Background and Purpose Improvement of cognitive deficits in schizophrenia remains an unmet need owing to the lack of new therapies and drugs. Recent studies have reported that fingolimod, an immunomodulatory drug for treating multiple sclerosis, demonstrates anti‐inflammatory and neuroprotective effects in several neurological disease models. This suggests its usefulness for ameliorating cognitive dysfunction in schizophrenia. Herein, we assessed the efficacy profile and mechanism of fingolimod in a rat model of phencyclidine (PCP)‐induced schizophrenia. Experimental Approach Male Sprague–Dawley rats were treated with PCP for 14 days. The therapeutic effect of fingolimod on cognitive function was assessed using the Morris water maze and fear conditioning tests. Hippocampal neurogenesis and the expression of astrocytes and microglia were evaluated using immunostaining. Cytokine expression was quantified using multiplexed flow cytometry. Brain‐derived neurotrophic factor expression and phosphorylation of extracellular signal‐regulated kinase were determined using western blot analysis. Key Results Fingolimod attenuated cognitive deficits and restored hippocampal neurogenesis in a dose‐dependent manner in PCP‐treated rats. Fingolimod treatment exerted anti‐inflammatory effects by inhibiting microglial activation and IL‐6 and IL‐1β pro‐inflammatory cytokine expression. The underlying mechanism involves the upregulation of brain‐derived neurotrophic factor protein expression and activation of the ERK signalling pathway. Conclusion and Implications This is the first preclinical assessment of the effects of fingolimod on cognitive function in a model for schizophrenia. Our results suggest the immune system plays an crucial role in cognitive alterations in schizophrenia and highlight the potential of immunomodulatory strategies to improve cognitive deficits in schizophrenia.
Introduction This study aimed to compare the efficacy between patient-controlled caudal epidural analgesia (PCCA) and patient-controlled intravenous analgesia (PCIA) after perianal surgery, to provide a feasible solution to postoperative pain. Methods This was a prospective, randomized controlled trial comprising 100 patients who underwent caudal epidural block on perianal surgery at Chengdu Shang Jin Nan Fu Hospital of West China Hospital at Sichuan University between April and August 2020. Patients were randomly divided into the PCCA and PCIA groups. Visual analog scale (VAS) scores were recorded at 2, 4, 6, 24, 48, and 72 h after surgery, and at the first dressing change and first defecation. The lower limb mobility in the post-anesthetic recovery room (PACU) was determined. The analgesic effect, usage amount of patient-controlled analgesia (PCA), usage amount and frequency of remedial analgesic measures, number of individuals who must be catheterized, and incidence of adverse reactions were recorded. Satisfaction of postoperative analgesic effect and convenience of PCA were also assessed. Results The patients in the PCCA group had significantly lower VAS scores at 4, 6, 24, 48, 72 h, the first dressing change, and the first defecation compared with the PCIA group. There were more patients receiving postoperative remedial analgesics in the PCIA group than in the PCCA group. The outcome of the number of PCA and catheterization rates did not differ significantly between the groups. There were two cases of sensory numbness below the S3 plane. The major postoperative complications in the PCIA group were pruritus (3/47, 6.4%), nausea, and vomiting (6/47, 12.8%) (one case combined with pruritus). Patients in the PCCA group were more satisfied with the analgesic effect, while those in the PCIA group were more satisfied with the convenience. Conclusion In the postoperative analgesia program of perianal surgery, PCCA may provide a better analgesic effect without increasing the incidence of complications. Trial Registration Chinese Clinical Trial Registry identifier, ChiCTR2000038425, September 2020, retrospectively registered. Supplementary Information The online version contains supplementary material available at 10.1007/s40122-022-00411-y.
A 50-year-old female presented with a history of fatigue after activities. Transthoracic echocardiography showed a 2.8 cm dilatation at the ostium of the left coronary artery and a 7.1×7.4 cm cyst-like aneurysm at the upper back of the left atrium, interlinking an anomalous fistula from the left coronary artery to the right atrial appendage, accompanied by moderate mitral and tricuspid regurgitation. Cardiac 3D-computed tomography identified the diagnosis of ruptured aortic sinus aneurysm (RASA) and a giant left coronary artery aneurysm fistula to the right atrium. Transesophageal echocardiogram and surgical vision confirmed these findings. Surgeries including RASA repair, coronary artery bypass grafting, and mitral and tricuspid valvuloplasty were then performed. Procedures proceeded successfully, the patient was fully recovered and discharged home.
A 49-year-old male presented to hospital with symptoms of acute cerebral infarction and pulmonary embolism who underwent transcatheter closure of atrial septal defect a year ago. Transthoracic echocardiography showed a 13×9 mm hypoechoic mass attached to the left-atrial side of the device, which was suspected to be neoplasm or thrombus. The patient was indicated for surgery after multidisciplinary discussion due to ineffective medical therapy and typical stroke and pulmonary embolism symptoms. Three-dimensional transesophageal echocardiography (3D-TEE) revealed left-atrial vegetation (21×16 mm) and right-atrial vegetation (8×6 mm) attached to the device, which were confirmed as thrombus by surgical separation and laboratory examination. This case highlights the importance of 3D-TEE and a multidisciplinary team in the diagnosis and therapy of device-related thrombus.
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