Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective:To explore the binding characteristics of N, N-diethyl-2-(2-(4-(2- 18F-fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-DPA-714) and ( R)- N-sec-butyl- N-methyl-4-(3-( 18F-trifluoromethyl)phenyl)quinazoline-2-carboxamide ( 18F-TFQC) to the single nucleotide polymorphisms of the 18×10 3 translocator protein (TSPO), and to evaluate the imaging efficacy and feasibility of those 2 molecular probes in neuroinflammation rat models. Methods:To test the selectivity of 18F-DPA-714 and 18F-TFQC for TSPO polymorphisms, the wild-type (high-affinity binding, HAB) and mutant (low-affinity binding, LAB) sequences of the human TSPO gene were transfected into 293T cells respectively. A competitive inhibition assay was carried out with N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)-3-isoquinoline carboxamide (PK11195) as an inhibitor to determine the binding affinities of 2 probes to TSPO polymorphisms. Rat neuroinflammation models ( n=6) were established using lipopolysaccharide. Three days after modeling, small animal PET/CT imaging was performed using 18F-DPA-714 and 18F-TFQC, respectively, to observe and compare the uptake of the tracers, and the ratio of SUV mean of the right striatum to SUV mean of the left striatum (SUVR) was calculated. After the imaging, the expression and distribution of microglia and TSPO were detected by tissue immunofluorescence. Repeated-measures analysis of variance was used to analyze the SUVR data of different groups. Results:The inhibition constants ( Ki) of 18F-TFQC on 293T-LAB and 293T-HAB cells were 23.51 and 14.60 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 1.61, indicating low sensitivity to TSPO single nucleotide polymorphisms. The Ki of 18F-DPA-714 for binding to 293T-LAB and 293T-HAB cells were 45.23 and 6.47 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 6.99. Small animal PET/CT imaging demonstrated that specifically uptake of both probes could be found in neuroinflammatory lesions. The overall SUVR of 18F-DPA-714 in the lesions within 60minutes was slightly higher than that of 18F-TFQC, but no significant difference was observed ( F values: inter-group 0.40, time effect 0.30, cross-effect 0.03; all P>0.05). Conclusions:Compared with 18F-DPA-714, 18F-TFQC is less sensitive to TSPO gene polymorphisms, thus being more suitable for clinical application and promotion. It holds promise for the early identification of neuroinflammation and the efficacy monitoring of anti-inflammatory drug treatments.

Objective:To explore the binding characteristics of N, N-diethyl-2-(2-(4-(2- 18F-fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-DPA-714) and ( R)- N-sec-butyl- N-methyl-4-(3-( 18F-trifluoromethyl)phenyl)quinazoline-2-carboxamide ( 18F-TFQC) to the single nucleotide polymorphisms of the 18×10 3 translocator protein (TSPO), and to evaluate the imaging efficacy and feasibility of those 2 molecular probes in neuroinflammation rat models. Methods:To test the selectivity of 18F-DPA-714 and 18F-TFQC for TSPO polymorphisms, the wild-type (high-affinity binding, HAB) and mutant (low-affinity binding, LAB) sequences of the human TSPO gene were transfected into 293T cells respectively. A competitive inhibition assay was carried out with N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)-3-isoquinoline carboxamide (PK11195) as an inhibitor to determine the binding affinities of 2 probes to TSPO polymorphisms. Rat neuroinflammation models ( n=6) were established using lipopolysaccharide. Three days after modeling, small animal PET/CT imaging was performed using 18F-DPA-714 and 18F-TFQC, respectively, to observe and compare the uptake of the tracers, and the ratio of SUV mean of the right striatum to SUV mean of the left striatum (SUVR) was calculated. After the imaging, the expression and distribution of microglia and TSPO were detected by tissue immunofluorescence. Repeated-measures analysis of variance was used to analyze the SUVR data of different groups. Results:The inhibition constants ( Ki) of 18F-TFQC on 293T-LAB and 293T-HAB cells were 23.51 and 14.60 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 1.61, indicating low sensitivity to TSPO single nucleotide polymorphisms. The Ki of 18F-DPA-714 for binding to 293T-LAB and 293T-HAB cells were 45.23 and 6.47 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 6.99. Small animal PET/CT imaging demonstrated that specifically uptake of both probes could be found in neuroinflammatory lesions. The overall SUVR of 18F-DPA-714 in the lesions within 60minutes was slightly higher than that of 18F-TFQC, but no significant difference was observed ( F values: inter-group 0.40, time effect 0.30, cross-effect 0.03; all P>0.05). Conclusions:Compared with 18F-DPA-714, 18F-TFQC is less sensitive to TSPO gene polymorphisms, thus being more suitable for clinical application and promotion. It holds promise for the early identification of neuroinflammation and the efficacy monitoring of anti-inflammatory drug treatments.

The translocator protein (TSPO) positron emission tomography (PET) can noninvasively detect neuroinflammation associated with epileptogenesis and epilepsy. This study explored the role of the TSPO-targeting radioligand [¹⁸F]F-TFQC, an m-trifluoromethyl ER176 analog, in the PET neuroimaging of epileptic rats. Initially, [¹⁸F]F-TFQC was synthesized with a radiochemical yield of 8%-10% (EOS), a radiochemical purity of over 99%, and a specific activity of 38.21 ± 1.73 MBq/nmol (EOS). After determining that [¹⁸F]F-TFQC exhibited good biochemical properties, [¹⁸F]F-TFQC PET neuroimaging was performed in epileptic rats at multiple time points in various stages of disease progression. PET imaging showed specific [¹⁸F]F-TFQC uptake in the right hippocampus (KA-injected site, i.e., epileptogenic zone), which was most pronounced at 1 week (T/NT 1.63 ± 0.21) and 1 month (T/NT 1.66 ± 0.20). The PET results were further validated using autoradiography and pathological analysis. Thus, [¹⁸F]F-TFQC can reflect the TSPO levels and localize the epileptogenic zone, thereby offering the potential for monitoring neuroinflammation and guiding anti-inflammatory treatment in patients with epilepsy.

BACKGROUND:The recovery of function after spinal cord injury depends on the functional remodeling of the motor cortex.However,the anatomical evidence underlying the functional remodeling of the motor cortex is still illusive.Analyzing the anatomical changes in the motor cortex after spinal cord injury can provide new ideas and research directions for regulating functional recovery and rehabilitation after spinal cord injury. OBJECTIVE:To analyze the neural circuit structural basis of functional remodeling of the primary motor cortex after spinal cord injury. METHODS:C57BL/6J mice were randomly divided into a sham operation group and a spinal cord injury group.The adeno-associated virus vectors expressing the fusion protein of Cre recombinase were injected into C4 of mice of both groups.The adeno-associated virus vectors with Cre recombinase-inducible expression of avian sarcoma/leukosis envelope glycoprotein receptor TVA and rabies glycoprotein were injected into the primary motor cortex.Fourteen days later,a C6 dorsal hemisection mice model was established in the spinal cord injury group.The pseudotyped rabies virus was injected into the primary motor cortex of mice of both groups.After 7 days,brain samples were collected and frozen sections were made.The distribution of input neurons innervating corticospinal motor neurons in the brain was observed and analyzed quantitatively. RESULTS AND CONCLUSION:Fluorescence microscopy observation and quantitative analysis found that input neurons innervating corticospinal motor neurons of the primary motor cortex in mice of both groups were distributed in the cerebral cortex,thalamus and midbrain.Among them,in the sham operation group,the number of input neurons in the mouse cerebral cortex accounted for(84.0±3.6)%of total brain input neurons;that in the thalamus accounted for(10.6±2.3)%,and that in the midbrain accounted for(0.7±0.4)%.Direct synaptic input neurons in the spinal cord injury group accounted for(81.7±1.0)%,(13.1±0.5)%,and(1.6±0.8)%in the cerebral cortex,thalamus and midbrain,respectively.The proportion and number of primary motor cortex input neurons in the three regions of the spinal cord injury group did not differ significantly from that of the sham operation group.After spinal cord injury,the number of input neurons innervating corticospinal pyramidal motor neurons in various brain regions did not change significantly,suggesting that functional remodeling of the motor cortex after spinal cord injury may not only depend on changes in synaptic input related to injured corticospinal motor neurons,but also on transcriptional regulation changes within the injured neurons themselves.

Objective:To learn about the iodine nutrition level of school-age children aged 8 - 10 in Shaanxi Province.Methods:From 2017 to 2020, in counties (cities, districts) under the jurisdiction of Shaanxi Province, one township (street) was selected from five directions: East, West, South, North and Middle, one primary school was selected from each township (street), and 42 non-boarding school-age children aged 8 - 10 (age balanced, half male and half female) were selected from each primary school. Random urine samples of children were collected once, and urinary iodine was detected by arsenic-cerium catalytic spectrophotometry.Results:A total of 91 766 children's urine samples were tested from 2017 to 2020, and the median urinary iodine was 221.7 μg/L. Urinary iodine < 100 μg/L accounted for 10.4% (9 554/91 766), 100 - < 200 μg/L accounted for 32.3% (29 602/91 766), 200 - < 300 μg/L accounted for 30.6% (28 065/91 766), and ≥300 μg/L accounted for 26.7% (24 545/91 766). The median of children's urinary iodine in each year was 228.5, 218.0, 211.7, and 230.1 μg/L, respectively, the difference between years was statistically significant ( H = 278.66, P < 0.001). Conclusion:From 2017 to 2020, the iodine nutrition of school-age children aged 8 - 10 in Shaanxi Province is generally in an ultra-suitable state.

Objective:To master the iodine nutrition status of children and pregnant women after adjustment of salt iodization content in Shaanxi Province, and provide scientific basis for preventing and treating iodine deficiency disorders.Methods:In 2018, 107 counties (cities, districts) in Shaanxi Province were divided into three districts in Guanzhong, northern Shaanxi and southern Shaanxi for studying iodine nutrition based on terrain distribution. Among them, each monitoring county (city, district) was further divided into 5 sampling areas according to east, west, south, north, and middle locations. One township (street) was selected in each location, and forty-two 8 - 10 years old non-boarding children (age and sex balanced) and 21 pregnant women were selected in each township (street), edible salt samples and random urine samples were collected for salt iodine, urinary iodine testing, and goiter of children was examined.Results:A total of 34 264 edible salt samples from 8 - 10 years old children and pregnant women were collected, the median salt iodine was 23.80 mg/kg, and the qualified iodized salt consumption rate was 96.98% (33 229/34 264). The median salt iodine and the qualified iodized salt consumption rate were statistically significantly different among the three regions in Guanzhong, northern Shaanxi, and southern Shaanxi ( H = 26.471, χ 2 = 32.371, P < 0.05). A total of 22 895 urine samples were collected from children, with a median urinary iodine of 218.00 μg/L, which was at an ultra-suitable level of iodine nutrition; and 11 369 urine samples from pregnant women were collected, with a median urinary iodine of 181.03 μg/L, which was at an appropriate level of iodine nutrition. The median urinary iodine of pregnant women in Guanzhong, northern Shaanxi, and southern Shaanxi was 186.39, 177.52, and 176.00 μg/L, respectively. A total of 22 895 children aged 8 to 10 years old were examined, the goiter rate was 1.35% (309/22 895), and there was no significant difference between different regions (χ 2 = 3.395, P > 0.05). Conclusions:Shaanxi Province has reached the standard for elimination of persistent iodine deficiency, children's iodine nutrition is at a ultra-suitable level, and pregnant women is at an appropriate level.

Objective:This study aims to provide scientific evidence for prevention and treatment of iodine deficiency disorders through monitoring the iodine nutrition status of children and pregnant women in Shaanxi Province.Methods:Totally 110 counties (cities, districts) in Shaanxi Province in 2019 were surveyed. Each of the counties (cities, districts) was further divided into five sampled regions along five different geographic directions: east, west, south, north and middle. From each region, one town was selected and then one primary school was selected from each town. Finally, there were a total of 42 non-boarding students aged 8 - 10 years old (age and gender balanced) selected from each school, who would be tested household salt iodine's level and urinary iodine's level. Also, we did the same test for 21 pregnant women who were selected from each town randomly. Additionally, we examined the children's thyroid by B-scan ultrasonograph in 39 counties (cities, districts).Results:A total of 23 101 salt and urine samples were collected from children aged 8 - 10 years old, the average of salt iodine content of the children' family was (24.07 ± 3.71) mg/kg; the consumption rate of qualified iodized salt was 97.55% (22 536/23 101); the median urinary iodine was 211.68 μg/L; and the thyroid goiter rate (TGR) was 1.50% (123/8 191). A total of 11 555 salt and urine samples from pregnant women were collected, the salt iodine content was (24.05 ± 3.66) mg/kg; and the consumption rate of qualified iodized salt was 97.57% (11 274/11 555); the median urinary iodine was 182.74 μg/L.Conclusions:In 2019, the iodine nutrition of children in Shaanxi Province is in the super appropriate level, and the iodine nutrition of pregnant women is appropriate. The iodine content of edible salt can be adjusted. It is suggested that pregnant women should be supplied special iodized salt.

Objective To evaluate the urinary iodine detection ability of Iodine Deficiency Disorder Laboratory in Shaanxi Province,and to test the quality of laboratory construction.Methods In Shaanxi Province,ten city-level and 107 county-level urinary iodine labs of Center for Disease Control and Prevention or Institute for Endemic Disease Prevention and Control were selected in 2018,and two urinary iodine quality-control samples were measured by As3+-Ce4+ catalytic spectrophotometry.The results of urinary iodine quality control were evaluated through standard Z score generated from all the participatory labs.Results All 117 labs had feedback their testing results.There was one lab with an inter-laboratory |Z| score≥3,and 3 labs with inter-laboratory |Z| score≥3,and the qualified rate was 96.58％ (113/117).In 107 county-level urinary iodine labs,there was one lab with an interlaboratory | Z| score ≥ 3,and 3 labs with inter-laboratory | Z[score ≥ 3,and the qualified rate was 96.26％ (103/107).Conclusions The construction of urinary iodine lab has achieved great results in Shaanxi Province,the testing ability of iodine determination laboratory is maintained at a high level,which has laid a solid foundation for prevention and treatment of iodine deficiency disorders in Shaanxi Province.

Objective To compare selenium content in hair samples of people in Kaschin-Beck disease (KBD) areas and control areas in Shaanxi Province two years after stopping the selenium salt prevention,and to provide a scientific basis for development of targeted prevention measures and for decision-making.Methods In July 2014,the four KBD counties of Yongshou,Yuyang,Linyou and Nanzheng were selected as survey counties,meanwhile,four non KBD counties of Wugong,Mizhi,Qishan and Chenggu were selected as rural control groups and Lianhu District in Xi'an City was selected as a urban settlement control county.Four villages (communities) were selected as monitoring sites according to four directions as east,west,south and north in each county.In each monitoring site,hair samples of 8 children aged 7-12 years old (gender balanced) and 8 adults over the age of 16 (gender balanced) were selected to determine hair selenium.Samples were prepared by wet digestion method,the content of selenium was determined by 2,3-diaminonaphthalene fluorescence method.Results A total of 576 hair samples were collected.The average hair selenium in each monitoring site was more than 0.20 mg/kg.Hair selenium was compared in KBD areas,rural non KBD areas,and urban non KBD areas,the differences were not statistically significant [(0.35 ± 0.18),(0.41 ± 0.28),(0.46 ± 0.19) mg/kg,F =1.544,P ＞ 0.05].In KBD areas and non KBD areas,there were 45 and 45 people with selenium content ＜ 0.20 mg/kg,accounting for 17.58％ and 14.06％;47 and 25 people with selenium content 0.20-＜ 0.25 mg/kg,accounting for 18.36％ and 7.81％;113 and 159 people with 0.25-＜ 0.50 mg/kg,accounting for 44.14％ and 49.69％;51 and 91 people with ≥0.50 mg/kg,accounting for 19.92％ and 28.44％.Hair selenium content of children aged 7-12 and adults was compared in KBD areas,rural non KBD areas,and urban non KBD areas [children:(0.43 ± 0.35),(0.38 ± 0.19),(0.50 ± 0.16) mg/kg;adults:(0.32 ± 0.17),(0.38 ± 0.19),(0.42 ± 0.21) mg/kg],the differences were not statistically significant (F =2.131,1.789,P ＞ 0.05).Hair selenium content was compared in different gender in KBD areas,rural non KBD areas,and urban non KBD areas [male:(0.35 ± 0.18),(0.44 ± 0.33),(0.52 ± 0.15) mg/kg;female:(0.35 ± 0.19),(0.38 ± 0.22),(0.41 ± 0.21) mg/kg],the differences were not statistically significant (F=1.598,1.790,P ＞ 0.05).Conclusion Two years after stopping the selenium salt prevention in Shaanxi Province,the selenium of population in Kashin-Beck disease areas in Shaanxi Province exceeds the human health threshold (0.20 mg/kg),and most people are in the medium or high levels of selenium,and are close to the levels of selenium in non-endemic areas.