G-protein coupled receptor 35 (GPR35) regulates the colonic epithelial cell response to enterotoxigenic Bacteroides fragilis

G protein-coupled receptor (GPR)35 is highly expressed in the gastro-intestinal tract, predominantly in colon epithelial cells (CEC), and has been associated with inflammatory bowel diseases (IBD), suggesting a role in gastrointestinal inflammation. The enterotoxigenic Bacteroides fragilis (ETBF) toxin (BFT) is an important virulence factor causing gut inflammation in humans and animal models. We identified that BFT signals through GPR35. Blocking GPR35 function in CECs using the GPR35 antagonist ML145, in conjunction with shRNA knock-down and CRISPRcas-mediated knock-out, resulted in reduced CEC-response to BFT as measured by E-cadherin cleavage, beta-arrestin recruitment and IL-8 secretion. Importantly, GPR35 is required for the rapid onset of ETBF-induced colitis in mouse models. GPR35-deficient mice showed reduced death and disease severity compared to wild-type C57Bl6 mice. Our data support a role for GPR35 in the CEC and mucosal response to BFT and underscore the importance of this molecule for sensing ETBF in the colon

Primary hepatic carcinoid tumor

Abstract Primary hepatic carcinoid tumor is rare and poses a challenge for diagnosis and management. We presented a case of primary hepatic carcinoid tumor in a 53-year-old female with a complaint of right upper abdominal pain. Computer tomography scans revealed a hypervascular mass in segment 4 of the liver. An ultrasonography-guided biopsy showed a carcinoid tumor. No other lesions were found by the radiological investigations. Surgery resection was performed and histopathological examination revealed a primary hepatic carcinoid tumor. Three years later, recurrence was found and transcatheter arterial chemoembolization was performed. After transcatheter arterial chemoembolization, the patient has been free of symptom and had no radiological disease progression for over 6 months. Surgical resection combination with transcatheter arterial chemoembolization is effective to offer excellent palliation.</p

Statistical damage classification method based wavelet packet analysis

A novel damage classification method based on wavelet packet transform and statistical analysis is developed in this study for structural health monitoring. The response signal of a structure under an impact load is normalized and then decomposed into wavelet packet components. Energies of these wavelet packet components are then calculated to obtain the energy distribution. Statistical similarity comparison based on an F-test is used to classify the structure from changes in the wavelet packet energy distribution. A statistical indicator is developed to describe the damage extent of the structure. This approach is applied to the test results from simply supported reinforced concrete beams in the laboratory. Cases with single and two damages are created from static loading, and accelerations of the structure from under impact loads are analyzed. Results show that the method can be used with no reference baseline measurement and model for the damage monitoring and assessment of the structure with alarms at a specified significance level

One-year unplanned readmission after total hip arthroplasty in patients with osteonecrosis of the femoral head: rate, causes, and risk factors

Abstract Background The primary objectives of this study were to focus on one - year unplanned readmissions after THA in ONFH patients and to investigate rates, causes, and independent risk factors. Methods Between October 2014 and April 2019, eligible patients undergoing THA were enrolled and divided into unplanned readmission within one year and no readmission in this study. All unplanned readmissions within 1 year of discharge were reviewed for causes and the rate of unplanned readmissions was calculated. Demographic information, ONFH characteristics, and treatment-related variables of both groups were compared and analysed. Results Finally, 41 out of 876 patients experienced unplanned readmission. The readmission rate was 1.83% in 30 days 2.63% in 90 days, and 4.68% in 1 year. Prosthesis dislocation was always the most common cause at all time points studied within a year. The final logistic regression model revealed that higher risks of unplanned readmission were associated with age > 60 years (P = 0.001), urban residence (P = 0.001), ARCO stage IV (P = 0.025), and smoking (P = 0.033). Conclusions We recommend the introduction of a strict smoking cessation program prior to surgery and the development of comprehensive management strategies, especially for the elderly and end-stage ONFH patients, and pay more attention to preventing prosthesis dislocation in the early days after surgery

Regulatory T cell response to enterotoxigenic Bacteroides fragilis colonization triggers IL-17-dependent colon carcinogenesis.

Many epithelial cancers are associated with chronic inflammation. However, the features of inflammation that are pro-carcinogenic are not fully understood. Tregs typically restrain overt inflammatory responses and maintain intestinal immune homeostasis. Their immune suppressive activity can inhibit inflammation-associated cancers. Paradoxically, we show that colonic Tregs initiate IL-17-mediated carcinogenesis in multiple intestinal neoplasia mice colonized with the human symbiote ETBF. Depletion of Tregs in ETBF-colonized C57BL/6 Foxp3(DTR) mice enhanced colitis but diminished tumorigenesis associated with shifting of mucosal cytokine profile from IL-17 to IFN-γ; inhibition of ETBF-induced colon tumorigenesis was dependent on reduced IL-17 inflammation and IFN-γ-independent. Treg enhancement of IL-17 production is cell-extrinsic. IL-2 blockade restored Th17 responses and tumor formation in Treg-depleted animals. Our findings demonstrate that Tregs limit the availability of IL-2 in the local microenvironment, allowing Th17 development necessary to promote ETBF-triggered neoplasia and thus unveil a new mechanism whereby Treg responses to intestinal bacterial infection can promote tumorigenesis

Pleiotropic ZIP8 A391T implicates abnormal manganese homeostasis in complex human disease

ZIP8 is a metal transporter with a role in manganese (Mn) homeostasis. A common genetic variant in ZIP8 (rs13107325; A391T) ranks in the top 10 of pleiotropic SNPs identified in GWAS; A391T has associations with an increased risk of schizophrenia, obesity, Crohn’s disease, and reduced blood Mn. Here, we used CRISPR/Cas9-mediated knockin (KI) to generate a mouse model of ZIP8 A391T (Zip8 393T-KI mice). Recapitulating the SNP association with blood Mn, blood Mn was reduced in Zip8 393T-KI mice. There was restricted abnormal tissue Mn homeostasis, with decreases in liver and kidney Mn and a reciprocal increase in biliary Mn, providing in vivo evidence of hypomorphic Zip8 function. Upon challenge in a chemically induced colitis model, male Zip8 393T-KI mice exhibited enhanced disease susceptibility. ZIP8 391-Thr associated with reduced triantennary plasma N-glycan species in a population-based cohort to define a genotype-specific glycophenotype hypothesized to be linked to Mn-dependent glycosyltransferase activity. This glycophenotype was maintained in a cohort of patients with Crohn’s disease. These data and the pleiotropic disease associations with ZIP8 391-Thr suggest underappreciated roles of Mn homeostasis in complex human disease