Convergent functional change of frontoparietal network in obsessive-compulsive disorder: a voxel-based meta-analysis.

Background: Obsessive-compulsive disorder (OCD) is a chronic psychiatric illness with complex clinical manifestations. Cognitive dysfunction may underlie OC symptoms. The frontoparietal network (FPN) is a key region involved in cognitive control. However, the findings of impaired FPN regions have been inconsistent. We employed meta-analysis to identify the fMRI-specific abnormalities of the FPN in OCD. Methods: PubMed, Web of Science, Scopus, and EBSCOhost were searched to screen resting-state functional magnetic resonance imaging (rs-fMRI) studies exploring dysfunction in the FPN of OCD patients using three indicators: the amplitude of low-frequency fluctuation/fractional amplitude of low-frequency fluctuation (ALFF/fALFF), regional homogeneity (ReHo) and functional connectivity (FC). We compared all patients with OCD and control group in a primary analysis, and divided the studies by medication in secondary meta-analyses with the activation likelihood estimation (ALE) algorithm. Results: A total of 31 eligible studies with 1359 OCD patients (756 men) and 1360 healthy controls (733 men) were included in the primary meta-analysis. We concluded specific changes in brain regions of FPN, mainly in the left dorsolateral prefrontal cortex (DLPFC, BA9), left inferior frontal gyrus (IFG, BA47), left superior temporal gyrus (STG, BA38), right posterior cingulate cortex (PCC, BA29), right inferior parietal lobule (IPL, BA40) and bilateral caudate. Additionally, altered connectivity within- and between-FPN were observed in the bilateral DLPFC, right cingulate gyrus and right thalamus. The secondary analyses showed improved convergence relative to the primary analysis. Conclusion: OCD patients showed dysfunction FPN, including impaired local important nodal brain regions and hypoconnectivity within the FPN (mainly in the bilateral DLPFC), during the resting state. Moreover, FPN appears to interact with the salience network (SN) and default mode network (DMN) through pivotal brain regions. Consistent with the hypothesis of fronto-striatal circuit dysfunction, especially in the dorsal cognitive circuit, these findings provide strong evidence for integrating two pathophysiological models of OCD.

Navigating the Evolving Landscape of Primary Hyperoxaluria: Traditional Management Defied by the Rise of Novel Molecular Drugs.

Primary hyperoxalurias (PHs) are inherited metabolic disorders marked by enzymatic cascade disruption, leading to excessive oxalate production that is subsequently excreted in the urine. Calcium oxalate deposition in the renal tubules and interstitium triggers renal injury, precipitating systemic oxalate build-up and subsequent secondary organ impairment. Recent explorations of novel therapeutic strategies have challenged and necessitated the reassessment of established management frameworks. The execution of diverse clinical trials across various medication classes has provided new insights and knowledge. With the evolution of PH treatments reaching a new milestone, prompt and accurate diagnosis is increasingly critical. Developing early, effective management and treatment plans is essential to improve the long-term quality of life for PH patients.

[18F]AlF-ND-bisFAPI PET imaging of fibroblast activation protein as a biomarker to monitor the progression of liver fibrosis.

BACKGROUND: Hepatic fibrosis is a progressive disease, which is reversible in the early stages. The current monitoring methods have notable limitations that pose a challenge to early detection. In this study, we evaluated the utility of [18F]AlF-ND-bisFAPI positron emission tomography imaging of fibroblast activation protein (FAP) to monitor the progression of liver fibrosis. METHODS: Two mouse models of liver fibrosis were established by bile duct ligation and carbon tetrachloride administration, respectively. Positron emission tomography imaging was performed with the FAP-specific radiotracer [18F]AlF-ND-bisFAPI for the evaluation of rat HSCs and mouse models of fibrosis and combined with histopathology, immunohistochemical staining, and immunoblotting to elucidate the relationships among radioactivity uptake, FAP levels, and liver fibrosis progression. Furthermore, [18F]AlF-ND-bisFAPI autoradiography was performed to assess tracer binding in liver sections from patients with varying degrees of liver fibrosis. RESULTS: Cell experiments demonstrated that [18F]AlF-ND-bisFAPI uptake was specific in activated HSCs. Compared with control mice, [18F]AlF-ND-bisFAPI uptake in livers increased in the early stages of fibrosis and increased significantly further with disease progression. Immunohistochemistry and western blot analyses demonstrated that FAP expression increased with fibrosis severity. In accordance with the findings in animal models, ex vivo autoradiography on human fibrotic liver sections showed that radioactivity increased as fibrosis progressed from mild to severe. CONCLUSIONS: [18F]AlF-ND-bisFAPI positron emission tomography imaging is a promising noninvasive method for monitoring the progression of liver fibrosis.

Comparison of Disease Severity, Anxiety and Depression in Obsessive-Compulsive Disorder Patients with Different Insight.

BACKGROUND: Significant individual differences exist in the insight of patients with obsessive-compulsive disorder (OCD), and the clinical characteristics of OCD patients with varying levels of insight are not entirely uniform. This study aims to investigate disparities in disease severity, anxiety, and depression status among OCD patients with differing levels of insight, with the goal of generating novel treatment strategies for OCD. METHODS: A total of 114 patients diagnosed with OCD were recruited from the Department of Psychology at Affiliated Mental Health Center & Hangzhou Seventh People's Hospital to participate in this research. Based on their Total Insight and Treatment Attitude Questionnaire (ITAQ) scores, the patients were divided into two groups: Group OCD with high insight (referred to as Group OCD-HI, ITAQ score ≥20 points, n = 80) and Group OCD with low insight (referred to as Group OCD-LI, ITAQ score <20 points, n = 34). Subsequently, the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) scores were compared between the two groups. All questionnaires for this study were completed by experienced psychiatrists. RESULTS: The Y-BOCS scores for YB1, YB2, YB4, YB5, YB6, YB9, and the total Y-BOCS scores in Group OCD-HI were significantly higher than those in Group OCD-LI (p < 0.05). Conversely, Group OCD-HI exhibited significantly lower HAMA and HAMD scores compared to Group OCD-LI (p < 0.05). Furthermore, the total ITAQ score displayed a significant negative correlation with the total Y-BOCS, HAMA, and HAMD scores (p < 0.05). CONCLUSIONS: This study revealed that certain OCD patients exhibit incomplete insight, and this lack of insight is strongly associated with increased disease severity and heightened levels of anxiety and depression. It is hoped that by enhancing the insight of OCD patients, the goal of ameliorating disease symptoms and alleviating negative emotions can be attained.

A case report of fatal familial insomnia with cerebrospinal fluid leukocytosis during the COVID-19 epidemic and review of the literature.

Fatal familial insomnia (FFI) is a rare autosomal dominant genetic neurodegenerative disease. Generally, FFI patients will develop rapidly progressive dementia, sleep disturbance, autonomic dysfunction, and so on. Cerebrospinal fluid examination of FFI patients normally shows no obvious abnormalities. Here, we report a young male patient who was diagnosed with FFI during the COVID-19 epidemic. Clinical symptoms include psychobehavioral abnormality, cognitive decline, sleep disturbance, and autonomic dysfunction. No abnormalities were found in routine examinations after admission. However, the number of white blood cells in the cerebrospinal fluid increased. Though the patient was treated with anti-infection and immunotherapy, the symptoms were not relieved. A lumbar puncture was performed again, and it was found that the total Tau protein in the cerebrospinal fluid was elevated, and PET results showed that brain metabolism decreased. Finally, a genetic test was used to confirm the diagnosis of FFI. This case suggests that patients with FFI may also have elevated white blood cells in cerebrospinal fluid and timely detection of Tau protein in cerebrospinal fluid is helpful for early identification of FFI. And precise diagnosis relies on genetic testing.

Gastric and cardiac inflammatory myofibroblastic tumor: an extremely rare case.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a unique, rarely metastatic tumor composed of myofibroblasts and fibrous spindle cells with inflammatory cell infiltration that can affect any organ in the human body. By reviewing the relevant literature on PubMed, we found that this is the first case report of IMT with both gastric and cardiac involvement. CASE PRESENTATION: A 57-year-old male patient was admitted to the hospital with complaints of malaise, poor appetite, and epigastric pain with black stools. We found a mass in the patient's stomach and left atrium by contrast-enhanced computed tomography, 18 F-fluorodeoxyglucose positron emission tomography/computed tomography, and other tests. The patient underwent laparoscopic Billroth II subtotal gastrectomy and Braun's gastrointestinal reconstruction under general anesthesia. On the 46th day following stomach surgery, the cardiac tumor was removed under general anesthesia. The patient has treated with doxorubicin 70 mg of D1 chemotherapy two months after cardiac surgery. Postoperative pathological immunohistochemistry of the mass confirmed the diagnosis of an IMT. His review three months after the cardiac surgery suggested the progression of the left atrial mass, but he declined further treatment and finally died one month after the review. CONCLUSIONS: As a unique class of tumors that rarely metastasize, IMTs have an unknown etiology and pathogenesis, and distant metastasis is primarily observed in patients with negative activin receptor-like kinase (ALK) expression. The preferred treatment for IMT is complete surgical resection, and the effectiveness of adjuvant therapy for patients with distant metastases is still being determined. The clinical presentation of IMT lacks specificity and is often related to the location of tumor growth, which poses a diagnostic challenge. Pathological immunohistochemistry is the only way to confirm the diagnosis at present. Our case report reminds clinicians that a category of ALK-negative IMT with a tendency toward distant metastasis should not be ignored.

Comparison of Disease Severity, Anxiety and Depression in Obsessive-Compulsive Disorder Patients with Different Insight

Background: Significant individual differences exist in the insight of patients with obsessive-compulsive disorder (OCD), and the clinical characteristics of OCD patients with varying levels of insight are not entirely uniform. This study aims to investigate disparities in disease severity, anxiety, and depression status among OCD patients with differing levels of insight, with the goal of generating novel treatment strategies for OCD.Methods: A total of 114 patients diagnosed with OCD were recruited from the Department of Psychology at Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital to participate in this research. Based on their Total Insight and Treatment Attitude Questionnaire (ITAQ) scores, the patients were divided into two groups: Group OCD with high insight (referred to as Group OCD-HI, ITAQ score ≥20 points, n = 80) and Group OCD with low insight (referred to as Group OCD-LI, ITAQ score <20 points, n = 34). Subsequently, the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) scores were compared between the two groups. All questionnaires for this study were completed by experienced psychiatrists. Results: The Y-BOCS scores for YB1, YB2, YB4, YB5, YB6, YB9, and the total Y-BOCS scores in Group OCD-HI were significantly higher than those in Group OCD-LI (p < 0.05). Conversely, Group OCD-HI exhibited significantly lower HAMA and HAMD scores compared to Group OCD-LI (p < 0.05). Furthermore, the total ITAQ score displayed a significant negative correlation with the total Y-BOCS, HAMA, and HAMD scores (p < 0.05). Conclusions: This study revealed that certain OCD patients exhibit incomplete insight, and this lack of insight is strongly associated with increased disease severity and heightened levels of anxiety and depression. ... (AU)

177Lu-Labeled Bivalent Ligands of Prostate-Specific Membrane Antigen for Endoradiotherapy of Prostate Cancer.

Recently, we developed a bivalent prostate-specific membrane antigen (PSMA) radioligand ([18F]AlF-Bi-PSMA), which showed higher tumor uptake and retention in PSMA-positive mouse models than the clinically used radioligands, [68Ga]Ga-PSMA-11 and [18F]PSMA-1007. Here, we developed two 177Lu-labeled bivalent PSMA ligands with (DOTA-Alb-Bi-PSMA) or without an albumin-binding motif (DOTA-Bi-PSMA) to enhance radiotherapeutic efficacy with minimal toxicity. The results demonstrated that both 177Lu-labeled bivalent radioligands showed good stability, high binding affinity, and PSMA-targeting specificity in vitro. Compared with [177Lu]Lu-PSMA-617, both [177Lu]Lu-Bi-PSMA and [177Lu]Lu-Alb-Bi-PSMA showed a higher area under the curve (AUC) of tumor accumulation and superior therapeutic efficacy. However, [177Lu]Lu-Alb-Bi-PSMA exhibited a dose-dependent increase in acute damage to kidneys. In terms of the radionuclide therapy efficacy and side effects, [177Lu]Lu-Bi-PSMA exhibited well-balanced action with high tumor-to-organs AUC ratios, resulting in remarkable therapeutic efficacy and negligible side effects. These promising results warrant further investigations to achieve the clinical translation of [177Lu]Lu-Bi-PSMA.

Exploring structural and functional alterations in drug-naïve obsessive-compulsive disorder patients: An ultrahigh field multimodal MRI study.

BACKGROUND: Brain structural and functional alterations have been reported in obsessive-compulsive disorder (OCD) patients; however, these findings were inconsistent across studies due to several limitations, including small sample sizes, different inclusion/exclusion criteria, varied demographic characteristics and symptom dimensions, comorbidity, and medication status. Prominent and replicable neuroimaging biomarkers remain to be discovered. METHODS: This study explored the gray matter structure, neural activity, and white matter microstructure differences in 40 drug-naïve OCD patients and 57 matched healthy controls using ultrahigh field 7.0 T multimodal magnetic resonance imaging, which increased the spatial resolution and detection power. We also evaluated correlations among different modalities, imaging features and clinical symptoms. RESULTS: Drug-naïve OCD patients exhibited significantly increased gray matter volume in the frontal cortex, especially in the orbitofrontal cortex, as well as volumetric reduction in the temporal lobe, occipital lobe and cerebellum. Increased neural activities were observed in the cingulate gyri and precuneus. Increased temporal-middle cingulate and posterior cingulate-precuneus functional connectivities and decreased frontal-middle cingulate connectivity were further detected. Decreased fractional anisotropy values were found in the cingulum-hippocampus gyrus and inferior fronto-occipital fascicle in OCD patients. Moreover, significantly altered imaging features were related to OCD symptom severity. Altered functional and structural neural connectivity might influence compulsive and obsessive features, respectively. CONCLUSIONS: Altered structure and function of the classical cortico-striato-thalamo-cortical circuit, limbic system, default mode network, visual, language and sensorimotor networks play important roles in the neurophysiology of OCD.

A continuous learning approach to brain tumor segmentation: integrating multi-scale spatial distillation and pseudo-labeling strategies.

Introduction: This study presents a novel continuous learning framework tailored for brain tumour segmentation, addressing a critical step in both diagnosis and treatment planning. This framework addresses common challenges in brain tumour segmentation, such as computational complexity, limited generalisability, and the extensive need for manual annotation. Methods: Our approach uniquely combines multi-scale spatial distillation with pseudo-labelling strategies, exploiting the coordinated capabilities of the ResNet18 and DeepLabV3+ network architectures. This integration enhances feature extraction and efficiently manages model size, promoting accurate and fast segmentation. To mitigate the problem of catastrophic forgetting during model training, our methodology incorporates a multi-scale spatial distillation scheme. This scheme is essential for maintaining model diversity and preserving knowledge from previous training phases. In addition, a confidence-based pseudo-labelling technique is employed, allowing the model to self-improve based on its predictions and ensuring a balanced treatment of data categories. Results: The effectiveness of our framework has been evaluated on three publicly available datasets (BraTS2019, BraTS2020, BraTS2021) and one proprietary dataset (BraTS_FAHZU) using performance metrics such as Dice coefficient, sensitivity, specificity and Hausdorff95 distance. The results consistently show competitive performance against other state-of-the-art segmentation techniques, demonstrating improved accuracy and efficiency. Discussion: This advance has significant implications for the field of medical image segmentation. Our code is freely available at https://github.com/smallboy-code/A-brain-tumor-segmentation-frameworkusing-continual-learning.

Insight in obsessive-compulsive disorder: conception, clinical characteristics, neuroimaging, and treatment.

Obsessive-compulsive disorder (OCD) is a chronic disabling disease with often unsatisfactory therapeutic outcomes. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) has broadened the diagnostic criteria for OCD, acknowledging that some OCD patients may lack insight into their symptoms. Previous studies have demonstrated that insight can impact therapeutic efficacy and prognosis, underscoring its importance in the treatment of mental disorders, including OCD. In recent years, there has been a growing interest in understanding the influence of insight on mental disorders, leading to advancements in related research. However, to the best of our knowledge, there is dearth of comprehensive reviews on the topic of insight in OCD. In this review article, we aim to fill this gap by providing a concise overview of the concept of insight and its multifaceted role in clinical characteristics, neuroimaging mechanisms, and treatment for OCD.

An Exploratory Study of a Novel Combined Therapeutic Modality for Obsessive-Compulsive Disorder.

OBJECTIVE: To explore whether a systematic combined therapeutic modality (CTM) could quickly and effectively improve the severity of obsessive-compulsive disorder (OCD) and the insight of OCD patients. METHODS: Included in this study were 100 patients with OCD according to the 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), for a 2-week short-term treatment. They were assigned to a drug-alone group (n = 57), and a CTM group (n = 43) using drug treatment in combination with cognitive behavioral treatment (CBT) and repetitive transcranial magnetic stimulation (rTMS). The therapeutic outcome was assessed by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Brown Assessment of Beliefs Scale (BABS), 24-item Hamilton Depression Scale (HAMD-24) and Hamilton Anxiety Scale (HAMA) before and after treatment. All data were treated with SPSS25.0 Software. RESULTS: After the 2-week treatment, the success rate in the CTM group was significantly higher than that in the drug-alone group. Y-BOCS overall and factor scores were decreased as compared with those before treatment in both groups. HAMD, HAMA and BABS overall scores were all decreased after treatment in the CTM group. In addition, compared with the drug-alone group, the Y-BOCS overall score and factor score, HAMD overall score and HAMA overall score were all decreased significantly in CTM group, while the Y-BOCS score reduction rate was increased significantly. Insight was improved in eight cases (57.14%) in the CTM group containing 14 cases with poor insight. Multinomial logistic regression analysis showed that CTM was beneficial for the insight improvement of OCD patients (OR = 91.04-139.68); this improvement was more pronounced in patients with low baseline BABS overall scores (OR = 0.07). CONCLUSION: CTM may be an effective short-term strategy to improve the severity of OCD and insight of OCD patients and, therefore, is worthy of clinical promotion and application.

3D FRN-ResNet: An Automated Major Depressive Disorder Structural Magnetic Resonance Imaging Data Identification Framework.

Major Depressive Disorder (MDD) is the most prevalent psychiatric disorder, seriously affecting people's quality of life. Manually identifying MDD from structural magnetic resonance imaging (sMRI) images is laborious and time-consuming due to the lack of clear physiological indicators. With the development of deep learning, many automated identification methods have been developed, but most of them stay in 2D images, resulting in poor performance. In addition, the heterogeneity of MDD also results in slightly different changes reflected in patients' brain imaging, which constitutes a barrier to the study of MDD identification based on brain sMRI images. We propose an automated MDD identification framework in sMRI data (3D FRN-ResNet) to comprehensively address these challenges, which uses 3D-ResNet to extract features and reconstruct them based on feature maps. Notably, the 3D FRN-ResNet fully exploits the interlayer structure information in 3D sMRI data and preserves most of the spatial details as well as the location information when converting the extracted features into vectors. Furthermore, our model solves the feature map reconstruction problem in closed form to produce a straightforward and efficient classifier and dramatically improves model performance. We evaluate our framework on a private brain sMRI dataset of MDD patients. Experimental results show that the proposed model exhibits promising performance and outperforms the typical other methods, achieving the accuracy, recall, precision, and F1 values of 0.86776, 0.84237, 0.85333, and 0.84781, respectively.

Inhaled curcumin mesoporous polydopamine nanoparticles against radiation pneumonitis.

Radiation therapy is an effective method to kill cancer cells and shrink tumors using high-energy X-ray or γ-ray. Radiation pneumonitis (RP) is one of the most serious complications of radiation therapy for thoracic cancers, commonly leading to serious respiratory distress and poor prognosis. Here, we prepared curcumin-loaded mesoporous polydopamine nanoparticles (CMPN) for prevention and treatment of RP by pulmonary delivery. Mesoporous polydopamine nanoparticles (MPDA) were successfully synthesized with an emulsion-induced interface polymerization method and curcumin was loaded in MPDA via π‒π stacking and hydrogen bonding interaction. MPDA owned the uniform spherical morphology with numerous mesopores that disappeared after loading curcumin. More than 80% curcumin released from CMPN in 6 h and mesopores recovered. CMPN remarkably protected BEAS-2B cells from γ-ray radiation injury by inhibiting apoptosis. RP rat models were established after a single dose of 15 Gy 60Co γ-ray radiation was performed on the chest area. Effective therapy of RP was achieved by intratracheal administration of CMPN due to free radical scavenging and anti-oxidation ability, and reduced proinflammatory cytokines, high superoxide dismutase, decreased malondialdehyde, and alleviated lung tissue damages were observed. Inhaled CMPN paves a new avenue for the treatment of RP.

Chemo-photothermal immunotherapy for eradication of orthotopic tumors and inhibition of metastasis by intratumoral injection of polydopamine versatile hydrogels.

Cancer remains one of the leading causes of death globally and metastasis always leads to treatment failure. Here, we develop a versatile hydrogel loading photothermal agents, chemotherapeutics, and immune-adjuvants to eradicate orthotopic tumors and inhibit metastasis by combinational therapy. Hydrogel networks were synthesized via the thiol-Michael addition of polydopamine (PDA) with thiolated hyaluronic acid. PDA acted as a cross-linking agent and endowed the hydrogel with excellent photothermal property. Meanwhile, a chemotherapeutic agent, doxorubicin (DOX), was loaded in the hydrogel via π‒π stacking with PDA and an immune-adjuvant, CpG-ODN, was loaded via electrostatic interaction. The release of DOX from the hydrogel was initially slow but accelerated due to near infrared light irradiation. The hydrogels showed remarkably synergistic effect against 4T1 cancer cells and stimulated plenty of cytokines secreting from RAW264.7 cells. Moreover, the hydrogels eradicated orthotopic murine breast cancer xenografts and strongly inhibited metastasis after intratumoral injection and light irradiation. The high anticancer efficiency of this chemo-photothermal immunotherapy resulted from the strong synergistic effect of the versatile hydrogels, including the evoked host immune response. The combinational strategy of chemo-photothermal immunotherapy is promising for highly effective treatment of breast cancer.

Divergent and Convergent Imaging Markers Between Bipolar and Unipolar Depression Based on Machine Learning.

Distinguishing bipolar depression (BD) from unipolar depression (UD) based on symptoms only is challenging. Brain functional connectivity (FC), especially dynamic FC, has emerged as a promising approach to identify possible imaging markers for differentiating BD from UD. However, most of such studies utilized conventional FC and group-level statistical comparisons, which may not be sensitive enough to quantify subtle changes in the FC dynamics between BD and UD. In this paper, we present a more effective individualized differentiation model based on machine learning and the whole-brain "high-order functional connectivity (HOFC)" network. The HOFC, capturing temporal synchronization among the dynamic FC time series, a more complex "chronnectome" metric compared to the conventional FC, was used to classify 52 BD, 73 UD, and 76 healthycontrols (HC). We achieved a satisfactory accuracy (70.40%) in BD vs. UD differentiation. The resultant contributing features revealed the involvement of the coordinated flexible interactions among sensory (e.g., olfaction, vision, and audition), motor, and cognitive systems. Despite sharing common chronnectome of cognitive and affective impairments, BD and UD also demonstrated unique dynamic FC synchronization patterns. UD is more associated with abnormal visual-somatomotor inter-network connections, while BD is more related to impaired ventral attention-frontoparietal inter-network connections. Moreover, we found that the illness duration modulated the BD vs. UD separation, with the differentiation performance hampered by the secondary disease effects. Our findings suggest that BD and UD may have divergent and convergent neural substrates, which further expand our knowledge of the two different mental disorders.

Pulmonary delivery of resveratrol-ß-cyclodextrin inclusion complexes for the prevention of zinc chloride smoke-induced acute lung injury.

Smoke bombs are often used in military/fire training, which can produce a large amount of zinc chloride (ZnCl2) smoke. Inhalation of ZnCl2 smoke usually causes acute lung injury (ALI) that would likely develop to acute respiratory distress syndrome (ARDS). However, there is no effective prevention or treatment strategy for the smoke-induced ALI. Resveratrol (RES) is a natural polyphenol with good anti-inflammatory and anti-apoptotic activities, but its low solubility, stability, and bioavailability restrict its clinical application. In this study, an inhalable RES formulation composed of RES-ß-cyclodextrin inclusion complexes (RES-ß-CD) was prepared for the prevention of ZnCl2 smoke-induced ALI. RES-ß-CD powders had a small mass median aerodynamic diameter of 3.61 µm and a high fine particle fraction of 38.84%, suitable for pulmonary inhalation. RES-ß-CD exhibited low BEAS-2B cytotoxicity. Pulmonary delivery of RES-ß-CD to mice remarkably prevented the smoke-induced ALI with downregulation of TNF-α, IL-1ß, STAT3, and GATA3, and upregulation of T-bet and Foxp3. RES-ß-CD protected the respiratory function, percutaneous oxygen saturation, physical activity, lung capillary integrity, and lung liquid balance, alleviating inflammation and apoptosis. Pulmonary delivery of the positive drug, budesonide (BUD), also alleviated the smoke-induced ALI by reduction of inflammation and cell apoptosis. RES-ß-CD exhibited the regulation of the Th1/Th2 and Treg/Th17 balances, while BUD did not show any effect on immune balances. In conclusion, pulmonary delivery of RES-ß-CD is a promising anti-inflammatory and anti-apoptosis strategy for the prevention of ZnCl2 smoke-induced ALI by direct lung drug distribution and regulation of immune balance.

The concurrent disturbance of dynamic functional and structural brain connectome in major depressive disorder: the prefronto-insular pathway.

BACKGROUND: Robust evidence has shown that abnormal function networks, particularly the salience network (SN), are observed in depressed patients. Although white matter structural connectivity may predict time-varying functional connectivity, including symptom phenotype, in psychiatric disorders, there is still a gap in elucidating the concurrent dynamic functional and structural connectivity profiles of the SN in depressed patients. METHODS: We measured static and dynamic functional connectivity (FC) of the SN using resting-state fMRI BOLD time series in 76 subjects (21 with major depressive disorder (MDD), 27 with bipolar depression (BD), and 28 healthy controls (HC)). Hamilton Depression Scale total score was used to measure depression severity. Furthermore, we investigated the concurrent structural connectivity using diffusion kurtosis imaging (DKI)-based tractography. RESULTS: Our findings suggested that in the presence of MDD, both structural and dynamic (but not static) FC were reduced in the SN, particularly affecting the left prefronto-insular pathways (L.aPFC-L.insula). MDD patients showed decreased connectivity variability within the SN compared with HC. The aberrant dynamic FC in the prefronto-insular pathways of the SN related to severity of depressive symptoms in MDD. Furthermore, compared with BD patients, those with MDD showed significantly decreased dynamic FC in the left prefronto-parietal system (L.aPFC-lateral parietal cortex). LIMITATIONS: The generalizability of our findings is, to some extent, constrained by the small sample size. CONCLUSIONS: The integrity of SN connectivity, particularly the prefronto-insular pathway, appears to be a crucial signature of MDD. The perturbed dynamic interaction of SN with prefrontal regions may underlie the clinical severity in depressed patients.

Hydrogen sulfide alleviates cognitive deficiency and hepatic dysfunction in a mouse model of acute liver failure.

Acute liver failure (ALF) is a devastating clinical syndrome with a high mortality rate if not treated promptly. Previous studies have demonstrated the beneficial effects of hydrogen sulfide (H2S) on the brain and liver. The present study aimed to investigate the potential protective effects of H2S in ALF. A mouse model of ALF was established following treatment with thioacetamide (TAA). Mice with TAA-induced ALF were intraperitoneally injected with 30 or 100 µmol/kg/day sodium hydrosulfide (NaHS; a H2S donor drug) for two weeks. According to results from novel object recognition and Y-maze tests, in the present study, NaHS treatment alleviated cognitive deficiency and preserved spatial orientation learning ability in TAA-induced ALF mice compared with those of untreated mice. In addition, NaHS treatment reduced serum levels of aspartate transaminase (AST), alanine transaminase (ALT) and the concentration of ammonia compared with those that received control treatment, resulting in weight loss prevention. These findings suggested a beneficial effect of H2S on liver function. In conclusion, results from the present study suggested that H2S treatment may alleviate cognitive deficiency and hepatic dysfunction in mice with ALF, indicating the potential therapeutic benefits of applying H2S for the treatment of ALF.

The Insular Subregions Topological Characteristics of Patients With Bipolar Depressive Disorder.

The insular cortex appears to have a crucial role in emotional processing and cognitive control in bipolar disorder (BD). However, most previous studies focused on the entire insular region of BD, neglecting the topological profile of its subregions. Our study aimed to investigate its subregion topological characteristics using the resting-state functional connectivity (rsFC) in patients with BD on depression episode. The magnetic resonance imaging (MRI) data of 28 depressed BD patients and 28 age- and gender-matched healthy controls (HCs) were acquired. We observed that compared to HCs, depressed patients with BD exhibited significantly decreased rsFC between the right ventral anterior insula (vAI) and the left middle temporal gyrus/the right angular, the right dorsal anterior insula (dAI) and the left precuneus, as well as the right posterior insula and the right lingual gyrus. Furthermore, hyperconnectivity was observed between the left dAI and the left medial frontal gyrus, as well as right dAI and left superior temporal gyrus in BD depression. However, no significant group effect was observed between aberrant FC patterns and clinical variables. These findings revealed the functional connectivity patterns of insular subregions for the depressed BD patients, suggesting the potential neural substrate of insular subregions involved in depressive episode of BD. Hence, these results may provide a neural substrate for the potential treatment target of BD on depression episode.