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Objective To analyze the trends in Oncomelania hupensis distribution in Wuhan City, Hubei Province from 2003 to 2022, so as to provide insights into precision schistosomiasis control. Methods Data pertaining to O. hupensis snail survey in Wuhan City from 2003 to 2022 were collected. The trends in the proportion of areas with snail habitats, actual area with snail habitats, mean density of living snails and prevalence of Schistosoma japonicum infection in snails were evaluated in schistosomiasis-endemic areas of Wuhan City from 2003 to 2022 with the slope of trend curve (β), annual percent change (APC) and average annual percent change (AAPC) using a Joinpoint regression model. Results During the period from 2003 through 2022, there were two turning points for the proportion of areas with snail habitats in Wuhan City in 2005 and 2015, with a rise during the period from 2003 to 2005 (β1 = 5.93, t = 1.280, P > 0.05), a decline from 2005 to 2015 (β2 = −0.88, t = −2.074, P > 0.05) and a rise from 2015 to 2022 (β3 = 1.46, t = −2.356, P < 0.05). During the period from 2003 through 2022, there were two turning points for the proportion of areas with snail habitats in islet endemic areas of Wuhan City in 2006 and 2015, with no significant differences in the trends from 2003 to 2006 (β1 = 4.64, t = 1.888, P > 0.05) or from 2006 to 2015 (β2 = −1.45, t = −2.143, P > 0.05), and with a tendency towards a rise from 2015 to 2022 (β3 = 2.04, t = −3.100, P < 0.05). During the period from 2003 through 2022, there were two turning points for the proportion of areas with snail habitats in inner embankment endemic areas of Wuhan City in 2012 and 2020, with a tendency towards a decline from 2003 to 2012 (β1 = −0.39, t = −4.608, P < 0.05) and with no significant differences in the trends from 2012 to 2020 (β2 = 0.03, t = 0.245, P > 0.05) and from 2020 to 2022 (β3 = 1.38, t = 1.479, P > 0.05). During the period from 2003 to 2022, the actual area with snail habitats all appeared a tendency towards a decline in Wuhan City, and in islet and inner embankment endemic areas of Wuhan City from 2003 to 2022 (AAPC = −2.39%, −5.75% and −2.35%, all P values < 0.05). The mean density of living snails reduced from 0.087 snails/0.1 m2 in 2003 to 0.027 snails/0.1 m2 in 2022 in Wuhan City, with a significant difference in the tendency towards the decline (APC = AAPC = −11.47%, P < 0.05). The annual mean decline rate of the mean density of living snails was 17.36% in outside embankment endemic areas of Wuhan City from 2003 to 2022 (APC = AAPC = −17.36%, P < 0.05), and there was no significant difference in the trends in the mean density of living snails in islet endemic areas of Wuhan City from 2003 to 2022 (APC = AAPC = −0.97%, P > 0.05). In addition, the prevalence of S. japonicum infection in snails appeared a tendency towards a decline in Wuhan City from 2003 to 2022 (APC = AAPC = −12.45%, P < 0.05). Conclusions The proportion of areas with snail habitats, actual area with snail habitats, mean density of living snails and prevalence of S. japonicum infection in snails all appeared a tendency towards a decline in Wuhan City from 2003 to 2022. Intensified snail control, modification of snail habitats, shrinking of areas with snails and implementation of grazing prohibition in snail-infested settings are required, in order to facilitate the progress towards schistosomiasis elimination in Wuhan City.
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The development of medical research is completed by the cooperation of sponsors, investigators, subjects, and ethics committees. Clinically, it mainly includes clinical trials of medical devices, clinical medicine and new technology research. This paper analyzed the game and the relationship between rights, responsibilities and interests of relevant parties in medical research, combined with the relevant costs and sharing principles involved in medical research, and found that the use of the word "free" in the informed consent is easy to cause misunderstanding and the lack of relevant compensation costs in the informed consent, while the compensation and insurance costs had some problems, such as the imperfect subject compensation mechanism and the insufficient insurance purchase by the sponsor, which can not protect the basic rights and interests of the subjects. Therefore, in order to standardize the cost management of clinical medical research, it is necessary to standardize the process and content of informed consent, strengthen the supervision of medical research process, establish medical research damage compensation fund and research damage insurance system, so as to better protect the rights and interests of subjects.
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With the continuous progress of medical technology, some violations of ethical principles often occur in science experimental research targeting humans. Taking the type of human experimental research as the starting point, through ethical analysis and evaluation of different types of human experimental research, this paper concluded that in human experimental research, it was necessary to adhere to humanitarian principles of human experimental research, fully respect the research participants’ right to informed consent, select research participants fairly, fully protect the research participants’ rights and interests, and supervise the whole research process. So as to better regulate the behavior of medical researchers in human experimental research and protect the rights and interests of research participants.
ABSTRACT
The development of medical research is completed by the cooperation of sponsors, investigators, subjects, and ethics committees. Clinically, it mainly includes clinical trials of medical devices, clinical medicine and new technology research. This paper analyzed the game and the relationship between rights, responsibilities and interests of relevant parties in medical research, combined with the relevant costs and sharing principles involved in medical research, and found that the use of the word "free" in the informed consent is easy to cause misunderstanding and the lack of relevant compensation costs in the informed consent, while the compensation and insurance costs had some problems, such as the imperfect subject compensation mechanism and the insufficient insurance purchase by the sponsor, which can not protect the basic rights and interests of the subjects. Therefore, in order to standardize the cost management of clinical medical research, it is necessary to standardize the process and content of informed consent, strengthen the supervision of medical research process, establish medical research damage compensation fund and research damage insurance system, so as to better protect the rights and interests of subjects.
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Background Arsenic can be toxic to human by triggering oxidative stress, which is companied by epigenetic modifications. Objective To investigate the modification of N6-methyladenosine (m6A) in human embryonic lung fibroblasts (HELF) during oxidative stress induced by sodium arsenite (NaAsO2). Methods HELF cells were treated by designed concentrations of NaAsO2 (0, 2.5, 5, 10, and 20 μmol·L−1) for 48 h. Cell viability was detected by 3-(4,5-dimethylthia zol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium (MTS) method; the activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) as well as the content of malondialdehyde (MDA) were detected with corresponding kits; the level of m6A methylation in total RNA was detected by enzyme-linked immunosorbent assay; the mRNA expressions of m6A modified enzymes were detected by real-time fluorescence quantitative PCR, including methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), Wilms' tumor 1-associated protein (WTAP), fat mass and obesity-associated protein (FTO), alkB family of Fe(II)/α-ketoglutarate-dependent dioxygenases 5 (ALKBH5), YTH domain containing protein 2 (YTHDC2), YTH domain family protein 2 (YTHDF2), and YTH domain family protein 3 (YTHDF3); the protein expressions of METTL3, FTO, YTHDC2, YTHDF3, and nuclear factor erythroid 2-related factor 2 (NRF2) were detected by Western blotting. The enrichment of m6A in NRF2 mRNA was detected by RNA methylated immunoprecipitation combined with real-time fluorescence quantitative PCR (MeRIP-qPCR). Results After the 0, 2.5, 5, 10, and 20 μmol·L−1 NaAsO2 treatment, the MTS results showed that compared with the control group, the cell viability of the 20 μmol·L−1 group decreased to 84% (P<0.05). The colorimetry results showed that compared with the control group, the activities of T-SOD in the 10 and 20 μmol·L−1 groups decreased (P<0.05); the activities of GSH-Px in the 2.5 and 10 μmol·L−1 groups decreased (P<0.05); the contents of MDA in the 10 and 20 μmol·L−1 groups increased. The results of enzyme-linked immunosorbent assay showed that the overall m6A methylation levels in the 0, 2.5, 5, 10, and 20 μmol·L−1 groups were (0.193 ± 0.023)%, (0.247 ± 0.021)%, (0.253 ± 0.006)%, (0.233 ± 0.006)%, and (0.262 ± 0.010)%, respectively, and compared with the control group, the m6A methylation levels in all the NaAsO2 treated groups increased (P<0.05). The real-time fluorescence quantitative PCR results showed that compared with the control group, the mRNA relative expression level of METTL3 decreased in the 2.5, 10, and 20 μmol·L−1 groups (P<0.05); the mRNA relative expression level of FTO decreased in the 20 μmol·L−1 group; the mRNA relative expression level of YTHDC2 increased in the 10 and 20 μmol·L−1 groups (P<0.05); the mRNA relative expression level of YTHDF3 increased in the 2.5, 10, and 20 μmol·L−1 groups (P<0.05). The Western blotting results showed that compared with the control group, the relative protein expression of METTL3 decreased in the 10 and 20 μmol·L−1 groups; the relative protein expression of FTO decreased in the 5 and 20 μmol·L−1 groups; the relative protein expression of YTHDC2 decreased in the 20 μmol·L−1 group (P<0.05); the relative nuclear protein expression of NRF2 decreased in the 10 and 20 μmol·L−1 groups (P<0.05). The MeRIP-qPCR results showed that m6A enrichment was significantly increased in the 20 μmol·L−1 NaAsO2 exposure group compared with the control group (P<0.05). After over-expression of FTO, the mRNA and protein relative expression levels of FTO and the relative expression level of nuclear protein of NRF2 in the FTO group were higher than those in the control group (P<0.05); the mRNA and protein relative expression levels of FTO in the NaAsO2 + FTO group and the nuclear protein expression level of NRF2 were higher than those in the NaAsO2 group (P<0.05). Conclusion In the process of oxidative stress induced by NaAsO2, m6A methylation level, m6A modified enzymes, m6A modification of NRF2 mRNA, and NRF2 expression could change in HELF cells.
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We synthesized the superparamagnetic paclitaxel nanoparticles from modified chitosan tangling around Fe3O4 ferrofluid and taxol, and observed the nanoparticles with transmission electronic microscopy (TEM). Then we evaluated the paramagnetism of the particles by vibration specimen magnetometer (VSM) and tested their cytotoxicity with flow cytometry (FCM). The prepared nanoparticle solution was black without any floccule or sediment and appeared transparent after diluted. The nanoparticles were spherical and dispersed in water with mean diameter of 15 nm under TEM and showed superparamagnetic character. FCM test showed the nanoparticles had significant toxic effects against malignant astrocytoma U251 cell lines, equal to taxol alone. These results showed that the superparamagnetic nanoparticle not only enhanced the solubility of paclitaxel in water, but also was superparamagnetic and cytotoxic, which make suitable tools for magnetic targeting chemotherapy of brain gliomas.
Subject(s)
Humans , Antineoplastic Agents, Phytogenic , Pharmacology , Apoptosis , Brain Neoplasms , Pathology , Cell Line, Tumor , Chitosan , Pharmacology , Drug Carriers , Chemistry , Drug Compounding , Methods , Ferric Compounds , Glioma , Pathology , Magnetics , Metal Nanoparticles , Chemistry , Nanoparticles , Paclitaxel , PharmacologyABSTRACT
Objective To evaluate and compare the effect of early environmental enrichment on spatial learning and memory in wild house mouse and Kunming mouse,one kind of laboratory mouse which evolved from wild house mouse.Methods The wild house mouse F1 generation were employed to control the environmental enrichment.Offspring were weaned on PND22 and housed in usual or rich environment for one month randomly,then engaged the morris maze:house moutse rich environment(n=7),house mouse poor environment(n=6),Kunming mouse rich environment(n=10),Kunming mouse poor environment(n=10).Results (1)Early environmental enrichment improve the performance of house mouse(poor environment:(39.5±3.8)s;rich environment:(25.2±4.5)s;F(1,22)=8.115,P<0.01),but had no effect on that of Kunming mouse in tests of spatial memory (poor environment:(8.5±2.4)s;rich environment:(7.5±1.7)s;F(1,36)=0.149,P=0.702).(2)Early environmental enrichment improve the performance of house mouse(F(1,132)=15.307,P<0.01)and Kunming mouse (F(1,216)=8.701,P<0.01)in spatial learn session.Conclusion The wild house mouse is more sensitive to the enrich environment than laboratory mouse.Therefore,it has higher validity of model.