The predictive value of blood pressure (BP) for cardiovascular morbidity and mortality diminishes in the elderly, which may be confounded and compensated by the BP differences across the 4 limbs, ...markers of peripheral arterial disease. In a prospective elderly (≥60 years) Chinese study, we performed simultaneous 4-limb BP measurement using an oscillometric device in the supine position, and calculated BP differences between the 4 limbs. At baseline, the mean age of the 3133 participants (1383 men) was 69 years. During 4 years (median) of follow-up, all-cause and cardiovascular deaths occurred in 203 and 93 subjects, respectively. In multiple regression analyses, arm BPs on the higher arm side of systolic BP did not predict mortality (P≥0.06) except for a negative association between mean arterial pressure and total mortality (P=0.04). However, in adjusted analyses, the hazard ratios associated with a 1-SD decrease in ankle-brachial BP index or increase in interarm or interankle BP difference were 1.15 to 1.23 for total mortality (P≤0.01) and 1.17 to 1.24 for cardiovascular mortality (P≤0.04). In categorical analyses, similar results were observed for a decreased ankle-brachial index (≤0.90, ≤0.95, or ≤1.00) or increased interarm or interankle difference (≥15 mm Hg or ≥10 mm Hg). In conclusion, in the elderly, above and beyond arm BP level and together with ankle-brachial index, the interarm and interankle BP differences improve prediction of mortality. Simultaneous 4-limb BP measurement has become feasible with current technology and might be useful in cardiovascular prevention.
Steroid-resistant nephrotic syndrome (SRNS) is a special kidney disease. SRNS is characterized by steroid-resistant, clinical variability, and genetic heterogeneity. Patients with SRNS often may ...eventually need renal transplantation.
A 10-month-old Chinese male infant presented with oliguria, renal dysfunction, hypertension, and anemia.
Combined with clinical manifestations, laboratory testing and sequencing results, the patient was diagnosed as SRNS.
Combined intravenous methylprednisolone and cefoperazone sulbactam did not improve the patient's condition. Thus, SRNS associated with hereditary nephrotic syndrome was strongly suspected. Genetic testing for hereditary renal disease of the patient revealed 2 novel heterozygous mutations in the Nucleoporin 93 (NUP93) gene, which were predicted pathogenic and harmful by bioinformatic softwares of SIFT, PolyPhen_2 and REVEL.
As general physical health deterioration and renal dysfunction, the patient died of a severe infection.
The novel NUP93 heterozygous mutations identified in the current study broadened the genetic spectrum of SRNS and further deepened our insight into pathogenic mutations of NUP93 to improve disease diagnosis.
Abstract
Backgrounds
Solitary fibrous tumor of the pleura (SFTP) is a rare thoracic tumor and usually asymptomatic. Massive SFTP may affect adjacent organs and tissues including pulmonary ...vasculature, bronchus and heart. A thoracotomy for massive SFTP is necessary in severe case. Therefore, it is important for anesthesiologists to understand the condition of patients with massive SFTP and develop an appropriate anesthetic management strategy.
Case summary
A 76-year-old woman with massive SFTP presented to our clinical center and was evaluated as requiring thoracotomy. She received multidisciplinary cooperation treatment from the radiology, cardiac, thoracic surgery and anesthetic teams. The perioperative management of anesthesiologists played a crucial role in the great prognosis of this woman.
Conclusions
This case report demonstrates the importance of comprehensive and meticulous perioperative management and provides guidance to the multidisciplinary team on the potential risk and the rational treatment strategy of patients with massive SFTP during the perioperative period.
Marine euphotic zone is the pivotal region for interplay of light-mineral-microorganism and elements cycle, in which semiconducting minerals exist widely and iron-bearing goethite is a typical and ...widespread one. In this work, we have conducted in-depth researches on the effect of ferrous Fe(II) ions dissolved by photoreduction of goethite on microbial community structure and diversity. The mineral phase, structure and morphology of synthesized goethite were characterized by Raman, X-ray diffraction (XRD), energy disperse spectroscopy (EDS), environmental scanning electron microscope (ESEM), and atomic force microscope (AFM). Photoelectrochemical measurements tested photoelectric response and redox activity of goethite, having proved its significant property of photoelectric response with 44.11% increment of the average photocurrent density relative to the dark current density. The photoreduction experiments of goethite were conducted under light condition in simulated seawater. It has suggested the photoreduction of goethite could occur and Fe(III) was reduced to Fe(II). The dissolved Fe(II) from the photoreduction of goethite under light condition was nearly 11 times than that group without light after a 10-day reaction. Furthermore, results of microbial community sequencing analysis indicated that dissolved Fe(II) could affect the structure and regulate the decrease of microbial community diversity. The emergence of dominant bacteria associated with iron oxidation and transport protein has suggested their obvious selectivity and adaptability in the environment with adding dissolved Fe(II). This work revealed the photoreduction process of semiconducting goethite was remarkable, giving rise to a non-negligible dissolved Fe(II) and its selective effect on the structure, diversity, as well as the function of microbial community. This light-induced interaction between minerals and microorganisms may also further regulate correlative metabolic pathways of carbon cycle in the marine euphotic zone.
Prediction of drug candidates for mutagenicity is a regulatory requirement since mutagenic compounds could pose a toxic risk to humans. The aim of this investigation was to develop a novel prediction ...model of mutagenicity by using a naïve Bayes classifier. The established model was validated by the internal 5-fold cross validation and external test sets. For comparison, the recursive partitioning classifier prediction model was also established and other various reported prediction models of mutagenicity were collected. Among these methods, the prediction performance of naïve Bayes classifier established here displayed very well and stable, which yielded average overall prediction accuracies for the internal 5-fold cross validation of the training set and external test set I set were 89.1±0.4% and 77.3±1.5%, respectively. The concordance of the external test set II with 446 marketed drugs was 90.9±0.3%. In addition, four simple molecular descriptors (e.g., Apol, No. of H donors, Num-Rings and Wiener) related to mutagenicity and five representative substructures of mutagens (e.g., aromatic nitro, hydroxyl amine, nitroso, aromatic amine and N-methyl-N-methylenemethanaminum) produced by ECFP_14 fingerprints were identified. We hope the established naïve Bayes prediction model can be applied to risk assessment processes; and the obtained important information of mutagenic chemicals can guide the design of chemical libraries for hit and lead optimization.
•A novel prediction model of mutagenicity of chemicals was developed by using a naïve Bayes classifier.•Four molecular descriptors considered as important for the mutagenicity were identified.•Substructures for mutagenicity were produced by ECFP_14 fingerprints.
Zwitterionic colloid particles (ZCPs), a novel type of membrane material endowed with tunable selectivity and improved antifouling properties, were synthesized from 3-dimethyl(methacryloyloxyethyl) ...ammonium propane sulfonate (DMAPS) and 2-hydroxyethyl acrylate (HEA) by means of aqueous free-radical polymerization. Atomic force microscopy and dynamic light scattering analyses indicated that the water dispersed ZCPs nanoparticles (300-600 nm) were formed owing to the competitive balance between the electrostatic attraction of DMAPS and the hydrophilic dispersion effect of HEA. As such, when the DMAPS content in ZCPs was selected in the range of 19.4 to 37.1 mol%, ZCP membranes (ZCPMs) were prepared viasurface coating, followed by glutaraldehyde crosslinking at 50 degree C for 3 h. The ZCPMs have a good separation performance to organic molecules (polyethylene glycol, PEG) and inorganic salts (Na sub(2)SO sub(4)). For example, the average rejection of ZCPMs to PEG1000, PEG600, PEG200 and Na sub(2)SO sub(4) is about 96%, 88%, 60%, and 20%, respectively. Noteworthy, the nanostructures of ZCPs and their membrane performances could be conveniently adjusted by tuning the monomer ratio in copolymerization, the H sub(2)SO sub(4) concentration in the casting solution and the pH value of the feed solution. Furthermore, by using humic acid and bovine serum album as model organic foulant molecules, the antifouling properties of ZCPMs proved to be excellent as exemplified by the stable water flux and salt rejection versusfiltration time.
The deformation behavior of particles under pressure dominates the mechanical properties of solid dosage forms. In this study, the in situ 3D deformation of two polymorphs (I and II) of clopidogrel ...bisulfate (CLP) was determined to illustrate pressure distribution profiles within the tablet by the deformation of the crystalline particles for the first time. Synchrotron radiation X-ray computed microtomography (SR-μCT) was utilized to visualize and quantify the morphology of thousands crystalline particles of CLP I and CLP II before and after compression. As a result, the deformation was examined across scale dimensions from microns to the size of the final dosage form. Three dimensional parameters such as volume, sphericity, oblate and prolate of individual particle and distributions were computed and analyzed for quantitative comparison to CLP I and CLP II. The different degrees of deformation under the same compression conditions of CLP I and CLP II were observed and characterized quantitatively. The map of deformation degrees within the tablet illustrated the heterogeneous pressure distribution in various regions of the compacted tablet. In conclusion, the polymorph deformation behaviors demonstrated by SR-μCT quantitative structure analysis deepen understanding of tableting across dimensions from microns to millimeters for the macrostrcuture of tablet.
There is a small amount of clinical data regarding the safety and feasibility of autologous peripheral blood mononuclear cell transplantation into the subarachnoid space for the treatment of ...amyotrophic lateral sclerosis.The objectives of this retrospective study were to assess the safety and efficacy of peripheral blood mononuclear cell transplantation in 14 amyotrophic lateral sclerosis patients to provide more objective data for future clinical trials.After stem cell mobilization and collection,autologous peripheral blood mononuclear cells（1 × 109） were isolated and directly transplanted into the subarachnoid space of amyotrophic lateral sclerosis patients.The primary outcome measure was incidence of adverse events.Secondary outcome measures were electromyography 1 week before operation and 4 weeks after operation,Functional Independence Measurement,Berg Balance Scale,and Dysarthria Assessment Scale 1 week preoperatively and 1,2,4 and 12 weeks postoperatively.There was no immediate or delayed transplant-related cytotoxicity.The number of leukocytes,serum alanine aminotransferase and creatinine levels,and body temperature were within the normal ranges.Radiographic evaluation showed no serious transplant-related adverse events.Muscle strength grade,results of Functional Independence Measurement,Berg Balance Scale,and Dysarthria Assessment Scale were not significantly different before and after treatment.These findings suggest that peripheral blood mononuclear cell transplantation into the subarachnoid space for the treatment of amyotrophic lateral sclerosis is safe,but its therapeutic effect is not remarkable.Thus,a large-sample investigation is needed to assess its efficacy further.
Information on HPV-associated sinonasal squamous cell carcinoma (SNSCC) is very limited in China. The aim of this study was to determine the prevalence of HPV in a large cohort of SNSCC patients in ...China.
Clinical records and formalin-fixed and paraffin-embedded tumor specimens from 30 SNSCC patients with associated inverted papilloma (IP-SNSCC) and 84 de novo SNSCC (DN-SNSCC) patients were retrieved between 2010 and 2017. HPV status was determined for each specimen using a combination of p16 immunohistochemistry and GP5+/6+ PCR.
Immunohistochemistry for p16 was positive in two IP-SNSCC patients (2/30, 6.7%) and in 16 DN-SNSCC patients (16/84, 19.0%). HPV DNA was detected in six IP-SNSCC patients (6/30, 20%) and in three DN-SNSCC patients (3/84, 3.8%). Expression of p16 was not correlated with the presence of HPV DNA (
= 0.150). Among 18 p16-positive SNSCC patients, only three were HPV DNA-positive. Furthermore, only three of nine HPV DNA-positive tumors exhibited high p16 expression. In IP-SNSCC patients, only one of six HPV DNA-positive tumors exhibited high p16 expression. In DN-SNSCC patients, two of three HPV DNA-positive tumors exhibited high p16 expression. The positive rates for both HPV DNA and p16 in IP-SNSCC patients and DN-SNSCC patients were 3.3 and 2.4%, respectively.
Immunostaining for p16 is not a reliable surrogate marker of HPV status in SNSCC. The presence of HPV is rarely detected in DN-SNSCC patients in Eastern China. IP-SNSCC patients frequently lack of p16 overexpression despite the presence of high-risk HPV DNA.
Recent studies demonstrated that the ligand-activated transcription factor peroxisome proliferator-activated receptorα (PPARα) acts in association with histone deacetylase sirtuin 1 (SIRT1) in the ...regulation of metabolism and inflammation involved in cardiovascular diseases. PPARα activation also participates in the modulation of cell apoptosis. Our previous study found that SIRT1 inhibits the apoptosis of vascular adventitial fibroblasts (VAFs). However, whether the role of PPARα in apoptosis of VAFs is mediated by SIRT1 remains unknown. In this study, we aimed to determine the effect of PPARα agonist fenofibrate on cell apoptosis and SIRT1 expression and related mechanisms in ApoE−/− mice and VAFs in vitro. We found that fenofibrate inhibited cell apoptosis in vascular adventitia and up-regulated SIRT1 expression in aorta of ApoE−/− mice. Moreover, SIRT1 activator resveratrol (RSV) further enhanced these effects of fenofibrate. In vitro study showed that activation of PPARα by fenofibrate inhibited TNF-α-induced cell apoptosis and cell cycle arrest in VAFs. Meanwhile, fenofibrate up-regulated SIRT1 expression and inhibited SIRT1 translocation from nucleus to cytoplasm in VAFs stimulated with TNF-α. Moreover, the effects of fenofibrate on cell apoptosis and SIRT1 expression in VAFs were reversed by PPARα antagonist GW6471. Importantly, treatment of VAFs with SIRT1 siRNA or pcDNA3.1(+)-SIRT1 showed that the inhibitory effect of fenofibrate on cell apoptosis in VAFs through SIRT1. On the other hand, knockdown of FoxO1 decreased cell apoptosis of VAFs compared with fenofibrate group. Overexpression of FoxO1 increased cell apoptosis of VAFs compared with fenofibrate group. Further study found that fenofibrate decreased the expression of acetylated-FoxO1 in TNF-α-stimulated VAFs, which was abolished by SIRT1 knockdown. Taken together, these findings indicate that activation of PPARα by fenofibrate inhibits cell apoptosis in VAFs partly through the SIRT1-mediated deacetylation of FoxO1.
•Fenofibrate inhibits apoptosis and increases SIRT1 expression in vivo and in vitro.•Fenofibrate inhibits cell apoptosis in VAFs through SIRT1.•Fenofibrate inhibits apoptosis through SIRT1-mediated deacetylation of FoxO1.•Fenofibrate inhibits apoptosis and increases SIRT1 expression via PPARα activation.
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