Background: This research aimed to study the associations between XPD (G751A, rs13181), hOGG1 (C326G, rs1052133) and XRCC4 (G1394T, rs6869366) gene polymorphisms and the risk of colorectal cancer (CRC) in a Chinese Han population. Method: A total of 225 Chinese Han patients with CRC were selected as the study group, and 200 healthy subjects were recruited as the control group. The polymorphisms of XPD G751A, hOGG1 C326G and XRCC4 G1394T loci were detected by the RFLP-PCR technique in the peripheral blood of all subjects. Results: Compared with individuals carrying the XPD751 GG allele, the A allele carriers (GA/AA) had a significantly increased risk of CRC (adjusted OR = 2.109, 95%CI = 1.352–3.287, P=0.003). Similarly, the G allele (CG/GG) of hOGG1 C326G locus conferred increased susceptibility to CRC (adjusted OR = 2.654, 95%CI = 1.915–3.685, P<0.001). In addition, the T allele carriers (GT/TT) of the XRCC4 G1394T locus have an increased risk of developing CRC (adjusted OR = 4.512, 95%CI = 2.785–7.402, P<0.001). The risk of CRC was significantly increased in individuals with both the XPD locus A allele and the hOGG1 locus G allele (adjusted OR = 1.543, 95%CI = 1.302–2.542, P=0.002). Furthermore, individuals with both the hOGG1 locus G allele and the XRCC4 locus T allele were predisposed to CRC development (adjusted OR = 3.854, 95%CI = 1.924–7.123, P<0.001). The risks of CRC in XPD gene A allele carriers (GA/AA) (adjusted OR = 1.570, 95%CI = 1.201–1.976, P=0.001), hOGG1 gene G allele carriers (CG/GG) (adjusted OR = 3.031, 95%CI = 2.184–4.225, P<0.001) and XRCC4 gene T allele carriers (GT/TT) (adjusted OR = 2.793, 95%CI = 2.235–3.222, P<0.001) were significantly higher in patients who smoked ≥16 packs/year. Conclusion: Our results suggest that XPD G751A, hOGG1 C326G and XRCC4 G1394T gene polymorphisms might play an important role in colorectal carcinogenesis and increase the risk of developing CRC in the Chinese Han population. The interaction between smoking and these gene polymorphisms would increase the risk of CRC.

Background Visceral hypersensitivity (VH) is one of the most common causes of irritable bowel syndrome (IBS). The anti-hyperalgesic effects of metabotropic glutamate receptor 8 (mGluR8) has been identified in the central nervous system (CNS). However, whether this receptor has a similar function in the gastrointestinal tract has not been well studied. The present study aimed to explore the role of this receptor in a visceral hypersensitivity-related IBS rat model. Methods Neonatal rats were separated from their mothers for 3 hours daily from postnatal day 2 to day 14 to establish neonatal maternal separation (NMS) models. The mGluR8 agonist (S)-3,4-DCPG (10 mg/kg) and the mGluR8 antagonist (RS)-α- methylserine-O-phosphate (MSOP) (10 mg/kg) were used to examine the role of mGLuR8 in the NMS rats. The expression of mGluR8, related inflammatory factors, and inflammatory signal pathways were assessed in colon tissues. Results Our data showed that mGluR8 expression was increased in the colonic mucosa of NMS rats compared to controls. In addition, selective activation of mGluR8 ameliorated visceral hypersensitivity, whereas antagonization of mGluR8 aggravated visceral hypersensitivity. Treatment with (S)-3,4-DCPG (10 mg/kg) reduced the expression of myeloperoxidase (MPO) in intestinal mucosa of NMS rats. Furthermore, activating mGluR8 reduced the expression of tumor necrosis factor-α (TNF-α), whereas antagonizing mGluR8 promoted that. The expressions of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) did not significantly change upon activation or antagonization of mGluR8 receptor. Conclusions The activation of mGluR8 receptor ameliorates visceral hypersensitivity in NMS rats, and the underlying mechanisms may be associated with the inhibition of TNF-α and the suppression of colonic inflammatory response.

Coeliac disease (CD) is an autoimmune small bowel disease that occurs in susceptible individuals that develop an immunological reaction to gluten. A strict gluten-free diet (GFD) is the primary treatment for CD. This case report describes a patient with CD recurrence due to a discontinuation of a strict GFD by the patient. After recurrence, the patient developed fever and pancytopaenia, and quickly died of haemophagocytic lymphohistiocytosis (HLH). To the best of our knowledge, this is the first description of a case of CD associated with HLH due to discontinued GFD, which may contribute to improving the awareness of the importance of maintaining a strict GFD and having regular follow-up examinations.