The entire process of Clostridium difficile colonization to infection develops in large intestine. However, the real colonization pattern of C. difficile in preoperative colorectal cancer patients has not been studied. In this study, 33 C. difficile strains (16.1%) were isolated from stool samples of 205 preoperative colorectal cancer patients. C. difficile colonization rates in lymph node metastasis patients (22.3%) were significantly higher than lymph node negative patients (10.8%) (OR=2.314, 95%CI=1.023-5.235, P =0.025). Meanwhile, patients positive for stool occult blood had lower C. difficile colonization rates than negative patients (11.5% vs. 24.0%, OR=0.300, 95%CI=0.131-0.685, P =0.019). A total of 16 sequence types were revealed by multilocus sequence typing. Minimum spanning tree and time-space cluster analysis indicated that all C. difficile isolates were epidemiologically unrelated. Antibiotic susceptibility testing showed all isolates were susceptible to vancomycin and metronidazole. The results suggested that the prevalence of C. difficile colonization is high in preoperative colorectal cancer patients, and the colonization is not acquired in the hospital. Since lymph node metastasis colorectal cancer patients inevitably require adjuvant chemotherapy and C. difficile infection may halt the ongoing treatment, the call for sustained monitoring of C. difficile in those patients is apparently urgent.

Hypertension is a global health issue, and a reduced exercise capacity is unavoidable for older people. According to recent clinical studies, the intestinal microbiota play a crucial role in the pathogenesis of many human diseases. We investigated whether specific alterations in the gut microbiota contribute to the reduced exercise capacity of elderly patients with hypertension. This study enrolled 56 subjects, and all patients performed a cardiopulmonary exercise test and underwent fecal bacteria sequencing (16 s ribosomal RNA V4 region). According to peak oxygen uptake values, patients were divided into three groups (Weber A = 19, Weber B = 20, and Weber C = 17). The alpha diversity was not significantly different among the three groups. Regarding the beta diversity, Weber A samples were separate from the other two groups in the nonmetric multidimensional scaling ordination plot (ANOSIM pairwise comparisons generated an R > 0.5; p < 0.05). The abundance of Betaproteobacteria, Burkholderiales, Alcaligenaceae, Faecalibacterium and Ruminococcaceae was diminished in subjects with a reduced exercise capacity (LDA score > 4.0). Escherichia coli are a primary producer of trimethylamine and inflammation in the human gut, and the abundance of this bacteria was increased in patients with a reduced exercise capacity (LDA score > 4.0). On the other hand, Lachnospiraceae- Eubacterium_hallii _group, Lachnospiraceae- Lachnoclostridium , Lachnospiraceae- Blautia - Ruminococcus _sp__5_1_39BFAA, and Ruminococcaceae- Faecalibacterium belong to the order Clostridiales that are likely to produce short-chain fatty acids (LDA score > 4.0), and some of these species were enriched in the Weber B or Weber C group in multiple comparisons. Our data pointed to an altered gut microbiota as a potential contributor to the pathogenesis and progression of the reduced exercise capacity of elderly patients with hypertension.

Our initial experience showed that combined CT-guided (125)I radioactive seed implantation and GP chemotherapy are effective and safe for treating advanced NCSLC.

Resistance to chemotherapeutic drugs is a major obstacle in non-small cell lung cancer (NSCLC) therapy. The molecular determinants of NSCLC resistance to doxorubicin are unknown. In the present study, we investigated whether topoisomerase IIβ binding protein 1 (TopBP1) was involved in the chemoresistance to doxorubicin in NSCLC cancer. We found that p53-deficient lung cancer cells (NCI-H1299) displayed the greatest resistance to doxorubicin compared with NCI-H358, A549, and HCC827 cells with p53 expression. The expression of TopBP1 was significantly higher in NCI-H1299 cells than the other three tumor cell lines. In addition, TopBP1 knockdown with specific small interfering RNA in NCI-H1299 cells enhanced the doxorubicin chemosensitivity and decreased the expression of p53 in the presence of doxorubicin. After doxorubicin administration, co-immunoprecipitation assay showed that TopBP1 promoted the expression of p53 in NCI-H1299 cells. These results for the first time demonstrated that TopBP1 plays an important role in NSCLC chemoresistance via upregulation of p53. Therefore, inhibition of TopBP1, in combination with chemotherapy, may represent a novel strategy for the treatment of chemotherapy-resistant NSCLC.

Background: The published literature contains conflicting results regarding the impact of the glutathione S-transferase T1 (GSTT1) null genotype on the susceptibility to inflammatory bowel disease. Therefore, we conducted a meta-analysis of observational studies to assess the association. Methods: We searched four online databases for eligible studies. The odds ratio (OR) with 95% CI was used to assess the gene-disease association. We also performed subgroup analyses by type of inflammatory bowel disease and ethnicity. Results: There were 16 individual studies from 11 publications included in the analysis. There were 3366 cases with inflammatory bowel disease and 6013 controls. The meta-analysis of all 16 studies showed the GSTT1 null genotype was associated with increased susceptibility to inflammatory bowel disease (OR = 1.98, 95%CI 1.39-2.84, P < 0.001). The subgroup analysis by ethnicity further identified an association between the GSTT1 null genotype and inflammatory bowel disease in Caucasians, Asians, and Africans. The GSTT1 null genotype was associated with both ulcerative colitis (OR = 1.96, P = 0.004) and Crohn’s disease (OR = 2.01, P = 0.022). The GSTT1 null genotype was still significantly associated with ulcerative colitis (OR = 1.63, P < 0.0001) and Crohn’s disease (OR = 1.40, P = 0.023) after adjusting for study heterogeneity. Conclusion: The GSTT1 null genotype is significantly associated with an increased susceptibility to inflammatory bowel disease and is a risk factor for both ulcerative colitis and Crohn’s disease.

OR = 0.87, 95 % CI 0.62-1.21, P = 0.395). For CYP2E1 96-bp insertion polymorphism, meta-analysis showed that there was a significant association between the CYP2E1 96-bp insertion polymorphism and colorectal cancer risk under the allele contrast model and the dominant contrast model (for the allele contrast model: OR = 1.20, 95 % CI 1.06-1.36, P = 0.005; for the dominant contrast model: OR = 1.25, 95 % CI 1.07-1.45, P = 0.005). Subgroup analysis by race suggested that there was an obvious association between the CYP2E1 96-bp insertion polymorphism and colorectal cancer risk in Asians under the codominant contrast model. In conclusion, our meta-analysis demonstrates that there is a significant association between the CYP2E1 96-bp insertion polymorphism and colorectal cancer risk, and CYP2E1 9-bp insertion polymorphism is a risk factor for developing colorectal cancer.

Calcein acetoxymethyl ester (calcein-AM) treatment has been reported to exert antitumor effects in certain cancer cells; however, the detailed mechanism of action of calcein-AM in cancers remains unclear, especially in nonsmall cell lung cancer (NSCLC). This study focused on the function and mechanism of action of calcein-AM in NSCLC. We used cell viability assays, western blotting, and EdU proliferation assay combined with calcein-AM treatment or siRNA interference to investigate the role of topoisomerase IIβ binding protein 1 (TopBP1) and p53 in NSCLC chemotherapy. We found that calcein-AM has antitumor effects in lung cancer and enhances the antitumor effects of doxorubicin in NSCLC. Furthermore, we found that TopBP1, which we previously showed was involved in doxorubicin resistance through upregulation of aberrant p53, was involved in calcein-AM-mediated increased doxorubicin sensitivity. Doxorubicin upregulated the expression of aberrant p53. Calcein-AM repressed the expression of TopBP1, which resulted in reduced expression of aberrant p53 and disrupted the antiapoptotic activity mediated by the TopBP1/mutp53 pathway in NSCLC. Together, our findings show that calcein-AM, the cell-permeable derivative of calcein, exerts significant antitumor effects in NSCLC, and can enhance the antitumor effect of doxorubicin by regulating the TopBP1/mutp53 pathway. These findings provide novel insight into lung cancer treatment.

Objective: Overexpression of microRNA-21 (miR-21) increases the radiation resistance of esophageal squamous cell carcinoma (ESCC). However, the molecular mechanism responsible for this action is still unclear. In the present study, we investigated the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in miR-21-enhanced radiation resistance in patients with ESCC. Methods: We evaluated the association between miR-21 levels and radiation resistance in patients with ESCC. We also investigated the role of PTEN in the proliferation and apoptosis of ESCC cells transfected with miR-21 inhibitor during irradiation, using PTEN small interfering RNA (siRNA). Results: MiR-21 levels were significantly higher in radiation-resistant patients. Downregulation of miR-21 during irradiation suppressed the radiation resistance of ESCC cells, demonstrated by decreased cell proliferation and increased cell apoptosis. PTEN siRNA attenuated miR-21induced suppression of radiation resistance in ESCC cells. Conclusions: These results suggest that miR-21 enhanced the radiation resistance of ESCC by inhibiting PTEN. MiR-21 and PTEN are potential therapeutic biotargets for ESCC.