QSPR modeling of bioconcentration factor of nonionic compounds using Gaussian processes and theoretical descriptors derived from electrostatic potentials on molecular surface.

In the present study, geometrical structures were constructed and optimized for 122 nonionic organic compounds at the quantum-mechanical HF/6-31G level of theory. The electrostatic potentials and subsequent structural descriptors derived from them were obtained. Gaussian process, and for comparison purpose, multiple linear regression (MLR) and support vector machine (SVM), were then employed to build the quantitative structure-bioconcentration factor relationships. Systematical validations including internal leave-one-out cross-validation, the validation for external test set, as well as a more rigorous Monte Carlo cross-validation were made to confirm the reliability of the constructed models. It has been found that the quantities derived from electrostatic potential, V(min) and ∑V(s,ind)(-), together with the molecular volume (V(mc)), dipole moment (µ) and the energy level of highest occupied molecular orbital (E(HOMO)) can be well used to express the quantitative structure-property relationship of this sample set. Both linear and nonlinear models can give satisfactory results, and the GP, which be capable of handing with linear and nonlinear-hybrid relationship through a mixed covariance function, appears to have better fitting and predictive abilities than other two statistical methods. The coefficient of determination r(pred)(2) and root mean square error of prediction (RMSEP) for the external test set are 0.953 and 0.337, respectively.

Treatment strategies and indications for interventional management of pseudoaneurysms / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pseudoaneurysms (PAs) are common vascular abnormalities predominantly arising from a disruption in the integrity of the arterial wall. The potential complications of PAs are usually unpredictable and carry high rates of morbidity and mortality. This paper presents our experience with various treatment strategies for PAs.</p><p><b>METHODS</b>Fifty-four patients with 55 PAs were diagnosed by non-invasive imaging examination. The etiology of PAs included trauma (33/55), infection (5/55), iatrogenic (6/55), and idiopathic (11/55). Different procedures including ultrasound (US)-guided compression, endovascular treatment, and surgery were performed depending on the location of PAs, size of the sac and neck, and characteristics of the donor artery. The methods of endovascular treatment included embolization of parent artery, the PA sac, or implantation of a stent-graft. Follow-up was performed using US or CT and ranged from 1 day to 24 months (average 16.7 months).</p><p><b>RESULTS</b>In all 54 patients, 3 patients with superficial PAs were treated by US-guided compression, while 44 patients with 45 PAs located in the head and neck (n = 20), viscera (n = 10) or extremities (n = 15) were treated by endovascular treatment. Nine patients with PAs located in the head and neck (n = 2) or extremities (n = 7) were treated by surgery. Among them, one patient underwent endovascular treatment combined with surgery and 1 was treated by surgery after unsuccessful US-guided compression. In the 3 patients treated with US-guided compression, 2 were successfully treated while the remaining patient required additional surgery. Primary technical success of endovascular management was 97.7% (43/44) and the cure rate was 95.5% (42/44). In the surgery group, 4 patients recovered well, 1 patient was cured by endovascular treatment combined with surgery, 2 cases underwent amputation, 1 patient died of multi-organ failure and 1 patient was paralysed.</p><p><b>CONCLUSIONS</b>Minimally invasive interventional techniques are established treatment methods for PA with favorable success rates and minimal morbidity. The therapeutic options should be tailored to the location, size and rupture risk of PA, condition of the donor artery and existing comorbidity.</p>

QSPR/QSAR models for prediction of the physico-chemical properties and biological activity of polychlorinated diphenyl ethers (PCDEs).

Polychlorinated diphenyl ethers (PCDEs) are a group of important persistent organic pollutants. In the present study, geometrical optimization and electrostatic potential calculations have been performed for all 209 PCDE congeners at the HF/6-31G(*) level of theory. A number of statistically-based parameters have been obtained. Linear relationships between gas-chromatographic relative retention time (RRT), n-octanol/water partition coefficient (log K(OW)), 298 K supercooled liquid vapour pressures (log p(L)), aqueous solubilities (logS(w,L)) and the immunotoxicity values (log ED(50)) of PCDEs and the structural descriptors have been established by multiple linear regression method. The result shows that the quantities derived from electrostatic potential V(s,min), SigmaV(s)(+),V(s,av)(-),Pi,sigma(tot)(2),sigma(+)(2),nu, and N(v)(+), together with the number of the chlorine atoms on the two phenyl rings (N(Cl)) can be well used to express the quantitative structure-property (activity) relationships of PCDEs. Good predictive capabilities have also been demonstrated by leave-group(1/5)-out cross-validation and external test set. Based on these equations, the predicted values have been presented for those PCDE congeners whose experimentally determined physico-chemical properties are unavailable.

Exclusion of the association of five known mutations with congenital stationary nyctalopia in a large Chinese family / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To detect gene mutations associated with autosomal dominant congenital stationary night blindness(ADCSNB) in a large Chinese family.</p><p><b>METHODS</b>Genomic DNAs were extracted from peripheral blood samples of 16 affected and 14 unaffected family members. According to 5 missense mutations in 3 genes reported previously, 4 pairs of primers were designed and corresponding exons containing the five mutation sites were amplified by polymerase chain reaction. Amplified products were purified and sequenced by MegaBACE1000 capillary array electrophoresis DNA sequencer. Full field electroretinogram (ERG, ISCEV) of patients was recorded and analyzed by Roland Consult System.</p><p><b>RESULTS</b>Dark-adapted ERG showed a-wave was normal, but b-wave of the patients was markedly decreased. None of the five missense mutations were detected in 16 affected and 14 unaffected family members.</p><p><b>CONCLUSION</b>The molecular pathogenesis of ADCSNB in this family does not involve point mutations or deletions of these five sites, which indicates the heterogeneity of ADCSNB.</p>