PTEN deficiency induces an extrahepatic cholangitis-cholangiocarcinoma continuum via aurora kinase A in mice.

BACKGROUND & AIMS: The PTEN-AKT pathway is frequently altered in extrahepatic cholangiocarcinoma (eCCA). We aimed to evaluate the role of PTEN in the pathogenesis of eCCA and identify novel therapeutic targets for this disease. METHODS: The Pten gene was genetically deleted using the Cre-loxp system in biliary epithelial cells. The pathologies were evaluated both macroscopically and histologically. The characteristics were further analyzed by immunohistochemistry, reverse-transcription PCR, cell culture, and RNA sequencing. Some features were compared to those in human eCCA samples. Further mechanistic studies utilized the conditional knockout of Trp53 and Aurora kinase A (Aurka) genes. We also tested the effectiveness of an Aurka inhibitor. RESULTS: We observed that genetic deletion of the Pten gene in the extrahepatic biliary epithelium and peri-ductal glands initiated sclerosing cholangitis-like lesions in mice, resulting in enlarged and distorted extrahepatic bile ducts in mice as early as 1 month after birth. Histologically, these lesions exhibited increased epithelial proliferation, inflammatory cell infiltration, and fibrosis. With aging, the lesions progressed from low-grade dysplasia to invasive carcinoma. Trp53 inactivation further accelerated disease progression, potentially by downregulating senescence. Further mechanistic studies showed that both human and mouse eCCA showed high expression of AURKA. Notably, the genetic deletion of Aurka completely eliminated Pten deficiency-induced extrahepatic bile duct lesions. Furthermore, pharmacological inhibition of Aurka alleviated disease progression. CONCLUSIONS: Pten deficiency in extrahepatic cholangiocytes and peribiliary glands led to a cholangitis-to-cholangiocarcinoma continuum that was dependent on Aurka. These findings offer new insights into preventive and therapeutic interventions for extrahepatic CCA. IMPACT AND IMPLICATIONS: The aberrant PTEN-PI3K-AKT signaling pathway is commonly observed in human extrahepatic cholangiocarcinoma (eCCA), a disease with a poor prognosis. In our study, we developed a mouse model mimicking cholangitis to eCCA progression by conditionally deleting the Pten gene via Pdx1-Cre in epithelial cells and peribiliary glands of the extrahepatic biliary duct. The conditional Pten deletion in these cells led to cholangitis, which gradually advanced to dysplasia, ultimately resulting in eCCA. The loss of Pten heightened Akt signaling, cell proliferation, inflammation, fibrosis, DNA damage, epigenetic signaling, epithelial-mesenchymal transition, cell dysplasia, and cellular senescence. Genetic deletion or pharmacological inhibition of Aurka successfully halted disease progression. This model will be valuable for testing novel therapies and unraveling the mechanisms of eCCA tumorigenesis.

Albumin infusion may decrease the mortality of hypoalbuminemia patients with severe acute pancreatitis: a retrospective cohort study.

BACKGROUND: At present, the relationship between severe acute pancreatitis (SAP) and albumin infusion is not clear. We aimed to identify the impact of serum albumin on the prognosis of SAP and the association between albumin infusions and mortality for hypoalbuminemia patients. METHODS: This was a retrospective cohort study that analyzed 1000 patients with SAP who were admitted to the First Affiliated Hospital of Nanchang University between January 2010 and December 2021 using data from a prospectively maintained database. Multivariate logistic regression analysis was conducted to reveal the relationship between serum albumin within 1 week after admission and poor prognosis of SAP. Propensity score matching (PSM) analysis was adopted to evaluate the effect of albumin infusion for hypoalbuminemia patients with SAP. RESULTS: The prevalence of hypoalbuminemia (≤ 30 g/L) was 56.9% within 1 week after admission. Multivariate logistic regression identified that age (OR: 1.02; 95% CI: 1.00-1.04; P = 0.012), serum urea (OR: 1.08; 95% CI: 1.04-1.12; P < 0.001), serum calcium (OR: 0.27; 95% CI: 0.14-0.50; P < 0.001), lowest albumin level within 1 week after admission (OR: 0.93; 95% CI: 0.89-0.97; P = 0.002), and APACHE II score ≥ 15 (OR: 1.73; 95% CI: 1.19-2.51; P = 0.004) were independently associated with mortality. The PSM analysis demonstrated that mortality (OR: 0.52, 95% CI: 0.29-0.92, P = 0.023) was less common in albumin-infused than non-albumin-infused hypoalbuminemia patients. In subgroup analyses, doses > 100 g within 1 week after admission for hypoalbuminemia patients with albumin infusions was associated with lower mortality than doses ≤ 100 g (OR: 0.51, 95% CI: 0.28-0.90, P = 0.020). CONCLUSIONS: Hypoalbuminemia in early-stage SAP is significantly related to poor prognosis. However, albumin infusions could significantly decrease mortality in hypoalbuminemia patients with SAP. Additionally, infusing sufficient albumin within a week after admission may decrease mortality in hypoalbuminemia patients.

Node-splitting optimized canonical correlation forest algorithm for sea fog detection using MODIS data.

In this paper, a node splitting optimized canonical correlation forest algorithm for sea fog detection is proposed by using active and passive satellites. The traditional canonical correlation forest (CCF) algorithm insufficiently accounts for the spectral characteristics and the reliability of each classifier during integration. To deal with the problem, the information gain rate of node entropy is used as the splitting criterion, and the spectral characteristics of clouds and fogs are also combined into the model generation process. The proposed algorithm was verified using the meteorological station data and compared with five state-of-the-art algorithms, which demonstrated that the algorithm has the best performance in sea fog detection and can identify mist better.

MiR155 Disrupts the Intestinal Barrier by Inducing Intestinal Inflammation and Altering the Intestinal Microecology in Severe Acute Pancreatitis.

BACKGROUND: Intestinal dysfunction is a common complication of acute pancreatitis. MiR155 may be involved in the occurrence and development of intestinal dysfunction mediated by acute pancreatitis, but the specific mechanism is not clear. AIMS: To investigate the effect of miR155 on severe acute pancreatitis (SAP)-associated intestinal dysfunction and its possible mechanism in a mice model. METHODS: In this study, SAP mice model was induced by intraperitoneal injection of caerulein and LPS in combination. Adeno-associated virus (AAV) was given by tail vein injection before the SAP model. The pancreatic and intestinal histopathology changes were analyzed. Cecal tissue was collected for 16S rRNA Gene Sequencing. Intestinal barrier proteins ZO-1 and E-cad were measured by Immunohistochemistry Staining and Western Blot, respectively. Intestinal tissue miR155 and inflammatory factors TNF-α, IL-1ß, and IL-6 were detected by Q-PCR. The expression levels of protein associated with TNF-α and TLR4/MYD88 pathway in the intestinal were detected. RESULTS: In miR155 overexpression SAP group, the levels of tissue inflammatory factor were significantly increased, intestinal barrier proteins were significantly decreased, and the injury of intestinal was aggravated. Bacterial 16S rRNA sequencing was performed, showing miR155 promotes gut microbiota dysbiosis. The levels of TNF-α, TLR4, and MYD88 in the intestinal were detected, suggesting that miR155 may regulate gut microbiota and activate the TLR4/MYD88 pathway, thereby affecting the release of inflammatory mediators and regulating SAP-related intestinal injury. After application of miR155-sponge, imbalance of intestinal flora and destruction of intestinal barrier-related proteins have been alleviated. The release of inflammatory mediators decreased, and the histopathology injury of intestinal was improved obviously. CONCLUSION: MiR155 may play an important role in SAP-associated intestinal dysfunction. MiR155 can significantly alter the intestinal microecology, aggravated intestinal inflammation through TLR4/MYD88 pathway, and disrupts the intestinal barrier in SAP mice.

Effects of Lacidophilin Tablets, Yogurt, and Bifid Triple Viable Capsules on the Gut Microbiota of Mice with Antibiotic-Associated Diarrhea.

Antibiotic-associated diarrhea (AAD) is a common morbidity caused by antibiotic use and is characterized by the dysbiosis of the gut microbiota. Several clinical trials have shown that probiotics can prevent AAD. This study aimed at investigating the effects of Lacidophilin tablets (LB), yogurt (YG), and bifid triple viable capsules (BT) on the gut microbiota of mice with AAD. Mice with diarrhea were randomly allocated to treatment groups or the control group and were treated with either LB, YG, BT, or vehicle control. The body weight, diarrhea scores, cecum index, and cecal length were determined. Fecal samples of all mice were analyzed using 16S rRNA high-throughput sequencing. The results showed that LB, YG, and BT significantly decreased the diarrhea scores and inhibited increases in the cecum index and cecal length induced by AAD. In addition, they significantly changed the composition and richness of the gut microbiota. Specifically, they increased the abundance of the phylum Firmicutes and decreased the abundance of the phyla Bacteroidetes and the family Bacteroidaceae. Treatment with LB and YG also decreased the abundance of the phylum Proteobacteria and only LB could mediate the reduced levels of Lactobacillaceae in AAD mice. At the genus level, YG and BT treatment decreased the abundance of Bacteroides or Parasutterella. To our surprise, only LB treatment dramatically increased the abundance of Lactobacillus and decreased that of potential pathogens, such as Bacteroides, Parabacteroides, and Parasutterella, to almost normal values. Our findings indicate that LB, YG, and BT ameliorated diarrhea by regulating the composition and structure of the gut microbiota and that LB plays an important role in regulating the gut microbiota.

Heparin-Binding Protein Levels at Admission and Within 24 h Are Associated with Persistent Organ Failure in Acute Pancreatitis.

BACKGROUND: Identification of patients at risk for persistent organ failure (POF) early in the course of acute pancreatitis (AP) is critical for early intervention. Heparin-binding protein (HBP) levels are closely related to inflammation. Therefore, we investigated the relationship between HBP levels and POF in patients with AP. METHODS: This observational cohort study analyzed 66 patients with AP and 14 healthy volunteers between June 2019 and December 2019. Baseline characteristics, laboratory data, and severity scores of patients with different degrees of AP were compared. Levels of HBP were measured by ELISA. Serum HBP levels were analyzed using receiver operating characteristic curves to identify POF in AP. RESULTS: Concentrations of serum HBP in healthy volunteers, MAP, MSAP, and SAP groups were 3.9 (range: 3.4-5) ng/ml, 5.2 (3.9-6.8) ng/ml, 5.9 (4.6-7.7) ng/ml, and 11 (8.0-13.8) ng/ml, respectively. The level of HBP in SAP patients was significantly elevated compared to the other groups (P < 0.01). HBP levels ≥ 7 ng/ml showed a specificity of 74%, a sensitivity of 90%, and an AUC of 0.82 for predicting POF. CONCLUSIONS: HBP levels in patients with POF were significantly elevated. HBP is a useful marker for predicting severe AP.

HIV prevalence and incidence estimates among blood donors in five regions in China.

BACKGROUND: Previous data, although scant, indicated that the incidence of HIV in China has increased over the past decade. There is a growing concern about the impact of the HIV epidemic on blood safety. METHODS AND MATERIALS: We used donation data from five geographically-disperse blood centers in 2013-2016 participating in the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) China program to estimate HIV prevalence and incidence among blood donors. Multivariable logistic regression model was used to examine factors associated with HIV infection in Chinese blood donors. RESULTS: The overall HIV prevalence among first-time donors from 2013 through 2016 was 68.04 per 100,000 donors (95% CI 61.68-74.40). The HIV incidence rate was estimated to be 37.93 per 100,000 person-years (95% CI 30.62-46.97) among first-time donors and 20.55 per 100,000 person-years (95% CI 16.95-24.91) among repeat donors. There was substantial variation in HIV prevalence and incidence rates across blood centers. Multivariable logistic regression results showed that among first-time donors, being male, older than 25 years, minority ethnicity, less than college education, and certain occupations (commercial services, factory workers, retired, unemployed, or self-employed) were associated with positive HIV confirmatory testing results. CONCLUSION: HIV prevalence and incidence among blood donors remain low in the selected five regions in China; however, an increasing trend is observed at some blood centers. It is important to monitor HIV epidemiology in Chinese blood donors on a continuous basis, especially among populations and regions of higher risk.

Initially elevated arterial lactate as an independent predictor of poor outcomes in severe acute pancreatitis.

BACKGROUND: The present study aimed to investigate the relationships between arterial lactate levels and outcomes in severe acute pancreatitis. METHODS: The study retrospectively analyzed the medical data of 329 patients with severe acute pancreatitis from January 2014 to February 2019. We compared baseline characteristics, laboratory data, severity scores, types of persistent organ failure, and primary and secondary outcomes of patients with and without elevated arterial lactate levels at admission. A multivariate logistic regression analysis model and receiver operating characteristic curve were adopted to evaluate the value of arterial lactate ≥4 mmol/L for identifying high-risk patients. Trends in arterial lactate levels were compared between patients in the survivor and nonsurvivor groups over a period of 7 days. RESULTS: Compared to normal arterial lactate levels, patients with elevated arterial lactate levels show significantly higher incidences of multiple persistent organ failure (3% vs 30%, P < 0.01), death (2% vs 11%, P < 0.01), septic shock (4% vs 24%, P < 0.01), pancreatic infection (12% vs 37%, P < 0.01), abdominal compartment syndrome (3% vs 20%, P < 0.01), pancreatic necrosis (41% vs 63%, P < 0.01), and a need for ventilator support (26% vs 54%, P < 0.01). For predicting mortality, arterial lactate levels ≥4 mmol/L had a high hazard ratio (10, 95% CI; 3.7-27; P < 0.01) and the highest area under the curve (0.78). CONCLUSIONS: Our results indicate that initially elevated arterial lactate is independently associated with poor outcomes and death in patients with severe acute pancreatitis and may serve as an early high-risk stratification indicator.

Comparison of percutaneous vs endoscopic drainage in the management of pancreatic fluid collections: A prospective cohort study.

BACKGROUND AND AIM: Currently, endoscopic drainage (ED) and percutaneous drainage (PD) are both widely used effective interventions in the management of patients with symptomatic pancreatic fluid collections (PFCs). This study aimed to compare the clinical effectiveness and safety of ED to those of PD in the treatment of PFCs. METHODS: A prospective cohort study of PFC patients who underwent ED or PD was conducted between January 2009 and December 2017. In this study, the initial success rate, adverse events, intervention, requirement of surgical treatment, hospital mortality within 30 days, length of hospital stay, and expenses during hospitalization were monitored, and a follow-up investigation of treatment outcome was conducted. Long-term recovery, recurrence, and mortality were determined according to telephone follow up. RESULTS: In total, 129 patients were included in the study; 62 patients underwent ED, and 67 patients underwent PD during the 8-year study period. Initial treatment success was considerably higher in patients whose PFCs were managed by ED than in patients whose PFCs were managed by PD (94.9% vs 65.0%, P = 0.003). The rate of procedural adverse events, reintervention, length of hospitalization, and expense were all higher in the PD group than in the ED group, but the long-term recovery rate and requirement of surgical intervention were not clearly different between patients who underwent the two treatment measures. CONCLUSION: ED of symptomatic PFCs was associated with higher rates of initial treatment success, lower rates of reintervention and adverse events, and a shorter hospital stay than PD of symptomatic PFCs.

Synthesis and antibacterial activity of 11,12-cyclic carbonate 4″-O-aralkylacetylhydrazineacyl azithromycin derivatives.

Two series of novel 4″-O-aralkylacetylhydrazineacyl azithromycin derivatives were synthesized and evaluated for their in vitro antibacterial activities. Among them, compound B4, B5, B13 and B18 were found to display significantly improved activity than control drugs (MIC > 128 µg/mL) against methicillin-resistant strain S. aureus ATCC 43,300 with an MIC value 2-4 µg/mL. Remarkably, compound B5 and B13 showed potent activity against penicillin-resistant S. aureus ATCC31007 (MIC = 4 µg/mL) and methicillin-resistant S. aureus ATCC 43,300 (MIC = 2 µg/mL).

Opportunities and challenges of using five-membered ring compounds as promising antitubercular agents.

Tuberculosis (TB), a chronic infectious disease, is one of the greatest risks to human beings and 10 million people were diagnosed with TB and 1.6 million died from this disease in 2017. In addition, with the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the TB situation has become even worse, which has aggravated the mortality and spread of this disease. To overcome this problem, research into novel antituberculosis agents with enhanced activities against MDR-TB, reduced toxicity, and shortened duration of therapy is of great importance. Fortunately, many novel potential anti-TB drug candidates with five-membered rings, which are most likely to be effective against sensitive and resistant strains, have recently entered clinical trials. Different five-membered rings such as furans, pyranoses, thiazoles, pyrazolines, imidazoles, oxazolidinone, thiazolidins, isoxazoles, triazoles, oxadiazoles, thiadiazoles, and tetrazoles have been designed, prepared, and evaluated for their antimycobacterial activity against Mycobacterium tuberculosis. In this article, we highlight the recent advances made in the discovery of novel five-membered ring compounds and focus on their antitubercular activities, toxicity, structure-activity relationships, and mechanisms of action.

Elevated intracellular trypsin exacerbates acute pancreatitis and chronic pancreatitis in mice.

Intra-acinar trypsinogen activation occurs in the earliest stages of pancreatitis and is believed to play important roles in pancreatitis pathogenesis. However, the exact role of intra-acinar trypsin activity in pancreatitis remains elusive. Here, we aimed to examine the specific effects of intra-acinar trypsin activity on the development of pancreatitis using a transgenic mouse model. This transgenic mouse model allowed for the conditional expression of a mutant trypsinogen that can be activated specifically inside pancreatic acinar cells. We found that expression of this active mutated trypsin had no significant effect on triggering spontaneous pancreatitis. Instead, several protective compensatory mechanisms, including SPINK1 and heat shock proteins, were upregulated. Notably, these transgenic mice developed much more severe acute pancreatitis, compared with control mice, when challenged with caerulein. Elevated tissue edema, serum amylase, inflammatory cell infiltration and acinar cell apoptosis were dramatically associated with increased trypsin activity. Furthermore, chronic pathological changes were observed in the pancreas of all transgenic mice, including inflammatory cell infiltration, parenchymal atrophy and cell loss, fibrosis, and fatty replacement. These changes were not observed in control mice treated with caerulein. The alterations in pancreata from transgenic mice mimicked the histological changes common to human chronic pancreatitis. Taken together, we provided in vivo evidence that increased intra-acinar activation of trypsinogen plays an important role in the initiation and progression of both acute and chronic pancreatitis. NEW & NOTEWORTHY Trypsinogen is activated early in pancreatitis. However, the roles of trypsin in the development of pancreatitis have not been fully addressed. Using a genetic approach, we showed trypsin activity is critical for the severity of both acute and chronic pancreatitis.

The prevalence of human T-cell leukemia virus in blood donors in China.

BACKGROUND: China has not yet incorporated routine human T-lymphotropic virus (HTLV)-1/2 blood donor screening, even though HTLV has been reported in the southeastern coastal region. This study was conducted to investigate the prevalence of HTLV in five major regions across of China. METHODS: From January 2016 to December 2017, blood samples were collected in 20 blood centers located in different regions of China. These samples were screened for HTLV-1/2 antibodies using enzyme-linked immunosorbent assay (ELISA). If the test samples were reactive, the samples were confirmed with a western blot (WB) assay. If the results of WB were indeterminate, the donor was interviewed after a minimum lapse of 8 weeks. All follow-up samples from donors were tested for anti-HTLV-1/2 with ELISA and WB. RESULTS: There were 875,453 donor samples tested for anti-HTLV-1/2 by ELISA. In all, 365 samples tested negative, 22 samples tested positive by WB, and 14 samples with HTLV status undetermined due to being lost to follow-up. The prevalences were 11.09, 5.96, 3.16, 2.88 and 0.98 per 100,000 in Xiamen, Changsha, Beijing, Shenzhen, and Nanjing blood center, respectively. The prevalences were 0 per 100,000 for all 15 other blood centers. There was significant differences in the prevalence of HTLV in different regions of China (p = 0.0011). CONCLUSION: In China, HTLV-1 confirmed positive donors are mainly from southeastern coastal areas. It may be necessary to conduct HTLV screening in these areas to reduce the risk of transfusion-transmitted HTLV.

Elevated arterial lactate level as an independent risk factor for pancreatic infection in moderately severe acute pancreatitis.

PURPOSE: The present study aimed to research the relationships between arterial lactate levels and pancreatic infection in moderately severe acute pancreatitis. METHODS: This study retrospectively analyzed data from 503 patients with moderately severe acute pancreatitis from January 1, 2013, to March 31, 2018. The baseline characteristics on admission were compared between patients with and without elevated arterial lactate levels. The parameters and laboratory data were compared between patients with and without pancreatic infections at admission. Univariate and multivariate logistic regression analyses were used to assess the value of elevated arterial lactate levels for identifying high-risk patients. P ≤ 0.05 was considered statistically significant. RESULTS: A total of 49 (9.2%) patients were diagnosed with pancreatic infections. Compared with patients without pancreatic infections, pancreatic infection patients had significantly increased arterial lactate levels at admission (1.5 ±â€¯0.7 vs. 2.5 ±â€¯0.9; P < 0.01). Multivariate logic analysis still showed that higher arterial lactate levels in moderately severe acute pancreatitis was an independent risk factor for developing pancreatic infections (hazard ratio: 6.31, 95% CI 3.01-13.24; P < 0.01). Arterial lactate level ≥2.1 mmol/L and procalcitonin level ≥0.5 ng/mL at admission had area under the receiver operating characteristic curves of 0.83 and 0.72, with sensitivity of 67.2% and 87%, and specificity of 82.0% and 60%, respectively, for the prediction of pancreatic infection in moderately severe acute pancreatitis. CONCLUSIONS: Our results indicate that a higher arterial lactate level is independently associated with pancreatic infection in patients with moderately severe acute pancreatitis and may be used as a tool to identify high-risk patients.

Serum D-dimer levels at admission for prediction of outcomes in acute pancreatitis.

BACKGROUND: Systemic alterations in coagulation are associated with complications of acute pancreatitis (AP). D-dimer, a fibrin degradation product, was recently described as a marker of pancreatitis outcome. Early prediction is essential for reducing mortality in AP. The present study aims to assess the relationship between elevated serum D-dimer levels and the severity of AP. METHODS: We performed an observational retrospective study with data from 3451 enrolled patients with AP. Serum D-dimer levels were measured upon admission, after 24 h and during the week after admission by immunoturbidimetry. Univariate and multivariate analyses were used to determine whether elevated D-dimer levels were independently associated with the severity of AP. RESULTS: Of the 3451 AP patients, 2478 (71.8%) had serum D-dimer levels measured within 24 h of hospital admission; 1273 of these patients had D-dimer levels ≤2.5 mg/L, and 1205 had D-dimer levels > 2.5 mg/L (934 patients had mild AP (MAP); 1086, moderately severe AP (MSAP); and 458, severe AP (SAP)). Patients with D-dimer levels > 2.5 mg/L (n = 1205) had higher incidences of SAP (75.5% vs. 24.5%), acute peripancreatic fluid collection (APFC) (53.3% vs. 46.7%), acute necrotic collection (ANC) (72.4% vs. 27.6%), pancreatic necrosis (PN) (65.2% vs. 34.8%), infected pancreatic necrosis (IPN) (77.7% vs. 22.8%), organ failure (OF) (68.5% vs. 31.5%), persistent organ failure (POF) (75.5% vs. 24.5%), ICU requirement (70.2% vs. 29.8%), and mortality (79.2% vs. 20.8%) than did patients with D-dimer levels ≤2.5 mg/L (n = 1273). The multivariate analysis showed that patients with higher serum D-dimer levels had poorer prognoses that worsened over time. CONCLUSION: The measurement of D-dimer levels at admission may be useful for risk stratification of AP.

Association of Serum Levels of Silent Information Regulator 1 with Persistent Organ Failure in Acute Pancreatitis.

BACKGROUND/AIMS: Early assessment is a key factor for adequate and comprehensive treatment of acute pancreatitis (AP). Silent information regulator 1 (SIRT1) plays an important role in inflammation. The aim was to explore the relationship between serum SIRT1 and persistent organ failure (POF) in patients with AP. METHODS: Thirty-seven healthy controls (HCs) and 113 patients with AP were recruited for this study. All 113 patients whose blood samples were collected on the first morning after admission were within 48 h of the onset of AP symptoms. The concentration of serum SIRT1 protein was determined by enzyme-linked immunosorbent assay. RESULTS: The serum SIRT1 protein levels were 1495.7 ± 185.9, 2098.3 ± 153.6, 2498.4 ± 198.2, and 3674.3 ± 170.8 pg/ml in the HCs, mild AP, moderately severe AP, and severe AP groups, respectively. Obvious differences were observed between HCs and patients with AP (P < 0.05). Significant increases were observed in SIRT1 concentrations in patients with POF compared with non-POF patients (P < 0.05). When the cut-off of the SIRT1 concentration was 4065.4 pg/ml, the serum SIRT1 concentration had an area under the curve (AUC) of the receiver operating characteristic curve of 0.825 (95% CI 0.744-0.906) for predicting POF, with a sensitivity of 61.4% and specificity of 92.8%. Combining serum SIRT1 and bedside index for severity acute pancreatitis (BISAP) achieved 0.931 (95% CI 0.882, 0.980) of AUC for the predication of POF. CONCLUSIONS: High serum SIRT1 levels may serve as an early predictive marker for POF. Combining the serum SIRT1 concentration with BISAP increased the ability to predict outcomes.

Comparison of EUS with MRCP in idiopathic acute pancreatitis: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Idiopathic acute pancreatitis (IAP) poses a diagnostic challenge for gastroenterologists, because confirmation of the disease etiology has important implications for the selection of the best possible treatment and the prevention of possible recurrence or the development of chronic pancreatitis (CP). ERCP, EUS, and MRCP typically are used to diagnose IAP when conventional radiologic methods fail. However, their exact role in the diagnosis of IAP has not yet been determined. METHODS: We searched the PubMed, EMBASE, OVID, Cochrane Library (including CENTRAL), China National Knowledge Infrastructure (CNKI), and Wanfang databases from inception to April 2017. Studies involving the use of EUS and/or MRCP for the etiologic diagnosis of IAP were included. A meta-analysis was performed by using Review Manager Version 5.2 for comparative studies and R software 3.3.3 to determine diagnostic yield of the studies. RESULTS: Among the 34 studies that met the inclusion criteria (n = 2338), 7 studies used a combination of EUS and MRCP and totaled 249 patients. The results comparing EUS with MRCP showed a diagnostic yield of 153 of the 239 patients (64%) in the EUS group, which was higher than the yield of 82 of 238 patients (34%) in the MRCP group (P < .001) in the 7 studies, and the diagnostic yield was 60% in the EUS group, 24% in the MRCP group, and 43% in the MRCP after secretin stimulation (S-MRCP) group. In our subgroup analysis of CP and biliary disease, EUS was superior to MRCP (P < .001), but when comparing the efficacy of the modalities in the diagnosis of pancreatic divisum, S-MRCP was obviously superior to MRCP and EUS (12% vs 2% vs 2%). CONCLUSION: EUS and MRCP should both be used in the diagnostic work-up of IAP as complementary techniques. EUS had a higher diagnostic accuracy than MRCP (64% vs 34%) in the etiologic diagnosis of IAP and should be preferred for establishing a possible biliary disease and CP diagnosis, whereas S-MRCP was superior to EUS and MRCP in diagnosing a possible anatomic alteration in the biliopancreatic duct system, such as pancreatic divisum.

Emerging role of lncRNAs in the normal and diseased intestinal barrier.

OBJECTIVE: A significant effort has been made to understand the intestinal barrier, but the effective means to prevent, reduce, and restore intestinal mucosal damage remains unclear. Recently, a few of studies have explained the mechanism of the intestinal barrier in long noncoding RNAs (lncRNAs). This review aims to summarize recent views on the function of lncRNAs in the intestinal barrier and discuss the emerging role of lncRNAs in intestinal barrier diseases caused by inflammatory diseases. METHODS: Observations led us to believe that lncRNAs participate in inflammatory responses, cell proliferation, and control microbial susceptibility. In view of these, lncRNAs have been proved to involve in the intestinal barrier. RESULTS: lncRNAs directly or indirectly affect TJ mRNA translation and intestinal epithelial cells (IECs) paracellular permeability, as well as IECs proliferation and susceptibility to apoptosis, to modulate the function of the intestinal barrier. miRNAs play a pivotal role in this process. CONCLUSIONS: lncRNAs have been shown to be fundamentally involved in intestinal mucosal regeneration, protection, and epithelial barrier function. It may emerge as new and potential factors to be evaluated in the intestinal barrier diseases caused by acute pancreatitis, inflammatory bowel diseases, and imbalance of intestinal flora.

Regulation of Autophagy Affects the Prognosis of Mice with Severe Acute Pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a common inflammatory disease that may develop to severe AP (SAP), resulting in life-threatening complications. Impaired autophagic flux is a characteristic of early AP, and its accumulation could activate oxidative stress and nuclear factor κB (NF-κB) pathways, which aggravate the disease process. AIM: To explore the therapeutic effects of regulating autophagy after the onset of AP. METHODS: In this study, intraperitoneal injections of 3-methyladenine (3-MA) and rapamycin (RAPA) in the L-arginine or cerulein plus lipopolysaccharide (LPS) Balb/C mouse model. At 24 h after the last injection, pulmonary, intestinal, renal and pancreatic tissues were analyzed. RESULTS: We found that 3-MA ameliorated systemic organ injury in two SAP models. 3-MA treatment impaired autophagic flux and alleviated inflammatory activation by modulating the NF-κB signaling pathway and the caspase-1-IL-1ß pathway, thus decreasing the injuries to the organs and the levels of inflammatory cytokines. CONCLUSION: Our study found that the regulation of autophagy could alter the progression of AP induced by L-arginine or cerulein plus LPS in mice.