictors of ICU mortality. The Kaplan-Meier curve and Log rank test were used for survival analysis.Results: A total of 231 AIDS patients were admitted to ICU with respiratory failure over a 10-year period with a male predominance (95.7%). Pneumocystis jirovecii pneumonia was the main etiology of pulmonary infections (80.1%). The ICU mortality was 32.9%. In multivariate analysis, ICU mortality was independently associated with invasive mechanical ventilation (IMV) [odds ratio (OR), 27.910; 95% confidence interval (CI, 8.392– 92.818; p = 0.000) and the time before ICU admission (OR, 0.959; 95% CI, 0.920– 0.999; p = 0.046). In the survival analysis, patients with IMV and later admission to ICU had a higher probability of mortality.Conclusion: Pneumocystis jirovecii pneumonia was the primary etiology for respiratory failure in AIDS patients admitted to the ICU. Respiratory failure remains a severe illness with high mortality, and ICU mortality was negatively associated with IMV and later admission to ICU.Keywords: acquired immunodeficiency syndrome, AIDS, respiratory failure, pulmonary infections, ICU mortality

In order to study the dynamic development law of different regions in the spontaneous combustion process of coal, the spontaneous combustion process of loose coal under constant air volume from normal temperature to 140 °C was tested by using large coal spontaneous combustion simulation test bench, so as to analyze the change law of oxygen consumption rate and heat release intensity in time and space. The results showed that the temperature of the loose coal spontaneous combustion process varies with the height of the coal body at different temperature stages. The high temperature point moved from the upper middle position of the coal body to the air inlet side; the oxygen consumption rate and time of different coal body heights showed indexes Increase, and the rate of oxygen consumption coincided with the migration law of the high temperature point of the coal body height. The coal body exhibited slow and rapid growth in stages around 75 °C; the heat release intensity of the loose coal inlet gradually increased. After the temperature exceeds 75 °C, the heat release intensity of different coal heights gradually increased with time, and the intensity of heat release coincides with the migration law of the high temperature point of the coal body height.

In order to solve the shortcomings of the traditional mining anti-extinguishing gel material such as low strength and poor water retention, a high hydrocolloid anti-extinguishing material was developed with sodium alginate and light calcium carbonate as the base material and gluconolactone as the retarder, which was mixed and reacted. The base material ratio of highly efficient water-retaining colloidal material for coal void filling was determined as 2% SA + 0.5% PCC + 1% GDL with a moulding time of 4.5 min, while the base material ratio of highly efficient water-retaining colloidal material for extinguishing high temperature fires was 2.5% SA + 1% PCC + 1% GDL with a moulding time of 2.5 min. The highly efficient water-retaining colloidal material was found to reduce the concentration of signature gas and delay the characteristic temperature point and increase the activation energy of coal oxidation, which indicates that the highly efficient water-retaining colloidal material can effectively inhibit the spontaneous combustion process of coal at low temperature stage. Infrared spectroscopy experiments were conducted to investigate the microscopic resistance mechanism of the highly efficient water-retaining colloidal material, and the results showed that the highly efficient water-retaining colloidal material mainly reduce the activity of Ar-C-O-, -COO-, -CH3, -CH2 and -OH in coal to inhibit the spontaneous combustion of coal.

Background: The bromodomain and extra-terminal proteins (BET), in particular BRD4, has recently emerged as a potential therapeutic target for the treatment of many human disorders such as cancer, inflammation, obesity and cardiovascular disease, which draw more and more attention to discover potent BRD4 inhibitors in the past years. In this article, we described the discovery process of an entirely new chemotype of BRD4 inhibitors. Methods: A fragment-based drug discovery strategy was employed in attempting to find a novel chemotype of BRD4 inhibitors. Thus, the potential hits were firstly identified by docking study with KAc binding pocket and AlphaScreen assay. Then the elected hit was further structurally optimized based on the interaction revealed by the docking study and the Structure-Activity Relationship (SAR). Results: A 1-(2-hydroxyphenyl)ethan-1-one fragment was first identified as an efficient hit to BRD4 with a weak inhibition activity and high ligand efficiency (IC50 = 8.9 μM, LE > 0.5) based on virtual screening and biochemical assay. Then, two-rounds optimization of the hit by a fragmentbased drug discovery approach enabled the discovery of a potent BRD4 inhibitor 9, which exhibit nanomolar potency in biochemical assays (IC50 = 0.18 μM). Conclusion: The title compounds displayed potent inhibitory activity to BRD4, implying acetophenone core is an effective KAc residue mimic, suggesting acetophenone derivatives as a new chemotype may be promising for developing novel BRD4 inhibitors.

Background: Acute respiratory failure (ARF) remains the most common diagnosis for intensive care unit (ICU) admission in acquired immunodeficiency syndrome (AIDS) patients. Methods: We conducted a single-center, prospective, open-labeled, randomized controlled trial at the ICU, Beijing Ditan Hospital, China. AIDS patients with ARF were enrolled and randomly assigned in a 1:1 ratio to receive either high-flow nasal cannula (HFNC) oxygen therapy or non-invasive ventilation (NIV) immediately after randomization. The primary outcome was the need for endotracheal intubation on day 28. Results: 120 AIDS patients were enrolled and 56 patients in the HFNC group and 57 patients in the NIV group after secondary exclusion. Pneumocystis pneumonia (PCP) was the main etiology for ARF (94.7%). The intubation rates on day 28 were similar to HFNC and NIV (28.6% vs. 35.1%, p = 0.457). Kaplan–Meier curves showed no statistical difference in cumulative intubation rates between the two groups (log-rank test 0.401, p = 0.527). The number of airway care interventions in the HFNC group was fewer than in the NIV group (6 (5–7) vs. 8 (6–9), p < 0.001). The rate of intolerance in the HFNC group was lower than in the NIV group (1.8% vs. 14.0%, p = 0.032). The VAS scores of device discomfort in the HFNC group were lower than that in the NIV group at 2 h (4 (4–5) vs. 5 (4–7), p = 0.042) and at 24 h (4 (3–4) vs. 4 (3–6), p = 0.036). The respiratory rate in the HFNC group was lower than that in the NIV group at 24 h (25 ± 4/min vs. 27 ± 5/min, p = 0.041). Conclusions: Among AIDS patients with ARF, there was no statistical significance of the intubation rate between HFNC and NIV. HFNC had better tolerance and device comfort, fewer airway care interventions, and a lower respiratory rate than NIV. Clinical Trial Number: Chictr.org (ChiCTR1900022241).

Background: The Fontan operation is the only treatment option to change the anatomy of the heart and help improve patients’ hemodynamics. After successful operation, patients typically recover the ability to engage in general physical activity. The mortality of patients diagnosed with acute respiratory distress syndrome (ARDS) ranges from 17.3 to 41.4% among critically ill patients with H1N1 infection. As a better ventilatory strategy, extracorporeal membrane oxygenation (ECMO) provides gas exchange via an extracorporeal circuit, and is increasingly being used to improve respiratory and circulatory function. As is known to all, after the modified Fontan operation, circulation was different compared with patients who were not subjected to the procedure. But very few articles describe the special circulation about the case who was post-operative of the modified Fontan operation especially when it received the treatment of E-CMO. This study aims to describe a successful case using E-CMO in curing the influenza A infection in a young man, who was diagnosed with Tausing-Bing syndrome and underwent Fontan operation thirteen years ago. We want to explore the special cardiac structure and circulatory characteristics in this case.Methods: To report a successful case using extracorporeal membrane oxygenation in curing the influenza A infection in a young man, who was diagnosed with Tausing-Bing syndrome and underwent Fontan operation thirteen years ago. In this article, we describe a 23-year-old man, with a history of modified Fontan operation for the Tausing-Bing syndrome, admitted to ICU with severe acute respiratory distress syndrome as a result of influenza A infection. The man was initially treated by V-V ECMO, five days later was switched to V-V-A E-CMO. Results: As circulation and respiratory function gradually improved, the VV-A ECMO equipment was removed on May 1, 2018.The patient was successfully withdrawn from artificial ventilation on May 28, 2018, then discharged from hospital on May 30, 2018.Conclusion: After the modified Fontan operation, circulation was different compared with patients who were not subjected to the procedure. There were certainly many differences between the two sides when they received the treatment of E-CMO. As the special cardiac structure and circulatory characteristics, an individualized liquid management strategy was necessary and it might be better for them to choose an active cycle support earlier.

Enteral nutrition plays an irreplaceable role in the nutritional treatment of critically ill patients. In order to help clinical medical staff to manage the common complications during the implementations of enteral nutrition for critically ill patients, the consensus writing team carried out literature retrieval, literature quality evaluation, evidence synthesis. Several topics such as diarrhea, aspiration, high gastric residual volume, abdominal distension, etc. were assessed by evidence-based methodology and Delphi method. After two rounds of expert investigations, Expert consensus on prevention and management of enteral nutrition therapy complications for critically ill patients in China (2021 edition) developed, and provided guidance for clinical medical staff.

1. Sophocarpine is a biologically active component isolated from the foxtail-like sophora herb and seed that is often orally administered for the treatment of cancer and chronic bronchial a...

We reported that the complete genome sequence of SARS-Coronavirus-2 (SARS-CoV-2) was obtained from a cerebrospinal fluid (CSF) sample by ultrahigh-depth sequencing. Fourteen days after onset, seizures, maxillofacial convulsions, intractable hiccups and a significant increase in intracranial pressure developed in an adult coronavirus disease 2019 patient. The complete genome sequence of SARS-CoV-2 obtained from the cerebrospinal fluid indicates that SARS-CoV-2 can invade the central nervous system. In future, along with nervous system assessment, the pathogen genome detection and other indicators are needed for studying possible nervous system infection of SARS-CoV-2.

Background Accurately differentiating pneumocystis from cytomegalovirus pneumonia is crucial for correct therapy selection in AIDS patients. Hence, the goal of this study was to compare the computerized tomography (CT) features of pneumocystis pneumonia and cytomegalovirus pneumonia in AIDS patients and identify clinical hallmarks to accurately distinguish these two pathologies. Methods A total of 112 AIDS patients (78 with pneumocystis pneumonia and 34 cytomegalovirus pneumonia) at Beijing Ditan Hospital from January 2017 to May 2019 were included in this study. Two experienced chest radiologists retrospectively reviewed CT images for 17 features including ground-glass opacity, consolidation, nodules, and halo sign. Binary logistic regression analyses were conducted to identify the significant parameters that distinguished pneumocystis pneumonia from cytomegalovirus pneumonia. Correlations were analyzed by Pearson or Spearman correlation analyses. Result were considered significant if P Results The presence of consolidation, halo signs, and nodules (all P P P > 0.05) were common in both groups. Conclusions Analysis of consolidation, nodules, and halo signs may contribute to the differential diagnosis of pneumocystis pneumonia or cytomegalovirus pneumonia. However, some CT features considered typical in one or other diseases appear with similar frequency in both cohorts of AIDS patients. CT features are potentially useful for the differential diagnosis of pneumocystis pneumonia and cytomegalovirus pneumonia in AIDS patients.

Background: SARS-Coronavirus-2 (SARS-CoV-2), the pathogen of coronavirus disease 2019 (COVID-19), not only infects the respiratory tract, but also other organs. About a third of the inpatients of COVID-19 have neurological symptoms and in vitro experiments revealed that SARS-CoV-2 could infect human neural progenitor cells and brain organoids. However, the traditional test often reports negative owing to the low number of virus in the cerebrospinal fluid. To date, timely diagnosis of central nervous system infection of SARS-CoV-2 remains a challenge.Case presentation: On day 14 of COVID-19, seizures, maxillofacial convulsions, intractable hiccups and significant increase in intracranial pressure developed in a 56-year-old man. The RT-PCR of SARS-CoV-2 was negative. SARS-CoV-2 nucleic acid were detected in cerebrospinal fluid (CSF) by ultrahigh depth sequencing. The patient was successfully treated after 14 days of mechanical ventilation and treatment of pneumonia and neurological dysfunction.Conclusions: This case suggests SARS-CoV-2 can invade the central nervous system and relevant examinations with CSF including ultrahigh depth sequencing of SARS-CoV-2 are needed among COVID-19 patients with neurological dysfunction.

Background: The outbreak of coronavirus disease 2019 (COVID-19) posed an enormous threat to public health. The use of antiviral drugs in patients with this disease have triggered people’s attentions. Whether interferon alfa-2b or Kaletra plus interferon alfa-2b treatment can against SARS-CoV-2 was unknown.Methods: This is a retrospective cohort study of 123 laboratory-confirmed COVID-19 patients between Jan.13 2020 and Apr. 23. All patients received standard supportive care and regular clinical monitoring, patients were assigned to standard care group (n=12), interferon alfa-2b group (n=44), and combination Kaletra plus interferon alfa-2b group (n=67) according to their therapies. The primary endpoint for this study was the duration of oxygen-support requirement and virus clearance time. The associations of therapies with these outcomes were assessed by Cox proportional hazards regression. Results: Baseline clinical and laboratory characteristics were similar among 3 groups (p＞0.05). There was no significant association of Kaletra /interferon alfa-2b with faster SARS-CoV-2 RNA clearance (HR, 0.85 [95% CI, 0.45–1.61]; P = 0.61 in interferon alfa-2b group vs HR, 0.59 [95% CI, 0.32–1.11]; P = 0.10 in Kaletra plus interferon alfa-2b group). The duration of oxygen-support requirement in therapy groups similarly showed no significant association. There were no differences among 3 groups in the incidence of adverse events (p＞0.05).Conclusions: In patients with confirmed SARS-CoV-2 infection, no benefit was observed with interferon alfa-2b and Kaletra plus interferon alfa-2b treatment beyond standard care. Further trials in appropriately randomized design may contribute to validate the effective role and safety profile of the test drugs.

Background There is currently a lack of nonspecific laboratory indicators as a quantitative standard to distinguish between the 2019 coronavirus disease (COVID-19) and an influenza A or B virus infection. Thus, the aim of this study was to establish a nomogram to detect COVID-19. Methods A nomogram was established using data collected from 457 patients (181 with COVID-19 and 276 with influenza A or B infection) in China. The nomogram used age, lymphocyte percentage, and monocyte count to differentiate COVID-19 from influenza. Results Our nomogram predicted probabilities of COVID-19 with an area under the receiver operating characteristic curve of 0.913 (95% confidence interval [CI], 0.883–0.937), greater than that of the lymphocyte:monocyte ratio (0.849; 95% CI, 0.812–0.880; P = .0007), lymphocyte percentage (0.808; 95% CI, 0.768–0.843; P < .0001), monocyte count (0.780; 95% CI, 0.739–0.817; P < .0001), or age (0.656; 95% CI, 0.610–0.699; P < .0001). The predicted probability conformed to the real observation outcomes of COVID-19, according to the calibration curves. Conclusions We found that age, lymphocyte percentage, and monocyte count are risk factors for the early-stage prediction of patients infected with the 2019 novel coronavirus. As such, our research provides a useful test for doctors to differentiate COVID-19 from influenza.

We propose a method for measuring the thermal effect of spontaneous combustion and the adiabatic spontaneous combustion period of coal based on the coupled thermal effects of coal and oxygen. A physical similarity reference test system was established by combining the characteristics of the thermal analyses. Using this system, coal samples from the main coal seam of the Zhao Xian mine, which has high propensity for spontaneous combustion, were tested and analyzed. The adiabatic spontaneous combustion period for coal was determined by curve fitting. Based on the heat equation, the adiabatic spontaneous combustion period for coal from the Zhao Xian coal mine was determined to be 95.9 h. Mutual verification among the adiabatic spontaneous combustion periods of coal was achieved through the same fitting procedure. The error between the two experimental results was less than 0.22 % with 0.01 variance, which proves that the experimental approach is applicable for calculating the adiabatic spontaneous combustion period of the Zhao Xian coal sample. Our results should facilitate theoretical and experimental evaluations of the likelihood of spontaneous coal combustion and its associated risks.

Herein, we embarked on a structural optimization campaign aiming at the discovery of second generation anti-angiogenesis agents with our previously reported BPS-7 as lead compound. A library of 27 compounds has been afforded based on the highly conserved ATP-binding pocket of VEGFR-2, Tie-2, and EphB4. Several title compounds exhibited simultaneous inhibitory effects against three angiogenic RTKs. These compounds with a 'triplet' inhibition profile have been identified as novel anti-angiogenic and anticancer agents. The representative VDAU11 displayed prominent anti-angiogenic and anticancer potency and could be considered as a candidate for further optimization. These results indicate that N-(pyridin-2-yl)acrylamide could serve as a novel hinge-binding group of triple inhibitors.

VEGFR-2, TIE-2, and EphB4 are essential for both angiogenesis and tumorigenesis. Herein, we designed and prepared three classes of multi-target inhibitors based on the extensive sequence homology along the kinase domain of angiogenic RTKs. Biological evaluation indicated that these multi-target inhibitors exhibited considerable potential as novel anti-angiogeneic and anticancer agents. Among them, a diaryl thiourea bearing 1H-indazole-3-amine (16a) displayed the most potent RTK inhibition and excellent selectivity. It also showed inhibition on viability of human umbilical vein endothelial cells and anti-proliferation against a broad spectrum of cancer cells. Therefore, 1H-indazole-3-amine could serve as a promising hinge binding group for multi-target inhibitors of VEGFR-2, Tie-2, and EphB4.

We aimed to explore whether maternal chronic hepatitis B virus (HBV) infection certainly affects preterm labor (birth) in pregnant women. Four databases were systematically searched up to May 31, 2017, without language restriction. Any study was included if it clearly defined exposure to chronic HBV infection, reported risk of preterm labor or birth in pregnant women, and reported relative risks (RRs) or odds ratios (ORs) or provided data for estimation. RRs (or ORs) with 95% confidence intervals were pooled using random-effects models. Statistical heterogeneity was assessed with Cochran's Q statistic and I2 statistic. Twenty-two observational studies involving 6 141 146 pregnant women (three prospective cohort studies, n = 1 116 799; 15 retrospective cohort studies, n = 5 022 513 and four case-control studies, n = 1834) were included. The risk of preterm labor was significantly intensified with chronic HBV infection compared with uninfected women, with substantial heterogeneity. Chronic HBV infection was also significantly associated with a 16% increase in the risk of preterm birth, with substantial heterogeneity. The risk of preterm birth significantly increased by 21% in HBsAg+/HBeAg+ pregnant women compared with uninfected pregnant women. Chronic HBV infection intensifies the risk of preterm labor and birth in pregnant women, but this conclusion should be interpreted with caution given the possibility of residual confounding and be confirmed by well-designed studies in the future.

Receptor tyrosine kinases (RTKs), especially VEGFR-2, TIE-2, and EphB4, play a crucial role in both angiogenesis and tumorigenesis. Moreover, complexity and heterogeneity of angiogenesis make it difficult to treat such pathological traits with single-target agents. Herein, we developed two classes of multi-target RTK inhibitors (RTKIs) based on the highly conserved ATP-binding pocket of VEGFR-2/TIE-2/EphB4, using previously reported BPS-7 as a lead compound. These multi-target RTKIs exhibited considerable potential as novel anti-angiogenic and anticancer agents. Among them, QDAU5 displayed the most promising potency and selectivity. It significantly suppressed viability of EA.hy926 and proliferation of several cancer cells. Further investigations indicated that QDAU5 showed high affinity to VEGFR-2 and reduced the phosphorylation of VEGFR-2. We identified QDAU5 as a potent multiple RTKs inhibitor exhibiting prominent anti-angiogenic and anticancer potency both in vitro and in vivo. Moreover, quinazolin-4(3H)-one has been identified as an excellent hinge binding moiety for multi-target inhibitors of angiogenic VEGFR-2, Tie-2, and EphB4.

BackgroundSevere ill patients with 2019 novel coronavirus (2019-nCoV) infection progressed rapidly to acute respiratory failure. We aimed to select the most useful prognostic factor for severe illness incidence.MethodsThe study prospectively included 61 patients with 2019-nCoV infection treated at Beijing Ditan Hospital from January 13, 2020 to January 31, 2020. Prognostic factor of severe illness was selected by the LASSO COX regression analyses, to predict the severe illness probability of 2019-CoV pneumonia. The predictive accuracy was evaluated by concordance index, calibration curve, decision curve and clinical impact curve.ResultsThe neutrophil-to-lymphocyte ratio (NLR) was identified as the independent risk factor for severe illness in patients with 2019-nCoV infection. The NLR had a c-index of 0.807 (95% confidence interval, 0.676–0.38), the calibration curves fitted well, and the decision curve and clinical impact curve showed that the NLR had superior standardized net benefit. In addition, the incidence of severe illness was 9.1% in age ≥ 50 and NLR < 3.13 patients, and half of patients with age ≥ 50 and NLR ≥ 3.13 would develop severe illness. Based on the risk stratification of NLR with age, the study developed a 2019-nCoV pneumonia management process.ConclusionsThe NLR was the early identification of risk factors for 2019-nCoV severe illness. Patients with age ≥ 50 and NLR ≥ 3.13 facilitated severe illness, and they should rapidly access to intensive care unit if necessary.

Biocompatibility has been a major concern in the field of medical implants, and the “stress shielding” effect can be detrimental to the growth of bone cells. In this work, a parametric irregular porous structure model based on bionics design was established. The influence of different parameters on the elastic modulus, compressive strength, average pore size, and porosity was investigated. An optimization model using the grey relational analysis was established by controlling the irregularity, seed points, and strut diameter. With the goal of meeting biological requirements, the optimization results showed that the elastic modulus decreased by 40.21% and the porosity increased by 17.58%. Irregularity had little effect on the elastic modulus, porosity, and average pore size, and it was negatively correlated with compressive strength. The strut diameter and seed points were positively correlated with the elastic modulus and compressive strength but negatively correlated with the porosity and average pore size, and the seed count had the largest impact. By adjusting these parametric models, the optimization factors were obtained based on the elastic modulus, porosity, average pore size, and compressive strength of human bone. These results provide theoretical guidance for studying the mechanical properties of irregular porous structures fabricated via selective laser melting.

Acute lung injury (ALI), as a life-threatening syndrome, is mainly characterized with diffuse alveolar injury, excessive pulmonary inflammation, edema and apoptosis of lung epithelial cells. This study investigated the effects of LncRNA Hsp4 (Hsp4, ENSMUST00000175718) on lipopolysaccharide (LPS)-induced apoptosis of MLE-12 cells. In our research, we found that LPS treatment remarkably induced apoptosis of MLE-12 cells and decreased the expression of Hsp4. Overexpression of Hsp4 significantly reversed LPS-induced cell apoptosis through inhibiting mTOR signaling, while suppression of Hsp4 presented opposite effects. Further results showed that Hsp4 positively regulated the expression of miR-466m-3p. Knockdown of miR-466m-3p reversed LPS-induced cell apoptosis via increasing the levels of DNAjb6 which was confirmed to be the target gene of miR-466m-3p. This finding will be helpful for further understanding the critical roles of Hsp4 in ALI and may provide potential targets for ALI diagnosis and treatment.

The influence of polarization crosstalk of Y branch loop on scale factor is analyzed in detail. In the Y branch loop, the scale factor is affected by only the output alignment angle of the PBS. The experiment result shows the range of output alignment angle of the PBS should not exceed from 0.2 to 2.5 over a range from - 40°C to 70°C which corresponds to angle 1.8 at room temperature to make sure the measurement accuracy within ±0.2% from 0 to 100kA.

We designed and synthesized new kinds of near-infrared catechol-based multidentate polymers which were intended to yield compact NIR-active iron oxide nanoparticles with excellent stability and biocompatibility. The resulted multifunctional nanoprobes showed great potential as multimodal contrast agents for NIRF/PA/MR trimodal imaging in vivo.

A facile and simple one-step method was developed to fabricate aptamer-decorated self-assembled organic dots with aggregation-induced emission (AIE) characteristics. With integration of the advantages of AIE aggregates with strong emission and the cell-targeting capability of aptamers, the as-prepared Apt-AIE organic nanodots can specifically target to cancer cells with good biocompatibility, high image constrast, and photostability. On the basis of this universal method, a variety of versatile organic fluorescent nanoprobes with high brightness, specific recognition, and clinical-transitional potential could be facilely constructed for biological sensing and imaging applications.

The efficacy, safety and health-economic outcomes were compared between corticosteroid and non-corticosteroid treatments in acute gout patients. All electronic literatures comparing the curative effects or full economic evaluations of corticosteroids versus non-corticosteroids on acute pain in acute gout patients and published until June 30, 2017 in any language were searched through PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. Pooled odds ratios with 95% confidence intervals and standard(or weighted) mean difference were calculated using random-or fixed-effects models according to the I2 statistic test of heterogeneity. Economic elevations were combined through qualitative narrative synthesis. Finally, seven randomized controlled trials(RCTs) involving 929 patients were included here and suggested corticosteroids had comparable analgesic efficacy to non-corticosteroids on day 5. As for inflammation and PGA, corticosteroids might outperform non-corticosteroids in reducing tenderness and swelling. Corticosteroids versus non-corticosteroids could significantly reduce incidence of only serious adverse advents, but not total adverse advents, with substantial heterogeneity. Qualitative narrative synthesis of economic elevation involving only one study shows corticosteroids are more cost-effective than indomethacin. The existing RCTs do not provide sufficient or precise evidence that corticosteroids are superior to non-corticosteroids in pain relief of acute gout patients. Therefore, studies on chronic use of corticosteroids or comparative studies with colchicine, tramadol and/or opiates may be needed in the future, as is patient satisfaction with analgesic control.

Summary Background/objectives Liver cirrhosis and its complications are important factors contributing to mortality worldwide. Statin use is probably associated with lower risk of hepatic decompensation and mortality, but not with cirrhosis or fibrosis progression according to a recent systematic review. We aimed to evaluate the definite effects of statins on the risk of virus-related cirrhosis. Methods We systematically searched four databases up to May 7, 2017, without language restriction. Studies were included if they evaluated and clearly defined exposure to statins, reported fibrosis progression, risk of cirrhosis in patients with chronic viral hepatitis or decompensation in cirrhotic patients, and reported relative risks (RRs) or odds ratios (ORs), or provided data for their estimation. Pooled RRs (or ORs) with 95% confidence intervals were calculated using the random-effects models irrespective of statistical heterogeneity assessed with the Cochran's Q statistic and I2 statistic. Results Ten observational studies involving 12,3445 patients (8 cohort studies, n = 12,1823; 1 nested case-control, n = 1350; and 1 abstract, n = 272) were included. Statin use was associated with a statistically significant 51% reduction in the risk of virus-related cirrhosis (pooled RRs, 0.49; 95% CI, 0.30–0.80; P = 0.004), with substantial heterogeneity (I2 = 98.3%; P Conclusions The meta-analysis showed that statin use was associated with a significantly reduced risk of virus-related cirrhosis and decompensation. However, these results should be interpreted with caution given the possibility of residual confounding. Large randomized controlled trials are warranted in future studies.

Recently, we have identified a biphenyl-aryl urea incorporated with salicylaldoxime (BPS-7) as an anti-angiogenesis agent. Herein, we disclosed a series of novel anti-angiogenesis agents with BPS-7 as lead compound through combining diarylureas with N-pyridin-2-ylcyclopropane carboxamide. Several title compounds exhibited simultaneous inhibition effects against three pro-angiogenic RTKs (VEGFR-2, TIE-2 and EphB4). Some of them displayed potent anti-proliferative activity against human vascular endothelial cell (EA.hy926). In particular, two potent compounds (CDAU-1 and CDAU-2) could be considered as promising anti-angiogenesis agents with triplet inhibition profile. The biological evaluation and molecular docking results indicate that N-pyridin-2-ylcyclopropane carboxamide could serve as a hinge-binding group (HBG) for the discovery of multi-target anti-angiogenesis agents. CDAU-2 also exhibited promising anti-angiogenic potency in a tissue model for angiogenesis.

A novel location scheme based on the wavelet packet transform (WPT) for the phase-sensitive optical time-domain reflectometry (OTDR) is proposed. The wavelet packet energy of the backscattered signal at a time interval over the sensing fiber is provided to discriminate the disturbances regions from other regions. It is insensitive to the frequency drift of the laser. The simultaneous measurement of two disturbances at 5 km and 7 km positions is achieved by the location technique based on the WPT over a 9 km monitored length with a 50 m spatial resolution even when a laser with a frequency drift rate of 230 MHz/min is utilized. During 100 times experiments the false alarm rate is only 2% and the maximum location error is 150 m.

The influences of imperfect polarization induced effects are investigated in this paper for a novel optical voltage sensor (OVS), which consists of quasi-reciprocal reflective optical interferometer and digital closed-loop detection scheme. The numerical models are established to describe the relationship between the characteristic parameters of imperfect polarization and the performances of the OVS, which is also simulated to investigate quantitatively. The numerical models and the simulated results are experimentally verified with typical imperfect polarization induced errors. Accordingly, the primary characteristic parameters of imperfect polarization are illuminated. What's more, the conclusions of this paper can provide useful references for the design and performance improvement of the novel Pockels effect based OVS.

Angiogenesis is modulated by a multitude of pro-angiogenic factors including VEGFR-2, Tie-2, and EphB4. Moreover, their crosstalk also had been well elaborated. We have identified several diarylurea-based VEGFR-2 inhibitors as potential anti-angiogenesis agents. As a continuation to our previous research, two series of diaryl malonamide and diaryl thiourea derivatives have been developed as multiplex VEGFR-2/Tie-2/EphB4 inhibitors. Interestingly, the biological evaluation indicated that several compounds bearing trifluoromethyl or trifluoromethoxyl exhibited promising multiplex inhibition against angiogenesis-related VEGFR-2, Tie-2, and EphB4. The representative compound (18a) displayed both potent multi-targeted RTK inhibition and considerable antiproliferative activities against human umbilical vein endothelial cells (EA.hy926). These results will contribute to the discovery of novel muti-targeted anti-angiogenesis agents.

A novel digital active homodyne demodulation scheme to eliminate the signal fading in interferometric fiber-optic sensors is proposed. The error signal is obtained by the square-wave phase modulation and then the digital correlation detection technique is applied to demodulate the low-frequency environmental phase drift and generate the offset phase, which is then fed back the integrated optical phase modulator to lock the interferometer in quadrature. The high-frequency signal phase can be read out and recovered from the photodetector output with the interferometer in quadrature. The simulation and experimental results verify the feasibility of the proposed scheme, which obviates the feedback integrator saturation and the system resetting problem encountered in the conventional active homodyne detection schemes. © 2010 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:20–23, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.25640

A novel Pockels effect based optical voltage sensor (OVS) consisting of quasi-reciprocal reflective optical circuit is proposed and demonstrated in this paper. The quasi-reciprocal reflective optical circuit is realized so that a digital closed-loop detection technique adopted from fiber gyroscopes can be introduced to obtain the voltage-induced Pockels phase. Due to the digital closed-loop detection scheme, the proposed OVS is insensitive to the fluctuation of the light intensity and the dynamic range is independent of the half-wave voltage of the Pockels crystal compared to the conventional crystal bulk-type with the light intensity based detection scheme. A prototype of the proposed OVS is designed and evaluated. The calculated results of the electric field distribution show that the maximal measured voltage of the sensing element is up to 15 kV. The dc voltage from 0 to 3000 V and 50 Hz ac voltage from 0 to 5000 V are measured with good linearity. The proposed OVS achieves accuracy within ± 1% and ± 0.44% with the measured dc voltage above 800 V and ac voltage above 500 V, respectively. The influences of the alignment error in the sensing element on the measurement accuracy are also theoretically analyzed and experimentally verified.

Bias error, along with scale factor, is a key factor that affects the measurement accuracy of the fiber-optic current sensor. Because of polarization crosstalk, the coherence of parasitic interference signals could be rebuilt and form an output independent of the current to be measured, i.e., the bias error. The bias error is a variable of the birefringence optical path difference. Hence, when the temperature changes, the bias error shows a quasi-periodical tendency whose envelope curve reflects the coherence function of light source. By identifying the key factors of bias error and setting the propagation directions of a super-luminescent diode, polarization-maintaining coupler and polarizer to fast axis, it is possible to eliminate the coherence of parasitic interference signals. Experiments show that the maximum bias error decreases by one order of magnitude at temperatures between -40°C to 60°C.

A novel interferometric fiber-optic magnetometer with double digital closed-loop detection scheme is presented in this paper. The particular design of optical circuit is performed to the conventional Michelson interferometer based fiber-optic magnetometer. The digital correlation detection technique with double closed-loop is applied to demodulate the weak magnetic field. One digital closed-loop with square-wave phase modulation is realized to eliminate the low-frequency environmental phase drift. The other is utilized to suppress the hysteresis effects of the magnetostrictive material and recover the magnetic field to be measured. Simulation results on the digital closed-loop algorithms verify the feasibility of the proposed scheme.