Amplifying hepatic L-aspartate levels suppresses CCl4-induced liver fibrosis by reversing glucocorticoid receptor ß-mediated mitochondrial malfunction.

Liver fibrosis is a determinant-stage process of many chronic liver diseases and affected over 7.9 billion populations worldwide with increasing demands of ideal therapeutic agents. Discovery of active molecules with anti-hepatic fibrosis efficacies presents the most attacking filed. Here, we revealed that hepatic L-aspartate levels were decreased in CCl4-induced fibrotic mice. Instead, supplementation of L-aspartate orally alleviated typical manifestations of liver injury and fibrosis. These therapeutic efficacies were alongside improvements of mitochondrial adaptive oxidation. Notably, treatment with L-aspartate rebalanced hepatic cholesterol-steroid metabolism and reduced the levels of liver-impairing metabolites, including corticosterone (CORT). Mechanistically, L-aspartate treatment efficiently reversed CORT-mediated glucocorticoid receptor ß (GRß) signaling activation and subsequent transcriptional suppression of the mitochondrial genome by directly binding to the mitochondrial genome. Knockout of GRß ameliorated corticosterone-mediated mitochondrial dysfunction and hepatocyte damage which also weakened the improvements of L-aspartate in suppressing GRß signaling. These data suggest that L-aspartate ameliorates hepatic fibrosis by suppressing GRß signaling via rebalancing cholesterol-steroid metabolism, would be an ideal candidate for clinical liver fibrosis treatment.

ROR2 Regulates Cellular Plasticity in Pancreatic Neoplasia and Adenocarcinoma.

Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells into precancerous lesions, to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We discovered that normal acinar cell differentiation, maintained by the transcription factor Pdx1, suppresses a broad gastric cell identity that is maintained in metaplasia, neoplasia, and the classical subtype of PDAC in mouse and human. We have identified the receptor tyrosine kinase Ror2 as marker of a gastric metaplasia-like identity in pancreas neoplasms. Ablation of Ror2 in a mouse model of pancreatic tumorigenesis promoted a switch to a gastric pit cell identity that largely persisted through progression to the classical subtype of PDAC. In both human and mouse pancreatic cancer, ROR2 activity continued to antagonize the gastric pit cell identity, strongly promoting an epithelial to mesenchymal transition, conferring resistance to KRAS inhibition, and vulnerability to AKT inhibition.

Impact of dietary inflammatory index on gestational diabetes mellitus in normal and overweight women: a systematic review and meta-analysis of observational studies.

BACKGROUND AND OBJECTIVES: To systematically investigate the association between the dietary inflammatory index (DII) and gestational diabetes mellitus (GDM), with a focus on the role of BMI in this relationship. METHODS AND STUDY DESIGN: A comprehensive search was conducted in PubMed, Embase, Web of Science, The Cochrane Library, Medline, CINAHL Complete, Chinese Periodical Full-text Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Wanfang Database for rele-vant observational studies published up to August 2023. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. The pooled effect size was calculated using a random-effects model. Sub-group and meta-regression analyses were performed to explore potential sources of heterogeneity. RESULTS: The study included 54,058 participants from 10 studies. Pregnant women with a higher DII, indicating a pro-inflammatory diet, had a significantly increased risk of GDM compared to those with a lower DII, indicating an anti-inflammatory diet (pooled OR: 1.17, 95% CI: 1.01-1.36; I²=70%, p <0.001). Subgroup analyses revealed a stronger association in normal weight stratification (OR: 1.25, 95%CI: 1.04-1.51), case-control studies (OR: 1.45, 95%CI: 1.03-2.05), Asia (OR: 1.26, 95%CI: 1.10-1.43), Europe (OR: 1.27, 95%CI: 1.09-1.48), 3-day dietary record as a dietary assessment tool (OR: 1.30, 95%CI: 1.16-1.46), physical activity adjustment (OR: 1.28, 95%CI: 1.13-1.46), and energy intake adjustment (OR: 1.33, 95%CI: 1.19-1.48). Meta-regression analysis confirmed that geographical region significantly influenced heterogeneity between studies (p <0.05). CONCLUSIONS: An elevated DII is independently linked to a higher risk of GDM, especially in women of normal weight.

Dual Roles of the Photooxidation of Organic Amines for Enhanced Triplet-Triplet Annihilation Upconversion in Nanoparticles.

Oxygen-mediated triplet-triplet annihilation upconversion (TTA-UC) quenching limits the application of such organic upconversion materials. Here, we report that the photooxidation of organic amines is an effective and versatile strategy to suppress oxygen-mediated upconversion quenching in both organic solvents and aqueous solutions. The strategy is based on the dual role of organic amines in photooxidation, i.e., as singlet oxygen scavengers and electron donors. Under photoexcitation, the photosensitizer sensitizes oxygen to produce singlet oxygen for the oxidation of alkylamine, reducing the oxygen concentration. However, photoinduced electron transfer among photosensitizers, organic amines, and oxygen leads to the production of superoxide anions that suppress TTA-UC. To observe oxygen-tolerating TTA-UC, we find that alkyl secondary amines can balance the production of singlet oxygen and superoxide anions. We then utilize polyethyleneimine (PEI) to synthesize amphiphilic polymers to encapsulate TTA-UC pairs for the formation of water-dispersible, ultrasmall, and multicolor-emitting TTA-UC nanoparticles.

A near-infrared fluorescent probe for differentiating cancer cells from normal cells and early diagnosis of liver cirrhosis.

BACKGROUND: Cirrhosis represents the terminal stage of liver disease progression and timely intervention in a diseased liver can enhance the likelihood of recovery. Viscosity, a crucial parameter of the cellular microenvironment, is intricately linked to the advancement of cirrhosis. However, viscosity monitoring still faces significant challenges in achieving non-invasive and rapid early diagnosis of cirrhosis. Near-infrared (NIR) fluorescence imaging has the advantages of high sensitivity, non-destructive detection, and ignoring background fluorescence interference, plays an important role in diagnosing and treating various biological diseases. Hence, monitoring cellular viscosity changes with NIR fluorescence probe holds great significance in the early diagnosis of cirrhosis. RESULTS: In this study, the NIR fluorescence probe based on the intramolecular charge transfer (TICT) mechanism was developed for imaging applications in mouse model of liver cirrhosis. A molecular rotor-type viscosity-responsive probe was synthesized by linking dioxanthracene groups via carbon-carbon double bonds. The probe demonstrated remarkable sensitivity, high selectivity and photostability, with its responsiveness to viscosity largely unaffected by factors such as polarity, pH, and interfering ions. The probe could effectively detect various drug-induced changes in cellular viscosity, enabling the differentiation between normal cells and cancerous cells. Furthermore, the enhanced tissue penetration capabilities of probe facilitated its successful application in mouse model of liver cirrhosis, allowing for the assessment of liver disease severity based on fluorescence intensity and providing a powerful tool for early diagnosis of cirrhosis. SIGNIFICANCE: A NIR viscosity-sensitive fluorescent probe was specifically designed to effectively monitor alterations in cellular and organ viscosity, which could advance the understanding of the biological characteristics of cancer and provide theoretical support for the early diagnosis of cirrhosis. Overall, this probe held immense potential in monitoring viscosity-related conditions, expanding the range of biomedical tools available.

Cognitive benefits of folic acid, docosahexaenoic acid and a combination of both nutrients in mild cognitive impairment; possible alterations though mitochondrial function and DNA damage.

INTRODUCTION: It is uncertain whether folic acid (FA) combined with docosahexaenoic acid (DHA) could improve cognitive performance. This study evaluated the effects of a 12-month FA and DHA supplementation, in combination or alone, on cognitive function, DNA oxidative damage, and mitochondrial function in participants with mild cognitive impairment (MCI). METHODS: This randomized, double-blind, placebo-controlled trial recruited MCI participants aged 60 years and older. Two hundred and eighty participants were randomly divided in equal proportion into four groups: FA+DHA (FA 800µg/d + DHA 800mg/d), FA (800µg/d), DHA (800mg/d), and placebo groups daily orally for 12 months. The primary outcome was cognitive function evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-RC). Cognitive tests and blood mechanism-related biomarkers were determined at baseline and 12 months. RESULTS: During the 12-month follow, scores of full intelligence quotient (FIQ) (ßDHA: 1.302, 95%CI: 0.615, 1.990, p < 0.001; ßFA: 1.992, 95%CI: 1.304, 2.679, p < 0.001; ßFA+DHA: 2.777, 95%CI: 2.090, 3.465, p < 0.001), verbal intelligence quotient, and some subtests of the WAIS-RC were significantly improved in FA+DHA and single intervention groups compared to the placebo group. Moreover, the FA and DHA intervention combination was superior to either intervention alone (p < 0.001). Meanwhile, FA, DHA and their combined use significantly decreased 8-OHdG level and increased mitochondrial DNA copy number compared to the placebo (p < 0.05). CONCLUSIONS: Supplementation of FA and DHA, alone or combined, for 12 months can improve cognitive function in MCI participants, possibly through mitigating DNA oxidative damage and enhancing mitochondrial function. Combined supplementation may provide more cognitive benefit than supplementation alone. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000034351. Registered 3 July 2020 - Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=53345.

The Effect of Enhanced Rehabilitation Program on Upper Limb Function in Patients Undergoing Abdominal Pedicle Flap Surgery.

To investigate the effect of an enhanced rehabilitation program on upper limb function in patients with abdominal pedicle flap surgery, we retrospectively analyzed 70 patients received abdominal pedicled flap surgery between 2017 and 2022. Patients were categorized into the traditional rehabilitation group (rehabilitation initiated after the stage Ⅱ pedicle dissection of the abdominal pedicle flap) and the enhanced rehabilitation group (rehabilitation initiated on the first day following the stage Ⅰ abdominal pedicle flap surgery). All the patients received identical rehabilitation protocols. PROM, ADL, FIM, and MMT were assessed at five days and one month following the stage Ⅱ surgery. The main causes of injury were electrical burns in both groups. The hospital stay of patients in the enhanced group was significantly shorter than the traditional group. One month assessment indicated both groups showed significant improvements in the PROM of shoulder flexion, abduction, and elbow extension compared to the five days assessment. Notably, at five days assessment, the enhanced group had significantly higher PROM in shoulder abduction and elbow extension compared to the traditional group. Furthermore, the enhanced group continued to exhibit higher PROM in shoulder flexion and abduction than the traditional group at one month assessment. At one month assessment, a significant increase was observed in the ADL, FIM, and MMT of both groups compared to the five days. The study indicated the enhanced rehabilitation program immediately following the stage Ⅰ surgery can effectively improve the PROM of the shoulder and elbow and reduce the length of hospital stay for patients.

Analysis of hemorrhagic drug-drug interactions between P-gp inhibitors and direct oral anticoagulants from the FDA Adverse Event Reporting System.

BACKGROUND: Limited understanding exists regarding the hemorrhagic risk resulting from potential interactions between P-glycoprotein (P-gp) inhibitors and direct oral anticoagulants (DOACs). Utilizing the Food and Drug Administration Adverse Event Reporting System (FAERS) data, we analyzed hemorrhagic adverse events (AEs) linked with the co-administration of P-gp inhibitors and DOACs, aiming to offer guidance for their safe and rational use. METHODS: Hemorrhagic events associated with P-gp inhibitors in combination with DOACs were scrutinized from the FAERS database. Hemorrhagic signals mining was performed by estimating the reported odds ratios (RORs), corroborated by additive and multiplicative models and a combination risk ratio (PRR) model. RESULTS: Our analysis covered 4,417,195 cases, revealing 11,967 bleeding events associated with P-gp inhibitors. We observed a significantly higher risk of bleeding with the combination of apixaban and felodipine (ROR 118.84, 95% CI 78.12-180.79, additive model 0.545, multiplicative model 1.253, PRR 22.896 (2450.141)). Moreover, consistent associations were found in the co-administration analyzes of rivaroxaban with dronedarone and diltiazem, and apixaban with losartan, telmisartan, and simvastatin. CONCLUSION: Our FAERS data analysis unveils varying degrees of bleeding risk associated with the co-administration of P-gp inhibitors and DOACs, underscoring the importance of vigilance about them in clinical practice.

Gradual Increase in Birefringence of Antimony Oxalates through Precise Tuning of the Sb3+/[C2O4]2- Ratio.

Birefringent crystals play a crucial role in modulating and controlling the polarization of light in the optical communication and laser industries. Recently, adopting appropriate strategies to enhance the birefringence of crystals has become a prominent area of research focus. Herein, four UV antimony oxalate birefringent crystals, namely, K5Sb2(C2O4)5.5·3H2O, BaSb(C2O4)2.5·3H2O, Na4Sb2O(C2O4)4·6H2O, and Na3Sb(C2O4)2F2·2H2O, have been successfully synthesized. These compounds feature a similar zero-dimensional (0D) cluster structure and share the same functional groups, including π-conjugated [C2O4]2- groups and Sb3+-based distorted polyhedra with stereochemically active lone pairs (SCALPs). Interestingly, we achieved a stepwise increase in birefringence by precisely controlling the Sb3+/[C2O4]2- ratio, ultimately resulting in the compound Na3Sb(C2O4)2F2·2H2O exhibiting a large birefringence (0.21@546 nm). Additionally, we confirmed that the synergistic effects between the π-conjugated [C2O4]2- groups and the distorted polyhedra based on Sb3+ are responsible for the excellent optical properties observed in the reported compounds.

A review of uncertainty quantification in medical image analysis: Probabilistic and non-probabilistic methods.

The comprehensive integration of machine learning healthcare models within clinical practice remains suboptimal, notwithstanding the proliferation of high-performing solutions reported in the literature. A predominant factor hindering widespread adoption pertains to an insufficiency of evidence affirming the reliability of the aforementioned models. Recently, uncertainty quantification methods have been proposed as a potential solution to quantify the reliability of machine learning models and thus increase the interpretability and acceptability of the results. In this review, we offer a comprehensive overview of the prevailing methods proposed to quantify the uncertainty inherent in machine learning models developed for various medical image tasks. Contrary to earlier reviews that exclusively focused on probabilistic methods, this review also explores non-probabilistic approaches, thereby furnishing a more holistic survey of research pertaining to uncertainty quantification for machine learning models. Analysis of medical images with the summary and discussion on medical applications and the corresponding uncertainty evaluation protocols are presented, which focus on the specific challenges of uncertainty in medical image analysis. We also highlight some potential future research work at the end. Generally, this review aims to allow researchers from both clinical and technical backgrounds to gain a quick and yet in-depth understanding of the research in uncertainty quantification for medical image analysis machine learning models.

Heparan sulfate acts as an activator of the NLRP3 inflammasome promoting inflammatory response in the development of acute pancreatitis.

BACKGROUND: Accumulating evidence has shown that the NOD-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in the inflammatory cascades involved in the development of acute pancreatitis (AP). However, the specific agonist responsible for activating the NLRP3 inflammasome in this process has not yet been identified. The purpose of this study is to clarify whether heparan sulfate (HS) works as an NLRP3 inflammasome activator to evoke inflammatory cascades in the progression of AP. METHODS: Two experimental mouse models of AP were utilized to investigate the pro-inflammatory activity of HS in the development of AP by measuring the secretion of inflammatory cytokines and the neutrophil infiltration in pancreatic tissue. The ability of HS to activate the NLRP3 inflammasome was evaluated both in vitro and in vivo. The nuclear factor kappa B (NF-κB)-mediated expression of NLRP3 inflammasome components in response to HS treatment was determined to decipher the role of HS in transcriptional priming of NLRP3 inflammasome. Furthermore, HS-triggered deubiquitination of NLRP3 was analyzed to reveal the promoting effect of HS on the NLRP3 inflammasome priming via a non-transcriptional pathway. RESULTS: High plasma level of HS was observed with a positive correlation to that of inflammatory cytokines in AP mice. Administration of HS to mice resulted in an exacerbated inflammatory profile, while reducing HS production by an inhibitor of heparanase significantly attenuated inflammatory response. Pharmacological inhibition or genetic deletion of NLRP3 substantially suppressed the HS-stimulated elevation of IL-1ß levels in AP mice. The in vitro data demonstrated that HS primarily serves as a priming signal for the activation of the NLRP3 inflammasome. HS possesses the ability to increase the transcriptional activity of NF-κB and TLR4/NF-κB-driven transcriptional pathway is employed for NLRP3 inflammasome priming. Moreover, HS-induced deubiquitination of NLRP3 is another pathway responsible for non-transcriptional priming of NLRP3 inflammasome. CONCLUSIONS: Our current work has unveiled HS as a new activator of the NLRP3 inflammasome responsible for the secondary inflammatory cascades during the development of AP, highlighting the HS-NLRP3 pathway as a potential target for future preventive and therapeutic approaches of AP.

Exploring the impact of 40 Hz multi-luminaire light exposure in Alzheimer's dementia: insights from a convenient sampling, non-randomized case-control study.

BACKGROUND: Recent studies propose 40 Hz neural activity induction as a promising approach for managing Alzheimer's dementia (AD). However, traditional flickering light is suboptimal in addressing cognitive and neuropsychiatric symptoms (NPS) of AD. This study aims to investigate the clinical efficacy of a novel multi-luminaire lighting technology, with reduced perceptible flickering, for treating AD NPS. METHODS: This study is a prospective, convenient sampling, non-randomized case-control investigation involving seventy-eight clinically diagnosed AD patients from 7 daycare centers. Thirty-five were exposed to 40 Hz light through Delta M + BrainCare Light (M +), 4 h daily, 5 days/week, for 12 weeks. The other 43 patients served as controls. Sum of boxes of the Clinical Dementia Rating (CDR-SB) scale, Neuropsychiatric Inventory (NPI), and Zarit Burden Interview (ZBI) were assessed at baseline and the 13th week. RESULTS: At baseline, the cases had worse cognitive function, lower cognitive score (Mini-Mental State Examination, p = 0.04; Cognitive Abilities Screening Instrument, p = 0.04), and advanced caregiver burden with higher ZBI scores (p < 0.01) than the controls. After the intervention, the cases had significant improvements in NPS as assessed using the NPI (p = 0.02), especially depression and euphoria symptoms (p = 0.04 and < 0.01, respectively) and less caregiver burden (ZBI score, p < 0.01). In global function, the control group showed a significant decline in CDR-SB score (p < 0.01), while the cases did not. CONCLUSIONS: Results suggest M + may slow global function decline, preserve cognitive function, improve NPS, and reduce caregiver burden in AD patients. Larger studies with biomarkers are needed to explore underlying mechanisms.

Sb2O2SeO3 and Sb2O(SeO3)2: Two-Layered Antimony(III) Selenites with Enhanced Birefringence.

Two antimony selenites, Sb2O2SeO3 and Sb2O(SeO3)2, were synthesized by simultaneously incorporating stereochemically active lone pair electrons containing SeO32- and Sb3+. These compounds are structured with [SbOx] polyhedra and [SeO3] units within a two-dimensional framework. Both of them exhibit cutoffs at 300 and 330 nm within the ultraviolet (UV) range and demonstrate significant birefringence, with indices of 0.069 and 0.126 at 546 nm, respectively. These properties highlight their potential as UV birefringent materials. Structural analyses and theoretical calculations reveal that their exceptional birefringence results from the synergistic interactions between SeO32- anions and Sb3+ cations.

Role of Ferroptosis Regulation by Nrf2/NQO1 Pathway in Alcohol-Induced Cardiotoxicity In Vitro and In Vivo.

The aim of the present study was to evaluate the cardiotoxic effects of alcohol and its potential toxic mechanism on ferroptosis in mice and H9c2 cells. Mice were intragastrically treated with three different concentrations of alcohol, 7, 14, and 28%, each day for 14 days. Body weight and electrocardiography (ECG) were recorded over the 14 day period. Serum creatine kinase (CK), lactic dehydrogenase (LDH), MDA, tissue iron, and GSH levels were measured. Cardiac tissues were examined histologically, and ferroptosis was assessed. In H9c2 cardiomyocytes, cell viability, reactive oxygen species (ROS), labile iron pool (LIP), and mitochondrial membrane potential (MMP) were measured. The proteins of ferroptosis were evaluated by the western blot technique in vivo and in vitro. The results showed that serum CK, LDH, MDA, and tissue iron levels significantly increased in the alcohol treatment group in a dose-dependent manner. The content of GSH decreased after alcohol treatment. ECG and histological examinations showed that alcohol impaired cardiac function and structure. In addition, the levels of ROS and LIP increased, and MMP levels decreased after alcohol treatment. Ferrostatin-1 (Fer-1) protected cells from lipid peroxidation. Western blotting analysis showed that alcohol downregulated the expression of Nrf2, NQO1, HO-1, and GPX4. The expressions of P53 and TfR were upregulated in vivo and in vitro. Fer-1 significantly alleviated alcohol-induced ferroptosis. In conclusion, the study showed that Nrf2/NQO1-dependent ferroptosis played a vital role in the cardiotoxicity induced by alcohol.

Fried Soybean Oil Causes Systemic Low-Grade Inflammation by Disrupting the Balance of Gut Microbiota in Mice.

Previous reports have mainly investigated the long-term effects (>30 d), such as gut microbiota dysbiosis and systemic low-grade inflammation, in mice fed fried oil. However, short-term intake of deep-fried oil is more likely to occur in daily life, and such studies are lacking. This study aimed to investigate the short-term effects of fried oil intake on systemic low-grade inflammation. Male Kunming mice were fed non-fried soybean oil or low (25%), medium (50%), or high (100%)-fried oil at 4.4 g/kg for 6 d. Serum and fecal samples were collected on day 7. In all groups fed fried oil, the serum levels of tumor necrosis factor (TNF-α) were significantly elevated 2-4-fold. Among the gut microbiota, the abundance of Alloprevotella significantly decreased by up to 76%, while Lactobacilli significantly increased by up to 385%. The fecal valeric acid content was significantly increased and positively correlated with TNF-α levels. Both valeric acid and TNF-α levels were positively correlated with the abundance of Lactobacilli and negatively correlated with that of Alloprevotella. In summary, a short-term ingestion of even low doses of fried oil alters the gut microbiota Alloprevotella and Lactobacilli and increases fecal valeric acid content, which correlates with increased serum TNF-α levels.

1,6-Nucleophilic Di- and Trifluoromethylation of para-Quinone Methides with Me3SiCF2H/Me3SiCF3 Facilitated by CsF/18-Crown-6.

The direct 1,6-nucleophilic difluoromethylation, trifluoromethylation, and difluoroalkylation of para-quinone methides (p-QMs) with Me3SiRf (Rf = CF2H, CF3, CF2CF3, CF2COOEt, and CF2SPh) under mild conditions are described. Although Me3SiCF2H shows lower reactivity than Me3SiCF3, it can react with p-QMs promoted by CsF/18-Crown-6 to give structurally diverse difluoromethyl products in good yields. The products can then be further converted into fluoroalkylated para-quinone methides and α-fluoroalkylated diarylmethanes.

Microbiome and Metabolite Analysis Insight into the Potential of Shrimp Head Hydrolysate to Alleviate Depression-like Behaviour in Growth-Period Mice Exposed to Chronic Stress.

Chronic stress (CS) endangers the physical and mental health of adolescents. Therefore, alleviating and preventing such negative health impacts are a top priority. This study explores the effect of feeding shrimp head hydrolysate (SHH) on gut microbiota, short-chain fatty acids (SCFAs), and neurotransmitters in growing C57BL/6 mice subjected to chronic unpredictable mild stress. Mice in the model group and three SHH groups were exposed to CS for 44 days, distilled water and SHH doses of 0.18, 0.45, 0.90 g/kg·BW were given respectively by gavage daily for 30 days from the 15th day. The results showed that SHH can significantly reverse depression-like behaviour, amino acids degradation, α diversity and ß diversity, proportion of Firmicutes and Bacteroidota, abundance of genera such as Muribaculaceae, Bacteroides, Prevotellaceae_UCG-001, Parabacteroides and Alistipes, concentration of five short-chain fatty acids (SCFAs), 5-HT and glutamate induced by CS. Muribaculaceae and butyric acid may be a controlled target. This study highlights the potential and broad application of SHH as an active ingredient in food to combat chronic stress damage.

Abnormal dynamic functional connectivity and topological properties of cerebellar network in male obstructive sleep apnea.

PURPOSE: To investigate dynamic functional connectivity (dFC) within the cerebellar-whole brain network and dynamic topological properties of the cerebellar network in obstructive sleep apnea (OSA) patients. METHODS: Sixty male patients and 60 male healthy controls were included. The sliding window method examined the fluctuations in cerebellum-whole brain dFC and connection strength in OSA. Furthermore, graph theory metrics evaluated the dynamic topological properties of the cerebellar network. Additionally, hidden Markov modeling validated the robustness of the dFC. The correlations between the abovementioned measures and clinical assessments were assessed. RESULTS: Two dynamic network states were characterized. State 2 exhibited a heightened frequency, longer fractional occupancy, and greater mean dwell time in OSA. The cerebellar networks and cerebrocerebellar dFC alterations were mainly located in the default mode network, frontoparietal network, somatomotor network, right cerebellar CrusI/II, and other networks. Global properties indicated aberrant cerebellar topology in OSA. Dynamic properties were correlated with clinical indicators primarily on emotion, cognition, and sleep. CONCLUSION: Abnormal dFC in male OSA may indicate an imbalance between the integration and segregation of brain networks, concurrent with global topological alterations. Abnormal default mode network interactions with high-order and low-level cognitive networks, disrupting their coordination, may impair the regulation of cognitive, emotional, and sleep functions in OSA.

Pulmonary tumor thrombotic microangiopathy: Two case reports and literature review.

RATIONALE: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but serious complication in patients with malignancy; its main manifestation includes acute pulmonary hypertension with severe respiratory distress. More than 200 cases have been reported since it was first identified in 1990. PTTM accounts for approximately 0.9% to 3.3% of deaths due to malignancy, but only a minority of patients are diagnosed ante-mortem, with most patients having a definitive diagnosis after autopsy. PATIENT CONCERNS: Two middle-aged women both died within a short period of time due to progressive dyspnea and severe pulmonary hypertension. DIAGNOSES: One patient was definitively confirmed as a gastrointestinal malignant tumor by liver puncture biopsy pathology. Ultimately, the clinical diagnosis was pulmonary tumor thrombotic microangiopathy. INTERVENTIONS: The patient was treated symptomatically with oxygen, diuresis, and anticoagulation, while a liver puncture was perfected to clarify the cause. OUTCOMES: Two cases of middle-aged female patients with rapidly progressive pulmonary hypertension and respiratory failure resulted in death with malignant neoplasm. LESSONS: PTTM has a rapid onset and a high morbidity and mortality rate. Our clinicians need to be more aware of the need for timely diagnosis through a targeted clinical approach, leading to more targeted treatment and a better prognosis.