Objective:To explore the feasibility of chemical exchange saturation transfer (CEST) imaging at 3.0 T MRI in quantifying renal redox metabolism in vitro models and experimental animals.Methods:Redox metabolites in vitro models with physiological concentrations were prepared, including reduced metabolites (glutamate, alanine, glutathione) and oxidized metabolites (2-ketoglutarate, pyruvate, glutathione disulfide, ammonium hydroxide). CEST examinations were performed at 3.0 T MRI. The imaging parameters were as follows: CEST images with different saturation pulse intensity (B 1) (1, 2, 3, 4 μT) and a fixed radio frequency (RF) duration of 2 000 ms; CEST images with different RF durations (1 500 and 2 000 ms) were acquired with a fixed B 1 value of 2 μT to obtain the optimal scanning parameters. CEST examinations with optimized parameters were performed on the left kidneys of seven healthy rabbits, and the differences in magnetic resonance ratio asymmetry (MTR asym) between rabbit renal cortex and outer medulla were measured. A paired t-test was used to compare the differences. Results:The optimal B 1 for CEST examination of redox metabolites was 2 μT, and the optimal RF duration was 2 000 ms. The MTR asym peaks of glutathione disulfide, glutathione, glutamic acid, and alanine were at 3.75, 3.5, 3, and 1.5 ppm, respectively. The MTR asym peaks of pyruvate, 2-ketoglutarate, and ammonium hydroxide were at 1 ppm. The MTR asym peak values of reduced metabolites were higher than those of oxidized metabolites. When the B 1 value was 2 μT and the RF duration was 2 000 ms, the MTR asym signal of the renal cortex was (2.60±1.10) %, (2.86±1.32) %, (3.04±1.06) %, and (2.98±0.91) % at 1, 3, 3.5, and 3.75 ppm, respectively. The MTR asym signal of the outer medulla was (1.00±0.56) %, (2.43±0.94) %, (2.29±0.88) % and (1.98±0.58) %, respectively. The MTR asym signal of the renal cortex was higher than that of the outer medulla, and the differences were statistically significant ( t=3.04, P=0.023; t=2.56, P=0.043; t=3.50, P=0.013; t=3.45, P=0.014). Conclusion:CEST imaging at 3.0 T MRI can be used to quantitatively evaluate redox metabolism of healthy rabbit kidneys in vitro model and normal experimental rabbits.

Objective:To investigate the feasibility of 3.0 T glutamate chemical exchange saturation transfer (GluCEST) imaging in evaluating renal redox metabolism in renal ischemia-reperfusion injury (IRI).Methods:Rabbits in the IRI group ( n=56) underwent surgery by clamping the left renal artery for 45 min and then releasing to establish IRI. Rabbits in the sham group ( n=8) underwent the same operation without clamping the left renal artery. GluCEST MRI was performed before and at 1 h, 12 h, 1 day, 3 days, 7 days, and 14 days after the operations, with eight rabbits in the IRI group sacrificed immediately after each scanning and eight in the sham group sacrificed at 14 days after scanning. The left kidneys were removed for histopathological examination and reactive oxygen species (ROS) fluorescence staining. Differences in the magnetic resonance ratio asymmetry (MTR asym) of the renal cortex and outer medulla among different groups were compared. Correlations between the MTR asym and ROS were analyzed. Results:The MTR asym of the renal cortex in the sham and IRI subgroups were higher than that of the outer medulla ( t=8.16, P<0.001; t=4.78, P=0.002; t=4.94, P=0.002; t=5.76, P=0.001, t=6.68, P<0.001; t=6.40, P<0.001; t=5.16, P=0.001; t=3.30, P=0.013). The MTR asym of the renal cortex and outer medulla in the IRI-1h, IRI-12h, IRI-1d, IRI-3d, IRI-7d, and IRI-14d groups were lower than in the sham and IRI-pre groups (all P<0.05). The MTR asym of the renal cortex and outer medulla in the IRI-1h group were lower than in the IRI-12h, IRI-1d, IRI-3d, IRI-7d, and IRI-14d groups (all P<0.05). The MTR asym of the renal cortex in the IRI-12h group was lower than in the IRI-7d and IRI-14d groups (1.84%±0.09% vs.2.42%±0.19%, 2.41%±0.31%, all P<0.05). The MTR asym of the renal cortex in the IRI-1d group was lower than in the IRI-7d group (1.99%±0.17% vs. 2.42%±0.19%, P=0.008). The MTR asym of the outer medulla in the IRI-12h group was lower than in the IRI-3d, IRI-7d, and IRI-14d groups (1.32%±0.27% vs. 1.79%±0.31%, 1.98%±0.18%, 1.66%±0.40%, respectively, all P<0.05]. The MTR asym of the outer medulla in the IRI-7d group was higher than in the IRI-1d and IRI-14d groups (1.98%±0.18% vs. 1.52%±0.31%, 1.66%±0.40%, all P<0.05). The MTR asym of the renal cortex and outer medulla had a strong negative correlation with the mean fluorescence intensity of ROS ( ρ=-0.889, P<0.001; ρ=-0.784, P<0.001). Conclusion:3.0 T GluCEST imaging can indirectly reflect the changes of renal redox metabolism in renal IRI.

Unlike chemosynthetic drugs designed for specific molecular and disease targets,active small-molecule natural products typically have a wide range of bioactivities and multiple targets,necessitating extensive screening and development.To address this issue,we propose a strategy for the direct in situ micro-dynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of action.As a proof-of-concept,we investigated the behavior of mussel oligosaccharide(MOS-1)by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured cells.We recorded the entire dynamic process of the localization of fluorescein isothiocyanate(FITC)-MOS-1 to the lysosomes and visualized the distribution of the drug within the cell.Remarkably,lysosomes containing FITC-MOS-1 actively recruited lipid droplets,leading to fusion events and increased cellular lipid consumption.These drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related diseases.Furthermore,in a high-fat HepG2 cell model and in high-fat diet-fed apolipoprotein E(ApoE)-/-mice,MOS-1 significantly promoted triglyceride degradation,reduced lipid droplet accumulation,lowered serum triglyceride levels,and mitigated liver damage and steatosis.Overall,our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase,as this methodology contributes to the rapid identification of drug indications.Collectively,this methodology is significant for the screening and development of selective small-molecule drugs,and is expected to expedite the identification of candidate molecules with me-dicinal effects.

Complex brain diseases seriously endanger human health, and early diagnostic biomarkers and effective treatments are currently lacking. Due to ethical constraints on human research, establishing monkey models is crucial to address these issues. With the rapid development of technology, transgenic monkey models of a range of brain diseases, especially autism spectrum disorder (ASD), have been successfully established. However, to establish practical and effective brain disease models and subsequently apply them to disease mechanism and treatment studies, there is still a lack of a standard tool, i.e., a system for collecting and analyzing the daily behaviors of brain disease model monkeys. Therefore, with the goal of undertaking a comprehensive and quantitative study of behavioral phenotypes, we established a standard daily behavior collection and analysis system, including behavioral data collection protocols and a monkey daily behavior ethogram (MDBE) for rhesus and cynomolgus monkeys, which are the most commonly used non-human primates in model construction. Then, we used ASD as an application example after referring to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), which is widely used in clinical disease diagnosis to obtain ASD core clinical symptoms. We then established a sub-ethogram (ASD monkey core behavior ethogram (MCBE-ASD)) specifically for quantitative assessment of the core clinical symptoms of an ASD monkey model based on MDBE. Subsequently, we demonstrated the high reproducibility of the system.
Animals ; Autism Spectrum Disorder ; Macaca mulatta ; Disease Models, Animal ; Behavior, Animal ; Macaca fascicularis ; Male ; Humans

Objective: To investigate the changes in mass spectrometry of proteins in patients with 1-bromopropane (1-BP) poisoning after treatment and their biological functions. Methods: From May 2016 to December 2017, 3 male patients aged 31-47 years with 1-BP poisoning in Bao'an District of Shenzhen, China were enrolled in this study. The whole blood sample (2 ml) was collected before and after treatment. Label-free mass spectrometry-based proteomics was used for protein identification and quantification. The differentially expressed proteins after treatment were analyzed. Bioinformatics tools were used to analyze the functions of the identified proteins and the biological processes they were involved in. Results: Proteomic analysis showed that there were 47 proteins that were differentially expressed more than 2-fold (P<0.05) after treatment in the patients with 1-BP poisoning; of them, 27 were up-regulated and 20 were down-regulated in the serum of treated patients. The identified proteins were mainly involved in proteolysis, protein modification, immune response, complement activation, lipoprotein metabolism, signal transduction, and coagulation. Conclusion The differentially expressed proteins after treatment can help with the diagnosis, treatment, and prognosis monitoring of 1-BP poisoning and provide potential therapeutic and prognostic markers for 1-BP poisoning treatment.

Objective: To investigate the current status and influencing factors of occupational stress among couriers. Methods: Couriers (n=925) were selected on this study used cluster sampling method from January to March 2018. They were from SF and Zhongtong Express Co., Ltd., on the Wechat platform, and surveyed by a job stress questionnaire based on a job demand-control model.Valid questionnaires(n=617) were obtained. Results: A total of 418 workers were occupational stress positive (67.7%). The results of Chi-square analysis showed that there were significant differences in occupational stress among workers categorized by job position, working years, mealtime, sleeping time, and weekly work time (P<0.05). The multivariate logistic analysis indicated that non-regular meals, short-term sleep and less than 0.5 working years were risk factors for occupational stress(P<0.05). Conclusion Couriers generally have occupational stress. The main influencing factors are job position, working years mealtime, sleeping time, and weekly work time. It is necessary to guide healthy lifestyle, rationally organize labor and assign tasks, and improve working environment to relieve their occupational stress.

Objective: This study focused on the proteomicchanges between workers exposed to methylbenzene (WMB) and healthy individuals (HI) . Methods: The serum of WMB and HI was collected and the unmarked label free mass spectrometry was utilized for protein identification and quantitative comparison. The differentlyexpressed proteins in WMB and the HI were screened, followed by the analysis of protein and biological functions by bioinformatics tools. Results: Thirty nine proteins were differently expressed between WMB and HI. Compared with HI, 24 proteins were up regulated and 15 proteins were down regulated over 2 fold change in WMB. Theseproteins were mainly involved in signal transduction, serine endopeptidase activity, inflammatory response, protein modification, stress reaction, coagulation reaction and so on. Conclusion The differently expressed proteins provide a potential protein marker for the health assessment of WMB and early diagnosis of methylbenzene poisioning and expand our understanding of the molecular mechanism of methylbenzene intoxication.

A male preterm infant,who was born at 28 weeks+2 of gestational age and diagnosed as preterm hyaline membrane disease (PHMD)2 hours after birth,was given nasal continuous positive airway pressure (nCAPA)therapy,intratracheal instillation of poractant alfa injection,intravenous infusion of ceftazidime and penicillin for infection,and caffeine for stimulating respiration. On day 4 of treatment,the infant′s heart rate reached 160-170 beats/min. It was suspected that caffeine induced tachycardia,and the heart rate restored when caffeine was withdrawn. On day 16,the infant′s condition was improved significantly,nCAPA was changed to noninvasive positive pressure ventilation and caffeine was given again to stimulate respiration. On day 24,cimetidine was given due to bile reflux. On day 28,intravenous infusion of erythromycin was given because of positive Ureaplasma urealyticum DNA in sputum. On day 29,cimetidine was stopped. Since day 25 after treatment,the systolic pressure was higher than 83 mmHg for 9 continuous days and elevated to 106/75 mmHg on day 34. The severe hypertension was considered to be caused by caffeine. When caffeine was stopped,the blood pressure returned to normal. On day 46,the infant′s symptoms were improved significantly,high flow oxygen was given,erythromycin was stopped,and caffeine was added for the third time. Hypertension did not recur. The relationship between the hypertension and drugs was evaluated by Karch-Lasagna method,indicating that the hypertension was probably related to combined use of caffeine and cimetidine or erythromycin.

A male preterm infant,who was born at 28 weeks+2 of gestational age and diagnosed as preterm hyaline membrane disease (PHMD)2 hours after birth,was given nasal continuous positive airway pressure (nCAPA)therapy,intratracheal instillation of poractant alfa injection,intravenous infusion of ceftazidime and penicillin for infection,and caffeine for stimulating respiration. On day 4 of treatment,the infant′s heart rate reached 160-170 beats/min. It was suspected that caffeine induced tachycardia,and the heart rate restored when caffeine was withdrawn. On day 16,the infant′s condition was improved significantly,nCAPA was changed to noninvasive positive pressure ventilation and caffeine was given again to stimulate respiration. On day 24,cimetidine was given due to bile reflux. On day 28,intravenous infusion of erythromycin was given because of positive Ureaplasma urealyticum DNA in sputum. On day 29,cimetidine was stopped. Since day 25 after treatment,the systolic pressure was higher than 83 mmHg for 9 continuous days and elevated to 106/75 mmHg on day 34. The severe hypertension was considered to be caused by caffeine. When caffeine was stopped,the blood pressure returned to normal. On day 46,the infant′s symptoms were improved significantly,high flow oxygen was given,erythromycin was stopped,and caffeine was added for the third time. Hypertension did not recur. The relationship between the hypertension and drugs was evaluated by Karch-Lasagna method,indicating that the hypertension was probably related to combined use of caffeine and cimetidine or erythromycin.

OBJECTIVETo analyze the literature on power frequency electric field testing data and to propose views and suggestions for current testing.

METHODSThe literature on power frequency electric field testing data published in the previous years was searched to identify 306 articles involving 193 valid testing data. Mann-Whitney test and Wilcoxon W test were used for analyzing the testing data.

RESULTSThe classification of data was carried out according to one quarter of occupational exposure limit (1.25 kV/m), one half of the exposure limit (2.5 kV/m), and the exposure limit (5 kV/m). The structure of testing data showed a significant difference between the non-power facility group and the power facility group (P<0.05).

CONCLUSIONAs occupational hazard factors, the radiation exposure from power frequency electric field is extensive. However, the power frequency electric field testing data in actual workplaces except high-voltage power facilities are far less than the occupational exposure limit with little harmfulness. There is a phenomenon of excessive testing at present.