Background: and Purpose Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions. Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states. Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis. Conclusions Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.

Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.

Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

Objective:To investigate the relationship between retinoblastoma binding protein 1 (RB1) gene deletion and the prognosis of multiple myeloma (MM) patients, and the possible effect of renal insufficiency on it.Methods:A retrospective cohort study was conducted. The clinical data and follow-up information of MM patients who were treated in the Second Affiliated Hospital of Xuzhou Medical University and the Affiliated Hospital of Xuzhou Medical University from December 2020 to November 2023 were collected. According to the presence of RB1 gene deletion in bone marrow samples detected by fluorescence in situ hybridization (FISH), the patients were divided into the RB1 gene deletion group and the RB1 gene non-deletion group, and the clinicopathological characteristics and hematological index levels were compared between the two groups. Renal insufficiency was determined by renal function assessment indicator serum creatinine (Scr) >177 μmol/L. The Spearman test was used to analyze the relationship between the number of RB1 gene deletion positive cells and levels of Scr, hemoglobin and serum calcium in MM patients. The Kaplan-Meier method was used to analyze progression-free survival (PFS), and the Cox proportional hazards model was used to determine the influencing factors of PFS in all MM patients and RB1 gene deletion and non-deletion MM patients.Results:A total of 75 MM patients were enrolled, of whom 24 (32.0%) had RB1 gene deletion. There were no significant differences in gender, age ≥65 years old, bone destruction and lactate dehydrogenase level between the RB1 gene deletion and non-deletion groups (all P > 0.05). There were significant differences in the distributions of patients in each stage of MM International Staging System (ISS) and revised International Staging System (R-ISS) between the two groups, as well as in hemoglobin, serum calcium, Scr, β 2-microglobulin, serum albumin levels, and the proportion of bone marrow plasma cells (all P < 0.05). The number of RB1 gene deletion positive cells was positively correlated with Scr level ( r = 0.863, P = 0.016), but not with hemoglobin and serum calcium levels (both P > 0.05). The PFS of the RB1 gene non-deletion group was better than that of the RB1 gene deletion group (1-year PFS rate: 83.5% vs. 71.7%, 2-year PFS rate: 56.3% vs. 26.3%), and the difference was statistically significant ( P = 0.012). PFS in the non-renal insufficiency group was better than that in the renal insufficiency group (1-year PFS rate: 85.6% vs. 61.9%, 2-year PFS rate: 58.0% vs. 13.5%), and the difference was statistically significant ( P = 0.001). The PFS of patients without renal insufficiency in both the RB1 gene deletion and non-deletion groups was better than that in patients with renal insufficiency, and the differences were statistically significant (both P < 0.05). Multivariate Cox regression analysis showed that ISS stage Ⅲ was an independent risk factor for poor PFS in MM patients (stage Ⅲ vs. stage Ⅰ, HR = 11.317, 95% CI: 1.220-104.979, P = 0.033). Multivariate Cox regression analysis in RB1 gene deletion and non-deletion groups showed that ISS stage Ⅲ (stage Ⅲ vs. stageⅠ, HR = 4.166, 95% CI: 1.419-12.225, P = 0.009), R-ISS stage Ⅲ (stage Ⅲ vs. stage Ⅰ, HR = 3.800, 95% CI: 1.005-14.367, P = 0.049), serum calcium > 2.52 mmol/L (> 2.52 mmol/L vs. ≤2.52 mmol/L, HR = 2.398, 95% CI: 1.037-5.546, P = 0.041) and renal insufficiency (yes vs. no, HR = 2.363, 95% CI: 1.021-5.472, P = 0.045) were independent risk factors for poor PFS in RB1 gene non-deletion MM patients, and serum calcium >2.52 mmol/L (>2.52 mmol/L vs. ≤ 2.52 mmol/L, HR = 3.673, 95% CI: 1.160-11.627, P = 0.027) and renal insufficiency (yes vs. no, HR = 3.985, 95% CI: 1.220-13.016, P = 0.022) were independent risk factors for poor PFS in RB1 gene deletion MM patients. Conclusions:The PFS of MM patients with RB1 gene deletion is worse than that of patients without RB1 gene deletion, RB1 gene deletion may be related to renal insufficiency in MM patients, and the prognosis of MM patients with RB1 gene deletion and renal insufficiency may be worse.

Objective To assess the exposure levels of heavy metals,including lead,arsenic,mercury,and cadmium,in the local population in Sichuan and Chongqing,China,to compare and analyze the differences in reference intervals(RIs)obtained from direct and indirect sampling methods,and to explore the interchangeability and limitations of these two sampling methods.Methods RIs were obtained by the direct sampling method and the indirect sampling method.In the direct sample method,the levels of blood arsenic,urinary cadmium,urinary mercury,and blood lead levels of 5562 healthy participants aged 22-50 years in Sichuan and Chongqing,China were measured by atomic absorption spectrometry and inductively coupled plasma-mass spectrometry.Using the human biomonitoring(HBM)data,we established RIs for the population by a nonparametric method.On the other hand,in the indirect sampling method,RIs were established via a nonparametric method based on data from the laboratory information system(LIS)of a local hospital after stratifying healthy individuals using a Gaussian mixture model(GMM).Comparative analysis of the RIs derived from the two sampling methods were then conducted.Results The RI for blood arsenic was 0.11-1.3 μmol/L.The RI for urinary cadmium was 0.51-2.80 μmol/mol creatine for adults aged 22 to under 43 years and 0.66-2.96 μmol/mol creatine for adults aged 43-50 years.The RI for urinary mercury was 0.12-1.10 μmol/mol creatine.The RI for blood lead was 14.00-47.00 pg/L for adults aged 22 to under 41 year,16.00-53.38 pg/L for males aged 41-50 year,and 15.00-51.02 pg/L for females aged 41-50 year.Most of the RIs established by the direct sampling method had a narrower range compared to those established by the indirect sampling method,and the RIs established by both sampling methods were partially biased.Conclusions The RIs for blood arsenic,urine cadmium,urine mercury,and blood lead in healthy individuals aged 22-50 years in Sichuan and Chongqing,China were established using both direct and indirect sampling methods,which contributes to a better understanding of environmental exposure to metals in the general population and provides a reference for metal poisoning.For data from the same lab,the GMM-based indirect sampling method demonstrated relatively consistent performance in establishing RIs compared with the direct sampling method.

Abstract The application of artificial intelligence (AI) technology in the field of mental health is becoming increasingly extensive and in depth. As digital natives, children and adolescents are experiencing a significant shift in the prevention, identification, and intervention of their mental health issues:transitioning from traditional models to intelligent and digital approaches. At present, the mental health status of children and adolescents in China is not optimistic, with emotional disorders such as depression and anxiety showing a trend toward younger onset. However, the traditional mental health service model faces multiple challenges, including a shortage of professionals, low service accessibility, and difficulties in early identification. The study systematically reviews the current application status of AI technology in the mental health field of children and adolescents, including the latest progress in screening, assessment, intervention, and treatment; deeply analyzes the key challenges currently faced; and proposes suggestions for promoting the deep integration of AI technology and mental health services for children and adolescents, providing theoretical support and practical guidance for the intelligent, precise, and inclusive development of mental health services.

Objective: To evaluate the efficacy and prognosis of loop cutaneous ureterostomy (LCU) in the treatment of primary obstructive megaureter (POM) with severe hydroureteronephrosis (HUN) in infants under 1 year of age，so as to provide reference for infants unsuitable for stage-Ⅰ ureteral reimplantation. Methods: A retrospective analysis was conducted on 12 infants with POM and severe HUN treated with LCU in our hospital during Jan.2019 and Dec.2023.The clinical characteristics，surgical techniques，indications，postoperative complications，stage-Ⅱ surgical approaches，and follow-up outcomes were summarized. Results: All operations were successful，with an average operation time of (37.08±7.53) min (6 left-sided LCU and 6 right-sided LCU).During the mean follow-up of (10.12±2.70) months，all infants showed clinical improvement，with complete resolution or significant alleviation of hydronephrosis，reduced ureteral diameter，and increased renal cortical thickness.Complications included asymptomatic bacteriuria in 3 cases (25%) and urinary tract infection (UTI) in 1 case，all resolved with oral antibiotics.Four cases developed peristomal rashes，which improved with topical treatment.Eleven infants underwent stage-Ⅱ Cohen ureterovesical reimplantation at a mean age of (15.20±2.07) months.Notably，27.3%(3/11) required ureteral tailoring or plication during reimplantation，which reduced the risk of ischemic necrosis from excessive trimming.During the follow-up of (22.17±13.93) months，hydronephrosis and renal function improved，and no febrile UTI or bladder dysfunction occurred. Conclusion: LCU is a safe and effective method，which can provide adequate urinary drainage，relieve obstruction，stabilize renal function，and allow time for ureteral maturation and renal parenchymal recovery.LCU also facilitates subsequent stage-Ⅱ surgery by reducing ureteral dilation.

Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

Objective:To investigate the relationship between retinoblastoma binding protein 1 (RB1) gene deletion and the prognosis of multiple myeloma (MM) patients, and the possible effect of renal insufficiency on it.Methods:A retrospective cohort study was conducted. The clinical data and follow-up information of MM patients who were treated in the Second Affiliated Hospital of Xuzhou Medical University and the Affiliated Hospital of Xuzhou Medical University from December 2020 to November 2023 were collected. According to the presence of RB1 gene deletion in bone marrow samples detected by fluorescence in situ hybridization (FISH), the patients were divided into the RB1 gene deletion group and the RB1 gene non-deletion group, and the clinicopathological characteristics and hematological index levels were compared between the two groups. Renal insufficiency was determined by renal function assessment indicator serum creatinine (Scr) >177 μmol/L. The Spearman test was used to analyze the relationship between the number of RB1 gene deletion positive cells and levels of Scr, hemoglobin and serum calcium in MM patients. The Kaplan-Meier method was used to analyze progression-free survival (PFS), and the Cox proportional hazards model was used to determine the influencing factors of PFS in all MM patients and RB1 gene deletion and non-deletion MM patients.Results:A total of 75 MM patients were enrolled, of whom 24 (32.0%) had RB1 gene deletion. There were no significant differences in gender, age ≥65 years old, bone destruction and lactate dehydrogenase level between the RB1 gene deletion and non-deletion groups (all P > 0.05). There were significant differences in the distributions of patients in each stage of MM International Staging System (ISS) and revised International Staging System (R-ISS) between the two groups, as well as in hemoglobin, serum calcium, Scr, β 2-microglobulin, serum albumin levels, and the proportion of bone marrow plasma cells (all P < 0.05). The number of RB1 gene deletion positive cells was positively correlated with Scr level ( r = 0.863, P = 0.016), but not with hemoglobin and serum calcium levels (both P > 0.05). The PFS of the RB1 gene non-deletion group was better than that of the RB1 gene deletion group (1-year PFS rate: 83.5% vs. 71.7%, 2-year PFS rate: 56.3% vs. 26.3%), and the difference was statistically significant ( P = 0.012). PFS in the non-renal insufficiency group was better than that in the renal insufficiency group (1-year PFS rate: 85.6% vs. 61.9%, 2-year PFS rate: 58.0% vs. 13.5%), and the difference was statistically significant ( P = 0.001). The PFS of patients without renal insufficiency in both the RB1 gene deletion and non-deletion groups was better than that in patients with renal insufficiency, and the differences were statistically significant (both P < 0.05). Multivariate Cox regression analysis showed that ISS stage Ⅲ was an independent risk factor for poor PFS in MM patients (stage Ⅲ vs. stage Ⅰ, HR = 11.317, 95% CI: 1.220-104.979, P = 0.033). Multivariate Cox regression analysis in RB1 gene deletion and non-deletion groups showed that ISS stage Ⅲ (stage Ⅲ vs. stageⅠ, HR = 4.166, 95% CI: 1.419-12.225, P = 0.009), R-ISS stage Ⅲ (stage Ⅲ vs. stage Ⅰ, HR = 3.800, 95% CI: 1.005-14.367, P = 0.049), serum calcium > 2.52 mmol/L (> 2.52 mmol/L vs. ≤2.52 mmol/L, HR = 2.398, 95% CI: 1.037-5.546, P = 0.041) and renal insufficiency (yes vs. no, HR = 2.363, 95% CI: 1.021-5.472, P = 0.045) were independent risk factors for poor PFS in RB1 gene non-deletion MM patients, and serum calcium >2.52 mmol/L (>2.52 mmol/L vs. ≤ 2.52 mmol/L, HR = 3.673, 95% CI: 1.160-11.627, P = 0.027) and renal insufficiency (yes vs. no, HR = 3.985, 95% CI: 1.220-13.016, P = 0.022) were independent risk factors for poor PFS in RB1 gene deletion MM patients. Conclusions:The PFS of MM patients with RB1 gene deletion is worse than that of patients without RB1 gene deletion, RB1 gene deletion may be related to renal insufficiency in MM patients, and the prognosis of MM patients with RB1 gene deletion and renal insufficiency may be worse.