Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

Objective To explore the the detection of MMP-2,-7,-9,and-12 enzymatic activity using the CEACAM1-derived fluorescent peptide substrate Site 84,investigating the application of substrate Site 84 to distinguishing between MMP-2 and MMP-9 in the gelatinase spectrum of MMPs.Methods The fluorescent enzymatic method was employed to observe the detection of MMP-2,-7,-9,and-12 enzymatic activity using substrate Site 84;further observations were made on the sensitivity and specificity of substrate Site 84 to enzymatic activity of MMP-2 and MMP-9 within the gelatinase spectrum;the kinetic parameters(Km and Kcat)of the enzymatic reaction between substrate Site 84 and MMP-2 were obtained.Results Using Site 84 as a substrate,enzymic kinetics curves for MMP-12,-7,-2 were obtained,but no enzymatic activity curve for MMP-9 was observed.Furthermore,Site 84 specifically detected the enzymatic activity of MMP-2 within the gelatinase spectrum,capable of detecting low concentration(0.6 μM)of MMP-2 enzymatic activity,but no obvious enzymatic reaction was observed for high concentration(6 μM)of MMP-9;the kinetics parameters for the enzymatic reaction between Site 84 and MMP-2 were Km=315 μM,Kcat/Km=2 565/MS.Conclusion The CEACAM1-derived substrate Site 84 serves as a novel fluorescent peptide substrate,enabling the acquisition of enzymatic activity curves for MMP-12,-7 and-2,and specifically detecting the enzymatic activity of MMP-2 within the MMP gelatinase spectrum.

Diabetic erectile dysfunction is a com-mon complication of diabetes that severely affects the quality of life of men and their sexual partners.Active participation in scientific research on diabet-ic erectile dysfunction is particularly important,and animal models are an important basis for exploring the pathogenesis of the disease,evaluating the effi-cacy of drug treatments,and developing new drugs.The pathogenesis of diabetic erectile dys-function is complex,and current treatments mainly focus on regulating blood sugar,anti-oxidative stress,PDE5 inhibitors,stem cell therapy,inhibiting neurovascular injury,anti-fibrosis,traditional Chi-nese medicine,and other aspects.In particular,cor-recting hyperglycemia is crucial for preventing or stopping the progression of the disease.This article summarizes and updates existing treatment meth-ods by reviewing the latest literature,and reviews the animal models used in different treatment methods,in order to provide a reference for animal experiments and clinical treatment.

Objective To investigate the effects of chronic restraint stress for 28 days(day and night)on mood and cognitive-like behavior in male and female ICR mice,to provide a basis for the selection of sex and restraint period in chronic restraint stress model animals.Methods A total of 72 male and female(1∶1)ICR mice were divided into six groups:male control,daytime restraint,and nighttime restraint groups,and female control,daytime restraint,and nighttime restraint groups.Mice in all but the control groups were bound for 10 h/d and restrained continuously for 28 days to establish a chronic restraint stress model.The emotional and cognitive behaviors induced by restraint in male and female mice at different times were observed by open field,Y maze,novel inhibition feeding,elevated cross maze,tail suspension,forced swimming,and dark-avoidance experiments.Results In the tail suspension experiment,the immobility time of male mice in the daytime restraint group was significantly increased compared with that in the control group(P＜0.05),and the immobility times of male mice in the daytime and nighttime restraint groups were also significantly increased in the forced swimming experiment,compared with those in the control group(P＜0.05).There was no significant difference between the female daytime restraint and female control groups in the novelty inhibition feeding experiment,but the feeding latency of the nighttime restraint group was significantly longer than that of the control group(P＜0.05)and the daytime restraint group(P＜0.05).The feeding latency of female mice was significantly longer than that of males during nighttime restraint(P＜0.05).In the open field test,compared with the male control group,the female control group showed a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).Compared with the female control group,the female daytime restraint group exhibited a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).There was no significant difference between the groups in the elevated cross maze and Y maze experiments.There was no significant difference in dark latency between the daytime restraint group and the control group,but darkness latency was significantly shorter in the nighttime restraint group compared with those in the control group(P＜0.05).When male and female mice were combined,the immobility time in the daytime restraint group was significantly increased in the tail suspension experiment(P＜0.05),the immobility times of mice in the daytime and nighttime restraint groups were significantly increased in the forced swimming experiment(P＜0.01,P＜0.05),and the central zone time and the ratio of central area time to peripheral area time of daytime restraint mice were significantly shorter compared with those in the control group(P＜0.05,P＜0.01).There was no significant difference in the central zone time and the ratio of central area time to peripheral area time in the nighttime restraint groups,and no significant difference in average speed or total distance between the daytime and nighttime restraint groups.Conclusions Male mice exhibited depression after 28 d of chronic restraint stress during the daytime,while female mice were prone to anxiety after 28 d of chronic restraint stress.Male mice experienced learning and memory impairment after 28 d of chronic restraint stress during the night.

Objective To investigate the effects of chronic restraint stress for 28 days(day and night)on mood and cognitive-like behavior in male and female ICR mice,to provide a basis for the selection of sex and restraint period in chronic restraint stress model animals.Methods A total of 72 male and female(1∶1)ICR mice were divided into six groups:male control,daytime restraint,and nighttime restraint groups,and female control,daytime restraint,and nighttime restraint groups.Mice in all but the control groups were bound for 10 h/d and restrained continuously for 28 days to establish a chronic restraint stress model.The emotional and cognitive behaviors induced by restraint in male and female mice at different times were observed by open field,Y maze,novel inhibition feeding,elevated cross maze,tail suspension,forced swimming,and dark-avoidance experiments.Results In the tail suspension experiment,the immobility time of male mice in the daytime restraint group was significantly increased compared with that in the control group(P＜0.05),and the immobility times of male mice in the daytime and nighttime restraint groups were also significantly increased in the forced swimming experiment,compared with those in the control group(P＜0.05).There was no significant difference between the female daytime restraint and female control groups in the novelty inhibition feeding experiment,but the feeding latency of the nighttime restraint group was significantly longer than that of the control group(P＜0.05)and the daytime restraint group(P＜0.05).The feeding latency of female mice was significantly longer than that of males during nighttime restraint(P＜0.05).In the open field test,compared with the male control group,the female control group showed a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).Compared with the female control group,the female daytime restraint group exhibited a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).There was no significant difference between the groups in the elevated cross maze and Y maze experiments.There was no significant difference in dark latency between the daytime restraint group and the control group,but darkness latency was significantly shorter in the nighttime restraint group compared with those in the control group(P＜0.05).When male and female mice were combined,the immobility time in the daytime restraint group was significantly increased in the tail suspension experiment(P＜0.05),the immobility times of mice in the daytime and nighttime restraint groups were significantly increased in the forced swimming experiment(P＜0.01,P＜0.05),and the central zone time and the ratio of central area time to peripheral area time of daytime restraint mice were significantly shorter compared with those in the control group(P＜0.05,P＜0.01).There was no significant difference in the central zone time and the ratio of central area time to peripheral area time in the nighttime restraint groups,and no significant difference in average speed or total distance between the daytime and nighttime restraint groups.Conclusions Male mice exhibited depression after 28 d of chronic restraint stress during the daytime,while female mice were prone to anxiety after 28 d of chronic restraint stress.Male mice experienced learning and memory impairment after 28 d of chronic restraint stress during the night.

Diabetic erectile dysfunction is a com-mon complication of diabetes that severely affects the quality of life of men and their sexual partners.Active participation in scientific research on diabet-ic erectile dysfunction is particularly important,and animal models are an important basis for exploring the pathogenesis of the disease,evaluating the effi-cacy of drug treatments,and developing new drugs.The pathogenesis of diabetic erectile dys-function is complex,and current treatments mainly focus on regulating blood sugar,anti-oxidative stress,PDE5 inhibitors,stem cell therapy,inhibiting neurovascular injury,anti-fibrosis,traditional Chi-nese medicine,and other aspects.In particular,cor-recting hyperglycemia is crucial for preventing or stopping the progression of the disease.This article summarizes and updates existing treatment meth-ods by reviewing the latest literature,and reviews the animal models used in different treatment methods,in order to provide a reference for animal experiments and clinical treatment.

In vivo confocal microscopy of the cornea is a non-invasive, rapid, and comprehensive technique for real-time, dynamic observation of all layers of the cornea. Confocal microscopy allows the examination of the morphology and cell density in the different layers of the cornea through direct visualization. With the increasing prevalence of diabetes, ocular complications have become common and have garnered more interest and in-depth research from clinical and scientific communities. This paper provides a comprehensive review of research progress made using in vivo confocal microscopy to observe various layers of cornea tissue in diabetic patients.

Objective:To analyze the clinical characteristics of three patients with Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome.Methods:Three patients with IPEX syndrome diagnosed at the Children′s Hospital of Fudan University from January 24, 2013 to July 29, 2019 were selected as the study subjects. Their clinical features, laboratory investigations and results of genetic testing were summarized. Treatment and prognosis were also explored.Results:All of the three children had developed the disorder during infancy. One child had initial features including diabetes and diabetic ketoacidosis, whilst the other two had initiated by diarrhea. All patients had gastrointestinal involvement, and one was diagnosed as very early onset inflammatory bowel disease by colonoscopy and biopsy. Two children also had endocrine glands involvement. One child had manifested type 1 diabetes and positivity for thyroglobulin and thyroid peroxidase antibodies, though his thyroid function had remained normal. Another one had hypothyroidism and was treated by levothyroxine. Genetic testing revealed that all children had harbored missense variants of the FOXP3 gene, including c. 1222G>A (p.V408M), c. 767T>C (p.M256T) and c. 1021A>G (p.T341A). The clinical symptoms of one patient were alleviated following allogeneic hematopoietic stem cell transplantation. One patient was stable after treatment with infliximab plus insulin, and one child had died of refractory septic shock and multiple organ dysfunction syndrome at 3 months old. Conclusion:FOXP3 gene variant-associated IPEX syndrome may have very early onset and diverse clinical manifestations. For male patients with infantile onset chronic diarrhea, multiple endocrine or multiple system involvement, genetic testing is recommended, which may facilitate early diagnosis, treatment and genetic counseling.

Objective:To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China.Methods:A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test.Results:A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) μg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region ( χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference ( χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) ( χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant ( χ2=0.51, P=0.476). Conclusions:There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.

Objective: To explore the intervention effect of sedentary interval on body composition and blood lipid metabolism of obese female college students, so as to provide reference for health promotion among obese students. Methods: Eighty obese female college students from first and second grades were randomly assigned into three groups, the control group ( n =28), experimental group A ( n =26), and experimental group B ( n =26), between September and November 2022. The participants received appropriate dietary guidance, a 90-minute optional physical education course was offered to control group once a week, on the basis of the control group, experimental group A performed 5-minute-intermittent brisk walking (6 km/h) during each break. Experimental group B performed 5-minute-intermittent brisk walking (6 km/h) during each break for the first 4 weeks, then changed to 4-minute-brisk walking (6 km/h) and 1-minute-rope skipping (60 skips/min) during each break for weeks 5-8, and changed to 4-minute-brisk walking (6 km/h) and 1-minute-rope skipping (80 skips/min) during each break for 9-12 weeks. The intervention was performed 10 times per day, with the interruption time and frequency on weekends remaining the same. Body mass index (BMI), body fat rate (BFR), waist hip ratio (WHR), visceral fat index (VFI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured before and after the experiment. Results: After 12 weeks intervention, there were no significant differences in body composition and blood lipids in control group ( P >0.05), BMI, BFR, VFI and TG in Group A were lower than those before intervention ( t=3.20, 2.80, 8.19, 2.21, P <0.05), BMI, BFR, WHR, VFI, TG, TC, LDL-C were lower and HDL-C in group B were higher than those before intervention ( t=6.27, 5.85, 10.82 , 19.91, 3.86, 3.29, 7.20, -4.93, P <0.01). There were significant differences in BMI, BFR, WHR, VFI and HDL-C among the three groups ( F=24.01, 23.77, 10.00, 15.28, 6.72, P <0.01), and the intervention effects of BMI, BFR and HDL-C in group B were better than those in group A and control group ( P <0.01). Conclusion The intervention of brisk walking and rope skipping had a good effect on improving body composition and blood lipid metabolism of obese female college students. Schools should make good use of the time between classes and adopt short-time and high-intensity exercise intervention to improve the body composition and blood lipid metabolism of obese students.