Search

This article analyses Ne Zha’s image evolution through different animated films in the PRC from 1961 to 2019. Three key Ne Zha films are Uproar in Heaven, Ne Zha Conquers the Dragon King and Ne Zha, representing the era of ‘classical Chinese animation’, ‘modern Chinese animation’ and ‘postmodern Chinese animation’, respectively. In 2019, Ne Zha became the summer hit and the highest-grossing Chinese original animation earning ¥5.035 billion at the Chinese box office. Explorations of how classical artistic traditions and legendary stories have been transposed into these films shows that Chinese animation has retreated from the peak of national style in the 1960s and undergone change with globalization’s cultural and ideological impacts. In sum, artistic techniques associated with fine arts film, traditional narrative methods and plot stylization have gradually weakened. Contemporary elements such as Hollywood classic three-act pattern and Japanese comic character relationships and images have significantly influenced Chinese animation in the twenty-first century.

The application of 3D printing in planning endoscopic endonasal transsphenoidal surgery is illustrated based on the analysis of patients with intracranial skull base diseases who received treatment in our department. Cranial computed tomography/magnetic resonance imaging data are attained preoperatively, and three-dimensional reconstruction is performed using MIMICS (Materialise, Leuven, Belgium). Models of intracranial skull base diseases are printed using a 3D printer before surgery. The models clearly demonstrate the morphologies of the intracranial skull base diseases and the spatial relationship with adjacent large vessels and bones. The printing time of each model is 12.52–15.32 h, and the cost ranges from 900 to 1500 RMB. The operative approach was planned in vitro, and patients recovered postoperatively well without severe complications or death. In a questionnaire about the application of 3D printing, experienced neurosurgeons achieved scores of 7.8–8.8 out of 10, while unexperienced neurosurgeons achieved scores of 9.2–9.8. Resection of intracranial skull base lesions is demonstrated to be well assisted by 3D printing technique, which has great potential in disclosing adjacent anatomical relationships and providing the required help to clinical doctors in preoperative planning.

The discovery of the rapid antidepressant effects of ketamine has arguably been the most important advance in depression treatment. Recently, it was reported that repeated long-term ketamine administration is effective in preventing relapse of depression, which may broaden the clinical use of ketamine. However, long-term treatment with ketamine produces cognitive impairments, and the underlying molecular mechanisms for these impairments are largely unknown. Here, we found that chronic in vivo exposure to ketamine for 28 days led to decreased expression of the glutamate receptor subunits GluA1, GluA2, GluN2A, and GluN2B; decreased expression of the synaptic proteins Syn and PSD-95; decreased dendrite spine density; impairments in long-term potentiation (LTP) and synaptic transmission in the hippocampal CA1 area; and deterioration of learning and memory in mice. Furthermore, the reduced glutamate receptor subunit and synaptic protein expression and the LTP deficits were still observed on day 28 after the last injection of ketamine. We found that the expression and phosphorylation of CaMKIIβ, ERK1/2, CREB, and NF-κB were inhibited by ketamine. The reductions in glutamate receptor subunit expression and dendritic spine density and the deficits in LTP, synaptic transmission, and cognition were alleviated by overexpression of CaMKIIβ. Our study indicates that inhibition of CaMKIIβ-ERK1/2-CREB/NF-κB signaling may mediate chronic ketamine use-associated cognitive impairments by restraining synaptic signaling. Hypofunction of the glutamatergic system might be the underlying mechanism accounting for chronic ketamine use-associated cognitive impairments. Our findings may suggest possible strategies to alleviate ketamine use-associated cognitive deficits and broaden the clinical use of ketamine in depression treatment.

Alcohol dependence (AD) is a condition of alcohol use disorder in which the drinkers frequently develop emotional symptoms associated with a continuous alcohol intake. AD characterized by metabolic disturbances can be quantitatively analyzed by metabolomics to identify the alterations in metabolic pathways. This study aimed to: i) compare the plasma metabolic profiling between healthy and AD-diagnosed individuals to reveal the altered metabolic profiles in AD, and ii) identify potential biological correlates of alcohol-dependent inpatients based on metabolomics and interpretable machine learning. Plasma samples were obtained from healthy (n = 42) and AD-diagnosed individuals (n = 43). The plasma metabolic differences between them were investigated using liquid chromatography-tandem mass spectrometry (AB SCIEX® QTRAP 4500 system) in different electrospray ionization modes with scheduled multiple reaction monitoring scans. In total, 59 and 52 compounds were semi-quantitatively measured in positive and negative ionization modes, respectively. In addition, 39 metabolites were identified as important variables to contribute to the classifications using an orthogonal partial least squares-discriminant analysis (OPLS-DA) (VIP > 1) and also significantly different between healthy and AD-diagnosed individuals using univariate analysis (p-value < 0.05 and false discovery rate < 0.05). Among the identified metabolites, indole-3-carboxylic acid, quinolinic acid, hydroxy-tryptophan, and serotonin were involved in the tryptophan metabolism along the indole, kynurenine, and serotonin pathways. Metabolic pathway analysis revealed significant changes or imbalances in alanine, aspartate, glutamate metabolism, which was possibly the main altered pathway related to AD. Tryptophan metabolism interactively influenced other metabolic pathways, such as nicotinate and nicotinamide metabolism. Furthermore, among the OPLS-DA-identified metabolites, normetanephrine and ascorbic acid were demonstrated as suitable biological correlates of AD inpatients from our model using an interpretable, supervised decision tree classifier algorithm. These findings indicate that the discriminatory metabolic profiles between healthy and AD-diagnosed individuals may benefit researchers in illustrating the underlying molecular mechanisms of AD. This study also highlights the approach of combining metabolomics and interpretable machine learning as a valuable tool to uncover potential biological correlates. Future studies should focus on the global analysis of the possible roles of these differential metabolites and disordered metabolic pathways in the pathophysiology of AD.

Objective Chronic methamphetamine use causes aberrant changes in cytokines. Our aim was to analyze the serum levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-18 in chronic methamphetamine users. Associations between cytokines levels with the demographic properties, methamphetamine use properties, and psychiatric symptoms in chronic methamphetamine users were also evaluated. Methods Seventy-eight chronic methamphetamine users who did not continue methamphetamine exposure since hospitalization and 64 healthy controls were enrolled. Serum levels of TNF-α, IL-6, and IL-18 were detected using an enzyme-linked immunosorbent assay. Psychopathological symptoms of chronic methamphetamine users were evaluated by the Positive and Negative Syndrome Scale, Beck Depression Inventory (BDI), and Beck Anxiety Inventory. Results Serum levels of TNF-α, IL-6, and IL-18 were significantly increased in methamphetamine users who did not continue methamphetamine exposure since hospital admission (average days since last methamphetamine use = 39.06 ± 7.48) when compared to those in controls. Serum IL-6 levels showed significant positive associations with BDI score and current frequency of methamphetamine use in chronic methamphetamine users. Conclusions Our results suggest that increased TNF-α, IL-6, and IL-18 levels may have an important role in chronic methamphetamine use-associated psychopathological symptoms.

Background: Previous studies have examined the effects of long-term ketamine use on gray matter volume. But it is unclear whether chronic ketamine use alters cortical thickness and whether cortical thickness changes in chronic ketamine users are associated with cognitive deficits observed in chronic ketamine users.Methods: Here, 28 chronic ketamine users and 30 healthy controls (HCs) were recruited. Cortical morphometry based on Computational Anatomy Toolbox (CAT12) was used to measure cortical thickness. Cognitive performance was measured by MATRICS Consensus Cognitive Battery (MCCB). Two-sample t-test was used to assess differences in cortical thickness and cognitive performance between the two groups. Partial correlation analysis was used for assessing correlations between cortical thickness changes and clinical characteristics, cognitive performance in chronic ketamine users.Results: Chronic ketamine users exhibited significantly reduced cortical thickness in frontal, parietal, temporal, and occipital lobes compared to HC [false discovery rate (FDR) corrected at p < 0.05]. In chronic ketamine users, the average quantity (g) of ketamine use/day was negatively correlated with cortical thickness in the left superior frontal gyrus (SFG), right caudal middle frontal gyrus (MFG), and right paracentral lobule. The frequency of ketamine use (days per week) was negatively correlated with cortical thickness in the left isthmus cingulate cortex. Duration of ketamine use (month) was negatively correlated with cortical thickness in the left precentral gyrus. The chronic ketamine users showed significantly poorer cognitive performance on the working memory (P = 0.009), visual learning (P = 0.009), speed of processing (P < 0.000), and Matrics composite (P = 0.01). There was no correlation between scores of domains of MCCB and reduced cortical thickness.Conclusion: The present study observed reduced cortical thickness in multiple brain areas, especially in the prefrontal cortex (PFC) in chronic ketamine users. Dose, frequency, and duration of ketamine use was negatively correlated with cortical thickness of some brain areas. Our results suggest that chronic ketamine use may lead to a decrease of cortical thickness. But the present study did not observe any correlation between reduced cortical thickness and decreased cognitive performance in chronic ketamine users.

Background Aerosolized Azacitidine has been shown to inhibit orthotopic lung cancer growth and induce re-expression of methylated tumor suppressor genes in murine models. We hypothesized that inhaled Azacitidine is safe and effective in reversing epigenetic changes in the bronchial epithelium secondary to chronic smoking. Patients and Methods We report the first in human study of inhaled Azacitidine. Azacitidine in aqueous solution was used to generate an aerosol suspension of 0.25–5 μm particle size. Main inclusion criteria: Stage IV or recurrent NSCLC with predominantly lung involvement, ≥1 prior systemic therapy, ECOG PS 0–1, and adequate pulmonary function. Patients received inhaled Azacitidine daily on days 1–5 and 15–19 of 28-day cycles, at 3 escalating doses (15, 30 and 45 mg/m2 daily). The primary objective was to determine the feasibility and tolerability of this new therapeutic modality. The key secondary objectives included pharmacokinetics, methylation profiles and efficacy. Results From 3/2015 to 2/2018, eight patients received a median number of 2 (IQR = 1) cycles of inhaled Azacitidine. No clinically significant adverse events were observed, except one patient treated at the highest dose developed an asymptomatic grade 2 decreased DLCO which resolved spontaneously. One patient receiving 12 cycles of therapy had an objective and durable partial response, and two patients had stable disease. Plasma Azacitidine was only briefly detectable in patients treated at the higher doses. Moreover, in 2 of 3 participants who agreed and underwent pre- and post-treatment bronchoscopy, the global DNA methylation in the bronchial epithelium decreased by 24 % and 79 % post-therapy, respectively. The interval between last inhaled treatment and bronchoscopy was 3 days. Conclusions Inhaled Azacitidine resulted in negligible plasma levels compared to the previously reported subcutaneous administration and was well-tolerated. The results justify the continued development of inhaled Azacitidine at non-cytotoxic doses for patients with lung-confined malignant and/or premalignant lesions.

Background Anxiety, an important factor that affects the therapeutic effect and preservation rate of methadone maintenance treatment, has a high prevalence among MMT patients. This study aims to investigate the effects of treatment status and life quality on anxiety in MMT patients. Methods One hundred and Seventy-seven methadone maintenance treatment users in Guangzhou, China were evaluated. The socio-demographic, duration and MMT-related characteristics were documented. Anxiety level and quality of life were evaluated by Beck Anxiety inventory (BAI) and the Quality of Life-Drug Addiction (QOL-DA) respectively. The correlation between different factors and BAI score was also analyzed. Results The BAI total score and the QOL-DA score were 7.1±8.2, 163.5±21.4 respectively. 30.5% of the subjects showed mild to severe anxiety. Treatment interruption and QOL-DA score had strong correlations with the score of BAI, with correlation coefficients of 0.17 and − 0.08 respectively. Conclusions Anxiety symptoms were commonly presented in MMT patients. Treatment interruption and quality of life are two major factors affecting anxiety of MMT patients.

Objective: We previously found that chronic ketamine usages were associated with various psychotic and cognitive symptoms mimicking schizophrenia. The blockade of the NMDA receptor and subsequent nitric oxide synthase 1 (NOS1) dysfunction were found to be closely correlated with schizophrenia including NOS1 gene polymorphisms. We examined the allelic variants of the gene coding neuronal nitric oxide synthase 1 (NOS1) in chronic ketamine users in the Chinese population and analyzed the association between NOS1 gene polymorphism and psychopathological symptoms in chronic ketamine users. The association between the NOS1 polymorphism and ketamine use characteristics was also examined.Methods: One hundred ninety seven male chronic ketamine users and 82 controls were recruited. Four common SNPs of the NOS1 gene, rs6490121, rs41279104, rs3782206, and rs3782219, were examined by real-time PCR with the TaqMan® assay system. Psychopathological symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI), and the Beck Anxiety Inventory (BAI).Results: The genotype distribution of rs6490121 and rs41279104 in chronic ketamine users was significantly different from that in the control (p = 0.0001 and p = 0.002). The G allele frequency of rs6490121 in ketamine users was higher than that in the control (p = 2.23 * 10−6, OR = 3.07, 95% CI = 1.93–4.90). The T allele frequency of rs41279104 in chronic ketamine users was higher than that in the control (p = 0.01, OR = 1.76, 95% CI = 1.14–2.72). The BAI score was significantly different among the three genotypic groups of rs6490121 (F = 6.21, p = 0.002) in ketamine users; subjects of genotype AG and GG had a lower score than subjects of genotype AA. The score of the negative symptom subscale of PANSS was significantly different among the three genotypic groups of rs41279104 (F = 5.39, p = 0.005); in ketamine users, subjects of genotype CT and TT had a higher score than subjects of genotype CC. There was no difference in drug use characteristics in different genotypes of the four NOS1 gene polymorphisms tested in ketamine users (p > 0.05).

Background: Anxiety, a major factor that affects the therapeutic effect and dropout rate of methadone maintenance treatment, has a high prevalence among MMT users. This study aims to investigate the prevalence of anxiety in MMT users and explore the main influencing factors of anxiety of methadone maintenance treatment users.Methods: 177 methadone maintenance treatment users in Guangzhou, China were evaluated. The socio-demographic, duration and MMT-related characteristics were documented. Anxiety, quality of life and sleep quality were evaluated by Beck Anxiety inventory (BAI), the Quality of Life-Drug Addiction (QOL-DA) and Pittsburgh Sleep Quality Index (PSQI) respectively. The correlation between different factors and BAI score was also analyzed.Results: The BAI total score, QOL-DA score, PSQI score were 7.1±8.2, 163.5±21.4, 6.0±4.0 respectively. 30.5% of the subjects showed mild to severe anxiety. Treatment interruption, QOL-DA score and PSQI score had strong correlations with the score of BAI, with correlation coefficients of 0.17, -0.08 and 0.50 respectively.Conclusions: Anxiety symptoms were commonly presented in MMT users. Treatment interruption, quality of life and sleep quality are the major factors affecting anxiety of MMT users.

Anxiety, a common and devastating mental disorder, has raised widespread interests. The impacts of air pollution on physical health are well known, whereas few studies have explored the association of atmospheric pollution, especially short-term air pollution exposure, with the risk of anxiety disorders. In addition, there are increasing concerns in emerging evidence supporting a possible etiological link. Therefore, our aim was to evaluate the relationship between short-term exposure to atmospheric pollutants and anxiety outpatient visits in Xi'an, a city of northwestern China and a metropolis with relatively heavy air pollution. We collected the data of both daily outpatient visits and daily air pollution (SO2, NO2, and PM10) between January 1, 2010 and January 31, 2016 (2222 days). To clarify the association between short-term ambient atmospheric pollution exposure and anxiety outpatient visits, an over-dispersed Poisson generalized additive model was applied by adjusting the day of the week and weather conditions (including temperature, humidity, sunlight hours, and rainfalls). Positive association between gaseous air pollutants (SO2 and NO2) and anxiety daily outpatient visits was observed. Moreover, the largest estimated values of both SO2 and NO2 were evidence at lag 03 (4-day moving average lag), with 10 μg/m3 increase corresponded to the increase of outpatient anxiety visits at 4.11% (95% CI: 2.15%, 6.06%) for SO2 and 3.97% (95% CI: 1.90%, 6.06%) for NO2. However, there was no differences in susceptibility to air pollutants between different genders as well as different ages. Taken together, short-term exposure to ambient air pollutants, especially gaseous air pollutants (NO2 and SO2), can be related to higher risk of anxiety outpatient visits.

In early 2020, the COVID-19 outbreak complicated the diagnosis, treatment and rehabilitation of patients with substance use disorders and increased the risks of substance abuse and addictive behaviours, such as online gaming disorders, in the general public. Substance use disorder is a chronic recurrent brain disease characterised by strong cravings, high recurrence rates, and a high proportion of comorbidity of mental and physical disorders.1 Therefore, regular long-term therapeutic interventions are critical to preventing drug relapses while maintaining withdrawal. COVID-19 severely affects normal medical diagnoses, treatments and managements of patients with substance use disorder coupled with addiction-related behaviour. It also adversely impacts the mental state of the general public in several ways and leads to broader symptoms, including anxiety, tension and insomnia, that may increase the risk of alcohol abuse, sedative and hypnotic drug abuse, and other addictive behaviours. The State Council’s Comprehensive Team for Joint Prevention and Control of COVID-19 released a series of documents to address the importance of focusing on the prevention and control of both imported cases and internal transmission in particularly vulnerable places, such as supervision sites, pension facilities, welfare homes and mental health institutions.2 3 It is also of utmost importance to ensure the continuous, regular and effective treatment of existing patients with addiction problems, reduce the risk of drug relapse and prevent new cases of addiction during the pandemic. To this end, the Chinese Association of Drug Abuse Prevention and Treatment, the Academic Group of Drug Dependence of the Chinese Society of Psychiatry, the Academic Group of Addiction of the Chinese Society of Psychosomatic Medicine, and the Specialty Committee of Addiction Medicine of the Chinese Psychiatrist Association jointly published an expert consensus to inform the public with proper guidance to prevent addiction and provide professional diagnoses, treatment and management of these addictions. …

Introduction Electroconvulsive therapy (ECT) is an effective treatment for patients with mood disorders and is most often used for treatment‐resistant cases. This study aimed to examine the effectiveness of ECT in a real‐world treatment sample in a Chinese psychiatric hospital which included both treatment‐resistant and nontreatment‐resistant patients. Methods An observational study of symptom outcomes from admission to the time of discharge was conducted with 37 inpatients diagnosed with unipolar or bipolar depression treated with ECT. Symptom severity was assessed with the 17‐item Hamilton Rating Scales for Depression (HRSD‐17) and treatment‐resistance with the Maudsley Staging Model (MSM). Stratifying at the MSM median admission characteristics and symptom change was compared between patients who were treatment‐resistant (n = 18) and who were not (n = 19). The outcome difference between groups was compared using analyses of covariance adjusted for baseline characteristics including symptom severity, followed by linear regression to identify factors associated symptom improvement in the entire sample. Results The sample (n = 37) showed moderate treatment‐resistance (MSM = 7.30 ± 1.13) at admission and both groups received 8.3 ± 2 ECT sessions. The treatment‐resistant group had a smaller proportion of bipolar patients and more severe symptoms, but showed no significant difference from the nontreatment‐resistant group in HDRS‐17 scores at the time of discharge (adjusted means = 6.23 ± 1.00 vs. 5.94 ± 0.97, Partial η 2 = 0.001, p = .845). Baseline symptom severity was the strongest correlate of reduction in HDRS‐17 scores (β = 0.891, p, The reduction of depressive symptoms with ECT does not appear to be affected by overall “treatment‐resistance” but is greatest for those with the most severe symptoms at baseline.

OBJECTIVE The serum kynurenine pathway metabolites kynurenic acid (KYNA), kynurenine (KYN), and tryptophan (TRP) were examined in chronic ketamine users and in schizophrenic patients. The correlations of the metabolites with sociodemographic data, clinical characteristics, and drug use status were analyzed. METHODS Seventy-nine healthy controls, 78 ketamine users, and 80 schizophrenic patients were recruited. Serum TRP, KYN, and KYNA levels were measured by high-performance liquid chromatography following tandem mass spectrometry (MS/MS). Psychotic symptoms were evaluated using the positive and negative syndrome scale (PANSS), the Beck Depression Inventory (BDI), and the Beck Anxiety Inventory (BAI). RESULTS Serum levels of TRP, KYNA, and KYN (in ketamine users only) were lower in ketamine users and schizophrenic patients than in controls (p

Objective Recent studies have expressed concern about the infrequent and declining use of electroconvulsive therapy (ECT) in the United States. However, it is not known whether the US experience reflects changing global practice or one that varies between countries. This observational study examined use of ECT in the largest psychiatric hospital in China's third largest city over a 4-year period, 2014 to 2017. Methods Unduplicated electronic medical records concerning all inpatients with psychiatric diagnoses were examined. Electroconvulsive therapy utilization rates, correlates of ECT use, and its association with readmission within the 6 months following discharge were evaluated using bivariate and multivariate logistic regression analyses. Results Of 13,831 hospitalized patients, 2460 (17.8%) received ECT. Logistic regression analysis showed ECT utilization was independently associated with being female, younger age, being employed, nonlocal residence, involuntary admission, having no health insurance, longer length of stay, and the diagnoses of bipolar disorder and major depressive disorder. Use of ECT has increased since 2014 but was not significantly related to readmission 6 months after discharge. Conclusions Electroconvulsive therapy use appears to be substantially higher in China than in the United States and is associated with indicators of higher rather than lower functioning as reflected by independent associations with youth, employment, and fewer past hospitalizations, but also with behavioral noncompliance as reflected by involuntary admission, and has increased in recent years. Understanding United States-China discrepancies may further international understanding of the diverse roles of ECT in psychiatric practice.

Background Electroconvulsive therapy (ECT) is a rapid acting and effective treatment for both major depressive disorder (MDD) and bipolar disorder (BP). Both propofol and ketamine are commonly used anesthetic agents but recent clinical studies suggest that ketamine has rapid-acting antidepressant properties, itself, at sub-anesthetic doses. Methods A total of 77 inpatients (41 MDD and 36 BP) were randomly assigned to receive ECT with propofol (1 mg/kg) anesthesia or with ketamine (0.5 mg/kg) plus propofol (0.5 mg/kg). Depressive symptoms were assessed with the 24-item Hamilton Depression Rating Scale (HAMD-24) and Montgomery–Asberg Rating Scale (MADRS), before and after 1, 2, 4, and 6 ECT treatments, and 1–4 weeks following the last treatment. The MATRICS Consensus Cognitive Battery (MCCB) was evaluated at baseline,after the sixth ECT, and 1–4 weeks following the final ECT. Adverse effects were assessed at baseline and 4 weeks after the last treatment. Results There were no significant differences in depressive symptoms, MCCB performance, or adverse effects between the treatment groups at any time. The electrical dose required to generate seizures in the ketamine plus propofol group was lower than that of the propofol only group at every time point. The seizure energy index and seizure duration in the ketamine plus propofol group was higher and longer than those in the propofol only group. Limitations The diagnoses of MDD and BP were unevenly distributed across treatment groups. Conclusions Ketamine plus propofol anesthesia in the ECT treatment of MDD and BP was not superior on any measure to propofol alone.

Background 17α-hydroxylase deficiency is a rare autosomal recessive disorder caused by mutations in the cytochrome P450 family 17 subfamily A member 1 gene. The major clinical presentation includes hypertension, hypokalemia, male pseudohermaphroditism and female gonadal dysplasia. Hundreds of pathogenic variants have been reported in this disorder, and some common mutations were found to be race-specific. Case presentation In this study, we reported 5 Chinese girls with 17α-hydroxylase deficiency from Henan Province. The patients all came to the hospital for hypertension, and they also presented with sexual infantilism. The average age of the patients was 14 years old, ranging from 12 to 17 years old. They all had reduced blood cortisol, estradiol (E2), and testosterone (TESTO) and increased adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). They all had the appearance of females; however, three of the chromosome karyotypes were 46XX, and two were 46XY. Conclusions All of the patients carried a mutation on the 329 amino acid of CYP17A1 exon 6. By summarizing the currently known pathogenic mutations of 17α-hydroxylase deficiency, we demonstrated the prevalence of these gene mutations in Chinese Han and non-Chinese populations.

Menstrual disorders are common diseases among reproductive-aged women with increasing concerns. Until now, there have been limited studies about the association between menstrual disorders and air pollution. This study aimed to investigate the association between short-term (concurrent day and within 1 week prior) ambient air pollution exposure and menstrual disorder outpatient visits in Xi'an, a metropolis in northwestern China. Daily baseline outpatient data of menstrual disorders from January 1, 2010 to February 18, 2016 (2239 days) were obtained. An over-dispersed Poisson generalized additive model was applied to discover the relationship between short-term air pollution exposure and the number of menstrual disorder outpatient visits by adjusting the day of the week and weather conditions. A total of 51,893 outpatient visits for menstrual disorders were recorded. A 10 μg/m3 increase of PM10 and NO2 concentrations corresponded to 0.236% (95% Cl: 0.075%, 0.397%) and 2.173% (95% Cl: 0.990%, 3.357%) elevations in outpatient-visits for menstrual disorders at lag 7 and lag 01 (concurrent day and previous 1 day), respectively. The association was more significant in young females (18–29 years) and there was no obvious association observed between SO2 and menstrual disorder outpatient visits. This is the first evidence that short-term exposure to ambient air pollution can be associated with an increased risk of menstrual disorder attacks. The results of our study may help to establish more comprehensive understanding of the health effects of ambient air pollution on menstrual disorders and other reproductive diseases.

BACKGROUND AND OBJECTIVES We examined the allelic variants of N-methyl- d-aspartate receptor 2B (GRIN2B) and analyzed the associations between GRIN2B gene polymorphism with ketamine use conditions and psychopathological symptoms in chronic ketamine users. METHODS A total of 231 subjects were recruited. Four single nucleotide polymorphisms of GRIN2B, rs1805502, rs7301328, rs890, and rs1806201 were examined in 151 male chronic ketamine users and 80 controls. Psychopathological symptoms in chronic ketamine users were evaluated using the Positive and Negative Syndrome Scale, the Beck Depression Inventory, and the Beck Anxiety Inventory. RESULTS The genotype CC of rs1806201 had a lower frequency in ketamine users than that in control subjects (χ2 = 8.167, P = .004) and the T allele frequency of rs1806201 in ketamine users was higher than that in the control subjects (P = .009, odds ratio = 2.019 [1.196-3.410]). Ketamine users of genotype TT and CC of rs1806201 had an earlier onset of ketamine use than subjects of genotype TC (P = .038, P = .049, respectively). The dose of ketamine consumption per day of use was higher in genotype GG of rs7301328 than that in those with CG in ketamine users (P = .026). There were no significant differences of the severity of psychopathologic symptoms among different genotypes tested. CONCLUSION AND SCIENTIFIC SIGNIFICANCE GRIN2B gene polymorphism may play a role in ketamine abuse. (Am J Addict 2020;29:105-110).

Botanical triterpene celastrol is a candidate drug for the treatment of obesity, except for concerns over the safety in clinical application. The present study was designed to investigate the anti-obesity, anti-inflammatory and toxic activities of celastrol-loaded nanomicelles (nano-celastrol) in diet-induced obese mice. Celastrol was loaded into PEG-PCL nanoparticles, yielding nano-celastrol with optimal size, spherical morphology, good bioavailability, slower peak time and clearance in mice. Nano-celastrol (5 or 7.5 mg/kg/d of celastrol) was administered into diet-induced obese C57BL/6 N male mice for 3 weeks. As result, higher dose nano-celastrol reduced body weight and body fat mass in an equally effective manner as regular celastrol, although lower dose nano-celastrol showed less activity. Similarly, nano-celastrol improved glucose tolerance in mice equally well as regular celastrol, whereas higher dose nano-celastrol improved the response to insulin. As for macrophage M1/M2 polarization in liver, nano-celastrol reduced the expression of macrophage M1 biomarkers (e.g., IL-6, IL-1β, TNF-α, iNOS) in a dose-dependent manner and marginally increased the expression of macrophage M2 biomarkers (e.g., Arg-1, IL-10). Moreover, celastrol could cause anus irritation and disturb intestinal and colonic integrity, whereas nano-celastrol did not cause any injury to mice. Collectively, nano-celastrol represents a translatable therapeutic opportunity for treating diet-induced obesity in humans.

// Wei Wang 1, * , Gang Ji 2, * , Xin Xiao 3, * , Xu Chen 1 , Wei-Wei Qin 1 , Fan Yang 1 , Yu-Fang Li 1 , Lin-Ni Fan 4 , Wen-Jin Xi 1 , Yi Huo 1 , Wei-Hong Wen 1 , An-Gang Yang 1 , Tao Wang 1, 5 1 State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi’an, Shaanxi, PR China 2 Department of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, PR China 3 Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, PR China 4 Department of Pathology, Fourth Military Medical University, Xi’an, Shaanxi, PR China 5 Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an, Shaanxi, PR China * These authors have contributed equally to this work Correspondence to: An-Gang Yang, email: agyang@fmmu.edu.cn Tao Wang, email: wangt@fmmu.edu.cn Keywords: colorectal cancer, metastasis, miR-145, LASP1, histone methylation Received: May 27, 2016 Accepted: August 25, 2016 Published: September 09, 2016 ABSTRACT MiR-145 is a tumor-suppressive microRNA that participates in the malignant progression of colorectal cancer (CRC). Although miR-145 has been reported to inhibit proliferation and to induce apoptosis of CRC cells, the reports about its role in invasion and metastasis are controversial. The regulation of miR-145 its own expression also requires further elucidation. In this study, we firstly found that miR-145 is markedly downregulated in the metastatic tumors of CRC patients. Then through gain- and loss-of function studies, we demonstrated that miR-145 suppresses the invasion and metastasis of CRC cells. We also provided experimental evidences which include direct binding assays and verifications on tissue specimens to confirm that LIM and SH3 protein 1 (LASP1) is a direct target of miR-145. Furthermore, we identified the core promoter regions of miR-145 and observed the cooperation between histone methylation and transcription factors through binding to these core promoter regions to regulate the expression of miR-145 in CRC cells. Our study provides an insight into the regulatory network in CRC cells, thus offering new targets for treating CRC patients.

Objective Although concern about chronic ketamine abuse has grown, the characteristic symptomatology of chronic ketamine users has yet to be examined. This study aims to measure the psychotic, depressive and anxiety symptoms in chronic ketamine users. Methods A group of chronic ketamine users in Guangzhou, China were evaluated. The socio-demographic and drug use characteristics of subjects were documented. Symptoms of psychosis, depression, anxiety were evaluated by the Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). The severity of the symptoms was identified by standard severity cutoffs. Results The PANSS total score, positive symptom, negative symptom, general psychopathology subscale score were 45.3±8.4, 8.0±1.7, 13.2± 3.9 and 24.2± 4.9 respectively. BDI and BAI score was 13.1±6.5 and 15.7±9.6 respectively. 77.5% and 46.0% of the subjects showed moderate to severe depressive symptoms and anxiety symptoms respectively. The BDI score was positively correlated with ketamine use frequency. The BAI score was positively correlated with ketamine use frequency. Conclusions Depressive symptoms were commonly presented in chronic ketamine users. The higher ketamine use frequency and dosage were associated with more severe depressive symptoms.

Exposing to NMDAR receptor antagonists, such as ketamine, produces schizophrenia-like symptoms in humans and deteriorates symptoms in schizophrenia patients. Meanwhile, schizophrenia is associated with alterations of cytokines in the immune system. This study aims to examine the serum TNF-α, IL-6 and IL-18 levels in chronic human ketamine users as compared to healthy subjects. The correlations between the serum cytokines levels with the demographic, ketamine use characteristics and psychiatric symptoms were also assessed.155 subjects who fulfilled the criteria of ketamine dependence and 80 healthy control subjects were recruited. Serum TNF-α, IL-6 and IL-18 levels were measured using an enzyme-linked immunosorbent assay (ELISA). The psychiatric symptoms of the ketamine abusers were assessed using the Positive and Negative Syndrome Scale (PANSS).Serum IL-6 and IL-18 levels were significantly higher, while serum TNF-α level was significantly lower among ketamine users than among healthy controls (p0.05). Serum TNF-α levels showed a significant negative association with PANSS total score (r=-0.210, p0.01) and negative subscore (r=-0.300, p0.01). No significant association was found between PANSS score and serum levels of IL-6 and IL-18.Serum levels of TNF-α, IL-6 and IL-18 were altered in chronic ketamine abusers which may play a role in schizophrenia-like symptoms in chronic ketamine abusers.

Carbon monoxide (CO) is a well-known “toxic gas”. It represents a toxic inhalation hazard at high concentration and is commonly found in polluted air. However, a series of recent studies have suggested that low concentration of CO can also produce protective functions. This study was performed to investigate the association between ambient CO exposure and vaginitis outpatient visits. Daily baseline outpatient data of vaginitis from January 1, 2013 to December 31, 2015 were obtained from Xi'an, a heavily-polluted metropolis in China. The over-dispersed Poisson generalized additive model was applied to discover the relations between short-term ambient CO exposure and the number of vaginitis outpatient visits by adjusting day of the week and weather conditions. A total of 16,825 outpatient hospital visits for vaginitis were recorded. The mean daily concentration of carbon monoxide (CO) was well below Chinese and WHO guidelines. During the study period, increased levels of ambient CO was associated with reduced outpatient-visits through concurrent to lag 5 days, and the most significant association was evidenced at lag 05. A 0.1 mg/m3 increase in daily average CO at lag 05 corresponded to −1.25% (95%CI: −1.85%, −0.65%) change in outpatient-visits for vaginitis. Moreover, the association was more significant in those women aged 20–29 years. After adjustment for PM10, PM2.5, SO2, and NO2, and O3, the negative associations of CO with vaginitis kept significant, suggesting relative stability of effect estimates. In summary, this is the first evidence that increased ambient CO exposure can be related to reduced daily outpatient visits for vaginitis. The results of our study may not only help to establish more comprehensive understanding of the health effects of ambient air on vaginitis and other gynecological diseases, but also provide a clue to new potential interventions.

Background To study the correlation between blood pressure variability (BPV) and plasma renin activity (PRA), angiotensin II (AngII), aldosterone levels in patients with essential hypertension. Methods A total of 300 patients with mild to moderate essential hypertension were analyzed retrospectively. The subjects were divided into 3 age groups: 100 patients aged 18–44 years (young group), 110 patients aged 45–64 years (middle-aged group), and 90 patients aged over 65 years (elderly group). PRA, AngII, and aldosterone levels were assessed. Blood pressure (BP) was measured by 24-hour ambulatory BP monitoring. The relationships between BP variability and the PRA, AngII, aldosterone levels were compared among the 3 groups. Results Supine and upright PRA and aldosterone levels were significantly higher in the young group than those in the middle-aged and elderly groups. The coefficient of variation (CV) of 24-hour systolic (24hSBPCV), diastolic BP (24hDBPCV), CV of daytime systolic (dSBPCV), diastolic (dDBPCV), and nighttime systolic BP (nSBPCV) in the elderly group was higher than those in the young group and the middle-aged group (all P < 0.05). Spearman correlation analysis showed that in the young and middle-aged groups, BPV was significantly correlated with the levels of PRA, AngII, and aldosterone (all P < 0.05). In the elderly group however, only 24hDBPCV, nDBPCV, and nSBPCV were correlated with AngII and aldosterone levels (all P < 0.05). Conclusions BPV is correlated with plasma renin–angiotensin–aldosterone levels in young and middle-aged patients with mild to moderate essential hypertension.

3597 Background: Approximately 20% to 50% of patients with advanced lung cancer develop brain metastases, which are associated with debilitating neurologic impairment and a dismal prognosis. There have been very limited studies investigating the genomics of brain metastases in lung cancer. Methods: We comprehensively investigated the frequency of PI3K/AKT/RICTOR/mTOR pathway aberrations in primary and metastatic sites using an extensive database of 11845 cases of lung adenocarcinoma by NGS (FoundationOne). The potential roles of RICTOR amplification in the development of brain metastases were studied both in vitro and in vivo in orthotopic mouse models. Results: Compared to the primary tumor, PI3K/AKT/mTOR gene alterations were more frequent in metastatic sites, with particular enrichment noted in brain metastases. RICTOR amplification alone accounted for the observed higher frequency both in brain metastases (brain vs. primary: 9.73% vs 3.50%, P = 2.6E-14; brain vs. other mets: 9.73% vs. 7.3%, P = 0.03) and other metastatic sites (other mets vs. primary: 7.3% vs.3.5%, P = 10E-15), whereas the frequency of PTEN, AKT1, PK3CA or mTOR genetic alterations was not different in the primary tumor, brain and other metastatic sites. In vitro, inducible RICTOR knockdown in H23 lung cancer cells (parental line with RICTOR amplification) was associated with reduced cell migration and invasion, whereas upregulation of RICTOR in HCC827 lung cancer cells (parental line with normal RICTOR copy numbers) was associated with an increase of both processes. These results were confirmed with pharmacological inhibition using mTOR1/2 inhibitors with known CNS penetration. In vivo, both inducible ablation of RICTOR and the mTOR1/2 inhibitor TAK228 (Sapanisertinib) significantly inhibited lung cancer H23-R4-Luc tumor growth in the brain, including a number of near complete responses. Mechanistic studies suggest that RICTOR may regulate the brain metastasis process through AKT and CXCL12 chemokine-CXCR4 axis. Conclusions: RICTOR amplification is the first identified actionable target that is markedly enriched in brain metastases. Our study provides a strong rationale for the development of RICTOR-targeted therapeutic strategies for the treatment and/or prevention of these major causes of lung cancer morbidity and mortality.

The aim of the present study was to prospectively evaluate the recurrence and survival outcome of primary central nervous system lymphoma (PCNSL) with intraocular involvement. For this purpose, a prospective cohort of 103 pathologically confirmed patients with PCNSL was enrolled in this study. Ophthalmologic examinations were performed both at diagnosis and during follow‑up. The patients with PCNSL with suspected intraocular involvement underwent vitrectomy for confirmation. Patients who presented with intraocular involvement either at diagnosis or during disease progression were allocated to the intraocular lymphoma (IOL) group. All patients with PCNSL received systemic methotrexate (MTX)‑based chemotherapy with or without radiotherapy. MTX intravitreal injection combined with systemic MTX‑based chemotherapy was recommended once ocular lesions were confirmed. Recurrent intraocular and central nervous system (CNS) events, progression‑free survival (PFS) and overall survival (OS) outcomes were analyzed. The findings of this study revealed that 21 patients with PCNSL exhibited intraocular involvement. One patient with IOL presented with isolated ocular lymphoma at the initial diagnosis, and the others presented with ocular involvement along with CNS invasion during the course of the disease. A total of 14 patients received systemic MTX‑based chemotherapy prior to the diagnosis of IOL. The recurrence rates in patients with or without intraocular involvement were 71.4 and 46.3%, respectively (P=0.04) and the relapse sites in the patients with IOL included the brain (3 patients), eyes (6 patients), and both brain and eyes (6 cases). The median PFS was 13 months in the IOL group and 19 months in the patients without intraocular involvement (non‑IOL) (P=0.019). The median OS was 51 months vs. 56 months, respectively (P=0.312). There was no significant difference in the 2‑year PFS and OS rates between the 2 groups (23.8% vs. 23.2%, P=0.951; and 61.9% vs. 41.4%, P=0.093, respectively). On the whole, the findings of this study suggest that patients with IOL have a high risk of relapse and a poor PFS compared to patients without IOL, but a similar OS.

Objective Schizophrenia is correlated with aberrant cytokine concentrations. The goal of our study was to detect the serum concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-18, and IL-6 concentrations in patients with chronic schizophrenia in the acute relapse state at admission and at discharge and to analyze the correlations between the three cytokine concentrations with psychosis symptoms. Methods Enzyme-linked immunosorbent assay (ELISA) was used to analyze serum concentrations of TNF-α, IL-18, and IL-6 in 68 patients with chronic schizophrenia at admission and at discharge and in 80 controls. The Positive and Negative Syndrome Scale (PANSS) was used to analyze psychosis symptoms of the patients. Results Serum concentrations of TNF-α, IL-18, and IL-6 in patients at admission were significantly elevated compared to those in controls. After treatment, IL-6 concentrations in patients at discharge were significantly reduced compared to those in patients at admission, and IL-6 concentrations showed no significant difference between patients at discharge and controls. In contrast, TNF-α and IL-18 concentrations showed no significant difference between patients at discharge and patients at admission, and TNF-α and IL-18 concentrations in patients at discharge were still significantly elevated compared to those in controls. IL-6 concentrations in patients at admission showed a positive correlation with negative scores, and IL-6 concentrations in patients at discharge showed positive correlations with positive, negative, and total scores. Reduction in IL-6 concentrations showed positive correlations with reduction in positive, negative, and total scores in patients at discharge. Conclusion Serum concentrations of TNF-α, IL-18, and IL-6 were significantly elevated in patients with chronic schizophrenia in the acute relapse state. After treatment, IL-6 concentrations in patients at discharge were significantly reduced compared to these in patients at admission.

Previous studies have shown that peripheral ionotropic glutamate receptors are involved in the increase in sensitivity of a cutaneous branch of spinal dorsal ramus (CBDR) through antidromic electrical stimulation (ADES) of another CBDR in the adjacent segment. CBDR in the thoracic segments run parallel to each other and no synaptic contact at the periphery is reported. The present study investigated whether the increased sensitivity of peripheral sensory nerves via ADES of a CBDR induced Fos expression changes in the adjacent segments of the spinal cord. Fos expression increased in the T8 - T12 segments of the spinal cord evoked by ADES of the T10 CBDR in rats. The increased Fos expression in the T11 and T12, but not T8 - T10 spinal cord segments, was significantly blocked by local application of either N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine maleate (MK-801) or non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the receptive field of T11 CBDR. The results suggest that endogenous glutamate released by ADES of sensory nerve may bind to peripheral ionotropic glutamate receptors and activate adjacent sensory nerve endings to increase the sensitivity of the spinal cord. These data reveal the potential mechanisms of neuron activation in the spinal cord evoked by peripheral sensitization.

To evaluate the serum level of vascular endothelial growth factor (VEGF) in a group of chronic ketamine abusers in comparison to healthy controls.Eighty-one ketamine abusers who were hospitalized for the treatment of ketamine dependence and 39 healthy controls were recruited. Serum VEGF level was measured by enzyme linked immunosorbent assay (ELISA). Psychopathological symptoms were assessed using Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI).Serum level of VEGF was significantly lower in chronic ketamine abusers compared to healthy controls (64.6±42.1 vs. 92.4±59.4pg/ml, F=7.243, p=0.008).Serum level of VEGF decreased in chronic ketamine abusers compared to healthy controls.

Primary myelofibrosis (PMF) is one of the BCR/ABL-negative myeloproliferative neoplasms (MPNs), characterized by the diffuse fibrous hyperproliferation, bone marrow osteosclerosis, extramedullary hematopoiesis, and marked splenomegaly. The patients with PMF have an insidious onset, a long duration of clinical course, and the deteriorated quality of life. It has been reported that the CALR gene 9 exon mutations were detected in 25-30% PMF patients, particularly as high as 80% in the JAK2/MPL-negative ones. As the second most common mutation in BCR/ABL-negative MPNs, CALR mutation has been included in the latest World Health Organization (WHO) classification criteria as one of the main diagnostic criteria for both essential thrombocythemia (ET) and PMF. Moreover, the CALR mutations indicated a favorable prognosis, which the mechanism is still under investigation. It was demonstrated that a characterized high expression of EZH2 and SUZ12 in CALR-mutated patients. Taking EZH2 as the research entry point, we initially discussed the mechanism that the CALR-positive patients with PMF exhibited a better prognosis in the current study.

The aim of this study was to examine the cognitive function in chronic ketamine users. Factors correlated to cognition impairments were analyzed. Sixty-three chronic ketamine users and 65 healthy subjects were recruited. Cognitive function was assessed by using immediate/delayed visual reproduction (IVR/DVR) tasks, immediate/delayed logical memory (ILM/DLM) tasks, Stroop test, Wisconsin card sorting test (WCST), and continuous performance test (CPT). Psychopathological symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Ketamine users performed worse than controls on the IVR, ILM, DLM, Stroop and auditory CPT tests. IVR and DVR, color-naming and color-interference-reading scores were positively correlated with education level. In ketamine users ILM scores were negatively correlated with the negative subscale of PANSS. DLM score was positively correlated with average dose of ketamine use. Word-reading score was positively correlated with education level, and negatively correlated with duration of ketamine use. False hits in auditory CPT was positively correlated with duration of ketamine use. Number of trials to complete the first category and perseverative errors on WCST were positively correlated with the duration between the test and last ketamine use. Chronic ketamine users had cognitive impairments across multiple domains.

Neuropathic pain is a complex, chronic pain state that often accompanies tissue damage, inflammation or injury of the nervous system. However the underlying molecular mechanisms still remain unclear. Here, we showed that CXCL12 and CXCR4 were upregulated in the dorsal root ganglion (DRG) after chronic compression of DRG (CCD), and some CXCR4 immunopositive neurons were also immunopositive for the nociceptive neuronal markers IB4, TRPV1, CGRP, and substance P. The incidence and amplitude of CXCL12-induced Ca2+ response in primary sensory neurons from CCD mice was significantly increased compared to those from control animals. CXCL12 depolarized the resting membrane potential, decreased the rheobase, and increased the number of action potentials evoked by a depolarizing current at 2X rheobase in neurons from CCD mice. The mechanical and thermal hypernociception after CCD was attenuated by administration of a CXCR4 antagonist AMD3100. These findings suggest that CXCL12/CXCR4 signaling contributes to hypernociception after CCD, and targeting CXCL12/CXCR4 signaling pathway may alleviate neuropathic pain.

Background: Molecularly-targeted therapy has significantly improved the therapeutic efficiency and clinical outcome in a subgroup of NSCLC patients. However, drug resistance inevitably emerges, such as resistance to EGFR TKIs in EGFR-mutated NSCLC. RICTOR is a key component of the mTORC2 complex and plays important roles in cell survival, proliferation, migration and invasion. RICTOR has also been suggested to play a part in the regulation of drug resistance to HER2-targeted therapy in HER2-amplified breast cancer, a niche close to EGFR-targeted therapy. In our current study, we hypothesize that RICTOR modulates the activity of EGFR TKIs in EGFR-mutated NSCLC. Co-targeting RICTOR and EGFR signaling pathways could be a new therapeutic strategy for patients with EGFR-mutated lung cancer. Results: Genetically modified EGFR-mutated NSCLC cell lines with different RICTOR expression levels have been developed. RICTOR knockdown significantly increases the sensitivity to all three generations of TKI inhibitors (erlotinib, afatinib and osimertinib), whereas overexpression of RICTOR renders the cells more resistant to EGFR TKIs. In addition, RICTOR knockdown restores the sensitivity of erlotinib-resistant HCC827 cells due to AXL overexpression (IC50: 216µM vs. 0.256 µM with RICTOR knockdown, P Conclusion: Our study provides a new insight into the role of RICTOR signaling modulation in increasing efficacy of EGFR TKI therapy in EGFR-mutated NSCLC. The combination of mTOR1/2 inhibitor and EGFR inhibitor could be a potential novel strategy leading to better therapeutic efficacy. Note: This abstract was not presented at the meeting. Citation Format: Ni Fan, Yiyu Zou, Balazs Halmos, Roman Perez-Soler, Haiying Cheng. RICTOR signaling modulates the activity of EGFR tyrosine kinase inhibitors (TKI) in EGFR-mutated non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4748.

Background : Extramedullary hematopoiesis (EMH) implies the production of erythroid and myeloid progenitor cells outside of the bone marrow. EMH in adults is typically seen in patients with myeloproliferative neoplasms (MPN). The current study examines the Mayo Clinic experience with EMH cited in the absence of MPN. The objectives were to describe associated conditions and involved sites and identify "idiopathic" cases and review their management and long-term outcome. Methods : After approval by the Mayo Clinic institutional review board, institutional databases were screened through the Mayo Clinic Advanced Cohort Explorer (ACE) Tool, in order to identify patients with EMH. We performed a retrospective database review of all identified patients between 1975 and 2018. Demographic, biochemical, genetic, radiological and pathological data were collected and reviewed. Results : ACE identified 1,933 cases of "EMH". Extensive review confirmed the absence of associated MPN in 336 cases. Among these, 27 cases involved pathology remarks during tissue biopsy for liver transplant and were excluded from further analysis. The most frequent associated conditions in the remaining 309 cases included myelodysplastic syndromes (n=41; 13%), acute myeloid leukemia (n=28; 9%), hemolytic anemia (n=24; 8%), thalassemia (n=22; 7%), non-Hodgkin's lymphoma (n=19; 6%), immune thrombocytopenic purpura (n=17; 6%), metastatic cancer (n=17; 6%), plasma cell neoplasms (n=12; 4%) and a spectrum of other hematologic and non-hematologic conditions, including chronic lymphocytic leukemia, natural killer cell disorders, Hodgkin's lymphoma and Hemophagocytic lymphohistiocytosis. in 12 (4%) cases, no overt associated condition was evident and the cases were accordingly assigned "idiopathic". The most frequent involved sites included spleen (n=162), liver (n=78) and lymph nodes (n=20). A diagnosis of "idiopathic" EMH was established in 12 (4%) patients (median age 71 years, range 23-78; 50% females). Most of these cases presented with non-specific symptoms including abdominal and back pain and the EMH was an incidental discovery (Table 1). Involved sites included 4 pre-sacral, 3 para-spinal, 2 spleen and one each retroperitoneal, pleural-based chest mass and right upper lobe lung mass. All cases were evaluated with imaging studies and diagnosis was subsequently confirmed by pathology review. Past medical history was non-contributory. Complete blood counts were normal in 7 cases, showed anemia in 4 cases and were not available in one case (Table 1). The median follow-up time since the discovery of EMH was 7 years (range 2-20). None of the patients showed evidence of any malignancy, including MPN or other hematologic disorders, either at presentation or during follow-up. Nine (75%) of the 12 patients were managed conservatively; the two patients with splenic EMH underwent splenectomy and one patient had surgical excision of the EMH mass in order to prevent compression of the ureter. The FUO in the patient with splenic EMH resolved with splenectomy. Conclusions : We present the largest experience in EMH without associated MPN, in adults. We describe associated conditions and elaborate further on "idiopathic" EMH (n=12), which often represented an incidental discovery during evaluation of unrelated symptoms. None of the patients with idiopathic EMH harbored occult malignancies or subsequently developed MPN or other myeloid malignancies. Our observations do not support undertaking extensive investigations targeting MPN or other malignancies in idiopathic EMH and simple monitoring might be adequate. Disclosures No relevant conflicts of interest to declare.

Introduction For many patients with psychiatric disorders, the course of illness is characterized by frequent relapses, resulting to re-hospitalization and high costs. While the correlates of readmission have been extensively studied in developed countries, few studies have examined readmission in low- and middle-income countries where bed supply is limited. Methods Using administrative data from the Guangzhou Psychiatric Hospital (GPH), we used Cox regression models to evaluate the relationship among age, gender, index length of stay (LOS), and the number of previous admissions to post-discharge readmission risk. Linear regression is used to evaluate predictors of total hospital days during the year after the index discharge. Results Between April 1, 2010 and March 31, 2011, 2,525 patients were discharged with International Classification of Diseases, 10th Revision psychiatric diagnoses from GPH, with an average LOS of 64.2 (SD = 69.0), and 317 (12.4%) were readmitted in the following year. Survival analysis showed older age (P

The bar line is one of the important products of iron and steel industry, It is widely used in the construction of infrastructure facilities, construction and metal products industry. The programmable controller control system to replace the traditional relay control to control the hydraulic station, to complete the motor sequence control, and the pressure of the hydraulic oil contamination, temperature, automatic detection and alarm. Can satisfy the control requirements, reduce control cost, but also improves the control precision.

Objective Depressive disorder is associated with abnormal changes in cytokines levels. This study aimed to assess serum concentrations of tumor necrosis factor (TNF) α, interleukin (IL) 6, and IL-18 in depressive patients. The correlations between these three cytokine concentrations and the patients' clinical characteristics were also assessed. Methods Serum TNF-α, IL-6, and IL-18 concentrations were assessed using enzyme-linked immunosorbent assay from 64 depressive patients and 80 healthy control subjects. Depressive symptoms of patients were assessed using Hamilton Depression Scale-17. Results Depressive patients had increased serum TNF-α and IL-6 concentrations but decreased IL-18 concentrations than controls. TNF-α and IL-6 concentrations were significantly positively associated with Hamilton Depression Scale-17 scores in depressive patients. Conclusion These findings provided additional evidence that altered TNF-α, IL-6, and IL-18 activities may contribute to the pathophysiology of depressive disorder.

The correlation between enteritis, a common digestive disease, and exposure to ambient air pollutants has not been examined in a comprehensive manner. The aim of this study was to determine whether an association between short-term air pollution exposure and outpatient visits for enteritis in Xi'an, China, occurred using a time-series investigation. Daily baseline data from January 1, 2013, to December 31, 2015, were obtained. The overdispersed Poisson generalized additive model was used to analyze the association between air pollutant levels and frequency of enteritis. A total of 12,815 outpatient hospital visits for enteritis were identified. A 10-µg/m3 increase in average concentrations of particulate matter (PM)10, PM2.5, nitrogen dioxide (NO2), and sulfur dioxide (SO2), and a 0.1-mg/m3 rise of carbon monoxide (CO) were associated with a significantly elevated number of outpatient visits for enteritis on concurrent days, while ozone (O3) did not markedly affect the frequency of enteritis clinical visits. There were no significant positive effects between two-pollutant and single-pollutant models. Lag models showed that the most prominent responses occurred on concurrent days. Confounding factors of gender and age played a significant role in the observations. Taken together, data indicate that air pollution may result in enhanced occurrence of enteritis attack.

// Ni Fan 1,* , Lu Zhang 1,* , Xiaoping Xu 1 , Bobin Chen 1 , Chen Zhu 1 , Pei Li 1 , Zi Chen 1 , Tianling Ding 1 , Yan Ma 1 , Yan Yuan 1 and Zhiguang Lin 1 1 Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China Correspondence to: Xiaoping Xu, email: // Bobin Chen, email: // Keywords : PCNSL, methotrexate, idarubicin, PFS Received : September 06, 2016 Accepted : February 07, 2017 Published : March 04, 2017 Abstract Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma with poor long-term survival. This study assessed methotrexate (MTX) plus idarubicin (IDA) in treating patients of PCNSL comparing to MTX alone therapy. A total of 100 patients were retrospectively enrolled and subjected to MTX alone ( n = 52) and MTX plus IDA ( n = 48). The completed response (CR) rate in patients treated with MTX plus IDA was 62.50%, and overall response (OR) rate was 79.17%, which in MTX alone cohort were 42.31% and 63.46% respectively. Median progression-free survival (PFS) of patients treated with MTX plus IDA was significantly better than those treated with MTX alone (18.35 months vs. 8.45months, P = 0.000). The MTX plus IDA regimen exhibited a significantly better control of PCNSL. Further studies would be needed to confirm these results.

Supplemental Digital Content is available in the text, Structural abnormalities in schizophrenia (SZ) patients have been well documented with structural magnetic resonance imaging (MRI) data using voxel-based morphometry (VBM) and region of interest (ROI) analyses. However, these analyses can only detect group-wise differences and thus, have a poor predictive value for individuals. In the present study, we applied a machine learning method that combined support vector machine (SVM) with recursive feature elimination (RFE) to discriminate SZ patients from normal controls (NCs) using their structural MRI data. We first employed both VBM and ROI analyses to compare gray matter volume (GMV) and white matter volume (WMV) between 41 SZ patients and 42 age- and sex-matched NCs. The method of SVM combined with RFE was used to discriminate SZ patients from NCs using significant between-group differences in both GMV and WMV as input features. We found that SZ patients showed GM and WM abnormalities in several brain structures primarily involved in the emotion, memory, and visual systems. An SVM with a RFE classifier using the significant structural abnormalities identified by the VBM analysis as input features achieved the best performance (an accuracy of 88.4%, a sensitivity of 91.9%, and a specificity of 84.4%) in the discriminative analyses of SZ patients. These results suggested that distinct neuroanatomical profiles associated with SZ patients might provide a potential biomarker for disease diagnosis, and machine-learning methods can reveal neurobiological mechanisms in psychiatric diseases.

Objective: To investigate Carnation-87C photon therapeutic apparatus combined with peal burn ointment in the clinical effect of breast cancer patients after operation with unhealed incision of skin flap necrosis. Method: The treatment groups in the conventional treatment supplemented by photon therapeutic apparatus combined with peal burn ointment, the control group using route dressing change, two groups of patients with other treatments are the same. The two groups were treated for 4 weeks, to observe fresh wound granulation tissue growth and healing time. Results: Two groups of patients after operation with unhealed incision of skin flap necrosis, fresh wound granulation tissue growth and healing time were statistically significant(P

Purpose: To investigate the clinical effect of photon therapeutic apparatus in the treatment of acute postpartum mastitis patients. Method: 48 cases of acute postpartum mastitis patients were randomly divided into two groups, treatment group and control group. Patients in the treatment group were treated with Carnation photon therapeutic apparatus once a day, while combing with antibiotics. Patients in the control group were treated with antibiotics. The two groups of patients should stop breast-feeding during treatment, empty the milk and clean nipple. Two groups would be observed curative effect after 7 days of treatment and one month follow-up. Results: In treatment group, there are 83.33% patients show healed, 12.5% patients show progressed, and only 4.17% shows reappeared after one month. Conclusion: Experiment results show that in the treatment group, the total efficiency was obviously higher than that of the control group. Visibly, treating the mastitis with carnation photon therapeutic apparatus is significant effective. Carnation photon therapeutic apparatus can anti-inflammatory, anti-infective, promote skin lesions healing, analgesia, reduce the exudation, and maintain the role of wound dry, which is worth in clinical application.

This paper discusses the role of appropriate technical support in the landscape architecture design for mountainous scenic area from four aspects, namely enjoying, relaxing, viewing and service management, and provides theoretical guidance for the method of landscape architecture design in mountainous scenic areas. This paper makes an evidential analysis of Balidian catering buildings in Mount Shaohua scenic area by the typical demonstration; This paper analyzes the factors which influence the landscape architecture design and develop a method of the appropriate technical support for the landscape architecture design in mountainous scenic areas. The integration of appropriate technology is good for the landscape architecture design in mountainous scenic areas. This method has a certain reference value for the landscape architecture design in mountainous scenic areas.

Landscape design is a kind of constructive activities to show the regional outdoor space feature. It reflects the cultural and natural value in an certain area. With 2011 Xi’an International Horticultural Exposition for example, it discusses a design method which is combine with the site feature, rely on the regional culture and reproduce the regional characteristics. Through the landscape practical activity, people can feel a special regional landscape and understand the typical regional landscape.