Valuable clinical indicators for identifying infantile-onset inflammatory bowel disease patients with monogenic diseases

BACKGROUND Infantile-onset inflammatory bowel disease(IO-IBD)occurs in very young children and causes severe clinical manifestations,which has poor responses to traditional inflammatory bowel disease(IBD)treatments.At present,there are no simple and reliable laboratory indicators for early screening IO-IBD patients,especially those in whom the disease is caused by monogenic diseases.AIM To search for valuable indicators for early identifying IO-IBD patients,especially those in whom the disease is caused by monogenic diseases.METHODS A retrospective analysis was performed in 73 patients with IO-IBD admitted to our hospital in the past 5 years.Based on the next-generation sequencing results,they were divided into a monogenic IBD group(M-IBD)and a non-monogenic IBD group(NM-IBD).Forty age-matched patients with allergic proctocolitis(AP)were included in a control group.The clinical manifestations and the inflammatory factors in peripheral blood were evaluated.Logistic regression analysis and receiver operating characteristic(ROC)curve analysis were used to identify the screening factors and cut-off values of IO-IBD as well as monogenic IO-IBD,respectively.RESULTS Among the 44 M-IBD patients,35 carried IL-10RA mutations,and the most common mutations were c.301C>T(p.R101W,30/70)and the c.537G>A(p.T179T,17/70).Patients with higher serum tumor necrosis factor(TNF)-αvalue were more likely to have IBD[odds ratio(OR)=1.25,95%confidence interval(CI):1.05-1.50,P=0.013],while higher serum albumin level was associated with lower risk of IBD(OR=0.86,95%CI:0.74-1.00,P=0.048).The cut-off values of TNF-αand albumin were 17.40 pg/mL(sensitivity:0.78;specificity:0.88)and 36.50 g/L(sensitivity:0.80;specificity:0.90),respectively.The increased ferritin level was indicative of a genetic mutation in IO-IBD patients.Its cut-off value was 28.20 ng/mL(sensitivity:0.93;specificity:0.92).When interleukin(IL)-10 level was higher than 33.05 pg/mL(sensitivity:1.00;specificity:0.84),or the onset age was earlier than 0.21 mo(sensitivity:0.82;specificity:0.94),the presence of diseasecausing mutations in IL-10RA in IO-IBD patients was strongly suggested.CONCLUSION Serum TNF-αand albumin level could differentiate IO-IBD patients from allergic proctocolitis patients,and serum ferritin and IL-10 levels are useful indicators for early diagnosing monogenic IO-IBD.

Expression and clinical significance of lncRNA SNHG3 in peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease

Objective: To investigate the expression of lncRNA SNHG3 in peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease (COPD), and to explore its clinical significance with chronic obstructive pulmonary disease. Methods: Mononuclear cells were collected from 120 patients with COPD and 110 normal controls. The expression of lncRNA SNHG3 in peripheral blood mononuclear cells was detected by RT-PCR and the difference between COPD group and normal group, and the difference between mild, moderate, severe, extremely severe COPD and health volunteers was analyzed. Results: The relative expression of SNHG3 in peripheral blood mononuclear cells of COPD patients was 1.52 ± 0.52, which was lower than that of the normal control group (2.51 ± 0.59) (P < 0.001). The relative expression of SNHG3 in peripheral blood mononuclear cells of mild COPD was 2.16 ± 0.23, which was higher than that of moderate group (1.55 ± 0.10) (P < 0.001), severe group 1.19 ± 0.11 (P< 0.001), and extremely severe group 0.89 ± 0.06(P < 0.001). In addition, lncRNA SNHG3 can bind to miR-186 and regulate its expression. Conclusions: The expression of lncRNA SNHG3 in peripheral blood mononuclear cells of COPD patients may be a risk factor for COPD and an indicator of the severity of COPD patients. The lncRNA SNHG3/miR-186 regulatory network may play an important role in the development of COPD.

Clinical significance of lncRNA LINC01410 in preeclampsia and its effect on trophoblast proliferation and invasion

Objective:To study the expression of lncRNA LINC01410 in preeclampsia and normal placenta,and to explore its function and mechanism of affecting the proliferation and migration of trophoblast cells.Methods:The expression level of LINC01410 in the placenta of preeclampsia patients and pregnant women with normal pregnancy was detected by qRTPCR.After silencing LINC01410 in trophoblast cells HTR-8/Svneo,CCK-8 measured cell proliferation,and Transwell detected trophoblast invasion.Nucleus and chromatin RNA scores were measured,and Fas was detected by qRT-PCR and Western blot to explore the possible mechanisms.Results:The relative expression of LINC01410 in the placenta of the preeclampsia group was 2.564±0.169,which was significantly higher than 0.821±0.052 in the placenta tissue of the normal control group.After silencing LINC01410,the proliferation of trophoblast HTR-8/Svneo slowed down and the invasion ability decreased;The expression in the nucleus is more than in the cytoplasm,and the expression of Fas mRNA and protein is significantly reduced after silencing LINC01410.Conclusion:The high expression of lncRNA LINC01410 in preeclampsia placenta may be a risk factor for preeclampsia,and its mechanism may be to promote the proliferation and invasion of trophoblast cells by upregulating Fas expression.

HER2-positive circulating tumor cells indicate poor clinical outcome in stageⅠto Ⅲ breast cancer patients

Metastases may occur in node-negative breast cancer patients. It indicates that breast cancer cells can bypass regional lymph nodes and hematogenously disseminate to distant organs. In a recent paper (Clin Cancer Res 2006, 12:1715-1720) , Wulfing et al. evaluated the prognostic value of blood-borne, HER2-positive circulating tumor cells (CTC) in the peripheral blood from 42 breast cancer patients with a median follow-up of 95 months. HER2-