PI3K/AKT/mTOR and PD­1/CTLA­4/CD28 pathways as key targets of cancer immunotherapy (Review).

T cells play an important role in cancer, and energy metabolism can determine both the proliferation and differentiation of T cells. The inhibition of immune checkpoint molecules programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) are a promising cancer treatment. In recent years, research on CD28 has increased. Although numerous reports involve CD28 and its downstream PI3K/AKT/mTOR signaling mechanisms in T cell metabolism, they have not yet been elucidated. A literature search strategy was used for the databases PubMed, Scopus, Web of Science and Cochrane Library to ensure broad coverage of medical and scientific literature, using a combination of keywords including, but not limited to, 'lung cancer' and 'immunotherapy'. Therefore, the present study reviewed the interaction and clinical application of the PD-1/CTLA-4/CD28 and PI3K/AKT/mTOR pathways in T cells, aiming to provide a theoretical basis for immunotherapy in clinical cancer patients.

Wandering spleen combined with pedicle torsion and splenic infarction: a rare case report and literature review.

Wandering spleen (WS) concurrent with splenic pedicle torsion and infarction has been described rarely. We reported our experience in diagnosing and treating such a condition in a 16-year-old girl with acute abdominal pain. A plain CT scan showed the wandering of the spleen from the left upper quadrant. Contrast-enhanced CT indicated dilatation and distortion in the splenic vein, a counterclockwise "whirl sign" in the splenic pedicle, pancreatic tail torsion, and splenic infarction. The patient was diagnosed with WS combined with splenic pedicle torsion and splenic infarction and underwent splenectomy for treatment. She showed a satisfactory outcome during the follow-up. To enhance our understanding of it, we performed a comprehensive literature research to summarize the clinical manifestations, treatment options, and outcomes among adolescent patients.

Radiomics based on MRI to predict recurrent L4-5 disc herniation after percutaneous endoscopic lumbar discectomy.

BACKGROUND: In recent years, radiomics has been shown to be an effective tool for the diagnosis and prediction of diseases. Existing evidence suggests that imaging features play a key role in predicting the recurrence of lumbar disk herniation (rLDH). Thus, this study aimed to evaluate the risk of rLDH in patients undergoing percutaneous endoscopic lumbar discectomy (PELD) using radiomics to facilitate the development of more rational surgical and perioperative management strategies. METHOD: This was a retrospective case-control study involving 487 patients who underwent PELD at the L4/5 level. The rLDH and negative groups were matched using propensity score matching (PSM). A total of 1409 radiomic features were extracted from preoperative lumbar MRI images using intraclass correlation coefficient (ICC) analysis, t-test, and LASSO analysis. Afterward, 6 predictive models were constructed and evaluated using ROC curve analysis, AUC, specificity, sensitivity, confusion matrix, and 2 repeated 3-fold cross-validations. Lastly, the Shapley Additive Explanation (SHAP) analysis provided visual explanations for the models. RESULTS: Following screening and matching, 128 patients were included in both the recurrence and control groups. Moreover, 18 of the extracted radiomic features were selected for generating six models, which achieved an AUC of 0.551-0.859 for predicting rLDH. Among these models, SVM, RF, and XG Boost exhibited superior performances. Finally, cross-validation revealed that their accuracy was 0.674-0.791, 0.647-0.729, and 0.674-0.718. CONCLUSION: Radiomics based on MRI can be used to predict the risk of rLDH, offering more comprehensive guidance for perioperative treatment by extracting imaging information that cannot be visualized with the naked eye. Meanwhile, the accuracy and generalizability of the model can be improved in the future by incorporating more data and conducting multicenter studies.

Radiomics-based Support Vector Machine Distinguishes Molecular Events Driving Progression of Lung Adenocarcinoma.

INTRODUCTION: An increasing number of early-stage lung adenocarcinoma (LUAD) are detected as lung nodules. The radiological features related to LUAD progression remain further investigation. Exploration is required to bridge the gap between radiomics features and molecular characteristics of lung nodules. METHODS: Consensus clustering was applied to the radiomics features of 1,212 patients to establish stable clustering. Clusters were illustrated using clinicopathological and next-generation sequencing (NGS). A classifier was constructed to further investigate the molecular characteristic in patients with paired CT and RNA-seq data. RESULTS: Patients were clustered into 4 clusters. Cluster 1 was associated with a low consolidation-to-tumor ratio (CTR), pre-invasion, grade I disease and good prognosis. Clusters 2 and 3 showed increasing malignancy with higher CTR, higher pathological grade and poor prognosis. Cluster 2 possessed more spread through air spaces (STAS) and cluster 3 showed higher proportion of pleural invasion. Cluster 4 had similar clinicopathological features with cluster 1 except higher proportion of grade II disease. RNA-seq indicated that cluster 1 represented nodules with indolent growth and good differentiation, whereas cluster 4 showed progression in cell development but still had low proliferative activity. Nodules with high proliferation were classified into clusters 2 and 3. Additionally, the radiomics classifier distinguished cluster 2 as nodules harboring an activated immune environment, while cluster 3 represented nodules with a suppressive immune environment. Furthermore, gene signatures associated with the prognosis of early-stage LUAD were validated in external datasets. CONCLUSION: Radiomics features can manifest molecular events driving progression of lung adenocarcinoma. Our study provides a molecular insight into radiomics features and assists in the diagnosis and treatment of early stage LUAD.

Single-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response in nasopharyngeal carcinoma.

Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.

Prediction of non-dipper blood pressure pattern in Chinese patients with hypertension using a nomogram model.

Non-dipper blood pressure has been shown to affect cardiovascular outcomes and cognitive function in patients with hypertension. Although some studies have explored the influencing factors of non-dipper blood pressure, there is still relatively little research on constructing a prediction model. This study aimed to develop and validate a simple and practical nomogram prediction model and explore relevant elements that could affect the dipper blood pressure relationship in patients with hypertension. A convenient sampling method was used to select 356 inpatients with hypertension who visited the Affiliated Hospital of Jining Medical College from January 2022 to September 2022. All patients were randomly assigned to the training cohort (75%, n = 267) and the validation cohort (25%, n = 89). Univariate and multivariate logistic regression were utilized to identify influencing factors. The nomogram was developed and evaluated based on the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and decision curve analyses. The optimal cutoff values for the prevalence of dipper blood pressure were estimated. The nomogram was established using six variables, including age, sex, hemoglobin (Hb), estimated glomerular filtration rate (eGFR), ejection fraction (EF), and heart rate. The AUC was 0.860 in the training cohort. The cutoff values for optimally predicting the prevalence of dipper blood pressure were 41.50 years, 151.00 g/L, 117.53 mL/min/1.73 m2, 64.50%, and 75 beats per minute for age, Hb, eGFR, ejection fraction, and heart rate, respectively. In summary, our nomogram can be used as a simple, plausible, affordable, and widely implementable tool to predict the blood pressure pattern of Chinese patients with hypertension.

Resolving conflict and promoting coordination for an integrated old-age healthcare service system in China: GMCR-AHP based decision analysis approach.

China faces a healthcare challenge due to its aging population, necessitating an integrated old-age healthcare system considering multiple stakeholders' interests. Conflict and inequality may arise from varying stakeholder interests. This study develops a conflict resolution strategy for the coordination of stakeholders involved in the old-age healthcare service system, promoting harmonization and minimizing conflict to establish an equitable system meeting elderly needs. It contributes to a robust healthcare system for comprehensive, quality care. The focus of the study is to identify relevant stakeholders and decision-makers involved in developing an integrated old-age healthcare service system and explore a feasible solution through stakeholder analysis using the Mitchell score-based technique and stakeholder theory. Decision-makers' preferences are estimated using the Analytic Hierarchy Process (AHP). Solution strategies are developed through multiple stability concepts within the graph model for conflict resolution (GMCR). The conflict resolution analysis based on the integrated AHP-GMCR approach reveals that the development of an integrated old-age healthcare system is feasible by addressing potential conflicts among the stakeholders. Considering the current predicament of comprehensive medical services in China, governments should distribute authority, simplify procedures, and improve the insurance system. Furthermore, medical institutions should explore funding options, expand services, and enhance accessibility. Elderly individuals should prioritize healthy aging and seek suitable healthcare providers. Stakeholder participation is crucial for effective implementation. These recommendations enable China to advance integrated elderly care successfully, addressing challenges posed by the aging population.

Two nomograms constructed for predicting the efficacy and prognosis of advanced non­small cell lung cancer patients treated with anti­PD­1 inhibitors based on the absolute counts of lymphocyte subsets.

BACKGROUND: Patients treated with immune checkpoint inhibitors (ICIs) are at risk of considerable adverse events, and the ongoing struggle is to accurately identify the subset of patients who will benefit. Lymphocyte subsets play a pivotal role in the antitumor response, this study attempted to combine the absolute counts of lymphocyte subsets (ACLS) with the clinicopathological parameters to construct nomograms to accurately predict the prognosis of advanced non-small cell lung cancer (aNSCLC) patients treated with anti-PD-1 inhibitors. METHODS: This retrospective study included a training cohort (n = 200) and validation cohort (n = 100) with aNSCLC patients treated with anti-PD-1 inhibitors. Logistic and Cox regression were conducted to identify factors associated with efficacy and progression-free survival (PFS) respectively. Nomograms were built based on independent influencing factors, and assessed by the concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve. RESULT: In training cohort, lower baseline absolute counts of CD3+ (P < 0.001) and CD4+ (P < 0.001) were associated with for poorer efficacy. Hepatic metastases (P = 0.019) and lower baseline absolute counts of CD3+ (P < 0.001), CD4+ (P < 0.001), CD8+ (P < 0.001), and B cells (P = 0.042) were associated with shorter PFS. Two nomograms to predict efficacy at 6-week after treatment and PFS at 4-, 8- and 12-months were constructed, and validated in validation cohort. The area under the ROC curve (AUC-ROC) of nomogram to predict response was 0.908 in training cohort and 0.984 in validation cohort. The C-index of nomogram to predict PFS was 0.825 in training cohort and 0.832 in validation cohort. AUC-ROC illustrated the nomograms had excellent discriminative ability. Calibration curves showed a superior consistence between the nomogram predicted probability and actual observation. CONCLUSION: We constructed two nomogram based on ACLS to help clinicians screen of patients with possible benefit and make individualized treatment decisions by accurately predicting efficacy and PFS for advanced NSCLC patient treated with anti-PD-1 inhibitors.

The prevention effect of Limosilactobacillus reuteri on acute kidney injury by regulating gut microbiota.

Acute kidney injury (AKI) has considerably high morbidity and mortality but we do not have proper treatment for it. There is an urgent need to develop new prevention or treatment methods. Gut microbiota has a close connection with renal diseases and has become the new therapy target for AKI. In this study, we found the oral administration of the probiotic Limosilactobacillus reuteri had a prevention effect on the AKI induced by lipopolysaccharide (LPS). It reduced serum concentration of creatinine and urea nitrogen and protected the renal cells from necrosis and apoptosis. Meanwhile, L. reuteri improved the gut barrier function, which is destroyed in AKI, and modulated the gut microbiota and relevant metabolites. Compared with the LPS group, L. reuteri increased the proportion of Proteobacteria and reduced the proportion of Firmicutes, changing the overall structure of the gut microbiota. It also influenced the fecal metabolites and changed the metabolite pathways, such as tyrosine metabolism, pentose and glucuronate interconversions, galactose metabolism, purine metabolism, and insulin resistance. These results showed that L. reuteri is a potential therapy for AKI as it helps in sustaining the gut barrier integrity and modulating gut microbiota and related metabolites.

MRD dynamics during maintenance therapy in 259 patients with nontransplant eligible multiple myeloma.

This study explored the impact of different maintenance therapies on survival outcomes in patients with multiple myeloma (MM), focusing on changes in minimal residual disease (MRD) during maintenance. Conducted at a single center, this retrospective study included 259 newly diagnosed MM patients who did not undergo autologous stem cell transplantation (ASCT). The results indicated that patients receiving lenalidomide as maintenance therapy showed significantly better progression-free survival (PFS) and overall survival (OS) compared to those treated with bortezomib or no maintenance therapy. However, bortezomib proved more effective in high-risk MM cases. Patients who were MRD-negative prior to starting maintenance therapy had a better prognosis than MRD-positive patients. Notably, lenalidomide was the most effective regimen irrespective of MRD status. Patients maintaining or achieving MRD-negativity within the first year of lenalidomide treatment exhibited improved prognoses, confirming lenalidomide as the optimal maintenance choice.

A Novel Tetramethylpyrazine Chalcone Hybrid- HCTMPPK, as a Potential Anti-Lung Cancer Agent by Downregulating MELK.

Purpose: Lung adenocarcinoma currently ranks the leading causes of cancer-related mortality worldwide. Many anti-inflammation herbs, like tetramethylpyrazine, have shown their anti-tumor potentials. Here, we evaluated the role of a novel chalcone derivative of tetramethylpyrazine ((E) -1- (E) -1- (2-hydroxy-5-chlorophenyl) -3- (3,5,6-trimethylpyrazin-2-yl) -2-propen-1, HCTMPPK) in lung adenocarcinoma. Methods: The effects of HCTMPPK on cell proliferation, apoptosis, and invasion were investigated by in-vitro assays, including CCK-8, colony formation assay, flow cytometry, transwell assay, and wound-healing assay. The therapeutic potential of HCTMPPK in vivo was evaluated in xenograft mice. To figure out the target molecules of HCTMPPK, a network pharmacology approach and molecular docking studies were employed, and subsequent experiments were conducted to confirm these candidate molecules. Results: HCTMPPK effectively suppressed the proliferative activity and migration, as well as enhanced the apoptosis of A549 cells in a concentration-dependent manner. Consistent with this, tumor growth was inhibited by HCTMPPK significantly in vivo. Regarding the mechanisms, HCTMPPK down-regulated Bcl-2 and MMP-9 and up-regulating Bax and cleaved-caspase-3. Subsequently, we identified 601 overlapping DEGs from LUAD patients in TCGA and GEO database. Then, 15 hub genes were identified by PPI network and CytoHubba. Finally, MELK was verified to be the HCTMPPK targeted site, through the molecular docking studies and validation experiments. Conclusion: Overall, our study indicates HCTMPPK as a potential MELK inhibitor and may be a promising candidate for the therapy of lung cancer.

Upf2-Mediated Nonsense-Mediated Degradation Pathway Involved in Genetic Compensation of TrpA1 Knockout Mutant Silkworm (Bombyx mori).

Genetic mutations leading to premature termination codons are known to have detrimental effects. Using the Lepidoptera model insect, the silkworm (Bombyx mori), we explored the genetic compensatory response triggered by mutations with premature termination codons. Additionally, we delved into the molecular mechanisms associated with the nonsense-mediated mRNA degradation pathway. CRISPR/Cas9 technology was utilized to generate a homozygous bivoltine silkworm line BmTrpA1-/- with a premature termination. Transcript levels were assessed for the BmTrpA paralogs, BmPyrexia and BmPainless as well as for the essential factors Upf1, Upf2, and Upf3a involved in the nonsense-mediated mRNA degradation (NMD) pathway. Upf2 was specifically knocked down via RNA interference at the embryonic stage. The results comfirmed that the BmTrpA1 transcripts with a 2-base deletion generating a premature termination codon in the BmTrpA1-/- line. From day 6 of embryonic development, the mRNA levels of BmPyrexia, BmPainless, Upf1, and Upf2 were significantly elevated in the gene-edited line. Embryonic knockdown of Upf2 resulted in the suppression of the genetic compensation response in the mutant. As a result, the offspring silkworm eggs were able to hatch normally after 10 days of incubation, displaying a non-diapause phenotype. It was observed that a genetic compensation response does exist in BmTrpA1-/-B. mori. This study presents a novel discovery of the NMD-mediated genetic compensation response in B. mori. The findings offer new insights into understanding the genetic compensation response and exploring the gene functions in lepidopteran insects, such as silkworms.

Crosstalk Between Cell Death and Spinal Cord Injury: Neurology and Therapy.

Spinal cord injury (SCI) often leads to neurological dysfunction, and neuronal cell death is one of the main causes of neurological dysfunction. After SCI, in addition to necrosis, programmed cell death (PCD) occurs in nerve cells. At first, studies recognized only necrosis, apoptosis, and autophagy. In recent years, researchers have identified new forms of PCD, including pyroptosis, necroptosis, ferroptosis, and cuproptosis. Related studies have confirmed that all of these cell death modes are involved in various phases of SCI and affect the direction of the disease through different mechanisms and pathways. Furthermore, regulating neuronal cell death after SCI through various means has been proven to be beneficial for the recovery of neural function. In recent years, emerging therapies for SCI have also provided new potential methods to restore neural function. Thus, the relationship between SCI and cell death plays an important role in the occurrence and development of SCI. This review summarizes and generalizes the relevant research results on neuronal necrosis, apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis after SCI to provide a new understanding of neuronal cell death after SCI and to aid in the treatment of SCI.

Hyposalinity stress reduces mussel byssus secretion but does not cause detachment.

Environmental stressors such as salinity fluctuations can significantly impact the ecological dynamics of mussel beds. The present study evaluated the influence of hyposalinity stress on the detachment and survival of attached mussels by simulating a mussel farming model in a laboratory setting. Byssus production and mechanical properties of thread in response to varying salinity levels were assessed, and histological sections of the mussel foot were analyzed to identify the changes in the byssus secretory gland area. The results showed that hyposalinity stress (20 and 15 psu) led to a significant decrease in mussel byssus secretion, delayed initiation of new byssus production, and reduced plaque adhesion strength and breaking force of byssal threads compared to the control (30 psu) (p < 0.05). The complete suppression of byssal thread secretion in mussels under salinity conditions of 10 and 5 psu, leading to lethality, indicates the presence of a blockade in byssus secretion when mussels are subjected to significant physiological stressors. Histological analysis further demonstrated a decrease in the percentage of foot secretory gland areas in mussels exposed to low salinities. However, contrary to expectations, the study found that mussels did not exhibit marked detachment from ropes in response to the reduced salinity levels during one week of exposure. Hyposalinity stress exposure reduced the byssal secretion capacity and the mechanical properties of threads, which could be a cause for the detachment of suspension-cultured mussels. These results highlight the vulnerability of mussels to hyposalinity stress, which significantly affects their byssus mechanical performance.

Dual function of activated PPARγ by ligands on tumor growth and immunotherapy.

As one of the peroxisome-proliferator-activated receptors (PPARs) members, PPARγ is a ligand binding and activated nuclear hormone receptor, which is an important regulator in metabolism, proliferation, tumor progression, and immune response. Increased evidence suggests that activation of PPARγ in response to ligands inhibits multiple types of cancer proliferation, metastasis, and tumor growth and induces cell apoptosis including breast cancer, colon cancer, lung cancer, and bladder cancer. Conversely, some reports suggest that activation of PPARγ is associated with tumor growth. In addition to regulating tumor progression, PPARγ could promote or inhibit tumor immunotherapy by affecting macrophage differentiation or T cell activity. These controversial findings may be derived from cancer cell types, conditions, and ligands, since some ligands are independent of PPARγ activity. Therefore, this review discussed the dual role of PPARγ on tumor progression and immunotherapy.

Case report: Mutation evolution in a patient with TdT positive high grade B cell lymphoma with MYC and BCL2 rearrangements following the treatment of concurrent follicular lymphoma and diffuse large B-cell lymphoma.

BACKGROUND: Concurrent follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL)was reported in some studies, while the diagnosis of TdT (terminal deoxynucleotydil transferase) positive high grade B cell lymphoma (HGBL) with MYC and BCL2 rearrangements ("double hit") transformed from FL/DLBCL has been rarely reported. Herein, we described the clinical features and mutation profiles of a case diagnosed with TdT positive "double hit" HGBL following the treatment of FL/DLBCL. CASE PRESENTATION: This is a 43-year-old Chinese man who was diagnosed with low grade FL (account for 80%) combined with DLBCL (20%) at a stage of IVB. The patient presented with BCL2/IGH translocation without MYC rearrangement, as well as the expressions of CD20, CD19, CD10 and BCL2 at the initial diagnosis of FL/DLBCL. MYC rearrangement and TdT expression occurred after the treatment. The targeted sequencing revealed mutations in KMT2D, FOXO1, CREBBP, ATM, STAT6, BCL7A, DDX3X, MUC4, FGFR3, ARID5B, DDX11 and PRKCSH genes were the co-mutations shared by the FL/DLBCL and TdT positive "double hit" HGBL, while CCND3, BIRC6, ROBO1 and CHEK2 mutations specifically occurred after the treatment. The overall survival time was 37.8 and 17.8 months after the initial diagnosis of FL/DLBCL and TdT positive "double hit" HGBL, respectively. CONCLUSION: This study reports a rare case of TdT positive "double hit" HGBL following the treatment of concurrent FL/DLBCL and highlights the mutation characteristics. Collectively, this study will help enrich the knowledge of TdT positive "double hit" HGBL transformed from FL/DLBCL.

Diagnostic value of LGE and T1 mapping in multiple myeloma patients'heart.

BACKGROUND: Unidentified heart failure occurs in patients with multiple myeloma when their heart was involved. CMR with late gadolinium enhancement (LGE) and T1 mapping can identify myocardial amyloid infiltrations. PURPOSE: To explore the role of CMR with late gadolinium enhancement (LGE) and T1 mapping for detection of multiple myeloma patients'heart. MATERIAL AND METHODS: A total of 16 MM patients with above underwent CMR (3.0-T) with T1 mapping (pre-contrast and post-contrast) and LGE imaging. In addition, 26 patients with non-obstructive hypertrophic cardiomyopathy and 26 healthy volunteers were compared to age- and sex-matched healthy controls without a history of cardiac disease, diabetes mellitus, or normal in CMR. All statistical analyses were performed using the statistical software GraphPad Prism. The measurement data were represented by median (X) and single sample T test was adopted. Enumeration data were represented by examples and Chi-tested was adopted. All tests were two-sided, and P values < 0.05 were considered statistically significant. RESULTS: In MM group, LVEF was lower than healthy controls and higher than that of non-obstructive hypertrophic cardiomyopathy group, but without statistically significant difference (%: 49.1 ± 17.5 vs. 55.6 ± 10.3, 40.4 ± 15.6, all P > 0.05). Pre-contrast T1 values of MM group were obviously higher than those of healthy controls and non-obstructive hypertrophic cardiomyopathy group (ms:1462.0 ± 71.3vs. 1269.3 ± 42.3, 1324.0 ± 45.1, all P < 0.05). 16 cases (100%) in MM group all had LGE. CONCLUSION: LGE joint T1 mapping wider clinical use techniques and follow-up the patients'disease severity.

Behavioural and ERP evidence of a contrary effect between active and passive suppression of facial expressions.

There has been disagreement regarding the relationship among the three components (subjective experience, external performance, and physiological response) of emotional responses. To investigate this issue further, this study compared the effects of active and passive suppression of facial expressions on subjective experiences and event-related potentials (ERPs) through two experiments. The two methods of expression suppression produced opposite patterns of ERPs for negative emotional stimuli: compared with the free-viewing condition, active suppression of expression decreased, while passive suppression increased the amplitude of the late positive potential (LPP) when viewing negative emotional stimuli. Further, while active suppression had no effect on participants' emotional experience, passive suppression enhanced their emotional experience. Among the three components of emotional responses, facial expressions are more closely related to the physiological response of the brain than to subjective experience, and whether the suppression was initiated by participants determines the decrease or increase in physiological response of the brain (i.e. LPP). The findings revealed the important role of individual subjective initiative in modulating the relationship among the components of emotional response, which provides new insights into effectively emotional regulation.

An investigation into the abnormal dynamic connection mechanism of generalized anxiety disorders based on non-homogeneous Markov models.

BACKGROUND: The dynamic and hierarchical nature of the functional brain network. The neural dynamical systems tend to converge to multiple attractors (stable fixed points or dynamical states) in long run. Little is known about how the changes in this brain dynamic "long-term" behavior of the connectivity flow of brain network in generalized anxiety disorder (GAD). METHODS: This study recruited 92 patients with GAD and 77 healthy controls (HC). We applied a reachable probability approach combining a Non-homogeneous Markov model with transition probability to quantify all possible connectivity flows and the hierarchical structure of brain functional systems at the dynamic level and the stationary probability vector (10-step transition probabilities) to describe the steady state of the system in the long run. A random forest algorithm was conducted to predict the severity of anxiety. RESULTS: The dynamic functional patterns in distributed brain networks had larger possibility to converge in bilateral thalamus, posterior cingulate cortex (PCC), right superior occipital gyrus (SOG) and smaller possibility to converge in bilateral superior temporal gyrus (STG) and right parahippocampal gyrus (PHG) in patients with GAD compared to HC. The abnormal transition probability pattern could predict anxiety severity in patients with GAD. LIMITATIONS: Small samples and subjects taking medications may have influenced our results. Future studies are expected to rule out the potential confounding effects. CONCLUSION: Our results have revealed abnormal dynamic neural communication and integration in emotion regulation in patients with GAD, which give new insights to understand the dynamics of brain function of patients with GAD.

Frequency-dependent alterations of global signal topography in patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is associated not only with disorders in multiple brain networks but also with frequency-specific brain activities. The abnormality of spatiotemporal networks in patients with MDD remains largely unclear. METHODS: We investigated the alterations of the global spatiotemporal network in MDD patients using a large-sample multicenter resting-state functional magnetic resonance imaging dataset. The spatiotemporal characteristics were measured by the variability of global signal (GS) and its correlation with local signals (GSCORR) at multiple frequency bands. The association between these indicators and clinical scores was further assessed. RESULTS: The GS fluctuations were reduced in patients with MDD across the full frequency range (0-0.1852 Hz). The GSCORR was also reduced in the MDD group, especially in the relatively higher frequency range (0.0728-0.1852 Hz). Interestingly, these indicators showed positive correlations with depressive scores in the MDD group and relative negative correlations in the control group. CONCLUSION: The GS and its spatiotemporal effects on local signals were weakened in patients with MDD, which may impair inter-regional synchronization and related functions. Patients with severe depression may use the compensatory mechanism to make up for the functional impairments.