Purpose Inulin is a type of fermentable dietary fiber, which is non-digestible, and can improve metabolic function by modulating intestinal microbiota. This study aimed to evaluate the role of inulin in hyperuricemia and microbial composition of the gut microbiota in a mouse model of hyperuricemia established through knockout of Uox (urate oxidase) gene. Methods KO (Uox-knockout) and WT (wild-type) mice were given inulin or saline by gavage for 7 weeks. The effect of inulin to combat hyperuricemia was determined by assessing the changes in serum UA (uric acid) levels, inflammatory parameters, epithelial barrier integrity, fecal microbiota alterations, and SCFA (short-chain fatty acid) concentrations in KO mice. Results Inulin supplementation can effectively alleviate hyperuricemia, increase the expressions of ABCG2 in intestine, and downregulate expression and activity of hepatic XOD (xanthine oxidase) in KO mice. It was revealed that the levels of inflammatory cytokines and the LPS (lipopolysaccharide) were remarkably higher in the KO group than those in the WT group, indicating systemic inflammation of hyperuricemic mice, but inulin treatment ameliorated inflammation in KO mice. Besides, inulin treatment repaired the intestinal epithelial barrier as evidenced by increased levels of intestinal TJ (tight junction) proteins [ZO-1 (zonula occludens-1) and occluding] in KO mice. Moreover, serum levels of uremic toxins, including IS (indoxyl sulfate) and PCS (p-cresol sulfate), were reduced in inulin-treated KO mice. Further investigation unveiled that inulin supplementation enhanced microbial diversity and raised the relative abundance of beneficial bacteria, involving SCFAs-producing bacteria (e.g., Akkermansia and Ruminococcus). Additionally, inulin treatment increased the production of gut microbiota-derived SCFAs (acetate, propionate and butyrate concentrations) in KO mice, which was positively correlated with the effectiveness of hyperuricemia relief. Conclusions Our findings showed that inulin may be a promising therapeutic candidate for the treatment of hyperuricemia. Moreover, alleviation of hyperuricemia by inulin supplementation was, at least, partially conciliated by modulation of gut microbiota and its metabolites.

Previous studies have demonstrated the effects of hyperuricemia on the damage to target organs, including the kidneys, joints and the heart. However, it is unclear whether hyperuricemia results in damage to the intestines. The aim of the present study was to investigate intestinal barrier dysfunction in a mouse model of hyperuricemia constructed by knocking out the urate oxidase (Uox) gene. The morphology of the intestine was assessed via hematoxylin and eosin, and alcian blue staining. The serum and intestinal tissue levels of uric acid, tumor necrosis factor (TNF)-α and interleukin (IL)-6, in addition to the presence of uremic toxins in the serum, were assessed. The levels of diamine oxidase (DAO), D-lactate (D-LAC) and endotoxins in the serum, which are markers of the intestinal permeability, were measured using ELISA. The expression of the intestinal tight junction proteins zona occludens-1 (ZO-1) and occludin were detected by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemical analysis. The Uox-knockout mice spontaneously developed hyperuricemia. Histopathological analysis indicated notable intestinal defects including sparse villi, mucosal edema and a declining mucus layer in hyperuricemic mice. The expression levels of ZO-1 and occludin in the intestines were downregulated, and the serum levels of DAO, D-LAC and endotoxins were higher in the hyperuricemic mice, compared with control mice. The serum and intestinal tissue levels of IL-6 and TNF-α were significantly increased. Additionally, the expression levels of the serum uremic toxins, serum creatinine, blood urea nitrogen were significantly increased in hyperuricemic mice compared with the control mice, while only a marked increase in indoxyl sulfate (IS) and p-cresol sulfate was reported. Collectively, the results of the present study suggested that intestinal barrier dysfunction and subsequent enhanced intestinal permeability may occur as a result of hyperuricemia in mice. Furthermore, we proposed that the loss of intestinal epithelium barrier function may be associated with uric acid-induced inflammatory responses; however, further investigation is required.

Background: Systemic inflammatory markers are associated with patient survival in pancreatic cancer (PC).The aim of this study was to investigate the prognostic significance of the systemic immune-inflammation index (SII) in PC patients who underwent radical surgery. Platelet-albumin-bilirubin (PALBI) grade is a composite evaluation index based on liver function. Patients with pancreatic head cancer are prone to obstructive jaundice, which leads to abnormal liver function. Based on this, we also explored the prognostic value of PALBI grade in PC patients.Methods: Patients with pathologically confirmed PC who had undergone radical surgery (with negative surgical margin) for the first time at the Affiliated Hospital of Qingdao University from January 2013 to December 2019 and followed up by December 2020 were retrospectively analyzed. Peripheral blood cell count is easily affected by infection or hematological diseases, which affects the results, so it is excluded.Clinical data and laboratory examination indexes were collected. The SII and PALBI grade were calculated.The cutoff values were determined using the Youden index. The Cox proportional hazards regression model was used to analyze the prognostic value of the SII and PALBI grade through univariate and multivariate survival analysis.Results: A total of 214 patients [median age, 60.29 years; 128 (59.8%) men] met the inclusion criteria.There were 140 patients (65.4%) with pancreatic head cancer according to the tumor location. They were divided into high and low SII or PALBI groups by cutoff values of 705 and −5.6, respectively. According to the multivariate analysis, SII (P<0.001) was an independent factor negatively associated with overall survival (OS) and disease-free survival (DFS). In patients with pancreatic head cancer, PALBI grade was associated with shorter OS (P=0.031). The combination of high SII and high PALBI grade had stronger predictive value for poor prognosis (log-rank test, P<0.001), which the OS was 11.3 months less than the combination of low two groups.Conclusions: SII was a promising prognostic biomarker in PC. And PALBI grade also showed predictive value for patients with pancreatic head cancer. Therefore, it can help predict the treatment outcomes in these patients

BACKGROUND Lymphangiomatosis is a multisystem disorder that is rarely localized to the gastrointestinal tract. Lymphangiomatosis usually has no specific clinical presentation and is easily misdiagnosed. A case report and review of the literature on lymphangiomatosis associated with protein-losing enteropathy will help to improve the overall understanding of this disease. CASE SUMMARY We report a case of lymphangiomatosis of the bowel and other solid organs. A 78-year-old man presented with recurrent bowel bleeding and protein-losing enteropathy, as well as cystic lesions in the spleen, liver, and kidney. Imaging examinations revealed many cystic lesions on the spleen, liver, kidney, and thickened wall of the ascending colon, as well as pleural effusion and ascites. Colonoscopy revealed a strawberry mucosa, variable spontaneous bleeding, and surface erosion located in the terminal ileum. Several cystic masses with a translucent and smooth surface as well as diffuse white spots were located in the colon. A laterally spreading tumor (LST) was located in the ascending colon. Pathology indicated highly differentiated adenocarcinoma (LST) and lymphangiomatoid dilation, and D2-40 was positive. The final diagnosis was lymphangiomatosis. The patient underwent surgery for LST and then was administered thalidomide 75-150 mg/d. His condition, however, did not improve. He eventually died 6 mo after the initial diagnosis. CONCLUSION Lymphangiomatosis usually occurs diffusely and can involve many organs, such as the spleen, kidney, liver, lung, mesentery, and bowel. Recurrent bowel bleeding or protein-losing enteropathy is an important indicator that should alert clinicians about the possibility of this disease when it afflicts the bowel. Doctors should improve the medical understanding of lymphangiomatosis.

PurposeSystemic inflammatory markers may be predictors of the survival rate of patients with pancreatic cancer (PC). The aim of this work was to investigate the prognostic value of markers, mainly the systemic immune inflammation index (SII), in patients with metastatic and unresectable PC and to explore the relationship between markers and liver metastasis.MethodsRecords of patients with metastatic and unresectable PC at the Affiliated Hospital of Qingdao University from January 2000 to December 2019 and who were followed until December 2020 were retrospectively analyzed. Clinical data and laboratory indexes were collected, and cut-off values for inflammatory markers were determined using median values. The Cox proportional hazard model was used to analyze the prognostic value of the markers through univariate and multivariate survival analysis.ResultsAll 253 patients met the inclusion criteria, and 102 (42.0%) patients had liver metastasis. The patients were divided into a high SII group and a low SII group, and the cut-off value was 533. In the multivariate analysis, high SII (HR = 2.151; p &lt; 0.001), chemotherapy (HR = 0.546; p &lt; 0.001), lymph node metastasis (HR = 4.053; p &lt; 0.001), and distant metastasis (HR = 1.725; p = 0.001) were independent risk markers of overall survival (OS). The level of markers, mainly SII, PLR and NLR, were higher in patients with liver metastasis.ConclusionsA high level of SII is an independent risk factor for short overall survival of patients with metastatic and unresectable PC. Patients with a high level of the inflammatory markers SII, PLR, and NLR, may be more prone to early liver metastasis.