Targeted metabolomics-based understanding of the sleep disturbances in drug-naïve patients with schizophrenia.

BACKGROUND: Sleep disturbances are a common occurrence in patients with schizophrenia, yet the underlying pathogenesis remain poorly understood. Here, we performed a targeted metabolomics-based approach to explore the potential biological mechanisms contributing to sleep disturbances in schizophrenia. METHODS: Plasma samples from 59 drug-naïve patients with schizophrenia and 36 healthy controls were subjected to liquid chromatography-mass spectrometry (LC-MS) targeted metabolomics analysis, allowing for the quantification and profiling of 271 metabolites. Sleep quality and clinical symptoms were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Positive and Negative Symptom Scale (PANSS), respectively. Partial correlation analysis and orthogonal partial least squares discriminant analysis (OPLS-DA) model were used to identify metabolites specifically associated with sleep disturbances in drug-naïve schizophrenia. RESULTS: 16 characteristic metabolites were observed significantly associated with sleep disturbances in drug-naïve patients with schizophrenia. Furthermore, the glycerophospholipid metabolism (Impact: 0.138, p<0.001), the butanoate metabolism (Impact: 0.032, p=0.008), and the sphingolipid metabolism (Impact: 0.270, p=0.104) were identified as metabolic pathways associated with sleep disturbances in drug-naïve patients with schizophrenia. CONCLUSIONS: Our study identified 16 characteristic metabolites (mainly lipids) and 3 metabolic pathways related to sleep disturbances in drug-naïve schizophrenia. The detection of these distinct metabolites provide valuable insights into the underlying biological mechanisms associated with sleep disturbances in schizophrenia.

Pretreatment mortality risk prediction model in patients with polymyositis/dermatomyositis-associated interstitial lung disease.

OBJECTIVES: Risk prediction for patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) is challenging due to heterogeneity in the disease course. We aimed to develop a mortality risk prediction model for PM/DM-ILD. METHODS: This prognostic study analysed patients with PM/DM-ILD admitted to Nanjing Drum Hospital from 2016 to 2021. The primary outcome was mortality within 1 year. We used a least absolute shrinkage and selection operator (LASSO) logistic regression model to identify predictive laboratory indicators. These indicators were used to create a laboratory risk score, and we developed a mortality risk prediction model by incorporating clinical factors. The evaluation of model performance encompassed discrimination, calibration, clinical utility and practical application for risk prediction and prognosis. RESULTS: Overall, 418 patients with PM/DM-ILD were enrolled and randomly divided into development (n=282) and validation (n=136) cohorts. LASSO logistic regression identified four optimal features in the development cohort, forming a laboratory risk score: C reactive protein, lactate dehydrogenase, CD3+CD4+ T cell counts and PO2/FiO2. The final prediction model integrated age, arthralgia, anti-melanoma differentiation-associated gene 5 antibody status, high-resolution CT pattern and the laboratory risk score. The prediction model exhibited robust discrimination (area under the receiver operating characteristic: 0.869, 95% CI 0.811 to 0.910), excellent calibration and valuable clinical utility. Patients were categorised into three risk groups with distinct mortality rates. The internal validation, sensitivity analyses and comparative assessments against previous models further confirmed the robustness of the prediction model. CONCLUSIONS: We developed and validated an evidence-based mortality risk prediction model with simple, readily accessible clinical variables in patients with PM/DM-ILD, which may inform clinical decision-making.

Sex-specific associations of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in patients with drug-naïve schizophrenia.

This present study aimed to investigate the sex-specific association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in drug-naïve schizophrenia patients for the first time. A total of 204 participants in this study, including 137 drug-naïve schizophrenia (DNS) patients and 67 healthy controls (HCs). All participants completed the Measurements and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), and were collected fasting venous blood for NGAL measurement. DNS patients also complete the Positive and Negative Syndrome Scale (PANSS). Partial correlation analysis and multiple linear regression were used to explore sex-specific associations between NGAL and cognition. All dimensions of MCCB scores were significantly lower in both male and female DNS patients than HCs. Sex differences were significant in cognitive performance in both DNS patients and HCs. Female DNS patients experienced poorer working memory and reason& problem solving than male patients. Female HCs performed a better attention/vigilance and visual learning, a poorer reason& problem solving than male HCs. In patients with DNS, NGAL levels were negatively associated with positive subscale of PANSS and positively associated with working memory and visual learning only in female. However, there was no significant correlation between NGAL levels and all cognitive tests in both male and female HCs. Regression model showed that higher level of NGAL was an independent protective factor for cognitive performance in female patients with DNS, whereas there was no such role in male patients. Our findings suggest sex specificity between NGAL levels and cognitive performance in DNS patients.

High prevalence of pneumocystis pneumonia in interstitial lung disease: a retrospective study.

BACKGROUND: Interstitial lung disease (ILD) is a new risk category for pneumocystis pneumonia (PCP) with a high mortality rate. The definite diagnostic criteria of PCP in ILD patients have not been established until now. The aims of this study were to identify potential risk factors of PCP in patients with ILD, and to evaluate the performance of metagenomic next-generation sequencing (mNGS), CD4 + T cell count, (1-3)-ß-D-Glucan (BG) and lactate dehydrogenase (LDH) in the diagnosis of PCP in ILD patients. METHODS: This is a retrospective, single-center, case-control study. ILD patients who underwent mNGS from December 2018 to December 2022 were included in the study. Based on the diagnosis criteria of PCP, these patients were divided into PCP-ILD and non-PCP-ILD groups. The potential risk factors for PCP occurrence in ILD patients were analysed via logistic regression. The diagnostic efficacy of mNGS was compared with serological biomarkers. RESULTS: 92 patients with ILD were enrolled, 31 of which had a definite PCP and were assigned to the PCP-ILD group while 61 were to the non-PCP-ILD group. The infection rate of PJ in ILD patients was 33.7% (31/92). The history of glucocorticoid therapy, CD4 + T cell count, BG level and traction bronchiectasis on HRCT were associated with PCP occurrence in ILD patients. LDH level did not reach statistical significance in the logistic regression analysis. mNGS was confirmed as the most accurate test for PCP diagnosis in ILD patients. CONCLUSION: ILD is a new risk group of PCP with high PCP prevalence. Clinicians should pay close attention to the occurrence of PCP in ILD patients who possess the risk factors of previous glucocorticoid therapy, decreased CD4 + T cell count, increased BG level and absence of traction bronchiectasis on HRCT. mNGS showed the most excellent performance for PCP diagnosis in ILD patients. Peripheral blood CD4 + T cell count and BG level are alternative diagnostic methods for PCP in ILD patients. However, the diagnostic value of serum LDH level was limited in ILD patients.

Effects of the COVID-19 pandemic on mental health and sleep quality in the Chinese general populations during sporadic and outbreak periods.

The different coronavirus disease 2019 (COVID-19) outbreak patterns may have different impact on the mental health, but there is no such report at present. This study was aimed to investigate general populations mental health and sleep quality during the sporadic and outbreak of COVID-19 in Tianjin of China. Two cross-sectional studies included 1090 participants during the COVID-19 sporadic period from 28th January to 28th February 2022 and 2036 participants during the COVID-19 outbreak period from 1st January to 1st February 2023. We used the propensity score matching method to match the 2 samples (sporadic and outbreak group) with a ratio of 1:1. Finally, 1087 participants were included in each group. The demographics, Patient Health Questionnaire-9, Generalized Anxiety Disorder Scale-7, Connor-Davidson Resilience Scale, and Pittsburgh Sleep Quality Index were collected from all participants. There was a significant difference between the sporadic and outbreak groups for COVID-19-infected status, anxiety levels, sleep quality, and phycological resilience (all P < .05). Logistic regression analysis showed that female (P < .05) and depression status (P < .05) were the risk factors for the incidence rate of anxiety and poor sleep quality in sporadic group, and outbreak group, while phycological resilience were robust related to the sleep quality (P < .01). Poor sleep quality (P < .01) was related to the incidence of anxiety in sporadic group but not the outbreak group; anxiety levels (P < .01) were related to sleep quality in sporadic group but not the outbreak group. During the COVID-19 pandemic, general populations experienced high anxiety and poor sleep quality incidence rates, especially in the outbreak period. Different risk models for anxiety and sleep quality were found in the different outbreak patterns.

40-Hz auditory steady-state response deficits are correlated with the severity of persistent auditory verbal hallucination in patients with schizophrenia.

BACKGROUND: Abnormal 40 Hz auditory steady-state response (ASSR) has been observed in some psychiatric disorders. Nevertheless, the role of 40 Hz ASSR in persistent auditory verbal hallucinations (pAVHs) schizophrenia (SCZ) is still unknown. This study aims to investigate whether the 40 Hz ASSR impairment is related to pAVHs and can detect pAVHs severity. METHODS: We analyzed high-density electroencephalography data that from 43 pAVHs patients (pAVH group), 20 moderate auditory verbal hallucinations patients (mid-AVH group), and 24 without auditory verbal hallucinations patients (non-AVH group). Event-related spectral perturbation and inter-trial phase coherence (ITPC) were calculated to quantify dynamic changes of the 40 Hz ASSR power and ITPC, respectively. RESULTS: Frontal-central, the 40 Hz ASSR power, and ITPC were significantly lower in the pAVH group than in the non-AVH group; There was no significant difference between the pAVH and mid-AVH group. The 40 Hz ASSR was significantly negatively correlated with the severity of pAVHs. The 40 Hz ASSR power, and ITPC could be used as a combinational marker to detect SCZ patients with and without pAVHs. CONCLUSION: Our findings have shed light on the pathological mechanism of pAVHs in SCZ patients. These results can provide potential avenues for therapeutic intervention of pAVHs.

Gender differences and clinical correlates in the age of the first hospitalization in patients with drug-naïve schizophrenia in China: a cross-sectional study.

Gender differences in the onset age of schizophrenia have been reported in many studies, but differences in the age of the first hospitalization and associated factors have not been explored. The present study investigated gender differences and clinical correlates in the age of the first hospitalization in drug-naïve schizophrenia (DNS). A total of 144 DNS patients and 67 health controls were included. Demographic information, duration of untreated psychosis (DUP), Positive and Negative Symptom Scale (PANSS) scores, the Brief Psychiatric Rating Scale (BPRS) scores, Global Assessment of Functioning (GAF) scores, and MATRICS Consensus Cognitive Battery (MCCB) scores were collected and analyzed. The age of the first hospitalization was significantly earlier in males than in females (P < 0.01). In addition, there were significant differences in the age of the first hospitalization in terms of marital status, occupation, family ranking, suicide attempt, and place of residence (all P < 0.05). After Bonferroni correction, only DUP had a positive correlation with the age of the first hospitalization (PBonferroni < 0.05/6 = 0.0083). Multivariate linear regression analysis showed that gender (ß = 0.141, t = 2.434, P = 0.016), marital status (ß = 0.219, t = 3.463, P = 0.001), family ranking (ß = 0.300, t = 4.918, P < 0.001), suicide attempt (ß = 0.348, t = 5.549, P < 0.001), and DUP (ß = 0.190, t = 2.969, P < 0.004) positively predicted the age of the first hospitalization. The age of the first hospitalization in male DNS was earlier than in females. In addition, gender, marital status, suicide attempt, DUP, and family rank were independent risk factors for the age of the first hospitalization.

Identification of Plasma Biomarkers in Drug-Naïve Schizophrenia Using Targeted Metabolomics.

OBJECTIVE: Schizophrenia (SCZ) is a severe psychiatric disorder with unknown etiology and lacking specific biomarkers. Herein, we aimed to explore plasma biomarkers relevant to SCZ using targeted metabolomics. METHODS: Sixty drug-naïve SCZ patients and 36 healthy controls were recruited. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale. We analyzed the levels of 271 metabolites in plasma samples from all subjects using targeted metabolomics, and identified metabolites that differed significantly between the two groups. Then we evaluated the diagnostic power of the metabolites based on receiver operating characteristic curves, and explored metabolites associated with the psychotic symptoms in SCZ patients. RESULTS: Twenty-six metabolites showed significant differences between SCZ patients and healthy controls. Among them, 12 metabolites were phosphatidylcholines and cortisol, ceramide (d18:1/22:0), acetylcarnitine, and γ-aminobutyric acid, which could significantly distinguish SCZ from healthy controls with the area under the curve (AUC) above 0.7. Further, a panel consisting of the above 4 metabolites had an excellent performance with an AUC of 0.867. In SCZ patients, phosphatidylcholines were positively related with positive symptoms, and cholic acid was positively associated with negative symptoms. CONCLUSION: Our study provides insights into the metabolite alterations associated with SCZ and potential biomarkers for its diagnosis and symptom severity assessment.

The relationship between inflammatory markers, clinical characteristics, and cognitive performance in drug-naïve patients with schizophrenia.

Increasing evidence implicates that inflammatory factors do play a crucial role in the pathophysiology of schizophrenia. However, the association between inflammatory markers and different symptom dimensions and cognitive function of schizophrenia remains unclear. A total of 140 drug-naïve patients with schizophrenia and 69 healthy controls matched for age and gender were enrolled. Peripheral blood plasma concentrations of S-100 calcium-binding protein B (S100B), neutrophil gelatinase-associated lipocalin (NGAL), and interferon-γ (IFN-γ) were detected by enzyme-linked immunosorbent assay (ELISA). Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS), and cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Compared with healthy controls, patients with schizophrenia had significantly worse cognitive function and lower levels of NGAL and IFN-γ (P < 0.001). In schizophrenia, plasma NGAL and IFN-γ levels negatively correlated with positive symptom scores (all P < 0.05). There was a positive correlation between plasma levels of NGAL and IFN-γ with visual learning, neurocognition, and MCCB total score (all P < 0.05). We found that NGAL levels (ß = 0.352, t = 5.553, 95% CI 0.228-0.477, P < 0.001) and negative symptoms subscale scores (ß = - 0.321, OR = 0.725, 95% CI 648-0.811, P < 0.001) were independently associated with the MCCB total score. Further, binary logistic regression analysis indicated that the concentrations of NGAL (ß = - 0.246, OR = 0.782, 95% CI 0.651-0.939, P = 0.008) were independently associated with the diagnosis of schizophrenia. There was a positive correlation between NGAL and IFN-γ levels and MCCB total score in schizophrenia. NGAL level was an independent protective factor for cognitive function and an independent risk factor for the diagnosis of schizophrenia.

Altered dynamic functional connectivity of the thalamus subregions in patients with schizophrenia.

BACKGROUND: Previous neuroimaging studies indicated that patients with schizophrenia showed impaired thalamus and thalamo-cortical circuits. However, the dynamic functional connectivity (dFC) patterns of the thalamus remain unclear. In this study, we explored the dFC of the thalamus in SZ patients and whether clinical features are correlated with altered dFC. METHODS: Forty-three patients with schizophrenia and 31 healthy controls underwent 3.0 T rs-fMRI. Based on the human Brainnetome atlas, the thalamus is divided into 8 subregions. Subsequently, we performed flexible least squares method to calculate the dFC of each thalamus subregions. RESULTS: Compared with healthy controls, patients with schizophrenia exhibited increased dFC between the thalamus and cerebellar, visual-related cortex, sensorimotor-related cortex, and frontal lobe. In addition, we found that the dFC of the thalamus and the right fusiform gyrus was negatively associated with age of onset. CONCLUSIONS: Our findings demonstrated that the dFC of specific thalamus sub-regions is altered in patients with schizophrenia. Our results further suggested the dysconnectivity of thalamus plays an important role in the pathophysiology of schizophrenia.

Sex Differences in Prevalence and Clinical Correlates of Depression in Individuals Infected with Omicron in China.

Purpose: Sex differences in depression have been well recognized. However, sex differences in depression among Omicron-infected individuals have received little systematic study. This study compared sex differences in depression in infected individuals during the 2022 Omicron pandemic in China. Patients and Methods: 506 individuals infected with Omicron (males/females = 268/238) were recruited from Tianjin and Shanghai in China. Self-developed Scale of Demographics were used to collect demographic and clinical data, Zung Self-Rating Depression Scale (SDS), Zung Self-Rating Anxiety Scale (SAS), the Connor-Davidson Resilience Scale (CD-RISC), De Jong Gierveld Scale (DJGLS), and the Penn State Worry Questionnaire (PSWQ) were used to measure respondents' depression, anxiety, resilience, loneliness and worry, respectively. Results: The prevalence rate of depression in male patients was significantly higher than in female patients (42.2% versus 31.9%; χ2 = 5.64, p = 0.018). Regression analysis showed that in female patients, depression was associated with anxiety [OR = 1.26, 95% CI (1.16-1.36), p < 0.001], and resilience [OR = 0.98, 95% CI (0.96-1.00), p < 0.05], while in male patients, depression was associated with anxiety [OR = 1.24, 95% CI (1.15-1.33), p < 0.001]. Conclusion: This on-site study demonstrates that depression is more frequent in male than female Omicron-infected patients and suggests that sex differences should be considered in prevention and treatment strategies for depression during the Omicron pandemic.

Negative symptoms and neurocognition in drug-naïve schizophrenia: moderating role of plasma neutrophil gelatinase-associated lipocalin (NGAL) and interferon-gamma (INF-γ).

Previous studies reported that peripheral inflammation was associated with cognitive performance and brain structure in schizophrenia. However, the moderating effect of inflammation has not been extensively studied. This study investigated whether inflammation markers moderated the association between negative symptoms and neurocognition in schizophrenia. This cross-sectional study included 137 drug-naïve schizophrenia patients (DNS) and 67 healthy controls (HC). We performed the Measurements and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) for cognitive assessment and the Positive and Negative Syndrome Scale (PANSS) for psychiatric symptoms. Plasma concentrations of interferon-gamma (IFN-γ), neutrophil gelatinase-associated lipocalin (NGAL), and nuclear factor kappa B (NF-κB) were measured. The MCCB neurocognition score, social cognition score, and total score; the plasma concentrations of NGAL, IFN-γ, and NF-κB were significantly decreased in DNS than in HC (all P's < 0.001). PANSS negative subscale (PNS), PANSS reduced expressive subdomain (RES) negatively correlated with neurocognition score (P = 0.007; P = 0.011, respectively). Plasma concentrations of IFN-γ and NGAL positively correlated with neurocognition score (P = 0.043; P = 0.008, relatively). The interactions of PNS × NGAL; PNS × IFN-γ; RES × IFN-γ accounted for significant neurocognition variance (P = 0.025; P = 0.029, P = 0.007, respectively). Simple slope analysis showed that all the above moderating effects only occurred in patients with near normal IFN-γ and NGAL levels. Plasma concentrations of IFN-γ and NGAL moderated the relationship between negative symptoms (especially RES) and neurocognition in schizophrenia. Treatment targeting inflammation may contribute to neurocognition improvement in schizophrenia.

Metabolic biomarkers of risperidone-induced weight gain in drug-naïve patients with schizophrenia.

Background: Risperidone is a commonly prescribed antipsychotic drug with a potential side effect of weight gain. However, the pathophysiological mechanism is still poorly understood. Here, we sought to identify potential biomarkers of risperidone-induced weight gain by using a targeted metabolomics approach. Methods: We enrolled 30 subjects who received risperidone monotherapy for 8 weeks from a prospective longitudinal cohort study for drug-naïve schizophrenia patients. Plasma metabolites were measured by targeted metabolomics Biocrates MxP® Quant 500 Kit at baseline and 8-week follow-up. Results: After 8 weeks of risperidone treatment, the levels of 48 differential metabolites were upregulated, including lysophosphatidylcholines (2), phosphatidylcholines (PC) (8), cholesteryl esters (CE) (3), and triglycerides (35), while 6 differential metabolites namely PC aa C38:6, methionine (Met), α-aminobutyric acid (AABA), TrpBetaine, CE (22:6), and Taurocholic acid (TCA) were downregulated. Interestingly, the reduction of PC aa C38:6, AABA and CE (22:6) was linearly related with increased BMI. Further multiple regression analysis showed that the changes of PC aa C38:6 and AABA were independent contributors of increased BMI. In addition, baseline levels of PC aa C36:5, CE (20:5) and AABA had positive relationships with the change of BMI. Conclusion: Our findings indicate phosphatidylcholines and amino acids may serve as biomarkers for risperidone-induced weight gain.

Increased serum levels of sCD40L were associated with rapidly progressive interstitial lung disease in idiopathic inflammatory myopathies.

OBJECTIVES: Whether coagulopathy exists in development of idiopathic inflammatory myopathies associated rapidly progressive interstitial lung disease (IIMs-RPILD) is unclear. In this study, we aimed to investigate soluble CD40 ligand and D-dimer levels in RPILD patients. METHODS: Patients with IIMs-ILD were enrolled and classified as RPILD and stable-ILD group. Clinical data, laboratory examinations including coagulation-associated parameters and the myositis antibodies status, chest high-resolution computed tomography (HRCT) findings and treatment regimens were collected and serum levels of sCD40L were detected by ELISA. Univariable and adjusted multivariable cox regression were performed to identify risk factors for 6-month mortality, and further to select predictors for establishing predictive model for RPILD. RESULTS: Eighty patients with IIMs-ILD were enrolled and 34 of them were diagnosed as RPILD while 46 as stable-ILD. Multivariable cox regression showed that albumin<32.4 g/L and sCD40L<1658.55 pg/ml were independent risk factors of short-term mortality in RPILD. A SMAD model consisting of serum sCD40L>1054 pg/ml, anti-MDA5 positivity, albumin<32.4 g/L and D-dimer>0.865 mg/L were generated. The odds for RPILD with SMAD score of 0, 1, 2, 3 and 4 were 0, 26.9%, 66.7%, 91.7% and 100%. The 6-month survival stratified by mild (SMAD score 0), moderate (SMAD score 1 and 2) and severe group (SMAD score 3 and 4) were 100%, 79.5% and 20%, respectively. CONCLUSIONS: We established a predictive model for IIMs-RPILD, which provided a clue that coagulopathy might exist in IIMs-RPILD and could help to better treat patients with RPILD. This model awaits further validations.

Associations between metabolic disorders and sleep disturbance in patients with schizophrenia.

BACKGROUND: Sleep disturbance plays a crucial role in mental illness and metabolic dysregulation. However, the clinical correlates of metabolic disorders (MD, only meeting 1 or 2 metabolic syndrome standards) and its relationship to sleep disturbance in patients with schizophrenia are uncertain. The study was to illuminate the association between MD and sleep disturbance in patients with schizophrenia. METHODS: One hundred and sixty-four patients with schizophrenia (157 drug-naive and 7 drug-free) were classified into 2 groups: MD and non-MD. The Pittsburgh Sleep Quality Index (PSQI) and the Positive and Negative Symptom Scale (PANSS) were employed to assess sleep quality and clinical symptoms. Weight, height, waistline, blood pressure, fasting glucose, and lipid metabolic levels were recorded. RESULTS: Sleep disturbance was more pronounced in the MD group compared to the non-MD group, including subjective sleep quality (z = -4.074, p = 0.000), sleep latency (z = -3.867, p = 0.000), sleep duration (z = -2.471, p = 0.013) and total scores (z = -3.074, p = 0.002). After controlling for confounding factors including age, sex, body mass index, smoking, marital status, and duration of illness, binary logistics regression showed that subjective sleep quality (p = 0.034) and sleep latency (p = 0.034) were significant independent predictors of MD. Further, partial correlation analysis showed that sleep latency (r = -0.200, p = 0.011) was significantly negatively correlated with HDLC. CONCLUSION: Our study suggests a high rate of MD in patients with schizophrenia, most of who were drug-naive, in a Chinese population. Longer sleep latency is associated with MD in schizophrenia patients, suggesting an important role of sleep disturbance in the development of MD in patients with schizophrenia. Interventions to improve sleep quality may prevent MD in patients with schizophrenia at an early stage.

An observational study of clinical recurrence in patients with interstitial lung disease related to the antisynthetase syndrome.

OBJECTIVE: To describe the clinical characteristics and risk factors of clinical recurrence in interstitial lung disease related to antisynthetase syndrome (ARS-ILD). METHODS: Patients diagnosed as ARS-ILD in Nanjing Drum Tower Hospital between January 2015 and November 2020 were retrospectively analyzed. Clinical information and treatment course were reviewed. The primary endpoint was the disease recurrence, and the secondary point was mortality. Univariate and multivariable Cox regression analyses were performed to identify risk factors for recurrence. RESULTS: Totally, 132 patients with ARS-ILD received immunomodulation treatment from diagnosis. During follow-ups, sixty-nine patients showed recurrence, with a recurrency rate yielding 52.3%. The median duration from treatment initiation to recurrence was 11 (5-18) months. The median tapering course in the recurrence group was 8 (3-12.5) months, which was significantly shorter than the 16 (10-32) months in the no-recurrence group (p < 0.001). Fifty-eight patients experienced recurrence when the glucocorticoids (GC) dose dropped to 10 (9.375-15) mg/day. Twelve patients discontinued GC with a median treatment course of 11.5 (8-16.75) months, and 11 patients developed recurrence after discontinuing GC for 3 (1-4) months. Twelve patients died, with a mortality rate of 9.1%, and recurrence was not associated with increased mortality. The adjusted multivariate analysis showed that age, increased serum lactate dehydrogenase (LDH) level, relatively shorter tapering duration, and inappropriate GC discontinuation were associated with recurrence. CONCLUSION: Recurrence of ARS-ILD was common during medication intensity reduction. Age, LDH, medication tapering duration, and discontinuation were risk factors for recurrence. Further efforts to reduce recurrence should take into consideration of these factors. Key Points • Recurrence is observed commonly with a recurrency rate 52.3% in patients with interstitial lung disease related to antisynthetase syndrome (ARS-ILD) when glucocorticoids (GC) tapering or discontinuation. • Age, increased serum lactate dehydrogenase (LDH) level, medication tapering duration, and GC discontinuation were identified to be significantly associated with the recurrence of ARS-ILD.

Prediction model for the pretreatment evaluation of mortality risk in anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with interstitial lung disease.

Background: Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with interstitial lung disease (anti-MDA5 DM-ILD) is a disease with high mortality. We sought to develop an effective and convenient prediction tool to estimate mortality risk in patients with anti-MDA5 DM-ILD and inform clinical decision-making early. Methods: This prognostic study included Asian patients with anti-MDA5 DM-ILD hospitalized at the Nanjing Drum Hospital from December 2016 to December 2020. Candidate laboratory indicators were retrospectively collected. Patients hospitalized from 2016 to 2018 were used as the discovery cohort and applied to identify the optimal predictive features using a least absolute shrinkage and selection operator (LASSO) logistic regression model. A risk score was determined based on these features and used to construct the mortality risk prediction model in combination with clinical characteristics. Results were verified in a temporal validation comprising patients treated between 2019 and 2020. The primary outcome was mortality risk within one year. The secondary outcome was overall survival. The prediction model's performance was assessed in terms of discrimination, calibration, and clinical usefulness. Results: This study included 127 patients, (72 men [56.7%]; median age, 54 years [interquartile range, 48-63 years], split into discovery (n = 87, 70%) and temporal validation (n=37, 30%) cohorts. Five optimal features were selected by LASSO logistic regression in the discovery cohort (n = 87) and used to construct a risk score, including lymphocyte counts, CD3+CD4+ T-cell counts, cytokeratin 19 fragment (CYFRA21-1), oxygenation index, and anti-Ro52 antibody. The retained predictive variables in the final prediction model were age, Heliotrope, fever, and risk score, and the most predictive factor was the risk score. The prediction model showed good discrimination (AUC: 0.915, 95% CI: 0.846-0.957), good calibration (Hosmer-Lemeshow test, P = 0.506; Brier score, 0.12), and fair clinical usefulness in the discovery cohort. The results were verified among patients in the temporal validation cohort (n = 38). We successfully divided patients into three risk groups with very different mortality rates according to the predictive score in both the discovery and validation cohorts (Cochran-Armitage test for trend, P < 0.001). Conclusions: We developed and validated a mortality risk prediction tool with good discrimination and calibration for Asian patients with anti-MDA5 DM-ILD. This tool can offer individualized mortality risk estimation and inform clinical decision-making.

Anti-Ro52 antibodies are associated with the prognosis of adult idiopathic inflammatory myopathy-associated interstitial lung disease.

OBJECTIVES: In the present study, we aimed to assess the prevalence and clinical significance of anti-Ro52 antibodies in a cohort of patients with idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) with different myositis-specific autoantibodies (MSAs). METHODS: A cohort of 267 IIM-ILD patients, including 62 patients with PM, 126 patients with DM and 79 patients with clinically amyopathic DM (CADM) were retrospectively analysed in this study. Clinical and laboratory findings, pulmonary function tests (PFTs), HRCT patterns and treatment information were compared between patients with and without anti-Ro52 antibodies. The association between prognosis and anti-Ro52 antibodies was also evaluated based on different MSA subgroups. RESULTS: Anti-Ro52 antibodies were more frequent in patients with anti-MDA5 (62.1%, P < 0.01) and anti-Jo1 (64.9%, P < 0.01) antibodies than in those with other MSAs. The proportion of patients with anti-Jo1 antibodies was higher in the anti-Ro52 antibody-positive group than in the anti-Ro52 antibody-negative group. Patients with anti-Ro52 antibodies were more likely to exhibit the Gottron sign than the anti-Ro52 antibody-negative group (P < 0.001). Furthermore, it was a predictive factor for rapid progression interstitial lung disease (RP-ILD) (P = 0.001) and was also associated with a higher mortality rate (log-rank test, P = 0.001). Furthermore, RP-ILD was more frequently exhibited in anti-MDA5- and anti-Ro52-positive patients. Moreover, anti-Ro52 antibody positivity was closely associated with a higher mortality rate in anti-MDA5-ILD patients (log-rank test, P < 0.05). CONCLUSIONS: Anti-Ro52 antibodies were highly prevalent in patients with anti-MDA5 and anti-Jo1 antibodies. Within all patients with IIM-ILD, those with anti-Ro52 autoantibodies had a higher frequency of RP-ILD and a poorer prognosis, especially in the anti-MDA5 antibody subgroup.

Improvement of adjunctive berberine treatment on negative symptoms in patients with schizophrenia.

The upregulation of immune and inflammatory response may play a role in the negative symptoms of schizophrenia. Berberine is an effective drug with anti-inflammatory property, and may be beneficial for the treatment of negative symptoms. The aim of this study is to test this hypothesis through a randomized, double-blind, placebo-controlled, clinical trial. Eligible patients with schizophrenia were randomized to receive placebo or berberine (900 mg/day) for 8 weeks as adjunctive treatment to single atypical antipsychotic drug. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate clinical symptoms at three time points (baseline, 4th and 8th week). Blood samples were collected at the above three time points to determine the concentrations of inflammatory markers including interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). 59 patients with intention-to-treat were analyzed, 32 in the berberine group and 27 in the placebo group. From the baseline to the 8th week, berberine treatment significantly improved the negative symptom subscale of PANSS (F = 18.981; p < 0.001). From the baseline to the 8th week, the plasma CRP concentration decreased in the berberine group, while increased in the placebo group (F = 5.373; p = 0.024). Furthermore, in the berberine group, the change of CRP concentration was significantly positively correlated with the change of PANSS negative symptom subscale within 8 weeks (r = 0.56; p = 0.002). There was no significant difference in adverse events between the two groups (p's > 0.05). Our study suggests that berberine treatment is well tolerated in patients with schizophrenia. Berberine may improve negative symptoms through anti-inflammatory effect.Trial registration: Clinicaltrials.gov identifier: NCT03548155.

Polymorphisms of COMT and CREB1 are associated with treatment-resistant depression in a Chinese Han population.

Genetic factors play a crucial role for the pathophysiology of treatment-resistant depression (TRD). It has been established that Catechol-O-methyltransferase (COMT) and cyclic amp-response element-binding protein (CREB) are associated with antidepressant response. The aim of this study was to explore the association between single nucleotide polymorphisms (SNPs) in COMT and CREB1 genes and TRD in a Chinese population. We recruited 181 patients with major depressive disorder (MDD) and 80 healthy controls, including 81 TRD patients. Depressive symptoms were assessed with the Hamilton Depression Rating Scale-17 (HDRS). Genotyping was performed using mass spectrometry. Genetic analyses were conducted by PLINK Software. The distribution of COMT SNP rs4818 allele and genotypes were significantly different between TRD and controls. Statistical differences in allele frequencies were observed between TRD and non-TRD groups, including rs11904814 and rs6740584 in CREB1 gene, rs4680 and rs4818 in COMT gene. There were differences in the distribution of HDRS total scores among different phenotypes of CREB1 rs11904814, CREB1 rs6740584, COMT rs4680 and rs4818. Gene-gene interaction effect of COMT-CREB1 (rs4680 × rs6740584) revealed significant epistasis in TRD. There findings indicate that COMT and CREB1 polymorphisms influence the risk of TRD and affect the severity of depressive symptoms of MDD.