Establishment and verification a nomogram for predicting portal vein thrombosis presence among admitted cirrhotic patients

BackgroundPortal vein thrombosis (PVT) is an increasingly recognized complication of cirrhosis and possibly associated with mortality. This study aims to evaluate provoking factors for PVT, then establish a concise and efficient nomogram for predicting PVT presence among admitted cirrhotic patients.Materials and methodsAll cirrhotic patients admitted in Hunan Provincial People's Hospital between January 2010 and September 2020 were retrospectively reviewed, the clinical and laboratory data were collected. Multivariate logistic regression analysis and the least absolute shrinkage and selection operator regression method were used for screening the independent predictors and constructing the nomogram. The calibration curve was plotted to evaluate the consistent degree between observed outcomes and predicted probabilities. The area under the receiver operating characteristics curve was used to assess the discriminant performance. The decision curve analysis (DCA) was carried out to evaluate the benefits of nomogram.ResultsA total of 4,479 patients with cirrhosis were enrolled and 281 patients were identified with PVT. Smoking history, splenomegaly, esophagogastric varices, surgical history, red blood cell transfusion, and D-dimer were independent risk factors for PVT in cirrhosis. A nomogram was established with a good discrimination capacity and predictive efficiency with an the area under the curve (AUC) of 0.704 (95% CI: 0.664–0.745) in the training set and 0.685 (95% CI: 0.615–0.754) in the validation set. DCA suggested the net benefit of nomogram had a superior risk threshold probability.ConclusionA concise and efficient nomogram was established with good performance, which may aid clinical decision making and guide best treatment measures

Targeting F-Box Protein Fbxo3 Attenuates Lung Injury Induced by Ischemia-Reperfusion in Rats

Background: Increasing evidence suggests that Fbxo3 signaling has an important impact on the pathophysiology of the inflammatory process. Fbxo3 protein inhibition has reduced cytokine-driven inflammation and improved disease severity in animal model of Pseudomonas-induced lung injury. However, it remains unclear whether inhibition of Fbxo3 protein provides protection in acute lung injury induced by ischemia-reperfusion (I/R). In this study, we investigated the protective effects of BC-1215 administration, a Fbxo3 inhibitor, on acute lung injury induced by I/R in rats.Methods: Lung I/R injury was induced by ischemia (40 min) followed by reperfusion (60 min). The rats were randomly assigned into one of six experimental groups (n = 6 rats/group): the control group, control + BC-1215 (Fbxo3 inhibitor, 0.5 mg/kg) group, I/R group, or I/R + BC-1215 (0.1, 0.25, 0.5 mg/kg) groups. The effects of BC-1215 on human alveolar epithelial cells subjected to hypoxia-reoxygenation (H/R) were also examined.Results: BC-1215 significantly attenuated I/R-induced lung edema, indicated by a reduced vascular filtration coefficient, wet/dry weight ratio, lung injury scores, and protein levels in bronchoalveolar lavage fluid (BALF). Oxidative stress and the level of inflammatory cytokines in BALF were also significantly reduced following administration of BC-1215. Additionally, BC-1215 mitigated I/R-stimulated apoptosis, NF-κB, and mitogen-activated protein kinase activation in the injured lung tissue. BC-1215 increased Fbxl2 protein expression and suppressed Fbxo3 and TNFR associated factor (TRAF)1–6 protein expression. BC-1215 also inhibited IL-8 production and NF-κB activation in vitro in experiments with alveolar epithelial cells exposed to H/R.Conclusions: Our findings demonstrated that Fbxo3 inhibition may represent a novel therapeutic approach for I/R-induced lung injury, with beneficial effects due to destabilizing TRAF proteins

滨螺卓越的耐高温能力，温度耐受上限竟高达55℃——潮间带 Echinolittorina 属滨螺细胞质苹果酸脱氢酶高温耐受机制的研究

研究团队以分布于高潮间带，具有高耐热性的两种滨螺为研究对象，通过生理生化学实验及计算机模拟手段，发现耐热的软体动物通过增强代谢关键酶的作用，避免了在高温条件下的解链；研究团队还提出，局部柔性的增长使得酶在低温条件下能够发挥其催化功能，同时能在极端高温条件下，起到稳定蛋白质的作用，确保了蛋白质功能的维持。这些发现对于查明环境温度对生物分布的影响及其机制，预测气候变暖的生态学效应将具有重要意义。 滨螺广泛分布于潮间带高潮区，是潮间带垂直分布区划分的标志性物种。塔结节滨螺（Echinolittorina malaccana）和粒结节滨螺（E. radiata）是我国岩相潮间带高潮区常见物种，其温度耐受上限高达 55-60°C。董云伟教授团队与美国斯坦福大学 George Somero 教授，以及华侨大学张光亚教授团队合作，进行了一系列研究，探索了高热耐受性滨螺在极端高温条件下，仍旧保持体内蛋白质微结构的完整、功能的维持的奥妙所在。【Abstract】Snails of the genus Echinolittorina are among the most heat-tolerant animals; they experience average body temperatures near 41–44℃ in summer and withstand temperatures up to at least 55℃. Here, we demonstrate that heat stability of function (indexed by the Michaelis–Menten constant of the cofactor NADH, KMNADH) and structure (indexed by rate of denaturation) of cytosolic malate dehydrogenases (cMDHs) of two congeners (E. malaccana and E. radiata) exceeds values previously found for orthologs of this protein from less thermophilic species. The ortholog of E. malaccana is more heat stable than that of E. radiata, in keeping with the congeners' thermal environments. Only two inter-congener differences in amino acid sequence in these 332 residue proteins were identified. In both cases (positions 48 and 114), a glycine in the E. malaccana ortholog is replaced by a serine in the E. radiata protein. To explore the relationship between structure and function and to characterize how amino acid substitutions alter stability of different regions of the enzyme, we used molecular dynamics simulation methods. These computational methods allow determination of thermal effects on fine-scale movements of protein components, for example, by estimating the root mean square deviation in atom position over time and the root mean square fluctuation for individual residues. The minor changes in amino acid sequence favor temperature-adaptive change in flexibility of regions in and around the active sites. Interspecific differences in effects of temperature on fine-scale protein movements are consistent with the differences in thermal effects on binding and rates of heat denaturation.This research was substantially supported by grants from National Natural Science Foundation of China (41476115), Program for New Century Excellent Talents of Ministry of Education, China, Nature Science Foundation for Distinguished Young Scholars of Fujian Province (2017J07003), China and the State Key Laboratory of Marine Environmental Science Internal Program, Xiamen University (MELRI1501)

miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions

MicroRNAs (miRNAs) are small non-coding RNA molecules capable of negatively regulating gene expression to control many cellular mechanisms. The miRTarBase database (http://mirtarbase.mbc.nctu.edu.tw/) provides the most current and comprehensive information of experimentally validated miRNA-target interactions. The database was launched in 2010 with data sources for >100 published studies in the identification of miRNA targets, molecular networks of miRNA targets and systems biology, and the current release (2013, version 4) includes significant expansions and enhancements over the initial release (2010, version 1). This article reports the current status of and recent improvements to the database, including (i) a 14-fold increase to miRNA-target interaction entries, (ii) a miRNA-target network, (iii) expression profile of miRNA and its target gene, (iv) miRNA target-associated diseases and (v) additional utilities including an upgrade reminder and an error reporting/user feedback system

AMiBA: Broadband Heterodyne CMB Interferometry

The Y. T. Lee Array for Microwave Background (AMiBA) has reported the first science results on the detection of galaxy clusters via the Sunyaev Zel'dovich effect. The science objectives required small reflectors in order to sample large scale structures (20') while interferometry provided modest resolutions (2'). With these constraints, we designed for the best sensitivity by utilizing the maximum possible continuum bandwidth matched to the atmospheric window at 86-102GHz, with dual polarizations. A novel wide-band analog correlator was designed that is easily expandable for more interferometer elements. MMIC technology was used throughout as much as possible in order to miniaturize the components and to enhance mass production. These designs will find application in other upcoming astronomy projects. AMiBA is now in operations since 2006, and we are in the process to expand the array from 7 to 13 elements.Comment: 10 pages, 6 figures, ApJ in press; a version with high resolution figures available at http://www.asiaa.sinica.edu.tw/~keiichi/upfiles/AMiBA7/mtc_highreso.pd

Adult mortality of diseases and injuries attributable to selected metabolic, lifestyle, environmental, and infectious risk factors in Taiwan: A comparative risk assessment

Background: To facilitate priority-setting in health policymaking, we compiled the best available information to estimate the adult mortality (>30 years) burden attributable to 13 metabolic, lifestyle, infectious, and environmental risk factors in Taiwan. Methods: We obtained data on risk factor exposure from nationally representative health surveys, cause-specific mortality from the National Death Registry, and relative risks from epidemiological studies and meta-analyses. We applied the comparative risk assessment framework to estimate mortality burden attributable to individual risk factors or risk factor clusters. Results: In 2009, high blood glucose accounted for 14,900 deaths (95% UI: 11,850-17,960), or 10.4% of all deaths in that year. It was followed by tobacco smoking (13,340 deaths, 95% UI: 10,330-16,450), high blood pressure (11,190 deaths, 95% UI: 8,190-14,190), ambient particulate matter pollution (8,600 deaths, 95% UI: 7,370-9,840), and dietary risks (high sodium intake and low intake of fruits and vegetables, 7,890 deaths, 95% UI: 5,970-9,810). Overweight-obesity and physical inactivity accounted for 7,620 deaths (95% UI: 6,040-9,190), and 7,400 deaths (95% UI: 6,670-8,130), respectively. The cardiometabolic risk factors of high blood pressure, high blood glucose, high cholesterol, and overweight-obesity jointly accounted for 12,120 deaths (95% UI: 11,220-13,020) from cardiovascular diseases. For domestic risk factors, infections from hepatitis B virus (HBV) and hepatitis C virus (HCV) were responsible for 6,300 deaths (95% UI: 5,610-6,980) and 3,170 deaths (95% UI: 1,860-4,490), respectively, and betel nut use was associated with 1,780 deaths from oral, laryngeal, and esophageal cancer (95% UI: 1,190-2,360). The leading risk factors for years of life lost were similar, but the impact of tobacco smoking and alcohol use became larger because the attributable deaths from these risk factors occurred among young adults aged less than 60 years. Conclusions: High blood glucose, tobacco smoking, and high blood pressure are the major risk factors for deaths from diseases and injuries among Taiwanese adults. A large number of years of life would be gained if the 13 modifiable risk factors could be removed or reduced to the optimal level

The Yuan-Tseh Lee Array for Microwave Background Anisotropy

The Yuan-Tseh Lee Array for Microwave Background Anisotropy (AMiBA) is the first interferometer dedicated to studying the cosmic microwave background (CMB) radiation at 3mm wavelength. The choice of 3mm was made to minimize the contributions from foreground synchrotron radiation and Galactic dust emission. The initial configuration of seven 0.6m telescopes mounted on a 6-m hexapod platform was dedicated in October 2006 on Mauna Loa, Hawaii. Scientific operations began with the detection of a number of clusters of galaxies via the thermal Sunyaev-Zel'dovich effect. We compare our data with Subaru weak lensing data in order to study the structure of dark matter. We also compare our data with X-ray data in order to derive the Hubble constant.Comment: accepted for publication in ApJ (13 pages, 7 figures); a version with high resolution figures available at http://www.asiaa.sinica.edu.tw/~keiichi/upfiles/AMiBA7/pho_highreso.pd

Management of granulomatous lobular mastitis: an international multidisciplinary consensus (2021 edition)

Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.Improving the Ability of Diagnosis and Treatment of Difficult Disease

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure