Neurostructural subgroup in 4291 individuals with schizophrenia identified using the subtype and stage inference algorithm.

Machine learning can be used to define subtypes of psychiatric conditions based on shared biological foundations of mental disorders. Here we analyzed cross-sectional brain images from 4,222 individuals with schizophrenia and 7038 healthy subjects pooled across 41 international cohorts from the ENIGMA, non-ENIGMA cohorts and public datasets. Using the Subtype and Stage Inference (SuStaIn) algorithm, we identify two distinct neurostructural subgroups by mapping the spatial and temporal 'trajectory' of gray matter change in schizophrenia. Subgroup 1 was characterized by an early cortical-predominant loss with enlarged striatum, whereas subgroup 2 displayed an early subcortical-predominant loss in the hippocampus, striatum and other subcortical regions. We confirmed the reproducibility of the two neurostructural subtypes across various sample sites, including Europe, North America and East Asia. This imaging-based taxonomy holds the potential to identify individuals with shared neurobiological attributes, thereby suggesting the viability of redefining existing disorder constructs based on biological factors.

Distribution of self-reported borderline personality disorder traits symptoms in a large-scale clinical population.

Introduction: Borderline Personality Disorder (BPD) traits play a crucial role in the prognosis of psychiatric disorders, as well as in assessing risks associated with negativity and impulsivity. However, there is a lack of data regarding the distribution characteristics of BPD traits and symptoms within clinical populations. Methods: A total of 3015 participants (1321 males, 1694 females) were consecutively sampled from outpatients at the psychiatric and psycho-counseling clinics at the Shanghai Mental Health Center. BPD symptoms were assessed using a self-reported personality diagnostic questionnaire. Having BPD traits is defined as having five or more positive items in self-reported BPD characteristics. Participants were stratified into male and female groups, age groups, and diagnostic groups (schizophrenia, mood disorders, anxiety disorders). Exploratory factor analysis using principal components analysis was conducted. Three factors were identified: "F1: Affective Instability and Impulsivity", "F2: Interpersonal Unstable and Extreme Reactions", and "F3: Identity Disturbance". Results: Among 3015 participants, 45.9% of the patients self-reported BPD traits. Comparing of male and female patients, there was no statistically significant difference in the occurrence rate of BPD traits (χ2 = 1.835, p=0.176). However, in terms of symptoms, female patients reported more symptoms than male patients. Female patients also exhibited more pronounced features on F2 compared to male patients (t =-1.972, p=0.049). There is a general decrease in BPD traits, symptoms, and factors with increasing age. Specifically, the proportion of positive BPD traits is approximately halved before the age of 30 and decreases to around one-third after the age of 30. BPD traits were most common in the Mood Disorders group at 55.7%, followed by the Anxiety Disorders group at 44.4%, and Schizophrenia group at 41.5% (χ2 = 38.084, p<0.001). Discussion: Our study revealed the pervasive presence of BPD traits and symptoms among psychiatric outpatients, exhibiting distinctive distributions across gender, age, and diagnostic categories. These findings emphasize the significance of identifying and addressing BPD pathology in the clinical care of psychiatric outpatients.

Neuroimaging epicenters as potential sites of onset of the neuroanatomical pathology in schizophrenia.

Schizophrenia lacks a clear definition at the neuroanatomical level, capturing the sites of origin and progress of this disorder. Using a network-theory approach called epicenter mapping on cross-sectional magnetic resonance imaging from 1124 individuals with schizophrenia, we identified the most likely "source of origin" of the structural pathology. Our results suggest that the Broca's area and adjacent frontoinsular cortex may be the epicenters of neuroanatomical pathophysiology in schizophrenia. These epicenters can predict an individual's response to treatment for psychosis. In addition, cross-diagnostic similarities based on epicenter mapping over of 4000 individuals diagnosed with neurological, neurodevelopmental, or psychiatric disorders appear to be limited. When present, these similarities are restricted to bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. We provide a comprehensive framework linking schizophrenia-specific epicenters to multiple levels of neurobiology, including cognitive processes, neurotransmitter receptors and transporters, and human brain gene expression. Epicenter mapping may be a reliable tool for identifying the potential onset sites of neural pathophysiology in schizophrenia.

Risk factors for hemoglobin decline in gastric cancer patients undergoing postoperative chemotherapy: a retrospective analysis.

OBJECTIVE: To investigate the independent risk factors for a decreased hemoglobin level in gastric cancer patients undergoing adjuvant chemotherapy. METHODS: A retrospective study was conducted on 142 gastric cancer patients who received chemotherapy between May 2017 and May 2021 at the Gansu Provincial Cancer Hospital. All patients were subjected to the same regimen of adjuvant chemotherapy combining platinum/taxane and fluorouracil. The correlation between patients' clinicopathological features and the decreased hemoglobin during adjuvant chemotherapy was analyzed. Logistic and LASSO regression analyses were employed to screen for independent risk factors for decreased hemoglobin during adjuvant chemotherapy. RESULTS: Univariate analysis revealed that intraoperative bleeding, pre-chemotherapy anemia, and hypoalbuminemia were risk factors for the decreased hemoglobin in patients during adjuvant chemotherapy (all P < 0.05). Both logistic and LASSO regression analyses corroborated these factors as influential factors in the decrease of hemoglobin (P < 0.05). In addition, both logistic and LASSO regression models demonstrated similar performance in this aspect. The nomogram model was subjected to internal validation, resulting in a C-index of 0.712 (0.629-0.796). The calibration curves exhibited satisfactory alignment with the ideal curve. CONCLUSION: Intraoperative blood loss, pre-chemotherapy anemia, and hypoalbuminemia are independent risk factors for hemoglobin reduction following chemotherapy. Moreover, both the logistic and LASSO regression models exhibited equivalent performance in this context. These findings bear substantial clinical implications, aiding physicians in the management of anemia in patients undergoing chemotherapy.

Cognitive Impairments in Drug-Naive Patients With First-Episode Negative Symptom-Dominant Psychosis.

Importance: Available antipsychotic medications are predominantly used to treat positive symptoms, such as hallucinations and delusions, in patients with first-episode psychosis (FEP). However, treating negative and cognitive symptoms, which are closely related to functional outcomes, remains a challenge. Objective: To explore the cognitive characteristics of patients with negative symptom-dominant (NSD) psychosis. Design, Setting, and Participants: This large-scale cross-sectional study of patients with FEP was led by the Shanghai Mental Health Center in China from 2016 to 2021, with participants recruited from 10 psychiatric tertiary hospitals. A comprehensive cognitive assessment was performed among 788 patients with FEP who were drug-naive. Symptom profiles were determined using the Positive and Negative Symptoms Scale (PANSS), and NSD was defined as a PANSS score for negative symptoms higher than that for positive and general symptoms. Positive symptom-dominant (PSD) and general symptom-dominant (GSD) psychosis were defined similarly. Data were analyzed in 2023. Exposure: Psychotic symptoms were categorized into 3 groups: NSD, PSD, and GSD. Main Outcomes and Measures: Neurocognitive performance, assessed using the Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. Results: This study included 788 individuals with FEP (median age, 22 [IQR, 17-28] years; 399 men [50.6%]). Patients with NSD exhibited more-pronounced cognitive impairment than did those with PSD or GSD. Specifically, cognitive differences between the NSD and PSD group, as well as between the NSD and GSD group, were most notable in the processing speed and attention domains (Trail Making [F = 4.410; P = .01], Symbol Coding [F = 4.957; P = .007], Verbal Learning [F = 3.198; P = .04], and Continuous Performance [F = 3.057; P = .05]). Patients with PSD and GSD showed no significant cognitive differences. Cognitive impairment was positively associated with the severity of negative symptoms. Most of the cognitive function tests used were able to differentiate patients with NSD from those with PSD and GSD, with significant differences observed across a range of tests, from Brief Visuospatial Memory Test-Revised (χ2 = 3.968; P = .05) to Brief Assessment of Cognition in Schizophrenia symbol coding (χ2 = 9.765; P = .002). Conclusions and Relevance: The findings of this cross-sectional study of patients with FEP suggest the presence of a clinical subtype characterized by a predominance of negative symptoms and cognitive impairment.

Abnormal Scanning Patterns Based on Eye Movement Entropy in Early Psychosis.

BACKGROUND: Restricted scan path mode is hypothesized to explain abnormal scanning patterns in patients with schizophrenia. Here, we calculated entropy scores (drawing upon gaze data to measure the statistical randomness of eye movements) to quantify how strategical and random participants were to process image stimuli. METHODS: Eighty-six patients with first-episode schizophrenia (FES), 124 individuals at clinical high risk (CHR) for psychosis, and 115 healthy controls (HCs) completed an eye-tracking examination for freely viewing 35 static images (each presented 10s) and cognitive assessments. We compared the group differences in overall entropy score, as well as entropy scores under various conditions. Furthermore, we also investigated the correlation between entropy scores and symptoms along with cognitive function. RESULTS: Increased overall entropy scores were noted in FES and CHR groups relative to HCs, and these differences were already apparent within 0∼2.5s. In addition, the CHR group exhibited higher entropy when viewing low-meaning images compared to HCs. Moreover, the entropy within 0∼2.5s showed significant correlations with negative symptoms in the FES group, Attention/Vigilance scores in the CHR group, as well as Speed of processing and Attention/Vigilance scores across all three groups. CONCLUSIONS: The results indicate that FES and CHR individuals scan pictures more randomly and less strategically than HCs. These patterns also correlate with clinical symptoms and neurocognition. The present study highlights the potential of the eye movement entropy measure as a neurophysiological marker for early psychosis.

Abnormal Global Cortical Responses in Drug-Naïve Patients With Schizophrenia Following Orbitofrontal Cortex Stimulation: A Concurrent Transcranial Magnetic Stimulation-Electroencephalography Study.

BACKGROUND: Abnormalities in cortical excitability and plasticity have been considered to underlie the pathophysiology of schizophrenia. Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) can provide a direct evaluation of cortical responses to TMS. Here, we employed TMS-EEG to investigate cortical responses to orbitofrontal cortex (OFC) stimulation in schizophrenia. METHODS: In total, we recruited 92 drug-naïve patients with first-episode schizophrenia and 51 age- and sex-matched healthy individuals. For each participant, one session of 1-Hz repetitive TMS (rTMS) was delivered to the right OFC, and TMS-EEG data were obtained to explore the change in cortical-evoked activities before and immediately after rTMS during the eyes-closed state. The MATRICS Consensus Cognitive Battery was used to assess neurocognitive performance. RESULTS: The cortical responses indexed by global mean field amplitudes (i.e., P30, N45, and P60) were larger in patients with schizophrenia than in healthy control participants at baseline. Furthermore, after one session of 1-Hz rTMS over the right OFC, the N100 amplitude was significantly reduced in the healthy control group but not in the schizophrenia group. In the healthy control participants, there was a significant correlation between modulation of P60 amplitude by rTMS and working memory; however, this correlation was absent in patients with schizophrenia. CONCLUSIONS: Aberrant global cortical responses following right OFC stimulation were found in patients with drug-naïve first-episode schizophrenia, supporting its significance in the primary pathophysiology of schizophrenia.

Excessive interstitial free-water in cortical gray matter preceding accelerated volume changes in individuals at clinical high risk for psychosis.

Recent studies show that accelerated cortical gray matter (GM) volume reduction seen in anatomical MRI can help distinguish between individuals at clinical high risk (CHR) for psychosis who will develop psychosis and those who will not. This reduction is suggested to represent atypical developmental or degenerative changes accompanying an accumulation of microstructural changes, such as decreased spine density and dendritic arborization. Detecting the microstructural sources of these changes before they accumulate into volume loss is crucial. Our study aimed to detect these microstructural GM alterations using diffusion MRI (dMRI). We tested for baseline and longitudinal group differences in anatomical and dMRI data from 160 individuals at CHR and 96 healthy controls (HC) acquired in a single imaging site. Of the CHR individuals, 33 developed psychosis (CHR-P), while 127 did not (CHR-NP). Among all participants, longitudinal data was available for 45 HCs, 17 CHR-P, and 66 CHR-NP. Eight cortical lobes were examined for GM volume and GM microstructure. A novel dMRI measure, interstitial free water (iFW), was used to quantify GM microstructure by eliminating cerebrospinal fluid contribution. Additionally, we assessed whether these measures differentiated the CHR-P from the CHR-NP. In addition, for completeness, we also investigated changes in cortical thickness and in white matter (WM) microstructure. At baseline the CHR group had significantly higher iFW than HC in the prefrontal, temporal, parietal, and occipital lobes, while volume was reduced only in the temporal lobe. Neither iFW nor volume differentiated between the CHR-P and CHR-NP groups at baseline. However, in many brain areas, the CHR-P group demonstrated significantly accelerated changes (iFW increase and volume reduction) with time than the CHR-NP group. Cortical thickness provided similar results as volume, and there were no significant changes in WM microstructure. Our results demonstrate that microstructural GM changes in individuals at CHR have a wider extent than volumetric changes or microstructural WM changes, and they predate the acceleration of brain changes that occur around psychosis onset. Microstructural GM changes, as reflected by the increased iFW, are thus an early pathology at the prodromal stage of psychosis that may be useful for a better mechanistic understanding of psychosis development.

Clinical Predictors of Bacteremia Outcome After Initial Empirical Antimicrobial Therapy in Patients with Hematological Malignancies: A Retrospective Analysis.

Objective: We performed a retrospective analysis to investigate the clinical predictors of bacteremia outcome involving Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) after initial empirical antimicrobial therapy among hematological malignancy cases. Methods: This retrospective study was conducted between April 2018 and April 2023. All bloodstream infections (BSIs) caused by E. coli and K. pneumoniae in hospitalized hematological malignancy (HM) patients were identified. Data on patient demographics, clinical characteristics, empirical antimicrobial treatment, outcomes and the antimicrobial susceptibility were collected from medical records. Multivariate analyses were utilized to assess the risk factors for all-cause mortality within 28 days and carbapenem resistance. Optimal cutoffs for continuous predictive variables were evaluated by receiver operating characteristic (ROC) curve analysis. Results: Among 61 individuals diagnosed with bacteremia, 39 cases were caused by E. coli bacteremia, while the remaining 22 were identified as K. pneumoniae bacteremia. Out of these, there were 10 cases of carbapenem-resistant Enterobacteriaceae (CRE) and 12 cases resulted in all-cause mortality within 28 days. Analysis indicated that Pitt score was an independent risk factor for mortality and a cut-off of 2.5 was a reliable predictor with 83.3% sensitivity and 85.7% specificity, respectively. Impaired mental status and elevated body temperature exceeding 38.6°C as well as a procalcitonin (PCT) level over 8.24 ng/mL on the third day (d3) after antimicrobial treatment were identified as independent risk factors for predicting carbapenem resistance. Conclusion: We found that Pitt score with a cut-off of 2.5 was a reliable predictor for mortality within 28 days in HM bacteremia cases. Impaired mental status and elevated temperature exceeding 38.6°C as well as a procalcitonin (PCT) level over 8.24 ng/mL on d3 after antimicrobial treatment were identified as predictive risk factors to carbapenem resistance.

Cognitive functions following initiation of antipsychotic medication in adolescents and adults at clinical high risk for psychosis: a naturalistic sub group analysis using the MATRICS consensus cognitive battery.

BACKGROUND: The effects of antipsychotic (AP) medications on cognitive functions in individuals at clinical high-risk (CHR) of psychosis are poorly understood. This study compared the effects of AP treatment on cognitive improvement in CHR adolescents and adults. METHODS: A total of 327 CHR participants, with an age range of 13 to 45 years, who underwent baseline neuropsychological assessments and a 1-year clinical follow-up were included. Participants with CHR were categorized into four groups based on their age: adolescents (aged < 18) and adults (aged ≥ 18), as well as their antipsychotic medication status (AP+ or AP-). Therefore, the four groups were defined as Adolescent-AP-, Adolescent-AP+, Adult-AP-, and Adult-AP+. RESULTS: During the follow-up, 231 CHR patients received AP treatment, 94 converted to psychosis, and 161 completed the 1-year follow-up. The Adolescent-AP+ group had more positive symptoms, lower general functions, and cognitive impairments than the Adolescent-AP- group at baseline, but no significant differences were observed among adults. The Adolescent-AP+ group showed a significant increase in the risk of conversion to psychosis (p < 0.001) compared to the Adolescent-AP- group. The Adult-AP+ group showed a decreasing trend in the risk of conversion (p = 0.088) compared to the Adult-AP- group. The Adolescent-AP- group had greater improvement in general functions (p < 0.001), neuropsychological assessment battery mazes (p = 0.025), and brief visuospatial memory test-revised (p = 0.020), as well as a greater decrease in positive symptoms (p < 0.001) at follow-up compared to the Adolescent-AP+ group. No significant differences were observed among adults. CONCLUSIONS: Early use of AP was not associated with a positive effect on cognitive function in CHR adolescents. Instead, the absence of AP treatment was associated with better cognitive recovery, suggesting that AP exposure might not be the preferred choice for cognitive recovery in CHR adolescents, but may be more reasonable for use in adults.

Sex Differences in Personality Disorder and Childhood Maltreatment of Patients with Schizophrenia.

Introduction: Despite numerous studies investigating personality disorder (PD) and childhood maltreatment (CM) characteristics in individuals with schizophrenia (SZ), there remains a scarcity of research focusing on sex differences in PD and CM within large samples of SZ patients. Methods: A total of 592 participants (257 males, 335 females) were consecutively sampled from patients diagnosed with SZ at the psychiatric and psycho-counseling clinics at Shanghai Mental Health Center. PDs were assessed using a self-reported personality diagnostic questionnaire and a structured clinical interview, while CMs were evaluated using the Chinese version of the Child Trauma Questionnaire Short Form. Results: Male patients exhibited a prominent self-reported trait of antisocial PD (t=1.972, p=0.049), while female patients demonstrated a notable emphasis on histrionic PD traits (t=-2.057, p=0.040). Structured interviews for PD diagnoses further indicated a higher comorbidity of schizotypal (χ2=4.805, p=0.028) and schizoid (χ2=6.957, p=0.008) PDs among male patients compared to female patients. Additionally, male patients reported a higher degree (t=2.957, p=0.003) and proportion (χ2=5.277, p=0.022) of experiences of physical abuse in their self-reported CM. Logistic regression analyses highlight distinct factors: higher antisocial PD traits and physical abuse are associated with male patients, while histrionic PD traits and emotional abuse are associated with female patients. Discussion: These findings underscore the importance of recognizing and addressing sex-specific manifestations of personality pathology and the nuanced impact of CM in the clinical management of individuals with SZ. The study advocates for tailored interventions that consider the distinct needs associated with sex differences in both personality traits and CM experiences among SZ patients.

Recurrent retroperitoneal liposarcoma with multiple surgeries: a case report.

Retroperitoneal liposarcoma (RPLPS) is a rare malignant tumor that is typically treated with surgical resection. However, RPLPS often has a high rate of local recurrence, making it crucial to explore new treatment options. In this report, we present the case of a middle-aged woman who experienced seven recurrences and underwent seven surgeries following the initial resection. Currently, the patient's condition remains stable after the eighth surgery. Although there have been numerous reports of RPLPS cases both domestically and internationally, instances of repeated recurrence like this are exceptionally rare. Therefore, we have gathered the patient's case data and conducted a retrospective analysis, incorporating relevant literature, to enhance the understanding of this disease among clinical practitioners.

Advancements and Future Directions in Prevention Based on Evaluation for Individuals With Clinical High Risk of Psychosis: Insights From the SHARP Study.

BACKGROUND AND HYPOTHESIS: This review examines the evolution and future prospects of prevention based on evaluation (PBE) for individuals at clinical high risk (CHR) of psychosis, drawing insights from the SHARP (Shanghai At Risk for Psychosis) study. It aims to assess the effectiveness of non-pharmacological interventions in preventing psychosis onset among CHR individuals. STUDY DESIGN: The review provides an overview of the developmental history of the SHARP study and its contributions to understanding the needs of CHR individuals. It explores the limitations of traditional antipsychotic approaches and introduces PBE as a promising framework for intervention. STUDY RESULTS: Three key interventions implemented by the SHARP team are discussed: nutritional supplementation based on niacin skin response blunting, precision transcranial magnetic stimulation targeting cognitive and brain functional abnormalities, and cognitive behavioral therapy for psychotic symptoms addressing symptomatology and impaired insight characteristics. Each intervention is evaluated within the context of PBE, emphasizing the potential for tailored approaches to CHR individuals. CONCLUSIONS: The review highlights the strengths and clinical applications of the discussed interventions, underscoring their potential to revolutionize preventive care for CHR individuals. It also provides insights into future directions for PBE in CHR populations, including efforts to expand evaluation techniques and enhance precision in interventions.

Association between serum cytokines and timeframe for conversion from clinical high-risk to psychosis.

AIM: Although many studies have explored the link between inflammatory markers and psychosis, there is a paucity of research investigating the temporal progression in individuals at clinical high-risk (CHR) who eventually develop full psychosis. To address this gap, we investigated the correlation between serum cytokine levels and Timeframe for Conversion to Psychosis (TCP) in individuals with CHR. METHODS: We enrolled 53 individuals with CHR who completed a 5-year follow-up with a confirmed conversion to psychosis. Granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-1ß, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) levels were measured at baseline and 1-year. Correlation and quantile regression analyses were performed. RESULTS: The median TCP duration was 14 months. A significantly shorter TCP was associated with higher levels of TNF-α (P = 0.022) and VEGF (P = 0.016). A negative correlation was observed between TCP and TNF-α level (P = 0.006) and VEGF level (P = 0.04). Quantile regression indicated negative associations between TCP and GM-CSF levels below the 0.5 quantile, IL-10 levels below the 0.3 quantile, IL-2 levels below the 0.25 quantile, IL-6 levels between the 0.65 and 0.75 quantiles, TNF-α levels below the 0.8 quantile, and VEGF levels below the 0.7 quantile. A mixed linear effects model identified significant time effects for IL-10 and IL-2, and significant group effects for changes in IL-2 and TNF-α. CONCLUSIONS: Our findings underscore that a more pronounced baseline inflammatory state is associated with faster progression of psychosis in individuals with CHR. This highlights the importance of considering individual inflammatory profiles during early intervention and of tailoring preventive measures for risk profiles.

Childhood maltreatment and personality disorders in adolescents and adults with psychotic or non-psychotic disorders.

Introduction: While the attention to personality disorders (PD) and childhood maltreatment (CM) has grown in recent years, there remains limited understanding of the prevalence and distinctions of PD and CM in clinical populations of Chinese adolescents in comparison to adults. Methods: A total of 1,417 participants were consecutively sampled from patients diagnosed with either psychotic or non-psychotic disorders in the psychiatric and psycho-counseling clinics at Shanghai Mental Health Center. The participants were categorized into two groups based on their age: adolescents (aged 15-21 years) and adults (aged 22-35 years). PDs were evaluated using a self-reported personality diagnostic questionnaire and a structured clinical interview, while CMs were assessed using the Chinese version of the Child Trauma Questionnaire Short Form. Results: When comparing self-reported PD traits and CM between adolescents and adults, differences emerge. Adolescents, particularly in the psychotic disorder group, exhibit more pronounced schizotypal PD traits (p=0.029), and this pattern extends to non-psychotic disorders (p<0.001). Adolescents in the non-psychotic disorder group also report higher levels of emotional abuse (p=0.014), with a notable trend in physical abuse experiences compared to adults (p=0.057). Furthermore, the most prevalent PDs in the clinical sample are avoidant, borderline, and obsessive-compulsive PDs. Among patients with psychotic disorders, adolescents exhibit higher rates of schizoid, schizotypal, and obsessive-compulsive PDs compared to adults. Logistic regression analyses highlight distinct predictors for psychotic and non-psychotic disorders in adolescents and adults. Discussion: The findings emphasize distinct differences in PDs and CMs between adolescent and adult groups, shedding light on their potential roles in psychotic and non-psychotic disorders.

Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation treatment for adolescent and adult Tlymphoblastic leukemia /lymphoma: a large cohort multicenter study in China.

T lymphoblastic leukemia /lymphoma (T-ALL/LBL) is a rare and highly aggressive neoplasm of lymphoblasts. We evaluated 195 T-ALL/LBL adolescent and adult patients who received ALL-type chemotherapy alone (chemo,n = 72) or in combination with autologous hematopoietic stem cell transplantation(auto-HSCT,n = 23) or allogeneic hematopoietic stem cell transplantation(allo-HSCT,n = 100) from January 2006 to September 2020 in three Chinese medical centers. 167 (85.6%) patients achieved overall response (ORR) with 138 complete response (CR) patients (70.8%) and 29 partial response (PR) patients (14.8%). Until October 1, 2023, no difference was found in 5-year overall survival (5-OS) and 5-year progression free survival(5-PFS) between allo-HSCT and auto-HSCT (5-OS 57.9% vs. 36.7%, P = 0.139, 5-year PFS 49.4% vs. 28.6%, P = 0.078) for patients who achieved CR, for patients who achieved PR, allo-HSCT recipients had higher 5-OS compared with chemo alone recipients (5-OS 23.8% vs. 0, P = 0.042). For patients undergoing allo-HSCT, minimal residual disease (MRD) negative population showed better 5-OS survival compared with MRD positive patients (67.8% vs. 19.6%, p = 0.000). There were no significant differences between early T-cell precursor (ETP), NON-ETP patients with or without expression of one or more myeloid-associated or stem cell-associated (M/S+) markers (NON-ETP with M/S+, NON-ETP without M/S+) groups in allo-HSCT population for 5-OS. (62.9% vs. 54.5% vs.48.4%, P > 0.05). Notch mutations were more common in patients with non-relapsed/refractory disease than relapsed/refractory disease (χ² =4.293, P = 0.038). In conclusion, Allo-HSCT could be an effective consolidation therapy not just for patients with CR, but also for those who achieved PR. The prognosis is significantly improved by obtaining MRD negative prior to allogeneic transplantation.

Repetitive transcranial magnetic stimulation can improve negative symptoms and/or neurocognitive impairments in the first psychosis episode: A randomized controlled trial.

OBJECTIVE: Negative symptoms and neurocognitive impairments in psychosis correlate with their severity. Currently, there is no satisfactory treatment. We aimed to evaluate and compare the effects of repetitive transcranial magnetic stimulation(rTMS) on negative symptoms and neurocognitive impairments in patients in first-episode of psychosis(FEP) in a randomized controlled trial(RCT). METHOD: This is a single-site RCT of 85 patients with FEP. Patients were randomized to receive a 4-week course of active(n = 45) or sham rTMS(n = 40). Factor analysis was applied to a cross-sectional dataset of 744 FEP patients who completed negative symptom evaluation and neurocognitive battery tests. Two independent dimensions were generated and used for the K-means cluster analysis to produce sub-clusters. rTMS of 1-Hz was delivered to the right orbitofrontal(OFC) cortex. RESULTS: Two distinct dimensional factors of neurocognitive functions(factor-1) and negative symptoms(factor-2), and three clusters with distinctive features were generated. Significant improvements in factor-1 and factor-2 were observed after 4-weeks of rTMS treatment in both the active and sham rTMS groups. The repeated-measures analysis of variance revealed a significant effect of time×group(F = 5.594, p = 0.021, η2 = 0.073) on factor-2, but no effect of time×group on factor-1. Only improvements in negative symptoms were significantly different between the active and sham rTMS groups(p = 0.028). Patients in cluster-3 characterized by extensive negative symptoms, showed greater improvement in the active rTMS group than in the sham rTMS group. CONCLUSIONS: The 1-Hz right OFC cortex rTMS is more effective in reducing negative symptoms than neurocognitive impairments. It is especially effective in patients with dominantly negative symptoms in FEP.

[A Real-World Single-Center Study of Adult Hodgkin's Lymphoma].

OBJECTIVE: To summarize the clinical characteristics, therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma (HL). METHODS: A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled, and their clinical data, including sex, age, pathological type, Ann Arbor stage, ECOG score, blood test, ß2-microglobulin, lactate dehydrogenase level, albumin level were collected. The clinical characteristics, therapeutic effect and long-term prognosis of the patients were summarized and analyzed. RESULTS: In classical HL, nodular sclerosis HL accounted for the highest proportion of 51.6%, followed by mixed cellularity HL (36.5%), lymphocyte-rich classical HL (3.2%), and lymphocyte depletion HL (0.7%), while nodular lymphocyte predominant HL accounted for 4.8%. The 3-year overall survival (OS) rate of HL patients was 89.8%, and 5-year OS was 85.0%. The 3-year progression-free survival (PFS) rate was 73.4%, and 5-year PFS was 63.1%. Multivariate regression analysis indicated that IPI score was an independent negative factor, while hemoglobin (Hb) level was an independent positive factor for OS in HL patients. When the mediastinal mass size was 9.2 cm, it was most significant to judge the survival status of HL patients. 5-year OS and 5-year PFS were 97.4% and 76.0% in early-stage HL patients without large mass, respectively, while in patients with advanced-stage HL was 83.4% and 55.9% (both P < 0.05). After 2-4 courses of treatment, the overall response rate (ORR) of patients who received chemotherapy combined with radiotherapy was 95.0%, while that was 89.6% in those with chemotherapy alone. CONCLUSIONS: The overall prognosis of patients with HL is satisfactory, especially those in early-stage without large mass. IPI score and Hb level are independent risk factors for the prognosis of HL patients. A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.

Gut bacteria-driven homovanillic acid alleviates depression by modulating synaptic integrity.

The gut-brain axis is implicated in depression development, yet its underlying mechanism remains unclear. We observed depleted gut bacterial species, including Bifidobacterium longum and Roseburia intestinalis, and the neurotransmitter homovanillic acid (HVA) in individuals with depression and mouse depression models. Although R. intestinalis does not directly produce HVA, it enhances B. longum abundance, leading to HVA generation. This highlights a synergistic interaction among gut microbiota in regulating intestinal neurotransmitter production. Administering HVA, B. longum, or R. intestinalis to mouse models with chronic unpredictable mild stress (CUMS) and corticosterone (CORT)-induced depression significantly improved depressive symptoms. Mechanistically, HVA inhibited synaptic autophagic death by preventing excessive degradation of microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1/p62 proteins, protecting hippocampal neurons' presynaptic membrane. These findings underscore the role of the gut microbial metabolism in modulating synaptic integrity and provide insights into potential novel treatment strategies for depression.

Correlative relationship between body mass index and heart rate variability in psychiatric disorders.

OBJECTIVE: Indicators of heart rate variability (HRV) have been used to assess the autonomic activity. However, the influence of obesity on HRV in these patients remains to be determined. This study aimed to examine how obesity (measured with the body mass index [BMI]) affects HRV and determine whether the effect varies among different psychiatric disorders. We recruited 3159 consecutive patients, including 1744 with schizophrenia, 966 with mood disorders, and 449 with anxiety disorders. Patients were divided into four groups based on BMI: underweight (< 18.5), normal weight (18.5-23.9), overweight (24-27.9), and obese (≥ 28). The cardiovascular status was assessed using several time- and frequency-based HRV indicators, measured via electrocardiogram signals recorded for 5 min. The mean BMI of the participants was 23.6 ± 4.0. The patients in the overweight and obese groups were 29.4% and 13.6% of the total, respectively. The HRV indicators were higher in underweight and normal-weight patients than in the overweight and obese ones. After stratification based on the psychiatric diagnosis, the patients with mood disorders showed lower HRV than those with schizophrenia or anxiety disorder in the normal-weight group. In contrast, in the overweight and obese groups the patients with mood disorders showed higher HRV than those with the other disorders. The HRV variables were significantly associated with BMI, and higher BMI was associated with higher heart rates and lower HRV. These results indicate that weight gain in psychiatric disorders is associated with an imbalance in autonomic nerve activity. However, the relationship between autonomic activity, weight gain, and psychiatric disorders warrants further investigation.