ObjectiveTo explore the mechanisms through which Si Junzitang （SJZD） ameliorates Alzheimer's disease （AD） induced by scopolamine （SCOP） in mice and the PC12 cell model induced by H₂O₂ based on the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsIn the animal experiments， an AD model was established in mice by intraperitoneal injection of SCOP （3 mg·kg^-1）. Morris water maze and open field tests （OFT） were conducted to assess learning and memory abilities. Hematoxylin-eosin （HE） staining and Nissl staining were performed to observe pathological changes in neurons. Immunofluorescence was used to detect amyloid β-protein_1-42 （Aβ_1-42） expression， and immunohistochemistry was employed to detect phosphorylated （p）-Tau expression. Transmission electron microscopy （TEM） was employed to observe ultrastructural changes in hippocampal neurons and synapses. Biochemical methods were used to measure the levels of acetylcholine （ACh）， acetylcholinesterase （AChE）， superoxide dismutase （SOD）， malondialdehyde （MDA）， catalase （CAT）， and lactate dehydrogenase （LDH）. Real-time PCR and Western blot were employed to measure the mRNA and protein levels of molecules in the Keap1/Nrf2/HO-1 pathway in the hippocampus. In the cell experiments， a PC12 cell model of oxidative damage model was established with H₂O₂. Cell count kit-8 （CCK-8） assays and flow cytometry were adopted to measure cell viability and apoptosis rates， and Western blot was employed to quantify the expression levels of proteins in the Keap1/Nrf2/HO-1 pathway. ResultsThe animal experiments showed that compared with the model group， the SJZD and donepezil groups showed shortened escape latency （P<0.01）， increased time in the target quadrant and platform crossings， and increased movement distance and duration in the central area of the open field （P<0.05， P<0.01）. HE and Nissl staining showed more organized neurons and increased Nissl bodies in the drug intervention groups （P<0.05， P<0.01）， and the Aβ_1-42 and p-Tau expression levels were downregulated （P<0.05， P<0.01）. TEM revealed reduced ultrastructural damage in hippocampal neurons and synapses in the drug intervention groups. In addition， the drug intervention groups showed declined levels of MDA， LDH， and AChE （P<0.05， P<0.01）， elevated levels of SOD， CAT， and ACh （P<0.05， P<0.01）， reduced Keap1 expression and increased Nrf2， HO-1， and NQO1 expression in the hippocampus （P<0.05， P<0.01）. The cell experiments showed that compared with the model group， the SJZD-containing serum increased the cell viability （P<0.05， P<0.01）， and decreased total apoptosis rates （P<0.05， P<0.01）. The drug intervention groups showed upregulated protein levels of Nrf2 and HO-1 and downregulated protein level of Keap1 （P<0.05， P<0.01）. ConclusionSJZD demonstrates protective effects against SCOP-induced AD in mice and H₂O₂-induced damage in PC12 cells through antioxidant mechanisms mediated by the Keap1/Nrf2/HO-1 pathway.

Objective:To investigate the alterations in voxel-mirrored homotopic connectivity (VMHC) of brain regions, association loop connectivity, and white matter microstructure in patients with white matter hyperintensities (WMH) of presumed vascular origin, and analyze the pathological basis of cognitive impairment in WMH patients.Methods:A prospective study was performed; 75 WMH patients (WMH group) admitted to Jiangsu Shengze Hospital Affiliated to Nanjing Medical University from January 2023 to September 2024 and 67 volunteers without obvious brain diseases (control group) recruited during the same period were enrolled. General data of these participants, and scores of neuropsychological scales such as mini-mental state examination (MMSE), frontal assessment battery (FAB), and trail making test (TMT) were compared between the two groups. Resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) data of all participants were collected; rs-fMRI data were then analyzed using VMHC algorithm to calculate and conform the brain regions with significantly different VMHC between the two groups, and these regions were used as seed points to perform functional connectivity with the whole brain; Pearson correlation analyses of VMHC and functional connectivity in these brain regions with scores of neuropsychological scales were performed. DTI data were processed using tract-based spatial statistics (TBSS) method to calculate and conform the brain regions with significantly different diffusion parameters of fiber tracts between the two groups; Pearson correlation analyses of diffusion parameters of the fiber tracts in these brain regions with scores of neuropsychological scales were performed.Results:(1) Comparison of general data and neuropsychological scale scores: proportion of participants with hypertension history was significantly different between the two groups ( P<0.05); scores of TMT-A, TMT-B, and Stroop C scales in the WMH group were significantly higher than those in the control group ( P<0.05). (2) Comparison of VMHC and seed point functional connectivity: compared with that in the control group, the VMHC in bilateral middle occipital gyrus, visual cortex, medial occipitotemporal gyrus, insula, and postcentral gyrus of the WMH group were statistically lower ( P<0.05). Compared with that in the control group, functional connectivity of right visual cortex with right middle temporal gyrus, bilateral precuneus, and right dorsolateral superior frontal gyrus in the WMH group was significantly weakened, and functional connectivity of right postcentral gyrus with right medial occipitotemporal gyrus, left middle temporal gyrus, left visual cortex, and left postcentral gyrus was statistically weakened ( P<0.05). In the WMH group, the VMHC of bilateral insula was negatively correlated with TMT-B score ( r=-0.381, P<0.001), and functional connectivity between right visual cortex and right dorsolateral superior frontal gyrus was negatively correlated with Stroop C score ( r=-0.401, P<0.001). (3) TBSS results: the diffusion parameters of the anterior corona radiata, superior corona radiata, corpus callosum, superior longitudinal fasciculus, and posterior thalamic radiation were statistically significant between the two groups ( P<0.05). In the WMH group, the fractional anisotropy in the genu of the corpus callosum was positively correlated with Stroop C score ( r=0.426, P<0.001), radial diffusivity was negatively correlated with Stroop C score ( r=-0.376, P<0.001), and mean diffusivity of the left anterior corona radiata was negatively correlated with TMT-A score ( r=-0.443, P<0.001). Conclusion:WMH patients have decreased coordination in homotopic brain regions and weakened functional connectivity of association loops, with widely distributed white matter microstructure damages, which may be involved in the neuropathological process of cognitive impairment.

Objective:To investigate the alterations in voxel-mirrored homotopic connectivity (VMHC) of brain regions, association loop connectivity, and white matter microstructure in patients with white matter hyperintensities (WMH) of presumed vascular origin, and analyze the pathological basis of cognitive impairment in WMH patients.Methods:A prospective study was performed; 75 WMH patients (WMH group) admitted to Jiangsu Shengze Hospital Affiliated to Nanjing Medical University from January 2023 to September 2024 and 67 volunteers without obvious brain diseases (control group) recruited during the same period were enrolled. General data of these participants, and scores of neuropsychological scales such as mini-mental state examination (MMSE), frontal assessment battery (FAB), and trail making test (TMT) were compared between the two groups. Resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) data of all participants were collected; rs-fMRI data were then analyzed using VMHC algorithm to calculate and conform the brain regions with significantly different VMHC between the two groups, and these regions were used as seed points to perform functional connectivity with the whole brain; Pearson correlation analyses of VMHC and functional connectivity in these brain regions with scores of neuropsychological scales were performed. DTI data were processed using tract-based spatial statistics (TBSS) method to calculate and conform the brain regions with significantly different diffusion parameters of fiber tracts between the two groups; Pearson correlation analyses of diffusion parameters of the fiber tracts in these brain regions with scores of neuropsychological scales were performed.Results:(1) Comparison of general data and neuropsychological scale scores: proportion of participants with hypertension history was significantly different between the two groups ( P<0.05); scores of TMT-A, TMT-B, and Stroop C scales in the WMH group were significantly higher than those in the control group ( P<0.05). (2) Comparison of VMHC and seed point functional connectivity: compared with that in the control group, the VMHC in bilateral middle occipital gyrus, visual cortex, medial occipitotemporal gyrus, insula, and postcentral gyrus of the WMH group were statistically lower ( P<0.05). Compared with that in the control group, functional connectivity of right visual cortex with right middle temporal gyrus, bilateral precuneus, and right dorsolateral superior frontal gyrus in the WMH group was significantly weakened, and functional connectivity of right postcentral gyrus with right medial occipitotemporal gyrus, left middle temporal gyrus, left visual cortex, and left postcentral gyrus was statistically weakened ( P<0.05). In the WMH group, the VMHC of bilateral insula was negatively correlated with TMT-B score ( r=-0.381, P<0.001), and functional connectivity between right visual cortex and right dorsolateral superior frontal gyrus was negatively correlated with Stroop C score ( r=-0.401, P<0.001). (3) TBSS results: the diffusion parameters of the anterior corona radiata, superior corona radiata, corpus callosum, superior longitudinal fasciculus, and posterior thalamic radiation were statistically significant between the two groups ( P<0.05). In the WMH group, the fractional anisotropy in the genu of the corpus callosum was positively correlated with Stroop C score ( r=0.426, P<0.001), radial diffusivity was negatively correlated with Stroop C score ( r=-0.376, P<0.001), and mean diffusivity of the left anterior corona radiata was negatively correlated with TMT-A score ( r=-0.443, P<0.001). Conclusion:WMH patients have decreased coordination in homotopic brain regions and weakened functional connectivity of association loops, with widely distributed white matter microstructure damages, which may be involved in the neuropathological process of cognitive impairment.

Objective:To investigate the alterations of brain resting-state functional connectivity in patients with leukoaraiosis(LA), and to explore its neuropathological mechanism of cognitive dysfunction.Methods:From August 2022 to February 2023, 28 patients with LA(LA group) and 30 gender, age and education level matched normal controls(NC group) in Jiangsu Shengze Hospital affiliated to Nanjing Medical University were prospectively recruited.Mini mental state examination, trail-making test, and Stroop color-word test were used to evaluate the cognitive function of participants, rs-fMRI images were processed by DPABI V6.1 based on MATLAB R2022a.Voxel-mirrored homotopic connectivity(VMHC) values were calculated and two-sample t test were performed to compare the differences in local brain activity between the two groups.The brain regions with significant differences were selected as the seeds to calculate the functional connectivity(FC) values of the whole brain, and Pearson correlation analyses were performed to evaluate the correlation between the FC values and neuropsychological scores. Results:The VMHC values of the calcarine fissure and surrounding cortex(CAL) (x=±18, y=-63, z=15), postcentral gyrus(PoCG) (x=±39, y=-27, z=48), lingual gyrus(LING) (x=±12, y=-51, z=-6), middle occipital gyrus(x=±27, y=-75, z=24) and insula(x=±36, y=6, z=3) in the LA group were lower than those in the NC group( P<0.05). The seed points FC results showed, FC values between right CAL(CAL.R) and bilateral precuneus(PCUN), right dorsolateral prefrontal cortex(DLPFC.R) and right temporal_mid were reduced in the LA group( P<0.05); FC values between PoCG.R and left CAL, left temporal_mid and right LING were reduced too( P<0.05). Additionally, the FC value in the LA group between CAL.R and DLPFC.R was negatively correlated with the Stroop C score( r=-0.39, P<0.05). The FC value in LA group and NC group between CAL.R and DLPFC.R was negatively correlated with the Stroop C score( r=-0.48, P<0.001)and also negatively correlated with the trail making test B(TMT-B) score( r=-0.40, P<0.01), and the FC value between CAL.R and PCUN.L was negatively correlated with the TMT-B score( r=-0.45, P<0.001). Conclusion:Desynchronized interhemispheric functional connectivity and abnormal cortical circuit functional connectivity were probably associated with the underlying neural mechanisms of cognitive impairment in LA.

Per-and polyfluoroalkylated substances (PFASs) are a group of persistent organic pollutants that are widespread in the environment and organisms. Given their unique hydrophobicity, oil-repellence, and chemical stability, PFASs are widely used in various industrial and commercial products. PFASs can accumulate and be biomagnified through the food chain, and its toxic effects have posed a certain threat to human health. The response of the immune system to PFASs exposure is one of the most sensitive human health effects, and has attracted remarkable attention from related scientists and organizations. We summarized international and domestic epidemiological studies on the associations between exposure to PFASs and immune system, including immunosuppression and immunoenhancement. We also reviewed experimental evidence of PFASs on immune system from perspectives of immune organs, immune cells, and cytokines. Furthermore, the possible mechanisms of peroxisome proliferator-activated receptor-α (PPAR-α)-dependent, nuclear factor-κB (NF-κB)-activated, and mitochondrial apoptosis pathways were summarized. While the relationships between PFASs and immune-related diseases in human are not yet conclusive, accumulative epidemiological studies provide evidence for associations between PFASs and reduced immune response to vaccination in children. In addition, previous studies mainly focus on the immunotoxicity of traditional PFASs, and our understanding of the molecular mechanism of the effects of PFASs on immune system is still in its infancy. Therefore, it is necessary to further explore the immunotoxicity of new PFASs and associated mechanism.

Objective To investigate the prevalence of allergic and infectious diseases in children， and to assess the influence of indoor and outdoor environmental factors on these two common diseases in children. Methods A questionnaire was used to investigate the prevalence of allergic and infectious diseases in 140 children of 7 years old in Laizhou Bay， Shandong Province. Logistic regression was used to analyze the associations between indoor and outdoor environmental factors and children’s allergic and infectious diseases， respectively. Results The prevalence of previous eczema and other allergic diseases for the past year in children was 37.9% and 15.0%， respectively， and the prevalence of infectious diseases for the past year was 35.7%. As for allergic diseases， eye irritation due to outdoor air （ OR =2.977； 95% CI ： 1.407‒6.296） and nose irritation due to outdoor air （ OR =5.147； 95% CI ： 1.272‒20.827） were the risk factors for previous eczema in children. Indoor musty taste increased the risks of urticaria （ OR =4.306； 95% CI ： 1.062‒17.454） and previous eczema （ OR =3.853； 95% CI ： 1.080‒13.743）. The use of cockroach killers indoors increased the risk of rhinitis （ OR =6.102； 95% CI ：1.297‒28.697）. As for infectious diseases， having outdoor pollution sources increased the risk of gastrointestinal infection （ OR =4.937； 95% CI ： 1.050‒23.216）， and the use of mosquito coils and clothing mothproofing agents increased the risks of respiratory （ OR =6.333； 95% CI ： 1.397‒28.714） and gastrointestinal infections （ OR =3.218； 95% CI ： 1.074‒9.644）， respectively. However， we did not find associations between indoor passive smoking and allergic or infectious diseases. Conclusion Except outdoor passive smoking， all the other indoor and outdoor environmental factors increase the risks of children’s allergies and infectious diseases.

Objective To investigate the correlation between subclinical hypothyroidism (SCH) and carotid atherosclerosis in patients with acute ischemic stroke.Methods Patients with acute ischemic stroke admitted to Nanjing Shengze Hospital Affiliated to Nanjing Medical University from July 2014 to July 2017 were enrolled retrospectively.SCH was defined as elevated levels of serum thyroid stimulating-hormone (TSH),but the free thyroxine (FT4) and free-triiodothyronine (FT3) levels were normal.Carotid plaque and carotid stenosis were assessed using carotid ultrasound.Multivariate logistic regression analysis was used to determine the correlation between SCH and carotid atherosclerosis.Resuts A total of 176 patients with acute ischemic stroke were enrolled,including 81 females and 95 males;36 complicated with SCH,126 complicated with carotid atherosclerotic plaques,and 9 had carotid stenosis.High-density lipoprotein cholesterol (1.36±0.48 mmol/L vs.1.18 ± 0.30 mmol/L;t =2.090,P =0.039) and TSH (6.29[5.44-7.01]mU/L vs.1.87[1.31-2.67] mU/L;Z =9.243,P =0.001) levels in the SCH group were significantly higher than those in the non-SCH group.There were significant differences in age (73.5[65.0-80.0]years vs.68.0[56.0-75.0]years;Z =2.707,P=0.007),stroke etiology classification (x2 =9.270,P=0.038),TSH level (2.19[1.47-3.72]mU/L vs.2.18[1.24-2.62]mU/L;Z=3.230,P=0.001),and the proportion of patients with SCH (26.98％ vs.4.00％;x2 =11.622,P =0.001) between the plaque group and the non-plaque group.There was no statistical difference in demographic and clinical data between the stenosis group and the non-stenosis group (all P ＞0.05).Multivariatelogistic regression analysis showed that advanced age (odds ratio 1.050,95％ confidence interval 1.014-1.088;P =0.006) and SCH (odds ratio 5.328,95％ confidence interval 1.322-21.468;P =0.019) were the independent risk factors for carotid atherosclerotic plaques.Conclusion Advanced age and SCH were the independent risk factors for carotid plaque in patients with acute ischemic stroke.

Objective To compare the effects of health education on fat intake behavior and its psychology in students with different BMI,provide evidence for improving individual healthy education.Methods A experimental epidemiology was used,Twenty-nine secondary school classes were randomly selected by multi-stage cluster sampling from two cities in Zhejiang province.Overweight or obesity group included all students who were judged overweight or obesity,normal group included students who were judged normal and basic matched by age,grade,sex and stage of baseline.Intervention based on transtheoretical mode was conducted on two groups and intervention results were measured by the adolescent fat intake behavior of psychological measurement scales (Chinese version).Chi-square tests,T-tests,non-parameters tests and binary logistic regression were performed for data analyses.Results Stage of students with overweight or obesity and with normal BMI all moved forward after intervention,while the proportion of stage advance for students with overweight or obesity was further than students with normal BMI.Change strategy(2.60±0.79),pros(3.58±0.90) and self-efficacy(3.01±0.72) of students with overweight or obesity better than students with normal BMI in baseline((2.34±0.86),(3.08±0.91),(2.79±0.81)) while difference was not significant after intervention.Logistic regression analysis discovered that the promotion of change strategy moved stage forward for students with normal BMI(OR=2.168,95％ CI:1.560-3.014)and promotion of self-efficiency moved stage forward for students with overweight or obesity (OR=1.801,95％ CI:1.026-3.159).Conclusion The intensity and duration of psychological intervention is essential to be reinforced for students with normal BMI,while for students with overweight and obesity,psychological intervention should be promoted in combination with social support.

Objective To analyze the outcome of patients receiving intrauterine insemination with husband sperm,in order to evaluate the effect of relative factors on pregnancy rate after intrauterine insemination. Methods Ninety-eight infertile couples who received intrauterine insemination in the Affiliated Hospital of Nantong University from March 2013 to May 2014 were selected as our subjects and 181 cycles were included. The information including clinical factors including maternal age,infertile time,infertile causes, ovulation induction protocol,time of insemination and postwash total motitle sperm(TMS)and pregnancy rate were recorded. Results (1)Totally 26 patients received clinical pregnancies,and clinical pregnancy rate(CPR) was 14. 36% per cycle. With age increase pregnancy rate decreased( χ2 = 1. 654 9,P = 0. 647).(2)The pregnancy rate of the patients was the same within the infertile time( χ2 = 1. 588 5,P = 0. 662).(3)The pregnancy rate of the patients with secondary infertility was lower than that of the patients with primary infertility,but there was no significant difference(χ2 = 0. 923 3,P = 0. 337).(4)The pregnancy rate of ovulation induction cycles was lower than that of nature cycles,but there was no significant difference(χ2 = 2. 222 0,P= 0. 136).(5)Postwash TMS was showed the same trend(χ2 = 0. 643 4,P = 0. 422). Conclusion In terms of intrauterine insemination with husband sperm,age,infertile time,infertile types,ovulation induction protocol and posrwash TMS can affect pregnancy rate,and the effects of various factors should be considered comprehensively in the process of therapy.

Objective To analyze the features of bone minimal density and bone quantitative ultrasound in men with different osteoporotic risk graded by osteoporosis self-assessment tool for Asian (OSTA).Methods After exclude the secondary osteoporosis,724 subjects over 50 years old were involved.The parameters of hight,weight,quantitative ultrasound index (QUI),QUS-T score were examined.The bone density (BMD) were measured by dual-energy X-ray absorptiometry (DXA)in 120 elderly men.All subjects were grouped into low (osteoporotic) risk group,moderate risk group and high risk group by OSTA index.120 subjects measured BMD were grouped into normal bone mass group,osteopenia group and osteoporosis group by WHO standard.The differences and correlation analysis in BMD,QUST,and QUI between these groups were analysed.Results The percents of low risk people,moderate risk people and high risk people were 56.4％ (408 cases),28.2％ (204cases),15.5％ (112 cases),respectively.There were 30.0％ (36 cases) normal bone mass people,58.3％ (70 cases) osteopenia people and 11.7％ (14 cases) osteoporosis people in groups measured BMD.QUS-T score,QUI were gradually decreased in groups of low risk,moderate risk and high risk (-0.56±1.09,-0.88±-1.28,-1.21±1.40; 98.47±19.04,92.62±22.49,87.68±24.43; all P ＜0.05) and had statistical significant differences between low risk and moderate risk,high risk groups,while had no differences between moderate risk and high risk groups.The femoral neck BMD and total BMD were gradually decreased in all the three groups (0.89±0.12,0.85±0.10,0.77± 0.10; 1.0±0.15,0.93 ± 0.11,0.83±0.1; all P＜0.01).Osteoporosis in the three groups were 3.4％ (2 cases),13.0％ (6 cases),37.5％ (6 cases),respectively and osteoporosis percents in moderate risk group and high risk group were higher compared with low risk group (x2=11.77,P＜0.01).QUS-T score and QUI decreased gradually in groups of normal mass,osteopenia and osteoporosis (0.99±0.08,-0.70±1.07,-1.96±0.73; 109.26±17.05,96.15±18.20,72.54±10.00; F=10.47,11.73,all P＜ 0.01).Except for lumbar BMD,a positive linear correlation emerged between OSTA and QUS-T score,QUI,hip BMD(all P＜0.01).The values of R with femoral neck BMD,torch BMD and total hip BMD were 0.45,0.38,0.39,respectively.And the same value with QUS-T score and QUI was 0.23.Conclusions With the decreasing of OSTA index,risk of osteoporosis is increased and QUS-T score,QUI and BMD are decreased gradually.There are positive linear correlation between OSTA index and QUS-T score,QUI,hip BMD.