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BACKGROUND:Exercise has been widely recognized in the prevention and treatment of diabetes.Aerobic exercise has become an important part of the treatment of type 1 diabetes.However,the effect of treadmill exercise on the metabolism and chronic neuroinflammation of type 1 diabetes in different sexes needs further discussion. OBJECTIVE:To study the effects of treadmill exercise on metabolism and chronic neuroinflammation in type 1 diabetes mice of different sexes. METHODS:Forty C57BL/6 mice were divided into male group and female group,with 20 mice in each group.Then,a diabetes model was established by continuous injection of streptozotocin at 80 mg/kg for 3 days.Ten rats from each group were randomly selected to perform 6-week treadmill exercise as the diabetes+exercise group and another 10 rats from each group were selected as the diabetes group.Serum sex hormones,liver tissue oxidative stress,brain tissue inflammatory factors,and liver pathology were detected,and Morris water maze was performed for the observation of behavioral changes in mice. RESULTS AND CONCLUSION:Compared with the diabetes group,the diabetes+exercise group delayed the rise of blood sugar in type 1 diabetes mice(P＜0.05)and showed a significant reduction in serum follicle-stimulating hormone,luteinizing hormone,liver superoxide dismutase,malondialdehyde,brain tumor necrosis factor α,interleukin-6 and interleukin-1β levels(P＜0.01),while serum estradiol,progesterone,estrogen,and liver glutathione peroxidase protein levels were significantly increased(P＜0.01,P＜0.05).Compared with male type 1 diabetes mice,female type 1 diabetes mice had significantly higher estradiol levels and lower luteinizing hormone levels(P＜0.05).Compared with the male diabetes+exercise group,the female diabetes+exercise group had lower liver glutathione peroxidase levels(P＜0.05).Compared with type 1 diabetes mice,the escape latency of exercise training mice was shorter(P＜0.01).In male mice,exercises significantly increased the time and platform crossing times of type 1 diabetes mice in the target quadrant(P＜0.01 or P＜0.05),while in female mice,exercises significantly increased the time of type 1 diabetes mice in the target quadrant(P＜0.05).Correlation analysis results showed that the levels of follicle-stimulating hormone,luteinizing hormone,progesterone,superoxide dismutase,malondialdehyde,tumor necrosis factor α,and interleukin-6 were positively correlated with the level of interleukin-1β(P＜0.05 or P＜0.01),whereas the levels of estradiol and progesterone were negatively correlated with the levels of superoxide dismutase,malondialdehyde,tumor necrosis factor α,interleukin-6 and interleukin-1β(P＜0.05 or P＜0.01).Overall,there are sex differences in the effects of treadmill exercise on metabolic indicators and chronic neuroinflammatory regulation in diabetes mice.Sex hormones are an important variable of treadmill exercise in the metabolic,inflammatory and cognitive responses in diabetes mice.
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Objective:To investigate the clinical profile of primary bilateral macronodular adrenal hyperplasia(PBMAH) and sex difference.Methods:One hundred and forty cases of PBMAH were recruited in our center from 2014, and all patients were evaluated for hormone secretion, adrenal imaging, and metabolic parameters.Results:Overt Cushing′s syndrome accounted for 76.4% of PBMAH cohort and 47.9% were female. The overt group had higher serum cortisol and 24 h urinary free cortisol levels, lower adrenocorticotropic hormone, higher serum cortisol after low-dose dexamethasone suppression tests, larger total adrenal size, and a higher percentage of obesity, hypertension, diabetes mellitus, and hypokalemia than the subclinical group(all P<0.05). When compared with the male group, the female group had smaller adrenal size( P<0.001), lower HbA 1C( P=0.003), higher total cholesterol( P=0.005), and lower density lipoprotein-cholesterol levels( P=0.035). Further, 24 h urinary free cortisol in the male group was found to be positively correlated with diastolic blood pressure, fasting glucose, 2 h postprandial glucose after oral glucose tolerance test(OGTT), and HbA 1C after adjusted for age, body mass index, and onset duration, and was negatively correlated with body mass index and potassium levels. While 24 h urinary free cortisol in the female group was positively correlated only with diastolic blood pressure, fasting glucose, and 2 h postprandial glucose after OGTT(all P<0.05). During follow-up, 80.0% of patients achieved remission after unilateral adrenalectomy, with a recurrence rate of 17.9%. Conclusion:PBMAH related metabolic disorder is more pronounced in overt Cushing′s syndrome and males. Unilateral adrenalectomy as an effective treatment can benefit the majority of patients.
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Objective@#To explore sex differences in 3D T1texture features in the progression of Alzheimer's disease (AD) and to predict the diagnosis of AD patients of different sex．@*Methods@#Seventy-seven AD patients (34 males and 42 females) ，74 amnestic mild cognitive impairment ( aMCI) patients ( 35 males and 39 females) and 75 healthy controls (HC) (35 males and 40 females) were recruited and high-resolution 3-dimensional T1 structural images were collected． Brain regions closely related to AD brain damage were selected as regions of interest ( ROIs) ，texture feature extraction and feature screening were performed．Analyses were performed by sex，and the support vector machine (SVM) was used for classification and prediction. @*Results @#In the AD vs HC，AD vs aMCI and aMCI VS HC groups by different sex，we obtained some brain regions with relatively high recognition index in different subgroups，and found that there were significant differences between female patients and male patients with high recognition index，and the recognition index of female patients ( area under the curve，accuracy，sensitivity and specificity were generally higher than that of male．@*Conclusion@#There are significant sex differences in texture features in AD process，and the classification and prediction ability of texture features in female patients is better， suggesting the importance of sex differences in AD research．This study provides some reliable biomarkers for early sex-specific identification of AD，which may be helpful for the early diagnosis and treatment of AD in the future.
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Liver injury occurs after ischemia and reperfusion (IR), as seen in transplant settings. Sex hormones have been implicated in many pathophysiological mechanisms in females and this could lead to liver protection under inflammatory reperfusion conditions where an excessive immune response occurs. Despite such assumptions, this fact needs to be further investigated. To address this, female and male C57BL/6J mice (8-12 weeks old) were studied. Bilateral ovariectomy (OVX) was performed in females to decrease estradiol levels. IR was performed, and after two weeks, all animals underwent a sham control operation or IR with euthanasia at the following time points after reperfusion: 6, 12, 24, and 48 h. IR triggered an inflammatory process in the liver with recruitment of neutrophils into the parenchyma of male mice. The female sham mice were protected against liver IR presenting no alteration of aminotransferase (ALT) levels compared to males. OVX caused loss of protection, increasing hepatic injury as represented by increased ALT levels and myeloperoxidase (MPO) activity. Female sham mice showed increased Akt phosphorylation and activation, while males showed reduced Akt activation. Estradiol pretreatment recovered ALT levels after IR injury, which was associated with decreased liver injury.
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A growing number of studies have identified sex differences in response to general anesthesia; however, the underlying neural mechanisms are unclear. The medial preoptic area (MPA), an important sexually dimorphic structure and a critical hub for regulating consciousness transition, is enriched with estrogen receptor alpha (ERα), particularly in neuronal clusters that participate in regulating sleep. We found that male mice were more sensitive to sevoflurane. Pharmacological inhibition of ERα in the MPA abolished the sex differences in sevoflurane anesthesia, in particular by extending the induction time and facilitating emergence in males but not in females. Suppression of ERα in vitro inhibited GABAergic and glutamatergic neurons of the MPA in males but not in females. Furthermore, ERα knockdown in GABAergic neurons of the male MPA was sufficient to eliminate sex differences during sevoflurane anesthesia. Collectively, MPA ERα positively regulates the activity of MPA GABAergic neurons in males but not in females, which contributes to the sex difference of mice in sevoflurane anesthesia.
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Animales , Femenino , Masculino , Ratones , Anestesia , Receptor alfa de Estrógeno/metabolismo , Área Preóptica , Sevoflurano/farmacología , Caracteres SexualesRESUMEN
Background Heavy metals are widely present in the environment, difficult to degrade, and bioaccumulative. Children's physical development are not mature, and exposure to heavy metals which may cause irreversible harm to them. However, the current research conclusions are still inconsistent. Therefore, it is very important to pay attention to the impact of heavy metal pollutants on physical development. Objective To detect the level of heavy metal exposure of school-age children in Laizhou Wan, Shandong Province, and to explore the relationship between heavy metal exposure level and physical development indexes of school-age children. Methods The subjects of this study were 318 children born to pregnant women recruited from Laizhou Wan Birth Cohort in Shandong Province from September 2010 to December 2013. The school-age children at age 7 were followed up from July to September 2019. Their urine samples were collected and the levels of arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg) in urine were detected by inductively coupled plasma mass spectrometry (ICP-MS). At the same time, the height, weight, body mass index (BMI), waist circumference, and body fat percentage of the children were evaluate to analyze the relationship between the four heavy metals in children's urine and the indicators related to children's physical development. Results Among the 318 school-age children with an age (\begin{document}$\bar x \pm s $\end{document}) of (7.77±0.67) years, the median (P25, P75) levels of As, Cd, Pb, and Hg in urine were 73.98 (44.81, 124.61), 0.40 (0.27, 0.58), 1.20 (0.71, 1.72), and 2.38 (1.32, 4.80) µg·g−1 (of creatinine), respectively. The children’s urinary Cd level was positively correlated with their weight, BMI, and waist circumference (P<0.05), and corresponding regression coefficients (b) and its 95% confidence intervals (CI) were 0.99 (0.14-1.83), 0.43 (0.06-0.81), and 1.35 (0.27-2.42), respectively; while the other heavy metals were not related to the above physical development indicators (P>0.05). After sex stratification, it was found that boys’ urinary Cd level was positively correlated with their height, weight, BMI, and waist circumference (P <0.05) with associated b (95%CI) of 1.73 (0.53-2.93), 2.03 (0.60-3.47), 0.75 (0.11-1.38), and 2.66 (0.85-4.47), respectively; such associations were not found in girls. After further stratification of boys’ BMI according to normal, overweight, and obesity, it was found that a higher urinary Cd level was correlated with an increased risk of obesity in boys (P<0.05), and the associated b (95%CI) was 2.34 (1.02-5.36). Conclusion The level of urinary Cd exposure of boys in Laizhou Wan, Shandong Province is positively correlated with their height, weight, BMI, and waist circumference, and may be related to obesity in boys.
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Objective To investigate the association between hot spring bathing behavior and hypertension and understand the mediation effect of sleep quality problems on the association. Methods A cross-sectional survey was conducted among adults aged 30 to 65 living and working around five hot springs in Guizhou Province, employing a self-designed questionnaire on the health status and hot spring bathing, and 3 708 qualified questionnaires were collected. Participants were divided into three groups according to their frequency of hot spring bathing: never, occasionally, and frequently. Stratified via sex and sleep quality, the binary logistic regression model was used to analyze the association between different hot spring bathing frequencies and self-reported hypertension. Results Significant difference was detected in the self-reported hypertension between groups who never bathe(13.7%), who occasional bathe(9.4%)and who frequently bathe(8.5%)among female participants(χ2=10.460, P=0.005). However, no significant difference was found among different bathing groups in males. Furthermore, multivariate analysis showed that compared with no bathing, occasional(OR=0.692)and frequent (OR=0.594)hot spring bathing were associated with lower hypertension prevalence among female population, and female groups of occasional and frequent bathing with sleep quality problems had smaller OR(OR=0.571 and 0.406, respectively). After sleep quality problems were included, hot spring bathing was still associated with lower hypertension risk, and the OR values of occasional bathing and frequent bathing groups were 0.723 and 0.611, respectively. The sleep quality problems of female population played a partial mediating role in the association between hot spring bathing and hypertension, and the relative mediating effects of occasional bathing and frequent bathing with hypertension were both statistically significant(Zm=-2.022 and -1.995, P < 0.05), which accounted for 34.34% and 30.15% of the total effects, respectively. Conclusion Regular hot spring bathing may play an auxiliary role in the prevention of hypertension, and it may provide a stronger protection for women, and especially those with sleep quality problems. Sleep quality problems may explain part of the association between hot spring bathing and hypertension in female population.
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Background Studies have shown that stress during pregnancy can affect the growth and development of fetuses and offspring, and this effect has sex differences, but the results are controversial, and there are few studies on the emotional damage of offspring of different sexes caused by stress during pregnancy. Objective This experiment is designed to observe the effect of chronic stress during pregnancy on emotional damage of offspring of different sexes. Methods Thirty-two SD female rats were randomly divided into a model group and a control group (16 rats in each group), 24 male rats were divided into a model mating group (n=16) and a control mating group (n=8). Each rat of the model group was reared in a single cage and received chronic unpredictable mild stress (CUMS) for 28 d, including hot water swimming for 5 min, cold water swimming for 5 min, tail pinching for 2 min, crowding for 24 h, moist bedding for 24 h, cage shaking for 30 min, and space restriction for 2 h. One stressor was administered daily and the same stressor did not repeat within 7 d. Blood was collected from the endocanthal vein of the two groups of female rats 1 d before and 1, 7, 14, 21, and 28 d after stress, the plasma was separated by centrifugation, and 131I radioimmunoassay was used to measure plasma corticosterone concentration. On postnatal day 21 (PND21), 16 offspring rats (half male and half male) were randomly selected from each group, their plasma corticosterone concentration was measured on PND28 and PND42, and their emotional damage was measured on PND42. Results The plasma corticosterone levels of dams in the model group on the 14th, 21th, and 28th days of stress [(394.02±97.40), (444.12±90.43), and (463.71±107.75) μg·L−1] were higher than those in the control group [(285.63±81.64), (341.78±48.39), and (320.42±84.76) μg·L−1] (all P< 0.05). On PND28 and PND42, the plasma corticosterone levels in the female model offspring group [(543.30±90.21) and (530.76±83.10) μg·L−1] were higher than those in the female control offspring group [(397.77±64.27) and (325.78±61.03) μg·L−1] (both P<0.05). In the sugar water preference test, the total fluid consumption [(10.74±1.28) mL], sugar water consumption [(5.50±1.30) mL], and 1% sucrose preference percentage [(20.36±3.41) %] in the female model offspring group were lower than those in the female control offspring group [(13.74±2.06) mL, (8.56±2.04) mL, and (62.11±8.05) %] (all P<0.05). In the open field test, the horizontal score, vertical score, and cleaning times of the male model offspring group were lower than those of the male control offspring group (all P<0.05). In the tail suspension test, the immobility time of the female and male model offspring groups [(126.95±39.88) and (70.24±28.98) s] was longer than the control offspring groups of the same sex [(54.30±24.99) and (38.63±18.91) s] (both P<0.05), and the duration of immobility time in the female model offspring group was longer (t=3.253, P=0.006). In the forced swimming test, the immobility time of the female model offspring group [(7.97±6.66) s] was longer than that of the female control offspring group [(1.85±2.12) s] (t=2.478, P=0.037). On PND42, the plasma corticosterone level of female offspring was negatively correlated with total fluid consumption, sugar water consumption, and 1% sucrose preference percentage (r=−0.621, r=−0.728, r=−0.699; P<0.05), and positively correlated with immobility time in the tail suspension test and immobility time in the forced swimming test (r=0.571, r=0.712; P<0.05), However, there was no correlation between plasma corticosterone and emotional indicators on PND42 in male offspring (P>0.05). Conclusion Chronic stress during pregnancy causes emotional damage to the offspring, and female offspring show depression-like behaviors.
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It is unknown whether the famous sex-related difference in emotion processing is accounted for by biological sex, gender role, or their interaction. To clarify the issue, in Study 1 we recorded event-related potentials in response to negative and positive images of diverse intensities when 47 masculine (26 males) and 47 feminine (22 males) subjects performed a non-emotional task. The occipital P1 and N1 amplitudes were larger in women than in men, while feminine subjects showed larger N1 amplitudes than masculine subjects, regardless of sex. Moreover, feminine subjects showed enhanced frontocentral N2 (210–270 ms) amplitudes for highly and mildly negative than for neutral stimuli, while masculine subjects showed an emotion effect only for highly negative stimuli. The feminine-specific effect for mildly negative stimuli was positively correlated to the feminine score, and this correlation was located to the anterior cingulate and the superior and medial frontal gyri. Furthermore, feminine but not masculine subjects showed enhanced parietal P3 (330–560 ms) amplitudes for highly and mildly positive than for neutral stimuli, an effect positively related to the feminine score and localized to the precuneus, posterior cingulate, and superior temporal gyrus. Machine learning analyses verified that single-trial N2 and P3 amplitudes of feminine subjects reliably discriminated the intensity of negative and positive stimuli, respectively. For ecological considerations, in Study 2 we used an observational approach (n = 300) and confirmed that feminine gender role, rather than biological sex, predicted individual differences in daily experience of emotion-related psychopathological symptoms. These findings provide solid evidence for the critical impact of gender role rather than sex on emotional susceptibility.
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Background@#Stroke is one of the leading causes of mortality and disability worldwide. Understanding sex differences in risk factors, clinical characteristics and death after stroke might provide valuable evidence for prevention and management of stroke. @*Aim@#We aimed to describe sex differences in risk factors, clinical characteristics and death after intracerebral hemorrhage (ICH) and ischemic stroke (IS) using hospital-based registry in 6 districts of Ulaanbaatar, Mongolia. @*Materials and methods@#We used hospital-based stroke registry in Ulaanbaatar Mongolia. From 2019 to 2020, total of 974 patients with acute ICH and 1612 patients with acute IS were enrolled in this study. The severity of stroke was measured by National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS). Risk factors for stroke were defined as patient’s history and their medical record. Death after stroke was registered at 28 days and 90 days by follow-up study. A comparison of categorical and continuous variables was analyzed using chi-squared test, Student’s t-test and Mann Whitney U test. Univariable and multivariable logistic regression analyses were also performed.@*Results@#The mean age of ICH patients was 58.41±11.56. There was significant difference in age (59 vs 57, p=0.009) between women and men. Men with ICH were more likely to drink alcohol (35.4% vs 5.2%, p=0.000) and to smoke (37.0% vs 8.4%, p=0.000) and to have arterial hypertension (72.7% vs 58.6%, p=0.000). However, there were no significant differences in other risk factors including atrial fibrillation, diabetes mellitus, prior stroke and other cardiac diseases. There were no sex differences in clinical characteristics including systole and diastole blood pressure, NIHSS scores and GCS. In our study, case fatality rate was 23.8% at 28 days and 1.9% at 90 days after ICH. By multivariable regression analyses, there were no significant association between sex and death at 28 days and at 90 days (OR:0.74; 95% CI:0.52-1.06, OR: 0.80; 95% CI:0.29-2.21).</br> The mean age of IS patients was 61.07±12.88. The women were older (63 vs 59, p=0.000) than men. Men with IS also were more likely to be current smokers (37.6% vs 9.0%, p=0.000), current drinkers (33.2% vs 3.4%, p=0.000) and to have arterial hypertension (74.7% vs 65.9%, p=0.000). There were no significant differences in other risk factors. For IS patients, there also was no sex difference in clinical characteristics. Case fatality rate was 13.3% at 28 days and 1.1% at 90 days after IS. By multivariable regression analyses, there were no significant association between sex and death at 28 days and at 90 days (OR:0.90; 95%CI: 0.64-1.26, OR:5.16; 95%CI: 0.99-23.9). @*Conclusion@#Our study showed sex differences in some vascular factors of both stroke subtypes which emphasized that we need to implement stroke prevention targeting sex-specific risk factors. While clinical characteristics and early mortality of intracerebral hemorrhage and ischemic stroke were not differed by gender.