Multivariate associations between behavioural dimensions and white matter across children and adolescents with and without attention-deficit/hyperactivity disorder.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder. Integrity of white matter microstructure plays a key role in the neural mechanism of ADHD presentations. However, the relationships between specific behavioural dimensions and white matter microstructure are less well known. This study aimed to identify associations between white matter and a broad set of clinical features across children and adolescent with and without ADHD using a data-driven multivariate approach. METHOD: We recruited a total of 130 children (62 controls and 68 ADHD) and employed regularized generalized canonical correlation analysis to characterize the associations between white matter and a comprehensive set of clinical measures covering three domains, including symptom, cognition and behaviour. We further applied linear discriminant analysis to integrate these associations to explore potential developmental effects. RESULTS: We delineated two brain-behaviour dimensional associations in each domain resulting a total of six multivariate patterns of white matter microstructural alterations linked to hyperactivity-impulsivity and mild affected; executive functions and working memory; externalizing behaviour and social withdrawal, respectively. Apart from executive function and externalizing behaviour sharing similar white matter patterns, all other dimensions linked to a specific pattern of white matter microstructural alterations. The multivariate dimensional association scores showed an overall increase and normalization with age in ADHD group while remained stable in controls. CONCLUSIONS: We found multivariate neurobehavioral associations exist across ADHD and controls, which suggested that multiple white matter patterns underlie ADHD heterogeneity and provided neural bases for more precise diagnosis and individualized treatment.

Aberrant intrinsic hippocampal and orbitofrontal connectivity in drug-naive adolescent patients with major depressive disorder.

Alterations in resting-state functional connectivity (rsFC) of hippocampus and orbitofrontal cortex (OFC) have been highly implicated in major depressive disorder (MDD) and the researches have penetrated to the subregional level. However, relatively little is known about the intrinsic connectivity patterns of these two regions in adolescent MDD (aMDD), especially that of their functional subregions. Therefore, in the current study, we recruited 68 first-episode drug-naive aMDD patients and 43 matched typically developing controls (TDC) to characterize the alterations of whole-brain rsFC patterns in hippocampus and OFC at both regional and subregional levels in aMDD. The definition of specific functional subregions in hippocampus and OFC were based on the prior functional clustering-analysis results. Furthermore, the relationship between rsFC alterations and clinical features was also explored. Compared to TDC group, aMDD patients showed decreased connectivity of the left whole hippocampus with bilateral OFC and right inferior temporal gyrus at the regional level and increased connectivity between one of the right hippocampal subregions and right posterior insula at the subregional level. Reduced connectivity of OFC was only found in the subregion of left OFC with left anterior insula extending to lenticula in aMDD patients relative to TDC group. Our study identifies that the aberrant hippocampal and orbitofrontal rsFC was predominantly located in the insular cortex and could be summarized as an altered hippo-orbitofrontal-insular circuit in aMDD, which may be the unique features of brain network dysfunction in depression at this particular age stage. Moreover, we observed the distinct rsFC alterations in adolescent depression at the subregional level, especially the medial and lateral OFC.

Nonsuicidal self-injury behaviour in a city of China and its association with family environment, media use and psychopathology.

INTRODUCTION: It is not clear whether there are differences in the risk factors for nonsuicidal self-injury (NSSI) between children and early adolescents. Clarifying this question is crucial for identifying actionable prevention strategies for NSSI in these two age groups. METHOD: The study, comprising 8611 children and early adolescents (4409 (51.2%) children, 4202 (48.8%) early adolescents), was based on the baseline data of the Chengdu Positive Child Development (CPCD) in China. NSSI behaviours, emotional and behavioural problems and family environment were assessed and obtained via self-reports and parent reports. RESULTS: Overall, 2520 (29.26%) participants reported having ever engaged in NSSI. There was a higher lifetime NSSI rate in males than in females during childhood, contrasting with higher NSSI rates in females than in males during early adolescence. Furthermore, NSSI shared similar risk factors, including major family conflict and poor relationships with caregivers, in both age groups. Specifically, in children, the risk of NSSI increased along with thought and attention problems (OR, 95% CI: 1.194, 1.106-1.288 and 1.114, 1.028-1.207, respectively), whereas in early adolescents, it increased with anxiety and depressive problems (OR, 95% CI: 1.259, 1.116-1.422). CONCLUSIONS: The findings suggested the need for difference in preventive strategies for NSSI in the two age groups. It may be more efficacious to screen for NSSI in children with thought and attention problems and in early adolescents with anxiety and depressive problems.

Effect of hypochlorous acid nasal spray as an adjuvant therapy after functional endoscopic sinus surgery.

OBJECTIVES: To evaluate the efficacy of hypochlorous acid (HOCl) nasal spray as an adjuvant therapy after functional endoscopic sinus surgery (FESS). MATERIAL AND METHODS: Patients with chronic rhinosinusitis who had received FESS for treatment were recruited and assigned to one of two groups at random at one month post-surgery. In the HOCl group, patients received 0.02% HOCl nasal spray three times a day for two months. In the control group, normal saline (NS) nasal irrigation was given. Before FESS and before and after nasal spray or irrigation, patients completed the Taiwanese version of the 22-item Sino-Nasal Outcome Test (TWSNOT-22). In addition, patients received endoscopic examination, acoustic rhinometry, smell test, saccharine transit test, and bacterial cultures obtained from their middle meatus. RESULTS: Seventy-eight patients completed the study. Among them, 41 received HOCl nasal spray, and 37 received NS irrigation. Endoscopic score significantly decreased after 2-month HOCl nasal spray (p = 0.036). TWSNOT-22 score also decreased, although insignificantly (p = 0.285). In contrast, TWSNOT-22 score significantly decreased after NS nasal irrigation (p = 0.017), but endoscopic score did not significantly decrease (p = 0.142). CONCLUSIONS: Our results showed that HOCl nasal spray had a similar effect to that of NS nasal irrigation in post-FESS care. It can be an alternative of NS nasal irrigation for its convenient application.

[Effect of Family Function on Suicide-Related Behaviors of Junior Middle School Students: The Mediating Effect of Depression].

Objective: To examine the prevalence of suicide-related behaviors among junior middle school students, and to explore the mediating role of depression in the relationship between suicide-related behaviors and family function. Methods: A total of 2572 junior middle school students from three middle schools in Chengdu were interviewed face-to-face by using suicide-related items from Youth Risk Behavior Surveillance System (YRBSS), Chinese Family Assessment Instrument (C-FAI), and Center for Epidemiologic Studies Depression Scale for Children (CES-DC). The mediating role of depression was analyzed with structural equation model. Results: The prevalence of suicide-related behaviors was 26.01% among the respondents. The prevalence of suicide ideation, suicide plan and suicide attempt were 24.38%, 13.49% and 10.77%, respectively. Depression played a partial mediating role in how family function impacted on suicide-related behaviors, presenting a direct effect value of 0.170 (95% CI: 0.117-0.218, P<0.001) and an indirect effect value of 0.205 (95% CI: 0.176-0.234, P<0.001), with the mediating effect accounting for 54.67% of the total effect. Conclusion: Poor family function may increase the risk of suicide-related behaviors, and this effect is produced mostly through the impact on children's mental health. Improving family function will not only improve children's psychological status, but also reduce suicide-related behaviors.

Temporal variability of regional intrinsic neural activity in drug-naïve patients with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) displays alterations in regional brain activity represented by the amplitude of low-frequency fluctuation (ALFF), but the time-varying characteristics of this local neural activity remain to be clarified. We aimed to investigate the dynamic changes of intrinsic brain activity in a relatively large sample of drug-naïve OCD patients using univariate and multivariate analyses. We applied a sliding-window approach to calculate the dynamic ALFF (dALFF) and compared the difference between 73 OCD patients and age- and sex-matched healthy controls (HCs). We also utilized multivariate pattern analysis to determine whether dALFF could differentiate OCD patients from HCs at the individual level. Compared with HCs, OCD patients exhibited increased dALFF mainly within regions of the cortical-striatal-thalamic-cortical (CSTC) circuit, including the bilateral dorsal anterior cingulate cortex, medial prefrontal cortex and striatum, and right dorsolateral prefrontal cortex (dlPFC). Decreased dALFF was identified in the bilateral inferior parietal lobule (IPL), posterior cingulate cortex, insula, fusiform gyrus, and cerebellum. Moreover, we found negative correlations between illness duration and dALFF values in the right IPL and between dALFF values in the left cerebellum and Hamilton Depression Scale scores. Furthermore, dALFF can distinguish OCD patients from HCs with the most discriminative regions located in the IPL, dlPFC, middle occipital gyrus, and cuneus. Taken together, in the current study, we demonstrated a characteristic pattern of higher variability of regional brain activity within the CSTC circuits and lower variability in regions outside the CSTC circuits in drug-naïve OCD patients.

Alterations in hippocampal subfield and amygdala subregion volumes in posttraumatic subjects with and without posttraumatic stress disorder.

The hippocampus and amygdala are important structures in the posttraumatic stress disorder (PTSD); however, the exact relationship between these structures and stress or PTSD remains unclear. Moreover, they consist of several functionally distinct subfields/subregions that may serve different roles in the neuropathophysiology of PTSD. Here we present a subregional profile of the hippocampus and amygdala in 145 survivors of a major earthquake and 56 non-traumatized healthy controls (HCs). We found that the bilateral hippocampus and left amygdala were significantly smaller in survivors than in HCs, and there was no difference between survivors with (n = 69) and without PTSD (trauma-exposed controls [TCs], n = 76). Analyses revealed similar results in most subfields/subregions, except that the right hippocampal body (in a head-body-tail segmentation scheme), right presubiculum, and left amygdala medial nuclei (Me) were significantly larger in PTSD patients than in TCs but smaller than in HCs. Larger hippocampal body were associated with the time since trauma in PTSD patients. The volume of the right cortical nucleus (Co) was negatively correlated with the severity of symptoms in the PTSD group but positively correlated with the same measurement in the TC group. This correlation between symptom severity and Co volume was significantly different between the PTSD and TCs. Together, we demonstrated that generalized smaller volumes in the hippocampus and amygdala were more likely to be trauma-related than PTSD-specific, and their subfields/subregions were distinctively affected. Notably, larger left Me, right hippocampal body and presubiculum were PTSD-specific; these could be preexisting factors for PTSD or reflect rapid posttraumatic reshaping.

Quantitative tractography reveals changes in the corticospinal tract in drug-naïve children with attention-deficit/hyperactivity disorder

Background: The specific role of the corticospinal tract with respect to inattention and impulsive symptoms in children with attention-deficit/hyperactivity disorder (ADHD) has been explored in the past. However, to our knowledge, no study has identified the exact regions of the corticospinal tract that are affected in ADHD. We aimed to determine comprehensive alterations in the white matter microstructure of the corticospinal tract and underlying neuropsychological substrates in ADHD. Methods: We recruited 38 drug-naïve children with ADHD and 34 typically developing controls. We employed a tract-based quantitative approach to measure diffusion parameters along the trajectory of the corticospinal tract, and we further correlated alterations with attention and response inhibition measures. Results: Compared with controls, children with ADHD demonstrated significantly lower fractional anisotropy and higher radial diffusivity at the level of cerebral peduncle, and higher fractional anisotropy at the level of the posterior limb of the internal capsule in the right corticospinal tract only. As well, increased fractional anisotropy in the posterior limb of the internal capsule was negatively correlated with continuous performance test attention quotients and positively correlated with reaction time on the Stroop Colour­Word Test; increased radial diffusivity in the right peduncle region was positively correlated with omissions in the Stroop test. Limitations: The sample size was relatively small. Moreover, we did not consider the different subtypes of ADHD and lacked sufficient power to analyze subgroup differences. Higher-order diffusion modelling is needed in future white matter studies. Conclusion: We demonstrated specific changes in the right corticospinal tract in children with ADHD. Correlations with measures of attention and response inhibition underscored the functional importance of corticospinal tract disturbance in ADHD.

Predictors of nasal bacterial culture rates in patients with chronic rhinosinusitis.

All nontechnical factors were analyzed to predict nasal bacterial culture results in patients with chronic rhinosinusitis (CRS). Four hundred and ninety-six CRS patients, who underwent functional endoscopic sinus surgery (FESS), were enrolled. Prior to FESS, the severity of each patient's CRS was evaluated using a questionnaire, endoscopic examination, acoustic rhinometry, smell test, saccharine transit test, and CT scan. Nasal bacterial cultures were collected from both middle meati using a cotton-tipped stick. Our results showed that the symptom severity complained of by patients and their loss of smell function did not influence the bacterial culture rate. We discovered that the bacterial culture rate was significantly higher in nostrils with nasal polyps than those without polyps, along with nostrils experiencing thick, purulent discharge as opposed to those without discharge. Additionally, this result also occurred in nostrils with a saccharin transit time of more than 30 min than it did in those with a saccharin transit time of less than or equal to 30 min. Both the total endoscopic score and anterior group CT score were significantly higher in nostrils with positive culture than those with negative culture, while the second minimal cross-sectional area (MCA2) of the nasal cavity was significantly lower in nostrils with positive culture than those with negative culture. Multiple logistic regression analysis showed that both nasal polyps and MCA2 were the predictors for positive nasal bacterial culture results. It was concluded that nasal polyps and MCA2 were the predictors for positive nasal bacterial culture results in CRS patients.

Application of a Y-type-DNA-functionalized nanogold probe featuring specific telomerase recognition and doxorubicin release in cancer cells.

A Y-type-DNA-functionalized nanogold probe was synthesized to identify telomerase and trigger drug release in cancer cells. This system involved a DNA-functionalized nanogold probe centered on gold nanoparticles with a dense modification of Y-type DNA molecular beacons on the surface. The Y-type DNA molecular beacons consisted of telomerase primers (TPs), a FAM-labeled single-strand DNA (Mismatch-DNA), and a single-strand DNA of two templates (Linker-DNA1 and Linker-DNA2). Doxorubicin (Dox), an anti-cancer drug molecule, was inserted into DNA double strands. When telomerase existed, TP was extended and the Mismatch-DNA was released, leading to the emission of fluorescent light from FAM while releasing Dox. This probe specifically detected cancer cells and did not affect normal cells. This drug delivery system will reduce the tumour size and cause minimal injury to normal tissues.

End-of-life care for head and neck cancer patients: a population-based study.

PURPOSE: Head and neck cancers (HNCs) usually present a poor prognosis and cause high morbidity rates. Recent surveys have demonstrated that HNC incidence rates are still on the increase in many countries. Our study objective was to assess the end-of-life care for patients with HNCs in Taiwan. METHODS: Data was retrieved from Taiwan's National Health Insurance Research Database, where we identified patients who had been diagnosed with HNCs from January 1997 to December 2010. Each patient's annual trend of opioid use and hospice care needs, along with the distribution of place of death in the study cohort, were all analyzed. RESULTS: A total of 98,211 HNC patients diagnosed between 1997 and 2010 were eligible for this study. The majority of HNC patients died in hospital. Patients who were male, lived in capital area, had a higher income, had received palliative hospice care, and had been prescribed opioids tended to choose to die at home or in hospice wards. Both opioid prescription and hospice care have increased during the past 10 years; however, the rate of palliative hospice care remained below 50%. CONCLUSIONS: Our results demonstrate that greater efforts are needed to implement palliative care for HNC patients in Taiwan.

The impact of chronic rhinosinusitis on sleep-disordered breathing.

BACKGROUND: The nose plays an important role in sleep quality. Very little is known about sleep problems in patients with chronic rhinosinusitis (CRS). The aim of this study was to investigate the impact of CRS on sleep-disordered breathing. METHODOLOGY: CRS patients who underwent functional endoscopic sinus surgery were collected between July 2010 and May 2015. Before surgery, they filled 20-item Sino-Nasal Outcome Test and Epworth Sleepiness Scale questionnaires, were asked about the severity of nasal obstruction, and received acoustic rhinometry, smell test, an endoscopic examination, sinus computed tomography, and a one-night polysomnography. Sleep quality was evaluated in these patients and was correlated with the severity of rhinosinusitis. RESULTS: One hundred and thirty-nine CRS patients were enrolled in the study. Among them, 38.1% complained of daytime sleepiness, and this sleep problem was correlated with the symptom of nasal obstruction. Obstructive sleep apnea syndrome (OSAS) was diagnosed in 64.7% of the patients, but there was no correlation with the severity of rhinosinusitis. Nasal polyps did not worsen sleep problems in the CRS patients. CONCLUSIONS: This study showed that CRS patents had a high prevalence of OSAS, and worse OSAS in CRS patients was not correlated with the severity of rhinosinusitis.

Efficacy and Safety of Xylitol Nasal Irrigation after Functional Endoscopic Sinus Surgery: A Randomized Controlled Study.

Xylitol is considered a naturally occurring antibacterial agent. It is generally believed to enhance the body's own innate bactericidal mechanisms. It also provides anti-adhesive effects against both Streptococcus pneumoniae and Haemophilus influenza. This study was performed to evaluate the efficacy and safety of xylitol nasal irrigation in the postoperative care of functional endoscopic sinus surgery (FESS). Patients with chronic rhinosinusitis who received FESS were recruited and randomly assigned to two groups at one month post-surgery. Thirty-five patients in the xylitol group received 400 mL of 5% xylitol nasal irrigation daily for 2 months, while another 35 in the normal saline (NS) group received 400 mL of NS nasal irrigation daily for 2 months. Prior to FESS, as well as before and after nasal irrigation, sinonasal symptoms were assessed through the 22-item Sino-Nasal Outcome Test Questionnaire. The patients also underwent an endoscopic examination while undergoing nasal function tests, and a cytokine measurement of the nasal lavage and a bacterial culture from the middle meatus were performed. The safety of the nasal irrigation was assessed through any self-reported adverse events, the Eustachian Tube Dysfunction Patient Questionnaire and the eustachian tube function test. The endoscopic scores and olfactory threshold significantly decreased after xylitol irrigation when compared with those before irrigation. The prevalence of Staphylococcus aureus in the nasal secretions also decreased significantly after xylitol irrigation. The amounts of Interleukin-5 and Interleukin-17A were significantly increased in the nasal lavage after xylitol irrigation. No side effects, including those related to eustachian tube function, were seen after nasal irrigation in both groups. Our results showed that xylitol nasal irrigation was both beneficial and safe during the postoperative care of FESS.

The Influence of Various Freezing-thawing Methods of Skin on Drug Permeation and Skin Barrier Function.

The selection of skin is crucial for the in vitro permeation test (IVPT). The purpose of this study was to investigate the influence of different freezing-thawing processes on the barrier function of skin and the transdermal permeability of granisetron and lidocaine. Rat and hairless mouse skins were thawed at three different conditions after being frozen at -20℃ for 9 days: thawed at 4℃, room temperature (RT), and 32℃. There were no significant differences in the steady-state fluxes of drugs between fresh and thawed samples, but compared with fresh skin there were significant differences in lag time for the permeation of granisetron in rat skins thawed at RT and 32℃. Histological research and scanning electron microscopy images showed no obvious structural damage on frozen/thawed skin, while immunohistochemical staining and enzyme-linked immunosorbent assay for the tight junction (TJ) protein Cldn-1 showed significantly impaired epidermal barrier. It was concluded that the freezing-thawing process increases the diffusion rate of hydrophilic drugs partly due to the functional degradation of TJs. It's recommended that hairless, inbred strains and identical animal donors should be used, and the selected thawing method of skin should be validated prior to IVPT, especially for hydrophilic drugs.

The P2 nucleic acid binding protein of Sugarcane bacilliform virus is a viral pathogenic factor.

Background: Saccharum spp. is the primary source of sugar and plays a significant role in global renewable bioenergy. Sugarcane bacilliform virus (SCBV) is one of the most important viruses infecting sugarcane, causing severe yield losses and quality degradation. It is of great significance to reveal the pathogenesis of SCBV and resistance breeding. However, little is known about the viral virulence factors or RNA silencing suppressors and the molecular mechanism of pathogenesis. Methods: To systematically investigate the functions of the unknown protein P2 encoded by SCBV ORF2. Phylogenetic analysis was implemented to infer the evolutionary relationship between the P2 of SCBV and other badnaviruses. The precise subcellular localization of P2 was verified in the transient infiltrated Nicotiana benthamiana epidermal mesophyll cells and protoplasts using the Laser scanning confocal microscope (LSCM). The post-transcriptional gene silencing (PTGS) and transcriptional gene silencing (TGS) RNA silencing suppressor activity of P2 was analyzed, respectively. Furthermore, restriction digestion and RT-qPCR assays were conducted to verify the probable mechanism of P2 on repressing DNA methylation. To explore the pathogenicity of P2, a potato virus X-based viral vector was used to heterologously express SCBV P2 and the consequent H2O2 accumulation was detected by the 3,3'-diaminobenzidine (DAB) staining method. Results: Phylogenetic analysis shows that SCBV has no obvious sequence similarity and low genetic relatedness to Badnavirus and Tungrovirus representatives. LSCM studies show that P2 is localized in both the cytoplasm and nucleus. Moreover, P2 is shown to be a suppressor of PTGS and TGS, which can not only repress ssRNA-induced gene silencing but also disrupt the host RNA-directed DNA methylation (RdDM) pathway. In addition, P2 can trigger an oxidative burst and cause typical hypersensitive-like response (HLR) necrosis in systemic leaves of N. benthamiana when expressed by PVX. Overall, our results laid a foundation for deciphering the molecular mechanism of SCBV pathogenesis and made progress for resistance breeding.

Divergent effects of sex on hippocampal subfield alterations in drug-naive patients with major depressive disorder.

BACKGROUND: The hippocampus is a crucial brain structure in etiological models of major depressive disorder (MDD). It remains unclear whether sex differences in the incidence and symptoms of MDD are related to differential illness-associated brain alterations, including alterations in the hippocampus. This study investigated divergent the effects of sex on hippocampal subfield alterations in drug-naive patients with MDD. METHODS: High-resolution structural MR images were obtained from 144 drug-naive individuals with MDD early in their illness course and 135 age- and sex-matched healthy controls (HCs). Hippocampal subfields were segmented using FreeSurfer software and analyzed in terms of both histological subfields (CA1-4, dentate gyrus, etc.) and more integrative larger functional subregions (head, body and tail). RESULTS: We observed a significant overall reduction in hippocampal volume in MDD patients, with deficits more prominent deficits in the posterior hippocampus. Differences in anatomic alterations between male and female patients were observed in the CA1-head, presubiculum-body and fimbria in the left hemisphere. Exploratory analyses revealed different patterns of clinical and memory function correlations with histological subfields and functional subregions between male and female patients primarily in the hippocampal head and body. LIMITATIONS: This cross-sectional study cannot clarify the causality of hippocampal alterations or their association with illness risk or onset. CONCLUSIONS: These findings represent the first reported sex-specific alterations in hippocampal histological subfields in patients with MDD early in the illness course prior to treatment. Sex-specific hippocampal alterations may contribute to diverse sex differences in the clinical presentation of MDD.

Functional connectivity of the default mode network in first-episode drug-naïve patients with major depressive disorder.

BACKGROUND: Alterations in the default mode network (DMN) have been reported in major depressive disorder (MDD), well-replicated robust alterations of functional connectivity (FC) of DMN remain to be established. Investigating the functional connections of DMN at the overall and subsystem level in early MDD patients has the potential to advance our understanding of the physiopathology of this disorder. METHODS: We recruited 115 first-episode drug-naïve patients with MDD and 137 demographic-matched healthy controls (HCs). We first compared FC within the DMN, within/between the DMN subsystems, and from DMN subsystems to the whole brain between groups. Subsequently, we explored correlations between clinical features and identified alterations in FC. RESULTS: First-episode drug-naïve patients with MDD showed significantly increased FC within the DMN, dorsal DMN and medial DMN. Each subsystem showed a distinct FC pattern with other brain networks. Increased FC between the subsystems (core DMN, dorsal DMN) and other networks was associated with more severe depressive symptoms, while medial DMN-related connectivity correlated with memory performance. LIMITATIONS: The relatively large "pure" MDD sample could only be generalized to a limited population. And, atypical asymmetric FCs in the DMN related to MDD might be missed for only left-lateralized ROIs were used to avoid strong correlations between mirrored (right/left) seed regions. CONCLUSION: These findings suggest patients with early MDD showed distinct patterns of FC alterations throughout DMN and its subsystems, which were related to illness severity and illness-associated cognitive impairment, highlighting their clinical significance.

Distinctive intrinsic functional connectivity alterations of anterior cingulate cortex subdivisions in major depressive disorder: A systematic review and meta-analysis.

Evidence of whether the intrinsic functional connectivity of anterior cingulate cortex (ACC) and its subregions is altered in major depressive disorder (MDD) remains inconclusive. A systematic review and meta-analysis were therefore performed on the whole-brain resting-state functional connectivity (rsFC) studies using the ACC and its subregions as seed regions in MDD, in order to draw more reliable conclusions. Forty-four ACC-based rsFC studies were included, comprising 25 subgenual ACC-based studies, 11 pregenual ACC-based studies, and 17 dorsal ACC-based studies. Specific alterations of rsFC were identified for each ACC subregion in patients with MDD, with altered rsFC of subgenual ACC in emotion-related brain regions, of pregenual ACC in sensorimotor-related regions, and of dorsal ACC in cognition-related regions. Furthermore, meta-regression analysis revealed a significant negative correlation between the pgACC-caudate hypoconnectivity and percentage of female patients in the study cohort. This meta-analysis provides robust evidence of altered intrinsic functional connectivity of the ACC subregions in MDD, which may hold relevance to understanding the origin of, and treating, the emotional, sensorimotor and cognitive dysfunctions that are often observed in these patients.

Long-term survival analysis of nasopharyngeal carcinoma by plasma Epstein-Barr virus DNA levels.

BACKGROUND: The objective of this study was to confirm the relation between plasma Epstein-Barr virus (EBV) DNA (pEBV DNA) load and treatment outcomes after long-term follow-up in patients with nasopharyngeal carcinoma (NPC). METHODS: In total, 210 patients with NPC were enrolled, including 99 previously reported patients and 111 new patients. They prospectively received treatment with induction chemotherapy plus radiotherapy and were followed for at least 6 years. In these patients, pEBV DNA levels were measured before treatment and 1 week after treatment. The plasma viral load was correlated with treatment outcomes in the group of new patients and in the entire group. RESULTS: By using previously defined pEBV DNA cutoff values (1500 copies/mL pretreatment and 0 copies/mL post-treatment), there was a significant correlation between the pEBV DNA value and relapse-free survival, overall survival, and subsequent relapse rates in the new, independent patient cohort. Outcome analyses for the entire group revealed a higher relapse rate (45.6% vs 21.5% [P = .0037] or 76.7% vs 26.1% [P < .0001]), a worse relapse-free survival rate (56.5% vs 79.3% [P < .0001] or 23.3% vs 75.6% [P < .0001]), and poorer overall survival (59.2% vs 86% [P = .0003] or 33.3% vs 79.4% [P < .0001]) in patients who had high pretreatment or persistently detectable post-treatment pEBV DNA levels, respectively, versus their respective counterparts. Multivariate Cox analysis also confirmed these results. CONCLUSIONS: In this expanded study, the prognostic significance of pEBV DNA was confirmed using predefined cutoff values in an independent patient group, and pEBV DNA was identified as an independent prognostic marker for NPC.