Objective:To explore the abnormal patterns of brain functional network connectivity in depression adolescents and their diagnostic value in adolescent depression.Methods:A total of 94 depression adolescents (adolescent depression group) admitted to Outpatient Department of Psychiatric Imaging, West China Hospital, Sichuan University from January 2020 to December 2022 were selected. In addition, 78 age- and gender-matched healthy adolescents were recruited from local community advertisements at the same time-period as healthy control group. Resting-state functional magnetic resonance imaging was performed; after image preprocessing, group-level spatial independent component analysis was performed to identify the intrinsic network connectivity, and differences in network connectivity between the two groups were compared. Functional connectivity edges were employed as classification features, and feature ranking and screening were then performed. A support vector machine (SVM) with linear kernel function was used to construct a classification model, and receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of this classification model in adolescent depression.Results:No significant difference was noted in age, gender, years of education, and body mass index between the two groups ( P>0.05). Compared with the healthy control group, the adolescent depression group had significantly decreased functional connectivity intensity within and between the networks of sensorimotor network (SMN), visual network (VN), auditory network (AN), default mode network (DMN), and cognitive control network (CCN), and significantly increased functional connectivity intensity within CCN ( P<0.05). When using the 75 top-ranked functional connectivity features, this classification model had the best performance (accuracy rate: 70.35%, sensitivity: 70.21%, specificity: 71.80%, P<0.001). ROC curve showed that area under the curve of this classification model in diagnosing adolescent depression was 0.724 (95% CI: 0.648-0.800, P<0.001). A total of 51 consistent functional connectivities were identified and they were mainly located within or between the networks of SMN, VN, AN, DMN, and CCN. Conclusion:The abnormal resting-state brain functional connectivity in depression adolescents can provide imaging basis for their clinical diagnosis.

Autism Spectrum Disorder (ASD) is marked by early-onset neurodevelopmental anomalies, yet the temporal dynamics of genetic contributions to these processes remain insufficiently understood. This study aimed to elucidate the role of the Shank3 gene, known to be associated with monogenic causes of autism, in early developmental processes to inform the timing and mechanisms for potential interventions for ASD. Utilizing the Shank3B knockout (KO) mouse model, we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex (ACC) across different postnatal stages. Our longitudinal analysis revealed that, while Shank3B KO mice displayed normal neuronal morphology at one week postnatal, significant impairments in dendritic growth and synaptic activity emerged by two to three weeks. These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.
Animals ; Nerve Tissue Proteins/metabolism* ; Mice, Knockout ; Dendrites/metabolism* ; Mice ; Synapses/metabolism* ; Gyrus Cinguli/metabolism* ; Male ; Mice, Inbred C57BL ; Autism Spectrum Disorder/genetics* ; Microfilament Proteins

Purpose To investigate the patterns of change in the topological organization of individual level gray matter morphological networks in children with autism spectrum disorder(ASD).Materials and Methods The clinical and high-resolution T1 structural image data of 52 ASD children and 69 typical developing children from Autism Brain Imaging Data Exchange public database were selected.The individual gray matter structural networks were constructed by calculating the similarities of regional gray matter morphology.The global and local topological metrics of individual gray matter networks were analyzed using a graph theory method and compared between the two groups.Partial correlation analysis was used to evaluate the correlation between topological metrics showing significant between group differences and clinical characteristics in the ASD group.Results The verbal IQ was significantly lower in the ASD group compared with the typical developing group(t=-3.151,P=0.002),and no significant differences were found in full scale IQ and performance IQ between the two groups(P>0.05).Compared with the typical developing group,the ASD group showed significantly higher global efficiency(P=0.014),lower clustering coefficient(P=0.044)and characteristic path length(P=0.020)of gray matter structural networks.In the ASD group,abnormal nodal centralities were found in multiple brain regions(P<0.05,false discovery rate corrected),including the bilateral dorsolateral superior frontal gyrus,bilateral precuneus,bilateral caudate nucleus,right superior temporal gyrus,left middle temporal gyrus and bilateral anterior cingulate gyrus.No significant associations were found between the abnormal network topological metrics and IQ scores in the ASD group(r=0.069-0.187,all P>0.05).Conclusion Altered topological organization of individualized gray matter morphological networks is found in children with ASD,as characterized by decreased local segregation and increased global integration of networks.The areas with abnormal nodal centralities in children with ASD are mainly located at the brain regions involved in emotional processing,social and high-order cognitive functions.

BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

Objective:To explore the abnormal patterns of brain functional network connectivity in depression adolescents and their diagnostic value in adolescent depression.Methods:A total of 94 depression adolescents (adolescent depression group) admitted to Outpatient Department of Psychiatric Imaging, West China Hospital, Sichuan University from January 2020 to December 2022 were selected. In addition, 78 age- and gender-matched healthy adolescents were recruited from local community advertisements at the same time-period as healthy control group. Resting-state functional magnetic resonance imaging was performed; after image preprocessing, group-level spatial independent component analysis was performed to identify the intrinsic network connectivity, and differences in network connectivity between the two groups were compared. Functional connectivity edges were employed as classification features, and feature ranking and screening were then performed. A support vector machine (SVM) with linear kernel function was used to construct a classification model, and receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of this classification model in adolescent depression.Results:No significant difference was noted in age, gender, years of education, and body mass index between the two groups ( P>0.05). Compared with the healthy control group, the adolescent depression group had significantly decreased functional connectivity intensity within and between the networks of sensorimotor network (SMN), visual network (VN), auditory network (AN), default mode network (DMN), and cognitive control network (CCN), and significantly increased functional connectivity intensity within CCN ( P<0.05). When using the 75 top-ranked functional connectivity features, this classification model had the best performance (accuracy rate: 70.35%, sensitivity: 70.21%, specificity: 71.80%, P<0.001). ROC curve showed that area under the curve of this classification model in diagnosing adolescent depression was 0.724 (95% CI: 0.648-0.800, P<0.001). A total of 51 consistent functional connectivities were identified and they were mainly located within or between the networks of SMN, VN, AN, DMN, and CCN. Conclusion:The abnormal resting-state brain functional connectivity in depression adolescents can provide imaging basis for their clinical diagnosis.

Purpose To investigate the patterns of change in the topological organization of individual level gray matter morphological networks in children with autism spectrum disorder(ASD).Materials and Methods The clinical and high-resolution T1 structural image data of 52 ASD children and 69 typical developing children from Autism Brain Imaging Data Exchange public database were selected.The individual gray matter structural networks were constructed by calculating the similarities of regional gray matter morphology.The global and local topological metrics of individual gray matter networks were analyzed using a graph theory method and compared between the two groups.Partial correlation analysis was used to evaluate the correlation between topological metrics showing significant between group differences and clinical characteristics in the ASD group.Results The verbal IQ was significantly lower in the ASD group compared with the typical developing group(t=-3.151,P=0.002),and no significant differences were found in full scale IQ and performance IQ between the two groups(P>0.05).Compared with the typical developing group,the ASD group showed significantly higher global efficiency(P=0.014),lower clustering coefficient(P=0.044)and characteristic path length(P=0.020)of gray matter structural networks.In the ASD group,abnormal nodal centralities were found in multiple brain regions(P<0.05,false discovery rate corrected),including the bilateral dorsolateral superior frontal gyrus,bilateral precuneus,bilateral caudate nucleus,right superior temporal gyrus,left middle temporal gyrus and bilateral anterior cingulate gyrus.No significant associations were found between the abnormal network topological metrics and IQ scores in the ASD group(r=0.069-0.187,all P>0.05).Conclusion Altered topological organization of individualized gray matter morphological networks is found in children with ASD,as characterized by decreased local segregation and increased global integration of networks.The areas with abnormal nodal centralities in children with ASD are mainly located at the brain regions involved in emotional processing,social and high-order cognitive functions.

Objective:To assess performance advantages of voxel-less optimization(VoLO)algorithm of CyberKnife-based S7 treatment plan system for the optimization of stereotactic body radiation therapy(SBRT)for liver cancer.Methods:The case data of 20 patients with hepatocellular carcinoma from Chinese PLA General Hospital during June 2022 and April 2023 were retrospectively selected,which included 10 patients with large hepatocellular carcinoma and 10 patients with small hepatocellular carcinoma.All patients adopted respectively sequential optimization(SO)and VoLO to conduct optimization for plan.The optimized quality of plan and execution efficiency of two kinds of algorithms were assessed,and the influences of different tumor volumes also were considered.The planed quality assessment included dosimetric parameters of the target region and organ at risk(OAR).The assessment parameters of execution efficiency included the numbers of monitor units(MUs),nodes and beams,and estimated treatment time.Paired t-test method was adopted to analyze quality of plan and treatment efficiency.Results:On the aspect of the dose of target region,for small hepatocellular carcinoma,the conformity index(CI)value(1.08±0.05)of target region of VoLO algorithm was significantly better than(1.17±0.06)of SO algorithm(t=4.631,P<0.05).The gradient index(GI),coverage rate and dose by 95%(D95%)of VoLO algorithm were better than those of SO algorithm,while the differences were not significant(P>0.05).According to the defined standards of liver surgery,for large hepatocellular carcinoma,the differences in CI,GI,coverage rate and D95%of target region between two kinds of algorithms were significant(t=3.337,4.238,-3.359,-3.311,P<0.05),respectively.On the aspect of dosimetry for OAR,for the target region of large hepatocellular carcinoma,the differences of liver Dmean and D700 cm3 between two kinds of algorithms were significant(t=4.114,3.415,P<0.05).However,for small hepatocellular carcinoma,there was no significant statistical difference in dosimetry parameters of OAR between two kinds of algorithms(P>0.05).The execution efficiency of the plan of VoLO group was obviously higher than that of SO group,and the differences of MU number,node number,beam number and estimated treatment time between two groups were significant(t=12.661,4.423,5.024,9.487,P<0.05).Conclusion:The quality of VoLO plan is significantly better than that of SO,which has a significant improvement in execution efficiency of treatment.For the cases of large hepatocellular carcinoma with more complexity,the VoLO optimization shows better advantages on the aspect of dose on target region,and protection for normal liver.

Objective:To compare the differential regulatory effects of corticotropin releasing hormone(CRH)neu-rons in periaqueductal gray(PAG)and medial preoptic area(MPA)downstream of paraventricular nucleus(PVN)in mediating stress-related abnormal behaviors.Methods:The anterograde labeled virus AAV2/9-hSyn-DIO-hChR2-EYFP and AAV2/9-mCrh-SV40 NLS-Cre was injected into the PVN brain region of mouse,and the projection distribution of PVN axons in the PAG and MPA brain regions was observed after statistical analysis of its projection distribution through Image J.The optogenetic inhibitory virus mixture of AAV2/9-DIO-stGtACR2-EGFP and AAV2/9-mCrh-SV40 NLS-Cre targeting CRH neurons was injected into the PAG and MPA brain regions receiving the corresponding PVN projection,respectively,and the CRH neurons in the PAG and MPA brain regions were inhibited by optogenetic blue light 460 nm to observe the anxiety-related behaviors of mice under acute restraint stress.Results:Densely distributed CRHergic PVN axon terminals were observed in PAG and MPA brain regions.Optogenetic inhibition of CRH neurons in the PAG region of acute stress mice showed no significant change in social preference behavior.The eating latency decreased in the novelty-suppressed feeding test,and the escape latency increased under visual fear stimulation.Optogenetic inhibi-tion of CRH neurons in the MPA brain region showed no significant change in social preference,significantly decreased eating latency in the novelty-suppressed feeding test,and no significant change in escape latency under visual fear stim-ulation.Conclusion:CRH neurons in PAG and MPA brain regions downstream of PVN have differential regulation in a-cute stress-related anxiety behavior,but no difference in social behavior regulation,which provides theoretical support and basis for in-depth exploration of stress-related brain regions and cellular mechanisms.

Objective:To compare the differential regulatory effects of corticotropin releasing hormone(CRH)neu-rons in periaqueductal gray(PAG)and medial preoptic area(MPA)downstream of paraventricular nucleus(PVN)in mediating stress-related abnormal behaviors.Methods:The anterograde labeled virus AAV2/9-hSyn-DIO-hChR2-EYFP and AAV2/9-mCrh-SV40 NLS-Cre was injected into the PVN brain region of mouse,and the projection distribution of PVN axons in the PAG and MPA brain regions was observed after statistical analysis of its projection distribution through Image J.The optogenetic inhibitory virus mixture of AAV2/9-DIO-stGtACR2-EGFP and AAV2/9-mCrh-SV40 NLS-Cre targeting CRH neurons was injected into the PAG and MPA brain regions receiving the corresponding PVN projection,respectively,and the CRH neurons in the PAG and MPA brain regions were inhibited by optogenetic blue light 460 nm to observe the anxiety-related behaviors of mice under acute restraint stress.Results:Densely distributed CRHergic PVN axon terminals were observed in PAG and MPA brain regions.Optogenetic inhibition of CRH neurons in the PAG region of acute stress mice showed no significant change in social preference behavior.The eating latency decreased in the novelty-suppressed feeding test,and the escape latency increased under visual fear stimulation.Optogenetic inhibi-tion of CRH neurons in the MPA brain region showed no significant change in social preference,significantly decreased eating latency in the novelty-suppressed feeding test,and no significant change in escape latency under visual fear stim-ulation.Conclusion:CRH neurons in PAG and MPA brain regions downstream of PVN have differential regulation in a-cute stress-related anxiety behavior,but no difference in social behavior regulation,which provides theoretical support and basis for in-depth exploration of stress-related brain regions and cellular mechanisms.

Objective:To assess performance advantages of voxel-less optimization(VoLO)algorithm of CyberKnife-based S7 treatment plan system for the optimization of stereotactic body radiation therapy(SBRT)for liver cancer.Methods:The case data of 20 patients with hepatocellular carcinoma from Chinese PLA General Hospital during June 2022 and April 2023 were retrospectively selected,which included 10 patients with large hepatocellular carcinoma and 10 patients with small hepatocellular carcinoma.All patients adopted respectively sequential optimization(SO)and VoLO to conduct optimization for plan.The optimized quality of plan and execution efficiency of two kinds of algorithms were assessed,and the influences of different tumor volumes also were considered.The planed quality assessment included dosimetric parameters of the target region and organ at risk(OAR).The assessment parameters of execution efficiency included the numbers of monitor units(MUs),nodes and beams,and estimated treatment time.Paired t-test method was adopted to analyze quality of plan and treatment efficiency.Results:On the aspect of the dose of target region,for small hepatocellular carcinoma,the conformity index(CI)value(1.08±0.05)of target region of VoLO algorithm was significantly better than(1.17±0.06)of SO algorithm(t=4.631,P<0.05).The gradient index(GI),coverage rate and dose by 95%(D95%)of VoLO algorithm were better than those of SO algorithm,while the differences were not significant(P>0.05).According to the defined standards of liver surgery,for large hepatocellular carcinoma,the differences in CI,GI,coverage rate and D95%of target region between two kinds of algorithms were significant(t=3.337,4.238,-3.359,-3.311,P<0.05),respectively.On the aspect of dosimetry for OAR,for the target region of large hepatocellular carcinoma,the differences of liver Dmean and D700 cm3 between two kinds of algorithms were significant(t=4.114,3.415,P<0.05).However,for small hepatocellular carcinoma,there was no significant statistical difference in dosimetry parameters of OAR between two kinds of algorithms(P>0.05).The execution efficiency of the plan of VoLO group was obviously higher than that of SO group,and the differences of MU number,node number,beam number and estimated treatment time between two groups were significant(t=12.661,4.423,5.024,9.487,P<0.05).Conclusion:The quality of VoLO plan is significantly better than that of SO,which has a significant improvement in execution efficiency of treatment.For the cases of large hepatocellular carcinoma with more complexity,the VoLO optimization shows better advantages on the aspect of dose on target region,and protection for normal liver.