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HOTAIR promoted LPS-induced inflammatory response and apoptosis of H9C2 cells by enhancing PDCD4 stability. RNA pull-down and RIP assay exhibited that Lin28, a highly conserved RNA-binding protein, was combined with HOTAIR and PDCD4. The in vivo experiments verified that the HOTAIR knockdown alleviated the cardiac function injury and secretion of inflammatory factors caused by sepsis. In conclusion, our findings supported that the HOTAIR/Lin28/PDCD4 axis serves as a critical regulator of sepsis, which may open a new direction for the development of sepsis therapeutic.Acid sphingomyelinase (ASM) and acid β-glucosidase 1 (GBA1) catalyze ceramide formation through different routes, and both are involved in rheumatoid arthritis (RA) pathogenesis as well as IL-6 production. However, whether ASM and GBA1 regulate IL-6 production in RA remains unknown. Serum ASM, GBA1, and ceramide levels were measured in RA patients and healthy controls by enzyme-linked immunosorbent assay, and their correlations with clinical indicators of patients were evaluated. Pharmacologic inhibitors or small hairpin RNAs of ASM and GBA1 were employed to explore the roles of ASM and GBA1 in IL-6 production, cell behavior, and MAPK signaling in fibroblast-like synoviocytes from RA patients (RAFLS). ASM, GBA1, and ceramide serum levels were significantly elevated in patients with RA. GBA1 and ceramide serum levels were negatively and positively correlated with IL-6 serum level in RA patients, respectively. ASM inhibitor or knockdown of ASM abolished IL-1β-induced IL-6 expression and secretion. Functionally, ASM inhibitor suppressed IL-1β-induced cell proliferation, migration, and invasion in RAFLS. Mechanistically, ASM inhibitor or knockdown of ASM effectively countered IL-1β-induced activation of p38 MAPK signaling. The pharmacologic inhibitor or knockdown of GBA1 exhibited the opposite effects. Importantly, p38 inhibitor blocked IL-1β-induced IL-6 production in RAFLS. ASM plays a pathogenic role in RA, whereas GBA1 plays a protective role in RA possibly by regulating IL-6 production in RAFLS at least partially via p38 signaling, serving as potential therapeutic targets in RA treatment.
Bariatric surgery provides a useful opportunity to perform intraoperative liver biopsy to screen for non-alcoholic steatohepatitis (NASH). There is currently no consensus on whether intraoperative liver biopsy should be systematically performed. The aim of this study was to develop and validate a decision tree to guide that choice.
This prospective study included 102 consecutive patients from the severe obesity outcome network (SOON) cohort in whom liver biopsy was systematically performed during bariatric surgery. A classification and regression tree (CART) was created to identify the nodes that best classified patients with and without NASH. External validation was performed. Seventy-one biopsies were of sufficient quality for analysis (median body mass index 43.3 [40.7; 48.0] kg/m
). NASH was diagnosed in 32.4% of cases. None of the patients with no steatosis on ultrasound had NASH. The only CART node that differentiated between a "high-risk" and a "low-risk" of NASH was alanine aminotransferase (ALT). ALT>53IU/L predicted NASH with a positive predictive value (PPV) of 68% and a negative predictive value (NPP) of 89%, a sensitivity of 77%, and a specificity of 84%. In the external cohort (n=258), PPV was 68%, NPV was 62%, sensitivity was 27%, and specificity was 90%.
The present work supports intraoperative liver biopsy to screen for NASH in patients with ALT>53IU/L; however, patients with no steatosis on ultrasound should not undergo biopsy. The CART failed to identify an algorithm with a good sensitivity to screen for NASH in patients with ultrasonography-proven steatosis and ALT≤53IU/L.
53IU/L; however, patients with no steatosis on ultrasound should not undergo biopsy. The CART failed to identify an algorithm with a good sensitivity to screen for NASH in patients with ultrasonography-proven steatosis and ALT≤53IU/L.
Sialidosis is an autosomal recessive glycoprotein storage disorder, caused by neuraminidase deficiency which leads to abnormal intracellular accumulation and urinary excretion of sialylated oligosaccharides, resulting in various morphological and functional disorders. Only a few reports have described the anesthetic managements of patients with sialidosis.
A 49-year-old woman with type 1 sialidosis suffered from all limb contractures, an ocular cherry-red spot, and myoclonic seizures of the limbs. She had been cognitively normal. She was separately scheduled for mastectomy under total intravenous anesthesia and total hysterectomy under combined general and epidural anesthesia uneventfully.
Our patient with type 1 sialidosis received both general and epidural anesthesia uneventfully. Anesthesiologists should carefully assess patients with sialidosis and give careful consideration to individually tailored anesthetic managements.
Our patient with type 1 sialidosis received both general and epidural anesthesia uneventfully. Anesthesiologists should carefully assess patients with sialidosis and give careful consideration to individually tailored anesthetic managements.
Pelvic fracture may be accompanied by severe bleeding. Computed tomography (CT) is a gold standard diagnostic tool in stable trauma patients. Contrast extravasation detected on CT of pelvis is a sign of hemorrhage, but its significance is not clear. We aimed to evaluate the need for angiography in patients with pelvic fracture and CT revealed contrast extravasation. We tried to identify parameters that might help to choose patients who will benefit from therapeutic angiography.
Electronic medical records of patients with pelvic fracture admitted to Level II Trauma Center during 10years were retrospectively reviewed. Navitoclax mouse Patients who had contrast extravasation on CT were included. Data base consisted of demographics, injury severity, initial physiologic parameters, laboratory data, results of CT and angiography.
Forty out of 396 patients had contrast extravasation detected by CT. Twelve patients underwent angiography and 4 of them benefited from embolization. The sensitivity of contrast extravasation in evaluating the need for embolization was 1.
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