Sex-specific grey matter abnormalities in individuals with chronic insomnia.

Previous studies have reported sex differences in altered brain function in patients with chronic insomnia (CI). However, sex-related alterations in brain morphology have rarely been investigated. This study aimed to investigate sex-specific grey matter (GM) alterations in patients with CI and to examine the relationship between GM alterations and neuropsychological assessments. Ninety-three (65 females and 28 males) patients and 78 healthy (50 females and 28 males) controls were recruited. Structural magnetic resonance imaging data were analysed using voxel-based morphometry to test for interactions between sex and diagnosis. Spearman's correlation was used to assess the associations among structure, disease duration, and sleep-, mood-, and cognition-related assessments. Males with CI showed reduced GM volume in the left inferior parietal lobe, left middle cingulate cortex, and right supramarginal gyrus. Females with CI showed increased GM volume in the right Rolandic operculum. Moreover, mood-related assessments were negatively correlated with GM volumes in the right supramarginal gyrus and left inferior parietal lobe in the male patients, and cognitive-related assessments were positively correlated with GM volumes in the Rolandic operculum in the female patients. Our findings indicate sex-specific alterations in brain morphology in CI, thereby broadening our understanding of sex differences in CI and potentially providing complementary evidence for the development of more effective therapies and individual treatments.

A nomogram for predicting 28-day mortality in elderly patients with acute kidney injury receiving continuous renal replacement therapy: a secondary analysis based on a retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious condition, particularly among elderly patients. It is associated with high morbidity and mortality rates, further compounded by the need for continuous renal replacement therapy in severe cases. To improve clinical decision-making and patient management, there is a need for accurate prediction models that can identify patients at a high risk of mortality. METHODS: Data were extracted from the Dryad Digital Repository. Multivariate analysis was performed using least absolute shrinkage and selection operator (LASSO) logistic regression analysis to identify independent risk factors and construct a predictive nomogram for mortality within 28 days after continuous renal replacement therapy in elderly patients with acute kidney injury. The discrimination of the model was evaluated in the validation cohort using the area under the receiver operating characteristic curve (AUC), and calibration was evaluated using a calibration curve. The clinical utility of the model was assessed using decision curve analysis (DCA). RESULTS: A total of 606 participants were enrolled and randomly divided into two groups: a training cohort (n = 424) and a validation cohort (n = 182) in a 7:3 proportion. A risk prediction model was developed to identify independent predictors of 28-day mortality in elderly patients with AKI. The predictors included age, systolic blood pressure, creatinine, albumin, phosphorus, age-adjusted Charlson Comorbidity Index (CCI), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score. These predictors were incorporated into a logistic model and presented in a user-friendly nomogram. In the validation cohort, the model demonstrated good predictive performance with an AUC of 0.799. The calibration curve showed that the model was well calibrated. Additionally, DCA revealed significant net benefits of the nomogram for clinical application. CONCLUSION: The development of a nomogram for predicting 28-day mortality in elderly patients with AKI receiving continuous renal replacement therapy has the potential to improve prognostic accuracy and assist in clinical decision-making.

Communication Matters: The Role of Patient-Centered Communication in Improving Old Adults' Health Competence and Health Outcomes.

Research has demonstrated links between patient-centered communication (PCC) and patients' health outcomes. However, little is known about the underlying processes that may mediate the relationship. This study is one of the first to examine the influence of PCC on older adults' health outcomes, as well as the mediation role of health competence, from a longitudinal perspective. With a general basis of Street et al.'s pathway model, we proposed and tested mediation pathways linking patient-centered communication to the older population's general and mental health, mediated by health competence. Data from 2011, 2017 and 2020 iterations of the Health Information National Trends Survey (HINTS) were used for this study. This study focused on older adults aged 60 and above. Results indicated that after controlling participants' age, gender, education, income and race, PCC is related to the older people's health outcomes either directly or indirectly, irrespective of time series. Specifically, health competence was found to significantly mediate the associations between PCC and the older adults' general health or mental health over the three iterations. Noteworthily, findings from this study also revealed that different dimensions of PCC might exert different influences on older patients' health competence and health outcomes.

Progressive gray matter hypertrophy with severity stages of insomnia disorder and its relevance for mood symptoms.

OBJECTIVE: To investigate the gray matter (GM) alterations in patients with insomnia disorder (ID) at different severity stages and the relationship between GM alterations and sleep, mood, and cognitive measures. METHODS: One hundred one ID patients and 63 healthy controls (HC) were included. Each patient underwent structural MRI and completed sleep-, mood-, and cognitive-related questionnaires. The ID patients were further grouped into subthreshold insomnia (SI) group and clinical insomnia (CI) group. We investigated changes in GM volumes in ID patients via diffeomorphic anatomical registration through exponentiated lie algebra voxel-based morphometry (DARTEL-VBM). We first compared voxel-wise differences in GM volumes between the HC group and the ID group. Analysis of variance was performed on individual GM maps in the SI, CI, and HC groups to further investigate the effects of different stages of ID severity on GM volumes. Multiple regression was used to model the relationship between altered GM volumes in SI and CI groups and clinical measures. RESULTS: GM hypertrophies in the left anterior and middle cingulate gyrus, right middle and inferior temporal gyrus, and right cerebellum Crus II were detected in ID. Increased GM volume in the right middle temporal gyrus was detected in the SI group, whereas all three regions in the CI group. Regression analysis showed that mood- and cognitive-related measures had a positive correlation with GM volumes, while sleep-related measures had a negative correlation with GM volumes in the CI group. CONCLUSIONS: Our findings of the progressively increased GM volumes in ID suggest that a hypertrophic cortical morphological mechanism may underlie the altered neuroanatomy induced by insomnia. KEY POINTS: • Insomnia-induced GM hypertrophies in the cingulate gyrus, temporal gyrus, and cerebellum Crus II. • The middle temporal gyrus was early detectable in the SI group. • The increased GM volumes in the CI group were correlated with clinical measures.

Abnormal white matter within brain structural networks is associated with high-impulse behaviour in codeine-containing cough syrup dependent users.

Codeine-containing cough syrup (CCS) is considered as one of the most popular drug of dependence among adolescents because of its inexpensiveness and easy availability. However, its relationship with neurobiological effects remains sparsely explored. Herein, we examined how high-impulse behaviours relate to changes in the brain structural networks. Forty codeine-containing cough syrup dependent (CCSD) users and age-, gender-, and number of cigarettes smoked per day -matched forty healthy control (HC) subjects underwent structural brain imaging via MRI. High-impulse behaviour was assessed using the 30-item self-rated Barratt Impulsiveness Scale (BIS-11), and structural networks were constructed using diffusion tensor imaging and AAL-90 template. Between-group topological metrics were compared using nonparametric permutations. Benjamin-Hochberg false discovery rate correction was used to correct for multiple comparisons (P < 0.05). The relationships between abnormal network metrics and clinical characteristics of CCS dependent (BIS-11 total score, CCS- dependent duration and mean dose) were examined by Spearman's correlation. Structural networks of the CCSD group demonstrated lower small-world properties than those of the HC group. Abnormal changes in nodal properties among CCSD users were located mainly in the frontal gyrus, inferior parietal lobe and olfactory cortex. NBS analysis further indicated disrupted structural connections between the frontal gyrus and multiple brain regions. There were significant correlations between abnormal nodal properties of the frontal gyrus and clinical characteristics (BIS-11 total score, CCS dependent duration and mean dose) in the CCSD group. These findings suggest that the high-impulse behavioural expression in CCS addiction is associated with widespread brain regions, particularly within those in the frontal cortex. Aberrant brain regions and disrupted connectivity of structural network may be the bases of neuropathology for underlying symptoms of high-impulse behaviours in CCSD users, which may provide a novel sight to better treat and prevent codeine dependency in adolescents.

Image-guided selection of Gd@C-dots as sensitizers to improve radiotherapy of non-small cell lung cancer.

BACKGROUND: Recently, gadolinium-intercalated carbon dots (Gd@C-dots) have demonstrated potential advantages over traditional high-Z nanoparticles (HZNPs) as radiosensitizers due to their high stability, minimal metal leakage, and remarkable efficacy. RESULTS: In this work, two Gd@C-dots formulations were fabricated which bore carboxylic acid (CA-Gd@C-dots) or amino group (pPD-Gd@C-dots), respectively, on the carbon shell. While it is critical to develop innovative nanomateirals for cancer therapy, determining their tumor accumulation and retention is equally important. Therefore, in vivo positron emission tomography (PET) was performed, which found that 64Cu-labeled pPD-Gd@C-dots demonstrated significantly improved tumor retention (up to 48 h post injection) compared with CA-Gd@C-dots. Indeed, cell uptake of 64Cu-pPD-Gd@C-dots reached close to 60% of total dose compared with ~ 5% of 64Cu-CA-Gd@C-dots. pPD-Gd@C-dots was therefore further evaluated as a new radiosensitizer for non-small cell lung cancer treatment. While single dose radiation plus intratumorally injected pPD-Gd@C-dots did lead to improved tumor suppression, the inhibition effect was further improved with two doses of radiation. The persistent retention of pPD-Gd@C-dots in tumor region eliminates the need of reinjecting radiosensitizer for the second radiation. CONCLUSIONS: PET offers a simple and straightforward way to study nanoparticle retention in vivo, and the selected pPD-Gd@C-dots hold great potential as an effective radiosensitizer.

RXH-Reactive 18F-Vinyl Sulfones as Versatile Agents for PET Probe Construction.

Efficient radiolabeling reactions are important chemical tools in biomedical research especially in probe construction. Herein, three 18F-labeled vinyl sulfones were prepared. In particular, 18F-PEG1-VS (((2-(2-(fluoro-18F)ethoxy)ethyl)sulfonyl)ethane) could not only allow chemoselective labeling of bioactive molecules containing -XH (X = S, NH) groups, but also react with red blood cells both in vitro and in living mice for potential cell tracking applications. In addition, these hydrophilic agents were found to cross the blood brain barrier (BBB) efficiently and localize at the cerebellum region. In summary, 18F-labeled vinyl sulfones provide a versatile platform for PET probe construction.

Development of Bispecific NT-PSMA Heterodimer for Prostate Cancer Imaging: A Potential Approach to Address Tumor Heterogeneity.

Prostate cancer is a heterogeneous disease with a poor survival rate at late stage. In this report, a dual targeting PET agent was developed to partially address the tumor heterogeneity issue. The heterodimer F-BCN-PSMA-NT was designed to target PSMA and neurotensin receptor1 (NTR1), both of which have demonstrated great potential in prostate cancer management. The heterodimer was synthesized through the conjugation of Glu-urea-lys(Ahx) (PSMA targeting motif) and NT20.3 (NTR1 targeting motif) to a symmetric trifunctional linker, bearing an azide group for further modification. Radio-labeling was performed using strain promoted azide-alkyne click reaction with high yield. Cell based assays suggested that F-BCN-PSMA-NT has comparable or only slightly reduced binding affinity with the corresponding monomers. Small animal PET clearly demonstrated that the heterodimer probe has prominent uptake not only in NTR1 positive/PSMA negative PC-3 tumors (1.4 ± 0.3%ID/g), but also in the PSMA positive/NTR1 negative LnCap tumors (1.3 ± 0.2%ID/g). The tracer showed comparable tumor to background ratio with each monomer. In summary, prostate cancer is a heterogeneous disease in need of improved diagnostics and treatments. The PSMA-NT heterodimer represents a new class of molecules that can be used to target two distinct antigens related to prostate cancer. In addition to the imaging applications demonstrated in this study, the agent also holds great potential on the treatment of heterogeneous prostate cancer.

Cortical morphology of chronic users of codeine-containing cough syrups: association with sulcal depth, gyrification, and cortical thickness.

OBJECTIVES: The study aimed to explore the effects of codeine-containing cough syrup (CCS) exposure on cortical morphology and the relationship between cortical characteristics and CCS dependence. METHODS: Cortical morphometry based on Computational Anatomy Toolbox (CAT12) was used to compare changes in sulcal depth, gyrification, and cortical thickness of the cerebral cortex from 40 CCS users and 40 healthy controls (HCs) with two-sample t tests (p < 0.05, multiple comparison corrected). Relationships between abnormal cortical morphological changes and the duration of CCS use, impulsivity traits, and age of first use were investigated with correlation analysis (p < 0.05, uncorrected). RESULTS: CCS users exhibited significantly increased sulcal depth in the bilateral insula, bilateral lingual, bilateral superior frontal, right precuneus, and right middle frontal regions; increased gyrification in the right precentral cortex; and increased cortical thickness in the bilateral precentral, bilateral precuneus, and right superior temporal cortices compared to HCs. In addition, we found significant correlations between the bilateral insula, right superior frontal cortex, and right precentral gyrus and Barratt Impulsiveness Scale (BIS) total scores. CONCLUSIONS: Chronic CCS abuse may be associated with aberrant sulcal depth, gyrification, and cortical thickness. These morphological changes might serve as an underlying neurobiological mechanism of impulsive behavior in the CCS users. KEY POINTS: • Cortical morphological changes were detected in CCS users. • Increased sulcal depth, gyrification, and cortical thickness of some regions were found in the CCS users. • Positive correlations between cortical morphological changes and BIS total scores were identified.

Imaging Neurotensin Receptor in Prostate Cancer With 64Cu-Labeled Neurotensin Analogs.

INTRODUCTION: Neurotensin receptor 1 (NTR-1) is expressed and activated in prostate cancer cells. In this study, we explore the NTR expression in normal mouse tissues and study the positron emission tomography (PET) imaging of NTR in prostate cancer models. MATERIALS AND METHODS: Three 64Cu chelators (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid [DOTA], 1,4,7-triazacyclononane-N,N',N″-triacetic acid [NOTA], or AmBaSar) were conjugated to an NT analog. Neurotensin receptor binding affinity was evaluated using cell binding assay. The imaging profile of radiolabeled probes was compared in well-established NTR+ HT-29 tumor model. Stability of the probes was tested. The selected agents were further evaluated in human prostate cancer PC3 xenografts. RESULTS: All 3 NT conjugates retained the majority of NTR binding affinity. In HT-29 tumor, all agents demonstrated prominent tumor uptake. Although comparable stability was observed, 64Cu-NOTA-NT and 64Cu-AmBaSar-NT demonstrated improved tumor to background contrast compared with 64Cu-DOTA-NT. Positron emission tomography/computed tomography imaging of the NTR expression in PC-3 xenografts showed high tumor uptake of the probes, correlating with the in vitro Western blot results. Blocking experiments further confirmed receptor specificity. CONCLUSIONS: Our results demonstrated that 64Cu-labeled neurotensin analogs are promising imaging agents for NTR-positive tumors. These agents may help us identify NTR-positive lesions and predict which patients and individual tumors are likely to respond to novel interventions targeting NTR-1.

Intrinsic brain network abnormalities in codeine-containing cough syrup-dependent male individuals revealed in resting-state fMRI.

PURPOSE: To identify codeine-containing cough syrups (CCS)-related modulations of intrinsic connectivity network (ICN) and to investigate whether these changes of ICN can be related to duration of CCS use and to impulsivity behavior in CCS-dependent individuals. MATERIALS AND METHODS: Resting-state functional magnetic resonance imaging (fMRI) data in 41 CCS-dependent individuals and 34 healthy controls (HC) were scanned at 1.5T and analyzed using independent component analysis (ICA), in combination with a "dual-regression" technique to identify the group differences of three important resting-state networks, the default mode network (DMN), the executive control network (ECN), and the salience network (SN) between the CCS-dependent individuals and HC. RESULTS: Compared with the HC, CCS-dependent individuals had aberrant intrinsic connectivity within the DMN, ECN, and SN (P < 0.05, AlphaSim corrected). Furthermore, a longer duration of CCS use was associated with greater abnormalities in the intrinsic network functional connectivity (FC, P < 0.05, Bonferroni correction). Intrinsic network FC also correlated with higher impulsivity in CCS-dependent individuals (P < 0.05, AlphaSim corrected). CONCLUSION: Our findings revealed aberrant DMN, ECN, and SN connectivity patterns in CCS-dependent patients, which may provide new insight into how neuronal communication and information integration are disrupted among DMN, ECN, and SN key structures due to long duration of CCS use. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:177-186.

Larger corpus callosum and reduced orbitofrontal cortex homotopic connectivity in codeine cough syrup-dependent male adolescents and young adults.

OBJECTIVES: To characterize interhemispheric functional and anatomical connectivity and their relationships with impulsive behaviour in codeine-containing cough syrup (CCS)-dependent male adolescents and young adults. METHODS: We compared volumes of corpus callosum (CC) and its five subregion and voxel-mirrored homotopic functional connectivity (VMHC) in 33 CCS-dependent male adolescents and young adults and 38 healthy controls, group-matched for age, education and smoking status. Barratt impulsiveness scale (BIS.11) was used to assess participant impulsive behaviour. Abnormal CC subregions and VMHC revealed by group comparison were extracted and correlated with impulsive behaviour and duration of CCS use. RESULTS: We found selective increased mid-posterior CC volume in CCS-dependent male adolescents and young adults and detected decreased homotopic interhemispheric functional connectivity of medial orbitofrontal cortex (OFC). Moreover, impairment of VMHC was associated with the impulsive behaviour and correlated with the duration of CCS abuse in CCS-dependent male adolescents and young adults. CONCLUSIONS: These findings reveal CC abnormalities and disruption of interhemispheric homotopic connectivity in CCS-dependent male adolescents and young adults, which provide a novel insight into the impact of interhemispheric disconnectivity on impulsive behaviour in substance addiction pathophysiology. KEY POINTS: • CCS-dependent individuals (patients) had selective increased volumes of mid-posterior corpus callosum • Patients had attenuated interhemispheric homotopic FC (VMHC) of bilateral orbitofrontal cortex • Impairment of VMHC correlated with impulsive behaviour in patients • Impairment of VMHC correlated with the CCS duration in patients.

Increased insular connectivity with emotional regions in primary insomnia patients: a resting-state fMRI study.

OBJECTIVE: To explore the abnormal connectivity patterns between the insular and the voxels of the brain in primary insomnia (PI) with insular-based functional connectivity (FC). METHODS: With the resting-state fMRI data acquired from 57 PI patients and 46 healthy controls, a two-sample t test was performed on individual FC correlation maps from two groups. The person correlation analysis was used to evaluate the relationship between the abnormal FC and clinical features. RESULTS: PI patients show enhanced connectivity between the left insula with the right anterior cingulate cortex (p < 0.05 and p < 0.001, AlphaSim-corrected), right frontal sup orb, bilateral thalamus and left precuneus,as well as decreased connectivity with the left middle temporal gyrus and right fusiform (p < 0.05, AlphaSim-corrected). Correlation analysis indicated the enhanced connectivities in the PI patients have significant negative correlations with Self-Rating Depression Scale(SDS)and Self-Rating Anxiety Scale(SAS)scores. In addition, the decreased functional connectivities showed positive correlations with SDS and SAS scores. CONCLUSION: Our study showed the increased connectivity regions with insula were mainly in the emotional circle and decreased connectivity was in cognitive-related regions. These provide additional evidence from functional integration view to understand the possible underlying neural- mechanisms of PI. KEY POINTS: • The aberrant insular-based connectivity pattern of PI patients was detected. • Regions showing increased connectivity with left insular were mainly in emotional circle. • Significant correlations between changed FC and SDS and SAS score were found.

Aberrant interhemispheric functional and structural connectivity in heroin-dependent individuals.

Models of heroin addiction emphasize the role of disrupted frontostriatal circuitry supporting cognitive control processes. However, heroin addiction-related alterations in functional and structural interactions among brain regions, especially between the cerebral hemispheres, are rarely examined directly. Resting-state functional magnetic resonance imaging (fMRI) approaches, which reveal patterns of coherent spontaneous fluctuations in the fMRI signal, offer a means to quantify directly functional interactions between the hemispheres. The corpus callosum (CC), which connects homologous regions of the cortex, is the major conduit for information transfer between the cerebral hemispheres and represents a structural connectivity index between hemispheres. We compared interhemispheric voxel-mirrored homotopic connectivity (VMHC) and CC volume between 45 heroin dependent-individuals (HDIs) and 35 non-addict individuals. We observed significant reduction of VMHC in a number of regions, particularly the striatum/limbic system regions, and significant decrease in splenium and genu sub-regions of CC in HDI. Importantly, within HDI, VMHC in the dorsal lateral prefrontal cortex (DLPFC) correlated with genu CC volume, VMHC in the putamen, VMHC in the DLPFC and genu CC volume and splenium CC volume were negatively correlated with heroin duration and impulsivity traits. Further analyses demonstrated that impairment of VMHC of bilateral DLPFC partially mediated the association between genu CC volumes decreased and increased impulsivity in HDI. Our results reveal a substantial impairment of interhemispheric coordination in the HDI. Further, interhemispheric connectivity correlated with the duration of heroin abuse and higher impulsivity behavior in HDI. Our findings provide insight into a heroin addicts' related pathophysiology and reinforce an integrative view of the interhemispheric cerebral functional and structural organization.

Regional homogeneity changes in patients with primary insomnia.

PURPOSE: The study aimed to explore the regional spontaneous activity changes in primary insomnia (PI) patients. MATERIALS AND METHODS: Based on the resting-state fMRI datasets acquired from 59 PI patients and 47 healthy controls, a two-sample t-test was performed on individual normalized regional homogeneity (ReHo) maps. Relationships between abnormal ReHo values and the Pittsburgh Sleep Quality Index (PSQI), the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS) were investigated with Pearson correlation analysis. RESULTS: In PI patients, we found increased ReHo in the left insula, right anterior cingulate gyrus, bilateral precentral gyrus and left cuneus, as well as decreased ReHo in the right middle cingulate cortex and left fusiform (p < 0.05, AlphaSim-corrected). We also found a significant positive correlation between increased ReHo in the left insula and SAS scores, decreased ReHo in the right middle cingulated cortex and SDS, SAS scores as well as a negative correlation between increased ReHo in the right precentral gyrus and SDS scores (p < 0.05). CONCLUSIONS: Our study found abnormal spontaneous activities in multiple brain regions, especially in emotion-related areas in PI patients. Alterative activities in these regions might contribute to an understanding the intrinsic functional architecture of insomnia and its clinical features. KEY POINTS: • Regional spontaneous activity changes were detected in PI patients. • Decreased or increased ReHo of some regions was identified in PI patients. • Significant correlations between mean ReHo and SDS scores were found.

Short-term UROD treatment on cerebral function in codeine-containing cough syrups dependent male individuals.

OBJECTIVE: To investigate alterations of resting brain function in codeine-containing cough syrups (CCS) dependent individuals before and after ultra-rapid opioid detoxification under general anaesthesia (UROD) combined with naltrexone treatment (NMT). METHODS: Fourteen CCS-dependent individuals were scanned using resting-state fMRI. After UROD and 2 weeks of NMT, CCS-dependent individuals were rescanned. Fourteen matched controls were studied at baseline and compared. The amplitude of low frequency fluctuations (ALFF) and seed-based functional connectivity (FC) were used to characterize resting-state cerebral function. RESULTS: After UROD and 2 weeks of NMT, CCS-dependent individuals had increased ALFF in the bilateral parahippocampal gyrus and right medial orbitofrontal cortex (mOFC), decreased ALFF in the left post-central gyrus (PoCG), left middle occipital cortex (MOC) and left dorsal lateral prefrontal cortex (DLPFC), and reduced FC between right mOFC and right DLPFC, and between left DLPFC and left inferior parietal lobe relative to pretreatment. Decreased ALFFs in the left PoCG and left MOC were associated with decreased withdrawal syndrome severity in CCS-dependent individuals. CONCLUSIONS: We offer the first report describing how regional and integral synchronous neural activity occurs after UROD and short-term NMT, accompanied by decreased withdrawal syndrome severity. These findings contribute to the understanding of complex systems involved in UROD-NMT effects. KEY POINTS: • CCS-dependent individuals had reduced ALFF and increased FC at baseline. • UROD treatment can change the regional and integral brain function of CCS-dependent individuals. • Attenuated ALFFs are correlated with the withdrawal syndrome after treatment.

Abnormal white matter structural networks characterize heroin-dependent individuals: a network analysis.

Neuroimaging studies suggested that drug addiction is linked to abnormal brain functional connectivity. However, little is known about the alteration of brain white matter (WM) connectivity in addictive drug users and nearly no study has been performed to examine the alterations of brain WM connectivity in heroin-dependent individuals (HDIs). Diffusion tensor imaging (DTI) offers a comprehensive technique to map the whole brain WM connectivity in vivo. In this study, we acquired DTI datasets from 20 HDIs and 18 healthy controls and constructed their brain WM structural networks using a deterministic fibre tracking approach. Using graph theoretical analysis, we explored the global and nodal topological parameters of brain network for both groups and adopted a network-based statistic (NBS) approach to assess between-group differences in inter-regional WM connections. Statistical analysis indicated the global efficiency and network strength were significantly increased, but the characteristic path length was significantly decreased in the HDIs compared with the controls. We also found that in the HDIs, the nodal efficiency was significantly increased in the left prefrontal cortex, bilateral orbital frontal cortices and left anterior cingulate gyrus. Moreover, the NBS analysis revealed that in the HDIs, the significant increased connections were located in the paralimbic, orbitofrontal, prefrontal and temporal regions. Our results may reflect the disruption of whole brain WM structural networks in the HDIs. Our findings suggest that mapping brain WM structural network may be helpful for better understanding the neuromechanism of heroin addiction.

Role of P311 in interleukin-1α-induced epithelial to myofibroblast transition in kidney tubular epithelial cells.

Tubular epithelial-myofibroblast transition (TEMT) is an important process in renal tubulointerstitial fibrosis. Interleukin-1α (IL-1α) and transforming growth factor-ß1 (TGF-ß1) have been demonstrated to be key inducers of TEMT. In mouse embryonic fibroblast cells (NIH3T3), P311 protein induces phenotypic changes that are consistent to myofibroblast transformation. In the present study, we investigated the role of P311 gene and protein as well as potential mechanisms underlying TEMT in normal rat kidney tubular epithelial cells (NRK52E). Morphological and molecular changes were determined in NRK52E cells that were treated with IL-1α and/or P311 antibodies. The results showed that the NRK52E cells triggered by IL-1α became fibroblast-like cells, exhibiting hypertrophy of elongated and fusiform-shaped cells. IL-1α induced a time-dependent increase in P311 gene expression in NRK52E cells, with a peak time at 4 days. The expression levels of P311 gene were positively correlated with α-SMA and TGF-ß1 gene expression levels. Anti-P311 antibody inhibited P311 and α-SMA expression in the presence of IL-1α. In contrast, anti-P311 antibody increased the expression of TGF-ß1 gene in cells cultured with IL-1α. Therefore, P311 gene, together with α-SMA and TGF-ß1 genes, was induced in the process of TEMT. P311 protein triggered by interleukin-1α may promote TEMT through a TGF-ß1-independent pathway.

Abnormal cortical thickness in heroin-dependent individuals.

Accumulating evidence from brain structural imaging studies on heroin dependence has supported links between brain morphological alterations and heroin exposure, particularly in gray matter volume or gray matter density. However, the effects of heroin exposure on cortical thickness and the relationship between cortical thickness and heroin addiction are not yet known. In this study, we acquired 3D high-resolution brain structural magnetic resonance imaging (MRI) data from 18 heroin-dependent individuals (HDIs) and 15 healthy controls (HCs). Using FreeSurfer, we detected abnormalities in cortical thickness in the HDIs. Based on a vertex-wise analysis, the HDIs showed significantly decreased cortical thickness in the bilateral superior frontal, left caudal middle frontal, right superior temporal, and right insular regions compared to the HCs but significantly increased cortical thickness in the left superior parietal, bilateral lingual, left temporal pole, right inferior parietal, right lateral occipital, and right cuneus regions. To supplement these results, a subsequent ROI-wise analysis was performed and showed decreased cortical thickness in the left superior frontal sulcus, left precuneus gyrus, left calcarine sulcus, left anterior transverse collateral sulcus, and the right medial occipital-temporal and lingual sulcus. These regions partially overlapped with the areas identified using the vertex-wise analysis. In addition, we found that the thickness in the right superior frontal and right insular regions was negatively correlated with the duration of heroin use. These results provide compelling evidence for cortical abnormality in HDIs and also suggest that the duration of heroin use may be a critical factor associated with the brain alteration.