OBJECTIVES: Psoriasis is associated with lipid metabolism disorders, but the underlying mechanisms remain unclear. This study aims to investigate the role of trimethylamine N-oxide (TMAO) in lipid metabolism dysregulation in psoriasis. METHODS: An imiquimod (IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters, TMAO levels, and liver flavin monooxygenase 3 (FMO3) mRNA expression. Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles. To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model, exogenous TMAO, choline, or 3,3-dimethyl-1-butanol (DMB) were administered via intraperitoneal injections or diet in IMQ-treated mice. Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways. RESULTS: IMQ-induced psoriatic mice exhibited abnormal glucose, insulin, and lipid levels. IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2 (Glut2) and silence information regulator 1 (Sirt1), while upregulating glucose transporter 4 (Glut4) and peroxisome proliferator-activated receptor gamma (PPARγ). Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice. Additionally, liver FMO3 mRNA expression was increased in the psoriatic mouse model. In patients, TMAO levels positively correlated with Psoriasis Area and Severity Index (PASI) scores, serum triglyceride (TG), and total cholesterol (TC) levels. The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice. A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice, whereas DMB treatment alleviated these effects. RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122 (miR-122), which may suppress the expression of gremlin 2 (GREM2), thus contributing to lipid metabolism disorder. CONCLUSIONS TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.
Animals ; Methylamines/blood* ; Mice ; Psoriasis/chemically induced* ; Lipid Metabolism/drug effects* ; Humans ; Male ; Liver/metabolism* ; Female ; Oxygenases/genetics* ; Disease Models, Animal ; Lipid Metabolism Disorders/etiology* ; Adult ; Mice, Inbred C57BL

Objective To investigate the clinical applications of goal-directed fluid therapy for pancreatoduodenectomy. Methods A total of 40 patients undergoing pancreatoduodenectomy under general anesthesia were randomly divided into two groups, G and C, with 20 cases in each group. Goal-directed fluid therapy was used in Group G, whereas conventional fluid therapy was used in group C. The intraoperative hemodynamics, liquid management, duration of the first postoperative gastrointestinal ventilation, postoperative renal function, serum lactate, and the incidence of postoperative complications were recorded. Results Compared with group C, the CI increased and SVV decreased (P ＜ 0.05) at T3 to T5, and MAP increased at T4 to T5 (P ＜ 0.05). The amount of fluid infusion and total infusion in group G were less than that of group C (P ＜ 0.05), and the number of vasoactive drugs was greater than that of group C (P ＜ 0.05). The duration of the first postoperative gastrointestinal ventilation in group G was shorter than that of group C (P ＜ 0.05). There were no significant differences between the 2 groups for the incidence of serum lactate, BUN, Cr, and the incidence of postoperative complications (P＞ 0.05).Conclusion For major complex operations, such as pancreaticoduodenectomy, goal-directed fluid therapy can guide intraoperative fluid therapy more accurately with individual optimizations, and has more advantages in maintaining intraoperative hemodynamics stability and improving postoperative outcome.

Neurofeedback may improve cognitive function and behaviour by regulating the cerebral neural activities. Neurofeedback works as a kind of therapy for patients with Parkinson's disease, primarily based on electroencephalogram signals and hemodynamic signals. It regulates abnormal neuronal rhythm oscillations in the cortical-spinal system by electroencephalogram neurofeedback and sensory motor rhythm as the main adjustment frequency band, and modulates activation in the cortical-basal ganglia-thalamic-cortical network of brain with the supplementary motor area as the target area via functional magnetic resonance imaging neurofeedback. Neurofeedback effectively improves the motor symptoms of Parkinson's patients, both dynamic and static. However, the number of samples is limited in these researches, and the assessments before and after neurofeedback training are not yet comprehensive. Neurofeedback technology might be a potential effective rehabilitation for patients with Parkinson's disease.

Background and objective Leptomeningeal carcinomatosis is a rare type of metastatic tumors of the central nervous system. In recent years, with the improvement of neoplasms therapies and longer survival of patients by better systemic control, incidence of leptomeningeal metastases has increased every year. However, there is still lack of effective thera-pies. hTe aim of this study is to investigate the effcacy, security and prognosis of intrathecal chemotherapy with methotrexate (MTX) in the treatment of neoplastic meningitis.Methods A total of 27 patients were enrolled. We investigated clinical fea-tures and cerebrospinal lfuid (CSF) examination results retrospectively, and analyzed the adverse reactions as well as prognosis atfer intrathecal chemotherapy.Results All 27 patients were treated by intrathecal MTX, 70.4% had clinical remission, how-ever, there was no signiifcant difference in CSF pressure and CSF biochemical changes. We observed that 55.6% patients were all appropriate, 25.9% appeared lower limb numbness and mild pain, no serious irreversible adverse reactions occurred. Median overall survival was 4 months.Conclusion We suggest that intrathecal administration of MTX is associated with improvement of symptoms of leptomeningeal metastasis patients and no severe adverse events observed.

Background and objectiveAdenosquamous carcinoma (ASC) is a rare subtype of lung cancer, it is mixed glandular and squamous cell carcinoma with a more aggressive behavior and poor prognosis than the other histologic subtypes. hTe aim of the study was to explore the clinicopathological characteristics and prognostic factors of ASC.Methods A total of 72 patients were enrolled. We investigated clinicalpathological features and prognostic factors retrospectively.Results hTe overall 72 ASC patients’ median age was 34.7 months, 5-year survival rate was 14.9%. hTe inlfuence of tumor size, M stage, and N stage, gene mutation and surgery on the prognosis of patients show statistical signiifcance.Conclusion ASC is charac-terized by both histologic aggressiveness and adverse prognosis. We suggest the comprehensive therapy based on surgery, and given small molecule tyrosine kinase inhibitors (TKIs) treatment may prolong patients’ overall survival.

Mammalian target of rapamycin( mTOR) is a key reg-ulator of aging and aging-related diseases. Rapamycin ( RAPA) induces and promotes the process of cell autophagy through in-hibiting mTOR pathway. Autophagy exerts a crucial role in main-taining the cellular meostasis, which provides essential materials for cell reconstruction, regeneration and repair via degradating the redundant, damaged, or senescent proteins and organelles. Hutchinson Gilford progeria syndrome ( HGPS ) patients are al-ways accompanied with abnormally accumulated progerin in cells. Similar to HGPS, abnormal protein accumulation is the common pathological feature of neurodegenerative diseases, in-cluding Huntington′s disease, Parkinson′s disease, Alzheimer′s disease and so on. Degradation of these abnormal proteins pre-dominantly depends on cell autophagy. Thus, rapamycin is a po-tential anti-aging drug for HGPS and aging-related diseases thera-py. This view focuses on the effects of rapamycin on cell autoph-agy and clinical application in HGPS and neurodegenerative dis-eases.