Screening of the Antagonistic Activity of Potential Bisphenol A Alternatives toward the Androgen Receptor Using Machine Learning and Molecular Dynamics Simulation.

Over the past few decades, extensive research has indicated that exposure to bisphenol A (BPA) increases the health risks in humans. Toxicological studies have demonstrated that BPA can bind to the androgen receptor (AR), resulting in endocrine-disrupting effects. In recent investigations, many alternatives to BPA have been detected in various environmental media as major pollutants. However, related experimental evaluations of BPA alternatives have not been systematically implemented for the assessment of chemical safety and the effects of structural characteristics on the antagonistic activity of the AR. To promote the green development of BPA alternatives, high-throughput toxicological screening is fundamental for prioritizing chemical tests. Therefore, we proposed a hybrid deep learning architecture that combines molecular descriptors and molecular graphs to predict AR antagonistic activity. Compared to previous models, this hybrid architecture can extract substantial chemical information from various molecular representations to improve the model's generalization ability for BPA alternatives. Our predictions suggest that lignin-derivable bisguaiacols, as alternatives to BPA, are likely to be nonantagonist for AR compared to bisphenol analogues. Additionally, molecular dynamics (MD) simulations identified the dihydrotestosterone-bound pocket, rather than the surface, as the major binding site of bisphenol analogues. The conformational changes of key helix H12 from an agonistic to an antagonistic conformation can be evaluated qualitatively by accelerated MD simulations to explain the underlying mechanism. Overall, our computational study is helpful for toxicological screening of BPA alternatives and the design of environmentally friendly BPA alternatives.

Therapeutic effect of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves on ischemic stroke via the microbiota-gut-brain axis.

Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves (ESL) are widely used to treat ischemic stroke (IS); however, the specific mechanism remains unclear. The microbiota-gut-brain axis plays a critical role in IS and has become a potential therapeutic target. This study aimed to reveal and verify the therapeutic effect of ESL on IS through the microbiota-gut-brain axis. Ultra-high-performance liquid chromatography coupled with mass spectrometry-based untargeted/targeted metabolomics combined with 16S rRNA microbiota sequencing strategy were used to investigate the regulatory effect of ESL on the metabolism and intestinal microenvironment after IS. Lactobacillus reuteri and Clostridium butyricum were used to treat rats with IS to verify that elevated levels of probiotics are key factors in the therapeutic effect of ESL. The results showed that IS significantly altered the accumulation of 41 biomarkers, while ESL restored their concentrations back to normal. Moreover, ESL alleviated the dysbiosis of gut microbiota brought on by IS, by reducing the abundance of pathogens and increasing the abundance of probiotics (e.g., Lactobacillus reuteri and Clostridium butyricum); this could reduce post-stroke injury, thereby having a certain protective effect on IS. This study reveals that ESL plays an important role in treating IS through the microbiota-gut-brain axis, maintaining metabolic homeostasis in vivo.

Investigation of the Binding Fraction of PFAS in Human Plasma and Underlying Mechanisms Based on Machine Learning and Molecular Dynamics Simulation.

More than 7000 per- and polyfluorinated alkyl substances (PFAS) have been documented in the U.S. Environmental Protection Agency's CompTox Chemicals database. These PFAS can be used in a broad range of industrial and consumer applications but may pose potential environmental issues and health risks. However, little is known about emerging PFAS bioaccumulation to assess their chemical safety. This study focuses specifically on the large and high-quality data set of fluorochemicals from the related environmental and pharmaceutical chemicals databases, and machine learning (ML) models were developed for the classification prediction of the unbound fraction of compounds in plasma. A comprehensive evaluation of the ML models shows that the best blending model yields an accuracy of 0.901 for the test set. The predictions suggest that most PFAS (∼92%) have a high binding fraction in plasma. Introduction of alkaline amino groups is likely to reduce the binding affinities of PFAS with plasma proteins. Molecular dynamics simulations indicate a clear distinction between the high and low binding fractions of PFAS. These computational workflows can be used to predict the bioaccumulation of emerging PFAS and are also helpful for the molecular design of PFAS to prevent the release of high-bioaccumulation compounds into the environment.

A multidimensional strategy to rapidly identify the chemical constituents in Shengxian Decoction by using ultra-performance liquid chromatography coupled with ion mobility spectrometry quadrupole time-of-flight mass spectrometry.

As a well-known traditional Chinese medicine formula, the chemical constituents of Shengxian Decoction still remain unclear due to its complexity. In this study, a multidimensional strategy based on ultra-performance liquid chromatography coupled with ion mobility spectrometry quadrupole time-of-flight mass spectrometry and informatics UNIFI platform was applied to achieve rapid and comprehensive identification of the complex composition of Shengxian Decoction. Data-independent acquisition, fast data-directed analysis, and high-definition MSE were used to obtain more and cleaner mass spectrum information. As a result, a total of 120 compounds including 74 saponins, 17 flavonoids, 7 cinnamic acid derivatives, 8 triterpenoids, and 14 others were identified or tentatively characterized by high-resolution molecular mass, fragment ions, and collision cross-section values. Furthermore, high-definition MSE was used to identify six pairs of co-eluting isomers that could not be detected from conventional data-independent acquisition and fast data-directed analysis. This research strategy has a certain potential for the analysis of other compound formulae and lays the foundation for the study of traditional Chinese medicine efficacy.

A Case of CD5-Positive Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type Secondary to Chronic Lymphedema.

ABSTRACT: Primary cutaneous lymphoma occurring at the site of lymphedema is a rare complication. A total of 13 cases of primary cutaneous lymphoma associated with chronic lymphedema have been reported in international studies. We reported a case of cutaneous diffuse large B-cell lymphoma (DLBCL) (leg type) secondary to chronic lymphedema of the lower limbs. Histopathology showed hyperkeratosis of epidermis, acanthosis, and significant edema in the superficial dermis, with diffuse mononuclear infiltration in the dermis. Immunohistochemical studies revealed the expression of CD5, CD20, Pax-5, Bcl-2, Bcl-6, MUM-1, c-myc, and Ki-67. Therefore, the diagnosis of cutaneous DLBCL (leg type) was made. The study further confirmed the association between lymphoma and lymphedema. Especially, it showed CD5 expression. CD5-positive DLBCLs is a specific subgroup of DLBCLs, only approximately 10% of DLBCLs express CD5.

Monitoring AuNP Dynamics in the Blood of a Single Mouse Using Single Particle Inductively Coupled Plasma Mass Spectrometry with an Ultralow-Volume High-Efficiency Introduction System.

Gold nanoparticles (AuNPs) are increasingly being used as diagnostic and therapeutic agents owing to their excellent properties; however, there is not much data available on their dynamics in vivo on a single particle basis in a single mouse. Here, we developed a method for the direct analysis of nanoparticles in trace blood samples based on single particle inductively coupled plasma-mass spectrometry (spICP-MS). A flexible, highly configurable, and precisely controlled sample introduction system was designed by assembling an ultralow-volume autosampler (flow rate in the range of 5-5000 µL/min) and a customized cyclonic spray chamber (transfer efficiency up to 99%). Upon systematic optimization, the detection limit of the nanoparticle size (LODsize) of AuNPs in ultrapure water was 19 nm, and the detection limit of the nanoparticle number concentration (LODNP) was 8 × 104 particle/L. Using a retro-orbital blood sampling method and subsequent dilution, the system was successfully applied to track the dynamic changes in size and concentration for AuNPs in the blood of a single mouse, and the recovery for the blood sample was 111.74%. Furthermore, the concentration of AuNPs in mouse blood reached a peak in a short period of time and, then, gradually decreased. This study provides a promising technique for analyzing and monitoring the size and concentration of nanoparticles in ultralow-volume blood samples with low concentrations, making it a powerful tool for analyzing and understanding the fate of nanoparticles in vivo.

Uniportal thoracoscopic pulmonary lobectomy in the treatment of Lung Cancer.

OBJECTIVE: To investigate the clinical efficacy of uniportal thoracoscopic pulmonary lobectomy in the treatment of lung cancer. METHODS: One hundred and ten patients with lung cancer who were admitted to our hospital from February 2017 to June 2018 were enrolled and they were divided into the control group (55 patients) and observation group (55 patients) according to the random number table method. The patients in the observation group received uniportal thoracoscopic pulmonary lobectomy, and patients in the control group underwent triportal thoracoscopic pulmonary lobectomy. The surgical condition, postoperative pulmonary functions, postoperative complication incidence, and postoperative quality of life were compared between the two groups. RESULTS: The intraoperative blood loss and number of dissected lymph nodes of the observation group were (125.31±12.63) mL and (13.91±2.41) respectively, which were not significantly different with (127.54±13.60) mL and (13.96±2.69) of the control group (P>0.05). The incision length of the observation group was (4.22±0.31) cm, shorter than (6.97±0.42) cm of the control group, the postoperative pain score was (2.87±0.69) points, lower than (4.31±1.09) points of the control group, and the operation time was (195.21±19.42) minutes, longer than (162.68±18.52) min of the control group; the differences were significantly different (P<0.05). The postoperative forced vital capacity (FVC), Maximum Ventilatory Volume (MVV) and Forced Expiratory Volume in 1s (FEV1) in the observation group were (1.90±0.75) L, (54.59±16.03) L/minutes and (1.60±0.53) L respectively, larger than (1.06±0.28) L, (38.41±15.59) L/min and (1.02±0.15) L respectively (P<0.05). The scores of Short Form 36-item Health Survey (SF-36) of patients in the observation group was observed one month after surgery, significantly higher than those in the control group, and the difference was statistically significant (P<0.05). The incidence of complications of the postoperative complication of the observation group was 12.7%, which was not significantly different with 14.5% of the control group (P>0.05). CONCLUSION: Patients who receive uniportal video-assisted thoracoscopic pulmonary lobectomy have milder trauma, which is beneficial to the lung functions and postoperative recovery. Moreover, the number of dissected lymph nodes in uniportal thoracoscopic pulmonary lobectomy is equivalent with that in triportal thoracoscopic pulmonary lobectomy. Hence it is worth clinical promotion.

Screening of Potential PFOS Alternatives To Decrease Liver Bioaccumulation: Experimental and Computational Approaches.

Perfluorooctanesulfonate (PFOS) is a persistent organic pollutant with significant bioaccumulation potential in liver tissues. Exposure to PFOS could cause increase of liver weight, induce adenomas of the liver, and cause hepatomegaly. Alternatives of PFOS might be designed and synthesized that have significantly lower liver bioaccumulation. In this study, we conducted animal exposure experiments to investigate tissue accumulations of 14 per- and polyfluoroalkyl substances. Correlation analysis demonstrated that accumulation of the compounds in rat liver had strong correlations with their binding affinities of liver fatty acid binding protein (LFABP). Thus, we combined a quantitative structure-activity relationship model with molecular dynamics (MD) simulations to develop computational models to predict the LFABP binding affinities of two newly synthesized alternatives, perfluorodecalin-2-sulfonic acid and N-diperfluorobutanoic acid. The binding characteristics of the PFOS alternatives for LFABP were elaborated to explore how the different structural modifications of molecules influenced the underlying binding mechanisms. Subsequent animal experiments demonstrated that the binding free energy calculations based on the MD simulations provided a good indicator to reflect the relative degree of liver accumulation of the PFOS alternatives in the same exposure doses and durations. Our findings from the combination of experimental exposure and computational model can provide helpful information to design potential alternatives of PFOS with weak LFABP binding capability and low liver accumulation.

Correlation Analysis of Pathways and Operons of Helicobacter pylori Resistance Genes Using Bibliometrics.

BACKGROUND: Helicobacter pylori is a gram-negative bacterium infecting approximately 50% of the world's population. Antibiotic resistance in H. pylori has significantly increased due to the overuse and misuse of common antibiotics. Mutations in the 23S rRNA gene and other H. pylori genetic mutations have been identified as significant drivers in the emergence of resistance. Therefore, there is an urgent need for genetic analysis of H. pylori antibiotic resistance. METHODS: Published H. pylori resistance genes were collected from PubMed websites by bibliometrics. Pathway analysis and operon analysis were performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), the Database for Annotation, Visualization and Integrated Discovery (DAVID), and Database of prOkaryotic OpeRons (DOOR) databases to investigate pathways and biological functions of resistance genes and statistically discover novel resistance genes. RESULTS: A total of 148 genes were mined from the literature using bibliometrics, and 46 enriched pathways were identified using KEGG. Subsequently, 7 novel resistant genes of H. pylor, including HP0776, HP0192, HP0193, HP0475, HP1057, HP0632, and HP0633, were identified and predicted by functional enrichment analysis of pathways and operons. CONCLUSIONS: The discovery of these novel H. pylori resistance genes is of great significance to treat H. pylori-induced diseases and develop optimal treatment regimens. They also provide theoretical fundamentals for epidemiological prevention and strengthen our understanding of the molecular mechanism of H. pylori resistance to antibiotics.

Protonation state effects of estrogen receptor α on the recognition mechanisms by perfluorooctanoic acid and perfluorooctane sulfonate: A computational study.

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been reported to cause adverse health effects on wildlife as well as humans. Numerous studies demonstrated that PFOA and PFOS could interfere with the transcriptional activation of estrogen receptor α (ERα) by mimicking the function of endogenous ligand, whereas some reports suggested that the two compounds present non-estrogenic activities. These conflicting results bring a confusion to understand their molecular mechanism on the ERα-mediated signaling pathway. To address this issue, we performed the molecular docking and molecular dynamics simulations to elaborate the structural characteristics for the binding of PFOA and PFOS to ERα. Our results indicated that the two opposite binding orientations were modulated by the protonation states of key residue His524. In sub-acidic condition, PFOA and PFOS prefer to form the H-bonding interactions with the protonated His524, whereas Arg394 provided the H-bonding interactions for stable binding in sub-alkaline condition. Conformational analyses implied that the diverse binding modes were closely related to the conformational propensity of ERα for subsequent coactivator recruitment and transcription activation. Generally, our findings provide a flexible strategy to assess the pH impacts of microenvironment on the toxicities of perfluoroalkyl acids by their interactions with proteins.

Fluorometric determination of antioxidant capacity in human plasma by using upconversion nanoparticles and an inner filter effect mechanism.

The balance between free oxygen radicals and antioxidant defense systems is usually assessed by an antioxidant capacity assay. A rapid and sensitive antioxidant capacity assay is described here. It is making use of NaYF4:Yb/Er@NaYF4 core-shell upconversion nanoparticles (UCNPs) and potassium permanganate (KMnO4). In this strategy, added KMnO4 reduces the green (540 nm) emission of the UCNPs (under 980 nm photoexcitation) due to an inner filter effect. The antioxidants cysteine, ascorbic acid and glutathione (GSH) reduce the intense purple color of KMnO4 because it is reduced to Mn(II) ion. Hence, the green upconversion fluorescence is restored after the addition of antioxidants. Figures of merit for this assay (for the case of GSH) include a detection limit of 3.3 µM, a detection range that extends from 10 µM to 2.5 mM, and an assay time of a few seconds. The assay was applied to the evaluation of antioxidant capacity in human plasma samples spiked with GSH and gave satisfactory repeatability and specificity. Graphical abstract Schematic presentation of a fluorometric assay based on inner filter effect (IFE) between upconversion nanoparticles (UCNPs) and potassium permanganate (KMnO4) for the determination of antioxidant capacity in human plasma.

Application of a Novel Coarse-Grained Soil Organic Matter Model in the Environment.

Soil organic matter (SOM) is ubiquitous in the environment. Intensive efforts have been made to find effective ways to assess the interaction of SOM with contaminants since such interactions are one of the important criteria used to evaluate the migration, persistency and bioavailability of chemicals in the environment. This study aims to extend the application of coarse-grained (CG) dissipative particle dynamics (DPD) to the water/SOM system and predict contaminant mobility in the system. The CG model was based on the Vienna Soil-Organic-Matter Modeler, which can generate flexible condensed-phase models of SOM. A series of DPD simulations was performed to investigate the mobility of perfluorinated sulfonic acids (PFSAs) and hexachlorobutadiene (HCBD). The results indicated that the mobility of PFSAs decreased with increasing length in the carbon chain. In addition, HCBD and hexachlorobenzene (HCB) have similar diffusion coefficients, indicating analogous behavior in SOM. Moreover, water-containing SOM layers may reflect a more realistic situation. This work, coupling the CG method with DPD simulation, provides a new high-efficiency tool to assess the behavior of contaminants in the environment.

Nerve growth factor in combination with Oxiracetam in the treatment of Hypertensive Cerebral Hemorrhage.

OBJECTIVE: To compare the clinical efficacy of nerve growth factor (NGF) in combination with oxiracetam and single use of oxiracetam in the treatment of hypertensive cerebral hemorrhage. METHODS: One hundred and forty patients with hypertensive cerebral hemorrhage who were admitted to the hospital from July 2015 to September 2016 were selected as research subjects and randomly divided into a treatment group which was treated by NGF in combination with oxiracetam and a control group which was treated by oxiracetam only. The clinical efficacy was observed, and the death of both groups was recorded. RESULTS: The National Institutes of Health Stroke Scale (NIHSS) score, Glasgow Coma Scale (GCS) score and limbs muscle force of both groups improved after treatment, and the improvement of the treatment was superior to that of the control group, suggesting a significant difference (P<0.05). The reduction of serum inflammatory factor level of the treatment group was much larger than that of the control group after treatment, and the difference had statistical significance (P<0.05). The survival analysis suggested that the survival rates of the two groups had a statistically significant difference (P<0.05). CONCLUSION: NGF in combination with oxiracetam is significantly effective in treating hypertensive cerebral hemorrhage as it can apparently recover neurologic impairment and limbs muscle force. The therapy has important clinical application values.

Structure-Dependent Hematological Effects of Per- and Polyfluoroalkyl Substances on Activation of Plasma Kallikrein-Kinin System Cascade.

Per- and polyfluoroalkyl substances (PFASs) are a global concern because of their ubiquitous occurrence and high persistence in human blood, and increasing amounts of unidentified fluorinated compounds are now becoming new exposure issues. This study aims to investigate the structure-related effects of PFASs on the activation of the plasma kallikrein-kinin system (KKS). The effects of 20 PFASs and the related long-chain aliphatic compounds were screened, and their binding affinities for the initial zymogen, Hagmen factor XII (FXII) in the KKS, were evaluated by molecular docking analysis. PFASs were demonstrated to activate the KKS in a structure-dependent mode. More specifically, PFASs with longer carbon chain length, higher fluorine atom substitution degree, and terminal acid group exhibited relatively higher activities in activating the KKS. The binding affinities of PFASs with FXII determined their capabilities for inducing KKS activation. The alternative binding modes of PFASs with FXII, together with van der Waals and hydrogen bonds, specifically accommodated the distinctive chemical structures. To our knowledge, PFASs, for the first time, were found to induce the activation of the KKS in plasma, and their chemical structure-related effects would be extremely important for risk assessment on emerging PFASs in addition to the listing in Stockholm Convention.

Thiolated arsenicals in arsenic metabolism: Occurrence, formation, and biological implications.

Arsenic (As) is a notoriously toxic pollutant of health concern worldwide with potential risk of cancer induction, but meanwhile it is used as medicines for the treatment of different conditions including hematological cancers. Arsenic can undergo extensive metabolism in biological systems, and both toxicological and therapeutic effects of arsenic compounds are closely related to their metabolism. Recent studies have identified methylated thioarsenicals as a new class of arsenic metabolites in biological systems after exposure of inorganic and organic arsenicals, including arsenite, dimethylarsinic acid (DMAV), dimethylarsinous glutathione (DMAIIIGS), and arsenosugars. The increasing detection of thiolated arsenicals, including monomethylmonothioarsonic acid (MMMTAV), dimethylmonothioarsinic acid (DMMTAV) and its glutathione conjugate (DMMTAVGS), and dimethyldithioarsinic acid (DMDTAV) suggests that thioarsenicals may be important metabolites and play important roles in arsenic toxicity and therapeutic effects. Here we summarized the reported occurrence of thioarsenicals in biological systems, the possible formation pathways of thioarsenicals, and their toxicity, and discussed the biological implications of thioarsenicals on arsenic metabolism, toxicity, and therapeutic effects.

Chlorination pattern effect on thermodynamic parameters and environmental degradability for C10-SCCPs: Quantum chemical calculation based on virtual combinational library.

Short-chain chlorinated paraffins (SCCPs) are still controversial candidates for inclusion in the Stockholm Convention. The inherent mixture nature of SCCPs makes it rather difficult to explore their environmental behaviors. A virtual molecule library of 42,720 C10-SCCP congeners covering the full structure spectrum was constructed. We explored the structural effects on the thermodynamic parameters and environmental degradability of C10-SCCPs through semi-empirical quantum chemical calculations. The thermodynamic properties were acquired using the AM1 method, and frontier molecular orbital analysis was carried out to obtain the E(HOMO), E(LUMO) and E(LUMO)-E(HOMO) for degradability exploration at the same level. The influence of the chlorination degree (N(Cl)) on the relative stability and environmental degradation was elucidated. A novel structural descriptor, µ, was proposed to measure the dispersion of the chlorine atoms within a molecule. There were significant correlations between thermodynamic values and N(Cl), while the reported N(Cl)-dependent pollution profile of C10-SCCPs in environmental samples was basically consistent with the predicted order of formation stability of C10-SCCP congeners. In addition, isomers with large µ showed higher relative stability than those with small µ. This could be further verified by the relationship between µ and the reactivity of nucleophilic substitution and OH attack respectively. The C10-SCCP congeners with less Cl substitution and lower dispersion degree are susceptible to environmental degradation via nucleophilic substitution and hydroxyl radical attack, while direct photolysis of C10-SCCP congeners cannot readily occur due to the large E(LUMO)-E(HOMO) values. The chlorination effect and the conclusions were further checked with appropriate density functional theory (DFT) calculations.

Clinical effect of peripherally inserted central catheters based on modified seldinger technique under guidance of vascular ultrasound.

OBJECTIVE: To observe and analyze the application effect of ultrasound-guided modified Seldinger technique (MST) in Peripherally Inserted Central Catheter (PICC) catheterization. METHODS: Two hundred patients treated with PICC catheterization from January 2013 to December 2015 were selected and randomly divided into two groups, namely, observation group and control group. The observation group adopted ultrasound-guided MST for catheterization while the control group applied traditional puncture technique for catheterization. Then efficacy of catheterization, success rate of catheterization and incidence rates of complications were compared between two groups. RESULTS: Various indicators of catheterization effects of the observation group were better than those of the control group, and the differences were statistically significant (P<0.05); one-time success rate of puncture and catheterization of the observation group was both higher than the control group (P<0.05);. Moreover, the incidence of puncture points bleeding, phlebitis and thrombus were all lower than those of the control group (P<0.05). CONCLUSION: Implementing PICC catheterization based on ultrasound-guided modified Seldinger puncture technique can increase success rate of puncture, improve the effect of catheterization, lower incidence rate of adverse effects of catheterization and improve satisfaction and comfort level of patients.

[Percutaneous minimally invasive pedicle screw fixation for cervical fracture using intraoperative three-dimensional fluoroscopy-based navigation].

OBJECTIVE: To retrospectively assess the feasibility and safety of percutaneous minimally invasive pedicle screw fixation for cervical fracture using intraoperative three-dimensional fluoroscopy-based navigation. METHODS: Thirty patients admitted from April 2012 to May 2014 in Beijing Jishuitan Hospital with cervical fracture underwent pedicle screw fixation using intraoperative three-dimensional fluoroscopy-based navigation, with 8 patients using minimally invasive technique (CAOS-MIS group), and the other 22 patients using conventional open approach (CAOS-open group). Operative time, blood loss and postoperative neurovascular complications were recorded. Screw positions were studied by postoperative CT scan. All patients were followed up for at least 6 months. Neck visual analogue score (VAS) and American Spinal Injury Association (ASIA) classification were evaluated preoperatively and at 6-month follow-up. Independent-sample t test and Chi-Square test were used for statistical analysis. RESULTS: Operation time was (139 ± 18) minutes and blood loss was (73 ± 40) ml in CAOS-MIS group and correspondingly (154 ± 42) minutes and (296 ± 171) ml in CAOS-open group. The blood loss in CAOS-MIS group was significantly lower than that in CAOS-open group (t = 5.695, P < 0.01). No screw-related injury to nerve or vertebral artery was observed. Thirty-four screws were placed in CAOS-MIS group with 28 screws (82.4%) classified as Grade I, meanwhile in CAOS-open group 108 screws were placed with 96 screws (88.9%) classified as Grade I. There was no statistical difference between the two groups (χ² = 0.998, P > 0.01). VAS score showed no statistical difference preoperatively (t = 0.334, P > 0.01), however statistical difference existed at 6 months follow-up (t = 4.111, P < 0.01) with (0.4 ± 0.5) in CAOS-MIS group and (1.5 ± 0.7) in CAOS-open group. There were 1 patient from class B to improve to D, 1 case from D to E in CAOS-MIS group, and 1 patient from class A to improve to B, 1 case from B to D, 2 cases from C to D, 3 cases from D to E in CAOS-open group 6 months after surgery. Cervical X-ray demonstrated fractures healed well in all cases at 6 months follow-up. CONCLUSION: It is feasible and safe for percutaneous minimally invasive pedicle screw fixation for cervical fracture using intraoperative three-dimensional fluoroscopy-based navigation, which can also decreases the incidence of postoperative neck pain.

[Ethyl acetate-soluble chemical constituents from branch of Hypericum petiolulatum].

The stems and branches of Hypericum petiolulatum were extracted by alcohol and liquid-liquid extraction. Seven furofuran lignans were isolated from the ethyl acetate fraction of ethanol extract of H. petiolulatum by using silica gelchromatography, Sephadex LH-20 chromatography, medium-pressure liquid chromatography and preparative HPLC. Their structures were identified by the spectroscopic methods as pinoresinol (1), medioresinol (2), 8-acetoxypinoresinol (3), epipinoresinol (4), (+)-syringaresinol (5), (+)-1-hydroxysyringaresinol (6) and erythro-buddlenolE (7). All the isolates were firstly found in H. petiolulatum. In the bioassay, compound 7 showed remarkable antioxidative activity inhibiting Fe(+2)-cystine induced rat liver microsomal lipid peroxidation with inhibitory rate 38% at a concentration of 1 x 10(-6) mol · L(-1) (positive control Vit E with the inhibitory rate of 35% at the same concentration).

NeuTox: A weighted ensemble model for screening potential neuronal cytotoxicity of chemicals based on various types of molecular representations.

Chemical-induced neurotoxicity has been widely brought into focus in the risk assessment of chemical safety. However, the traditional in vivo animal models to evaluate neurotoxicity are time-consuming and expensive, which cannot completely represent the pathophysiology of neurotoxicity in humans. Cytotoxicity to human neuroblastoma cell line (SH-SY5Y) is commonly used as an alternative to animal testing for the assessment of neurotoxicity, yet it is still not appropriate for high throughput screening of potential neuronal cytotoxicity of chemicals. In this study, we constructed an ensemble prediction model, termed NeuTox, by combining multiple machine learning algorithms with molecular representations based on the weighted score of Particle Swarm Optimization. For the test set, NeuTox shows excellent performance with an accuracy of 0.9064, which are superior to the top-performing individual models. The subsequent experimental verifications reveal that 5,5'-isopropylidenedi-2-biphenylol and 4,4'-cyclo-hexylidenebisphenol exhibited stronger SH-SY5Y-based cytotoxicity compared to bisphenol A, suggesting that NeuTox has good generalization ability in the first-tier assessment of neuronal cytotoxicity of BPA analogs. For ease of use, NeuTox is presented as an online web server that can be freely accessed via http://www.iehneutox-predictor.cn/NeuToxPredict/Predict.