Predicting Severity in Hypertriglyceridemia-Induced Acute Pancreatitis: The Role of Neutrophils, Calcium, and Apolipoproteins.

BACKGROUND Hypertriglyceridemia-induced acute pancreatitis (HTG-AP), representing 10% of all acute pancreatitis cases, is characterized by younger onset age and more severe progression, often leading to higher ICU admission rates. This condition poses a significant challenge due to its rapid progression and the potential for severe complications, including multiple organ failure. HTG-AP is distinct from other forms of pancreatitis, such as those caused by cholelithiasis or alcohol, in terms of clinical presentation and outcomes. It's essential to identify early markers that can predict the severity of HTG-AP to improve patient management and outcomes. MATERIAL AND METHODS This study divided 127 HTG-AP patients into mild acute pancreatitis (MAP, n=71) and moderate-to-severe acute pancreatitis (MSAP/SAP, n=56) groups. Blood biological indicators within the first 24 hours of admission were analyzed. Risk factors for HTG-AP progression were determined using binary logistic regression and ROC curves. RESULTS Elevated levels of HCT, NLR, TBI, DBI, AST, Cre, and AMS were noted in the MSAP/SAP group, with lower levels of LYM, Na⁺, Ca²âº, ApoA, and ApoB compared to the MAP group (p<0.05). NEUT%, Ca²âº, ApoA, and ApoB were significantly linked with HTG-AP severity. Their combined ROC analysis yielded an area of 0.81, with a sensitivity of 61.8% and specificity of 90%. CONCLUSIONS NEUT%, Ca²âº, ApoA, and ApoB are significant risk factors for progressing to MSAP/SAP in HTG-AP. Their combined assessment provides a reliable predictive measure for early intervention in patients at risk of severe progression.

Penfluroidol Attenuates the Imbalance of the Inflammatory Response by Repressing the Activation of the NLRP3 Inflammasome and Reduces Oxidative Stress via the Nrf2/HO-1 Signaling Pathway in LPS-Induced Macrophages.

Objectives: Excessive inflammatory responses and reactive oxygen species (ROS) formation play pivotal roles in the pathogenesis of sepsis. Penfluroidol (PF), an oral long-acting antipsychotic drug, has been suggested to possess diverse biological properties, including antischizophrenia, antitumour effect, and anti-inflammatory activity. The purpose of this research was to explore the anti-inflammatory and antioxidative effects of penfluroidol on lipopolysaccharide (LPS)-related macrophages. Methods: The viability of RAW264.7 and THP-1 cells was measured by Enhanced Cell Counting Kit-8 (CCK-8). The production of nitric oxide was evaluated by the Nitric Oxide Assay Kit. The generation of pro-inflammatory monocytes was detected by qRT-PCR (quantitative real-time PCR) and ELISA (enzyme-linked immunosorbent assay). Oxidative stress was assessed by measuring ROS, malondialdehyde (MDA), and superoxide dismutase (SOD) activity. The protein expression of the Nrf2/HO-1/NLRP3 inflammasome was detected by western blotting. Results: Our results indicated that no cytotoxic effect was observed when RAW264.7 and THP-1 cells were exposed to PF (0-1 µm) and/or LPS (1 µg/ml) for 24 hr. The data showed that LPS, which was repressed by PF, facilitated the generation of the pro-inflammatory molecules TNF-α and IL-6. In addition, LPS contributed to increased production of intracellular ROS compared with the control group, whereas the administration of PF effectively reduced LPS-related levels of ROS. Moreover, LPS induced the generation of MDA and suppressed the activities of SOD. However, PF treatment strongly decreased LPS-induced MDA levels and increased SOD activities in the RAW264.7 and THP-1 cells. Furthermore, our research confirmed that penfluroidol repressed the secretion of pro-inflammatory molecules by limiting the activation of the NLRP3 inflammasome and reducing oxidative effects via the Nrf2/HO-1 signaling pathway. Conclusion: Penfluroidol attenuated the imbalance of the inflammatory response by suppressing the activation of the NLRP3 inflammasome and reduced oxidative stress via the Nrf2/HO-1 signaling pathway in LPS-induced macrophages.

Predictive value of hyperglycemia on infection in critically ill patients with acute pancreatitis.

To analyze the predictive value of hyperglycemia on the extrapancreatic infection (EPI) and infected pancreatic necrosis (IPN) of severe patients with acute pancreatitis (AP). We enrolled 234 patients with acute pancreatitis admitted to the intensive care unit (ICU) of the Second Affiliated Hospital of Nanchang University from July 2017 to July 2022 for a retrospective cohort study. We collected maximum blood glucose values three times after admission to the ICU within 120 h (Glu1: 0-24 h, Glu2: 24-48 h, Glu3: 48-120 h), the levels of leucocyte, blood urea nitrogen (BUN), C-reactive protein (CRP), procalcitonin (PCT), and albumin within 24 h after admission to the ICU, and the BISAP and SIRS scores of all patients within 24 h. EPI was taken as the primary outcome indicator and IPN as the secondary outcome indicator. The accuracy of blood glucose values in predicting acute pancreatitis infection was measured by the area under the curve (AUC). A total of 56 patients appeared EPI. Univariate analysis showed that Glu3 was associated with IPN in critically ill patients with AP. Multivariate logistic regression analysis showed that Glu2, Glu3, and SIRS > 48 h were associated with EPI in critically ill patients with AP. The AUCs of Glu2 and Glu3 to predict EPI were 0.805(95%CI: 0.717-0.892) and 0.782(95%CI: 0.685-0.878), respectively, and the cutoff values were 12.60 mmol/L and 14.75 mmol/L, respectively. The AUC of Glu2 combined with Glu3 to predict EPI was 0.812(0.725-0.899). The maximum blood glucose on Day2-5 after admission to the ICU can predict infection in critically ill patients with AP. There are differences in etiology while glucose predicting infection. Patients with hypertriglyceridemia AP need to intervene blood glucose levels more actively and earlier, and control it more strictly.

Ultrasound dynamic monitoring of IVCD to guide application of CRRT in patients with renal failure combined with acute heart failure.

We explored the application value of bedside ultrasound dynamic monitoring of the inferior vena cava diameter (IVCD) and collapse with sniff (inferior vena cava collapsibility index [IVCCI]) to guide dehydration adjustment in continuous renal replacement therapy (CRRT) in patients with combined renal failure and acute heart failure. We selected 90 patients with combined renal and acute heart failure who required CRRT in the intensive care unit (ICU) from January 2019 to June 2021. According to different blood volume assessment methods, patients were randomly divided into ultrasound, experience, and control groups. We compared serum creatinine, potassium, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels; time to improved heart failure symptoms; CRRT time; ventilator use; ICU length of stay; vasopressor use; and incidence of adverse events among groups. There were no significant differences in serum creatinine, potassium, and NT-proBNP levels in pairwise comparisons among groups before and after CRRT (P > 0.05). The time to improved heart failure symptoms, CRRT time, and ICU length of stay in the ultrasound and experience groups were lower than those in the control group; the differences were statistically significant (P < 0.05). Ventilator use duration was lower in the ultrasound and experience groups compared with the control group, with a statistically significant difference between the ultrasound and control groups (P < 0.05). The duration of vasopressor use in the ultrasound and control groups was lower than that in the experience group; the difference was statistically significant (P < 0.05). The incidence of adverse events was lower in the ultrasound group compared with the experience and control groups; the difference was statistically significant (P < 0.05). Ultrasound dynamic monitoring of IVCD and collapse with sniff can accurately assess blood volume status, and provide guidance for dehydration adjustments in CRRT and rapid relief of heart failure symptoms in patients with combined renal and acute heart failure.

SVD-CNN: A Convolutional Neural Network Model with Orthogonal Constraints Based on SVD for Context-Aware Citation Recommendation.

Context-aware citation recommendation aims to automatically predict suitable citations for a given citation context, which is essentially helpful for researchers when writing scientific papers. In existing neural network-based approaches, overcorrelation in the weight matrix influences semantic similarity, which is a difficult problem to solve. In this paper, we propose a novel context-aware citation recommendation approach that can essentially improve the orthogonality of the weight matrix and explore more accurate citation patterns. We quantitatively show that the various reference patterns in the paper have interactional features that can significantly affect link prediction. We conduct experiments on the CiteSeer datasets. The results show that our model is superior to baseline models in all metrics.

Volatile organic compounds analysis as a potential novel screening tool for colorectal cancer: A systematic review and meta-analysis.

The purpose of this meta-analysis was to assess the usefulness of volatile organic compounds (VOC) as a potential novel biomarker for colorectal cancer (CRC).We systematically searched PubMed, Embase, Web of Science, and Cochrane Library databases for observational studies (published before November 25th, 2019; no language restrictions) comparing the VOC analysis between patients with CRC and healthy controls. We evaluated the pooled sensitivity, specificity, diagnostic odds ratio, positive and negative likelihood ratio, as well as summary receiver operating characteristic curve and area under the curve.We identified a total of 10 observational studies that included 381 patients with CRC and 436 healthy controls. Bivariate analysis yielded a pooled sensitivity of 0.82 (95% confidence interval [CI] = 0.77-0.86), specificity of 0.79 (95% CI = 0.71-0.85), positive likelihood ratio of 3.8 (95% CI = 2.8-5.3), and negative likelihood ratio of 0.23 (95% CI = 0.17-0.30). The area under the curve was 0.87 (95% CI = 0.84-0.90). The pooled diagnostic odds ratio was 17 (95% CI = 10-28). Sensitivity analysis indicated that the pooled results were stabilized. The Deeks' funnel plot asymmetry test (P = .41) suggested no potential publication bias.Our pooled data confirmed the associations between VOC analysis and CRC, highlighting the usefulness of VOC analysis as a potential novel screening tool for CRC. However, standardization of VOC collection and analysis methods for CRC screening is required in future research.

Effect of parenteral glutamine supplementation combined with enteral nutrition on Hsp90 expression and Peyer's patch apoptosis in severely burned rats.

OBJECTIVES: The aim of this study was to investigate the effects of parenteral glutamine (GLN) supplementation combined with enteral nutrition (EN) on heat shock protein (Hsp) 90 expression and Peyer's patch (PP) apoptosis in severely burned rats. METHODS: Male Sprague-Dawley (SD) rats were randomly assigned to four groups: Sham burn + EN + GLN-free amino acid (AA; n = 10), sham burn + EN + GLN (n = 10), burn + EN + AA (n = 10), and burn + EN + GLN (n = 10). Two hours after a 30% total body surface area (TBSA), full-thickness scald burn injury on the back, burned rats in two of the experimental groups (burn + EN + AA and burn + EN + GLN groups) were fed with a conventional EN solution by oral gavage for 7 d. Simultaneously, rats in the burn + EN + GLN group were given 0.35 g GLN/kg body weight/d once via a tail vein injection for 7 d and rats in the burn + EN + AA group were administered isocaloric/isonitrogenous GLN-free amino acid solution (Tyrosine) for comparison. Rats in two sham burn control groups (sham burn + EN + AA and sham burn + EN + GLN groups) were treated in the same manner except for the burn injury. All rats in the four groups were given 175 kcal/kg body wt/d. There was isonitrogenous, isovolumic, and isocaloric intake among the four groups. At the end of the seventh day after completion of the nutritional program, all rats were anesthetized and samples were collected for further analysis. PP apoptosis was measured by terminal deoxyuridine nick-end labeling (TUNEL). The expression of Hsp90 in PPs was analyzed by western blotting. Caspase-3 activity of PPs was also assessed. Levels of proinflammatory cytokines of gut tissues were evaluated by enzyme-linked immunosorbent assay (ELISA). The intestinal immunoglobulin A (IgA) content was also determined by ELISA. RESULTS: The results revealed that intestinal IgA content in rats of the burn + EN + GLN group were significantly increased compared with those in the burn + EN + AA group (P < 0.05). The expression of Hsp90 of PPs in rats in the burn + EN + GLN group was significantly upregulated compared with those in the burn + EN + AA group (P < 0.05). On the other hand, levels of proinflammatory cytokines of gut tissues, caspase-3 activity, and the number of TUNEL-stained cells of PPs in rats of the burn + EN + GLN group were markedly decreased compared with those of the burn + EN + AA group (P < 0.05). CONCLUSIONS: The results of this study show that parenteral glutamine supplementation combined with EN may upregulate the expression of Hsp90, reduce caspase-3 activity, lessen the release of proinflammatory cytokines, attenuate PP apoptosis, and improve intestinal IgA response in burned rats. Clinically, therapeutic efforts to improve intestinal immunity may contribute to a favorable outcome in severely burned patients.

Glutamine reduces myocardial cell apoptosis in a rat model of sepsis by promoting expression of heat shock protein 90.

BACKGROUND: Myocardial cell injury and cardiac myocyte apoptosis are associated with sepsis. Glutamine (Gln) has been reported to repair myocardial cell injury. The aim of this study was to explore the role of Gln on cardiac myocytes in a cecal ligation and puncture (CLP) model of sepsis in Wistar rats. MATERIALS AND METHODS: Following induction of sepsis in a CLP rat model, viral encoding heat shock protein 90 (Hsp90) gene and Hsp90dsDNA were designed to express and knockdown Hsp90, respectively. Rat cardiac tissues were examined histologically, and apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, Hsp90, p53 upregulated modulator of apoptosis, and p53 was measured by western blotting and real-time polymerase chain reaction. Caspase-3, caspase-8, and caspase-9 were detected by enzyme-linked immunosorbent assay. RESULTS: Rat cardiac myocyte damage induced by CLP was reduced by Gln treatment and Hsp90 overexpression, and these changes were reversed by Hsp90 knockdown. Bcl-2 expression, Bcl-2-associated X protein, p53, p53 upregulated modulator of apoptosis, caspase-8, caspase-9, and caspase-3 activities were significantly upregulated in the CLP model, which were reduced by Gln treatment and Hsp90 overexpression. CONCLUSIONS: Gln reduced apoptosis of cardiac myocytes in a rat model of sepsis, by promoting Hsp90 expression. Further studies are needed to determine the possible therapeutic action of Gln in sepsis in human tissue.

Effects of enteral nutrition with parenteral glutamine supplementation on the immunological function in septic rats.

The aim of the present study was to investigate the effects of enteral nutrition (EN) with parenteral glutamine (GLN) supplementation on inflammatory response, lymphatic organ apoptosis, immunological function and survival in septic rats by caecal ligation and puncture (CLP). Male rats were randomly assigned into two experimental groups and two sham CLP control groups (n 10 per group). After CLP or sham CLP model and nutrition programme were completed, the GLN concentrations of plasma and tissues and several indices of immunological function including serum Ig content, circulating lymphocyte number, the CD4:CD8 ratio, the neutrophil phagocytosis index (NPI), the organ index and apoptosis of thymus and spleen, and plasma cytokine levels were determined. Moreover, the survival in septic rats was observed. The results revealed that EN with parenteral GLN supplementation remarkably increased the GLN concentrations of plasma and tissues, serum Ig content, the circulating lymphocyte number, the CD4:CD8 ratio, the indexes of thymus and spleen, NPI and survival compared with the control group (P< 0·05). In contrast, the apoptosis of thymus and spleen and the levels of TNF-α, IL-1ß and IL-6 in plasma were obviously decreased compared with the control group (P< 0·05). These results show that EN with parenteral GLN supplementation diminished the release of inflammatory cytokines, attenuated lymphatic organ apoptosis, enhanced the immunological function and improved survival in septic rats.

Parenteral glutamine supplementation in combination with enteral nutrition improves intestinal immunity in septic rats.

OBJECTIVES: The gut-associated lymphoid tissue is continuously exposed to antigens in the gut lumen and becomes the first line of defense against enteric bacteria and associated toxin. The aim of this study was to investigate the effects of parenteral glutamine (GLN) supplementation in combination with enteral nutrition (EN) on intestinal mucosal immunity in septic rats by cecal ligation and puncture (CLP). METHODS: Male Sprague-Dawley rats were randomly assigned into four groups: A sham CLP + EN + saline group (n = 10), a sham CLP + EN + GLN group (n = 10), a CLP + EN + saline group (n = 10), and a CLP + EN + GLN group (n = 10). At 2 h after CLP or sham CLP, all rats in each of the four groups received an identical enteral nutrition solution as their base formula. Then, the rats in the sham CLP + EN + GLN group and CLP + EN + GLN group were given 0.35 g GLN/kg body weight daily for 7 d, all at the same time, via a tail vein injection; whereas those in the sham CLP + EN + saline group and CLP + EN + saline group were daily administered isovolumic sterile 0.9% saline for comparison. All rats in each of the four groups were given 290 kcal/kg body wt/d for 7 d. At the end of the seventh day after the nutritional program was finished, all rats were euthanized and the entire intestine was collected. Total Peyer's patches (PP) cell yield was counted by a hemocytometer. The percentage of PP lymphocyte subsets was analyzed by flow cytometry. The number of intestinal lamina propria IgA plasma cells was determined by the immunohistochemistry technique. The intestinal immunoglobulin A (IgA) levels were assessed by ELISA. PP apoptosis was evaluated by terminal deoxyuridine nick-end labeling. RESULTS: The results revealed total PP cell yield, the numbers of PP lymphocyte subsets, intestinal lamina propria IgA plasma cells, and intestinal IgA levels in the CLP + EN + GLN group were significantly increased when compared with the CLP + EN + saline group (P < 0.05). On the other hand, the number of TUNEL-stained cells within PPs in the CLP + EN + GLN group was markedly decreased as compared with the CLP + EN + saline group (P < 0.05). CONCLUSION: The results of this study show that parenteral glutamine supplementation in combination with enteral nutrition may attenuate PP apoptosis, increase PP cell yield and intestinal lamina propria IgA plasma cells, and subsequently improve intestinal mucosal immunity. Clinically, these results suggest therapeutic efforts at improving intestinal immunity may contribute to the prevention and treatment of sepsis.

[Preliminary exploration of transcription factor Nkx2.5 mutations and congenital heart diseases].

OBJECTIVE: To explore the association between the gene mutation of transcription factor Nkx2.5 and Chinese patients with congenital heart disease (CHD). METHODS: Polymerase chain reaction (PCR) and DNA sequencing were used to check 99 CHD patients and 90 normal control subjects from the Zhong Da Hospital of Southeast University. After amplifying the exons 1 of the Nkx2.5 gene by PCR, we purified the PCR products and conducted the sequencing reaction, analyzed the mutation screening of the exon 1 of the Nkx2.5, investigated whether or not the Nkx2.5 is related with the CHD in Chinese population. RESULTS: A mutation (A239G) in the exon 1 of the Nkx2.5 was identified in 3 of 90 normal control subjects and 12 of 99 CHD patients, including 3 of 24 with VSD, 7 of 35 with ASD, 1 of 13 with PS and 1 of 21 with PDA. CONCLUSION: There are some associations between the Nkx2.5 gene mutation and occurrence of congenital heart disease in Chinese people.