Development and external validation of a nomogram to predict the risk of Upper gastrointestinal precancerous lesions in a non-high-incidence area.

BACKGROUND: Upper gastrointestinal precancerous lesions (UGPL) is the major preventable disease in non-high-incidence area. A prognostic nomogram was constructed to predict and identity susceptible population of UGPL before endoscope screening. METHODS: We recruited 300 ,016 eligible participants for upper gastrointestinal cancer (UGC) screening aged 40-74 years from two cities in Hunan province from 2012 to 2019. Individuals at high risk of UGC on basis of questionnaire estimation underwent endoscopic screening. Participants in two cities accepting endoscopy were used as training and external validation cohorts, respectively. A nomogram was developed based on independent prognostic factors of UGPL determined in multivariable logistic regression analysis. RESULTS: Of 35, 621 with high risk for UGC, 10, 364 subjects undertook endoscopy (participation rate of 29.1%). The detection rate for UGPL was 4.55%. The nomogram showed that age, gender, mental trama, picked food, and atrophic gastritis history in a descending order were significant contributors to UGPL risk. The C-index value of internal and external validation of the model is 0.612 and 0.670, respectively. The calibration data for UGPL showed optimal agreement between the nomogram prediction and actual observation. Furthermore, high-risk and low-risk group divided based on score from the nomogram predicted a significantly distinct detection rate. CONCLUSION: The nomogram provides screening workers a simple and accurate tool for identifying individuals at a higher risk of UGPL as primary screening before endoscopy among Chinese population in non-high-risk areas, thus reducing the incidence of UGC by improving the UGPL detection.

Community-Based Upper Gastrointestinal Cancer Screening in a Randomized Controlled Trial: Baseline Results in a Non-high-incidence Area.

A cluster-randomized controlled trial (RCT) was conducted to evaluate to the effectiveness of reducing mortality of upper gastrointestinal cancer (UGC) and feasibility of screening through a questionnaire combined with endoscopy in non-high-incidence urban areas in China. The trial design, recruitment performance, and preliminary results from baseline endoscopy are reported. Seventy-five communities in two urban cities with a non-high-incidence of UGC were randomized to a screening endoscopy arm (n = 38) or a control arm (n = 37). In the screening arm, individuals at high risk of UGC underwent endoscopic screening. The primary outcome was the UGC mortality, and secondary outcomes included the UGC detection rate, incidence rate, survival rate, and clinical stage at the time of diagnosis. A total of 10,416 and 9,565 individuals were recruited into the screening and control arms, respectively. The participation rate was 74.3%. In the screening arm, 5,242 individuals (50.3%) were estimated to be high-risk. Among them, 2,388 (45.6%) underwent endoscopic screening. Age and household income were associated with undergoing endoscopy. Three early esophageal cancer (0.13%), one gastric cancer (0.04%), 29 precancerous esophageal lesions (1.21%), and 53 precancerous gastric lesions (2.22%) were detected. Age, sex, a family history of cancer, intake of meat-egg-milk frequently, superficial gastritis, and clinical symptoms of gastric cancer were associated with the presence of precancerous lesions. The detection rate was low using endoscopic screening in non-high-incidence area given the relatively low compliance rate. These findings provide a reference for designing effective community-based UGC screening strategies in non-high-incidence urban areas.

Development and validation of two prognostic nomograms for predicting survival in patients with non-small cell and small cell lung cancer.

PURPOSE: This study aimed to construct two prognostic nomograms to predict survival in patients with non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) using a novel set of clinical parameters. PATIENTS AND METHODS: Two nomograms were developed, using a retrospective analysis of 5384 NSCLC and 647 SCLC patients seen during a 10-year period at Xiang Ya Affiliated Cancer Hospital (Changsha, China). The patients were randomly divided into training and validation cohorts. Univariate and multivariate analyses were used to identify the prognostic factors needed to establish nomograms for the training cohort. The model was internally validated via bootstrap resampling and externally certified using the validation cohort. Predictive accuracy and discriminatory capability were estimated using concordance index (C-index), calibration curves, and risk group stratification. RESULTS: The largest contributor to overall survival (OS) prognosis in the NSCLC nomogram was the therapeutic regimen and diagnostic method parameters, and in the SCLC nomogram was the therapeutic regimen and health insurance plan parameters. Calibration curves for the nomogram prediction and the actual observation were in optimal agreement for the 3-year OS and acceptable agreement for the 5-year OS in both training datasets. The C-index was higher for the NSCLC cohort nomogram than for the TNM staging system (0.67 vs. 0.64, P = 0.01) and higher for the SCLC nomogram than for the clinical staging system (limited vs. extensive) (0.60 vs. 0.53, P = 0.12). CONCLUSION: Treatment regimen parameter made the largest contribution to OS prognosis in both nomograms, and these nomograms might provide clinicians and patients a simple tool that improves their ability to accurately estimate survival based on individual patient parameters rather than using an averaged predefined treatment regimen.

MicroRNA-433 inhibits cell proliferation in hepatocellular carcinoma by targeting p21 activated kinase (PAK4).

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. P21-activated kinase 4 (PAK4) has been identified as an oncogenic protein in a variety of cancers. However, the contribution and regulation of PAK4 in HCC remain poorly understood. In the present study, we found that inhibition of PAK4 expression by specific shRNA significantly attenuated HCC cell proliferation. Moreover, we show that microRNA-433 (miRNA-433) could directly target PAK4 through the miRNA-433 binding sequence at the 3'-UTR of PAK4 mRNA, and inhibit PAK4 protein expression. We further show that miRNA-433 expression was downregulated in HCC tissues and cell culture as well, which inversely correlated with PAK4 expression levels. Overexpression of miRNA-433 significantly suppressed the proliferation of HepG2 cells, while this effect was partially rescued by forced expression of PAK4 through restoring PI3K/AKT signaling in HepG2 cells. These findings will shed light on the roles and mechanisms of miRNA-433 in regulating HCC proliferation, and may benefit future development of therapeutics targeting miRNA-433 and PAK4 in HCC.

Relationship between red cell distribution width and serum uric acid in patients with untreated essential hypertension.

We assessed whether red cell distribution width (RDW) is associated with serum uric acid (UA) level in a group of 512 patients with newly diagnosed hypertension, recruited in Beijing. Patients were divided into high uric acid group and low uric acid group according to the median (334.9 µmol/L) of serum uric acid. Compared with the low uric acid group, the patients with high uric acid had higher red blood cell count (P < 0.001) and RDW (P = 0.032). The multiple linear regression analysis showed that RDW (P = 0.001) was positively correlated with uric acid level after the adjustment of related factors. Stepwise multiple logistic regression model confirmed that RDW (odds ratio: OR = 1.75) was independent determinants of high serum uric acid as well as sex (OR = 6.03), triglycerides (OR = 1.84), and Blood Urea Nitrogen (BUN, OR = 1.30). RDW may be independently associated with serum UA level in patients with newly diagnosed hypertension. To firmly establish the causal role of RDW in the incidence of high uric acid level among hypertensive patients, large cohort studies are needed.