Ovarian hormones influence immune response to liver ischemia-reperfusion

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.

Association between heavy metal exposure level and physical development indicators among school-age children / 环境与职业医学

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.

Estrogen Receptor-A in Medial Preoptic Area Contributes to Sex Difference of Mice in Response to Sevoflurane Anesthesia / 神经科学通报·英文版

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.

Gender Role, But Not Sex, Shapes Humans’ Susceptibility to Emotion / 神经科学通报·英文版

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.

Effects of chronic stress during pregnancy on sex-specific offspring emotional damage / 环境与职业医学

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.

Sex differences on risk factors, clinical characteristics and early death of stroke / Монголын Анагаах Ухаан

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.

Association between hot spring bathing behavior and hypertension and the mediating effect of sleep quality problems in typical hot spring areas of Guizhou Province / 上海预防医学

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.

Sex and age-related changes in performance in the duathlon world championships / Sexo e mudanças relacionadas com a idade no desempenho em campeonatos mundiais de duatlo / Sexo y cambios relacionados con la edad en el desempeño en campeonatos mundiales de duatlón

ABSTRACT Objective Our study analyses differences in performance between sexes, and changes in performance between age groups at Olympic distance during the ITU Duathlon World Championships, held between 2005 and 2016. During this period, a total of 9,772 duathletes were analysed (6,739 men and 3,033 women). Methods Two-way analyses of variance (ANOVA) were used to examine sex- and age-related differences in performance (time, percentage of time and performance ratio) in the first running and cycling legs, the second running leg, and total race for the top 10 male and female athletes in each age group at the Duathlon World Championships. Results The age group with the highest participation, in both male and female categories, was 40-44 years, and it was found that the mean age of female finisher participants across all age groups was 23.5±12. With regards to performance, the best results for total race time and the cycling segment were achieved in the 30-34-year age group, for both male and female athletes. With regards to performance in the first and third segments (running legs), the best times were achieved in the 25-29 and 30-34 age groups, for men and women respectively. Conclusion According to the results of our study, the best results in the professional career of a duathlete are achieved at between 30 and 35 years, therefore the athlete should incorporate this factor into their training plan. Level of evidence III; Retrospective comparative study.

RESUMO Objetivo Nosso estudo analisa as diferenças de desempenho entre os sexos e as mudanças do desempenho entre as faixas etárias quanto à distância olímpica durante o Campeonato Mundial de Duatlo da ITU, realizado entre 2005 e 2016. Nesse período, foram analisados 9.772 duatletas (6.739 homens e 3.033 mulheres). Métodos As análises de variância bidirecional (ANOVA) foram usadas para examinar as diferenças de desempenho relacionadas com sexo e idade (tempo, porcentagem de tempo e coeficiente de desempenho) na primeira corrida, ciclismo, segunda corrida e competição total dos 10 melhores atletas do sexo masculino e feminino em cada faixa etária no Campeonato Mundial de Duatlo. Resultados A faixa etária com maior participação, tanto dos homens quanto das mulheres foi de 40 a 44 anos, e verificou-se que a média de idade das participantes do sexo feminino que concluíram a competição em todas as faixas etárias foi de 23,5 ± 12. Com relação ao desempenho, os melhores resultados para o tempo total de competição e o segmento de ciclismo foram na faixa etária de 30 a 34 anos, tanto em atletas masculinos quanto femininos. Com relação ao desempenho no primeiro e terceiro segmentos (corridas), o melhor desempenho foi alcançado nas faixas de 25 a 29 e 30 a 34 anos, em homens e mulheres, respectivamente. Conclusão De acordo com os resultados obtidos neste estudo, os melhores resultados na carreira profissional de um duatleta poderiam ser alcançados entre 30 e 35 anos, portanto o atleta deve incorporar esse fator em seu plano de treinamento. Nível de evidência III; Estudo retrospectivo comparativo.

RESUMEN Objetivo Nuestro estudio analiza las diferencias de desempeño entre los sexos y los cambios de desempeño entre los grupos de edad con respecto a la distancia olímpica durante el Campeonato Mundial de Duatlón de ITU, realizado entre 2005 y 2016. En ese período, fueron analizados 9.772 duatletas (6.739 hombres y 3.033 mujeres). Métodos Los análisis de variancia bidireccional (ANOVA) fueron usados para examinar las diferencias de desempeño relacionadas con sexo y edad (tiempo, porcentaje de tiempo y coeficiente de desempeño) en la primera carrera, ciclismo, segunda carrera y competición total de los 10 mejores atletas de sexo masculino y femenino en cada grupo de edad en el Campeonato Mundial de Duatlón. Resultados El grupo de edad con mayor participación, tanto de los hombres como de las mujeres, fue de 40 a 44 años y se verificó que la edad promedio de las participantes femeninas que concluyeron la competición en todos los grupos de edad fue de 23,5 ± 12,5. Con relación al desempeño, los mejores resultados para el tiempo total de competición y el segmento de ciclismo fueron en el grupo de edad de 30 a 34 años, tanto en atletas masculinos como femeninos. Con relación al desempeño en el primer y tercer segmentos (carreras), el mejor desempeño fue alcanzado en los grupos de 25 a 29 y 30 a 34 años, en hombres y mujeres, respectivamente. Conclusión De acuerdo con los resultados obtenidos en este estudio, los mejores resultados en la carrera profesional de un duatleta podrían ser alcanzados entre 30 y 35 años, por lo tanto el atleta debe incorporar ese factor en su plan de entrenamiento. Nivel de evidencia III; Estudio retrospectivo comparativo.

Sex-Specific Lower Extremity Biomechanics of Amateur Runners with Patellofemoral Pain / 医用生物力学

Objective To study the sex-specific lower extremity biomechanics of amateur runners with patellofemoral pain (PFP). Methods Fifteen male and ten female amateur runners with PFP were identified and enrolled in PFP group, twenty-five healthy amateur runners matched with the PFP group were recruited as control group. The kinematics and kinetics, surface electromyography (EMG) data from all the subjects in the running task were collected.Two-way analysis of variance was performed to determine the influence of group and sex on lower extremity biomechanics during running. Results Compared with control group, male amateur runners with PFP showed a greater peak knee flexion angle during the landing phase of running. Compared with control group, male and female amateur runners with PFP showed a greater peak hip adduction angle during the landing phase of running, while the peak hip adduction angle of female participants was significantly greater than that of male participants. Conclusions Amateur runners with PFP showed sex-specific lower extremity biomechanics in the running task, and the clinical intervention for PFP should be sex-specific.

Sex-differential effects of olanzapine vs. aripiprazole on glucose and lipid metabolism in first-episode schizophrenia

Abstract Objective To compare sex difference in metabolic effect of olanzapine versus aripiprazole on schizophrenia. Methods A twelve-week prospective open-label cohort study to compare four subgroups according to first-episode schizophrenia patients' type of drug usage and sex: female aripiprazole (n = 11), male aripiprazole (n = 11), female olanzapine (n = 10), and male olanzapine (n = 11) for body mass index, fasting serum triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fasting glucose. Results Aripiprazole may be associated with weight gain in female patients with low-baseline weight. Aripiprazole may have an adverse effect of weight and favorable effects of circulating glucose and lipid on female over male schizophrenia patients. The aripiprazole-induced changes in glucose and lipid may be independent of body fat storage, especially for female schizophrenia patients. Olanzapine may have adverse effects of weight, glucose and lipid profiles on female over male schizophrenic patients. Discussion Our findings fill the gap in knowledge and provide a sex-specific guidance to psychiatrist better tailoring treatment to individual sex-differential characteristics and a key clue to understand the sex-differential mechanism of antipsychotics-induced metabolic dysfunction.

Sex difference in aversive stimulation is associated with the activity of lateral habenula in mice / 西安交通大学学报(医学版)

Objective: To explore the difference in response to aversive stimulation and the expression of CaMK-2β in the lateral habenula between male and female mice. Methods: Male and female mice were given the non-condition stimulation with electric shock associated with the condition-stimulation with the light and tone context. After 24 hours, the mice were placed into the stimulation context and their responses were recorded and analyzed. At 48 hours after non-condition stimulation, the effects on extinction were observed in the male and female mice. Immunohistochemical method was used to detect the number of CaMK-2β positive cells in the lateral habenula nucleus. The expression of CaMK-2β protein in the lateral habenula was detected by Western blot. Results: Female mice were more sensitive to context cue compared with the male mice. Similarly, the female mice were more tolerant to extinction than their male counterparts. Consistently, at 48 hours after aversive stimulation, the CaMK-2β-positive cells in lateral habenula of female mice outnumbered those of the male mice. Additionally, the expression of CaMK-2β in habenula protein was higher in the female mice than in the male mice after aversive stimulation. Conclusion: Male and female mice showed different responses to the same stress stimulation, which determined the consolidation to stress information. The sex difference in aversive stimulation may contribute to the expression of CaMK-2β in the lateral habenula.

Analysis of the Health Expenditure and Medical Usage Difference of the Baby Boomers between Male and Female: Depression as a Mediators / 보건행정학회지

BACKGROUND: This study purposed to compare the difference on medical utilization and health expenditure of baby boomer generation by depression between gender. METHODS: Korea Welfare Panel Survey 2016, provided by the Korea Institute for Health and Social Affairs, was used for the analysis. For the research, we used the two-part model, yes or no of use (part 1), and frequency of use (part 2) for medical utilization. The dependent variables are the whether or not to use of hospitalization services, outpatient services, length of stay, outpatient service visits, and health expenditure. And the independent variables are used as the predisposing (education, spouse presence), enabling (insurance type, private insurance, economic activity, income), and need (chronic disease, self-rated health, disability) factors in the Andersen behavior model. Depression was used as intervening variables. Structural equation model and multiple group analysis by gender were used. RESULTS: There were differences in the medical care usage and cost between men and women in baby boomer. For men, mediating effects of depression were present at the hospitalization (yes/no), length of stay, and health expenditure. On the other hand, for women, the mediating effect of depression was found only at the outpatient visits. Specially, depression was working at the medical services by the different way between gender. The size of effect (multiple group analysis) was affected by significant differences between men and women. CONCLUSION: This study found that the mediating effect of depression is increased medical usage and health expenditure and the effect factors are different by gender. Therefore, it is necessary to establish a medical care policy considering the socio-economic characteristics of baby boomers.

Comparison of the anesthetic effects of 2,2,2-tribromoethanol on ICR mice derived from three different sources / 한국실험동물학회지

This study was conducted to compare the anesthetic effects of 2,2,2-tribromoethanol (TBE, Avertin®) in ICR mice obtained from three different sources. TBE (2.5%) was intraperitoneally injected at three doses: high-dose group (500 mg/kg), intermediate-dose group (250 mg/kg), and low-dose group (125 mg/kg). Anesthesia time, recovery time, end-tidal peak CO2 (ETCO₂), mean arterial blood pressure, heart rate, oxygen saturation (SpO₂), body temperature, pH, PCO₂, and PO₂ of the arterial blood were measured. Stable anesthesia was induced by all doses of TBE and the anesthesia time was maintained exhibited dose dependency. No significant differences in anesthetic duration were found among the three different strains. However, the anesthesia time was longer in female than in male mice, and the duration of anesthesia was significantly longer in female than in male mice in the high-dose group. The recovery time was significantly longer for female than male mice in the intermediate- and high-dose groups. In the ICR strains tested, there were no significant differences in the mean arterial blood pressure, SPO₂, arterial blood PCO₂, and PO₂, which decreased after TBE anesthesia, or in heart rate and ETCO₂, which increased after TBE anesthesia. In addition, body temperature, blood biochemical markers, and histopathological changes of the liver, kidney, and lung were not significantly changed by TBE anesthesia. These results suggested that ICR mice from different sources exhibited similar overall responses to a single exposure to TBE anesthesia. In conclusion, TBE is a useful drug that can induce similar anesthetic effects in three different strains of ICR mice.

Sex Differences in Cancer: Epidemiology, Genetics and Therapy

The incidence and mortality of various cancers are associated with sex-specific disparities. Sex differences in cancer epidemiology are one of the most significant findings. Men are more prone to die from cancer, particularly hematological malignancies. Sex difference in cancer incidence is attributed to regulation at the genetic/molecular level and sex hormones such as estrogen. At the genetic/molecular level, gene polymorphism and altered enzymes involving drug metabolism generate differences in cancer incidence between men and women. Sex hormones modulate gene expression in various cancers. Genetic or hormonal differences between men and women determine the effect of chemotherapy. Until today, animal studies and clinical trials investigating chemotherapy showed sex imbalance. Chemotherapy has been used without consideration of sex differences, resulting in disparity of efficacy and toxicity between sexes. Based on accumulating evidence supporting sex differences in chemotherapy, all clinical trials in cancer must incorporate sex differences for a better understanding of biological differences between men and women. In the present review, we summarized the sex differences in (1) incidence and mortality of cancer, (2) genetic and molecular basis of cancer, (3) sex hormones in cancer incidence, and (4) efficacy and toxicity of chemotherapy. This review provides useful information for sex-based chemotherapy and development of personalized therapeutic strategies against cancer.

Sex Differences in Cardiovascular Risk Factors for Dementia

Dementia, characterized by a progressive cognitive decline and a cumulative inability to behave independently, is highly associated with other diseases. Various cardiovascular disorders, such as coronary artery disease and atrial fibrillation, are well-known risk factors for dementia. Currently, increasing evidence suggests that sex factors may play an important role in the pathogenesis of diseases, including cardiovascular disease and dementia. Recent studies show that nearly two-thirds of patients diagnosed with Alzheimer's disease are women; however, the incidence difference between men and women remains vague. Therefore, studies are needed to investigate sex-specific differences, which can help understand the pathophysiology of dementia and identify potential therapeutic targets for both sexes. In the present review, we summarize sex differences in the prevalence and incidence of dementia by subtypes. This review also describes sex differences in the risk factors of dementia and examines the impact of risk factors on the incidence of dementia in both sexes.

Sex-specific Behavioral Features of Rodent Models of Autism Spectrum Disorder

Sex is an important factor in understanding the clinical presentation, management, and developmental trajectory of children with neuropsychiatric disorders. While much is known about the clinical and neurobehavioral profiles of males with neuropsychiatric disorders, surprisingly little is known about females in this respect. Animal models may provide detailed mechanistic information about sex differences in autism spectrum disorder (ASD) in terms of manifestation, disease progression, and development of therapeutic options. This review aims to widen our understanding of the role of sex in autism spectrum disorder, by summarizing and comparing behavioral characteristics of animal models. Our current understanding of how differences emerge in boys and girls with neuropsychiatric disorders is limited: Information derived from animal studies will stimulate future research on the role of biological maturation rates, sex hormones, sex-selective protective (or aggravating) factors and psychosocial factors, which are essential to devise sex precision medicine and to improve diagnostic accuracy. Moreover, there is a strong need of novel strategies to elucidate the major mechanisms leading to sex-specific autism features, as well as novel models or methods to examine these sex differences.

Sex Differences in Neuropathology and Cognitive Behavior in APP/PS1/tau Triple-Transgenic Mouse Model of Alzheimer's Disease / 神经科学通报·英文版

Alzheimer's disease (AD) is the most common form of dementia among the elderly, characterized by amyloid plaques, neurofibrillary tangles, and neuroinflammation in the brain, as well as impaired cognitive behaviors. A sex difference in the prevalence of AD has been noted, while sex differences in the cerebral pathology and relevant molecular mechanisms are not well clarified. In the present study, we systematically investigated the sex differences in pathological characteristics and cognitive behavior in 12-month-old male and female APP/PS1/tau triple-transgenic AD mice (3×Tg-AD mice) and examined the molecular mechanisms. We found that female 3×Tg-AD mice displayed more prominent amyloid plaques, neurofibrillary tangles, neuroinflammation, and spatial cognitive deficits than male 3×Tg-AD mice. Furthermore, the expression levels of hippocampal protein kinase A-cAMP response element-binding protein (PKA-CREB) and p38-mitogen-activated protein kinases (MAPK) also showed sex difference in the AD mice, with a significant increase in the levels of p-PKA/p-CREB and a decrease in the p-p38 in female, but not male, 3×Tg-AD mice. We suggest that an estrogen deficiency-induced PKA-CREB-MAPK signaling disorder in 12-month-old female 3×Tg-AD mice might be involved in the serious pathological and cognitive damage in these mice. Therefore, sex differences should be taken into account in investigating AD biomarkers and related target molecules, and estrogen supplementation or PKA-CREB-MAPK stabilization could be beneficial in relieving the pathological damage in AD and improving the cognitive behavior of reproductively-senescent females.

Sex-Dependent Glial Signaling in Pathological Pain: Distinct Roles of Spinal Microglia and Astrocytes / 神经科学通报·英文版

Increasing evidence suggests that spinal microglia regulate pathological pain in males. In this study, we investigated the effects of several microglial and astroglial modulators on inflammatory and neuropathic pain following intrathecal injection in male and female mice. These modulators were the microglial inhibitors minocycline and ZVEID (a caspase-6 inhibitor) and the astroglial inhibitors L-α-aminoadipate (L-AA, an astroglial toxin) and carbenoxolone (a connexin 43 inhibitor), as well as U0126 (an ERK kinase inhibitor) and D-JNKI-1 (a c-Jun N-terminal kinase inhibitor). We found that spinal administration of minocycline or ZVEID, or Caspase6 deletion, reduced formalin-induced inflammatory and nerve injury-induced neuropathic pain primarily in male mice. In contrast, intrathecal L-AA reduced neuropathic pain but not inflammatory pain in both sexes. Intrathecal U0126 and D-JNKI-1 reduced neuropathic pain in both sexes. Nerve injury caused spinal upregulation of the astroglial markers GFAP and Connexin 43 in both sexes. Collectively, our data confirmed male-dominant microglial signaling but also revealed sex-independent astroglial signaling in the spinal cord in inflammatory and neuropathic pain.

Is There a Sex-Related Difference in the Obesity Paradox in Systolic Heart Failure? Sex-Related Difference in the Obesity Paradox

PURPOSE: Obesity is often associated with better clinical outcomes in heart failure (HF). This so-called obesity paradox remains controversial. The aim of present study was to investigate the prognostic value of obesity in patients hospitalized for systolic HF. MATERIALS AND METHODS: We performed a pooled analysis of data from two multicenter, observational HF studies. Patients hospitalized for systolic HF were eligible for the present study. We divided the subjects into two groups, a normal body mass index (BMI) group and a high BMI group. Study endpoints included all-cause mortality and any re-hospitalization within 1 year. RESULTS: We enrolled 3145 patients (male, 1824; female, 1321). The high BMI group was significantly associated with lower 1-year mortality rate [odds ratio (OR), 0.543; 95% confidence interval (CI), 0.355−0.832] after adjusting for age, hypertension, diabetes, ischemic HF, previous myocardial infarction, serum creatinine level, anemia, and ejection fraction in men. After adjustment for clinical characteristics, high BMI was not significantly associated with 1-year mortality (OR, 0.739; 95% CI, 0.450−1.216) or 1-year re-hospitalization (OR, 0.958; 95% CI, 0.696−1.319) in women. CONCLUSION: In pooled analysis of data from two Korean HF registries, the high BMI group was independently associated with lower 1-year mortality rate from systolic HF, especially in men.

The curative effects of autograft and allograft in anterior cruciate ligament reconstruction / 实用医学杂志

Objective To investigate gender differences in the curative effects of allograft and autologous hamstring tendon in anterior cruciate ligament reconstruction. Methods One hundred and forty-eight patients with the anterior cruciate ligament injury received surgical treatment were enrolled from January 2011 to January 2015 and divided into two groups,including group M(Men)and group W(Women). Patients in each group were also divided in the allograft group (Group A) and the autologous hamstring tendon group (Group B). The patient condition was separately assessed with the Lysholm,Tegner,VAS score and the value of KT-1000 before and after surgery. Results All patients received an average of 16(13-18)-month follow-up visit. No severe complication , such as blood-vessel and nerve injury ,infection and rupture of graft ,occurred in patients after operations. Compared with those before operation,the Lysholm,Tegner,VAS score and the value of KT-1000 after operation in four groups were significantly improved (P 0.05). Conclusions The curative effect of ACL reconstruction between allograft ligament and autologous hamstring tendon has no significant difference in gender. The selection of graft should be considered in more aspects.