Impact of perioperative low-molecular-weight heparin therapy on clinical events of elderly patients with prior coronary stents implanted > 12 months undergoing non-cardiac surgery: a randomized, placebo-controlled trial.

BACKGROUND: Little is known about the safety and efficacy of discontinuing antiplatelet therapy via LMWH bridging therapy in elderly patients with coronary stents implanted for > 12 months undergoing non-cardiac surgery. This randomized trial was designed to compare the clinical benefits and risks of antiplatelet drug discontinuation via LMWH bridging therapy. METHODS: Patients were randomized 1:1 to receive subcutaneous injections of either dalteparin sodium or placebo. The primary efficacy endpoint was cardiac or cerebrovascular events. The primary safety endpoint was major bleeding. RESULTS: Among 2476 randomized patients, the variables (sex, age, body mass index, comorbidities, medications, and procedural characteristics) and percutaneous coronary intervention information were not significantly different between the bridging and non-bridging groups. During the follow-up period, the rate of the combined endpoint in the bridging group was significantly lower than in the non-bridging group (5.79% vs. 8.42%, p = 0.012). The incidence of myocardial injury in the bridging group was significantly lower than in the non-bridging group (3.14% vs. 5.19%, p = 0.011). Deep vein thrombosis occurred more frequently in the non-bridging group (1.21% vs. 0.4%, p = 0.024), and there was a trend toward a higher rate of pulmonary embolism (0.32% vs. 0.08%, p = 0.177). There was no significant difference between the groups in the rates of acute myocardial infarction (0.81% vs. 1.38%), cardiac death (0.24% vs. 0.41%), stroke (0.16% vs. 0.24%), or major bleeding (1.22% vs. 1.45%). Multivariable analysis showed that LMWH bridging, creatinine clearance < 30 mL/min, preoperative hemoglobin < 10 g/dL, and diabetes mellitus were independent predictors of ischemic events. LMWH bridging and a preoperative platelet count of < 70 × 109/L were independent predictors of minor bleeding events. CONCLUSIONS: This study showed the safety and efficacy of perioperative LMWH bridging therapy in elderly patients with coronary stents implanted > 12 months undergoing non-cardiac surgery. An alternative approach might be the use of bridging therapy with half-dose LMWH. TRIAL REGISTRATION: ISRCTN65203415.

Accelerating Charge Kinetics in Photocatalytic CO2 Reduction by Modulating the Cobalt Coordination in Heterostructures of Cadmium Sulfide/Metal-Organic Layer.

Artificial photocatalytic CO2 reduction (CO2 R) holds great promise to directly store solar energy into chemical bonds. The slow charge and mass transfer kinetics at the triphasic solid-liquid-gas interface calls for the rational design of heterogeneous photocatalysts concertedly boosting interfacial charge transfer, local CO2 concentration, and exposure of active sites. To meet these requirements, in this study heterostructures of CdS/MOL (MOL = metal-organic layer) furnishing different redox Co sites are fabricated for CO2 R photocatalysts. It is found that the coordination environment of Co is key to photocatalytic activity. The best catalyst ensemble comprising ligand-chelated Co2+ with the bipyridine electron mediator demonstrates a high CO yield rate of 1523 µmol h-1 gcat -1 , selectivity of 95.8% and TON of 1462.4, which are ranked among the best seen in literature. Comprehensive photochemical and electroanalytical characterizations attribute the high CO2 R performance to the improved photocarrier separation and charge kinetics originated from the proper energy band alignment and coordination chemistry. This work highlights the construction of 2D heterostructures and modulation of transition metal coordination to expedite the charge kinetics in photocatalytic CO2 reduction.

A genomic DNA-based NGS method for the simultaneous detection of multiple fusion genes in pediatric leukemia.

Fusion genes are products of chromosomal translocations that generate either a dysregulated partner gene or a chimeric fusion protein with new properties, and contribute significantly to leukemia development and clinical risk stratification. However, simultaneous detection of several hundreds of fusion genes has always been a challenge in a clinical laboratory setting. In the present study, a total of 182 pediatric patients with leukemia were screened for fusion genes by employing a novel genomic DNA-, instead of RNA-, based next-generation sequencing (NGS) method. This involved the comparison of the multiply targeted capture sequencing method with a detection panel of 270 fusion genes (MTCS-270) with an RNA-based multiplex reverse transcription-PCR technique with a detection panel of 57 fusion genes (MRTP-57). MRTP-57 has been well established in the clinical lab at Beijing Hightrust Diagnostics, Co. (Beijing, China) for an up-front leukemia diagnosis and served as the control technique in the present study. In the series, MTCS-270 and MRTP-57 yielded a positive fusion gene detection rate of 50.0% (91/182) and 41.8% (76/182), respectively, indicating an advantage of MTCS-270 over MRTP-57 in overall detection sensitivity. Specifically, all the fusion genes detected by MRTP-57 were also identified by MTCS-270, clearly signifying the respectable detection accuracy of MTCS-270. Notably, across the patients screened, MTCS-270 identified more samples with fusion genes than MRTP-57, illustrating a broader fusion gene detection coverage by MTCS-270. The present study provides solid evidence that this DNA-based NGS approach can be used as a potential detection tool together with other well-established molecular cytogenetic methods for leukemia management, and to the best of our knowledge, represents the largest leukemia fusion gene identification analysis by genomic NGS.

Hydrophobically Associating Polymers Dissolved in Seawater for Enhanced Oil Recovery of Bohai Offshore Oilfields.

As compared to China's overall oil reserves, the reserve share of offshore oilfields is rather significant. However, offshore oilfield circumstances for enhanced oil recovery (EOR) include not just severe temperatures and salinity, but also restricted space on offshore platforms. This harsh oil production environment requires polymers with relatively strong salt resistance, solubility, thickening ability, rapid, superior injection capabilities, and anti-shearing ability. As a result, research into polymers with high viscosity and quick solubility is recognized as critical to meeting the criteria of polymer flooding in offshore oil reservoirs. For the above purposes, a novel hydrophobically associating polymer (HAP) was prepared to be used for polymer flooding of Bohai offshore oilfields. The synthetic procedure was free radical polymerization in aqueous solutions starting at 0 °C, using acrylamide (AM), acrylic acid (AA), 2-acrylamido-2-methylpropane sulfonic acid (AMPS), and poly(ethylene glycol) octadecyl methacrylate (POM) as comonomers. It was discovered that under ideal conditions, the molecular weight of HAP exceeds 2.1 × 107 g⋅mol-1. In a simulated reservoir environment, HAP has substantially greater solubility, thickening property, and salt resistance than conventional polyacrylamide (HPAM), with equivalent molecular weight. Finally, the injectivity and propagation of the two polymers in porous media were investigated. Compared with HPAM, which has a similar molecular weight, HAP solution with the concentration of 0.175% had a much better oil displacement effect in the porous medium, which can enhance oil recovery by 8.8%. These discoveries have the potential to pave the way for chemical EOR in offshore oilfields.

A "Blockchain" Synergy in Conductive Polymer-Filled Metal-Organic Frameworks for Dendrite-Free Li Plating/Stripping with High Coulombic Efficiency.

The performance of lithium-metal batteries is severely hampered by uncontrollable dendrite growth and volume expansion on the metal anodes. Inspired by the "blockchain" concept in data mining, here we utilize a conductive polymer-filled metal-organic framework (MOF) as the lithium host, in which polypyrrole (PPy) serves as the "chain" to interlink Li "blocks" stored in the MOF pores. While the N-rich PPy guides fast Li+ infiltration/extrusion and serves as the nucleation sites for isotropic Li growth, the MOF pores compartmentalize bulk Li deposition for 3D matrix Li storage, leading to low-barrier and dendrite-free Li plating/stripping with superb Coulombic efficiency. The as-fabricated lithium-metal anodes operate over 700 cycles at 5 mA cm-2 in symmetric cells, and 800 cycles at 1 C in full cells with a per-cycle capacity loss of only 0.017 %. This work might open a new chapter for Li-metal anode construction by introducing the concept of "blockchain" management of Li plating/stripping.

The exocyst acting through the primary cilium is necessary for renal ciliogenesis, cystogenesis, and tubulogenesis.

The exocyst is a highly conserved protein complex found in most eukaryotic cells and is associated with many functions, including protein translocation in the endoplasmic reticulum, vesicular basolateral targeting, and ciliogenesis in the kidney. To investigate the exocyst functions, here we exchanged proline for alanine in the highly conserved VXPX ciliary targeting motif of EXOC5 (exocyst complex component 5), a central exocyst gene/protein, and generated stable EXOC5 ciliary targeting sequence-mutated (EXOC5CTS-m) Madin-Darby canine kidney (MDCK) cells. The EXOC5CTS-m protein was stable and could bind other members of the exocyst complex. Culturing stable control, EXOC5-overexpressing (OE), Exoc5-knockdown (KD), and EXOC5CTS-m MDCK cells on Transwell filters, we found that primary ciliogenesis is increased in EXOC5 OE cells and inhibited in Exoc5-KD and EXOC5CTS-m cells. Growing cells in collagen gels until the cyst stage, we noted that EXOC5-OE cells form mature cysts with single lumens more rapidly than control cysts, whereas Exoc5-KD and EXOC5CTS-m MDCK cells failed to form mature cysts. Adding hepatocyte growth factor to induce tubulogenesis, we observed that EXOC5-OE cell cysts form tubules more efficiently than control MDCK cell cysts, EXOC5CTS-m MDCK cell cysts form significantly fewer tubules than control cell cysts, and Exoc5-KD cysts did not undergo tubulogenesis. Finally, we show that EXOC5 mRNA almost completely rescues the ciliary phenotypes in exoc5-mutant zebrafish, unlike the EXOC5CTS-m mRNA, which could not efficiently rescue the phenotypes. Taken together, these results indicate that the exocyst, acting through the primary cilium, is necessary for renal ciliogenesis, cystogenesis, and tubulogenesis.

Management of greenlight laser plus transurethral resection of prostate for elderly men.

The study is aiming to evaluate the treatment safety and efficacy of greenlight laser photovaporization of the prostate (PVP) combined with transurethral electrovaporization resection (TUVP) for elderly (≥ 70 years) men with lower urinary tract symptoms due to benign prostatic hyperplasia (BPH/LUTS) with a large prostate volume (≥ 80 mL). One hundred twelve BPH/LUTS patients treated with PVP were divided into 2 groups according to prostate volume (PV), the outcomes of the 2 groups were assessed at 12 months after the operation. Patients in the PV ≥ 80 group (n = 51) had a higher level of maximum detrusor pressure (Pdet.max) than those in the PV < 80 group (n = 61) (97.14  ±â€Š 36.68 vs 70.70 ±â€Š32.55, P < .001). Pdet.max level of the 2 groups was significantly decreased at the end of follow-up. International Prostate Symptom Score questionnaires (IPSS) score, maximum flow rate (Qmax), and residual urine volume (PVR) were significantly improved in comparison to the preoperative status (P < .001). PVP combined with TUVP can significantly improve outcomes (IPSS, Qmax, PVR) and is a safe and effective technique for elderly BPH/LUTS patients with a large prostate volume.

GreenLight laser photoselective vaporization of the prostate for treatment of benign prostate hyperplasia/lower urinary tract symptoms in patients with different post-void residual urine.

The purpose of this study is to assess the safety and efficacy of GreenLight laser photoselective vaporization of the prostate (PVP) for the treatment of benign prostate hyperplasia/lower urinary tract symptoms (BPH/LUTS) in patients with different post-void residual urine (PVR). BPH/LUTS patients treated with PVP from January 2014 to January 2016 were enrolled in the present study. All patients were divided into PVR > 50, 50 ≤ PVR < 400, and PVR ≥ 400 ml groups, and standard general and urological methods for BPH/LUTS were carried out. PVP surgery was performed, and the follow-up outcome was investigated 6 months after surgery. A total of 429 patients were included, and there were no significant differences in comorbid diseases or habits among the three groups. The maximum urinary flow rate (Qmax) differed significantly among the groups (P < 0.001), while patients in the PVR < 50 ml group had higher maximum detrusor pressure (Pdet.max) level than the other two groups (P < 0.001). Patients in 50 ≤ PVR < 400 (P < 0.001) and PVR ≥ 400 (P < 0.001) ml groups were more likely to develop detrusor underactivity than those in the PVR < 50 ml group. All patients were treated with PVP, and there were no severe complications requiring rehospitalization or reoperation except nine designed re-treatments. Follow-up data of 387 patients were available. Significant improvement in outcome parameters (International Prostate Symptom Score [IPSS], Qmax, and PVR) was observed in comparison with baseline measurements for the three groups. PVP significantly improved the IPSS, Qmax, and PVR in patients with different PVR; PVP is a safe and effective procedure for BPH/LUTS patients.

Prognostic implications of preoperative anemia in urothelial carcinoma: A meta-analysis.

The prognostic significance of preoperative anemia (PA) has been identified in various malignancies. However, its predictive role in urothelial carcinoma (UC) remains controversial. The aim of this study was to investigate the prognostic value of PA in UC patients. We performed a meta-analysis of the association between PA and survival outcome in UC patients. Electronic databases were searched up to June 30, 2016. Study characteristics and prognostic data were extracted from each included study. Cancer-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS) were pooled using hazard ratio (HR) with corresponding 95% confidence intervals (CI). Herein, 12 studies comprising 3815 patients were included in the meta-analysis. There were 1593 (41.76%) patients in the PA group and 2222 (58.24%) in the control group. The overall pooled HRs of PA for CSS, RFS, and OS were significant at 2.21, (95% CI: 1.83-2.65, Pheterogeneity = 0.49, I2 = 0%), 1.87 (95% CI: 1.59-2.20, Pheterogeneity = 0.22, I2 = 28%), and 2.04(95% CI: 1.76-2.37, Pheterogeneity = 0.36, I2 = 9%) respectively. Stratified analyses indicated that PA was a predictor of poor prognosis based on ethnicity, sample size, tumor T stage, G grade, lymphovascular invasion (LVI), concomitant carcinoma in situ (CIS), and follow-up values. Our findings show that PA has negative prognostic effects on the survival outcome (CSS, RFS, and OS) in UC patients and can serve as a useful and cost-effective marker to aid prognosis prediction.

Assessment of noninvasive predictors of bladder detrusor underactivity in BPH/LUTs patients.

PURPOSE: To retrospectively assess the diagnostic predictive value of clinical characteristics to improve the diagnostic accuracy of bladder detrusor underactivity (DU) among benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) patients who cannot undergo urodynamic examinations. METHODS: A total of 704 BPH/LUTS patients at Tianjin Medical Union Center from January 2013 through June 2016 were enrolled in the study. All cases were stratified by maximum detrusor pressure (Pdet.max) into two groups (DU and control). Patient and clinical variables were analyzed in both groups. RESULTS: One hundred twelve and 592 cases were classified into the DU and control group, respectively. PV (OR 0.976, 95% CI 0.961-0.991, P = 0.002) and PVR (OR 1.004, 95% CI 1.001-1.007, P = 0.004) were independent predictors of DU. In addition, Pdet.max was positively correlated with HTN (≥10 years) (r = 0.373, P = 0.001), smoking (r = 0.108, P = 0.039), IPSS (20-23) (r = 0.257, P = 0.013), PV (r = 0.305, P < 0.001), PSA (1-2.2 ng/mL) (r = 0.428, P = 0.002), PSAD (0-0.02) (r = 0.430, P = 0.02), and Q max (≤4 mL/s) (r = 0.372, P < 0.001), and inversely correlated with age (>76 years) (r = -0.265, P = 0.015), BMI (21-23) (r = -0.382, P = 0.001), DM (0-20 years) (r = 0.365, P = 0.009) and PVR (50-400 mL) (r = 0.423, P = 0.001). The AUCs for BMI, PV, tPSA, PSAD, Q max, and PVR were 0.762, 0.739, 0.727, 0.681, 0.749, and 0.716, respectively. Combined ROC analysis showed the AUC for PV + PVR was 0.774 with sensitivity of 77.78% and specificity of 73.68%. CONCLUSION: Clinical factors were effective for predicting DU and could help improve the diagnostic accuracy for BPH/LUTS patients who cannot undergo urodynamic examinations.

Prognostic impact of preoperative anemia on non-muscle-invasive bladder carcinoma treated with GreenLight laser vaporization.

In this study, we aimed to evaluate the impact of preoperative anemia (PA) on oncological outcomes among patients with non-muscle-invasive bladder cancer (NMIBC) treated with GreenLight laser vaporization of bladder tumor (PV-BT). Between January 2010 and December 2015, 407 patients with NMIBC who underwent PV-BT surgery were stratified into normal and anemia groups based on the World Health Organization classification (anemia cutoff value: hemoglobin level, <13.0 m g/dL in men and <12.0 mg/dL in women). The Student's t test and chi-square test were performed to assess the effects of PA on clinical and pathological characteristics of patients with NMIBC. The Kaplan-Meier method was used to investigate the influence of PA on oncological survival outcomes. Before PV-BT, 139 patients (34.2%) were anemic. No significant differences in age, sex, smoking habit, tumor size, focality, grade, and stage were found between the anemia and normal groups. At a median follow-up period of 32.5 months (range, 8-60 months), 74 patients (18.2%) had urothelial recurrence, 30 (7.4%) died from any cause, and 21 (5.2%) died from bladder cancer. In the Kaplan-Meier analysis, preoperative anemia was significantly associated with decreased cancer-specific survival (CSS) and overall survival (OS) of the patients with NMIBC. However, recurrence-free survival (RFS) showed no statistically significant difference between the PA and normal groups. The preoperative anemic patients with NMIBC who underwent PV-BT surgery had worse CSS and OS. PA can be a useful and cost-effective prognostic marker in the clinical practice for NMIBC treatment.

Identification and expression analysis of the interferon-induced protein with tetratricopeptide repeats 5 (IFIT5) gene in duck (Anas platyrhynchos domesticus).

The interferon-induced proteins with tetratricopeptide repeats (IFITs) protein family mediates antiviral effects by inhibiting translation initiation, cell proliferation, and migration in the interferon (IFN) dependent innate immune system. Several members of this family, including IFIT1, IFIT2, IFIT3 and IFIT5, have been heavily studied in mammals. Avian species contain only one family member, IFIT5, and little is known about the role of this protein in birds. In this study, duck IFIT5 (duIFIT5) full-length mRNA was cloned by reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of the cDNA ends (RACE). Based on the sequence obtained, we performed a series of bioinformatics analyses, and found that duIFIT5 was most similar to homologs in other avian species. Also, duIFIT5 contained eight conserved TPR motifs and two conserved multi-domains (TPR_11 and TPR_12). Finally, we used duck hepatitis virus type 1 (DHV-1) and polyriboinosinicpolyribocytidylic acid (poly (I:C)) as a pathogen or a pathogen-associated molecular pattern induction to infect three-day-old domestic ducklings. The liver and spleen were collected to detect the change in duIFIT5 transcript level upon infection by quantitative real-time PCR (qRT-PCR). DuIFIT5 expression rapidly increased after DHV-1 infection and maintained a high level, while the transcripts of duIFIT5 peaked at 8h after poly (I:C) infection and then returned to normal. Taken together, these results provide a greater understanding of avian IFIT5.

SWI2/SNF2 chromatin remodeling ATPases overcome polycomb repression and control floral organ identity with the LEAFY and SEPALLATA3 transcription factors.

Patterning of the floral organs is exquisitely controlled and executed by four classes of homeotic regulators. Among these, the class B and class C floral homeotic regulators are of central importance as they specify the male and female reproductive organs. Inappropriate induction of the class B gene APETALA3 (AP3) and the class C gene AGAMOUS (AG) causes reduced reproductive fitness and is prevented by polycomb repression. At the onset of flower patterning, polycomb repression needs to be overcome to allow induction of AP3 and AG and formation of the reproductive organs. We show that the SWI2/SNF2 chromatin-remodeling ATPases SPLAYED (SYD) and BRAHMA (BRM) are redundantly required for flower patterning and for the activation of AP3 and AG. The SWI2/SNF2 ATPases are recruited to the regulatory regions of AP3 and AG during flower development and physically interact with two direct transcriptional activators of class B and class C gene expression, LEAFY (LFY) and SEPALLATA3 (SEP3). SYD and LFY association with the AP3 and AG regulatory loci peaks at the same time during flower patterning, and SYD binding to these loci is compromised in lfy and lfy sep3 mutants. This suggests a mechanism for SWI2/SNF2 ATPase recruitment to these loci at the right stage and in the correct cells. SYD and BRM act as trithorax proteins, and the requirement for SYD and BRM in flower patterning can be overcome by partial loss of polycomb activity in curly leaf (clf) mutants, implicating the SWI2/SNF2 chromatin remodelers in reversal of polycomb repression.

Cysteine scanning mutagenesis of alpha4, a putative pore-lining helix of the Bacillus thuringiensis insecticidal toxin Cry1Aa.

Helix alpha4 of Bacillus thuringiensis Cry toxins is thought to line the lumen of the pores they form in the midgut epithelial cells of susceptible insect larvae. To define its functional role in pore formation, most of the alpha4 amino acid residues were replaced individually by a cysteine in the Cry1Aa toxin. The toxicities and pore-forming abilities of the mutated toxins were examined, respectively, by bioassays using neonate Manduca sexta larvae and by a light-scattering assay using midgut brush border membrane vesicles isolated from M. sexta. A majority of these mutants had considerably reduced toxicities and pore-forming abilities. Most mutations causing substantial or complete loss of activity map on the hydrophilic face of the helix, while most of those having little or only relatively minor effects map on its hydrophobic face. The properties of the pores formed by mutants that retain significant activity appear similar to those of the pores formed by the wild-type toxin, suggesting that mutations resulting in a loss of activity interfere mainly with pore formation.

Unique, shared, and redundant roles for the Arabidopsis SWI/SNF chromatin remodeling ATPases BRAHMA and SPLAYED.

Chromatin remodeling is emerging as a central mechanism for patterning and differentiation in multicellular eukaryotes. SWI/SNF chromatin remodeling ATPases are conserved in the animal and plant kingdom and regulate transcriptional programs in response to endogenous and exogenous cues. In contrast with their metazoan orthologs, null mutants in two Arabidopsis thaliana SWI/SNF ATPases, BRAHMA (BRM) and SPLAYED (SYD), are viable, facilitating investigation of their role in the organism. Previous analyses revealed that syd and brm null mutants exhibit both similar and distinct developmental defects, yet the functional relationship between the two closely related ATPases is not understood. Another central question is whether these proteins act as general or specific transcriptional regulators. Using global expression studies, double mutant analysis, and protein interaction assays, we find overlapping functions for the two SWI/SNF ATPases. This partial diversification may have allowed expansion of the SWI/SNF ATPase regulatory repertoire, while preserving essential ancestral functions. Moreover, only a small fraction of all genes depends on SYD or BRM for expression, indicating that these SWI/SNF ATPases exhibit remarkable regulatory specificity. Our studies provide a conceptual framework for understanding the role of SWI/SNF chromatin remodeling in regulation of Arabidopsis development.

The N-terminal ATPase AT-hook-containing region of the Arabidopsis chromatin-remodeling protein SPLAYED is sufficient for biological activity.

The SNF2-like chromatin-remodeling ATPase SPLAYED (SYD) was identified as a co-activator of floral homeotic gene expression in Arabidopsis. SYD is also required for meristem maintenance and regulates flowering under a non-inductive photoperiod. SNF2 ATPases are structurally and functionally conserved from yeast to humans. In addition to the conserved protein features, SYD has a large unique C-terminal domain. We show here that SYD is present as two forms in the nucleus, full-length and truncated, with the latter apparently lacking the C-terminal domain. The ratio of the two forms of endogenous SYD differs in juvenile and in adult tissues. Furthermore, an SYD variant lacking the C-terminal domain (SYDDeltaC) rescues the syd null mutant, indicating that the N-terminal ATPase AT-hook-containing region of SYD is sufficient for biological activity. Plants expressing SYDDeltaC show molecular and morphological phenotypes opposite to those of the null mutant, suggesting that the construct results in increased activity. This increased activity is at least in part due to elevated SYD protein levels in these lines. We propose that the C-terminal domain may control SYD accumulation and/or specific activity in the context of the full-length protein. The presence of the C-terminal domain in rice SYD suggests that its role is probably conserved in the two classes of flowering plants.