The toxicity assessment of neorudin in cynomolgus monkeys.

In this study, the toxicity effects on circulatory system and respiratory system, and the acute toxicity test of recombinant neorudin (EPR-hirudin, EH) in cynomolgus monkeys were evaluated to provide reference information for clinical studies. Eighteen cynomolgus monkeys were randomly divided into three groups for single intravenous administration of 3, 30 mg/kg EH and normal saline, respectively. The changes of respiratory frequency, respiratory intensity, blood pressure and electrocardiogram before and after administration were recorded. In acute toxicity test, six cynomolgus monkeys were intravenously received EH at a single dose of 171, 257, 385, 578, 867 and 1300 mg/kg respectively. The vital signs, hematology, serum biochemistry, coagulation indexes and electrocardiogram indexes of the animals were determined before administration and on the 7th and 14th day after administration. As the results showed that there were no significant abnormal changes in respiratory frequency, respiratory intensity, blood pressure or electrocardiogram in cynomolgus monkeys after receiving EH at 3 mg/kg and 30 mg/kg, and there was no statistical difference between the treated groups and normal saline group. In the acute toxicity test, no significant abnormalities were observed in vital signs, hematology, serum biochemistry, coagulation indexes and electrocardiogram indexes of six cynomolgus monkeys at day 7 and 14 after EH administration. Furthermore, autopsies of all cynomolgus monkeys showed no abnormalities. The results of toxicokinetics showed that AUClast of the drug increased in proportion to the EH dose in the range of 171-578 mg/kg, and increased in over proportion to the EH dose in the range of 578-1300 mg/kg. The variation of Cmax was basically consistent with AUClast. In a sum, A single intravenous injection of 3 and 30 mg/kg of EH did not affect the circulatory system and respiratory system in cynomolgus monkeys and the maximum tolerated dose of EH in cynomolgus monkey is over 1300 mg/kg (equivalent to 619-1300 times of the proposed clinical equivalent dose).

Event-Related Potential Assessment of Visual Perception Abnormality in Patients With Obstructive Sleep Apnea: A Preliminary Study.

This study investigated the effect of obstructive sleep apnea (OSA) on the neural mechanism of visual perception. A preliminary case-control study was conducted. Seventeen patients with moderate to severe OSA in the sleep center of Civil Aviation General Hospital and 20 healthy controls matched for age, sex, and education were recruited. The participants accepted the perceptual contour integration task, compared the differences in behavioral indicators between the two groups, and compared the differences in electroencephalography (EEG) data between the two groups through event-related potential (ERP) technology. The groups did not differ significantly in age and gender, but they differed significantly in body mass index (BMI) (OSA higher than healthy controls, p < 0.05). The groups were not statistically different in terms of sleep structure and total sleep time. AHI, sleep efficiency, and minimal SaO2 value in the OSA group were significantly different from those of the control group. The results showed that the average reaction time of the OSA group was significantly longer than that of the healthy control group in the contour integration task. There was no significant difference in the accuracy rate. The results of EEG showed that the amplitudes of N100 of the OSA group were significantly higher than those of the control group at O1, Oz, and O2 electrodes. There was no significant difference in latency between the two groups. At the FCz electrode, the amplitudes of N200 of the OSA group were significantly higher than those of the control group. Therefore, we concluded that in the early stage of the perceptual integration task, although the neural response activity of patients with moderate and severe OSA was not accelerated, they need to call on more psychological resources, activate more neurons in the contour global recognition processing stage, and the compensatory effect of frontal lobe appeared in the stage of visual perception.

Method validation, residue analysis and dietary risk assessment of trifloxystrobin and trifloxystrobin acid in milk, eggs and pork.

Trifloxystrobin (TFS) is a widely used strobilurin fungicide and its residues accumulating in animal-derived food could result in potential harm to consumers. By optimization of extraction solvents and cleanup sorbents, a residue analysis method for TFS and its metabolite trifloxystrobin acid (TFSA) was established in milk, eggs and pork based on QuEChERS sample preparation and LC-MS/MS. The calibration curves exhibited good linearity with determination coefficients (R2 ) >0.9930 over the range of 0.5-250 ng/ml for both TFS and TFSA. The recoveries of the two analytes were 81-100% with RSD 3-10% and 76-96% with RSD 2-13%, respectively. The limit of quantification (LOQ) was 1 ng/g for both analytes. The milk, egg and pork samples, 30 each, were collected from the 30 main producing regions in China, and residues of TFS and TFSA were analyzed. The concentrations of both analytes were lower than the corresponding LOQs and maximum residue limits. Long-term dietary risk assessment showed that the hazard quotients were 0.001-0.003%, indicating an absence of unacceptable risks in milk, eggs and pork to the health of common consumers in China.

A comprehensive assessment of fungi in urban sewer biofilms: Community structure, environmental factors, and symbiosis patterns.

Sewers are important parts of wastewater treatment facilities and the fungal microbial communities therein make large contributions to the biotransformation of wastewater. Therefore, this experiment constructed an experimental sewer system and characterized the fungal microbial communities using ITS high-throughput sequencing technology in combination with network structure analysis and statistical correlation analysis methods. The results demonstrated that the overall diversity of the fungal communities gradually increased as growth phases progressed, but the dominant groups differed significantly among phases. In the early growth phase (RS1) the dominant genera were Apiotrichum and Inocybe, with abundances of 34% and 14%, respectively, while the middle and late growth phases (RS2 and RS3) were dominated by Candida, with a relative abundance of 47%-66%. CCA and correlation analysis showed that the fungal communities diversity from the artificial sewers had significant positive correlations with COD (r2 = 0.44, p < 0.05) and NH4+ (r2 = 0.64, p < 0.05) and that environmental factors significantly influenced the abundances of Fusarium and Aspergillus. Network analysis revealed differences in the fungal groups representing key nodes during different periods. Candida, Trichosporon, Fusarium, and Aspergillus played important roles in the microbial ecosystem of the simulated sewer systems. This study provides data-supported insight into the bacterial-fungal interaction mechanisms and associated pollutant biodegradation technologies in sewers.

[Analysis of RCT outcome indicators of traditional Chinese medicine for essential hypertension in recent two years].

To find the status of outcome indicators reported in published randomized controlled trial(RCT) of traditional Chinese medicine(TCM) for essential hypertension in the past two years, we searched for relevant information from four Chinese databases, three English databases and two clinical trial registries in this study, from January 2018 to September 2019. The outcome indicators of RCT were extracted and categorized from trials and the risk of bias was assessed by ROB tools from the Cochrane Collaboration. A total of 125 RCTs and 15 RCT protocols were finally included after study screening. The results showed that the RCT outcomes mainly included efficacy and safety outcomes. Efficacy indicators mainly included blood pressure measurement, quality of life assessment, blood biochemical indicators, urine analysis, arterial ultrasound, vascular endothelial function indicators, hematocrit, hemorheology indicators and other indicators. The safety indicators mainly included general physical examination items, heart, liver and kidney function tests, blood, urine, and stool routine examinations as well as adverse drug reactions/events. The current RCTs cannot distinguish primary and secondary outcomes, and the RCT protocols didn't report efficacy criteria clearly. They both didn't report health economic indicators and the methodological qualities were relatively low. In view of the current status on outcome indicators reported in TCM RCTs, constructing a core outcome set of TCM for essential hypertension and improving the methodology quality of RCTs will help to accurately reflect the actual efficacy of TCM intervention.

The Disparity of Impairment of Neurogenesis and Cognition After Acute or Fractionated Radiation Exposure in Adolescent BALB/c Mice.

The effect of acute X-ray irradiation with 2 Gy or fractionated exposure with 0.2 Gy continuously for 10 days (0.2 Gy × 10 = 2 Gy) was evaluated in the postnatal day 21 (P21) BALB/c mouse model. Both acute and fractionated irradiation induced impairment of cell proliferation and neurogenesis in the subgranular zone of the dentate gyrus labeled by Ki67 and doublecortin, respectively. Parvalbumin immunopositive interneurons in the subgranular zone were also reduced significantly. However, the 2 patterns of irradiation did not affect animal weight gain when measured at ages of P90 and P180 or 69 and 159 days after irradiation. Behavioral tests indicated that neither acute nor fractionated irradiation with a total dose of 2 Gy induced deficits in the contextual fear or spatial memory and memory for novel object recognition. Animal motor activity was also not affected in the open-field test. The disparity of the impairment of neurogenesis and unaffected cognition suggests that the severity of impairment of neurogenesis induced by acute or fractionated irradiation with a total dose of 2 Gy at P21 may not be worse enough to induce the deficit of cognition.

Environmental risk assessment in livestock manure derived biochars.

Livestock-manure-derived biochar is one of major products obtained from the pyrolysis of livestock manure. This study quantitatively assesses the pollution level and ecological risks associated with heavy metals in livestock manure and the biochar produced by its pyrolysis. The geo-accumulation index (GAI) values of heavy metals in livestock manure were significantly decreased (P < 0.05) and indicated to be at the grade of uncontaminated expected for Zn in pig-manure-derived biochar (PMB, 0.94, 800 °C) via pyrolysis. Therefore, Zn should be paid more attention in PMB. The risk factors (E r i ) result shows that heavy metals in biochars were significantly decreased (P < 0.05) with increasing pyrolysis temperature. Potential ecological risk index values revealed that the integrated risks from the heavy metals were significantly decreased (P < 0.05) after pyrolysis. Similarly, the risk assessment code values indicated that the risks from the heavy metals in livestock-manure-derived biochars were significantly decreased (P < 0.05) after pyrolysis. In summary, pyrolysis represents an effective treatment method for livestock manure and can provide an effective method to reduce the risks of environmental pollution.

Rapid quantitation of multiple ions released from HeLa cells during emodin induced apoptosis by low-cost capillary electrophoresis with capacitively coupled contactless conductivity detection.

Change in cation concentration, including that of potassium and sodium, is characteristic of apoptosis, therefore it is significant to detect cation concentration changes. In this work a rapid, sensitive, and practical method was developed for the determination of Na+ and K+ concentration in HeLa cells during emodin induced apoptosis by a low-cost capillary electrophoresis device with capacitively coupled contactless conductivity detection (CE-C4D). Under the optimized conditions, both ions were baseline separated in 4 min with 40 mM MES/40 mM His containing 1 mM 18-crown-6 as the separation buffer at pH 6.0. The limit of detections (LODs) and limit of quantifications (LOQs) were 0.47-1.15 µM and 1.58-3.86 µM, respectively. The precision for migration times and peak areas was below 0.56% and 3.74%, respectively. The data proved that the concentration of cations in cells can be accurately quantified. It was found that the K+ concentration decreased from 82.2 µM to 52.7 µM, and the Na+ concentration increased from 62.4 µM to 127.2 µM during the process of apoptosis when the cell density was 1 × 105 cells per mL. The low-cost CE-C4D provides a convenient way to decipher the interaction of Na+ and K+ in the regulation of cell apoptosis.

[Methodological quality assessment of community-acquired pneumonia clinical practice guidelines in China based on AGREE â ¡ tool].

This study is aimed to identify and assess the methodological quality of community-acquired pneumonia (CAP) clinical practice guidelines (CPG) in China by using AGREE Ⅱ tool. CNKI, SinoMed, Wanfang, and VIP Chinese databases from database establishment to March 2017 were searched by manual retrieval to collect all the clinical practice guidelines prepared by various associations or organizations, then AGREE Ⅱtool was used to assess them. Data in each CPG were analyzed in terms of six domains, including scope and purpose, participants, rigor, clarity and readability, applicability and editorial independence. A total of 4 CPGs were included. The results showed that the scope and purpose scored 45.8%; the clarity of expression scored 44.75%; the participants scored 31.9%; the rigor scored 18.98%; the applicability scored 7%; and finally the editorial independence scored 1%. It is concluded that the quality of applicability and the editorial independence should attained paid more attention in future development or updating of the guidelines. In addition to strengthening the compliance with international general principles, we should also pay attention to the characteristics of traditional Chinese medicine treatment, especially the related evidences as complementary and alternative treatment for western intervention measures.

Physicochemical properties and intestinal protective effect of ultra-micro ground insoluble dietary fibre from carrot pomace.

Carrot pomace is an abundant, but underutilized, byproduct from the juice industry. In this study, the insoluble dietary fiber from carrot pomace was treated using an ultra-microgrinding process, and the resulting changes in its physicochemical properties and intestinal protective effect against heavy metal damage were examined. The SEM and fluorescence microscopy results showed that the grinding process could significantly decrease the particle size of carrot insoluble dietary fibre and increase its Brunauer-Emmett-Teller surface area from 0.374 to 1.835 m(2) g(-1). Correspondingly, the water-holding capacity, swelling capacity, and oil-holding capacity increased by 62.09%, 49.25% and 45.45%, respectively. The glucose-, nitrite-, and lead ion-adsorbing abilities also improved significantly compared with the raw samples. In addition, apoptosis assessment by AO/EB revealed that the ground fibre could effectively protect Caco-2 cells from lead ion damage. The MTT assay showed that carrot insoluble dietary fibre has no toxicity for Caco-2 cells at a concentration of 10.0 mg L(-1). The findings of this study highlighted the potential of the ultra-microgrinding process to produce a high added-value fibre ingredient from carrot residues.