The metabolite profiling of DAPA-7012 and DAAN-4442, the lead compounds from two new kinds of non-nucleoside reverse transcriptase inhibitors (NNRTIs), was performed using an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), with the assistance of a metabolite data processing software. By utilizing the mass defect filter (MDF) technique, the data acquired from the 0 h-incubation and the 2 h-incubation were compared and analyzed with the MetaboLynx software. After incubation, 14 metabolites of DAPA-7012 and 14 metabolites of DAAN-4442 were found in rat liver microsome. The MS2 spectra for some metabolites were obtained using the MS(E) technique to get fragment ions for structural elucidation. The results indicated that both compounds could undergo extensive metabolism in rat liver microsomes. The major phase I reaction was oxidation/hydroxylation. The major phase II reaction was S-glutathione conjugation. The metabolic pathways were similar between the two lead compounds, though they have different backbone structures. Besides, the 4-NO2 of ring B in DAAN-4442 was susceptible to reduction, the benzyl of ring C in DAPA-7012 was tend to be oxidized. The common metabolic soft spots were primary amine of ring B and two methyl groups of ring C. Early SAR results showed that the primary amine and methyl were necessary substituent groups. The stability of these active groups needs to be improved and optimized. The approach of combining metabolites information and structure-activity analysis can provide a reference for further structural optimization.

This article reviewed the concept of spirituality and spiritual needs of family caregivers of cancer patients, types of spiritual needs, assessment tools, priorities, and influencing factors, aiming to provide a reference for hospice teams to identify the spiritual needs of family caregivers of cancer patients and carry out spiritual care.

Objective To investigate radiation risk perception and nuclear acceptance after the 60Co stuck source incident in June 2009 in Qixian County,Henan Province.Methods From March to April 2010,23 hamlets and 2 schools from 5 towns in Qixian County were selected,while 3 hamlets and 2 schools from 3 towns were used as control in Huixian County,1 35 km away where no any impact of the incident was found.Face-to-face questionnaire survey was conducted among three groups including mass public,elite public(representatives of public opinion,such as physicians,teachers,govemmental officials,administrative personnel,private entrepreneurs),and middie school students(the third grade students in junior middle schools and the first grade students in senior middle schools).Results A total of 1 340 valid questionnaires were collected.The public knowledge levels about radiation and nuclear power were low among all groups in two areas and public knowledge levels in Qixian County were higher than those in Huixian County.In both areas.the knowledge levels of the students were higher tIIan those among the elite public,and that among the general public were the lowest.The knowledge levels of males and those with higher educational levels were higher than those of females and those with lower educational levels.More than 40.0% of the respondents supported the idea to build nuclear power plants in China.but only a small part of them supported to build nuclear power plants in their own areas.The percentages of opponents against local nuclear power plant construction were especially higher among the students and those with higher educational levels.More than 60% of the mass public and elite public believed the explanation of the government.More than 80% of the respondents held negative attitudes towards the performance of the Qixian County Government in dealing with this incident.The student gave the lowest evaluation of the credibility and the specific performance of the local government,whereas the elite public placed themselves between the students and the mass public.The reasons why the local people left their homes to evade risk included rumors(67.2%),lack of radiation knowledge(61.9%),group psychology(59.2%),and failure of the government to inform the truth to the public in time(42.3%).Conclusions The public still fails to know enough about radiation and nuclear power.Although they trust the government,they are dissatisfied with the performance of the local government in dealing with the incident.The negative evaluation of the students is worth concerning.

Objective:To explore the intervention effect of acceptance and commitment therapy on the psychological flexibility, self-compassion, anxiety and depression of the primary caregivers of patients with primary liver cancer, so as to provide reference for the clinical care of the primary caregivers of cancer patients.Methods:This was a prospective study. A total of 80 primary caregivers of patients with primary liver cancer treated in Tianyou Hospital Affiliated to Wuhan University of Science and Technology from July to December 2021 were selected as the observation objects, and they were randomly divided into the control group and the intervention group according to the random drawing method, with 40 cases in each group. The control group was given routine nursing measures, while the intervention group was given acceptance and commitment therapy on the basis of routine nursing. The intervention effect was evaluated by the Acceptance and Action Questionnaire-2nd Edition (AAQ-Ⅱ), Self-Compassion Scale Short-Form (SCS-SF) and Hospital Anxiety and Depression Scale (HADS) before the intervention, on the day of discharge, and one month after discharge.Results:Finally, 71 primary caregivers completed the intervention and follow-up, 36 in the control group and 35 in the intervention group. Before the intervention, there was no statistically significant difference in the scores of AAQ-Ⅱ, SCS-SF, Anxiety subscale of HADS(HADS-A) and Depression subscale of HADS(HADS-D) between the two groups ( P>0.05). The AAQ-Ⅱscores of the intervention group on the day of discharge and one month after discharge were (19.63±2.59), (19.12 ± 2.20) points, which were significantly lower than those of the control group (23.14 ± 2.49), (22.56 ± 2.40) points. The differences were statistically significant ( t=5.83, 6.25, both P<0.01). The SCS-SF scores of the intervention group on the day of discharge and one month after discharge were (39.34 ± 2.68), (39.89 ± 2.81) points, which were significantly higher than those of the control group (36.69 ± 3.08), (37.72 ± 2.41) points, the differences were statistically significant ( t=-3.86, -3.49, both P<0.01). The HADS-A/HADS-D scores of the intervention group on the day of discharge and one month after discharge were (9.31 ± 1.95), (9.09 ± 1.60) points and (8.80 ± 2.15), (8.54 ± 1.75) points,which were significantly lower than those of the control group(11.42 ± 1.50), (11.03 ± 1.70) points and (10.11 ± 1.92), (10.03 ± 1.84) points, the differences were statistically significant( t values were 2.71-5.10, all P<0.01). The scores of AAQ-Ⅱ, SCS-SF, HADS-A and HADS-D of the two groups were analyzed by repeated measures analysis of variance, and there were significant differences in time effect, inter-group effect and interaction effect ( F vaules were 3.42-37.90, all P<0.05). Conclusions:Acceptance and commitment therapy can improve the self-compassion and psychological flexibility, reduce anxiety and depression of the primary caregivers of patients with primary liver cancer.

Objective To analyze the role of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) in bone toxicity in rats co-exposed to fluoride and arsenite.Methods One hundred and ninety-two 8-week-old clean-grade Wistar rats weighing (200 ± 50) g were divided into 16 groups by weight using random number table method of 12 rats in each group by 2 × 4 factorial experimental design (half female and half male),and treated with different doses of fluoride,arsenite and fluoride plus arsenite in deionized water (untreated control group containing 0.0 mg/kg fluoride and 0.0 mg/kg arsenite;low-,moderate-,and high-fluoride groups supplemented with 5.0,10.0 and 20.0 mg/kg fluoride and 2.5,5.0 and 10.0 mg/kg arsenite) for 6 months.Rats were divided into control (F0As0),low fluorine (F5.0As0),moderate fluoride (F10.0As0),high fluoride (F20.0As0),low arsenic (F0As2.5),moderate arsenic (F0As5.0),high arsenic (F0As10.0),low fluorine and low arsenic (F5.0As2.5),low fluorine and moderate arsenic (F5.0As5.0),low fluorine and high arsenic (F5.0As10.0),moderate fluorine and low arsenic (F10.0As2.5),moderate fluorine and moderate arsenic (F10.0As5.0),moderate fluorine and high arsenic (F10.0As10.0),high fluorine and low arsenic (F20.0As2.5),high fluorine and moderate arsenic (F20.0As5.0),high fluorine and high arsenic (F20.0As10.0) groups.The protein expressions of OPG and RANKL in bone were measured via the enzyme-linked immunosorbent assay method.The mRNA expressions of OPG and RANKL were measured with quantitative real-time PCR.Results Compared with F0As0 [(2.678 ± 0.136) ng/mg,(29.658 ± 0.662) pg/mg],the protein expressions of OPG [(2.857 ± 0.162),(2.983 ± 0.272),(3.117 ± 0.143) ng/mg],and RANKL [(32.533 ± 0.999),(32.698 ± 1.932),(33.331 ± 1.140) pg/mg] in F5.0As0,F10.0As0,F20.0As0 were increased with increasing of fluoride doses;increased first and then decreased was observed in levels of RANKL protein [(32.348 ± 2.838),(31.589 ±1.359),(28.843 ± 1.908) pg/mg] in F0As2.5,F0As5.0,F0As10.0 with increasing of arsenic doses (P＜0.05).Compared with F0As0 (0.83 ± 0.19,0.92 ± 0.23),the mRNA expressions of OPG (1.14 ± 0.27,1.33 ± 0.39,1.69 ± 0.77) and RANKL (1.02 ± 0.21,1.17 ± 0.15,1.25 ± 0.31) in F5.0As0,F10.0As0,F20.0As0 were increased with increasing of fluoride dose.Fluoride had a significant effect on protein and mRNA expressions of OPG and RANKL (F=11.530,21.765,6.320,3.543,P ＜ 0.05).There was interaction between fluoride and arsenite on the expressions of RANKL protein and mRNA,OPG protein (F =9.496,2.217,3.375,P ＜ 0.05).Conclusion When rat is co-exposed to fluorine and arsenic,fluorine plays a leading role in regulating RANKL and OPG,and arsenic is indirectly involved in the fluorine bone toxicity in rats,fluorine and arsenic has a antagonistic effect on OPG and RANKL expressions.

Objective To investigate the effects of chronic fluoride and arsenic co-exposure on bone morphogenetic proteins 2 (BMP-2) and runt-related transcription factor 2 (Runx2) gene expressions of bone tissue in rats. Methods One hundred and sixty 8-week-old clean-grade Wistar rats weighting (200 ± 50) g were randomly divided into 16 groups by weight via the random number table method of 10 rats in each group by 2 × 4 factorial experimental design (half female and half male), and treated with different doses of fluoride, arsenite and fluoride plus arsenite in deionized water (untreated control group with 0.0 mg/kg fluoride and 0.0 mg/kg arsenite; low-, moderate- and high-fluoride groups were supplemented with 5.0, 10.0 and 20.0 mg/kg fluoride and 2.5, 5.0 and 10.0 mg/kg arsenite) for 6 months. Rats were divided into control (F0.0As0.0), low fluorine (F5.0As0.0), moderate fluorine (F10.0As0.0), high fluorine (F20.0As0.0), low arsenic (F0.0As2.5), moderate arsenic (F0.0As5.0), high arsenic (F0.0As10.0), low fluorine and low arsenic (F5.0As2.5), low fluorine and moderate arsenic (F5.0As5.0), low fluorine and high arsenic (F5.0As10.0), moderate fluorine and low arsenic (F10.0As2.5), moderate fluorine and moderate arsenic (F10.0As5.0), moderate fluorine and high arsenic (F10.0As10.0), high fluorine and low arsenic (F20.0As2.5), high fluorine and moderate arsenic (F20.0As5.0), high fluorine and high arsenic (F20.0As10.0) groups. The concentrations of urinary fluoride (UF) and urinary arsenic (UAs) were determined as exposure biomarkers via the fluoride ion selective electrode method and the flame atomic fluorescence method. The mRNA expressions of BMP-2 and Runx2 were measured with quantitive real-time PCR. Results There were no dental fluorosis found in F0.0As0.0, F0.0As2.5, F0.0As5.0 and F0.0As10.0 groups, and there was a dose-response relationship between the occurrence of dental fluorosis and fluoride doses. Under exposure of fluorine and arsenic combined with high dose of fluorine (20.0 mg/kg), with increasing of arsenic exposure doses, the degree of injury of dental fluorosis increased (χ2 = 9.124, P < 0.05). Compared with F0.0As0.0 (0.99 ± 0.08, 0.99 ± 0.07), the mRNA expressions of BMP-2 (1.01 ± 0.07, 1.06 ± 0.06, 1.21 ± 0.05) and Runx2 (1.03 ± 0.04, 1.24 ± 0.03, 1.33 ± 0.10) in F5.0As0.0, F10.0As0.0, F20.0As0.0 groups were increased with increasing of fluoride doses. Fluoride had a significant effect on mRNA expressions of BMP-2 and Runx2 (F=3.067, 2.927, P<0.05). There was a significant interaction between fluoride and arsenic combination and BMP-2 and Runx2 mRNA expression levels (F = 3.817, 4.802, P < 0.05). Conclusion When rat is co-exposed to fluorine and arsenic, fluorine plays a leading role on BMP-2 and Runx2 mRNA expressions, and arsenic is indirectly involved in fluoride-induced bone toxicity; fluorine and arsenic has a antagonistic effect on BMP-2 and Runx2 mRNA expressions.