RESUMEN
Background In the process of radiotherapy, when radiation kills tumor cells, it inevitably damages normal tissue cells. Objective To investigate the role of Toll-like receptor 4 (TLR4)/nuclear factor−kappa B (NF-κB) signaling pathway in the improvement of cognitive impairment induced by ionizing radiation by hydrogen-rich water before and after whole brain irradiation in rats. Methods Fifteen male SD rats were randomly divided into three groups: control group, irradiated group (IR group), and hydrogen-rich water intervention group (IR+HRW group), with 5 rats in each group. The control group was not irradiated, but was given purified water (20 mL·kg−1) by gavage every day, while the IR group and the IR+HRW group were irradiated with a single dose of 20 Gy. Three days before, 10 min before, and 30 days after irradiation, purified water/hydrogen-rich water (20 mL·kg−1) was given by continuous gavage every day. The general condition of the rats was observed every day, and the body weight were measured on the 7th, 14th, 21st, and 30th days after irradiation. On the 30th day after irradiation, the learning and memory ability of the rats was tested by Morris water maze; the pathological changes of hippocampus were detected by hematoxylin-eosin (HE) staining after sacrificing the rats; the contents of glutathione (GSH), malondialdehyde (MDA), interleukin-1β (IL-1β), and hydroxyl radicals in brain tissues were detected by enzyme linked immunosorbent assay (ELISA); the mRNA and protein expression levels of TLR4, NF-κB, NOD-like receptor pyrin domain 3 (NLRP3), and cysteinyl aspartate specific proteinase 1 (Caspase 1) were detected by quantitative real-time PCR (qRT-PCR) and Western blotting in the hippocampus of rats. Results After irradiation, the rats in the IR group showed symptoms such as head hair removal and salivation, while the symptoms of the rats in the IR+HRW group were milder. No animal died in the control and the IR+HRW groups, while one rat died in the IR group. From day 14 to day 30 after irradiation, the body weight of the rats in the IR+HRW group tended to be higher than that in the IR group, but the difference was not statistically significant (P>0.05). The Morris water maze results showed that the escape latency of the IR+HRW group was shortened compared with that of IR group from day 1 to day 5 except day 3, but the difference was not statistically significant (P>0.05). For the rats in the IR+HRW group, it took less time to reach the original location of the platform after removing the platform on day 6 and the number of crossing the platform and the residence time in the original platform quadrant increased (P<0.05). The HE staining showed that the number of hippocampal cells in the IR+HRW group was slightly reduced and arranged neatly, without obvious nuclear hyperchromatic and pyknotic phenomenon. The ELISA results showed that the MDA and hydroxyl radical levels were decreased in the IR+HRW group compared with the IR group (P<0.05), the GSH content was increased, and the IL-1β concentration was decreased, but the differences were not statistically significant (P>0.05). The results of qRT-PCR showed that the mRNA expression levels of TLR4 and Caspase 1 in the hippocampus of the IR+HRW group were decreased compared with the IR group (P<0.05), and the mRNA expression levels of NF-κB and NLRP3 were also decreased, but the differences were not statistically significant (P>0.05). The results of Western blotting showed that the expression levels of TLR4 and Caspase 1 protein in the hippocampus of the IR+HRW group were decreased compared with the IR group (P<0.05), and the expression levels of NF-κB p65 and NLRP3 protein were also decreased, but the differences were not statistically significant (P>0.05). Conclusion Hydrogen-rich water can improve cognitive impairment induced by ionizing radiation in rats, and its mechanism may be related to regulating TLR4/NF-κB signaling pathway, inhibiting inflammatory factors, and attenuating oxidative stress.
RESUMEN
Background At present, radiation therapy is widely used in clinical treatment of tumors. However, while radiation therapy damages tumor cells, it also injures surrounding normal tissues. Studies have shown that hydrogen is a potential radiation-protective agent. Objective To investigate the neuroprotective mechanisms of hydrogen-rich water activating phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/cysteinyl aspartate specificproteinase-9 (Caspase-9) signaling pathway in acute radiation-induced brain injury. Methods Forty male SD rats were randomly divided into four groups: control group, irradiation only group (IR), high-dose hydrogen-rich water intervention group (IR+HHRW), and low-dose hydrogen-rich water intervention group (IR+LHRW), 10 rats in each group. Except for the control group, animals in each group received a single 20 Gy whole brain irradiation. Animals in all groups were gavaged once a day from 3 d before irradiation to 7 d after irradiation, pure water (20 mL·kg−1) was given to the control and the IR groups, and hydrogen-rich water (20 mL·kg−1, 10 mL·kg−1) was given to the IR+HHRW and the IR+LHRW groups. After 7 d of intervention, 5 rats in each group were selected for the Morris water maze experiment for behavioral evaluation. Autopsies were conducted after anesthesia for the remaining animals and blood samples were collected for hematological analysis. Rat brains were harvested for TUNEL staining to observe neuronal apoptosis. HE staining was performed to observe histopathological changes, enzyme-linked immunosorbent assay was adopted to detect oxidative stress-related indicators, and real-time PCR and Western blotting were used to measure the expressions of PI3K/AKT/Caspase-9 pathway-related genes and proteins. Results The body weight of rats receiving irradiation decreased after 7 d of irradiation compared with the control group (P<0.05), and the symptoms such as arched back and malaise occurred to varying degrees, and the symptoms of rats in the IR+HHRW group were significantly milder than those in the IR group. The behavioral test results showed that the escape latency of rats in the IR+HHRW group or the IR+LHRW group was shorter than that in the IR group from day 2 to day 5 (P<0.05), and it took less time for rats in the IR+HHRW group to reach the original position after removing the platform on day 6 (P<0.05). The hematological test results showed that red blood cell (RBC) count, hemoglobin (HGB) level, and white blood cell (WBC) count were significantly decreased in the IR group (P<0.05), and the changes in the IR+HHRW group were improved (P<0.05). The HE staining results showed that the number of abnormal nerve cells, broken and dissolved nuclei, and the degree of damage in the IR+HHRW group were significantly reduced than those in the IR group. The results of oxidative stress evaluation showed that the ability of the IR group to inhibit free radicals decreased, the level of malondialdehyde (MDA) increased (P<0.01); the MDA level decreased after LHRW intervention (P<0.05); the SOD activity was elevated after HHRW intervention (P<0.05). The TUNEL staining results showed that the apoptosis signals in the IR+HHRW group were sparser than those in the IR group (P<0.05). The real-time PCR results showed that compared with the IR group, the mRNA expression levels of PI3K and AKT in the IR+HHRW group and the IR+LHRW group increased (P<0.05), while the mRNA expression levels of Cytc and Caspase-9 decreased (P<0.05). The Western blotting results showed that compared with the IR group, the phospho-AKT (pAKT) protein expression level in the IR+HHRW group increased significantly (P<0.05), while the expression of Caspase-9 and Cytc proteins decreased significantly (P<0.05). Conclusion Hydrogen-rich water can significantly reduce inflammation and oxidative stress caused by acute irradiation-induced brain injury, and decrease neuronal apoptosis. The mechanism may be related to the PI3K/AKT/Caspase-9 signaling pathway.
RESUMEN
Objective@#To investigate the use of diabetes medications and their effects on the community diabetic patients in Shanghai, China, and provide the evidence for the use of antidiabetic drugs in diabetic patients in the region.@*Methods@#The data were from a database of a 2018 Survey on Community Diabetes Mellitus in Shanghai, China. There were 4 612 subjects included in this cross-sectional study in 2018. According to the use of antidiabetic drugs, the population was divided into untreated group, single drug group, double drugs combination group and multi-drugs combination group, to compare the fasting blood glucose, glycosylated hemoglobin, BMI and prevalence of diabetic complications in different groups.@*Results@#About 70.9% of the 4 612 patients used hypoglycemic agents, 34.8% used metformin, 35.1% used sulfonylureas, 22.9% used alpha glycosidase inhibitors, and 13.8% used insulin. The prevalence of diabetic nephropathy, retinopathy, neuropathy, stroke, and diabetic foot was higher in the combination than in the untreated and single-drug users (P<0.01). Only 41.3% subjects had HbA1C<7%. The fasting blood glucose and HbA1C values were lower in the untreated group than in other three medication groups, and the rate of the HbA1C reaching target in the untreated group was higher than the other medication groups (P<0.01). As the types of drug increased, HbA1C was less likely to reach the target (P<0.01). There were 42.2% of patients with BMI<24 kg/m2, and there was no significant difference in the proportion of BMI reaching target among the four groups (P>0.05).@*Conclusion@#The most common used antidiabetic drugs in diabetic patients in Shanghai are metformin, sulfonylureas, α-glycosides inbibitor, and insulin. The blood glucose control in diabetic patients in Shanghai community is not good enough. Patients with a longer duration of diabetes, a lower rate of HbA1C at goal, and a higher prevalence of diabetic complications may be more prone to use multiple hypoglycemic drugs.
RESUMEN
Objective To study the effect of high-dose methylprednisolone intravenous pulse therapy on immunoglobulins and CD series in patients with active moderate-to-severe Graves' orbitopathy. Methods Twenty-seven patients with active moderate-to-severe Graves' orbitopathy were enrolled in this study. All the patients received iv methylprednisolone pulse therapy for 12 weeks according to the 2016 European Thyroid Association/European Group on Graves'Orbitopathy(EUGOGO) Guidelines. Serum thyroidal autoantibodies, such as thyroid-stimulating hormone receptor antibody ( TRAb) , anti-thyroperoxidase antibody ( TPOAb) , and serum immunoglobulins, such as IgG, IgE, IgA, IgM were evaluated at the baseline, at the end of 4th and 12th week. Percentages of CD3+ T cells, CD4+ T cells, CD8+T cells and CD19+ B cells, CD16+ or CD56+ NK cells were also evaluated at each time point. Results TRAb, TPOA and IgE, IgG, IgA were significantly decreased both after 4th week and after 12th week (all P<0.05). Percentages of CD3+ T cells, CD4+ T cells and CD4+/CD8+ ratio were gradually decreased after treatment. However, change of CD8+T cells was not significant (P>0.05). Conclusion High-dose methylprednisolone may exert an immunosuppressive effect not only by modifying humoral and cellular immune functions, but also by decreasing serum immunoglobulins.
RESUMEN
Objective We aimed to investigate whether sex hormone levels including total testosterone, estradiol, estradiol/total testosterone, and dehydroepiandrosterone ( DHEA ) were associated with macrovascular complications among Shanghai community-dwelling diabetic men. Methods Relying on the Environmental Pollutant Exposure and Metabolic Diseases in Shanghai (METAL) study (ChiCTR1800017573, www.chictr.org.cn), 2147 male diabetic participants were recruited from 10 communities. Carotid plaques and common carotid artery ( CCA) diameters were detected by carotid ultrasound. Cardiovascular disease ( CVD) was defined as a self-reported diagnosis of CVD, including coronary heart disease, myocardial infarction, or stroke. Results ( 1) The prevalence of CVD in this study was 36. 0％, and patients with CVD had higher rates of hypertension and dyslipidemia than those without CVD. ( 2) After controlling for multiple factors, serum DHEA levels were negatively correlated with the prevalence of CVD while estradiol levels were positively correlated with both the prevalences of CVD and carotid plaque, estradiol/total testosterone ratio was also positively correlated with the prevalence of CVD. ( 3) In subgroup with unilateral/bilateral CCA plaque, and after controlling for multiple factors, total serum testosterone was negatively associated with the mean CCA diameter. Conclusion The incidence of macrovascular complications was lower in male diabetic patients with higher serum total testosterone and DHEA levels and lower estradiol levels, suggesting that sex hormone levels may be a window for the diagnosis and treatment of diabetic macrovascular complications.
RESUMEN
Objective@#To study the effect of high-dose methylprednisolone intravenous pulse therapy on immunoglobulins and CD series in patients with active moderate-to-severe Graves′ orbitopathy.@*Methods@#Twenty-seven patients with active moderate-to-severe Graves′ orbitopathy were enrolled in this study. All the patients received iv methylprednisolone pulse therapy for 12 weeks according to the 2016 European Thyroid Association/European Group on Graves′Orbitopathy(EUGOGO) Guidelines. Serum thyroidal autoantibodies, such as thyroid-stimulating hormone receptor antibody (TRAb), anti-thyroperoxidase antibody (TPOAb), and serum immunoglobulins, such as IgG, IgE, IgA, IgM were evaluated at the baseline, at the end of 4th and 12th week. Percentages of CD3+ T cells, CD4+ T cells, CD8+ T cells and CD19+ B cells, CD16+ or CD56+ NK cells were also evaluated at each time point.@*Results@#TRAb, TPOA and IgE, IgG, IgA were significantly decreased both after 4th week and after 12th week (all P<0.05). Percentages of CD3+ T cells, CD4+ T cells and CD4+ /CD8+ ratio were gradually decreased after treatment. However, change of CD8+ T cells was not significant (P>0.05).@*Conclusion@#High-dose methylprednisolone may exert an immunosuppressive effect not only by modifying humoral and cellular immune functions, but also by decreasing serum immunoglobulins.
RESUMEN
Objective@#To investigate the effects of cadmium exposure on cardiovascular system of occupational workers.@*Methods@#Cross-sectional study was applied to 992 workers in a nickel-cadmium battery plant in November, 2011, of which 749 were cadmium exposed workers and 243 were controls without cadmium and other expose. Urinary cadmium、electrocardiogram (ECG) and blood pressure were examined simultaneously among 992 workers. The risk factors of ECG abnormality rate and hypertension rate were analyzed by Logistic regression.@*Results@#The level of urinary cadmium in cadmium exposed workers was significantly higher than controls (8.89±4.00 vs 1.34±1.18 μg/g creatinine, P<0.01) . Urinary cadmium level in women was significantly higher than men in both exposure and control group (P<0.05) . According to the group of working years, Urinary cadmium level raised with the increase of working years (F=28.272, P<0.001) . The ECG abnormality rate and hypertension rate of cadmium exposed workers were higher than that of control group, the differences were all statistically significant (P<0.01) . The abnormal rate of ECG and the hypertension rate increased with the prolonging of working years and demonstrated dose-response relationship. With the increase of urinary cadmium level, the abnormal rate of ECG and hypertension rate raised (OR=1.11, P<0.01) and (OR=1.15, P<0.01) respectively.@*Conclusion@#Occupational cadmium exposure increased the abnormal rate of ECG and blood pressure and therefore damaged cardiovascular system of workers. This study provided base data for protecting health of cadmium exposed workers.
RESUMEN
Objective To develop real-time quantitative PCR method for measuring the amount of fetal DNA in maternal plasma and the changing patterns of fetal and maternal DNA with the pregnant progress. Methods Fifty-eight women were recruited at 7～42 weeks of gestation with singleton pregnancy determined by ultrasound scan. QIAGEN DNA kits was used to extract fetal DNA from maternal plasma. Fluorescent quantitative PCR(FQ-PCR) were applied to determine the concentration of ?-actin and SRY gene in extracted DNA. Results Thirty-seven male fetus were all identified among the 58 pregnant women (100%) and no Y signal was detected in the other 21 pregnancies with female foetus. The median level of fetal DNA in those pregnancies with male foetus was 9.08 copies/ml (3.5～12.8) in early pregnancy,45.41 copies/ml (14.38～76.5) in mid-pregnancy and 300.95 copies/ml (84～840) in late pregnancy. Conclusions The concentration of fetal DNA increases with the progress of pregnancy. Maternal plasma may be valuable in noninvasive prenatal diagnosis.