Low-grade inflammation for predicting severe acute pancreatitis in patients with hypertriglyceridemic acute pancreatitis.

OBJECTIVES: We aimed to evaluate the association between low-grade inflammation (LGI) and the severity of hypertriglyceridemic acute pancreatitis (HTG-AP). METHODS: We retrospectively reviewed 311 patients with HTG-AP who were admitted to the Department of Gastroenterology, Fujian Provincial Hospital between April 2012 and March 2021. Inpatient medical and radiological records were reviewed to collect the clinical manifestations, disease severity, and comorbidities. C-reactive protein (CRP) level, white blood cell (WBC) count, platelet (PLT) count, and neutrophil-to-lymphocyte ratio (NLR) were considered LGI components and were combined to calculate a standardized LGI score. The association between the LGI score and the severity of HTG-AP was analyzed using univariate and multivariate logistic regression analyses. RESULTS: Of the 311 patients with HTG-AP, 47 (15.1%) had mild acute pancreatitis (MAP), 184 (59.2%) had moderately severe acute pancreatitis (MSAP), and 80 (25.7%) had severe acute pancreatitis (SAP), respectively. Patients with MSAP and SAP had a higher LGI score than those with MAP (1.50 vs -6.00, P < 0.001). Univariate logistic regression analysis revealed that patients with LGI scores in the fourth quartile were more likely to have MSAP and SAP (odds ratio [OR] 21.925, 95% confidence interval [CI] 5.014-95.867, P < 0.001). The multivariate logistic regression analysis confirmed that low calcium (OR 0.105, 95% CI 0.011-0.969, P = 0.047) and high LGI score (OR 1.253, 95% CI 1.066-1.473, P = 0.006) were associated with MSAP and SAP. When predicting the severity of acute pancreatitis, the LGI score had the highest area under the receiver operating characteristic (ROC) curve (0.7737) compared to its individual components. CONCLUSION: An elevated LGI score was associated with a higher risk of SAP in patients with HTG-AP.

Incidence and clinical characteristics of hypertriglyceridemic acute pancreatitis: A retrospective single-center study.

BACKGROUND: The incidence of hypertriglyceridemic acute pancreatitis (HTG-AP) has increased yearly, but updated population-based estimates on the incidence of HTG-AP are lacking. Reducing serum triglyceride (TG) levels quickly is crucial in the early treatment of HTG-AP. Decreased serum TG levels are treated by non-invasive methods, which include anti-lipidemic agents, heparin, low-molecular weight heparin, and insulin, and invasive methods, such as blood purification including hemoperfusion (HP), plasmapheresis, and continuous renal replacement therapy. However, authoritative guidelines have not been established. Early selection of appropriate treatment is important and beneficial in controlling the development of HTG-AP. AIM: To evaluate the effect between patients treated with intravenous insulin (INS) and HP to guide clinical treatment. METHODS: We retrospectively reviewed 371 patients with HTG-AP enrolled in the Department of Fujian Provincial Hospital form April 2012 to March 2021. The inpatient medical and radiologic records were reviewed to determine clinical features, severity, complications, mortality, recurrence rate, and treatment. Multivariate logistic regression analyses were used to analyze risk factors for severe HTG-AP. Propensity score matching was used to compare the clinical outcomes of INS and HP. RESULTS: A total of 371 patients met the HTG-AP criteria. The incidence of HTG-AP was increased by approximately 2.6 times during the 10 years (8.4% in April 2012-March 2013 and 22.3% in April 2020-March 2021). The highest incidence rate of acute pancreatitis was observed for men in the age group of 30-39 years. The amylase level was elevated in 80.1% of patients but was only three times the normal value in 46.9% of patients. The frequency of severe acute pancreatitis (26.9%), organ failure (31.5%), rate of recurrence (32.9%), and mortality (3.0%) of HTG-AP was high. Improved Marshall score, modified computed tomography severity index score, baseline TG, baseline amylase, C-reactive protein (CRP), albumin, aspartate aminotransferase, low-density lipoprotein cholesterol, urea nitrogen, creatinine, calcium, hemoglobin, free triiodothyronine, admission to intensive care unit, and mortality were significantly different between patients with different grades of severity (P < 0.050). Multivariate logistic regression analysis confirmed that high CRP [P = 0.005, odds ratio (OR) = 1.011, 95%CI: 1.003-1.019], low calcium (P = 0.003, OR = 0.016, 95%CI: 0.001-0.239), and low albumin (P = 0.023, OR = 0.821, 95%CI: 0.693-0.973) were risk factors of severe HTG-AP. After propensity score matching adjusted by sex, age, severity of HTG-AP, and baseline TG, the serum TG significantly decreased in patients treated with INS (P < 0.000) and HP (P < 0.000) within 48 h. However, the clearance rate of TG (57.24 ± 33.70% vs 56.38 ± 33.61%, P = 0.927) and length of stay (13.04 ± 7.92 d vs 12.35 ± 6.40 d, P = 0.730) did not differ between the two groups. CONCLUSION: The incidence of HTG-AP exhibited a significant increase, remarkable severity, and recurrent trend. Patients with mild and moderately severe acute pancreatitis can be treated effectively with INS safely and effectively without HP.

MicroRNA-324-5p affects the radiotherapy response of cervical cancer via targeting ELAV-like RNA binding protein 1.

Cervical cancer (CC) seriously threatens the health of women. Radiation therapy (RT) is the major treatment for CC. However, the recurrent CC can acquire resistance to RT. Thus, it is necessary to find a new method for reversing RT resistance in CC. It has been reported that miR-324-5p can suppress the progression of multiple cancers. However, whether it can reverse resistance to RT in CC remains unclear. qRT-PCR and Western blotting were used to detect gene and protein expression in CC cells, respectively. Cell proliferation was tested by CCK-8 assay and colony formation assay. In addition, cell apoptosis was detected by flow cytometry. Transwell assays were performed to detect cell migration. Dual luciferase reporter assay and TargetScan were used to explore the targets of microRNA-324-5p (miR-324-5p). MiR-324-5p was downregulated in CC cells. Overexpression of miR-324-5p sensitized CC cells to RT. In addition, miR-324-5p mimics significantly induced apoptosis and inhibits the migration of CC cells in the presence of 137 Cs ionizing radiation. Furthermore, miR-324-5p sensitized CC cells to ionizing radiation by targeting ELAV-like RNA binding protein 1 (ELAVL1). MiR-324-5p overexpression affects the radiotherapy response of CC by targeting ELAVL1, which may serve as a new target for the treatment of CC.

Effects of forage source and particle size on chewing activity, ruminal pH, and saliva secretion in lactating Holstein cows.

The present study investigated the effects of dietary forage source (quality) and particle size on chewing activity, saliva secretion, and ruminal pH. Twelve multiparous lactating Holstein cows, four of which were ruminally cannulated, were used in a replicated 4 × 4 Latin square experimental design with a 2 × 2 factorial arrangement of treatments. Cows fed wild-rye hay diets had longer daily eating times than cows fed oaten hay diets. Treatments had no effect on ruminating time; therefore, resting time varied inversely to eating time. Neither the rate nor the amount of saliva secretion while eating, ruminating, or resting was affected by diet, resulting in similar total daily saliva secretions across treatments (231 L/day). Total volatile fatty acids (VFAs) in the ruminal fluid from animals fed oaten hay diets were higher than those from animals fed wild-rye hay diets; further, VFAs increased with decreasing forage particle size (FPS). Consistent with elevated VFA concentrations, reducing FPS and including oaten hay in the diet decreased mean ruminal pH and increased the daily time of ruminal pH under 5.8. Results of this study suggest that forage source and particle size affect ruminal pH might be via variations in VFA production rather than increased salivary recycling of buffering substrates.

[Expression and significance of elastin and fibulin-5 in anterior vaginal tissue of women with pelvic organ prolapse].

OBJECTIVE: To investigate the expression and significance of elastin and fibulin-5 in anterior vaginal tissue of women with pelvic organ prolapse (POP). METHODS: Between November 2006 and June 2008, 68 patients with POP underwent surgical treatment in Shengjing Hospital of China Medical University were enrolled in this study, who were classified into 10 patients with grade I, 21 patients with grade II, 25 patients with grade III and 12 patients with grade IV in accordance with pelvic organ prolapse quantitation (POP-Q). Meanwhile, 18 cases with early cervical cancer at stage of I b were treated by total hysterectomy and bilateral salpingo-oophorectomy, their anterior vaginal tissues were selected as controls. Immunohistochemical staining was performed to detect the expression of elastin and fibulin-5. RESULTS: (1) Elastin and fibulin-5 were mainly expressed at extracellular matrix(ECM). (2) The positive rate of fibulin-5 expression in anterior vaginal wall were 5% (2/37) in grade III/IV and 26% (8/31) in grade I/IV POP patients, which reached statistical difference (P = 0.035). However, no statistical different expression was found between postmenopausal (13%, 8/60) and non-menopausal patients (2/8), vaginal delivery < or =2 (19%, 5/27) and >2 patients (12%, 5/41, P > 0.05). (3) The positive rate of elastin expression in anterior vaginal wall in POP group was 31% (21/68), which was significantly lower than 72% (13/18) of control group (P = 0.002). Among POP group, 19% (7/37) of elastin expression in grade III/IV POP was significantly lower than 45% (14/31) in grade I/II of POP patients. However, no statistical difference was found between postmenopausal (30%, 18/60) and non-menopausal patients (3/8), vaginal delivery < or =2 (26%, 7/27) and >2 patients(34%, 14/41, P > 0.05). (4) In POP group, both positive expression of fibulin-5 and elastin of anterior vaginal wall was in 6 cases, both negative expression of fibulin-5 and elastin was in 43 cases. It was illustrated that elastin and fibulin-5 had an positive relationship (P = 0.031). CONCLUSION: The decreased expression of elastin and fibulin-5 was correlated with degree of POP, which indicated that elastin and fibulin-5 may play a role in the pathogenesis of POP.

CD3/CD28 costimulation-induced NF-kappaB activation is mediated by recruitment of protein kinase C-theta, Bcl10, and IkappaB kinase beta to the immunological synapse through CARMA1.

CARMA1 (also known as CARD11) is a scaffold molecule and contains a caspase-recruitment domain (CARD) and a membrane-associated guanylate kinase-like (MAGUK) domain. It plays an essential role in mediating CD3/CD28 costimulation-induced NF-kappaB activation. However, the molecular mechanism by which CARMA1 mediates costimulatory signals remains to be determined. Here, we show that CARMA1 is constitutively associated with the cytoplasmic membrane. This membrane association is essential for the function of CARMA1, since a mutant of CARMA1, CARMA1(L808P), that is defective in the membrane association cannot rescue CD3/CD28 costimulation-induced NF-kappaB activation in JPM50.6 CARMA1-deficient T cells. Although CD3/CD28 costimulation effectively induces the formation of the immunological synapse in CARMA1-deficient T cells, the recruitment of protein kinase C-theta (PKC-theta), Bcl10, and IkappaB kinase beta (IKKbeta) into lipid rafts of the immunological synapse is defective. Moreover, expression of wild-type CARMA1, but not CARMA1(L808P), restores the recruitment of PKC-theta, Bcl10, and IKKbeta into lipid rafts in CARMA1-deficient T cells. Consistently, expression of a mutant CARMA1, CARMA1(DeltaCD), that cannot associate with Bcl10 failed to restore CD3/CD28 costimulation-induced NF-kappaB activation in JPM50.6 cells, whereas expression of Bcl10-CARMA(DeltaCD) fusion protein effectively restored this NF-kappaB activation. Together, these results indicate that CARMA1 mediates CD3/CD28 costimulation-induced NF-kappaB activation by recruiting downstream signaling components into the immunological synapse.