Study on sex differences and potential clinical value of threedimensional computerized tomography pelvimetry in rectal cancer patients

BACKGROUND Laparoscopic rectal cancer radical surgery is a complex procedure affected by various factors.However,the existing literature lacks standardized parameters for the pelvic region and soft tissues,which hampers the establishment of consistent conclusions.AIM To comprehensively assess 16 pelvic and 7 soft tissue parameters through computerized tomography(CT)-based three-dimensional(3D)reconstruction,providing a strong theoretical basis to address challenges in laparoscopic rectal cancer radical surgery.METHODS We analyzed data from 218 patients who underwent radical laparoscopic surgery for rectal cancer,and utilized CT data for 3D pelvic reconstruction.Specific anatomical points were carefully marked and measured using advanced 3D modeling software.To analyze the pelvic and soft tissue parameters,we emp-loyed statistical methods including paired sample t-tests,Wilcoxon rank-sum tests,and correlation analysis.RESULTS The investigation highlighted significant sex disparities in 14 pelvic bone parameters and 3 soft tissue parameters.Males demonstrated larger measurements in pelvic depth and overall curvature,smaller measurements in pelvic width,a larger mesorectal fat area,and a larger anterior-posterior abdominal diameter.By contrast,females exhibited wider pelvises,shallower depth,smaller overall curvature,and an increased amount of subcutaneous fat tissue.However,there were no significant sex differences observed in certain parameters such as sacral curvature height,superior pubococcygeal diameter,rectal area,visceral fat area,waist circumference,and transverse abdominal diameter.CONCLUSION The reconstruction of 3D CT data enabled accurate pelvic measurements,revealing significant sex differences in both pelvic and soft tissue parameters.This study design offer potential in predicting surgical difficulties and creating personalized surgical plans for male rectal cancer patients with a potentially“difficult pelvis”,ultimately improving surgical outcomes.Further research and utilization of these parameters could lead to enhanced surgical methods and patient care in laparoscopic rectal cancer radical surgery.

Three-dimensional analysis of age and sex differences in femoral head asphericity in asymptomatic hips in the United States

BACKGROUND The sphericity of the femoral head is a metric used to evaluate hip pathologies and is associated with the development of osteoarthritis and femoral-acetabular impingement.AIM To analyze the three-dimensional asphericity of the femoral head of asymptomatic pediatric hips.We hypothesized that femoral head asphericity will vary significantly between male and female pediatric hips and increase with age in both sexes.METHODS Computed tomography scans were obtained on 158 children and adolescents from a single institution in the United States(8-18 years;50%male)without hip pain.Proximal femoral measurements including the femoral head diameter,femoral head volume,residual volume,asphericity index,and local diameter difference were used to evaluate femoral head sphericity.RESULTS In both sexes,the residual volume increased by age(P<0.05).Despite significantly smaller femoral head size in older ages(>13 years)in females,there were no sex-differences in residual volume and aspherity index.There were no age-related changes in mean diameter difference in both sexes(P=0.07)with no significant sex-differences across different age groups(P=0.06).In contrast,there were significant increases in local aspherity(maximum diameter difference)across whole surface of the femoral head and all quadrants except the inferior regions in males(P=0.03).There were no sex-differences in maximum diameter difference at any regions and age group(P>0.05).Increased alpha angle was only correlated to increased mean diameter difference across overall surface of the femoral head(P=0.024).CONCLUSION There is a substantial localized asphericity in asymptomatic hips which increases with age in.While 2D measured alpha angle can capture overall asphericity of the femoral head,it may not be sensitive enough to represent regional asphericity patterns.

Keep in mind sex differences when prescribing psychotropic drugs

Women represent the majority of patients with psychiatric diagnoses and also the largest users of psychotropic drugs.There are inevitable differences in efficacy,side effects and long-term treatment response between men and women.Psychopharmacological research needs to develop adequately powered animal and human trials aimed to consider pharmacokinetics and pharmacodynamics of central nervous system drugs in both male and female subjects.Healthcare professionals have the responsibility to prescribe sex-specific psychopharmacotherapies with a priority to differentiate between men and women in order to minimize adverse drugs reactions,to maximize therapeutic effectiveness and to provide personalized management of care.

Sex differences in the association between the muscle quality index and the incidence of depression: A cross-sectional study

BACKGROUND Depression presents significant challenges to mental health care.Although phy-sical activity is highly beneficial to mental and physical health,relatively few stu-dies have conducted on the relationship between them.AIM To investigate the association between muscle quality index(MQI)and incidence of depression.METHODS The data used in this cross-sectional study were obtained from the 2011-2014 National Health and Nutritional Examination Survey,which included informa-tion on MQI,depression,and confounding factors.Multivariable logistic regre-ssion models were employed,while taking into account the complex multi-stage sampling design.A restricted cubic spline model was utilized to investigate the non-linear relationship between the MQI and depression.Additionally,subgroup analyses were performed to identify influential factors.RESULTS The prevalence of depression in this population was 8.44%.With the adjusted model,the MQI was associated with depression in females(odds ratio=0.68,95%confidence interval:0.49-0.95)but not in males(odds ratio=1.08,95%confidence interval:0.77-1.52).Restricted cubic spline adjustment of all covariates showed a significant negative non-linear relationship between depression and the MQI in females.The observed trend indicated an 80%decrease in the risk of depression for each unit increase in MQI,until a value of 2.2.Subsequently,when the MQI exceeded 2.2,the prevalence of depression increased by 20%for every unit increase in the MQI.Subgroup analyses further confirmed that the MQI was negatively associated with de-pression.CONCLUSION The MQI was inversely correlated with depression in females but not males,suggesting that females with a higher MQI might decrease the risk of depression.

Sex differences in the scored Patient-Generated Subjective Global Assessment in 19,528 cancer patients

Background:The scored Patient-Generated Subjective Global Assessment(PG-SGA)has been widely used to assess the nutritional status of cancer patients.The purpose of this study is to compare the differences in PG-SGA scores and the 7 domain scores of the PG-SGA in male and female cancer patients.Methods:This study was conducted at 72 hospitals from July 2013 to December 2018,a part of the Investigation on Nutritional Status and its Clinical Outcomes of Common Cancers.The PG-SGA was recorded to evaluate the nutritional status of patients.A total of 19,528 patients with 13 common malignancies were included in this study.Student t test and the χ^(2) test were applied to analyze the sex diferences in the 7 domain scores.The Cancer Genome Atlas(TCGA)database was used to analyze the expression levels of symptom-related genes.Results:There were significant sex dfferences in the PG-SGA(P=0.032),notably in patients with gastric cancer(male vs female:9.09±4.86 vs 9.58±5.07,P=0.005)and esophageal cancer(9.64±4.90 vs 10.46±4.96,P=0.011)and the average total PG-SGA of female patients was slightly higher than that of male patients(7.64±4.98 vs 7.77±5.14).The differences were mainly related to the weight,eating,symptom,as well as activity and physical function scores in the stratified analysis.Possible causes of the sex differences were the rates of nausea,vomiting,dry mouth,and other symptoms,in both gastric and esophageal cancer patients.Analysis of the TCGA database suggested that most of the related genes were sex neutral,except for genes related to dysphagia in gastric cancer(VEGFC was higher in female patients,VEGFA and VEGFB higher in male patients).Conclusions:There are sex differences in the PG-SGA scores in patients with various tumor types(female patients generally had higher scores than male patients),with differences mainly in the weight,eating,symptom,as well as activity and physical function scores.The sex differences in PG-SGA scores might be due to the differences in the clinical manifestations of the disease,and further studies should be carried out to investigate other factors influencing the PG-SGA scores in cancer patients.This study provides basic data supporting the individualized nutritional treatment of cancer patients in clinical practice.

Sex differences and effects of oestrogen in rat gastric mucosal defence

AIM To evaluate sex differences and the effects of oestrogen administration in rat gastric mucosal defence.METHODS Sex differences in gastric mucus thickness and accumulation rate, absolute gastric mucosal blood flow using microspheres, the integrity of the gastric mucosal epithelium in response to a chemical irritant and the effects of oestrogen administration on relative gastric mucosal blood flow in an acute setting was assessed in an in vivo rat experimental model. Subsequently, sex differences in the distribution of oestrogen receptors and calcitonin gene related peptide in the gastric mucosa of animals exposed to oestrogen in the above experiments was evaluated using immunohistochemistry.RESULTS The absolute blood flow in the GI-tract was generally higher in males, but only significantly different in the corpus part of the stomach (1.12 ± 0.12 m L/min·g in males and 0.51 ± 0.03 m L/min·g in females) (P = 0.002). After removal of the loosely adherent mucus layer the thickness of the firmly adherent mucus layer in males and females was 79 ± 1 μm and 80 ± 3 μm respectively. After 60 min the mucus thickness increased to 113 ± 3 μm in males and 121 ± 3 μm in females with no statistically significant difference seen between the sexes. Following oestrogen administration(0.1 followed by 1 μg/kg·min), mean blood flow in the gastric mucosa decreased by 31% [68 ± 13 perfusion units (PFU)] in males which was significantly different compared to baseline(P = 0.02). In females however, mean blood flow remained largely unchanged with a 4% (5 ± 33 PFU) reduction. The permeability of the gastric mucosa increased to a higher level in females than in males (P = 0.01) after taurocholate challenge. However, the calculated mean clearance increase did not significantly differ between the sexes [0.1 ± 0.04 to 1.1 ± 0.1 m L/min·100 g in males and 0.4 ± 0.3 to 2.1 ± 0.3 m L/min·100 g in females(P = 0.065)]. There were no significant differences between 17β-Estradiol treated males (mean ratio of positive staining ± SEM)(0.06 ± 0.07) and females(0.11 ± 0.11) in the staining of ERα (P = 0.24). Also, there were no significant differences between 17β-Estradiol treated males (0.18 ± 0.21) and females (0.06 ± 0.12) in the staining of ERβ (P = 0.11). Finally, there were no significant differences between 17β-Estradiol treated males (0.04 ± 0.05) and females (0.11 ± 0.10) in the staining of CGRP(P = 0.14).CONCLUSION Gastric mucosal blood flow is higher in male than in female rats and is reduced in male rats by oestrogen administration.

Associations of gut microbiota with dyslipidemia based on sex differences in subjects from Northwestern China

BACKGROUND The gut microbiota(GM)has been proven to play a role in the regulation of host lipid metabolism,which provides a new theory about the pathogenesis of dyslipidemia.However,the associations of GM with dyslipidemia based on sex differences remain unclear and warrant elucidation.AIM To investigate the associations of GM features with serum lipid profiles based on sex differences in a Chinese population.METHODS This study ultimately recruited 142 participants(73 females and 69 males)at Honghui Hospital,Xi’an Jiaotong University.The anthropometric and blood metabolic parameters of all participants were measured.According to their serum lipid levels,female and male participants were classified into a high triglyceride(H_TG)group,a high total cholesterol(H_CHO)group,a low high-density lipoprotein cholesterol(L_HDL-C)group,and a control(CON)group with normal serum lipid levels.Fresh fecal samples were collected for 16S rRNA gene sequencing.UPARSE software,QIIME software,the RDP classifier and the FAPROTAX database were used for sequencing analyses.RESULTS The GM composition at the phylum level included Firmicutes and Bacteroidetes as the core GM.Different GM features were identified between females and males,and the associations between GM and serum lipid profiles were different in females and males.The GM features in different dyslipidemia subgroups changed in both female patients and male patients.Proteobacteria,Lactobacillaceae,Lactobacillus and Lactobacillus_salivarius were enriched in H_CHO females compared with CON females,while Coriobacteriia were enriched in L_HDL-C females.In the comparison among the three dyslipidemia subgroups in females,Lactobacillus_salivarius were enriched in H_CHO females,and Prevotellaceae were enriched in L_HDL-C females.Compared with CON or H_TG males,Prevotellaceae,unidentified_Ruminococcaceae,Roseburia and Roseburia_inulinivorans were decreased in L_HDL-C males(P value<0.05),and linear discriminant analysis effect size analysis indicated an enrichment of the above GM taxa in H_TG males compared with other male subgroups.Additionally,Roseburia_inulinivorans abundance was positively correlated with serum TG and total cholesterol levels,and Roseburia were positively correlated with serum TG level.Furthermore,Proteobacteria(0.724,95%CI:0.567-0.849),Lactobacillaceae(0.703,95%CI:0.544-0.832),Lactobacillus(0.705,95%CI:0.547-0.834)and Lactobacillus_salivarius(0.706,95%CI:0.548-0.835)could distinguish H_CHO females from CON females,while Coriobacteriia(0.710,95%CI:0.547-0.841),Coriobacteriales(0.710,95%CI:0.547-0.841),Prevotellaceae(0.697,95%CI:0.534-0.830),Roseburia(0.697,95%CI:0.534-0.830)and Roseburia_inulinivorans(0.684,95%CI:0.520-0.820)could discriminate H_TG males from CON males.Based on the predictions of GM metabolic capabilities with the FAPROTAX database,a total of 51 functional assignments were obtained in females,while 38 were obtained in males.This functional prediction suggested that cellulolysis increased in L_HDL-C females compared with CON females,but decreased in L_HDL-C males compared with CON males.CONCLUSION This study indicates associations of GM with serum lipid profiles,supporting the notion that GM dysbiosis may participate in the pathogenesis of dyslipidemia,and sex differences should be considered.

Sex differences in SARS-CoV-2 infections,anti-viral immunity and vaccine responses

The COVID-19 pandemic has revealed sex-based differences in anti-viral responses,with a higher rate of SARS-CoV-2 infections as well as a higher rate of morbidity and mortality in men than in women.Males and females also show disparate immune responses to COVID-19 infection,which may be important contributors to lower rates of infection,disease severity and deaths in women than in men.Here,the authors review sex differences in SARS-CoV-2 infections,anti-viral immunity and vaccine responses,putting forth the importance of sex,the underappreciated variables in vaccine response and disease infectivity.

Sex differences in exercise and drug addiction:A mini review of animal studies

Growing literature has demonstrated that exercise may be an effective prevention and treatment option for drug addiction. In the past few years, many studies have suggested that there were sex differences in all phases of drug addiction. However, very limited research has investigated sex differences in the effectiveness of exercise intervention in drug addiction and rehabilitation. In this mini review, we summarize the effect of sex on the results of using exercise to prevent and treat drug addiction. The studies we consider span various animal models and use multiple types of exercise to examine the effectiveness of exercise on the neurobiological mechanism of exercise rehabilitation. We believe that exercise as an adjuvant intervention strategy can be applied better in drug addiction prevention and recovery. Copyright 2014, Shanghai University of Sport. Production and hosting by Elsevier B.V. All rights reserved.

Sex Difference in the Repolarization Currents of Rabbit Ventricular Cells

The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, I_to, I_K,tail, I_K1 and I_Ca,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD_90 was longer in female rabbits (560.4±26.5 ms, n=15) than in male ones (489.0±20.7 ms, n=14), P<0.05. In female rabbit myocytes, I_K,tail, I_to, I_K1 and I_Ca,L were 0.71±0.05 pA/pF (n=17), 8.28±1.03 pA/pF (n=18), 24.5±3.6 pA/pF (n=12) and 9.0±2.3 pA/pF (n=15) respectively. In male rabbit myocytes, they were 0.84±0.07 pA/pF (n=18), 8.60±1.20 pA/pF (n=18), 25.9±4.5 pA/pF (n=14) and 9.3±2.6 pA/pF (n=16) respectively. I_K,tail in female rabbits was significantly lower than that of male rabbits (P<0.05), but there was no difference in I_to, I_K1 and I_Ca,L between male rabbits and female rabbits (P>0.05). The lower I_K,tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.

Sex Differences in Reconstructed Resting-State Functional Brain Networks for Children

Neuroscience studies have demonstrated that functional differences in human brains between males and females might result in their cognitive and psychological distinctions. To investigate sex differences in resting-state functional networks for children, the functional brain networks of two groups including boys and girls were reconstructed by functional connectivity with significant between-group differences respectively based on two brain atlases, and then the reconstructed functional networks were compared from the viewpoint of small-world properties. The functional brain networks of the two groups both displayed topological properties of the small-world network based on different brain atlases but exhibited some sex differences in certain measures. Specifically, for the automated anatomical labeling atlas, compared with girls, boys showed stronger small-world properties and higher ability of local information processing in brain networks;for the Harvard Oxford Atlas, the shortest path length of boys increased, indicating poorer performance in both global information transmission and resistance to the random attack.

Effects of Sex Differences and Problem-Solving Strategies on Digital Game Performance

Problem-solving strategy i,,; a critical skill in inquiry-based learning. Several studies have investigated how to use learning games to improve inquiry abilities. However, not every learner favors this kind of approach. Thus, we need to examine how human factors affect learners＇ reactions to the use of a digital game to support inquiry-based learning. This study addressed this issue by developing a digital game, ＂Baking Town＂, and using the game to examine the effects of two central human factors, sex differences and problem-solving strategies, on students＇ performance. The results demonstrate that students＇ inquiry abilities were significantly improved after they participated in the digital game. The results also demonstrate that the digital game may be a feasible way to reduce differences between boys and girls in this domain. Finally, we used the findings to develop a framework that can be used to enhance our understanding of sex differences and the use of problem-solving strategies in the context of digital games.

Sex Differences in Clinical and Angiographic Characteristics in Acute Coronary Syndrome Patients in Dakar, Senegal

Background: Coronary artery disease (CAD) is in relentless progression, along with the adoption of western lifestyle in sub-Saharan Africa. In Senegal, the incidence of acute coronary syndrome (ACS) rose from 5% to 12% in Dakar during the last 20 years. That increase was observed in both women and men, and according to current data, the former paid the heaviest price in terms of mortality compared to men. In this study, we aim to retrospectively assess the clinical characteristics and angiographic profile of ACS in women compared to men in two tertiary care centers in Dakar. Methods: In this study, we retrospectively analyzed and compared data between men and women among 133 patients who underwent coronary angiogram for ACS in 2 tertiary centers from February 2019 to January 2020. Results: A total of 133 patients were included in our study of whom 97 (72.9%) were men. The mean age was 58 ± 13.6 years. Women were older than men (61.4 ± 14.3 years vs 56.6 ± 13.5 years (p = 0.07). Hypertension, sedentary lifestyle and obesity were significantly more frequent in women (69.4%, 52.7% and 19.4%) when compared to men (38.8%, 25.7% and 6.19%) respectively, (p = 0.001;0.002 and 0.03). Smoking was less frequent in women (2.8%) than in men (44.3%), (p Conclusion: In our study, women with ACS were older, had more cardiovascular risk factors but less angiographic extent of disease than men.

Sex differences in muscle health in simulated micro-and partial-gravity environments in rats

Skeletal muscle size and strength are important for overall health for astronauts.However,how male and female muscle may respond differently to micro-and partial-gravity environments is not fully understood.The purpose of this study was to determine how biological sex and sex steroid hormones influence the progression of muscle atrophy after long term exposure to micro and partial gravity environments in male and female rats.Male and female Fisher rats(n=120)underwent either castration/ovariectomy or sham surgeries.After two weeks recovery,animals were divided into microgravity(0g),partial-gravity(40%of weight bearing,0.4g),or full weight bearing(1g)interventions for 28 days.Measurements of muscle size and strength were evaluated prior to and after interventions.At 0g,females lost more dorsiflexion strength,plantar flexion strength,and other metrics of muscle size compared to males;castration/ovariectomy did not influence these differences.Additionally,at 0.4g,females lost more dorsiflexion strength,plantar flexion strength,and other metrics of muscle strength compared to males;castration/ovariectomy did not influence these differences.Females have greater musculoskeletal aberrations during exposure to both microgravity and partial-gravity environments;these differences are not dependent on the presence of sex steroid hormones.Correspondingly,additional interventions may be necessary to mitigate musculoskeletal loss in female astronauts to protect occupational and overall health.

Sex differences in eye movements and neural oscillations during mental rotation in virtual reality

Virtual reality(VR)has been a promising tool for developing visuospatial tasks.Among visuospatial tasks,mental rotation tasks are widely used in the assessment of visuospatial ability.Males have a distinct advantage in mental rotation ability compared to females,yet it is generally produced by investigations based on two-dimensional(2D)images on a computer screen.Sex differences in mental rotation tasks with three-dimensional(3D)objects in VR were not fully investigated.It is unclear whether the male's advantages in 2D mental rotation tasks are weakened in 3D tasks.The aim of this study was to provide new insights into the understanding of sex differences in mental rotation tasks presented in VR.Here,we developed a VR mental rotation task(VR-MRT)using 3D objects presented by a head-mounted display(HMD)and used VR-based eye tracking and electroencephalography(EEG)to examine eye movements and neural oscillations for males and females.Our results showed that females preferred a piecemeal strategy compared to males,suggesting a significant sex difference in visual strategy.More importantly,we found no significant sex differences in alpha-band and beta-band oscillations related to rotation processes of VR-MRT.These findings indicated that sex differences in the VR-MRT were mainly attributed to the selection of visual strategy rather than the rotation processes.The study helps to comprehensively understand the dominant factors contributing to the sex differences in the VR-MRT.

Hard life for sons in the nest?Sex-dependent offspring mortality in Great Tits in urban and forest areas

Sex-biased mortality can occur in birds during development,for example due to sexual differences in energy requirement and/or environmental sensitivity,or the effects of sex hormones or sex differences in the expression of mutations linked to sex chromosomes.The extent of sex-bias in mortality may also be related to environmental conditions that influence offspring development and survival.Urban areas often provide poorer conditions for nestling development resulting in higher offspring mortality compared to natural areas,which may accelerate sex differences in offspring mortality in cities.To test this hypothesis,we examined the sex ratio of dead offspring in Great Tits(Parus major),using 427 samples of unhatched eggs and dead nestlings collected in two urban and two forest sites between 2013 and 2019.The ratio of males in the whole sample of dead offspring(56.9%)was significantly higher than expected by an 1:1 ratio,and the strongest sex biases were detected in urban areas(57.6%males)and in young nestlings(<14 days old,59.0%males).However,the sex ratios of dead offspring did not differ significantly among study sites and between offspring developmental stages.29.3%of unhatched eggs contained a visible embryo,and the proportion of embryo-containing unhatched eggs did not differ significantly between urban and forest study sites.These results suggest male-biased offspring mortality in Great Tits,and highlight the need of large datasets to detect subtle differences between habitats and developmental stages.

Sex differences in morphine dependence and plasma levels of morphine and morphine-3-glucuronide in rats

To examine whether there are sex differences in morphine dependence and its metabolism. Naloxone-precipitated withdrawal study was performed. Twenty rats were induced by naloxone 1 h after a single dose of morphine injection. The withdrawal syndromes were recorded and an HPLC-UV method was set up to quantify the plasma levels of morphine and morphine-3-glucuronide（M3G）. In the spontaneous withdrawal study, 97 rats were treated with progressive morphine for 28 d to develop physical dependence. The spontaneous withdrawal syndromes were recorded and plasma levels of morphine and M3G were determined after the last injection. No significant differences were observed in withdrawal syndrome of naloxone precipitating. More severe spontaneous withdrawal syndromes were produced by chronic morphine injection in male rats than in female rats（P0.05）. Higher maximum plasma concentration（Cmax） of morphine was measured in male rats than female rats, while female rats had higher Cmax of M3G than male rats in both acute and chronic morphine administration. Our results indicated that sex differences existed in withdrawal syndrome of morphine-dependent rats, and the pharmacokinetics of morphine showed sex difference by both acute and chronic administration. There might be a relationship between the severity of withdrawal syndrome and the plasma concentrations of morphine, M3G, and the ratio of morphine to M3G（M3G/MOR）.

Sex Differences in Neuropathology and Cognitive Behavior in APP/PS1/tau Triple-Transgenic Mouse Model of Alzheimer's Disease

Alzheimer＇s disease （AD） is the most common form of dementia among the elderly, characterized by amyloid plaques, neurofibrillary tangles, and neuroinflam- mation 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/PSI/tau triple-trans- genic AD mice （3xTg-AD mice） and examined the molecular mechanisms. We found that female 3×Tg-AD mice displayed more prominent amyloid plaques, neurofib- rillary tangles, neuroinflammation, and spatial cognitive deficits than male 3×Tg-AD mice. Furthermore, the expres- sion 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.

Estrogen Receptor-A in Medial Preoptic Area Contributes to Sex Difference of Mice in Response to Sevoflurane Anesthesia

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(ERa),particularly in neuronal clusters that participate in regulating sleep.We found that male mice were more sensitive to sevoflurane.Pharmacological inhibition of ERαin 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 ERαin 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 ERαpositively regulates the activity of MPA GABAergic neurons in males but not in females,which contributes to the sexdifference of mice in sevoflurane anesthesia.

Sex-based differences in histology,staging,and prognosis among 2983 gastric cancer surgery patients

BACKGROUND Few studies have been conducted on sex differences in the incidence, pathophysiology, and prognosis of gastric cancer(GC).AIM To analyze the differences in GC characteristics according to sex in patients who underwent surgical treatment for GC.METHODS A total of 2983 patients diagnosed with gastric adenocarcinoma who received surgical treatment at the Seoul National University Bundang Hospital between 2003 and 2017 were included.Baseline clinicopathological characteristics, histologic type of GC, overall and GC-specific survival rates, and associated risk factors were analyzed.RESULTS Among the 2983 patients, 2005(67.2%) and 978(32.8%) were males and females, respectively.The average age of the female group(59.36 years) was significantly younger than that of the male group(61.66 years;P < 0.001).Cancer of the gastric body(P < 0.001) and diffuse-type histology(P < 0.001) were more common in females than in males.This trend was more prominent in females younger than 60 years of age, with a significantly higher proportion of diffuse-type cancer than in the male group.Regardless of sex, diffuse-type GC was more common in younger patients, and the proportion of intestinal-type GC increased with age.The overall survival rate was significantly higher in females(P < 0.001).However, this difference disappeared for GC-specific survival(P = 0.168), except for the poor GC-specific survival rate in advanced-stage cancer(stage Ⅲ or above) in females(P = 0.045).The risk factors for GC-related mortality were older age, upper location of GC, and diffuse-or mixed-type histology.In terms of comorbidities, more males died from diseases other than GC, including other malignancies such as lung cancer, hepatocellular carcinoma, and pancreatic cancer, and respiratory diseases such as interstitial lung disease and chronic obstructive pulmonary disease, while there were relatively more cardiovascular or cerebrovascular deaths in females.CONCLUSION Sex-based differences in GC were observed in clinicopathological features, including age at diagnosis, tumor location, histologic type, survival rate, and comorbidities.