Polyamine synthesis enzyme AMD1 is closely related to the tumorigenesis and prognosis of human breast cancer.

Adenosylmethionine decarboxylase 1 (AMD1) has been implicated in carcinogenesis and tumor progression. However, the potential biomechanism and biological implications of AMD1 in breast cancer (BC) remain unclear. The purpose of this study was to investigate the effect of abnormal expression of AMD1 in BC. The expression of AMD1 in different human BC cell lines was studied by using western blotting and qRT-PCR. In vitro cell proliferation, clone formation, cell cycle and apoptosis assays were performed to explore the effect of AMD1 on cellular proliferation. Xenograft mouse models were established to elucidate the role of AMD1 in BC growth. The expression profiles of AMD1 in 28 pairs of BC tissues and adjacent noncancerous tissues (ANTs) were investigated by using western blotting and immunohistochemistry. The clinical implication and prognostic evaluation of AMD1 in BC were examined by excavating the online database. We found that the expression levels of AMD1 in BC cell lines were significantly higher than those in the normal human breast epithelial cell line MCF-10A. In addition, AMD1 potentiated proliferation, induced cell cycle progression and inhibited apoptosis in BC cells. Subcutaneous tumor xenografts also supported the promotive role of AMD1 in BC growth. We discovered that the level of AMD1 in BC tissues was significantly higher than that in ANTs. Using the online database, increased AMD1 was found to be associated with clinical indicators and predicted a poor prognosis in patients with BC. Our findings indicate that AMD1 elicits potent oncogenic effects on the malignant progression of BC. AMD1 might serve as a promising diagnostic biomarker and therapeutic target for patients with BC.

Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells.

BACKGROUND: Undifferentiated carcinoma with osteoclast-like giant cells (OGCs) of pancreas (UCOGCP) is a rare subtype of pancreatic ductal adenocarcinoma (PDAC), which had poorly described histopathological and clinical features. METHODS: In this study, single-cell RNA sequencing (scRNA-seq) was used to profile the distinct tumor microenvironment of UCOGCP using samples obtained from one UCOGCP patient and three PDAC patients. Bioinformatic analysis was carried out and immunohistochemical (IHC) staining was used to support the findings of bioinformatic analysis. After quality control of the raw data, a total of 18,376 cells were obtained from these four samples for subsequent analysis. These cells were divided into ten main cell types following the Seurat analysis pipeline. Among them, the UCOGCP sample displayed distinct distribution patterns from the rest samples in the epithelial cell, myeloid cell, fibroblast, and endothelial cell clusters. Further analysis supported that the OGCs were generated from stem-cell-like mesenchymal epithelial cells (SMECs). RESULTS: Functional analysis showed that the OGCs cluster was enriched in antigen presentation, immune response, and stem cell differentiation. Gene markers such as LOX, SPERINE1, CD44, and TGFBI were highly expressed in this SMECs cluster which signified poor prognosis. Interestingly, in myeloid cell, fibroblasts, and endothelial cell clusters, UCOGCP contained higher percentage of these cells and unique subclusters, compared with the rest of PDAC samples. CONCLUSIONS: Analysis of cell communication depicted that CD74 plays important roles in the formation of the microenvironment of UCOGCP. Our findings illustrated the genesis and function of OGCs, and the tumor microenvironment (TME) of UCOGCP, providing insights for prognosis and treatment strategy for this rare type of pancreatic cancer.

Predictive value of serum cholinesterase in the mortality of acute pancreatitis: A retrospective cohort study.

BACKGROUND: Severe acute pancreatitis has a high mortality of 20%-40%, but there is a lack of optimal prognostic biomarker for the severity of acute pancreatitis (AP) or mortality. This study is designed to investigate the relationship between serum cholinesterase (ChE) level and poor outcomes of AP. METHODS: A total of 1904 AP patients were screened in the study, and we finally got 692 patients eligible for analysis. Patients were divided into 2 groups based on serum ChE. The primary outcome was mortality, and multivariable logistic regression analysis for mortality was completed. Additionally, we used receiver operating characteristic (ROC) curve analysis to clarify the predictive value of serum ChE for mortality and organ failure. RESULTS: Three hundred and seventy eight patients and 314 patients were included in the ChE-low and ChE-normal group, respectively. Patients in the ChE-low group were older (46.68 ± 12.70 vs. 43.56 ± 12.13 years old, p = .001) and had a lower percentage of man (62.4% vs. 71.0%, p = .017) when compared to the ChE-normal group. Mortality was significantly different in two groups (10.3% vs. 0.0%, p < .001). Moreover, organ failure also differed significantly in two groups (46.6% vs. 8.6%, p < .001). Decreased ChE level was independently associated with mortality in acute pancreatitis (odds ratio: 0.440; 95% confidence interval, 0.231, 0.838, p = .013). The area under the curve of serum ChE was 0.875 and 0.803 for mortality and organ failure, respectively. CONCLUSIONS: Lower level of serum ChE was independently associated with the severity and mortality of AP.

Identification of a novel LPL nonsense variant and further insights into the complex etiology and expression of hypertriglyceridemia-induced acute pancreatitis.

BACKGROUND: Hypertriglyceridemia (HTG) is a leading cause of acute pancreatitis. HTG can be caused by either primary (genetic) or secondary etiological factors, and there is increasing appreciation of the interplay between the two kinds of factors in causing severe HTG. OBJECTIVES: The main aim of this study was to identify the genetic basis of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) in a Chinese family with three affected members (the proband, his mother and older sister). METHODS: The entire coding and flanking sequences of LPL, APOC2, APOA5, GPIHBP1 and LMF1 genes were analyzed by Sanger sequencing. The newly identified LPL nonsense variant was subjected to functional analysis by means of transfection into HEK-293 T cells followed by Western blot and activity assays. Previously reported pathogenic LPL nonsense variants were collated and compared with respect to genotype and phenotype relationship. RESULTS: We identified a novel nonsense variant, p.Gln118* (c.351C > T), in the LPL gene, which co-segregated with HTG-AP in the Chinese family. We provided in vitro evidence that this variant resulted in a complete functional loss of the affected LPL allele. We highlighted a role of alcohol abuse in modifying the clinical expression of the disease in the proband. Additionally, our survey of 12 previously reported pathogenic LPL nonsense variants (in 20 carriers) revealed that neither serum triglyceride levels nor occurrence of HTG-AP was distinguishable among the three carrier groups, namely, simple homozygotes, compound heterozygotes and simple heterozygotes. CONCLUSIONS: Our findings, taken together, generated new insights into the complex etiology and expression of HTG-AP.

Downregulation of long non-coding RNA Opa interacting protein 5-antisense RNA 1 inhibits breast cancer progression by targeting sex-determining region Y-box 2 by microRNA-129-5p upregulation.

Several studies have shown an important role for long non-coding RNA (lncRNA) in breast cancer progression. The present study investigated the role of lncRNA Opa interacting protein 5-antisense RNA 1 (OIP5-AS1) in the progression of breast cancer. OIP5-AS1 was significantly upregulated in breast cancer tissues and in breast cancer cell lines, and OIP5-AS1 downregulation inhibited the malignant behavior of breast cancer in vitro and in vivo. For in-depth exploration of the mechanism of OIP5-AS1 in breast cancer, we found that expression of microRNA-129-5p(miR-129-5p), which was found to bind sites in the sequence of OIP5-AS1, in breast cancer tissues was negatively correlated with OIP5-AS1. Also, luciferase assays indicated that OIP5-AS1 acted as a miR-129-5p sponge, resulting in upregulated expression of the sex-determining region Y-box 2 (SOX2) transcription factor. Our study showed that OIP5-AS1 plays a critical role in promoting breast cancer progression and that OIP5-AS1 downregulation targets SOX2 by miR-129-5p upregulation.

Increase in serum chloride and chloride exposure are associated with acute kidney injury in moderately severe and severe acute pancreatitis patients.

OBJECTIVE: We aimed to evaluate whether early (first 48 h) hyperchloremia and/or the change of serum chloride concentration are associated with acute kidney injury (AKI) in patients with moderately severe and severe acute pancreatitis (MSAP and SAP). METHODS: We retrospectively collected the data of patients with a primary diagnosis of MSAP or SAP from a tertiary center between January 2014 and June 2017. Consecutive chloride levels within the first 48 h after admission were retrieved for further calculation. Logistic regression analysis and receiving operating characteristic (ROC) curve were used to assess the relationship between hyperchloremia and AKI. RESULTS: 145 patients were enrolled for analysis, of whom 33.5% (47/145) developed hyperchloremia during the observation period. The incidence of AKI was significantly higher in the hyperchloremia group (40.4% vs 7.1%; p < 0.001). On multivariate analysis, the increase in serum chloride (Δ[Cl-]) was independently associated with AKI [OR = 1.32 (1.00-1.74)], as was chloride exposure [OR = 1.01 (1.00-1.02)], and these associations were found to be stronger in patients identified as predicted SAP (PSAP). Moreover, even in patients without hyperchloremia, increase in serum chloride (Δ[Cl-]) was still associated with AKI [OR = 1.65 (1.18-2.32)]. Area under the curve of the ROC curve (AUCROC) analysis found that Δ[Cl-] is a good predictor of AKI with an optimal cutoff point at 3.5 mmol/L, showing an AUCROC of 0.81. CONCLUSION: Hyperchloremia is common in patients with AP and Δ[Cl-] and chloride exposure during the first 48 h were independent risk factors for AKI in MSAP and SAP patients.

Intestinal tuberculosis: clinico-pathological profile and the importance of a high degree of suspicion.

OBJECTIVES: Intestinal tuberculosis (ITB) remains prevalent and a big health hazard in China. The aim of this study was to retrospectively analyse its clinico-pathological features. METHODS: Retrospective study of 85 consecutive ITB patients in two tertiary hospitals in East China. Relevant clinical, laboratory examination, radiological, endoscopic and histopathological features of ITB were recorded. RESULTS: The mean age was 37.3 ± 16.0 years; 56 patients (65.9%) were male. 67.1% had ITB secondary to pulmonary tuberculosis. The overall median length of hospital stay was 28 days and was significantly longer in patients with intestinal complications (P = 0.003) and malnutrition (P = 0.042). Abdominal pain (88.2%) and weight loss (75.3%) were the commonest symptoms. The positive rate of the purified protein derivative (PPD) test was 88.2%; of the T-spot, 85.7%. Histopathology revealed caseating granuloma in 70.6% and caseating necrosis in 24.7% of patients. The most commonly affected sites were the ileocecal valve (56, 65.9%), terminal ileum (40, 47.1%) and caecum (33, 38.8%). Only 17 (20%) patients were initially diagnosed as ITB, the other 68 patients were misdiagnosed. Six patients with caecum tuberculosis were misdiagnosed as appendicitis, four of whom had improper surgical procedures followed by post-operative intestinal fistulas; two died due to MODS. CONCLUSIONS: Diagnosis of ITB is often misdirected and delayed, which may lead to inappropriate treatment and high mortality. High diagnostic suspicion is necessary for patients with unexplained abdominal complaints. Diagnosis is not easy but could benefit coexisting pulmonary tuberculosis, T-spot, CT imaging, colonoscopy, pathological features, acid-fast bacilli and response to anti-tuberculosis therapy (ATT).

Surgical Site Infection After Gastrointestinal Surgery in China: A Multicenter Prospective Study.

BACKGROUND: There is no nationwide database of information on surgical site infection (SSI) after gastrointestinal surgery in China. This study aimed to determine the incidence of SSI after gastrointestinal surgery in China and evaluate the related risk factors. MATERIALS AND METHODS: The multicenter, prospective, observational study enrolled adult patients who underwent gastrointestinal surgery from May 1, 2018 to June 30, 2018 in 30 hospitals in China. The demographic and perioperative characteristics were collected, and the primary outcome was 30-d SSI. Predictors of SSI were determined by multivariable logistic regressions. Subgroup analysis was performed to determine the predictors of SSI in different surgeries. RESULTS: A total of 1290 patients were enrolled and SSI occurred in 68 patients (5.2%). Multivariate analysis with adjustments revealed that normal body mass index, normal blood glucose level, low national nosocomial infection surveillance risk index score, noncolon surgery, laparoscopic or robotic surgery, and use of mechanical bowel preparation were associated with reduced SSI in gastrointestinal surgery. Subgroup analysis revealed diverse predictors of SSI in diverse surgeries. National nosocomial infection surveillance risk index score of 2 and a high blood glucose level increased the incidence of SSI in colorectal and noncolorectal surgery, respectively. Besides, mechanical bowel preparation and laparoscopic or robotic surgery were protective factors for SSI in colorectal and noncolorectal surgery, respectively. CONCLUSIONS: This study provides the newest data of SSI after gastrointestinal surgery in China and revealed some predictors of SSI in diverse surgeries, which can be a tool to look for areas to target quality improvement initiatives.

Clinical parameters and outcomes of necrotizing soft tissue infections secondary to gastrointestinal fistulas.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) is severe surgical infections which can occur following trauma or abdominal surgery. NSTIs secondary to gastrointestinal (GI) fistula is a rare but severe complication. METHODS: A retrospective cohort study was performed on all subjects presenting with GI fistulas associated NSTIs were included. Clinical characteristics, microbiological profile, operations performed, and outcomes of patients were analyzed. RESULTS: Between 2014 and 2017, 39 patients were finally enrolled. The mean age were 46.9 years and male were the dominant. For the etiology of fistula, 25 (64.1%) of the patients was due to trauma. Overall, in-hospital death occurred in 15 (38.5%) patients. Microbiologic findings were obtained from 31 patients and Klebsiella pneumoniae was the most common species (41.0%). Eight patients were treated with an open abdomen; negative pressure wound therapy was used in 33 patients and only 2 patients received hyperbaric oxygen therapy. Younger age and delayed abdominal wall reconstruction repair were more common in trauma than in non-trauma. Non-survivors had higher APACHE II score, less source control< 48 h and lower platelet count on admission than survivors. Multiple organ dysfunction syndrome, multidrug-resistant organisms and source control failure were the main cause of in-hospital mortality. CONCLUSIONS: Trauma is the main cause of GI fistulas associated NSTIs. Sepsis continues to be the most important factor related to mortality. Our data may assist providing enlightenment for quality improvement in these special populations.

Risk Factors for Nephrolithiasis in Adults with Short Bowel Syndrome.

INTRODUCTION: Patients with short bowel syndrome (SBS) commonly develop nephrolithiasis. However, the risk factors for nephrolithiasis in patients with SBS remain unclarified. The present study aimed to identify the risk factors for nephrolithiasis in adults with SBS. METHODS: All eligible adults diagnosed with SBS and admitted to a tertiary referral center from December 2008 to 2018 were retrospectively identified from a prospectively maintained database. Patients' demographic and clinical characteristics were analyzed using univariate and multivariate analyses to identify the risk factors for nephrolithiasis. RESULTS: Of 231 adults with SBS, 42 (18.2%) developed nephrolithiasis. The mean age was 46.4 ± 17.8 years, the mean body mass index was 18.2 ± 3.8 kg/m2, and median duration of SBS was 11 months (range 2-324 months). Multivariate binary logistic regression analysis revealed that the independent risk factors for nephrolithiasis in adults with SBS were jejuno-ileal anastomosis and colon-in-continuity (OR 4.335; 95% CI 1.175-16.002; p = 0.028), prolonged duration of SBS (OR 1.008; 95% CI 1.002-1.014; p = 0.010), and increased serum creatinine concentration (OR 1.005; 95% CI 1.001-1.009; p = 0.012). CONCLUSIONS: Nephrolithiasis is common in adults with SBS. As nephrolithiasis can have adverse clinical consequences, patients with SBS should be closely monitored, and prophylactic interventions should be considered.

Colon Ascendens Stent Peritonitis (CASP) Induces Excessive Inflammation and Systemic Metabolic Dysfunction in a Septic Rat Model.

The colon ascendens stent peritonitis (CASP) surgery induces a leakage of gut contents, causing polymicrobial sepsis related to post-operative multiple organ failure and death in surgical patient. To evaluate the effects of CASP on multiple organs, we analyzed the systemic metabolic consequences in liver, kidney, lung, and heart of rats after CASP by employing a combination of metabolomics, clinical chemistry, and biological assays. We found that CASP surgery after 18 h resulted in striking elevations of lipid, amino acids, acetate, choline, PC, and GPC in rat liver together with significant depletion of glucose and glycogen. Marked elevations of organic acids including lactate, acetate, and creatine and amino acids accompanied by decline of glucose, betaine, TMAO, choline metabolites (PC and GPC) nucleotides, and a range of organic osmolytes such as myo-inositol are observed in the kidney of 18 h post-operative rat. Furthermore, 18 h post-operative rats exhibited accumulations of lipid, amino acids, and depletions of taurine, myo-inositol, choline, PC, and GPC and some nucleotides including uridine, inosine, and adenosine in the lung. In addition, significant elevations of some amino acids, uracil, betaine, and choline metabolites, together with depletion of inosine-5'-monophosphate, were only observed in the heart of 18 h post-operative rats. These results provide new insights into pathological consequences of CASP surgery, which are important for timely prognosis of sepsis.

N-3 polyunsaturated fatty acids ameliorate hepatic steatosis via the PPAR-α/CPT-1α pathway in a mouse model of parenteral nutrition.

Parenteral nutrition (PN) is one of the basic therapies for patients with intestinal failure; however, hepatic steatosis associated with PN limits the long-term use of PN. N-3 polyunsaturated fatty acids (PUFAs) have been used to improve clinical outcomes of patients receiving PN; however, the mechanisms by which n-3 PUFAs ameliorate hepatic steatosis remain unclear. In the present study, C57BL/6J mice were randomly assigned to three treatment groups, namely, enteral nutrition (EN), n-3 PUFAs, and n-6 PUFAs. Additionally, MK 886 was used to inhibit PPAR-α. After 7 days of intervention, mice were sacrificed, and liver tissue and serum samples were collected. Results from liver weight and liver triglyceride measurements and Oil Red O staining showed that n-3 PUFAs significantly reduced the liver triglyceride levels. In addition, treatment with n-3 PUFAs resulted in a greater decrease in serum triglyceride and low-density lipoprotein cholesterol levels compared to n-6 PUFAs. The key enzymes involved in FA oxidation, namely, PPAR-α and CPT-1α, were significantly restored at both the mRNA and protein levels in the n-3 PUFAs group. However, the benefits of n-3 PUFAs in improving serum and liver TG levels were abolished when the PPAR-α/CPT-1α pathway was blocked by MK 886. The results of this study indicated that n-3 PUFAs ameliorated the PN-associated hepatic steatosis by activating the PPAR-α/CPT-1α pathway. The present study provided a reliable scientific basis supporting the potential beneficial effects of n-3 PUFAs for improving hepatic steatosis in patients receiving long-term parenteral nutrition.

microRNA-129-5p suppresses Adriamycin resistance in breast cancer by targeting SOX2.

Adriamycin resistance is closely related to therapeutic efficacy in breast cancer patients and their prognosis. Increasing evidence has suggested that miRNA functions in Adriamycin resistance in various types of cancer. microRNA-129-5p (miR-129-5p) has been considered a tumor-suppressive miRNA in several cancers, but its potential role in Adriamycin resistance in breast cancer has not been fully elucidate. By qRT-PCR assay, we revealed that the expression of miR-129-5p was significantly decreased in breast cancer tissues and Adriamycin-resistant breast cancer cells (MDA-MB-231/ADR, MCF-7/ADR). CCK-8, colony formation, wound healing, Transwell invasion, and flow cytometric profiles were examined to determine the influence of miR-129-5p on Adriamycin-resistant breast cancer in vitro. The upregulation of miR-129-5p decreased the IC50 concentration of Adriamycin and invasion and promoted the apoptosis of MDA-MB-231/ADR cells in the presence of Adriamycin, whereas the upregulation of Sex-Determining Region Y-Box 2 (SOX2) reversed these effects. A luciferase reporter assay confirmed the binding of miR-129-5p to the 3'UTR of SOX2. Collectively, it was suggested that miR-129-5p suppresses Adriamycin resistance in breast cancer by directly targeting SOX2.

Risk factors and clinical outcomes of hypervirulent Klebsiella pneumoniae induced bloodstream infections.

The prevalence of hypervirulent Klebsiella pneumoniae (hvKP) is high in China, but clinical characteristics and outcomes of hvKP induced bloodstream infections (BSIs) are not clear. The purpose of the present study was to determine the risk factors and clinical outcomes of hvKP-BSIs in populations admitted in a teaching hospital of Nanjing, China. The genetic characteristics and antibiotic resistance patterns of the hvKP strains were further analyzed. A retrospective study was conducted in 143 patients with K. pneumoniae BSIs at Jinling Hospital in China from September 2015 to December 2016. A positive polymerase chain reaction (PCR) amplification of the plasmid-borne rmpA (p-rmpA) and aerobactin (iucA) was identified as hvKP. Overall, 24.5% (35/143) of K. pneumoniae isolates were hvKP. Multivariate analysis implicated diabetes mellitus (OR = 3.356) and community-acquired BSIs (OR = 4.898) as independent risk factors for hvKP-BSIs. The 30-day mortality rate of the hvKP-BSIs group was 37.1% (13/35) compared with 40.7% (44/108) in the cKP-BSIs control group (P = 0.706). The KPC-producing isolates (OR = 2.851), underlying disease with gastrointestinal fistula (OR = 3.054), APACHE II score ≥ 15 (OR = 6.694) and Pitt bacteremia score ≥ 2 (OR = 6.232) at infection onset were independent predictors for 30-day mortality of K. pneumoniae bacteremia patients. A high percentage (57.1%, 20/35) of KPC-producing isolates was observed among hvKP strains and ST11 was dominant in hvKP strains (17/35, 48.6%). KPC-producing hvKP is emerging, indicating the importance of epidemiologic surveillance and clinical awareness of this pathogen.

Significantly different clinical features between hypertriglyceridemia and biliary acute pancreatitis: a retrospective study of 730 patients from a tertiary center.

BACKGROUND: Unlike western world, gallstones and hypertriglyceridemia (HTG) are among the first two etiologies of acute pancreatitis (AP) in China. But yet, detailed differences in clinical features and outcomes between hypertriglyceridemia and biliary acute pancreatitis have not been well described. METHODS: This retrospective study enrolled 730 acute pancreatitis patients from July 1, 2013 to October 1, 2016 in Jinling Hospital. The causes of the study patients were defined according to specific diagnostic criteria. The clinical features and outcomes of patients with hypertriglyceridemia acute pancreatitis (HTG-AP) and biliary acute pancreatitis (BAP) were compared in terms of general information, disease severity, laboratory data, system complications, local complications, and clinical outcome. RESULTS: In the enrolled 730 AP patients, 305 (41.8%) were HTG-AP, and 425 (58.2%) were BAP. Compared to BAP, the HTG-AP patients were found to be younger, with higher body mass Index (BMI), and much higher proportion of diabetes, fatty liver and high fat diet. Besides that, HTG-AP patients had significantly higher C-reactive protein (CRP) (p<0.01) and creatinine (p = 0.031), together with more acute respiratory distress syndrome (ARDS) (p = 0.039), acute kidney injury (AKI) (p<0.001), deep venous thrombosis (p = 0.008) and multiple organ dysfunction syndrome (MODS) (p = 0.032) in systematic complications. As for local complications, HTG-AP patients had significantly less infected pancreatitis necrosis (p = 0.005). However, there was no difference in mortality, hospital duration and costs between the groups. CONCLUSION: HTG-AP patients were younger, more male, having high fat diet and with higher BMI compared to BAP patients. The prevalence of AKI/ARDS/DVT/MODS in HTG-AP patients was higher than BAP patients, while BAP patients had a greater possibility in development of infected pancreatitis necrosis (IPN). According to the multivariate analysis, only the complication of AKI was independently related with the etiology of HTG, however, BMI contributes to AKI, ARDS and DVT.

Increased enteric glial cells in proximal margin of resection is associated with postoperative recurrence of Crohn's disease.

BACKGROUND AND AIM: The enteric nervous system can amplify or modulate intestinal inflammation through secretion of neuropeptides, and enteric glial cells have been implicated in the pathophysiology of Crohn's disease. The goal of the study was to search for an association between the density of neurons, neuropeptides, and enteric glial cells and postoperative recurrence. METHODS: The ileal proximal uninflamed section from ileocolonic sample was studied using immunohistochemistry with antibodies directed against vasoactive intestinal polypeptide (VIP), substance P (SP), neuron-specific enolase (NSE), and the glial marker protein S100. The density in the submucosa was calculated, and the relationship of the density of VIP, SP, NSE, and S100 and postoperative disease recurrence was assessed. RESULTS: There were no significant differences between patients with and without postoperative endoscopic recurrence or clinical recurrence for the density of NSE-positive, VIP-positive, or SP-positive neurons in the proximal margin. Interestingly, the density of S100-positive enteric glial cells was significantly increased in patients with endoscopic and clinical recurrence than in subjects without disease recurrence (P Ë‚ 0.001). The density of S100-positive enteric glial cells was independently associated with postoperative disease recurrence. CONCLUSIONS: Increased S100-positive enteric glial cells are associated with a high risk of both endoscopic and clinical recurrence after surgery. These findings have implications in individualized postoperative prophylaxis for Crohn's disease.

Anti-mouse CD52 Treatment Ameliorates Colitis through Suppressing Th1/17 Mediated Inflammation and Promoting Tregs Differentiation in IL-10 Deficient Mice.

Recent studies suggested that excessive T helper (Th)1/17 cells concomitant with regulatory T cell deficiency might play important roles in Crohn's disease. Anti-cluster of differentiation 52 (CD52) monoclonal antibody (mAb), which aims on CD52 antigen on mature immunocytes, has both T cell depletion and immunosuppressive activities. In this study, we evaluated the therapeutic effects and possible mechanisms of anti-CD52 treatment on interleukin-10 (IL-10) deficient mouse. Anti-mouse CD52 mAb was administered to C3H/HeJBir.IL-10-/- (C3H.IL-10-/-) mice intraperitoneally 20 µg per week for 2 weeks. The disease activity index, body weight, the histological grading of colitis, and levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-17 and IL-6 in colon were quantified after treatment. In addition, CD25, Forkhead box P3 (Foxp3) and transforming growth factor (TGF)-ß gene as well as the percentage of CD25+Foxp3+ T cells in colon were also measured. The severity of colitis in IL-10-/- mice was significantly decreased by the treatment, with improvement of colon histological grade. The treatment also decreased the TNF-α, IFN-γ, IL-17 and IL-6 levels in colon. Furthermore, the treatment up-regulated the mRNA expression of CD25, Foxp3 and TGF-ß gene as well as the percentage of CD25+Foxp3+ T cells in colon lamina propria mononuclear cells (LPMCs) of IL-10-/- mice. Our data might indicate that anti-CD52 treatment could ameliorate the colitis of C3H.IL-10-/- mice and it might be related to the suppression of Th1/17 related inflammation and the promotion of regulatory T cell differentiation. Thus, our data reveals that anti-CD52 treatment may hold potential for clinical applications for Crohn's disease treatment.

Compound but non-linked heterozygous p.W14X and p.L279 V LPL gene mutations in a Chinese patient with long-term severe hypertriglyceridemia and recurrent acute pancreatitis.

BACKGROUND: Variants in the lipoprotein lipase (LPL), apolipoprotein C-II (APOC2), apolipoprotein A-V (APOA5), GPIHBP1 and LMF1 genes may cause severe hypertriglyceridemia (HTG), which is now the second-leading aetiology of acute pancreatitis in China. METHODS: The patient and his family were assessed for gene variants by Sanger sequencing of exons and exon-intron junctions of the LPL, GPIHBP1, APOA5, APOC2, and LMF1 genes. Post-heparin blood was collected for LPL mass and activity detection. RESULTS: The patient had suffered from long-term severe hypertriglyceridemia and recurrent abdominal pain for over 30 years, since age 26, and 3 bouts of acute pancreatitis. Two heterozygous LPL single-nucleotide polymorphisms (SNPs) were compound but dislinked: a single-nucleotide substitution (c.42G > A) resulting in the substitution of tryptophan with a stop codon (p.W14X) in one allele, and a single-nucleotide substitution (c.835C > G) resulting in a leucine-to-valine substitution (p.L279 V) in another allele. Only one SNP, p.L279 V, was detected in his son. Post-heparin LPL activity and mass were also lower in the patient. CONCLUSION: Two heterozygous LPL SNPs, W14X and L279 V, were newly found to be compound but dislinked, which may cause long-term severe hypertriglyceridemia and recurrent acute pancreatitis.

Antibiotics-induced depletion of mice microbiota induces changes in host serotonin biosynthesis and intestinal motility.

BACKGROUND: The gastrointestinal motility is affected by gut microbiota and the relationship between them has become a hot topic. However, mechanisms of microbiota in regulating motility have not been well defined. We thus investigated the effect of microbiota depletion by antibiotics on gastrointestinal motility, colonic serotonin levels, and bile acids metabolism. METHODS: After 4 weeks with antibiotics treatments, gastrointestinal and colon transit, defecation frequency, water content, and other fecal parameters were measured and analyzed in both wild-type and antibiotics-treated mice, respectively. Contractility of smooth muscle, serotonin levels, and bile acids levels in wild-type and antibiotics-treated mice were also analyzed. RESULTS: After antibiotics treatment, the richness and diversity of intestinal microbiota decreased significantly, and the fecal of mice had less output (P < 0.01), more water content (P < 0.01), and longer pellet length (P < 0.01). Antibiotics treatment in mice also resulted in delayed gastrointestinal and colonic motility (P < 0.05), and inhibition of phasic contractions of longitudinal muscle from isolated proximal colon (P < 0.01). In antibiotics-treated mice, serotonin, tryptophan hydroxylase 1, and secondary bile acids levels were decreased. CONCLUSION: Gut microbiota play an important role in the regulation of intestinal bile acids and serotonin metabolism, which could probably contribute to the association between gut microbiota and gastrointestinal motility as intermediates.

The role of hypertriglyceridemia for acute kidney injury in the course of acute pancreatitis and an animal model.

OBJECTIVE: The aim of this study was to investigate the role of hypertriglyceridemia for acute kidney injury (AKI) in the course of acute pancreatitis. METHODS: Patients with acute pancreatitis were retrospectively divided into four groups according to admission triglyceride: normal group, mild HTG group, moderate HTG group and severe HTG group. Clinical characteristics were compared among these groups. Wild type (WT) mice and Human ApoC III transgenic (ApoCIIItg) mice were used in the next animal experiments. Severe acute pancreatitis (SAP) model was established by retrograde injection of 0.5% sodium taurocholate (0.1 ml/100 g) from duodenum to pancreatic duct. Histological scores, serum amylase, creatinine, usea nitrogen were compared between WT mice and ApoCIIItg mice. RESULTS: Two hundred and sixty-two patients were classified into 4 groups: normal TG (104, 39.7%), mild HTG (72, 27.5%), moderate HTG (47, 17.9%), and severe HTG (39, 14.9%) groups. The proportions of AKI were 13.5% (14/104, normal), 13.9% (10/72, mild), 21.3% (10/47, moderate), and 38.5% (15/39, severe), respectively. After establishing SAP model, the levels of serum amylase (P < 0.05) and pancreatic histological score (P < 0.05) of ApoCIII-SAP-9h group were significantly higher than that of WT-SAP-9h group, respectively. ApoCIII-SAP-9h group had significantly higher levels of serum creatinine (P < 0.001), usea nitrogen (P < 0.001), and kidney histological score (P < 0.05) than that of WT-SAP-9h group, respectively. CONCLUSIONS: Mild HTG has little adverse impact on disease severity of acute pancreatitis; severe HTG can aggravate kidney injury in the course of acute pancreatitis. ApoCIII-SAP mice have more serious pancreatic damage and kidney injury than WT-SAP mice.