Emerging roles of non-coding RNAs in colorectal cancer oxaliplatin resistance and liquid biopsy potential.

Colorectal cancer (CRC) is one of the most common malignancies of the digestive tract, with the annual incidence and mortality increasing consistently. Oxaliplatin-based chemotherapy is a preferred therapeutic regimen for patients with advanced CRC. However, most patients will inevitably develop resistance to oxaliplatin. Many studies have reported that non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs, and circular RNAs, are extensively involved in cancer progression. Moreover, emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation, and by epigenetic modification. In this review, we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin. Furthermore, we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy. This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.

Inhibitor of Differentiation 1 (ID1) Facilitates the Efficacy of Sorafenib in Non-Small Cell Lung Cancer Cells through Suppressing Epithelial to Mesenchymal Transition.

BACKGROUND Sorafenib, which is a multitargeted kinase inhibitor, has shown some antitumor effects in patients with non-small cell lung cancer (NSCLC). However, the potential target of sorafenib's antitumor activity is largely unknown. Moreover, definitive predictive biomarkers of benefit have rarely been reported. MATERIAL AND METHODS The alteration in inhibitor of differentiation 1 (ID1) expression in NSCLC cells with sorafenib treatment was detected by western blotting. The sensitivity of NSCLC cells to sorafenib was observed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) assay. Loss-of-function and gain-of-function experiments were performed to observe the role of ID1 expression in epithelial to mesenchymal transition (EMT) progression. RESULTS Initially, we observed that ID1 was downregulated in NSCLC cells treated with sorafenib. The response of NSCLC cells to sorafenib was inhibited by the transfection of small interfering RNAs (siRNAs) targeting ID1. In contrast, the transfection of ID1-overexpressing plasmids improved the response of NSCLC cells to sorafenib. Further experiments indicated that ID1 is expressed at high levels in epithelial H460 cells and expressed at low levels in mesenchymal H358 cells. Loss-of-function and gain-of-function experiments suggested that ID1 negatively regulates EMT in NSCLC. CONCLUSIONS The expression of ID1 is dose-dependently inhibited by sorafenib, and the overexpression of ID1 contributes to the antitumor activity of sorafenib by suppressing EMT development. Our results indicate that ID1 might be a potential target for the antitumor activity of sorafenib in NSCLC and that targeting ID1 is a feasible strategy to improve the sensitivity of NSCLC cells to sorafenib.

Association between bile acid metabolism and bone mineral density in postmenopausal women.

OBJECTIVES: Previous studies have not shown any correlation between bile acid metabolism and bone mineral density (BMD) in women with postmenopausal osteoporosis. Thus, the current study evaluated the association between bile acid levels as well as BMD and bone turnover marker levels in this group of women. METHODS: This single-center cross-sectional study included 150 postmenopausal Chinese women. According to BMD, the participants were divided into three groups: osteoporosis group, osteopenia group, and healthy control group. Serum bile acid, fibroblast growth factor 19 (FGF19), and bone turnover biomarker levels were assessed. Moreover, the concentrations of parathyroid hormone, 25-hydroxy vitamin D [25(OH)D], procollagen type I N-peptide (P1NP), and beta-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide (ß-CTX) were evaluated. The BMD of the lumbar spine and proximal femur were examined via dual-energy X-ray absorptiometry. RESULTS: The serum total bile acid levels in the osteoporosis and osteopenia groups (5.28±1.56 and 5.31±1.56 umol/L, respectively) were significantly lower than that in the healthy control group (6.33±2.04 umol/L; p=0.002 and 0.018, respectively). Serum bile acid level was positively associated with the BMD of the lumbar spine, femoral neck, and total hip. However, it negatively correlated with ß-CTX concentration. Moreover, no correlation was observed between bile acid and P1NP levels, and the levels of the other biomarkers that were measured did not differ between the groups. CONCLUSION: Serum bile acid was positively correlated with BMD and negatively correlated with bone turnover biomarkers reflecting bone absorption in postmenopausal women. Thus, bile acid may play an important role in bone metabolism.

Association between bile acid metabolism and bone mineral density in postmenopausal women

OBJECTIVES: Previous studies have not shown any correlation between bile acid metabolism and bone mineral density (BMD) in women with postmenopausal osteoporosis. Thus, the current study evaluated the association between bile acid levels as well as BMD and bone turnover marker levels in this group of women. METHODS: This single-center cross-sectional study included 150 postmenopausal Chinese women. According to BMD, the participants were divided into three groups: osteoporosis group, osteopenia group, and healthy control group. Serum bile acid, fibroblast growth factor 19 (FGF19), and bone turnover biomarker levels were assessed. Moreover, the concentrations of parathyroid hormone, 25-hydroxy vitamin D [25(OH)D], procollagen type I N-peptide (P1NP), and beta-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide (β-CTX) were evaluated. The BMD of the lumbar spine and proximal femur were examined via dual-energy X-ray absorptiometry. RESULTS: The serum total bile acid levels in the osteoporosis and osteopenia groups (5.28±1.56 and 5.31±1.56 umol/L, respectively) were significantly lower than that in the healthy control group (6.33±2.04 umol/L; p=0.002 and 0.018, respectively). Serum bile acid level was positively associated with the BMD of the lumbar spine, femoral neck, and total hip. However, it negatively correlated with β-CTX concentration. Moreover, no correlation was observed between bile acid and P1NP levels, and the levels of the other biomarkers that were measured did not differ between the groups. CONCLUSION: Serum bile acid was positively correlated with BMD and negatively correlated with bone turnover biomarkers reflecting bone absorption in postmenopausal women. Thus, bile acid may play an important role in bone metabolism.

The Value of the Inferior Vena Cava Area Distensibility Index and its Diameter Ratio for Predicting Fluid Responsiveness in Mechanically Ventilated Patients.

INTRODUCTION: It is necessary to evaluate fluid responsiveness before fluid resuscitation. We evaluated the value of inferior vena cava (IVC) area respiratory variation and the IVC diameter ratio (IVC DR) for predicting fluid responsiveness in mechanically ventilated patients. METHODS: A prospective observational study was performed in the intensive care unit between December 2017 and March 2018. Mechanically ventilated patients were enrolled and received ultrasound monitoring. IVC diameter distensibility index from the subxiphoid area (IVC-sx DDI), IVC diameter distensibility index from the right midaxillary line (IVC-rm DDI), IVC area distensibility index (IVC ADI), and IVC DR in cross-section were calculated by ultrasound monitoring IVC parameters. The enrolled patients were classified as nonresponders group and responders group according to whether the cardiac output increased by >10% after passive leg raising. RESULTS: Data from 67 mechanically ventilated patients were analyzed. 55.2% of patients had positive fluid responsiveness. The area of receiver operating characteristic curves evaluating the ability of the IVC-sx DDI, IVC-rm DDI, IVC ADI, and IVC DR to predict the fluid responsiveness were 0.702, 0.686, 0.749, and 0.829, respectively. IVC DR level of 1.43 was predictive of positive fluid responsiveness with 90.0% specificity and 67.6% sensitivity. IVC ADI level of 10.2% was predictive of positive fluid responsiveness with 40.0% specificity and 97.3% sensitivity. CONCLUSIONS: IVC ADI and its diameter ratio in cross-section had more value than IVC diameter distensibility index for predicting fluid responsiveness in mechanically ventilated patients.

What do patients expect from treatment with Dental Implants? Perceptions, expectations and misconceptions: a multicenter study.

OBJECTIVE: While research in terms of patient-centered care in implant therapy is growing, few studies have investigated patients' initial perceptions prior to consultation with the implant dentist. The aim of this cross-sectional study was to capture patients' initial information level, perceptions, as well as expectations from the implant therapy. METHOD: A 34-item questionnaire was developed to investigate patients' preoperative information, perceptions and expectations from treatment with Dental Implants. The study was conducted in three locations (Hong Kong, SiChuan and JiangSu) during 2014-2015 with 277 patients. RESULTS: The main information source about implant therapy was the dentist or hygienist for less than half of the patients (n = 113, 42%). About 62.8% of participants considered that they were in general informed about implants, but only 17.7% felt confident with the information they had. More than 30% of the sample appeared to maintain dangerous misperceptions about Dental Implants: "Dental Implants require less care than natural teeth"; "Treatment with Dental Implants is appropriate for all patients with missing teeth"; "Dental Implants last longer than natural teeth"; and "Treatments with Dental Implants have no risks or complications." Patients were divided when asked whether "Dental Implants are as functional as natural teeth" (agreement frequency = 52.7%). Expectations from treatment outcome were commonly high, while there was a significant correlation between the overall mean of perception scores and outcome expectation scores (r = 0.32, P < 0.001). Overall, younger subjects (<45 years) and those with higher education level (bachelor and postgraduate) tended to present more realistic perceptions and lower outcome expectations. CONCLUSION: The majority of patients in this study presented relatively realistic perceptions. However, an alarming portion of the sample presented with inaccurate perceptions and unrealistic expectations, which the dental team would need to diagnose and correct prior to initiating implant treatment.

[Asthma at acute attack stage treated with "Shao's five needling therapy": a multi-central randomized controlled study].

OBJECTIVE: To evaluate the clinical efficacy of asthma at acute attack stage treated with "Shao's five needling therapy". METHODS: The randomized controlled method was applied to divide 210 cases into an observation group and a control group, 105 cases in each one. In the observation group, "Shao's five needling therapy" [Feishu (BL 13), Dazhui (GV 14), Fengmen (BL 12)] and the combined therapy were adopted, including oxygen uptake, aerosol inhalation and oral administration of prednisone. In the control group, the oral administration of theophylline sustained release tablet and the combined therapy were applied. The treatment was continued for 7 days. The clinical symptoms and physical signs such as wheezing, cough, expectoration, chest stuffiness, wheezing rale and shortness of breath, as well as lung function indices such as forced expiratory volume one second (FEV1) and peak expiratory flow (PEF) were observed before and after treatment in the two groups. METHODS: In the observation group, 69 cases were cured clinically, 20 cases effective remarkably, 7 cases effective and 0 case failed. In the control group, 49 cases were cured clinically, 31 cases effective remarkably, 15 cases effective and 0 case failed. The difference in the efficacy was significant in comparison of the two groups (P < 0.05). The therapeutic effect in the observation group was better than that in the control group. The total score of the symptoms and physical signs, FEV1 and PEF after treatment were all improved significantly in the two groups (all P < 0.01). And the results in the observation group were better than those in the control group (all P < 0.01). CONCLUSION: "Shao's five needling therapy" achieves the significant efficacy on asthma at acute attack stage. It significantly relieves the symptoms and physical signs of the patients and improves lung functions. The effect is better than that of theophylline sustained release tablet.