Long-term psychological profile of general population following COVID-19 outbreak: symptom trajectories and evolution of psychopathological network.

AIMS: COVID-19 has long-term impacts on public mental health, while few research studies incorporate multidimensional methods to thoroughly characterise the psychological profile of general population and little detailed guidance exists for mental health management during the pandemic. This research aims to capture long-term psychological profile of general population following COVID-19 by integrating trajectory modelling approaches, latent trajectory pattern identification and network analyses. METHODS: Longitudinal data were collected from a nationwide sample of 18 804 adults in 12 months after COVID-19 outbreak in China. Patient Health Questionnaire-9, Generalised Anxiety Disorder-7 and Insomnia Severity Index were used to measure depression, anxiety and insomnia, respectively. The unconditional and conditional latent growth curve models were fitted to investigate trajectories and long-term predictors for psychological symptoms. We employed latent growth mixture model to identify the major psychological symptom trajectory patterns, and ran sparse Gaussian graphical models with graphical lasso to explore the evolution of psychopathological network. RESULTS: At 12 months after COVID-19 outbreak, psychological symptoms generally alleviated, and five psychological symptom trajectories with different demographics were identified: normal stable (63.4%), mild stable (15.3%), mild-increase to decrease (11.7%), mild-decrease to increase (4.0%) and moderate/severe stable (5.5%). The finding indicated that there were still about 5% individuals showing consistently severe distress and approximately 16% following fluctuating psychological trajectories, who should be continuously monitored. For individuals with persistently severe trajectories and those with fluctuating trajectories, central or bridge symptoms in the network were mainly 'motor abnormality' and 'sad mood', respectively. Compared with initial peak and late COVID-19 phase, aftermath of initial peak might be a psychologically vulnerable period with highest network connectivity. The central and bridge symptoms for aftermath of initial peak ('appetite change' and 'trouble of relaxing') were totally different from those at other pandemic phases ('sad mood'). CONCLUSIONS: This research identified the overall growing trend, long-term predictors, trajectory classes and evolutionary pattern of psychopathological network of psychological symptoms in 12 months after COVID-19 outbreak. It provides a multidimensional long-term psychological profile of the general population after COVID-19 outbreak, and accentuates the essentiality of continuous psychological monitoring, as well as population- and time-specific psychological management after COVID-19. We believe our findings can offer reference for long-term psychological management after pandemics.

A systematic review and meta-analysis on prevalence of and risk factors associated with depression, anxiety and insomnia in infectious diseases, including COVID-19: a call to action.

Infectious disease epidemics have become more frequent and more complex during the 21st century, posing a health threat to the general public and leading to psychological symptoms. The current study was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14th, 2020. Prevalence of mental symptoms among different populations including the general public, health workers, university students, older adults, infected patients, survivors of infection, and pregnant women across all types of epidemics was pooled. In addition, prevalence of mental symptoms during COVID-19 was estimated by time using meta-regression analysis. A total of 17,506 papers were initially retrieved, and a final of 283 studies met the inclusion criteria, representing a total of 948,882 individuals. The pooled prevalence of depression ranged from 23.1%, 95% confidential intervals (95% CI: [13.9-32.2]) in survivors to 43.3% (95% CI: [27.1-59.6]) in university students, the pooled prevalence of anxiety ranged from 25.0% (95% CI: [12.0-38.0]) in older adults to 43.3% (95% CI: [23.3-63.3]) in pregnant women, and insomnia symptoms ranged from 29.7% (95% CI: [24.4-34.9]) in the general public to 58.4% (95% CI: [28.1-88.6]) in university students. Prevalence of moderate-to-severe mental symptoms was lower but had substantial variation across different populations. The prevalence of mental problems increased over time during the COVID-19 pandemic among the general public, health workers and university students, and decreased among infected patients. Factors associated with increased prevalence for all three mental health symptoms included female sex, and having physical disorders, psychiatric disorders, COVID infection, colleagues or family members infected, experience of frontline work, close contact with infected patients, high exposure risk, quarantine experience and high concern about epidemics. Frequent exercise and good social support were associated with lower risk for these three mental symptoms. In conclusion, mental symptoms are common during epidemics with substantial variation across populations. The population-specific psychological crisis management are needed to decrease the burden of psychological problem and improve the mental wellbeing during epidemic.

Accessibility to Digital Mental Health Services among the General Public throughout COVID-19: Trajectories, Influencing Factors and Association with Long-Term Mental Health Symptoms.

Digital mental health services (DMHSs) have great potential for mitigating the mental health burden related to COVID-19, but public accessibility (ease of acquiring services when needed) to DMHSs during the pandemic is largely unknown. Accessibility to DMHSs was tracked longitudinally among a nationwide sample of 18,804 adults in China from before to one year after COVID-19 outbreak. Unconditional and conditional latent growth curve models and latent growth mixture models were fitted to explore the overall growth trend, influencing factors, and latent trajectory classes of accessibility to DMHSs throughout COVID-19. Generalized estimating equation models and generalized linear mixed models were employed to explore the association between accessibility to DMHSs and long-term mental health symptoms. We found that people generally reported increased difficulty in accessing DMHSs from before to one year after COVID-19 outbreak. Males, youngsters, individuals with low socioeconomic status, and individuals greatly affected by COVID-19 reported greater difficulty in accessing DMHSs. Four DMHS accessibility trajectory classes were identified: "lowest-great increase" (6.3%), "moderate low-slight increase" (44.4%), "moderate high-slight decrease" (18.1%) and "highest-great decrease" (31.2%). Trajectory classes reporting greater difficulty in accessing DMHSs were at higher risk for long-term mental symptoms. In conclusion, an overall increase in difficulty in accessing DMHSs is observed throughout COVID-19, and heterogeneity exists in DMHS accessibility trajectories. Our results suggest that easy access to DMHSs should be consistently facilitated. Moreover, access gaps should be reduced across demographic groups, and target populations for service allocation should alter as the pandemic evolves.

The Impact of Quarantine on Pain Sensation among the General Population in China during the COVID-19 Pandemic.

During the pandemic era, quarantines might potentially have negative effects and disproportionately exacerbate health condition problems. We conducted this cross-sectional, national study to ascertain the prevalence of constant pain symptoms and how quarantines impacted the pain symptoms and identify the factors associated with constant pain to further guide reducing the prevalence of chronic pain for vulnerable people under the pandemic. The sociodemographic data, quarantine conditions, mental health situations and pain symptoms of the general population were collected. After adjusting for potential confounders, long-term quarantine (≥15 days) exposures were associated with an increased risk of constant pain complaints compared to those not under a quarantine (Odds Ratio (OR): 1.26; 95% Confidence Interval (CI): 1.03, 1.54; p = 0.026). Risk factors including unemployment (OR: 1.55), chronic disease history (OR: 2.38) and infection with COVID-19 (OR: 2.15), and any of mental health symptoms including depression, anxiety, insomnia and PTSD (OR: 5.44) were identified by a multivariable logistic regression. Additionally, mediation analysis revealed that the effects of the quarantine duration on pain symptoms were mediated by mental health symptoms (indirect effects: 0.075, p < 0.001). These results advocated that long-term quarantine measures were associated with an increased risk of experiencing pain, especially for vulnerable groups with COVID-19 infection and with mental health symptoms. The findings also suggest that reducing mental distress during the pandemic might contribute to reducing the burden of pain symptoms and prioritizing interventions for those experiencing a long-term quarantine.

Analysis of the Mediating Effect of Risk Perception on the Relationship Between Time Perception and Mental Health of College Students During the COVID-19 Epidemic.

Background: COVID-19 has had a wide impact on the mental health of college students. This study aims to explore the relationship between time perception, risk perception, and the mental health of college students during COVID-19 through a questionnaire survey. Subjects: One thousand two hundred and eighteen college students, 449 male and 769 female, who studied online during the COVID-19 epidemic were selected. Methods: Time Perception Scale, Risk Perception Scale, and SCL-90 were used to investigate the relationship using correlation analysis. Results: During the COVID-19 period, mental health problems of college students were widespread, and 65.93% of college students reported moderate to severe mental health problems. The correlation analysis showed that risk perception, time perception, and the mental health of college students were significantly related. Risk perception played a partial mediating role between present enjoyment and mental health, and risk perception played a partial mediating role between future time perception and mental health. Conclusion: In the case of sudden public crises, we should pay close attention to the mental health of college students, adjust their attitude toward the present and the future, and pay attention to their perception of risk so as to improve their mental health level under crisis.

Neuropsychiatric manifestations of COVID-19, potential neurotropic mechanisms, and therapeutic interventions.

The coronavirus disease 2019 (COVID-19) pandemic has caused large-scale economic and social losses and worldwide deaths. Although most COVID-19 patients have initially complained of respiratory insufficiency, the presence of neuropsychiatric manifestations is also reported frequently, ranging from headache, hyposmia/anosmia, and neuromuscular dysfunction to stroke, seizure, encephalopathy, altered mental status, and psychiatric disorders, both in the acute phase and in the long term. These neuropsychiatric complications have emerged as a potential indicator of worsened clinical outcomes and poor prognosis, thus contributing to mortality in COVID-19 patients. Their etiology remains largely unclear and probably involves multiple neuroinvasive pathways. Here, we summarize recent animal and human studies for neurotrophic properties of severe acute respiratory syndrome coronavirus (SARS-CoV-2) and elucidate potential neuropathogenic mechanisms involved in the viral invasion of the central nervous system as a cause for brain damage and neurological impairments. We then discuss the potential therapeutic strategy for intervening and preventing neuropsychiatric complications associated with SARS-CoV-2 infection. Time-series monitoring of clinical-neurochemical-radiological progress of neuropsychiatric and neuroimmune complications need implementation in individuals exposed to SARS-CoV-2. The development of a screening, intervention, and therapeutic framework to prevent and reduce neuropsychiatric sequela is urgently needed and crucial for the short- and long-term recovery of COVID-19 patients.

Long-Term Impact of COVID-19 on Mental Health among the General Public: A Nationwide Longitudinal Study in China.

COVID-19 might have long-term mental health impacts. We aim to investigate the longitudinal changes in mental problems from initial COVID-19 peak to its aftermath among general public in China. Depression, anxiety and insomnia were assessed among a large-sample nationwide cohort of 10,492 adults during the initial COVID-19 peak (28 February 2020 to 11 March 2020) and its aftermath (8 July 2020 to 8 August 2020) using the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Insomnia Severity Index. We used generalized estimating equations and linear mixed models to explore factors associated with long-term mental health symptoms during COVID-19. During the five months, mental health symptoms remained consistently elevated (baseline 46.4%; follow-up 45.1%). Long-term depression, anxiety and insomnia were associated with several personal and work-related factors including quarantine (adjusted OR for any mental health symptoms 1.31, 95%CI 1.22-1.41, p < 0.001), increases in work burden after resuming work (1.77, 1.65-1.90, p < 0.001), occupational exposure risk to COVID-19 (1.26, 1.14-1.40, p < 0.001) and living in places severely affected by initial COVID-19 peak (1.21, 1.04-1.41, p = 0.01) or by a COVID-19 resurgence (1.38, 1.26-1.50, p < 0.001). Compliance with self-protection measures, such as wearing face masks (0.74, 0.61-0.90, p = 0.003), was associated with lower long-term risk of mental problems. The findings reveal a pronounced and prolonged mental health burden from the initial COVID-19 peak through to its aftermath in China. We should regularly monitor the mental health status of vulnerable populations throughout COVID-19.

SP1-induced long non-coding RNA SNHG6 facilitates the carcinogenesis of chondrosarcoma through inhibiting KLF6 by recruiting EZH2.

Small nucleolar RNA host gene 6 (SNHG6) is a newly discovered long non-coding RNA (lncRNA), while the regulatory mechanism of SNHG6 in chondrosarcoma is largely unknown. Here we found that SNHG6 expression was upregulated and showed positive correlation with the progression of chondrosarcoma. Functional assays demonstrated that SNHG6 was required for the proliferation, migration, and invasion of chondrosarcoma cells. Mechanistic study revealed that SNHG6 could recruit EZH2 and maintain high level of H3K27me3 to repress the transcription of tumor-suppressor genes, including KLF6. KLF6 was found to bind to the promoter region of SP1 and restrained its transcription, while SP1 could be recruited to the promoter region of SNHG6 and promoted its transcription to form a positive loop. In summary, this study reveals that SP1-induced SNHG6 forms a positive loop to facilitate the carcinogenesis of chondrosarcoma through the suppression of KLF6 by recruiting EZH2, which manifests the oncogenic function of SNHG6 in chondrosarcoma.

Cardiovascular effects of repeated subanaesthetic ketamine infusion in depression.

BACKGROUND: Ketamine produces significant rapid-onset and robust antidepressant effects in patients with major depressive disorder. However, this drug also has transient cardiovascular stimulatory effects, and there are limited data about potential predictors of these cardiovascular effects. METHODS: A total of 135 patients with unipolar and bipolar depression received a total of 741 ketamine infusions (0.5 mg/kg over 40 min). Blood pressure and pulse were monitored every 10 min during the infusions and 30 min after the infusions. Depressive, psychotomimetic and dissociative symptom severity was assessed at baseline and 4 hours after each infusion. RESULTS: The maximum blood pressure and pulse values were observed at 30-40 min during infusions. The largest mean systolic/diastolic blood pressure increases were 7.4/6.0 mmHg, and the largest mean pulse increase was 1.9 beats per min. No significant change in blood pressure and pulse was found in the second to sixth infusions compared with the first infusion. Patients who were older (age⩾50 years), hypertensive and receiving infusions while exhibiting dissociative symptoms showed greater maximal changes in systolic and diastolic blood pressure than patients who were younger (age<50 years), normotensive and without dissociative symptoms (all p < 0.05). Hypertensive patients had less elevation of pulse than normotensive patients (p < 0.05). Ketamine dosage was positively correlated with changes in systolic and diastolic blood pressure (all p < 0.05). CONCLUSIONS: Blood pressure and pulse elevations following subanaesthetic ketamine infusions are transient and do not cause serious cardiovascular events. Older age, hypertension, large ketamine dosage and dissociative symptoms may predict increased ketamine-induced cardiovascular effects.

Volumetric changes in subcortical structures following repeated ketamine treatment in patients with major depressive disorder: a longitudinal analysis.

Abnormal subcortical structures have been associated with major depressive disorder (MDD) and could be reversed by antidepressant treatment. To date no study has examined the relationship between subcortical volumes and repeated ketamine treatment. The current study investigated volume changes in specific subcortical structures and hippocampal subfields after six ketamine infusions. Forty-four patients with MDD received six subanesthetic dose infusions of ketamine. Depressive symptoms were assessed and magnetic resonance imaging scans were performed before and after six ketamine infusions. FreeSurfer software was used to process the T1 images and analyze the volumes of the subcortical regions and hippocampal subfields. After six ketamine infusions, increases were observed in the volumes of the left amygdala; the right hippocampus; the cornu ammonis 4 body, granule cell and molecular layer of the dentate gyrus body in the left hippocampus; and the cornu ammonis 4 head and molecular layer head in the right hippocampus. Positive correlations were found between symptom improvement and the pretreatment volumes of the right thalamus (r = 0.501; P = 0.001) and left subiculum head of the hippocampus (r = 0.471; P = 0.002), and changes in the volumes of the left amygdala (r = -0.452; P = 0.003) and the left cornu ammonis 4 body (r = -0.537; P < 0.001). Our findings provided evidence for critical roles of the amygdala and specific hippocampal subfields in the antidepressant effect of repeated ketamine treatment. Relatively larger volumes in right thalamus and left subiculum head in the hippocampus can predict a superior clinical outcome of ketamine treatment in MDD patients.

A preliminary study of adjunctive ketamine for treatment-resistant bipolar depression.

OBJECTIVES: Ketamine has shown rapid antidepressant effects in depressed patients. However, the antidepressant and antisuicidal effects of repeated ketamine infusions in patients with treatment-resistant bipolar depression (TRBD) are not known. METHODS: TRBD patients received six intravenous infusions of 0.5 mg/kg ketamine over 40 min on a Monday-Wednesday-Friday schedule during a 12-day period followed by a 2-week follow-up period. Depressive symptoms were measured by the Montgomery-Asberg Depression Rating Scale (MADRS) at baseline and at each follow-up visit. RESULTS: Nineteen patients with TRBD were enrolled in the study, and 16 patients (84.2%) received all six ketamine infusions. After the first infusion, the rates of response and remission were 21.1% (95% CI: 0.9 to 21.2) and 15.8% (95% CI: 0 to 33.9), respectively, and after the sixth infusion, the rates of response and remission were 73.7% (95% CI: 51.9 to 95.5) and 63.2% (95% CI: 39.3 to 87.0), respectively. The average times for nineteen patients who responded and remitted were 9.1 and 12.5 days, respectively. There were large decreases in the scores on the MADRS and the Scale for Suicidal Ideation-part 1 within 4 h after the first infusion, and the decreases were maintained across subsequent infusions. There were no significant increases in dissociative and psychotomimetic symptoms as measured by the Clinician-Administered Dissociative States Scale (CADSS) and the Brief Psychiatric Rating Scale (BPRS)-4 items, respectively. CONCLUSION: These pilot findings suggest the feasibility of repeated ketamine infusions at subanaesthetic doses for patients with TRBD. Future controlled studies are needed to confirm and expand these findings.

Adjunctive Reboxetine for Schizophrenia: Meta-analysis of Randomized Double-blind, Placebo-controlled Trials.

BACKGROUND: Results of previous studies on the safety and efficacy of adjunctive reboxetine for schizophrenia have been inconsistent. AIM: The aim of this study was to examine the efficacy and tolerability of reboxetine as an adjunct medication to antipsychotic treatment in a meta-analysis of randomized controlled trials (RCTs). METHODS: Two independent investigators extracted data for a random effects meta-analysis and assessed the quality of studies using risk of bias and the Jadad scale. Weighted and standardized mean differences (WMDs/SMDs) and risk ratio (RR)±95% confidence intervals (CIs) were calculated. RESULTS: Nine RCTs (n=630) with double-blind design were identified. Reboxetine outperformed placebo in improving negative (9 RCTs, n=602, SMD: -0.47 [95% CI: -0.87, -0.07], p=0.02; I2=82%), but not the overall, positive, and general psychopathology scores. The significant therapeutic effect on negative symptoms disappeared in the sensitivity analysis after removing an outlying study and in 50% (6/12) of the subgroup analyses. Reboxetine outperformed placebo in reducing weight (3 RCTs, n=186, WMD: -3.83 kg, p=0.04; I2=92%) and body mass index (WMD: -2.23 kg/m2, p=0.04; I2=95%). Reboxetine caused dry mouth but was associated with less weight gain overall and weight gain of ≥7% of the initial weight. All-cause discontinuation and other adverse events were similar between reboxetine and placebo. CONCLUSION: Adjunctive reboxetine could be useful for attenuating antipsychotic-induced weight gain, but it was not effective in treating psychopathology including negative symptoms in schizophrenia.

Investigation of medical effect of multiple ketamine infusions on patients with major depressive disorder.

OBJECTIVE: Single-dose intravenous ketamine has rapid but time-limited antidepressant effects. We aimed to examine the sustained effects of six consecutive ketamine infusions in Chinese patients with major depressive disorder. METHODS: Seventy-seven patients with major depressive disorder were eligible to receive augmentation with six ketamine infusions (0.5 mg/kg over 40 min) administered over the course of 12 days (Monday-Wednesday-Friday). The coprimary outcome measures were the rates of response and remission as measured on the 10-item Montgomery-Asberg Depression Rating Scale. Psychotomimetic and dissociative symptoms were measured with the Brief Psychiatric Rating Scale-positive symptoms and the Clinician Administered Dissociative States Scale, respectively. RESULTS: After the first ketamine infusion, only 10 (13.0%) and 6 (7.8%) patients responded and remitted, respectively; after six ketamine infusions, 52 (67.5%) patients responded and 37 (48.1%) remitted. There was a significant mean decrease in Montgomery-Asberg Depression Rating Scale score at four hours after the first ketamine infusion (7.0±7.5, p<0.001), and this decrease was maintained for the duration of the infusion period. The response to ketamine treatment was positively associated with no history of psychiatric hospitalization (odds ratio=3.56, p=0.009). Suicidal ideation rapidly decreased across the entire study sample, even among the nonresponder group. No significant differences were found regarding Brief Psychiatric Rating Scale and Clinician Administered Dissociative States Scale scores from the first infusion at baseline to four hours post-infusion. CONCLUSION: Six ketamine infusions increased rates of response and remission when compared to a single-dose ketamine infusion in patients with major depressive disorder. Future controlled studies are warranted to confirm and expand these findings.

Neurocognitive performance and repeated-dose intravenous ketamine in major depressive disorder.

OBJECTIVE: Ketamine has demonstrated a rapid antidepressant and antisuicidal effect in patients with major depressive disorder (MDD), but the neurocognitive effects of ketamine are relatively unknown. This study aims to examine the neurocognitive effects of six ketamine infusions and the association of baseline neurocognitive function and the change in severity of depressive symptoms after the last infusions. METHODS: Sixty-four patients with MDD completed six intravenous infusions of ketamine (0.5 mg/kg over 40 min) administered over a 12-day period (Monday-Wednesday-Friday), and were followed by a 2-week observational period. Four domains of neurocognitive function (including speed of processing, working memory, visual learning and verbal learning) were assessed using the MATRICS Consensus Cognitive Battery (MCCB) at 0, 13 and 26 days. RESULTS: In linear mixed model, significant improvements were found in terms of speed of processing (F = 20.7, p < 0.001) and verbal learning (F = 11.1, p < 0.001). The Sobel test showed the improvement of speed of processing (Sobel test = 2.8, p < 0.001) and verbal learning (Sobel test = 3.6, p < 0.001) were significantly mediated by change in depressive symptoms. Other two neurocognitive domains showed no significant changes over time. Correlation analysis showed no significant association of change in depressive symptoms with neurocognitive function at baseline. CONCLUSION: Our findings suggest that six ketamine infusions were associated with the improvement of speed of processing and verbal learning, which were partly accounted for by improvement in the severity of depression symptoms over time.

Organochlorine pesticides in ambient air from the littoral cities of northern China: Spatial distribution, seasonal variation, source apportionment and cancer risk assessment.

Concentrations, composition and seasonal variations of organochlorine pesticides (OCPs) in the atmosphere (particulate phase and gaseous phase) at coastal cities in northern China were determined. OCP transport from emission source areas and lifetime excess cancer risks by inhalation exposure to specific OCPs were also investigated. The annual average concentration of total OCPs in gaseous phase ranged from 1.0ng/m3 to 6.3ng/m3, with the peak observed in summer at most sites. Particulate phase concentrations ranged from 29.9pg/m3 to 103.3pg/m3, with the maximum found in the local heating period at most locations. The detection rates of gaseous samples were considerably higher than those of particulate ones. The dominant components included endosulfan (I and II), (α- and γ-) chlordane, pentachlorobiphenyl (PeCB), hexachlorobenzene (HCB), heptachlor, (α-, ß- and γ-) hexachlorocyclohexane (HCH), dichloro-diphenyl-trichloroethane (DDT) and their metabolic products. The specific ratios indicated different applications of DDT, technical HCH and endosulfan at most sites. Large differences in compositional profiles occurred in January (typical heating period) and July (representative non-heating period), and diurnal changes in component concentrations may have been influenced by local emission pattern. The potential source contribution function (PSCF) manifested seasonal concentrations of airborne OCPs affected by the input of potential sources in different regions. The emission sources with higher contribution probabilities to the sites were primarily distributed in the surrounding areas. The lifetime excess cancer risks for the local residents by inhalation exposure to specific components were not high, though the potential threat of α-HCH and HCB should be concerned. CAPSULE: Gaseous OCPs reached peak values in summer and dominated relative to particulate (PM10) values; meanwhile, surrounding sources affected air OCP concentrations, and cancer risks of OCPs by inhalation exposure were not high.

Rapid and longer-term antidepressant effects of repeated-dose intravenous ketamine for patients with unipolar and bipolar depression.

OBJECTIVE: Single-dose intravenous (IV) injection of ketamine has shown rapid but transient antidepressant effects. The strategy of repeated-dose ketamine infusions to maintain antidepressant effects has received little systematic study. This study was conducted to examine the efficacy and tolerability of six ketamine infusions in Chinese patients with unipolar and bipolar depression. METHODS: Ninety seven patients with unipolar (n = 77) and bipolar (n = 20) depression received repeated ketamine infusions (0.5 mg/kg over 40 min) with continuous vital sign monitoring. Depressive symptoms were measured by the Montgomery-Asberg Depression Rating Scale (MADRS). Suicidal ideation was assessed using the Scale for Suicidal Ideations (SSI)-part 1. Anxiety symptoms were evaluated with the 14-item Hamilton Anxiety Scale (HAMA). Adverse psychopathological and dissociative effects were assessed using the Brief Psychiatric Rating Scale (BPRS)-positive symptoms and Clinician Administered Dissociative States Scale (CADSS), respectively. Patients were assessed at baseline, 4 and 24 h, and 3, 4, 5, 6, 8, 9, 10, 11, 12, 13 and 26 days. RESULTS: After six ketamine infusions, the response and remission rates were 68.0% and 50.5%, respectively. There were significant decreases in MADRS, SSI-part 1, and HAMA scores within four hours following the first ketamine infusion, and the decreases were sustained over the subsequent infusion period. The nonresponder subgroup manifested rapid significant improvement in suicidal ideations throughout the course of treatment. After the six ketamine infusions, the response was positively associated with the response at 24 h after the first infusion (OR = 8.94), personal income ≥4000 yuan/month (OR = 3.04), and no history of psychiatric hospitalization (OR = 3.41). Only CADSS scores had a mild but marginally significant increase after the first infusion but with a significant BPRS score decrease. CONCLUSION: Six ketamine infusions were safe and effective in patients with unipolar and bipolar depression. The rapid and robust antidepressant and antisuicidal effects of ketamine infusion within four hours were sustained following the subsequent infusions.

[Concentrations and Component Profiles PAHs in Surface Soils and Wheat Grains from the Cornfields Close to the Steel Smelting Industry in Handan, Hebei Province].

In this study, paired surface soil and mature wheat grain samples were collected in the cornfields near the large Handan Steel Manufacturer; and the total concentrations and compositional profiles of the parent PAHs were measured, then the spatial distribution characteristics and correlation with total organic carbon fractions in soil were determined. Accordingly, a preliminary source identification was performed, and the association between PAHs in surface soil and wheat grain was briefly discussed. The median concentration of total PAHs in surface soils from the cornfields of Handan was 398.9 ng x g(-1) (ranged from 123.4 ng x g(-1) to 1626.4 ng x g(-1), where around 18% and 10% of all the studied soil samples were over the corresponding quality criteria for total PAHs and B [a] P in soils, respectively. The MMW and HMW species were the main components in the compositional profiles of surface soils. Based on the specific isomeric ratios of PAHs species, coal/biomass combustion and transportation fuel (tail gas) were the dominant mixed sources for the local PAHs emission. The fractions of surface soil TOC had significant positive correlations with the total PAHs and also with the individual components with different rings. In addition, the median concentration of total PAHs in wheat grains collected in the cornfields near the Handan Steel Manufacture was 27.0 ng x g(-1) (ranged from 19.0-34.0 ng x g(-1)). The levels in wheat grains were not high, and lower than the related hygienic standards of food proposed by EU and China. The LMW and MMW PAHs with 2 to 4 rings occupied a larger proportion, more than 84% of the total PAHs, which was largely different from the component profiles in surface soils. This situation suggested that the local sources of PAHs in wheat grains may originate not only from surface soil via root absorption and internal transportation, but also from ambient air through dry and wet deposition on the leaf surface (stoma).

[Variations and Influencing Factors of Oral Bioaccessibility of Polybrominated Diphenyl Ethers in Soils Using an In-vitro Gastrointestinal Model].

Intake of contaminated soils is considered as an important exposure pathway of polybrominated diphenyl ethers (PBDEs) to humans, especially for children during their outdoor hand-to-mouth activities. Oral bioaccessibility is an essential tool to quantitatively assess the exposure risk of pollutants. In this study, we employed an in vitro digestion model to mimic the gastrointestinal digestion of typical PBDEs (BDE-28, BDE-47, BDE-99 and BDE-153 at a series of initial concentrations) in three natural soil samples with different TOC contents and to verify a previous hypothesis that the sorption of PBDE fraction mobilized from soil into digestive fluid on the surface of residual solid phase may lead to an underestimation of bioaccessibility of PBDEs. In addition, a method with multiple fluid-to-solid ratios was applied to calibrate the underestimation. The results indicated that the calibrated digestibility values were commonly higher than those without correction. For the different soil samples, the averaged increasing rates of PBDE digestibility at different initial concentrations ranged from 14.3% to 42.3%, from 11.1% to 32.1%, from 4.9% to 12.3% and from 0.0% to 7.7% for BDE-28, BDE-47, BDE-99 and BDE-153, respectively. Therefore, the bioaccessibility of PBDEs in gastrointestinal gut would be significantly underestimated without calibration, especially for tri- and tetra-BDEs and soil samples with low TOC contents or high PBDEs concentrations. The corrected digestibility values of BDE-28, BDE-47, BDE-99 and BDE-153 were 21.9%-54.7%, 18.8%-43.1%, 13.4%-27.2% and 9.3%-19.9%, respectively. The results indicated that the PBDEs digestibility was negatively correlated with lgK(ow); whereas there was no significant correlation of PBDE bioaccessibility with TOC contents in soils or with initial concentrations of PBDEs, particularly for the highly brominated components.

The Neural Mechanism by Which the Dorsal Vagal Complex Mediates the Regulation of the Gastric Motility by Weishu (RN12) and Zhongwan (BL21) Stimulation.

A large number of studies have been conducted to explore the mechanism of Back-Shu and Front-Mu points. While several lines of evidence addressed the acupuncture information of Shu acupoints and Mu acupoints gathering in the spinal cord, whether the convergence is extended to the high centre still remains unclear. The study selected gastric Mu points (RN12) and gastric Shu points (BL21) regulating gastric motility and its central neural mechanisms as the breakthrough point, using the technique of immunochemistry, nuclei lesion, electrophysiology, and nerve transection. Here, we report that gastric motility regulation of gastric Shu and Mu acupoints and their synergistic effect and the signals induced by electroacupuncture (EA) stimulation of acupoints RN12 and RN12 gather in the dorsal vagal complex (DVC), increasing the levels of gastrointestinal hormones in the DVC to regulate gastric motility through the vagus. In sum, our data demonstrate an important role of DVC and vagus in the regulation of gastric motility by EA at gastric Shu and Mu points.