Extracellular vesicle biomarkers for complement dysfunction in schizophrenia.

Schizophrenia, a complex neuropsychiatric disorder, frequently experiences a high rate of misdiagnosis due to subjective symptom assessment. Consequently, there is an urgent need for innovative and objective diagnostic tools. In this study, we used cutting-edge extracellular vesicles' (EVs) proteome profiling and XGBoost-based machine learning to develop new markers and personalized discrimination scores for schizophrenia diagnosis and prediction of treatment response. We analysed plasma and plasma-derived EVs from 343 participants, including 100 individuals with chronic schizophrenia, 34 first-episode and drug-naïve patients, 35 individuals with bipolar disorder, 25 individuals with major depressive disorder and 149 age- and sex-matched healthy controls. Our innovative approach uncovered EVs-based complement changes in patients, specific to their disease-type and status. The EV-based biomarkers outperformed their plasma counterparts, accurately distinguishing schizophrenia individuals from healthy controls with an area under curve (AUC) of 0.895, 83.5% accuracy, 85.3% sensitivity and 82.0% specificity. Moreover, they effectively differentiated schizophrenia from bipolar disorder and major depressive disorder, with AUCs of 0.966 and 0.893, respectively. The personalized discrimination scores provided a personalized diagnostic index for schizophrenia and exhibited a significant association with patients' antipsychotic treatment response in the follow-up cohort. Overall, our study represents a significant advancement in the field of neuropsychiatric disorders, demonstrating the potential of EV-based biomarkers in guiding personalized diagnosis and treatment of schizophrenia.

A case of ascetic fluid Mycobacterium aubagnense infection in a patient with severe peritoneal effusion.

BACKGROUND: Mycobacterium aubagnense, which was first characterized in 2006, is a non-tuberculosis mycobacterium (NTM) that has only been isolated from respiratory secretions and joint fluid. With only four cases globally, the microbe has rarely been reported in human clinical cases and the strain has not been isolated from ascites. CASE PRESENTATION: To the best of our knowledge, this is the first time that M. aubagnense has been isolated from ascites samples of a patient with severe peritoneal effusion and normal liver functions. Anti-NTM therapy with moxifloxacin, ethambutol, and isoniazid combined with furosemide and spironolactone diuretic therapy relieved the symptoms after six months. CONCLUSIONS: Increased puncture and drainage of ascites combined with diuretic treatment did not significantly relieve the ascites, leading to relapse with aggravated symptoms. The subsequent anti-NTM treatment with moxifloxacin, ethambutol, and isoniazid alleviated the degree of ascites. Therefore, we postulated that M. aubagnense infection was the potential cause of the difficult reduction of ascites in this patient. However, the ascites repeatedly occurred in the patient, which was attributed to M. aubagnense resistance due to insufficient medication time and repeated medication. The patient's underlying diseases may also result in ascites. Therefore, there is a need for careful analysis of the clinical significance of M. aubagnense.

Increased risk of atypical antipsychotics-induced metabolic syndrome associated with MIF CATT >5/6 among females with chronic schizophrenia.

The utilization of atypical antipsychotics (AAPs) often leads to metabolic syndrome (MetS) in schizophrenia (SZ) patients. Macrophage migration inhibitory factor (MIF) is an important MetS-related cytokine. To investigate the potential association between the MIF-794 CATT5-8 polymorphism and AAP-induced MetS in SZ patients, data from 375 chronic SZ patients who received AAP treatment for a minimum of one year were included. MIF-794 CATT polymorphism genotyping and plasma MIF quantification was performed. The metabolism status of all patients was assessed according to the NCEP-ATP III criteria. Individuals who displayed at least three of the five risk factors (waist circumference, high-density lipoprotein cholesterol, triglycerides, fasting glucose levels, and blood pressure) were diagnosed with MetS. The prevalence of MetS in SZ patients with MIF CATT >5/6 was significantly higher than in those with CATT 5/5-5/6. In female patients, MIF CATT >5/6 was associated with an elevated risk of AAP-induced MetS after adjusting for covariates, particularly regarding abdominal obesity, and the mediating effect of plasma MIF levels was significant. In conclusion, MIF CATT >5/6 increased the risk of AAP-induced MetS among females with chronic SZ. The MIF-794 CATT5-8 microsatellite polymorphism may be a unique indicator for AAP-induced metabolic adverse effects in female SZ patients.

High circulating MIF levels indicate the association with atypical antipsychotic-induced adverse metabolic effects.

Atypical antipsychotics (AAPs) are primary medications for schizophrenia (SZ). However, their use is frequently associated with the development of adverse metabolic effects, and the mechanisms behind these negative effects remain inadequately elucidated. To investigate the role of macrophage migration inhibitory factor (MIF) in regulating antipsychotic-induced metabolic abnormalities, between 2017 and 2020, a cross-sectional study was conducted, involving 142 healthy individuals and 388 SZ patients undergoing treatment with either typical antipsychotic (TAP) or AAP medications. Symptoms of SZ patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), and measurements of metabolic indices and plasma MIF levels were performed on all individuals. A significant increase in plasma MIF levels was observed in groups receiving five major AAP monotherapies in comparison to healthy controls (all p < 0.0001). There was no such increase shown in the group receiving TAP treatment (p > 0.05). Elevated plasma MIF levels displayed a notable correlation with insulin resistance (ß = 0.024, p = 0.020), as well as with the levels of triglycerides (ß = 0.019, p = 0.001) and total cholesterol (ß = 0.012, p = 0.038) in the groups receiving AAPs. However, while the TAP group also displayed certain metabolic dysfunction compared to healthy controls, no significant association was evident with plasma MIF levels (all p > 0.05). In conclusion, plasma MIF levels exhibit a distinctive correlation with metabolic abnormalities triggered by AAPs. Hence, there is potential for further development of MIF as a distinctive marker for monitoring adverse metabolic effects induced by AAPs in clinical settings.

Association Between Metabolic Risk Factors and Cognitive Impairment in Schizophrenia Based on Sex.

OBJECTIVE: Sex differences have been observed in many aspects of schizophrenia, including cognitive deficits. Despite extensive research into the relationship between metabolic factors and cognitive deficits in schizophrenia, few studies have explored the potential sex difference in their association. METHODS: We recruited 358 schizophrenia patients and 231 healthy controls. The participants underwent measurements of body mass index (BMI), waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose. Metabolic risk factors included abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. A collection of these metabolic risk factors has been defined as metabolic syndrome. These diagnoses were based on the criteria of the National Cholesterol Education Program's Adult Treatment Panel III. Cognitive performance was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A descriptive analysis, difference analysis, and linear regression model were used to identify the metabolic risk factors for cognitive function in schizophrenia. RESULTS: Our findings revealed sex differences in the rate of abdominal obesity and hypertension in schizophrenic patients. Additionally, we observed sex differences in the association between metabolic risk factors and cognitive impairment in schizophrenia. Specifically, hyperglycemia was associated with the immediate memory index score of RBANS in male patients, while dyslipidemia was associated with language, attention, delayed memory index scores, and RBANS total score in female patients. CONCLUSION: Our results suggest that sex should be considered when evaluating the impact of metabolic disorders on the cognitive function of schizophrenic patients. Moreover, our study identifies hyperglycemia and dyslipidemia as potential targets for precise treatment by sex stratification, which could benefit the improvement of cognitive impairment in schizophrenic patients.

Rare leptin in non-alcoholic fatty liver cirrhosis: A case report.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD)-related cirrhosis is mainly caused by NAFLD by causing inflammation which leads to fibrosis. The role of leptin in NAFLD-related cirrhosis has been rarely reported. CASE SUMMARY: This study presents the case of a 65-year-old male patient who was referred to The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi, China, for diagnosis and treatment for liver cirrhosis. Initially, the cause of liver cirrhosis was unknown. After radiology, laboratory examination, pathological results and analysis of the patient's signs and symptoms, the case was finally diagnosed with final NAFLD-related cirrhosis. Although this study reports a single case, the findings might expand the understanding of leptin's role in NAFLD-related cirrhosis and might provide a basis for the clinical diagnostic criteria, pathological features and treatment of NAFLD-related cirrhosis. CONCLUSION: Although the occurrence of marasmus NAFLD-related cirrhosis is rare, it needs to be distinguished from other liver diseases, including viral hepatitis, drug-induced liver disease, Wilson's disease and autoimmune liver disease. Aggressive treatment is needed to prevent the progression of NAFLD-related cirrhosis.