Integrated analysis identifies oxidative stress-related lncRNAs associated with progression and prognosis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in the world. Oxidative stress reactions have been reportedly associated with oncogenesis and tumor progression. By analyzing mRNA expression data and clinical information from The Cancer Genome Atlas (TCGA), we aimed to construct an oxidative stress-related long noncoding RNA (lncRNA) risk model and identify oxidative stress-related biomarkers to improve the prognosis and treatment of CRC. RESULTS: Differentially expressed oxidative stress-related genes (DEOSGs) and oxidative stress-related lncRNAs were identified by using bioinformatics tools. An oxidative stress-related lncRNA risk model was constructed based on 9 lncRNAs (AC034213.1, AC008124.1, LINC01836, USP30-AS1, AP003555.1, AC083906.3, AC008494.3, AC009549.1, and AP006621.3) by least absolute shrinkage and selection operator (LASSO) analysis. The patients were then divided into high- and low-risk groups based on the median risk score. The high-risk group had a significantly worse overall survival (OS) (p < 0.001). Receiver operating characteristic (ROC) and calibration curves displayed the favorable predictive performance of the risk model. The nomogram successfully quantified the contribution of each metric to survival, and the concordance index and calibration plots demonstrated its excellent predictive capacity. Notably, different risk subgroups showed significant differences in terms of their metabolic activity, mutation landscape, immune microenvironment and drug sensitivity. Specifically, differences in the immune microenvironment implied that CRC patients in certain subgroups might be more responsive to immune checkpoint inhibitors. CONCLUSIONS: Oxidative stress-related lncRNAs can predict the prognosis of CRC patients, which provides new insight for future immunotherapies based on potential oxidative stress targets.

Preoperative Anemia Is a Predictor of Worse Postoperative Outcomes Following Open Pancreatoduodenectomy: A Propensity Score-Based Analysis.

Background: Preoperative anemia is a common clinical situation proved to be associated with severe outcomes in major surgeries, but not in pancreatic surgery. We aim to study the impact of preoperative anemia on morbidity and mortality in patients undergoing open pancreatoduodenectomy and use propensity score matching (PSM) to balance the basal data and reduce bias. Methods: We analyzed the data of consecutive patients undergoing open pancreatoduodenectomy with a complete record of preoperative hemoglobin, at two pancreatic centers in China between 2015 and 2019. Anemia is defined as hemoglobin less than 12 g/dl for male and 11 g/dl for female, following Chinese criteria. We compared clinical and economic outcomes before and after PSM and used logistic regression analysis to assess the correlation between variables and anemia. Results: The unmatched initial cohort consisted of 517 patients. A total of 148 cases (28.6%) were diagnosed with anemia at admission, and no case received a preoperative blood transfusion or anti-anemia therapy. After PSM, there were 126 cases in each group. The rate of severe postoperative complications was significantly higher in the anemia group than in the normal group (43.7% vs. 27.0%, p = 0.006), among which the differences in prevalence of clinically relevant postoperative pancreatic fistula (CR-POPF) (31.0% vs. 15.9%, p = 0.005) and cardiac and cerebrovascular events (4.0% vs. 0.0%, p = 0.024) were the most significant. The costs involved were more in the anemia group (26958.2 ± 21671.9 vs. 20987.7 ± 10237.9 USD, p = 0.013). Among anemic patients, receiver operating characteristic (ROC) curve analysis shows the cut-off value of hemoglobin, below which, patients are prone to suffer from major complications (104.5 g/l in male and 90.5 g/l in female). Among all patients, multivariate analysis showed that preoperative obstructive jaundice [odds ratio (OR) = 1.813, 95% confidence interval (CI) (1.206-2.725), p = 0.004] and pancreatic ductal adenocarcinoma [OR = 1.861, 95% CI (1.178-2.939), p = 0.008] were predictors of anemia. Among paired patients, preoperative anemia [OR = 2.593, 95% CI (1.481-5.541), p = 0.001] and malignant pathology [OR = 4.266, 95% CI (1.597-11.395), p = 0.004] were predictors of postoperative severe complications. Conclusion: Preoperative anemia is a predictor of worse postoperative outcomes following open pancreatoduodenectomy and needs to be identified and treated.

Establishing a new body mass index cutoff value for malnutrition diagnosis using the Global Leadership Initiative on Malnutrition (GLIM) tool in Chinese older adults.

BACKGROUND: The body weight of the Chinese population rose rapidly over the past two decades. The old 2001 body mass index (BMI) cutoff value for malnutrition may underestimate malnutrition diagnosis. We explored the BMI cutoff value for malnutrition diagnosis based on national BMI data from the past 30 years and applied it to the Global Leadership Initiative on Malnutrition (GLIM) criteria when investigating malnutrition in hospitalized older patients. METHODS: To explore the BMI cutoff value for malnutrition, we established a linear stepwise model to predict the annual increasing BMI trend based on data from the national BMI data set. The new cutoff value was applied to a large-scale data set from a cross-sectional study pertaining to older hospitalized patients recruited from 30 large hospitals in China. RESULTS: The BMI increased from 21.8 to 23 kg/m2 in two decades. We calculated that the net BMI increase will be 1.49 kg/m2 from 1999 to 2019. We subsequently proposed that the BMI cutoff value for malnutrition should rise to 20 kg/m2 . This cutoff value was applied to the validation data set, containing 8725 patients, and the GLIM-determined malnutrition rate was 24.58% (using the Nutrition Risk Screening 2002 [NRS-2002]) and 23.32% (using the Mini Nutritional Assessment-Short Form [MNA-SF]). The results significantly differed from those obtained using the 2001 Chinese BMI criteria. CONCLUSION: The GLIM tool has good applicability in Asian populations, especially in Chinese older patients. The BMI cutoff value for malnutrition should be adjusted to 20 kg/m2 for Chinese adults.

Preoperative Nutrition Support May Reduce the Prevalence of Postoperative Pancreatic Fistula after Open Pancreaticoduodenectomy in Patients with High Nutritional Risk Determined by NRS2002.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a severe complication which may be caused by a perioperative nutrition problem. We aimed to study whether patients with high nutritional risk (NRS2002 score ≥ 5) might benefit from preoperative nutrition support regarding the risk of CR-POPF after open pancreaticoduodenectomy. METHODS: Consecutive patients undergoing open pancreaticoduodenectomy with complete record of NRS2002 at two Chinese institutions between 2013 and 2018 were analysed. CR-POPF was diagnosed following the 2016 ISGPS criteria. Nutrition support included oral nutrition supplement and enteral and parenteral nutrition. Clinical and economic outcomes were analysed. RESULTS: 522 cases were included. 135 cases (25.9%) were at high nutritional risk (NRS2002 score ≥ 5), among which 41 cases (30.4%) received preoperative nutrition support. The CR-POPF rate was significantly lower in the preoperative nutrition support group compared with the no nutrition support group (12.2% versus 28.7%, P = 0.038). Multivariate analysis showed that preoperative nutrition support was a protective factor for CR-POPF in patients at high risk [OR 0.339, 95% CI (0.115-0.965), P = 0.039]. Higher albumin and a larger diameter of the main pancreatic duct were found to be other protectors for CR-POPF. CONCLUSIONS: Patients with high nutritional risk (NRS2002 score ≥ 5) may profit from preoperative nutritional support manifested in the reduction of CR-POPF.

Total Psoas Area Index is Valuable to Assess Sarcopenia, Sarcopenic Overweight/Obesity and Predict Outcomes in Patients Undergoing Open Pancreatoduodenectomy.

BACKGROUND AND AIM: Sarcopenia has been proven to be a risk factor after pancreatoduodenectomy (PD). We aimed to evaluate if decreased psoas muscle area and density shown in CT scan, as measures for sarcopenia, were associated with postoperative major complications and adverse outcomes in patients who underwent PD. PATIENTS AND METHODS: We analyzed 152 consecutive patients who underwent open PD. Total psoas area and muscle attenuation were measured on CT images at the level of the third lumbar vertebra. Total psoas area index (TPAI) was calculated, the cut-off values of TPAI were estimated and validated. The relationship between radiographic characters and outcomes was analyzed. RESULTS: The optimal cut-off values of TPAI were 4.78 cm2/m2 for males and 3.46 cm2/m2 for females. The values were validated by outcomes with significant differences in the rate of major complications, re-operation, length of stay, and total cost. The prevalence of TPAI-defined sarcopenia and sarcopenic overweight/obesity was 38.8% and 17.1% in total. In multivariate logistic regression, rate of major complications was associated with TPAI [OR=0.605, 95% CI (0.414, 0.883), P=0.009], TPAI-defined sarcopenia [OR=8.256, 95% CI (2.890, 23.583), P=0.000] and sarcopenic overweight/obesity [OR=7.462, 95% CI (2.084, 26.724), P=0.002]; meanwhile, NRS2002-defined nutritional risk and GLIM-defined malnutrition did not show relationship with major complications. CONCLUSION: Both sarcopenia and sarcopenic overweight/obesity determined by new TPAI cut-off values were associated with a higher rate of major complications and adverse outcomes in Chinese patients undergoing open PD whereas usual nutritional assessment was not.

MicroRNA-4472 Promotes Tumor Proliferation and Aggressiveness in Breast Cancer by Targeting RGMA and Inducing EMT.

BACKGROUND: Breast cancer is the most common cause of cancer-related death in women worldwide. MicroRNA (miRNA) ectopic expression has been reported to be involved in the regulation of gene expression in breast cancer. We screened several differentially expressed miRNAs associated with breast cancer chemoresistance, growth, and metastasis using a miRNA microarray. Increased expression of miR-4472 has been associated with larger breast tumors and chemoresistance. However, the biologic function of miR-4472 and its molecular mechanisms in cancer progression have not yet been reported. MATERIALS AND METHODS: Real-time quantitative polymerase chain reaction was used to measure the expression of miR-4472 in breast cancer tissue and cell lines. The biologic functions of miR-4472 and its target gene were explored using Transwell, cell proliferation, and flow cytometry assays. Bioinformatics tools, dual-luciferase reporter assays, and Western blot were used to identify the target genes of miR-4472. Western blot was used to explain the participation of miR-4472 and target gene in epithelial-to-mesenchymal transition. RESULTS: miR-4472 was significantly upregulated in highly metastatic breast cancer tissues, and its expression was positively associated with larger tumor size and advanced pTNM stage. miR-4472 promoted breast cancer cell metastasis and growth. Repulsive guidance molecule A (RGMA) was a direct target gene of miR-4472. RGMA was identified as a suppressor in cancer metastasis. miR-4472 downregulated expression of RGMA and promoted epithelial-to-mesenchymal transition by suppressing E-cadherin and initiating vimentin, ß-catenin, and Slug. CONCLUSIONS: miR-4472 contributes to the progression of breast cancer by regulating RGMA expression and inducing epithelial-to-mesenchymal transition, indicating that miR-4472/RGMA might serve as a therapeutic target for breast cancer.

Effect of oral nutritional supplementation on the post-discharge nutritional status and quality of life of gastrointestinal cancer patients after surgery: a multi-center study.

BACKGROUND AND OBJECTIVES: To evaluate the effect of oral nutritional supplementation (ONS) on the postdischarge nutritional status and quality of life (QoL) of gastrointestinal cancer patients after surgery. METHODS AND STUDY DESIGN: A multi-center study was conducted on gastrointestinal cancer patients who received surgical treatment from 2013-2015. All patients were screened using the Nutrition Risk Screening 2002 (NRS 2002) to assess nutritional risk. Patients with nutritional risk were randomized into two groups: patients in the study group (n=55) were given dietary guidance and ONS, control group (n=59) received only dietary guidance. Anthropometric measurements, nutrition-related laboratory tests, and gastrointestinal function scores were also collected and analyzed using Student's t test and analysis of variance (ANOVA). In addition, the EQ-5D was used to evaluate patients' QoL. RESULTS: Compared with baseline measurements, the body weight of patients in the study group increased by 1.35±0.53 kg and 1.35±0.73 kg at 60 and 90 days, which were significantly higher than those in the control group (-1.01±0.54 kg, and -1.60±0.81 kg at 60 and 90 days). The results from ANOVA showed that only weight and BMI differed significantly between the study and control groups and also between different measurement times (p<0.01). No differences were found for the other indicators or QoL between the study groups. CONCLUSIONS: ONS may improve the weight and BMI of surgically treated gastrointestinal cancer patients postdischarge. However, these effects had little impact on patients' QoL.

Prevalence and predictors of malnutrition in elderly Chinese adults: results from the China Health and Retirement Longitudinal Study.

OBJECTIVE: China has the largest population of elderly citizens in the world, with 177 million adults aged 60 years or older. However, no national estimate of malnutrition in elderly Chinese adults exists. We estimated the prevalence and predictors of malnutrition in this population. DESIGN: Data from the second wave of the Chinese Health and Retirement Longitudinal Study (CHARLS) include interview and biomarker data for 6450 subjects aged 60 years or older from 448 different communities in twenty-eight provinces, allowing for nationally representative results. Malnutrition was identified based on the ESPEN (European Society of Parenteral and Enteral Nutrition and Metabolism) criteria. We used multivariable regression to investigate the predictors of malnutrition, including demographic factors, marital status, self-reported health status, self-reported standard of living, health insurance status and education. SETTING: China. SUBJECTS: Community-dwelling Chinese adults aged 60 years or older. RESULTS: The prevalence of malnutrition in elderly Chinese adults was 12·6 %. Malnutrition was most common among those who were older (OR=1·09; 95 % CI 1·07, 1·10), male (OR=1·41; 95 % CI 1·10, 1·79), lived in rural areas (v. urban: OR=0·75; 95 % CI 0·57, 1·00) or lacked health insurance (P<0·01). CONCLUSIONS: The burden of malnutrition on elderly Chinese adults is significant. Based on current population estimates, up to 20 million are malnourished. Malnutrition is strongly associated with demographic factors, shows a trend to association with health status and is not strongly associated with standard of living or education. A coordinated effort is needed to address malnutrition in this population.

Trends in Specific Immunotherapy for Allergic Rhinitis: A Survey of Chinese ENT Specialists.

PURPOSE: Specific immunotherapy (SIT) is a suitable but uncommon treatment option for allergic rhinitis (AR) in China. The current understanding and attitude of Chinese ENT (ear, nose, and throat) specialists in regards to SIT is unclear. This study investigates current trends in the awareness and application status of SIT among Chinese ENT specialists. METHODS: We performed a nationwide, cross-sectional survey with a specially designed questionnaire given to 800 ENT specialists in China. A member of the trained research group conducted face-to-face interviews with each respondent. RESULTS: Most of the respondents considered AR (96.0%) and allergic asthma (96.0%) the most suitable indications for SIT. Of all respondents, 77.0% recommended the application of SIT as early as possible; in addition, SIT was considered 'relatively controllable and safe' by most respondents (80.6%). The highest allergen-positive rate in AR was associated with house dust mite (47.7%) and obvious differences existed among geographical regions. Conventional subcutaneous immunotherapy was the most highly recommended treatment option (96.2%). 'The high cost of SIT' (86.6%) and 'lack of patient knowledge of SIT' (85.2%) were probably the main reasons for the lower clinical use of SIT in China. CONCLUSIONS: Most cases showed that the opinions of Chinese ENT specialists appeared to be in agreement with recent SIT progress and international guidelines; however, many areas still need to enhance the standardization and use of SIT in China. Clinical guidelines for SIT require improvement; in addition, Chinese ENT specialists need continuing medical education on SIT.

Aberrant expression of CD227 is correlated with tumor characteristics and invasiveness of breast carcinoma.

PURPOSE: Increasing evidences demonstrate that CD227 plays a crucial role in the development and progression of breast cancer. However, the function of CD227 in breast carcinoma was still controversial and the investigation on CD227 in Asian race was scarce. METHODS: To investigate the relationship between CD227 and tumor characteristics of breast carcinoma, CD227, estrogen receptor (ER), progesterone receptor (PR), Her2/neu and Ki-67 were detected by immunohistochemistry in a series of 227 patients. The Kaplan-Meier method and log-rank tests were used to estimate the correlation between CD227 expression and patients' prognosis. Furthermore, in vitro invasion assay was performed to examine the effect of CD227 on the invasiveness of breast carcinoma cells after transfection with CD227 cDNA or antisense phosphorothioate oligodeoxynucleotides (ASODN) against CD227 mRNA. RESULTS: Our data demonstrate that the cytoplasm staining and high expression of CD227 were positively related to the aggressiveness of breast cancer. Both circumferential membrane staining and cytoplasm staining were associated with lymph node metastasis. Moreover, the cytoplasm staining and overexpression of CD227 were found to be related to Her-2/neu positivity, higher Ki-67 positivity and poorer survival of patients. We further demonstrated that the invasion ability of breast carcinoma cells could be enhanced or inhibited by CD227 cDNA or ASODN, respectively. CONCLUSIONS: We conclude that the aberrant expression of CD227, especially cytoplasm staining could be predictive for tumor aggressiveness, lymph node metastasis, poorer outcome of patients with breast cancers. And CD227 could promote the invasion ability of breast cancer cells, suggesting a potential role of CD227 as an oncogene in breast carcinoma.

[Establishment of an albumin and cytokeratin 19 genetically-modified embryonic stem cell line and evaluation of its hepatoblast differentiation capacities].

OBJECTIVE: To establish a gene-modified embryonic stem (ES; E14.1-2) cell line with hepatoblast differentiation reporter genes, albumin (ALB) and cytokeratin 19 (CK19), labeled to facilitate study of their potential applicability as differentiated hepatoblasts. METHODS: Two expression vectors were constructed, one with the ALB promotor driving the enhanced green fluorescent protein (EGFP) and anti-neomycin genes (pAlb-EGFP), and the other with the CK19 promotor driving the red fluorescence protein and anti-hygromycin genes (pCK19-hCD25-IRES-tdTOMATO). The linearized vectors were electroporated into the E14.1 line, and double reporter genes-modified ES cells (E14.1-2) were selected by neomycin and hygromycin. E14.1-2 hepatoblast differentiation was induced by exposure to growth factors (BMP4 and bFGF) and evidenced by embryoid body formation. Fluorescence-activated cell sorting (FACS) and reverse transcription-polymerase chain reaction (RT-PCR) were used to confirm whether differentiated cells were hepatoblast-like and to quantify the differentiation efficiency. RESULTS: The pAlb-EGFP and pCK19-hCD25-IRES-tdTOMATO vectors were shown to specifically activate ALB and CK19 expression. The E14.1-2 cell line with labeled ALB and CK19 was established, and shown to have pluripotency by RT-PCR detection of pluripotent markers' expression, namely Oct4 and SSEA-1. After 22 days of induction, 21.27% of the differentiated hepatoblasts were detected by FACS as positive for ALB and CK19 expression. CONCLUSIONS: A gene-modified ES cell line was generated with hepatocyte differentiation reporter genes ALB and CK19 labeled. The differentiation of the resultant E14.1-2 line was technically simple to qualify and quantify, and will likely aid future studies of hepatoblast characteristics.

Impact of fish oil enriched total parenteral nutrition on elderly patients after colorectal cancer surgery.

BACKGROUND: Polyunsaturated omega-3 fatty acids may beneficially influence healing processes and patient outcomes. The aim of this research was to study the clinical efficacy of fish oil enriched total parenteral nutrition in elderly patients after colorectal cancer surgery. METHODS: Fifty-seven elderly patients with colorectal cancer were enrolled in this prospective, randomized, double-blind, controlled clinical trial. All patients received isocaloric and isonitrogenous total parenteral nutrition by continuous infusion (20 - 24 hours per day) for seven days after surgery. The control group (n = 28) received 1.2 g/kg soybean oil per day, whereas the treatment group (n = 29) received 0.2 g/kg fish oil and 1.0 g/kg soybean oil per day. Blood samples were taken pre-operatively, and at days one and eight after the operation. The plasma levels of CD4, CD8, CD4/CD8, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were measured. Clinical outcomes were then analysed. RESULTS: Patient characteristics were comparable between the two groups. At day eight post-surgery, IL-6, TNF-α and CD8 titres were lower in the treatment group when compared to the control group; these results reached statistical significance. In the treatment group, there were fewer infectious complications and incidences of systemic inflammatory response syndrome (SIRS), and shorter lengths of hospital stay were observed. The total cost of medical care was comparable for the two groups. No serious adverse events occurred in either group. CONCLUSIONS: Fish oil 0.2 g/kg per day administrated to elderly patients after colorectal surgery was safe and may shorten the length of hospital stay and improve clinical outcomes.

Suppression of the epidermal growth factor receptor inhibits epithelial-mesenchymal transition in human pancreatic cancer PANC-1 cells.

BACKGROUND: Aberrant expression of epidermal growth factor receptor (EGFR) has been detected in pancreatic cancer; however, the mechanisms of EGFR in inducing pancreatic cancer development have not been adequately elucidated. The objective of this study was to determine the role of EGFR in mediating epithelial-mesenchymal transition (EMT) in pancreatic cancer cells. METHODS: Pancreatic cancer cell line PANC-1 was transfected with small interfering RNA of EGFR by use of a lentiviral expression vector to establish an EGFR-knockdown cell line (si-PANC-1). PANC-1 cells transfected with lentiviral vector expressing negative control sequence were used as negative control (NC-PANC-1). Scratch assay and transwell study were used to analyze cell migration and invasion. Real-time PCR and Western blotting were used to detect the expression of EMT markers E-cadherin, N-cadherin, vimentin, and fibronectin and transcription factors snail, slug, twist1, and sip1 in PANC-1, NC-PANC-1, and si-PANC-1 cells. Immunofluorescent staining with these antibodies and confocal microscopy were used to observe their cellular location and morphologic changes. RESULTS: After RNA interference of EGFR, the migration and invasion ability of si-PANC-1 cells decreased significantly. The expression of epithelial phenotype marker E-cadherin increased and the expression of mesenchymal phenotype markers N-cadherin, vimentin, and fibronectin decreased, indicating reversion of EMT. We also observed intracellular translocation of E-cadherin. Expression of transcription factors snail and slug in si-PANC-1 cells decreased significantly. CONCLUSION: Suppression of EGFR expression can significantly inhibit EMT of pancreatic cancer PANC-1 cells. The mechanism may be related with the down-regulation of the expression of transcription factors snail and slug.