Predicting brain age using partition modeling strategy and atlas-based attentional enhancement in the Chinese population.

As a biomarker of human brain health during development, brain age is estimated based on subtle differences in brain structure from those under typical developmental. Magnetic resonance imaging (MRI) is a routine diagnostic method in neuroimaging. Brain age prediction based on MRI has been widely studied. However, few studies based on Chinese population have been reported. This study aimed to construct a brain age predictive model for the Chinese population across its lifespan. We developed a partition prediction method based on transfer learning and atlas attention enhancement. The participants were separated into four age groups, and a deep learning model was trained for each group to identify the brain regions most critical for brain age prediction. The Atlas attention-enhancement method was also used to help the models focus only on critical brain regions. The proposed method was validated using 354 participants from domestic datasets. For prediction performance in the testing sets, the mean absolute error was 2.218 ± 1.801 years, and the Pearson correlation coefficient (r) was 0.969, exceeding previous results for wide-range brain age prediction. In conclusion, the proposed method could provide brain age estimation to assist in assessing the status of brain health.

Predictive value of peripheral blood biomarkers in patients with non-small-cell lung cancer responding to anti-PD-1-based treatment.

BACKGROUND: The introduction of the anti-PD-1 antibody has greatly improved the clinical outcomes of patients with non-small cell lung cancer (NSCLC). In this study, we retrospectively analyzed the efficacy of PD-1 antibody-based therapy in patients with locally advanced inoperable or metastatic NSCLC and reported an association between peripheral blood biomarkers and clinical response in these patients. METHODS: This single-center study included medical record data of patients with NSCLC treated with the PD-1 antibody as a first-line or subsequent line of treatment, either as monotherapy or in combination with chemotherapy. The patients were enrolled from 2020 to 2022. We dynamically evaluated multiple Th1 and Th2 cytokines in the blood serum and analyzed the phenotype of T cells from the peripheral blood to explore the correlation between cytokine levels, T cell phenotypes, and clinical response. RESULTS: A total of 88 patients with stage IIIA-IV NSCLC were enrolled, out of which 60 (68.18%) achieved a partial response (PR), 13 (14.77%) had stable disease (SD), and 15 (17.05%) experienced disease progression (PD). The disease control rate was 82.95%. Our results suggested a significant reduction (P = 0.002, P < 0.005) in lymphocyte absolute counts after treatment in patients with PD. Higher levels of IFN-γ (P = 0.023, P < 0.05), TNF-α (P = 0.00098, P < 0.005), IL-4 (P = 0.0031, P < 0.005), IL-5 (P = 0.0015, P < 0.005), and IL-10 (P = 0.036, P < 0.05) were detected in the peripheral blood before treatment in the PR group compared to the PD group. Moreover, patients with high levels of IL-5, IL-13, IL-4, IL-6, IFN-γ, and TNF-α (> 10 ng/mL) had superior progression-free survival compared to those with low levels (< 10 ng/mL). Furthermore, PD-1 expression on CD8+ T cells was higher in patients who showed a PR than in those who did not show a response (SD + PD; P = 0.042, P < 0.05). CONCLUSIONS: The findings of this study imply that the decrease in absolute blood lymphocyte counts after treatment is correlated with disease progression. Serum cytokine levels may predict the effectiveness and survival rates of anti-PD-1 blockade therapy in patients with NSCLC. In addition, PD-1 expression on CD8+ T cells was positively associated with better clinical response. Our findings highlight the potential of peripheral blood biomarkers to predict the effectiveness of PD-1-targeted treatments in patients with NSCLC. Larger prospective studies are warranted to further clarify the value of these biomarkers.

Assessment of the glymphatic function in children with attention-deficit/hyperactivity disorder.

OBJECTIVES: Whether the alternation of the glymphatic system exists in neurodevelopmental disease still remains unclear. In this study, we investigated structural and functional changes in the glymphatic system in the treatment-naïve attention-deficit/hyperactivity disorder (ADHD) children by quantitatively measuring the Virchow-Robin spaces (VRS) volume and diffusion tensor image-analysis along the perivascular space (DTI-ALPS). METHODS: Forty-seven pediatric ADHD patients and 52 age- and gender-matched typically developing (TD) children were recruited in this prospective study. The VRS volume was calculated using a semi-automated approach in axial T2-weighted images. Diffusivities along the x-, y-, and z-axes in the projection, association, and subcortical neural fiber areas were measured. The ALPS index, a ratio that accentuated water diffusion along the perivascular space, was calculated. The Mann-Whitney U test was used to compare the quantitative parameters; Pearson's correlation was used to analyze the correlation with clinical symptoms. RESULTS: The cerebral VRS volume (mean, 15.514 mL vs. 11.702 mL) and the VRS volume ratio in the ADHD group were larger than those in the TD group (all p < 0.001). The diffusivity along the x-axis in association fiber area and ALPS index were significantly smaller in the ADHD group vs. TD group (mean, 1.40 vs.1.59, p < 0.05 after false discovery rate adjustment). Besides, the ALPS index was related to inattention symptoms of ADHD (r = - 0.323, p < 0.05). CONCLUSIONS: Our study suggests that the glymphatic system alternation may participate in the pathogenesis of ADHD, which may be a new research direction for exploring the mechanisms of psycho-behavioral developmental disorders. Moreover, the VRS volume and ALPS index could be used as the metrics for diagnosing ADHD. CLINICAL RELEVANCE STATEMENT: Considering the potential relevance of the glymphatic system for exploring the mechanisms of attention deficit/hyperactivity, the Virchow-Robin spaces volume and the analysis along the perivascular space index could be used as additional metrics for diagnosing the disorder. KEY POINTS: • Increased Virchow-Robin space volume and decreased analysis along the perivascular space index were found in the treatment-naïve attention-deficit/hyperactivity disorder children. • The results of this study indicate that the glymphatic system alternation may have a valuable role in the pathogenesis of attention-deficit/hyperactivity disorder. • The analysis along the perivascular space index is correlated with inattention symptoms of attention-deficit/hyperactivity disorder children.

Gray and white matter abnormalities in children with type 2 and 3 SMA: A morphological assessment.

This study investigated the changes in brain gray and white matter structure in SMA patients and their correlation with the severity of the disease. A total of 43 SMA patients (including 22 type II and 21 type III SMA patients) and 37 healthy controls were evaluated by MRI. The gray matter volume, gray matter thickness, gray matter surface area, and white matter volume of designated brain regions automatically segmented by FreeSurfer, were compared. We evaluate clinical characteristics of SMA and study the correlation between clinical characteristics and structural changes. SMA showed significant bilateral cortical superficial area loss in the frontal, parietal, and temporal lobes and global white matter volume decreases. Moreover, these patients were also found with an increased mean thickness of entire brain and right gray matter. An increased right postcentral gyrus superficial area, right central sulcus volume, and white matter volume of the right postcentral were associated with higher HFMSE scores. CONCLUSION: Type 2 and 3 children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. The lack of SMN protein possibly interacted with cerebellar structural changes in somatosensory areas. WHAT IS KNOWN: • MRI has found brain changes in SMA patients, however, there is no unified conclusion and lack of correlation with clinical degree in children SMA with type 2-3. WHAT IS NEW: • Type II and II children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. Cerebellar structural changes in somatosensory areas may attribute to the lack of SMN protein.

Altered neurovascular coupling in the children with attention-deficit/hyperactivity disorder: a comprehensive fMRI analysis.

The coupling between resting-state cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) signals reflects the mechanism of neurovascular coupling (NVC), which have not been illustrated in attention-deficit/hyperactivity disorder (ADHD). Fifty ADHD and 42 age- and gender-matched typically developing controls (TDs) were enrolled. The NVC imaging metrics were investigated by exploring the Pearson correlation coefficients between CBF and BOLD-derived quantitative maps (ALFF, fALFF, DCP maps). Three types of NVC metrics (CBF-ALFF, CBF-fALFF, CBF-DCP coupling) were compared between ADHD and TDs group, and the inner association between altered NVC metrics and clinical variables in ADHD group was further analyzed. Compared to TDs, ADHD showed significantly reduced whole-brain CBF-ALFF coupling (P < 0.001). Among regional level (all PFDR < 0.05), ADHD showed significantly lower CBF-ALFF coupling in bilateral thalamus, default-mode network (DMN) involving left anterior cingulate (ACG.L) and right parahippocampal gyrus (PHG.R), execution control network (ECN) involving right middle orbital frontal gyrus (ORBmid.R) and right inferior frontal triangular gyrus (IFGtriang.R), and increased CBF-ALFF coupling in attention network (AN)-related left superior temporal gyrus (STG.L) and somatosensory network (SSN))-related left rolandic operculum (ROL.L). Furthermore, increased CBF-fALFF coupling was found in the visual network (VN)-related left cuneus and negatively correlated with the concentration index of ADHD (R = - 0.299, PFDR = 0.035). Abnormal regional NVC metrics were at widespread neural networks in ADHD, mainly involved in DMN, ECN, SSN, AN, VN and bilateral thalamus. Notably, this study reinforced the insights into the neural basis and pathophysiological mechanism underlying ADHD.

Testing the generalizability of cfDNA fragmentomic features across different studies for cancer early detection.

cfDNA fragmentomic features have been used in cancer detection models; however, the generalizability of the models needs to be tested. We proposed a type of cfDNA fragmentomic feature named chromosomal arm-level fragment size distribution (ARM-FSD), evaluated and compared its performance and generalizability for lung cancer and pan-cancer detection with existing cfDNA fragmentomic features (as reference) by using cohorts from different institutions. The ARM-FSD lung cancer model outperformed the reference model by ∼10% when being tested by two external cohorts (AUC: 0.97 vs. 0.86; 0.87 vs. 0.76). For pan-cancer detection, the performance of the ARM-FSD based model is consistently higher than the reference (AUC: 0.88 vs. 0.75, 0.98 vs. 0.63) in a pan-cancer and a lung cancer external validation cohort, indicating that ARM-FSD model produces stable performance across multiple cohorts. Our study reveals ARM-FSD based models have a higher generalizability, and highlights the necessity of cross-study validation for predictive model development.

Potential role of blood pressure variability and plasma neurofilament light in the mechanism of comorbidity between Alzheimer's disease and cerebral small vessel disease.

INTRODUCTION: Long-term blood pressure variability (BPV) and plasma neurofilament light (pNfL) have been identified as potential biomarkers for Alzheimer's disease (AD) and cerebral small vessel disease (CSVD). However, the relationship between BPV, pNfL, and their association with the comorbidity of AD and CSVD remains unknown. METHODS: Participants with normal cognition and mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study were included in the data analysis. Linear mixed-effects regression models and causal mediation analyses were conducted to investigate the relationship among BPV, pNfL, comorbidity-related brain structural changes (hippocampal atrophy and white matter hyperintensities [WMH]), and cognitive function. RESULTS: BPV was associated with pNfL, volumes of hippocampus and WMH, and cognition. pNfL mediated the effects of BPV on brain structural changes and cognition. DISCUSSION: Our findings suggest a potential role of BPV and pNfL in the mechanism of comorbidity between AD and CSVD, underscoring the importance of BPV intervention in the general population. HIGHLIGHTS: Individuals with both Alzheimer's disease (AD) and cerebral small vessel disease (CSVD) pathologies had elevated blood pressure variability (BPV) and plasma neurofilament light (pNfL). The association between different components of BPV and brain structural changes may vary. BPV was associated with pNfL levels independent of average blood pressure. pNfL mediated the effects of BPV on comorbidity-related brain structural changes and cognitive performance.

[Development of green pesticides from traditional Chinese medicines based on artificial intelligence and compatibility of traditional Chinese medicines].

The food security of China as a big agricultural country is attracting increasing attention. With the progress in the traditional Chinese medicine industry, Chinese medicinal materials and their preparations have been gradually developed as agents for disease prevention and with antimicrobial and insecticidal functions in agriculture. Promoting pesticide innovation by interdisciplinary integration has become the trend in pesticide research globally. Considering the increasingly important roles of green pesticides from traditional Chinese medicines and artificial intelligence in pest target prediction, this paper proposed an innovative green control strategy in line with the concepts of ecological sustainable development and food security protection. CiteSpace was used for visual analysis of the publications. The results showed that artificial intelligence had been extensively applied in the pesticide field in recent years. This paper explores the application and development of biopesticides for the first time, with focus on the plant-derived pesticides. The thought of traditional Chinese medicine compatibility can be employed to creat a new promosing field: pesticides from traditional Chinese medicine. Moreover, artificial intelligence can be employed to build the formulation system of pesticides from traditional Chinese medicines and the target prediction system of diseases and pests. This study provides new ideas for the future development and market application of biopesticides, aiming to provide more healthy and safe agricultural products for human beings, promote the innovation and development of green pesticides in China, and protect the sustainable development of the environment and ecosystem. This may be the research hotspot and competition point for the green development of the pesticide industry chain in the future.

Disrupted small-world networks in children with drug-naïve atten-tion-deficit/hyperactivity disorder: a DTI-based network analysis.

OBJECTIVES: To explore the alterations in the white matter (WM) structural connectome in children with drug-naïve attention-deficit/hyperactivity disorder (ADHD). METHODS: Forty-nine pediatric ADHD and 51 age- and gender-matched typically developing (TD) children aged 6-14 years old were enrolled. This cross-sectional study applied graph theoretical analysis to assess the white matter organization based on deterministic diffusion tensor imaging (DTI). WM structural connectivity was constructed in 90 cortical and subcor-tical regions, and topological parameters of the resulting graphs were calculated. Networks were compared between two groups. The digit cancellation test (DCT) was taken to evaluate clinical symptom severity in pediatric ADHD, using the concentration index and the total cancellation test scores. Then, a partial correlation analysis was performed to explore the re-lationship between significant topologic metrics and clinical symptom severity. RESULTS: Compared to TDs, ADHD showed an increase in the characteristic path length (Lp), normalized clustering coefficient (γ), small-worldness (σ), and a decrease in the global effi-ciency (Eglob) (all P <0.05). Furthermore, ADHD showed reduced nodal centralities mainly in the regions of default mode (DMN), central executive network (CEN), basal ganglia, and bilateral thalamus (all P <0.05). After performing Benjamini-Hochberg's procedure, only left orbital part of superior frontal gyrus (ORBsup.L) and left caudate (CAU) were statistically significant (P < 0.05, FDR-corrected). In addition, the concentration index of ADHD was negatively correlated with the nodal betweenness of the left orbital part of the middle frontal gyrus (ORBmid.L) (r = -0.302, P = 0.042). CONCLUSIONS: Our findings revealed an ADHD-related shift of WM network topology toward "regularization" pattern, characterized by decreased global network integration, which is also reflected by changed nodal centralities involving DMN, CEN, basal ganglia, and bilateral thalamus. ADHD could be understood by examining the dysfunction of large-scale spatially distributed neural networks.

Exploring multimorbidity profiles in middle-aged inpatients: a network-based comparative study of China and the United Kingdom.

BACKGROUND: Multimorbidity is better prevented in younger ages than in older ages. This study aims to identify the differences in comorbidity patterns in middle-aged inpatients from China and the United Kingdom (UK). METHODS: We utilized 184,133 and 180,497 baseline hospitalization records in middle-aged populations (40-59 years) from Shaanxi, China, and UK Biobank. Logistic regression was used to calculate odds ratios and P values for 43,110 unique comorbidity patterns in Chinese inpatients and 21,026 unique comorbidity patterns in UK inpatients. We included the statistically significant (P values adjusted by Bonferroni correction) and common comorbidity patterns (the pattern with prevalence > 1/10,000 in each dataset) and employed network analysis to construct multimorbidity networks and compare feature differences in multimorbidity networks for Chinese and UK inpatients, respectively. We defined hub diseases as diseases having the top 10 highest number of unique comorbidity patterns in the multimorbidity network. RESULTS: We reported that 57.12% of Chinese inpatients had multimorbidity, substantially higher than 30.39% of UK inpatients. The complete multimorbidity network for Chinese inpatients consisted of 1367 comorbidities of 341 diseases and was 2.93 × more complex than that of 467 comorbidities of 215 diseases in the UK. In males, the complexity of the multimorbidity network in China was 2.69 × more than their UK counterparts, while the ratio was 2.63 × in females. Comorbidities associated with hub diseases represented 68.26% of comorbidity frequencies in the complete multimorbidity network in Chinese inpatients and 55.61% in UK inpatients. Essential hypertension, dyslipidemia, type 2 diabetes mellitus, and gastritis and duodenitis were the hub diseases in both populations. The Chinese inpatients consistently demonstrated a higher frequency of comorbidities related to circulatory and endocrine/nutritional/metabolic diseases. In the UK, aside from these comorbidities, comorbidities related to digestive and genitourinary diseases were also prevalent, particularly the latter among female inpatients. CONCLUSIONS: Chinese inpatients exhibit higher multimorbidity prevalence and more complex networks compared to their UK counterparts. Multimorbidity with circulatory and endocrine/nutritional/metabolic diseases among both Chinese and UK inpatients necessitates tailored surveillance, prevention, and intervention approaches. Targeted interventions for digestive and genitourinary diseases are warranted for the UK.

Glymphatic system dysfunction in pediatric acute lymphoblastic leukemia without clinically diagnosed central nervous system infiltration: a novel DTI-ALPS method.

BACKGROUND AND OBJECTIVE: Central nervous system (CNS) infiltration commonly occurs in children with acute lymphoblastic leukemia (ALL). Nevertheless, CNS infiltration is rarely detected at the initial diagnosis. The glymphatic system, which regulates cerebrospinal fluid (CSF) and interstitial fluid transport, is considered one of the possible routes of CNS infiltration by leukemia cells. In this study, we used diffusion tensor image analysis along the perivascular space (DTI-ALPS) method to investigate glymphatic system function and obtained CSF volume using synthetic magnetic resonance imaging (SyMRI) in pediatric ALL without clinically diagnosed CNS infiltration. MATERIALS AND METHODS: Twenty-nine ALL and 29 typically developing (TD) children were prospectively recruited (age 4-16 years) in the present study. Group differences in brain volumetric parameters, brain water diffusivities, and the ALPS index were evaluated after controlling for age, gender, and handedness. Furthermore, significant group-different parameters were correlated with clinical information using partial correlations analysis. RESULTS: Lower Dxassoc and ALPS index, and increased CSF volume were found in pediatric ALL (all pFDR-corrected < 0.05). Moreover, the ALPS index was negatively associated with the risk classification (r = - 0.59, pFDR-corrected = 0.04) in pediatric ALL. CONCLUSIONS: Dysfunction of the glymphatic system and accumulation of CSF were presented in pediatric ALL without clinically diagnosed CNS infiltration. These novel findings suggested that the glymphatic system might be essential in the early-stage process of ALL CNS infiltration, which provides a new direction for exploring underlying mechanisms and early detection of pediatric ALL CNS infiltration. KEY POINTS: • Lower Dxassoc and ALPS index, and increased CSF volume were found in pediatric ALL (all pFDR-corrected < 0.05). • The ALPS index was negatively associated with the risk classification (r = -0.59, pFDR-corrected = 0.04) in pediatric ALL. • Dysfunction of the glymphatic system and accumulation of CSF were presented in pediatric ALL without clinically diagnosed CNS infiltration, which suggested that the ALPS index and CSF volume might be promising imaging markers for early detection of pediatric ALL CNS infiltration.

Pathology of MRI and second-look ultrasound detected multifocal breast cancer.

INTRODUCTION: Targeted second-look ultrasound (US) is often performed following MRI of the breast to determine if an MRI-detected lesion is visible on US and thus amenable to US-guided biopsy. This study aimed to assess the pathology of lesions detected and biopsied on the second-look US. In particular, for multifocal cancers, whether the pathology of additional lesions detected by second-look US is different to the index lesion. METHODS: Multicentre single-institution retrospective study of 300 consecutive cases of second-look US biopsies from August 2017 to April 2022 was performed, with their histopathology and imaging characteristics recorded. For multifocal cancers, Wilcoxon Signed Ranks Tests were used to compare differences between the index and additional lesions in the histopathology category (i.e., high-risk benign, precursor or malignant) and BRE grade. RESULTS: 69 multifocal cancers were detected. For the purposes of this study, additional lesions were considered more invasive if they were of a higher histopathological category or BRE grade, or demonstrated lymphovascular invasion when the primary lesion did not. 15/69 additional lesions were not seen on the initial mammogram/tomography or ultrasound, seen on subsequent MRI and second look US, and were less invasive than the index lesion. 3/69 additional lesions were more invasive than their index lesions. Wilcoxon Signed Ranks test showed additional lesions were of either similar or lesser invasiveness compared to index lesions (z= -3.207, p = 0.001) in the histopathological category, and the same or lower BRE grade (z= -2.972, p = 0.003). CONCLUSION: In multifocal breast cancers, additional lesions detected on MRI and second-look US have the same or less invasive histopathology compared to the index lesion.

Total alkaloids from the seed embryo of Nelumbo nucifera Gaertn. improve cognitive impairment in APP/PS1 mice and protect Aß-damaged PC12 cells.

The seed embryo of Nelumbo nucifera Gaertn. is a famous traditional Chinese medicine and food which is considered conducive to the prevention of Alzheimer's disease (AD). In this study, the effect and mechanism of TASENN (total alkaloids from the seed embryo of Nelumbo nucifera Gaertn.) on AD mice and amyloid-ß (Aß) injured PC12 cells were evaluated. HPLC-UV analysis showed that the extracted TASENN (purity = 95.6%) mainly contains Liensinine, Isoliensinine, and Neferine (purity was 23.01, 28.02, and 44.57%, respectively). In vivo, oral treatment with TASENN (50 mg/kg/day for 28 days) improved the learning and memory functions of APP/PS1 transgenic mice, ameliorated the histopathological changes of cortical and hippocampal neurons, and inhibited neuronal apoptosis. We found that TASENN reduced the phosphorylation of Tau and the formation of neurofibrillary tangles (NFTs) in APP/PS1 mouse brain. Moreover, TASENN down-regulated the expression of APP and BACE1, ameliorated Aß deposition, and inhibited microglial proliferation and aggregation. The elevated protein expression of CaM and p-CaMKII in APP/PS1 mouse brain was also reduced by TASENN. In vitro, TASENN inhibited the apoptosis of PC12 cells injured by Aß25-35 and increased the cell viability. Aß25-35-induced increase of cytosolic free Ca2+ level and high expression of CaM, p-CaMKII, and p-Tau were decreased by TASENN. Our findings indicate that TASENN has a potential therapeutic effect on AD mice and a protective effect on PC12 cells. The anti-AD activity of TASENN may be closely related to its negative regulation of the CaM pathway.

Disparities in the medical expenditures of patients with cancer and concomitant mental disorder: analyzing the effects of diagnosis sequence order.

BACKGROUND: Cancer is the leading cause of death in Taiwan. Medical expenditures related to cancer accounted for 44.8% of all major illness insurance claims in Taiwan. Prior research has indicated that the dual presence of cancer and mental disorder in patients led to increased medical burden. Furthermore, patients with cancer and concomitant mental disorder could incur as much as 50% more annual costs than those without. Although previous studies have investigated the utilization of patients with both diseases, the effects of morbidity sequence order on patient costs are, however, uncertain. This study explored medical expenditures linked with the comorbidity of cancer and mental disorder, with a focus on the impact of diagnosis sequence order. METHODS: This population-based retrospective matched cohort study retrieved patients with cancer and mental disorder (aged ≥ 20 years) from the Ministry of Health and Welfare Data Science Center 2005-2015 database. 321,045 patients were divided based on having one or both diseases, as well as on the sequence of mental disorder and cancer diagnosis. Study subjects were paired with comparison counterparts free of both diseases using Propensity Score Matching at a 1:1 ratio. Annual Cost per Patient Linear Model (with a log-link function and gamma distribution) was used to assess the average annual cost, covarying for socio-demographic and clinical factors. Binomial Logistic Regression was used to evaluate factors associated with the risk of high-utilization. RESULTS: The "Cancer only" group had higher adjusted mean annual costs (NT$126,198), more than 5-times that of the reference group (e^ß: 5.45, p < 0.001). However, after exclusion of patients with non-cancer and inclusion of diagnosis sequence order for patients with cancer and concomitant mental disorder, the post-cancer mental disorder group had the highest expenditures at over 13% higher than those diagnosed with only cancer on per capita basis (e^ß: 1.13, p < 0.001), whereas patients with cancer and any pre-existing mental disorder incurred lower expenditures than those with only cancer. The diagnosis of post-cancer mental disorder was significantly associated with high-utilization (OR = 1.24; 95% CI: 1.047-1.469). Other covariates associated with high-utilizer status included female sex, middle to old age, and late stage cancer. CONCLUSION: Presence of mental disorder prior to cancer had a diminishing effect on medical utilization in patients, possibly indicating low medical compliance or adherence in patients with mental disorder on initial treatments after cancer diagnosis. Patients with post-cancer mental disorder had the highest average annual cost. Similar results were found in the odds of reaching high-utilizer status. The follow-up of cancer treatment for patients with pre-existing mental disorders warrants more emphasis in an attempt to effectively allocate medical resources.

Evaluation of individual-based morphological brain network alterations in children with attention-deficit/hyperactivity disorder: a multi-method investigation.

To investigate the topological organization of individual-based morphological brain networks (MBNs) in attention-deficit/hyperactivity disorder (ADHD) children with different methods. A total of 60 ADHD children and 60 typically developing (TD) controls matched for age and gender were enrolled. Each participant underwent a structural 3D T1-weighted scan. Based on the inter-regional morphological similarity of GM regions, Kullback-Leibler-based similarity (KLS), Multivariate Euclidean Distance (MED), and Tijms's method were used to construct individual-based MBNs, respectively. The between-group difference of global and nodal network topological profiles was estimated, and partial correlation analysis was used for further analysis. According to KLS and MED-based network, ADHD showed a decreased global efficiency (Eglob) and increased characteristic path length (Lp) compared to the TD group, while Tijms's method-based network showed no between-group difference in global and nodal profiles. Nodal profiles were significantly decreased in the bilateral caudate, and nodal efficiency of the bilateral caudate was negatively correlated with clinical symptom severity of ADHD (P < 0.05, FDR-corrected) by the KLS-based network. Nodal betweenness was significantly decreased in the left inferior occipital gyrus and correlated with clinical symptom severity of ADHD (P < 0.05, FDR-corrected) by the MED-based network. ADHD was found to have a significantly less integrated organization and a shift to a "weaker small-worldness" pattern, while abnormal nodal profiles were mainly in the corpus striatum and default-mode networks. Our study highlights the crucial role of abnormal morphological connectivity patterns in understanding the brain maturational effects in ADHD and enriching the insights into MBNs at an individual level.

Quantification of myelination in children with attention-deficit/hyperactivity disorder: a comparative assessment with synthetic MRI and DTI.

Evaluation of myelin content is crucial for attention-deficit/hyperactivity disorder (ADHD). To estimate myelin content in ADHD based on synthetic MRI-based method and compare it with established diffusion tensor imaging (DTI) method. Fifth-nine ADHD and fifty typically developing (TD) children were recruited. Global and regional myelin content (myelin volume fraction [MVF] and myelin volume [MYV]) were assessed using SyMRI and compared with DTI metrics (fractional anisotropy and mean/radial/axial diffusivity). The relationship between significant MRI parameters and clinical variables were assessed in ADHD. No between-group differences of whole-brain myelin content were found. Compared to TDs, ADHD showed higher mean MVF in bilateral internal capsule, external capsule, corona radiata, and corpus callosum, as well as in left tapetum, left superior fronto-occipital fascicular, and right cingulum (all PFDR-corrected < 0.05). Increased MYV were found in similar regions. Abnormalities of DTI metrics were mainly in bilateral corticospinal tract. Besides, MVF in right retro lenticular part of internal capsule was negatively correlated with cancellation test scores (r = - 0.41, P = 0.002), and MYV in right posterior limb of internal capsule (r = 0.377, P = 0.040) and left superior corona radiata (r = 0.375, P = 0.041) were positively correlated with cancellation test scores in ADHD. Increased myelin content underscored the important pathway of frontostriatal tract, posterior thalamic radiation, and corpus callosum underlying ADHD, which reinforced the insights into myelin quantification and its potential role in pathophysiological mechanism and disease diagnosis. Prospectively registered trials number: ChiCTR2100048109; date: 2021-07.

[Preparation of Huoluo Xiaoling gel plaster and its transdermal penetration in vitro].

Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects. To make it directly treat lesion and improve the effect, this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance, so as to provide a scientific basis for its development and utilization. Using primary viscosity, holding viscosity, and sensory score as evaluation indexes, the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method. The ultra-performance liquid chromatography(UPLC) method was established to determine the content of eight active ingredients, including Danshensu, ferulic acid, salvianolic acid B, salvianolic acid A, ligustilide, tanshinone Ⅱ_A, 11-keto-ß-boswellic(KBA), and 3-acetyl-11-keto-ß-boswellic acid(AKBA). A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion. The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g), glycerol(7.00 g), micropowder silica gel(1.25 g), sodium carboxymethyl cellulose(0.20 g), tartaric acid(0.06 g), and glyceryl aluminum(0.04 g). The mass fractions of eight active ingredients in the paste were successively 0.48, 0.014, 0.95, 0.39, 0.57, 0.055, 0.35, and 0.97 mg·g~(-1). The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients, and the law of drug penetration conformed to the zero equation or the Higuchi equation. The gel paste prepared by the optimal prescription has good appearance and adhesion, with no residue, and has the characteristics of skeletal slow-release preparation, which is easy to reduce the number of administration, la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.

[High-value utilization technology and approach of Chinese medicinal residues under background of "Dual Carbon"].

In recent years, the traditional Chinese medicine(TCM)industry has experienced rapid development, resulting in a significant amount of Chinese medicinal residues generated during the industrial manufacturing process. Currently, the main methods of handling Chinese medicinal residues include stacking, landfilling, and incineration, which lead to substantial resource waste and potential environmental pollution. With "carbon peak" and "carbon neutrality"( "Dual Carbon")becoming national strategic goals, the TCM industry is ushering in a new wave of "low-carbon" trends, and the high-value utilization of Chinese medicinal residues has become a breakthrough for implementing a low-carbon economy in the TCM sector. From the perspective of a low-carbon economy, this article reviewed literature in China and abroad to summarize the microbial transformation technology, enzymatic conversion technology, biomass pyrolysis, gasification, hydrothermal liquefaction, and other high-value utilization technologies for Chinese medicinal residues. It also overviewed the applications of Chinese medicinal residue in feed additives, organic fertilizers, edible mushroom cultivation substrates, preparation of activated carbon for wastewater treatment, and new energy batteries. Considering the current status of resource utilization of Chinese medicinal residues, feasible strategies and suggestions for resource development and utilization were proposed to improve the quality and efficiency of the Chinese medicinal resource industry chain and promote green development, thereby providing research ideas and theoretical basis for achieving carbon peak and carbon neutrality goals.

[Measures for waste and by-product recycling and circular economy of whole industry chain of traditional Chinese medicine resources facing carbon peak and carbon neutrality (dual carbon) goals].

It has become a common consensus that resource conservation and intensive recycling for improving resource utilization efficiency is an important way to achieve carbon peak and carbon neutrality(dual carbon). Traditonal Chinese medicine(TCM)resources as national strategic resources are the material basis and fundamental guarantee for the development of TCM industry and health services. However, the rapid growth of China's TCM industry and the continuous expansion and extension of the industrial chain have exposed the low efficiency of TCM resources. Resource waste and environmental pollution caused by the treatment and discharge of TCM waste have emerged as major problems faced by the development of the industry, which has aroused wide concern. Considering the dual carbon goals, this paper expounds the role and potential of TCM resource recycling and circular economy industry development. Taking the typical model of TCM resource recycling as the case of circular economy industry in reducing carbon source and increasing carbon sink, this paper puts forward the suggestions for the TCM circular economy industry serving the double carbon goals. The suggestions mainly include strengthening the policy and strategic leading role of the double carbon goals, building an objective evaluation system of low-carbon emission reduction in the whole industrial chain of TCM resources, building an industrial demonstration park for the recycling of TCM resources, and promoting the establishment of a circular economy system of the whole industrial chain of TCM resources. These measures are expected to guide the green transformation of TCM resource industry from linear economic model to circular economy model, provide support for improving the utilization efficiency and sustainable development of TCM resources, and facilitate the low-carbon and efficient development of TCM resource industry and the achievement of the double carbon goals.

Cytokines possibly involved in idiopathic epiretinal membrane progression after uncomplicated cataract surgery.

Epiretinal membrane (ERM) is a common retinal fibrotic disorder disease causing visual impairment and metamorphopsia. Recently, increasing attention has been devoted to ERM progression after uncomplicated cataract surgery. Cytokines, which play a role in diverse physiological and pathological activities in eyes, are suggested to be involved in these postoperative changes. However, few studies have investigated the post-cataract surgery cytokine expression changes in ERM eyes and their roles in the postoperative changes. The purpose of this study was to evaluate the aqueous levels of cytokines in eyes with idiopathic epiretinal membrane (iERM) both pre- and post-cataract surgery, and their correlations with postoperative iERM progression. In this study, aqueous humor (AH) samples were collected from iERM eyes (n = 25) and non-iERM eyes (n = 23) from 48 patients (48 eyes) undergoing uncomplicated cataract surgery preoperatively and 20 h postoperatively. Samples were analyzed for 48 cytokines with multiplex bead-based immunoassay. Correlations between cytokine level changes (postoperation vs. preoperation) and three-month postoperative best-corrected visual acuity (BCVA) and optical coherence tomography measure changes were evaluated in iERM eyes. We found that in iERM eyes, the levels of 4 cytokines exhibited significant elevations when compared with those in the controls (all p ≤ 0.0015) preoperatively. Postoperatively, the concentrations of 21 cytokines were higher than the preoperative levels in iERM eyes (all p ≤ 0.0015), among which GRO-α, IL-8, and MCP-3 levels showed more pronounced changes than the controls. Additionally, in iERM eyes, IL-4 level changes showed moderate positive correlations with MV (r = 0.492, p = 0.028) and MT (r = 0.481, p = 0.032) changes. LogMAR changes were positively correlated with IL-1α (r = 0.553, p = 0.011), IL-12(P40) (r = 0.544, p = 0.013), and MCP-3 (r = 0.588, p = 0.006) level changes. No significant cytokine-level-change differences were found between eyes with and without postoperative cystoid macular edema development. In conclusion, cataract surgery will bring great alterations to the specific intraocular cytokine microenvironment inherently in eyes with iERM. Many fibrotic and inflammatory cytokines showing elevated levels or relationships with clinical characteristics are suggested to be involved in the pathogenesis and post-cataract surgery progression of iERM; however, further investigations are needed to discern their real roles.