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Although aberrant brain regional responses are reported in social anxiety disorder (SAD), little is known about resting-state functional connectivity at the macroscale network level. This study aims to identify functional network abnormalities using a multivariate data-driven method in a relatively large and homogenous sample of SAD patients, and assess their potential diagnostic value.
Forty-six SAD patients and 52 demographically-matched healthy controls (HC) were recruited to undergo clinical evaluation and resting-state functional MRI scanning. We used group independent component analysis to characterize the functional architecture of brain resting-state networks (RSNs) and investigate between-group differences in intra-/inter-network functional network connectivity (FNC). Furtherly, we explored the associations of FNC abnormalities with clinical characteristics, and assessed their ability to discriminate SAD from HC using support vector machine analyses.
SAD patients showed widespread intra-network FNC abnormalities in the default mode network, the subcortical network and the perceptual system (i.e. sensorimotor, auditory and visual networks), and large-scale inter-network FNC abnormalities among those high-order and primary RSNs. Some aberrant FNC signatures were correlated to disease severity and duration, suggesting pathophysiological relevance. Furthermore, intrinsic FNC anomalies allowed individual classification of SAD v. HC with significant accuracy, indicating potential diagnostic efficacy.
SAD patients show distinct patterns of functional synchronization abnormalities both within and across large-scale RSNs, reflecting or causing a network imbalance of bottom-up response and top-down regulation in cognitive, emotional and sensory domains. Therefore, this could offer insights into the neurofunctional substrates of SAD.
Benzodiazepine receptor agonists (BZRAs) are commonly used clinically and data on their hazardous use from large populations of psychiatric patients is limited.
To assess the current status of hazardous BZRA use and related factors in Chinese out-patient psychiatric settings.
The study included out-patients with at least one BZRA prescription from five psychiatric settings in east, central and west China in 2018. Demographic and prescription information were extracted from the electronic prescription database. We defined the co-occurrence of overdose and long-term use as hazardous use, and patients whose recorded diagnoses did not meet any indications approved by the Chinese Food and Drug Administration as over-indication users. Additionally, 200 hazardous users were randomly selected for follow-up interview to confirm the actual situation.
Among 720 054 out-patients, 164 450 (22.8%) had at least one BZRA prescription; 55.9% of patients were prescribed over-indication and 3% were defined as hazardous users. Multilevel multivariate regression analysis with hospital as a random effect showed that factors associated with hazardous use were older age (18–64 years: β = 0.018; 95% CI 0.013–0.023; >65 years: β = 0.015; 95% CI 0.010–0.021), male (β = 0.005, 95% CI 0.003–0.007), over-indication (β = 0.013, 95% CI 0.012–0.015), more out-patient visits (β = 0.006, 95% CI 0.006–0.006) and more visits to different doctors (β = 0.007, 95% CI 0.007–0.008); 98.5% of hazardous users (197/200) could not be contacted.
BZRAs are commonly used and there is a relatively large proportion of over-indication users among Chinese psychiatric out-patients. However, only a small proportion of hazardous users were detected. The study highlights how to use prescription data to support improvements in clinical practice.
Studies have shown that people with internet gaming disorder (IGD) exhibit impaired executive control of gaming cravings; however, the neural mechanisms underlying this process remain unknown. In addition, these conclusions were based on the hypothesis that brain networks are temporally static, neglecting dynamic changes in cognitive processes.
Resting-state fMRI data were collected from 402 subjects [162 subjects with IGD and 240 recreational game users (RGUs)]. The community structure (recruitment and integration) of the executive control network (ECN) and the basal ganglia network (BGN), which represents the reward network, of patients with IGD and RGUs were compared. Mediation effects among the different networks were analyzed.
Compared to RGUs, subjects with IGD had a lower recruitment coefficient within the right ECN. Further analysis showed that only male subjects had a lower recruitment coefficient. Mediation analysis showed that the integration coefficient of the right ECN mediated the relationship between the recruitment coefficients of both the right ECN and the BGN in RGUs.
Male subjects with IGD had a lower recruitment coefficient than RGUs, which impairing their impulse control. The mediation results suggest that top-down executive control of the ECN is absent in subjects with IGD. Together, these findings could explain why subjects with IGD exhibit impaired executive control of gaming cravings; these results have important therapeutic implications for developing effective interventions for IGD.
Pharmacological treatment of major depressive disorder is often inefficient, and multiple strategies are used for inadequate response to antidepressants. Second-generation antipsychotics are used as augmentation measures in clinical practice; evidence of their efficacy and acceptability is insufficient, and it remains confusing as to which drug should be selected first. In this systematic review and network meta-analysis, we included randomised controlled trials of second-generation antipsychotics used as adjunctive treatment in patients with suboptimal responses. Outcome measures were efficacy (response and remission) and acceptability (dropout due to any reason and adverse events). Thirty-three trials comprising 10 602 participants were included. Regarding efficacy, response rates indicated that all antipsychotics except for ziprasidone were more efficacious than the placebo, with the odds ratios (ORs) ranging from 1.34 for olanzapine and cariprazine [95% credible interval (CrI) 1.04–1.73 and 1.07–1.67, respectively] to 2.17 for risperidone (95% CrI 1.38–3.42). When considering remission, cariprazine was not effective (OR 1.21, 95% CrI 0.96–1.54). For acceptability, quetiapine (OR 0.68, 95% CrI 0.50–0.91), brexpiprazole (OR 0.69, 95% CrI 0.55–0.86), and cariprazine (OR 0.61, 95% CrI 0.46–0.82) were worse than the placebo. With regards to tolerability, only olanzapine (OR 0.51, 95% CrI 0.25–1.07) and risperidone (OR 0.48, 95% CrI 0.10–2.21) showed no significant differences compared with placebo. The administration of adjunctive antipsychotics is associated with high effectiveness and low acceptability. Risperidone and aripiprazole are more efficacious and accepted than other atypical antipsychotics.
Persistent psychological distress associated with the coronavirus disease 2019 (COVID-19) pandemic has been well documented. This study aimed to identify pre-COVID brain functional connectome that predicts pandemic-related distress symptoms among young adults.
Baseline neuroimaging studies and assessment of general distress using the Depression, Anxiety and Stress Scale were performed with 100 healthy individuals prior to wide recognition of the health risks associated with the emergence of COVID-19. They were recontacted for the Impact of Event Scale-Revised and the Posttraumatic Stress Disorder Checklist in the period of community-level outbreaks, and for follow-up distress evaluation again 1 year later. We employed the network-based statistic approach to identify connectome that predicted the increase of distress based on 136-region-parcellation with assigned network membership. Predictive performance of connectome features and causal relations were examined by cross-validation and mediation analyses.
The connectome features that predicted emergence of distress after COVID contained 70 neural connections. Most within-network connections were located in the default mode network (DMN), and affective network-DMN and dorsal attention network-DMN links largely constituted between-network pairs. The hippocampus emerged as the most critical hub region. Predictive models of the connectome remained robust in cross-validation. Mediation analyses demonstrated that COVID-related posttraumatic stress partially explained the correlation of connectome to the development of general distress.
Brain functional connectome may fingerprint individuals with vulnerability to psychological distress associated with the COVID pandemic. Individuals with brain neuromarkers may benefit from the corresponding interventions to reduce the risk or severity of distress related to fear of COVID-related challenges.
Severe heat exposure causes mitochondrial fragmentation and dysfunction, which contribute to the pathogenesis of heat-related illness. l-Citrulline is a naturally occurring amino acid and has been suggested to influence heat shock responses. This study aimed to test whether l-citrulline supplementation would preserve mitochondrial integrity and attenuate heat-induced skeletal muscle injury and elucidate the underlying mechanisms. At 37°C, l-citrulline (2 mM) increased mitochondrial elongation in mouse C2C12 myoblasts, a process associated with a reduction in mitochondrial fission protein Drp1 levels. Mechanistic studies revealed that l-citrulline increased cellular nitric oxide (NO) levels, but not S-nitrosylation of Drp1. l-Citrulline caused a decrease in phosphorylation of Drp1 at Ser 616 and an increase in phosphorylation of Drp1 at Ser 637, which resulted in a reduced mitochondrial localisation of Drp1. L-NAME, a non-selective NO synthase inhibitor, abolished the increase in l-citrulline-induced NO levels and inhibited Drp1 phosphorylation changes and mitochondrial elongation, which indicates the involvement of a NO-dependent pathway. Under 43°C heat stress conditions, l-citrulline prevented translocation of Drp1 to mitochondria, mitochondrial fragmentation and decreased membrane potential. Finally, l-citrulline pretreatment inhibited heat-induced reactive oxygen species overproduction, caspase 3/7 activation, apoptotic cell death and improved cell viability. NO inhibitor l-NAME abolished all the above protective effects of l-citrulline under heat stress. Our results suggest that l-citrulline prevents heat-induced mitochondrial dysfunction and cell injury through NO-mediated Drp1 inhibition in C2C12 myoblasts. l-Citrulline may be an effective treatment for heat-related illnesses and other mitochondrial diseases.
This paper investigates the monolithic edge-cladding process for the elliptical disk of N31-type Nd-doped phosphate laser glass, which will be utilized under liquid cooling conditions for high-power laser systems. The thermal stress, interface bubbles and residual reflectivity, which are due to high-temperature casting and bonding during the monolithic edge-cladding process, are simulated and determined. The applied mould is optimized to a rectangular cavity mould, and the casting temperature is optimized to 1000°C. The resulting lower bubble density makes the mean residual reflectivity as low as 6.75 × 10−5, which is enough to suppress the amplified spontaneous emission generated in the Nd-glass disk, and the resulting maximum optical retardation is converged to 10.2–13.3 nm/cm, which is a favourable base for fine annealing to achieve the stress specification of less than or equal to 5 nm/cm. After fine annealing at the optimized 520°C, the maximum optical retardation is as low as 4.8 nm/cm, and the minimum transmitted wavefront peak-to-valley value is 0.222 wavelength (632.8 nm). An N31 elliptical disk with the size of 194 mm × 102 mm × 40 mm can be successfully cladded by the optimized monolithic edge-cladding process, whose edge-cladded disk with the size of 200 mm × 108 mm × 40 mm can achieve laser gain one-third higher than that of an N21-type disk of the same size.
We examined whether physical activity (PA) explains the association between dietary inflammatory potential and osteoarthritis (OA) in the elderly. A total of 1249 elderly people (≥65 years) were eligible for this study from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. The semi-quantitative Food Frequency Questionnaire (FFQ) and Global PA Questionnaire (GPAQ) were used to evaluate the diet and PA of the elderly, respectively. The multivariable logistic regression model estimated the odds ratio (OR) and 95% confidence interval (CI) between Energy-adjusted Dietary Inflammatory Index (E-DII) and OA. The interaction of E-DII and PA on depressive events was tested, and the mediation analysis of PA was performed. The average E-DII in this study was +0.68 (SE 0.08), and the score ranges from -5.32 (most anti-inflammatory) to +4.26 (most pro-inflammatory). In comparison with the first quartile, the elderly from the second quartile (OR: 1.16 [95% CI: 1.06, 1.68]) to the fourth quartile (OR: 1.64 [95% CI: 1.13, 2.37]) had a higher risk of OA before adjustment for PA. An interaction was observed between E-DII and PA in terms of the risk of OA (PInteraction < 0.001). The whole related part was mediated by PA (20.08%). Our findings indicated that the higher pro-inflammatory potential of diet was associated with a higher risk of OA, and low PA was an important part of the mediating factor in the relationship between systemic low-grade dietary inflammation and the risk of OA.
The joint effects of stimulus quality and semantic context in visual word recognition were examined with event-related potential (ERP) recordings. In one-character Chinese word recognition, we manipulated stimulus quality at two degradation levels (highly vs. slightly degraded) and semantic context at two priming levels (semantically related vs. unrelated). In a prime–target–probe trial flow, ERPs were recorded to the target character which was presented in either high or slight degradation and which was preceded by either a semantically related or unrelated prime character. The target character was then followed by a probe character which was either identical to or different from the target character. Subjects were instructed to make target–probe matching judgments. The ERP results demonstrated a degradation by priming interaction, with larger N400 semantic priming effects for slightly degraded targets. Moreover, the degradation effects were observed on the P200, N250, and N400. These findings provided evidence for the cascaded model of visual word recognition such that the visual processing cascaded into the semantic stage and thus interacted on the N400 amplitude. The results were compared to an earlier study with a null ERP degradation by priming interaction. The ramifications of these results for models of visual word recognition are discussed.
High-Mg andesites (HMAs) are crucial for the reconstruction of plate tectonics, continental margin formation and lithospheric evolution. In this study, we present new fossil age, whole-rock geochemical and Sr–Nd isotope data on the newly discovered Dundunshan Group HMAs in the Dundunshan area of the Beishan orogen (central-southern Central Asian Orogenic Belt). The Dundunshan HMA samples are characterized by high MgO (6.47–7.02 wt%) contents and high Mg# values (67.27–68.77), with SiO2 (58.57–62.13 wt%), Al2O3 (14.49–16.07 wt%) and CaO (5.05–6.24 wt%) resembling typical HMAs. The Dundunshan HMA samples are calc-alkaline and strongly enriched in light rare earth elements (LREEs) and large-ion lithophile elements (LILEs), with slightly negative Eu anomaly and high-field-strength element (HFSE) depletions. Their (87Sr/86Sr)i ratios (0.7041–0.7057) and ϵNd(t) (3.73–5.59) indicate that the Dundunshan HMAs were mainly formed by the interactions between subducted oceanic sediment-derived melts and mantle peridotites. Fossil evidence and published radiometric age data constrain the formation of the Dundunshan HMAs to early Late Devonian time. Sedimentological features of the Middle Devonian Sangejing Formation and regional tectonic correlation suggest that the Hongliuhe–Niujuanzi–Xichangjing Ocean in the Dundunshan area was likely closed during late Middle Devonian time, and that the Dundunshan HMAs were formed in a post-collision extensional setting.
We present a theoretical study of mode evolution in high-power distributed side-coupled cladding-pumped (DSCCP) fiber amplifiers. A semi-analytical model taking the side-pumping schemes, transverse mode competition, and stimulated thermal Rayleigh scattering into consideration has been built, which can model the static and dynamic mode evolution in high-power DSCCP fiber amplifiers. The mode evolution behavior has been investigated with variation of the fiber amplifier parameters, such as the pump power distribution, the length of the DSCCP fiber, the averaged coupling coefficient, the number of the pump cores and the arrangement of the pump cores. Interestingly, it revealed that static mode evolution induced by transverse mode competition is different from the dynamic evolution induced by stimulated thermal Rayleigh scattering. This shows that the high-order mode experiences a slightly higher gain in DSCCP fiber amplifiers, but the mode instability thresholds for DSCCP fiber amplifiers are higher than those for their end-coupled counterparts. By increasing the pump core number and reducing the averaged coupling coefficient, the mode instability threshold can be increased, which indicates that DSCCP fibers can provide additional mitigation strategies of dynamic mode instability.
The aim of the present study was to compare the rate of preterm birth (PTB) and growth from birth to 18 years between twins conceived by in vitro fertilization (IVF) and twins conceived by spontaneous conception (SC) in mainland China. The retrospective cohort study included 1164 twins resulting from IVF and 25,654 twins conceived spontaneously, of which 494 from IVF and 6338 from SC were opposite-sex twins. PTB and low birth weight (LBW), and growth, including length/height and weight, were compared between the two groups at five stages: infancy (0 year), toddler period (1–2 years), preschool (3–5 years), primary or elementary school (6–11 years), and adolescence (10–18 years). Few statistically significant differences were found for LBW and growth between the two groups after adjusting for PTB and other confounders. Twins born by IVF faced an increased risk of PTB compared with those born by SC (adjusted odds ratio [aOR] 8.21, 95% confidence interval [CI] [3.19, 21.13], p < .001 in all twins and aOR 10.12, 95% CI [2.32, 44.04], p = .002 in opposite-sex twins). Twins born by IVF experienced a similar growth at five stages (0–18 years old) when compared with those born by SC. PTB risk, however, is significantly higher for twins conceived by IVF than those conceived by SC.
Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40–69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29–9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (Pfor interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.
The findings regarding the associations between red meat, fish and poultry consumption, and the metabolic syndrome (Mets) have been inconclusive, and evidence from Chinese populations is scarce. A cross-sectional study was performed to investigate the associations between red meat, fish and poultry consumption, and the prevalence of the Mets and its components among the residents of Suzhou Industrial Park, Suzhou, China. A total of 4424 participants were eligible for the analysis. A logistic regression model was used to estimate the OR and 95 % CI for the prevalence of the Mets and its components according to red meat, fish and poultry consumption. In addition, the data of our cross-sectional study were meta-analysed under a random effects model along with those of published observational studies to generate the summary relative risks (RR) of the associations between the highest v. lowest categories of red meat, fish and poultry consumption and the Mets and its components. In the cross-sectional study, the multivariable-adjusted OR for the highest v. lowest quartiles of consumption was 1·23 (95 % CI 1·02, 1·48) for red meat, 0·83 (95 % CI 0·72, 0·97) for fish and 0·93 (95 % CI 0·74, 1·18) for poultry. In the meta-analysis, the pooled RR for the highest v. lowest categories of consumption was 1·20 (95 % CI 1·06, 1·35) for red meat, 0·88 (95 % CI 0·81, 0·96) for fish and 0·97 (95 % CI 0·85, 1·10) for poultry. The findings of both cross-sectional studies and meta-analyses indicated that the association between fish consumption and the Mets may be partly driven by the inverse association of fish consumption with elevated TAG and reduced HDL-cholesterol and, to a lesser extent, fasting plasma glucose. No clear pattern of associations was observed between red meat or poultry consumption and the components of the Mets. The current findings add weight to the evidence that the Mets may be positively associated with red meat consumption, inversely associated with fish consumption and neutrally associated with poultry consumption.
Polycarboxylate superplasticizer (PCE) is sensitive to the clay present in concrete aggregates. In particular, Montmorillonite (Mnt), an impurity inevitably contained in the aggregate, can significantly influence the performance of concrete. In an effort to improve the compatibility of PCE, a zwitterionic PCE with cationic amide groups and shorter side-chain lengths was synthesized via free radical copolymerization. The optimal synthesis condition was verified via Box-Behnken design. In addition to characterizing the PCE, the performance of PCE in cement pastes with or without Na-Mnt was examined and the underlying mechanism was explored. The results show that, compared with commercially available PCE, the required dosage of PCE for cements containing Na-Mnt decreased. Unlike commercially available PCE, no intercalation occured on the newly manufactured clay-tolerant PCE within the layers of Mnt, resulting in a greater sorption thickness and improved dispersion of the cements containing Na-Mnt.
High-quality primary care reduces premature mortality in the general population, but evidence for psychiatric patients in China is scarce.
To confirm excess mortality in patients with severe mental illness (SMI), and to examine the impact of community-based mental healthcare and other risk factors on their mortality.
We included 93 655 patients in 2012 and 100 706 in 2013 from the national mental health surveillance system in Sichuan, China to calculate the standardised mortality ratio (SMR). A total of 112 576 patients were followed up from 2009 to 2014 for model analyses. We used growth models to quantify the patterns of change for community management measures, high-risk behaviour, disease stability and medication adherence of patients over time, and then used multilevel proportional hazard models to examine the association between change patterns of management measures and mortality.
The SMR was 6.44 (95% CI 4.94–8.26) in 2012 and 7.57 (95% CI 5.98–9.44) in 2013 among patients with SMI aged 15–34 years, and diminished with age. Unfavourable baseline socioeconomic status increased the hazard of death by 38–50%. Positive changes in high-risk behaviour, disease stability and medication adherence had a 54% (95% CI 47–60%), 69% (95% CI 63–73%) and 20% (4–33%) reduction in hazard of death, respectively, versus in those where these were unchanged.
High excess mortality was confirmed among younger patients with SMI in Sichuan, China. Our findings on the relationships between community management and socioeconomic factors and mortality can inform community-based mental healthcare policies to reduce excess mortality among patients with SMI.
Echinococcus granulosus sensu lato has complex defence mechanisms that protect it from the anti-parasitic immune response for long periods. Echinococcus granulosus cyst fluid (EgCF) is involved in the immune escape. Nevertheless, whether and how EgCF modulates the inflammatory response in macrophages remains poorly understood. Here, real-time polymerase chain reaction and enzyme-linked immunosorbent assay revealed that EgCF could markedly attenuate the lipopolysaccharide (LPS)-induced production of pro-inflammatory factors including tumour necrosis factor-α, interleukin (IL)-12 and IL-6 but increase the expression of IL-10 at mRNA and protein levels in mouse peritoneal macrophages and RAW 264.7 cells. Mechanically, western blotting and immunofluorescence assay showed that EgCF abolished the activation of nuclear factor (NF)-κB p65, p38 mitogen-activated protein kinase (MAPK) and ERK1/2 signalling pathways by LPS stimulation in mouse macrophages. EgCF's anti-inflammatory role was at least partly contributed by promoting proteasomal degradation of the critical adaptor TRAF6. Moreover, the EgCF-promoted anti-inflammatory response and TRAF6 proteasomal degradation were conserved in human THP-1 macrophages. These findings collectively reveal a novel mechanism by which EgCF suppresses inflammatory responses by inhibiting TRAF6 and the downstream activation of NF-κB and MAPK signalling in both human and mouse macrophages, providing new insights into the molecular mechanisms underlying the E. granulosus-induced immune evasion.