Capillary leak syndrome (CLS) is a serious disorder characterized by hypotension and refractory systemic oedema. CLS with marked ascites rather than systemic oedema is rare and prone to misdiagnosis and delayed treatment. We report here a case of marked ascites in an elderly male patient with hepatitis B virus reactivation. Following investigations to exclude common diseases that may have accounted for diffuse oedema and hypercoagulable state, anti-cirrhosis therapy failed and severe refractory shock developed 48 hours after admission. The patient developed mild pleural effusions followed by swelling of the face, neck, and extremities. A high cytokine concentration gradient was detected between serum and ascites. Peritoneal biopsy showed lymphoma cells. The final diagnosis was lymphoma recurrence complicated with CLS. Our case suggests that cytokine detection in serum and ascitic fluid may be helpful in the differential diagnosis of CLS. In similar cases, decisive intervention, such as, hemodiafiltration, should be implemented to lessen the likelihood of serious complications.

Background:Patients with spontaneous bacterial peritonitis (SBP) often just receive empirical antibiotic therapy, as pathogens can be identified in only few patients using the techniques of conventional culture. Metagenomic next generation sequencing (mNGS) is a useful tool for diagnosis of infectious diseases. However, clinical application of mNGS in diagnosis of infected ascites of cirrhotic patients is rarely reported.Case presentation:A 53-year-old male with cirrhosis on regular hemodialysis presented with continuous abdominal pain. After treatment with empiric antibiotics, his inflammatory parameters decreased without significant relief of abdominal pain. Finally, based on ascites mNGS detection, he was diagnosed as infection of Staphylococcus cohnii (S.cohnii), a gram-positive opportunistic pathogen. With targeted antibiotic treatment, the bacterial peritonitis was greatly improved and the patient's abdominal pain was significantly alleviated.Conclusions:When conventional laboratory diagnostic methods and empirical antibiotic therapy fail, proper application of mNGS can help identify pathogens and significantly improve prognosis and patients' symptoms.

BACKGROUND:Infectious abscesses in the abdominal wall can be secondary to retained foreign bodies (e.g., stones, use of artificial mesh, use of silk yarn in surgical suture), inflammatory diseases (e.g., acute appendicitis), and perforated malignancies of the digestive tract (particularly the colon). Aseptic abscesses (AAs) are relatively rare. To the best of our knowledge, this is the first report of an AA in the abdominal wall accompanied by monoclonal gammopathy of undetermined significance (MGUS) at 5 years after laparoscopic proctectomy.CASE SUMMARY:A 72-year-old female patient presented with an enlarged painless mass in the lower abdomen for 1 year. She had a history of obesity, diabetes, and MGUS. Her surgical history was laparoscopic resection for rectal cancer 6 years prior, followed by chemotherapy. She was afebrile. Abdominal examination revealed a smooth abdomen with a clinically palpable solid mass under a laparotomy scar in the left lower quadrant. No obvious tenderness or skin redness was spotted. Laboratory data were not remarkable. Computed tomography scan revealed a low-density mass of 4.8 cm in diameter in the lower abdominal wall, which showed high uptake on positron emission tomography. The preoperative diagnosis was an abscess or tumor, and surgical resection was recommended. The mass was confirmed to be an AA by microbiological and pathological examinations. The patient recovered well after surgery. There was no evidence of recurrence 2 years later.CONCLUSION:It is important to consider underlying conditions (diabetes, chemotherapy, MGUS) which may contribute to AA formation in the surgical wound.

Tumor cells detachment from primary lesions is an early event for hepatocellular carcinoma (HCC) metastasis, in which cell adhesion molecules play an important role. The role of mechanical crowding has attracted increasing attention. Previous studies have found that overcrowding can induce live cells extrusion to maintain epithelial cell homeostasis, and normally, live extruded cells eventually die through a process termed anoikis, suggesting the potential of tumor cells resistant to anoikis might initiate metastasis from primary tumors by cell extrusion. We have demonstrated transmembrane adhesion molecule blood vessel epicardial substance (BVES) suppression as an early event in HCC metastasis. However, whether its suppression is involved in HCC cell extrusion, especially in HCC metastasis, remains unknown. This study aims to investigate the role of BVES in tumor cells extrusion in HCC metastasis, as well as the underlying mechanisms. Cells extrusion was observed by silicone chamber, petri dish inversion, and three-dimensional cell culture model. Polymerase chain reaction, western blotting, immunohistochemistry, immunofluorescence, co-immunoprecipitation, and RhoA activity assays were used to explore the underlying mechanisms of cell extrusion regulated by BVES. An orthotopic xenograft model was established to investigate the effects of BVES and cell extrusion in HCC metastasis in vivo. Tumor cell extrusion was observed in HCC cells and tissues. BVES expression was decreased both in HCC and extruded tumor cells. BVES overexpression led to the decrease in HCC cells extrusion in vitro and in vivo. Moreover, our data showed that BVES co-localized with ZO-1 and GEFT, regulating ZO-1 expression and localization, and GEFT distribution, thus modulating RhoA activity. The present study revealed that BVES downregulation in HCC enhanced tumor cells extrusion, thus promoting HCC metastasis, which contributed to a more comprehensive understanding of tumor metastasis, and provided clues for developing novel HCC therapy strategies.

BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease, which may develop into end-stage liver disease and endanger human life. miR-122-5p may be related to the progression of NAFLD disease, but the specific regulation mechanism is still unknown. It is helpful for us to optimize the prevention or treatment strategy of NAFLD.METHODS:Real-time PCR was applied to test miR-122-5p and KIF5B in serum, rat liver tissue induced by high fat diet (HFD), and primary hepatocytes exposed to oleic acid ester and palmitate (FFA) of NAFLD patients. The role of miR-122-5p on inflammatory factors (MCP-1, TNF-α, IL-10) and liver injury markers (AST, ALT) in vivo and in vitro was analyzed.RESULTS:miR-122-5p and KIF5B were both highly expressed in NAFLD patients' serum, rat liver tissue and primary hepatocytes, while KIF5B was low expressed. miR-122-5p expression enhanced with the increase of HFD feeding time. The dual luciferase reporter gene assay system confirmed that there was a targeting relationship between miR-122-5p and KIF5B, indicating that KIF5B and protein level were evidently up-regulated in primary hepatocytes. Down-regulation of miR-122-5p was helpful to improve the liver weight/body weight ratio (liver index) level of rats, as well as the levels of triglyceride (TG), inflammatory factors and liver injury markers in liver tissues in vivo and in vitro. Phosphorylation of AMPK/AKT pathway-related proteins and fat metabolism-related factors in rat liver tissues and cells in primary hepatocytes were notably reduced, while down-regulation of miR-122-5p was helpful to restore activation of the pathway and increase the level of fat metabolism-related factors.CONCLUSION:Decrease of miR-122-5p can target and enhance KIF5B, which can be applied for treating NAFLD.

Nerve growth factor (NGF), a prototypical neurotrophic factor essential for neuronal cell proliferation and survival, has been implicated as a marker of tumor progression, as well as a potential target for novel therapeutic approaches in cancer. To investigate the functional potential of NGF in liver cancer in the present study, a stable NGF-overexpressing HepG2 cell line was generated. The scratch-wound assay was used to investigate cell motility and polarity. Western blotting was performed to evaluate the expression levels of epithelial-mesenchymal transition (EMT)-related proteins, including E-cadherin, N-cadherin and vimentin. Moreover, immunofluorescence was performed to investigate the arrangement of the actin cytoskeleton. Cell anoikis resistance was examined using a suspension culture model and cell apoptosis was examined via flow cytometry. The present results indicated that NGF overexpression in HepG2 cells disrupted HepG2 cell polarity and promoted cell motility. Furthermore, NGF overexpression induced EMT and actin cytoskeleton rearrangement in HepG2 cells, as well as enhanced anoikis resistance and prevented cellular apoptosis. Notably, a tropomyosin receptor kinase A receptor inhibitor blocked NGF-induced cell motility and apoptosis. Therefore, it was suggested that NGF serves a critical role in the invasion and metastasis of liver cancer. The use of NGF as a biomarker or potential new target could lead to the development of novel factors for diagnosis or for improving therapeutic strategies in liver cancer.

重症急性胰腺炎(severe acute pancreatitis,SAP)是指急性胰腺炎伴有器官功能障碍,或胰腺出现坏死、脓肿、假性囊肿等局部并发症,具有起病急骤、进展迅速、病情危重复杂、病死率高等特点,可引起全身炎症反应,导致急性肾衰竭、急性呼吸窘迫综合征、肺栓塞等并发症[1].血液净化能有效降低患者的炎症水平和血脂,改善脏器功能和体液平衡,在SAP治疗中得到广泛的应用[2].本文报道2例SAP合并急性肺动脉栓塞(pulmonary thromboembolism,PTE)的病例,采取不同的治疗策略后,取得良好的疗效,并进行文献复习,供临床参考.

Background: Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease, which may develop into end-stage liver disease and endanger human life. miR-122-5p may be related to the progression of NAFLD disease, but the specific regulation mechanism is still unknown. It is helpful for us to optimize the prevention or treatment strategy of NAFLD. Methods: Real-time PCR was applied to test miR-122-5p and KIF5B in serum, rat liver tissue induced by high fat diet (HFD), and primary hepatocytes exposed to oleic acid ester and palmitate (FFA) of NAFLD patients. The role of miR-122-5p on inflammatory factors (MCP-1, TNF-alpha, IL-10) and liver injury markers (AST, ALT) in vivo and in vitro was analyzed. Results: miR-122-5p and KIF5B were both highly expressed in NAFLD patients' serum, rat liver tissue and primary hepatocytes, while KIF5B was low expressed. miR-122-5p expression enhanced with the increase of HFD feeding time. The dual luciferase reporter gene assay system confirmed that there was a targeting relationship between miR-122-5p and KIF5B, indicating that KIF5B and protein level were evidently up-regulated in primary hepatocytes. Down-regulation of miR-122-5p was helpful to improve the liver weight/body weight ratio (liver index) level of rats, as well as the levels of triglyceride (TG), inflammatory factors and liver injury markers in liver tissues in vivo and in vitro. Phosphorylation of AMPK/AKT pathway-related proteins and fat metabolism-related factors in rat liver tissues and cells in primary hepatocytes were notably reduced, while down-regulation of miR-122-5p was helpful to restore activation of the pathway and increase the level of fat metabolism-related factors. Conclusion: Decrease of miR-122-5p can target and enhance KIF5B, which can be applied for treating NAFLD.

Objective: Intestinal Behcet's disease (iBD) is an autoimmune disorder diagnosed by typical intestinal ulcers and systemic Behcet's disease (BD) manifestations. Haploinsufficiency of A20 (HA20) is a recently described autoinflammatory disease with a phenotype resembling BD, caused by heterozygous loss-of-function mutations in TNFAIP3 gene (encoding A20).Methods: We described a 29-year-old female with iBD-like symptoms including relapsing ulceration of intestinal anastomosis, recurrent oral ulcers and vasculitis in extremities. Due to the atypical intestinal ulcers with long segmental involvement and intestinal obstruction, whole exome sequencing (WES) was performed to screen for the underlying genetic defect and the identified gene was confirmed by Sanger sequencing. The expression levels of A20 was evaluated by Western blot. Sanger sequencing and Western blot were also performed in the patient's family members.Results: A heterozygous mutation of TNFAIP3 (c.305A>G, p. Asn 102 Ser) was identified in the patient. The identical TNFAIP3 mutation was also found in her father and brother who had suffered from recurrent oral ulcers since childhood. Functional experiments revealed that the expression of A20 was decreased in the peripheral blood mononuclear cells of the patient and her family members who carried the TNFAIP3 mutation.Conclusion: We described a Chinese patient with a novel heterozygous mutation in TNFAIP3 who developed iBD-like symptoms. We proposed that the TNFAIP3 heterozygous mutation (c.305A>G, p. Asn 102 Ser) with an insufficient expression of A20 may be associated with the iBD phenotype in patients.

目的 研究内镜下OTSC吻合夹与常规内镜下止血治疗急性非静脉曲张性上消化道大出血(ANVUGIB)患者的临床疗效.方法 选取我院2016年3月至2018年3月收治的64例ANVUGIB患者纳入研究对象,以随机数表法分为观察组与对照组,每组32例.对照组于内镜下行常规止血治疗,观察组于内镜下使用OTSC吻合夹治疗.对比两组临床疗效及止血时间、住院时间、输血量各项指标,对比两组治疗前后凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、D-二聚体(D-D)、血浆纤维蛋白原(FIB)水平变化,另外统计两组住院期间并发症发生情况.结果 观察组临床疗效总有效率(93.75％)显著高于对照组(75.00％),差异有统计学意义(P<0.05).观察组治疗期间止血时间、住院时间、输血量分别为(36.15±5.44)h、(8.84±2.33)d、(262.41±54.72)mL显著少于对照组,差异有统计学意义(P<0.05).两组治疗后PT、APTT、D-D水平显著低于治疗前,差异有统计学意义(P<0.05);两组治疗后FIB水平显著高于治疗前,差异有统计学意义(P<0.05),组间比较,观察组PT、APTT、D-D、FIB与对照组比较,差异无统计学意义(P>0.05).两组住院期间未出现消化道穿孔、消化道瘘等严重并发症.结论 内镜下OTSC吻合夹止血治疗ANVUGIB能够改善患者凝血功能、缩短住院时间,临床效果满意,其安全性较高,值得临床应用.

Objective To investigate the clinical effect of liposoluble vitamin injection combined with adenosylmethionine butyrate in the treatment of alcoholic liver disease with cholestasis and its effect on serum soluble adhesion molecule (sVCAM - 1) and phospholipid transport protein (PLTP). Methods 140 patients with alcoholic liver disease with cholestasis were selected from January 2016 to August 2017. According to the different treatment methods,the patients were divided into control group and observation group with 70 cases in each group. The control group was treated with adenosylmethionine butylate,and the observation group was treated with fat - soluble vitamin injection on the basis of the control group. The clinical efficacy,blood biochemical indexes,CBA,serum CG,sVCAM - 1 and PLTP were compared between the two groups before and after treatment,and the occurrence of adverse reactions were also analyzed. Results The total clinical effective rate of the observation group was 92. 9％,which was significantly higher than that of the control group (81. 4％). The difference was statistically significant (P ＜ 0. 05). After treatment,two groups of patients with aspartate aminotransferase (AST),total bile acid (TBA),gamma glutamyl transpeptidase (GGT),alanine aminotransferase (ALT),total bilirubin (TBIL),type III procollagen (PC - III),serum bilirubin (SB),hyaluronidase (HA) and type IV collagen (IV - C) were significantly reduced,and albumin (Alb) was significantly increased,and the indexes in observation group were more significant than those in the control group (P ＜ 0. 05). After treatment,the levels of CBAG CGN VCAM - 1 and PLTP in the two groups were significantly decreased,and those in the observation group were lower than those in the control group (P ＜ 0. 05). After treatment,the adverse symptoms of most of the patients in the two groups disappeared or weakened,and the patients in the observation group were better than those in the control group (P ＜ 0. 05). Conclusion Fat - soluble vitamin injection combined with adenosylmethionine butyrate can significantly improve liver function and bile acid metabolism in patients with alcoholic liver disease with cholestasis,which may be related to the decrease of serum sVCAM - 1,PLTP level.

Background:The differentiation between intestinal tuberculosis (ITB) and Crohn's disease (CD) is a challenge. The aim of this study was to investigate a predictive model for differential diagnosis between ITB and CD. Methods:A total of 268 patients who were suspected of having ITB or CD were prospectively recruited between January 2013 and September 2016. The clinical, laboratory, radiological, endoscopic, and histological features were investigated and subjected to univariate and multivariate analyses. The final predictive model was developed based on the regression coefficients of multivariate logistic regression. To validate the model, the same regression equation was tested on the other group. Results:A total of 239 patients had a final diagnosis, including 86 ITB and 153 CD. Five variables (perianal disease, pulmonary involvement, longitudinal ulcer, left colon, and ratio of tuberculosis-specific antigen to phytohaemagglutinin) were selected for the predictive model to discriminate between ITB and CD. In the predictive model of the training data set, the area under the receiver operating characteristic (ROC) curve, sensitivity, specificity, and accuracy, with a cutoff level of 0.29, were 0.975 (95% confidence interval [CI], 0.939-0.993), 96.7%, 90.7%, and 92.8%, respectively. Application of the predictive model to the validation data set showed similar performance in distinguishing ITB from CD. The area under the ROC curve, sensitivity, specificity, and accuracy were 0.950 (95% CI, 0.871-0.987), 88.5%, 93.5%, and 91.7%, respectively. Conclusions:This 5-marker predictive model could be conveniently used by clinicians to draw a reliable differential diagnosis between ITB and CD in clinical practice. 10.1093/ibd/izy154_video1izy154.video15790725497001.

Emerging evidence has indicated that microRNAs (miRNAs) arc frequently dysregulated and arc fundamental in the pathogenesis of hepatocellular carcinoma (HCC). However, the roles of miR-195 in HCC have not been well elucidated. In the present study, the expression of miR-195 was determined to he markedly downregulated in HCC tissues and cell lines, as compared with normal liver cells. Restoration of miR-195 expression resulted in significant inhibition of the proliferation and tumorigenicity of HCC cells in vitro and in vivo. Gene expression data and luciferase reporter assays revealed that miR-195 is able to directly inhibit the expression of astrocyte elevated gene 1 (AEG-1) through interaction with its 3' untranslated region. Consistently, an inverse correlation between miR-195 and AEG-1 expression was observed in HCC tissues. Furthermore, the overexpression of AEG-1 was able to partially attenuate the miR-195-induced inhibition of cell growth and promotion of apoptosis. Taken together, these findings indicate that miR-195 functions as a tumor suppressor by inhibiting AEG-1. This pathway may provide new insights into the potential molecular mechanisms of HCC.

Objective To investigate expression of PP2CE in human hepatocellular carcinoma(HCC)tissues and the clinical pathological significance,and test its sub-cellular localization in liver cells and HCC cells.Methods A total of 50 samples of HCC tissues and their para-carcinoma tissues were collected in Tongji Hospital(Wuhan).PP2CE mRNA and protein levels were detected in HCC tissues and their para-carcinoma tissues by qRT-PCR and immunohistochemistry method.Immunofluorescent assay was performed to test the sub-cellular localization of PP2CE in the cells.Results PP2CE mRNA and protein expression levels were significantly decreased in HCC tissues as compared with those in para-carcinoma tissues(both P＜0.05).Immunohistochemistry analysis found that PP2CE expression was associated with tumor size,differentiated degree,portal vein invasion and clinical stage(both P＜0.05).Immunofluorescent assay suggested that PP2CE was mainly located in the cytoplasm and perinuclear area.Conclusion PP2CE is reduced in HCC and may be implicated in the development and progression of HCC.

Macroamylasemia is characterized by an elevated serum amylase activity. It results from the circulation of a macromolecular complex consisting of amylase molecule and a serum component, often an immunoglobulin. The present study presents marked elevation of serum amylase level in a 43-year-old male, who had been admitted to our hospital for slight abdomen ache for 4 months. After treatment following pancreatitis, the symptom did not improve. Abdominal CT did not find any typical malignancy. The amylase clearance : creatinine clearance (C-AM: C-CR) ratio is 0.001. Polyethylene glycol (PEG) precipitation assay shows that the PEG-precipitated amylase activity for this patient is 77%, whereas all six healthy controls are below 52%. Therefore, in this case, the elevated amylase levels may be a result of marcroamylasemia.

with LPS in vitro.Overexpression of TGR5 resulted in increased PCNA, CCK8, EdU incorporation and the proportion of cells in S phase, whereas, knockdown of TGR5 caused an opposite effect.Conclusions: Bile acids could promote intestinal epithelial cell proliferation and reduce the mucosal injury by upregulating the expression of TGR5 in obstructive jaundice.

Invasion and metastasis are the major causes of death in patients with esophageal squamous cell carcinoma (ESCC). Recent studies have confirmed that SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 1 (SPOCK1) plays multiple roles in cancer progression. This study aims to explore the clinical characteristics of SPOCK1 in ESCC and its roles in the migration and invasion of ESCC cell lines. In this study, the up-regulation of SPOCK1 expression was frequently detected in primary ESCC tumor tissues compared with those in non-tumor tissues, which was significantly associated with tumor invasion ( p = 0.004) and distant metastasis ( p = 0.010). SPOCK1 was expressed at higher level in TE13 cells as compared to the low malignant Eca109 and TE1 cells. Overexpression of SPOCK1 in Eca109 cells decreased the expressions of epithelial marker E-cadherin and ZO-1, while increased mesenchymal marker Vimentin and N-cadherin levels. After ectopic expression of SPOCK1, Eca109 cells exhibited a morphological change from an epithelial cobblestone phenotype to an elongated fibroblastic phenotype, concomitant with cytoskeletal rearrangements and increased migration and invasion, suggesting that EMT occurs. While silencing SPOCK1 in TE13 cells had the opposite effects. These results suggest that up-regulation of SPOCK1 in ESCC induces EMT, thus promotes migration and invasion in ESCC cells.

Aims: The alarmin HMGB1 is released during cell damage and acts as an early or late stage inflammatory cytokine at multiple levels of target cells. The Na+/H+ exchanger Isoform 3 (NHE3) is the major intestinal salt and fluid absorptive transporter and its function is defective in intestinal inflammation. Aim of the study: We wanted to know if HMGB1 can affect NHE3 mRNA or protein expression as well as its localization in mucosal tissue form patients with ulcerative colitis and in NHE3-expressing Caco2bbe colonic cells. Methods and Results: We studied the mRNA and protein expression and localization of HMGB1 and NHE3 in rectal biopsies from the inflamed and noninflamed mucosa of patients with ulcerative colitis by quantitative qPCR and immunohistochemistry. TNF-α and IFN-γmRNA level was significantly elevated in lesions compared to that in its adjacent normal tissue samples of UC patient's rectal, suggesting a reliable endoscopic sampling of inflamed vs noninflamed tissue. HMGB1 mRNA and protein expression was increased in the inflamed as compared to adjacent normal tissues, and it was mostly distributed in cytoplasm and extracellular region. NHE3 protein was markedly reduced in inflamed compared to adjacent normal tissues, though its mRNA level was not significantly different between inflamed and noninflamed mucosa. When Caco2bbe cells overexpressing human NHE3 (Caco2bbe/ hNHE3) were incubated with high concentration of rh-HMGB1 (10μg/ml), NHE3 mRNA was found to be decreased at 1h (0.385±0.015 vs. 1.011±0.011, p 0.05). NHE3 protein, measured byWestern analysis, was not significantly changed when co-cultured with 10μg/ml rhHMGB1 for 1h or 6h, however, it was dramatically decreased at 24h of co-culture with 10μg/ml rhHMGB1. IFN-gamma levels were markedly increased when Caco2bbe/hNHE3 cells were incubated with 10 μg/ml rhHMGB1 for 1h as compared with normal group (29.855±0.055 vs. 29.525±0.050, p 0.05) and 24h (29.066±0.181 vs. 29.525±0.050, p>0.05) of co-culture with 10μg/ml rhHMGB1 as compared to normal group. This suggests that incubation with rhHMGB1 may down-regulate NHE3 mRNA expression via elevated IFN-gamma level at early stage (1h), resulting in a decrease in NHE3 protein expression at late stage (24h). Conclusion: Decreased NHE3 protein level was accompanied by elevated cytoplasm and extracellular HMGB1 in human ulcerative rectitis tissue. This may result from the regulatory effect of cytokines such as IFNgamma induced by exogenous HMGB1 at late stage of inflammation.