Developing a Prognostic Model for Primary Biliary Cholangitis Based on a Random Survival Forest Model.

Background: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease with few effective treatments and a poor prognosis, and its incidence is on the rise. There is an urgent need for more targeted treatment strategies to accurately identify high-risk patients. The use of stochastic survival forest models in machine learning is an innovative approach to constructing a prognostic model for PBC that can improve the prognosis by identifying high-risk patients for targeted treatment. Method: Based on the inclusion and exclusion criteria, the clinical data and follow-up data of patients diagnosed with PBC-associated cirrhosis between January 2011 and December 2021 at Taizhou Hospital of Zhejiang Province were retrospectively collected and analyzed. Data analyses and random survival forest model construction were based on the R language. Result: Through a Cox univariate regression analysis of 90 included samples and 46 variables, 17 variables with p-values <0.1 were selected for initial model construction. The out-of-bag (OOB) performance error was 0.2094, and K-fold cross-validation yielded an internal validation C-index of 0.8182. Through model selection, cholinesterase, bile acid, the white blood cell count, total bilirubin, and albumin were chosen for the final predictive model, with a final OOB performance error of 0.2002 and C-index of 0.7805. Using the final model, patients were stratified into high- and low-risk groups, which showed significant differences with a P value <0.0001. The area under the curve was used to evaluate the predictive ability for patients in the first, third, and fifth years, with respective results of 0.9595, 0.8898, and 0.9088. Conclusion: The present study constructed a prognostic model for PBC-associated cirrhosis patients using a random survival forest model, which accurately stratified patients into low- and high-risk groups. Treatment strategies can thus be more targeted, leading to improved outcomes for high-risk patients.

Cloud-Based Machine Learning Methods for Parameter Prediction in Textile Manufacturing.

In traditional textile manufacturing, downstream manufacturers use raw materials, such as Nylon and cotton yarns, to produce textile products. The manufacturing process involves warping, sizing, beaming, weaving, and inspection. Staff members typically use a trial-and-error approach to adjust the appropriate production parameters in the manufacturing process, which can be time consuming and a waste of resources. To enhance the efficiency and effectiveness of textile manufacturing economically, this study proposes a query-based learning method in regression analytics using existing manufacturing data. Query-based learning allows the model training to evolve its decision-making process through dynamic interactions with its solution space. In this study, predefined target parameters of quality factors were first used to validate the training results and create new training patterns. These new patterns were then imported into the solution space of the training model. In predicting product quality, the results show that the proposed query-based regression algorithm has a mean squared error of 0.0153, which is better than those of the original regression-related methods (Avg. mean squared error = 0.020). The trained model was deployed as an application programing interface (API) for cloud-based analytics and an extensive auto-notification service.

Development and validation of LightGBM algorithm for optimizing of Helicobacter pylori antibody during the minimum living guarantee crowd based gastric cancer screening program in Taizhou, China.

Gastric cancer continues to be a significant health concern in China, with a high incidence rate. To mitigate its impact, early detection and treatment is key. However, conducting large-scale endoscopic gastric cancer screening is not feasible in China. Instead, a more appropriate approach would be to initially screen high-risk groups and follow up with endoscopic testing as needed. We conducted a study on 25,622 asymptomatic participants aged 45-70 years from a free gastric cancer screening program in the Taizhou city government's Minimum Living Guarantee Crowd (MLGC) initiative. Participants completed questionnaires, blood tests, and underwent gastrin-17 (G-17), pepsinogen I and II (PGI and PGII), and H. pylori IgG antibody (IgG) assessments. Using the light gradient boosting machine (lightGBM) algorithm, we developed a predictive model for gastric cancer risk. In the full model, F1 score was 2.66%, precision was 1.36%, and recall was 58.14%. In the high-risk model, F1 score was 2.51%, precision was 1.27%, and recall was 94.55%. Excluding IgG, the F1 score was 2.73%, precision was 1.40%, and recall was 68.62%. We conclude that H. pylori IgG appears to be able to be excluded from the prediction model without significantly affecting its performance, which is important from a health economic point of view. It suggests that screening indicators can be optimized, and expenditures reduced. These findings can have important implications for policymakers, as we can focus resources on other important aspects of gastric cancer prevention and control.

Inhibition of UVA Damage on Human Skin Dermis Fibroblasts by the Isoflavonoid Intermediate Deoxybenzoin-3A.

Ultraviolet rays are the main cause of skin aging. Isoflavone structures are good anti-ultraviolet natural compounds and have an especially strong anti-ultraviolet B (UVB) effect. However, the anti-ultraviolet A (UVA) effect of isoflavones is more controversial. Therefore, this study aims to discover which isoflavone analogue possesses a strong anti-ultraviolet A. We found the isoflavonoid intermediate deoxybenzoin-3A (DOB-3A) to be a similar isoflavone structural compound with strong anti-ultraviolet A effects. Ultraviolet rays with a wavelength of 350 nm are used to irradiate the fibroblasts of the human skin. Western blot, flow cytometry, and transmission electron microscope analyses were used to explore its anti-ultraviolet A mechanism. We established the results that DOB-3A (1) reduced the death of fibroblasts caused by ultraviolet A, (2) avoided the damage to the organelles and structures after UVA irradiation, (3) inhibited the generation of intracellular reactive oxygen species (ROS) and hydrogen peroxide-induced damage, and (4) decreased the phosphorylation of mitogen-activated protein kinases (MAPK) caused by UVA. Based on the above findings, DOB-3A is a very good anti-ultraviolet A isoflavone-related structure. Because it is simple to synthesize and has good effects, DOB-3A is a suitable anti-ultraviolet A product with an isoflavone structure. Moreover, DOB-3A's structure provides a reference for the synthesis of anti-UVA isoflavones.

Risk of ankylosing spondylitis following human papillomavirus infection: A nationwide, population-based, cohort study.

OBJECTIVE: To assess the incidence rate and risk of ankylosing spondylitis (AS) in patients with previous human papillomavirus (HPV) infection compared with those without HPV infection. METHODS: All patients with HPV infection (n = 66,314) in the NHIRD (2003-2013) were individually matched with up to four control subjects without HPV infection by age and sex (n = 265,256). All of the patients were tracked until an AS event was noted. Chi-square test was used to analyze the distribution of sociodemographic characteristics in the HPV cohort and non-HPV cohort. Cox proportional hazards regression was used to calculate the HRs for the development of AS, adjusting for age, sex, urbanization, length of hospital stay, medications, and comorbidities adjustment. The Kaplan-Meier method was used to plot the cumulative incidence curves. RESULTS: The HPV cohort had a 1.329 (95% C.I. = 1.138-1.552) times higher risk of AS than that of the non-HPV cohort after adjusting for sex, age, urbanization, length of hospital stay, comorbidities, and medications. Additionally, we applied propensity score weighting to reconfirm the accuracy of our analysis, and the results showed a 1.348 (95% C.I. = 1.153-1.575) times greater risk of AS in the HPV cohort compared with the non-HPV cohort. The cumulative incidence curves plotted by the Kaplan-Meier method revealed that after 120 follow-up months, the HPV cohort displayed a higher cumulative incidence of AS than that of the non-HPV cohort. (Log-rank test p < 0.0001). CONCLUSIONS: Patients with HPV infection had a higher risk of developing AS compared with non-HPV patients.

Macrophage-mediated mechanisms of lung injury in the sensitization reaction to Echinococcus granulosus.

Objective: In this study, the impact of inhibiting the PI3K/AKT/NF-κB pathway on lung oxidative damage induced by Echinococcus granulosus cyst fluid was investigated. Methods: Twenty-four mice were randomly assigned to four groups. Three months after inoculation with hydatid cyst segments, mice in group A were treated with intraperitoneal and intratracheal saline injections; mice in group B were administered a caudal vein injection of a PI3K inhibitor, followed by cyst fluid sensitization; mice in group C received an AKT inhibitor via caudal vein, followed by cyst fluid sensitization; and mice in group D were subjected to cyst fluid sensitization without any inhibitor treatment. Cellular changes in lung tissues across all groups were evaluated, including pathological section analysis. Analysis of pulmonary tissue and serum from these mice included the assessment of PI3K/AKT/NF-κB pathway proteins, inflammatory factors, and related mRNA levels. Results: Mice in groups B and C exhibited a higher proportion of M2-type macrophages and significantly lower levels of PI3K/AKT/NF-κB pathway proteins, inflammatory factors (interleukin-6 [IL-6]/tumor necrosis factor-α [TNF-α]), and oxidative markers in lung tissues compared to mice in group D (P < 0.05). Conclusion: Our results in this study indicate that activation of the PI3K/AKT/NF-κB pathway contributed to an increase in the M1 macrophage phenotype, leading to enhanced secretion of peroxidases and inflammatory factors. This mechanism plays a crucial role in the oxidative and inflammatory lung damage associated with allergic reactions to E. granulosus cyst fluid.

Rural-urban disparities in Oral Health-related Quality of Life for middle-aged and older adults with diabetes in Taiwan.

Background: Public health faces a significant challenge in reducing rural-urban disparities in diabetes. Since dietary control is part of the medical regimen for diabetes management, how diabetic patients perceive the impact of oral health on their quality of life is critical. The present study aimed to compare the Oral Health-related Quality of Life (OHRQoL) between rural and urban diabetic patients. Methods: The study design was cross-sectional. The study sample included 831 self-reported diabetic patients, extracted from the first wave of the new-cohort Taiwan Longitudinal Study on Aging survey (NC_TLSA) that comprised a nationally representative sample of community-dwelling adults aged 50 and above in Taiwan. The composite score generated from the Oral Health Impact Profile-7 (OHIP-7), which has seven questions, was used to construct two OHRQoL measures, the severity of perceived poor OHRQoL and the prevalence of poor OHRQoL. These two OHRQoL measures were treated as dichotomous variables. Multivariate logistic regression models were applied for analysis. Results: Rural diabetic patients had a higher likelihood of experiencing the severity of perceived poor OHRQoL than those in urban areas (OR = 2.40, 95% CI: 1.30-4.40). Although rural diabetic patients also had a higher prevalence of poor OHRQoL than urban diabetic patients, the difference was not significant (OR = 1.47, 95% CI: 0.95-2.28). Social determinants, such as education, are essential factors attributed to both OHRQoL measures. Conclusion: Overall, rural diabetes community-dwelling patients had a poorer OHRQoL than those in urban areas. Given a bidirectional relationship between oral health and diabetes, improving oral health in rural areas may be a critical avenue to improve the quality of diabetes care in rural areas.

Causal effects of fatty acids on atopic dermatitis: A Mendelian randomization study.

Background: Some evidence suggests abnormalities in fatty acids in patients with atopic dermatitis (AD), and benefits of supplementation with these fatty acids have been reported. However, there is still substantial controversy on the correlation between fatty acids and AD. Therefore, the aim of this study was to determine whether fatty acid levels are causally related to AD using a Mendelian randomization approach. Methods: We evaluated the data about the fatty acids levels and AD with various methods from Genome-Wide Association Study (GWAS). GWAS results were available both from European ancestry. Mendelian randomization methods were used to analysis the casual inference of fatty acids on AD. MR Egger and MR-PRESSO were used to determine pleiotropy and heterogeneity. Further analysis was conducted using instruments associated with the FADS genes to address mechanisms involved. We also used Multivariate MR (MVMR) to show the independent casual inference of omega-3 (n-3) fatty acids on AD. Results: Mendelian randomization (MR) analysis suggests that n-3 fatty acid levels are associated with a lower risk of AD (n-3 ORIVW: 0.92, 95% confidence interval [CI]: 0.87-0.98; p = 0.01). Moreover, docosahexaenoic acids (DHA) levels, which is a kind of long-chain, highly unsaturated omega-3 (n-3) fatty acid, and its higher level was associated with a lower risk of AD (DHA ORIVW: 0.91, 95% CI: 0.84-0.98; p = 0.02). We ran multivariable MR analysis while controlling for variables within the other types of fatty acids. The effect estimates agreed with the preliminary MR analysis indicating the effect of n-3 fatty acids levels on AD was robust. MR-egger suggest no significant pleiotropy and heterogeneity on genetic instrumental variants. Outliers-corrected MR analyses after controlling horizontal pleiotropy were still robust. The single-SNP analyses revealed that n-3 fatty acids are likely linked to a decreased risk of AD through FADS cluster, highlighting the significance of the FADS gene in the fatty acids synthesis pathway in the development of AD. Conclusion: Our studies suggest that n-3 fatty acids may reduce the risk of AD. Risk prediction tools based on n-3 fatty acid levels may be valuable methods for improving AD screening and primary prevention. To reduce the risk of AD, individuals could enhance n-3 fatty acids intake through supplement or diet.

The role of memory T cells in Echinococcus granulosus-induced sensitization.

OBJECTIVE: To investigate the changes in memory T cells and the related factors in mice by the establishment of a BALB/c mouse model of Echinococcus granulosus-induced sensitization. METHODS: A sensitized BALB/c mouse model was established by intraperitoneal injection of E. granulosus. A control group (CTRL), a nonsensitized group infected with E. granulosus (CE), and a sensitized group infected with E. granulosus (ANPC) were set up. The pathological changes in lung tissue in mice, the change in memory T cells (CD4 Tm), and the change in peripheral blood nucleated interleukin-23 (IL-23) were detected using HE staining, flow cytometry, and liquid-phase multiple protein quantification techniques, respectively. RESULTS: The individual percentage of mouse memory T cells was 9.14 ± 0.45, 25.23 ± 0.17, and 13.29 ± 0.32 in the CTRL, CE, and ANPC groups, respectively. The percentage of memory T cells in the ANPC group was higher than that in the CTRL group (t = 18.410, p < .001) but lower than that in the CE group (t = -80.147, p < .001). The levels of IL-23 in peripheral blood of mice in the CTRL, CE, and ANPC groups were 225.76 ± 27.16, 359.21 ± 28.67, and 215.69 ± 22.69, respectively. The level of IL-23 in peripheral blood of mice in the ANPC group was lower than that in the CE group (t = 9.609, p < .001), and there was no statistical difference with the CTRL group (t = 0.697, p = .502). CONCLUSION: In the BALB/c mouse model of E. granulosus-induced sensitization, the expression of IL-23 in peripheral blood increased, and the memory T cell proliferated and became activated; there was a decrease in the content of IL-23 in peripheral blood and number of activated memory T cells in the sensitization group infected with E. granulosus. The E. granulosus-induced allergic reaction was related to IL-23 and the activation of memory T cells.

New hope for esophageal stricture prevention: A prospective single-center trial on acellular dermal matrix.

BACKGROUND: Given the high incidence of esophageal cancer in China, an increasing number of patients there are undergoing endoscopic mucosal dissection (ESD). Although the 5-year survival rate after ESD can exceed 95%, esophageal stricture, the most common and serious postoperative complication, affects the long-term prognosis of patients and the quality of life. Autologous mucosal grafts have proven to be successful in preventing stricture after ESD for early esophageal cancer. AIM: To examine the viability of acellular dermal matrix (ADM) as an alternative to autologous mucosa for the prevention of stricture after ESD. METHODS: This is a prospective, single-center, controlled study. Consecutive patients who underwent ESD surgery and were willing to undergo autologous mucosal transplantation were recruited between January 1 and December 31, 2017. Consecutive patients who underwent ESD surgery and were willing to undergo ADM transplantation were recruited between January 1 to December 31, 2019. A final three-year follow-up of patients who received transplants was conducted. RESULTS: Based on the current incidence of esophageal stricture, the sample size required for both the autologous mucosal graft group and the ADM group was calculated to be 160 cases. Due to various factors, a total of 20 patients with autologous mucosal grafts and 25 with ADM grafts were recruited. Based on the inclusion exclusion and withdrawal criteria, 9 patients ultimately received autologous mucosal grafts and completed the follow-up, while 11 patients received ADM grafts and completed the follow-up. Finally, there were 2 cases of stenosis in the autologous mucosal transplantation group with a stenosis rate of 22.22% and 2 cases of stenosis in the ADM transplantation group with a stenosis rate of 18.18%, with no significant difference noted between the groups (P = 0.94). CONCLUSION: In this prospective, single-center, controlled trial, we compared the effectiveness of autologous mucosa transplantation and ADM for the prevention of esophageal stricture. Due to certain condition limitations, we were unable to recruit sufficient subjects meeting our target requirements. However, we implemented strict inclusion, exclusion, and withdrawal criteria and successfully completed three years of follow-up, resulting in valuable clinical insights. Based on our findings, we hypothesize that ADM may be similarly effective to autologous mucosal transplantation in the prevention of esophageal stricture, offering a comparable and alternative approach. This study provides a new therapeutic idea and direction for the prevention of esophageal stricture.

Clinical significance of tumor-associated macrophage infiltration in supraglottic laryngeal carcinoma.

Tumor-associated macrophages (TAMs) can elicit contrasting effects on tumor progression, depending on different tumor microenvironment. This study aimed to explore the correlation between TAM infiltration and clinicopathologic characteristics, metastasis, and prognosis of supraglottic laryngeal carcinoma. TAMs in intratumoral and peritumoral regions of 84 specimens of supraglottic laryngeal carcinoma tissues were detected by immunohistochemical staining with monoclonal CD68 antibody. The density of peritumoral CD68(+) TAMs in recurrence cases (9/11) and in dead cases (17/23) were significantly higher than those in non-recurrence cases (33/73) and in survival cases (25/61), with significant differences (P = 0.024 and 0.007, respectively). The Kaplan-Meier survival analysis showed a significant relationship between the infiltration of both intratumoral and peritumoral CD68(+) TAMs and the overall survival of patients. The 5-year survival rate was significantly lower in the group with a high density of intratumoral CD68(+) TAMs than in the group with a low density (39.6% vs. 82.5%, P < 0.05). Similarly, the 5-year survival rate was significantly lower in the group with a high density of peritumoral CD68(+) TAMs than in the group with a low density (50.6% vs. 73.1%, P < 0.05). Cox regression analysis revealed that T classification, distant metastasis, and intratumoral or peritumoral CD68(+) TAMs were independent factors for disease-free survival, whereas T classification and intratumoral CD68(+) TAMs were independent factors for overall survival. The results indicate that TAM infiltration in supraglottic laryngeal carcinoma can be used to predict metastasis and prognosis and is an independent factor for prognosis.

Predictive Validity of the Bayley-III Cognitive Scores at 6 Months for Cognitive Outcomes at 24 Months in Very-Low-Birth-Weight Infants.

Purpose: To assess the predictive validity of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive scores at 6 months of corrected age (CA) for cognitive outcomes at 24 months of CA in very-low-birth-weight (VLBW) infants and investigate the predictors of change in cognitive outcomes. Methods: We retrospectively evaluated VLBW children enrolled in the Taiwan Premature Infant Follow-up Network between 2010 and 2015 and completed the Bayley-III at CA of 6 and 24 months. The predictive validity of the cognitive performance at 6-month CA for the cognitive outcomes at 24-month CA was analyzed. The positive and negative predictive factors were also evaluated using logistic regression. Cut-off scores of <70 and <85 were used to identify lower functioning groups based on the Bayley-III definition. Results: A total of 2,972 VLBW children, born with a mean weight of 1116.4 ± 257.5 g and mean gestational age of 29.0 ± 2.8 weeks, were evaluated. A cognitive score of <70 at 6-month CA had a positive predictive value (PPV) of 27.4% (95% confidence interval [CI]: 19.2-35.7%) for a cognitive score of <70 at 24-month CA, while the negative predictive value (NPV) was 97.3% (95% CI: 96.7-97.9%). A cut-off score of 85 had a PPV of 33.6% (95% CI: 28.1-39.0%) and an NPV of 87.7% (95% CI: 86.4-88.9%). Abnormal muscle tone at 6 months was a risk factor for cognitive function decline at 24 months for both Bayley-III cognitive cut-off scores: scores of 70 (adjusted odds ratio [AOR]: 2.8; 95% CI: 1.5-5.5) and 85 (AOR: 2.6; 95% CI: 1.6-4.1). Lower maternal socioeconomic status was associated with a worsening of the cognitive function in infants at 24 months who scored ≥85 at 6 months (AOR: 1.6; 95% CI: 1.2-2.0). Conclusion: Subnormal Bayley-III cognitive scores at 6-month CA were not predictive of subnormal cognitive function at 24-month CA. In children with normal cognition during early infancy, abnormal muscle tone and lower maternal socioeconomic status may influence the cognitive developing process; this highlighted the importance of early identification of high risk infants and complete preterm infant-associated public health policies to promote an improved neurodevelopmental outcome.

Multiple solid phase microextraction combined with ambient mass spectrometry for rapid and sensitive detection of trace chemical compounds in aqueous solution.

Multiple solid phase microextraction (mSPME) combined with thermal desorption-electrospray ionization/mass spectrometry (TD-ESI/MS) was developed to rapidly characterize trace analytes in aqueous solution. A number of commercial available SPME fibers (from 2 to 10 fibers) were simultaneously used for extracting the analytes in solution. The fibers were then bundled together on a holder and subjected for the ambient mass spectrometric analysis. Good linearity for calibration (R2 = 0.9995) and low limit of quantification (<1 ppb) were achieved by using 10 SPME fibers coated with polyacrylate (PA) to extract bisphenol A. It was also found that the analyte signals increased with the number of SPME fibers for extraction. Uncontroversial, a shorter extraction time was required by using mSPME to reach the same level of analyte signal as that by using single SPME fiber for a longer extraction time. Trace bisphenol A (4-20 ppb) in the polycarbonate (PC) baby milk bottles was rapidly detected using mSPME-TD-ESI/MS and the analysis was completed within 1 min. The use of multiple SPME fibers coated with different materials enable the concentration of different type of analytes in the solution. Ibuprofen, bisphenol A (BPA), and 4-n-nonylphenol (4-n-NP) were simultaneously detected by using PA and polydimethylsiloxane (PDMS) coated fibers for extraction.

PCK1 Deficiency Shortens the Replicative Lifespan of Saccharomyces cerevisiae through Upregulation of PFK1.

The cytosolic isozyme of phosphoenolpyruvate carboxykinase (PCK1) was the first rate-limiting enzyme in the gluconeogenesis pathway, which exerted a critical role in maintaining the blood glucose levels. PCK1 has been established to be involved in various physiological and pathological processes, including glucose metabolism, lipid metabolism, diabetes, and tumorigenesis. Nonetheless, the association of PCK1 with aging process and the detailed underlying mechanisms of PCK1 on aging are still far to be elucidated. Hence, we herein constructed the PCK1-deficient (pck1Δ) and PCK1 overexpression (PCK1 OE) Saccharomyces cerevisiae. The results unveiled that PCK1 deficiency significantly shortened the replicative lifespan (RLS) in the S. cerevisiae, while overexpression of PCK1 prolonged the RLS. Additionally, we noted that the ROS level was significantly enhanced in PCK1-deficient strain and decreased in PCK1 OE strain. Then, a high throughput analysis by deep sequencing was performed in the pck1Δ and wild-type strains, in an attempt to shed light on the effect of PCK1 on the lifespan of aging process. The data showed that the most downregulated mRNAs were enriched in the regulatory pathways of glucose metabolism. Fascinatingly, among the differentially expressed mRNAs, PFK1 was one of the most upregulated genes, which was involved in the glycolysis process and ROS generation. Thus, we further constructed the pfk1Δpck1Δ strain by deletion of PFK1 in the PCK1-deficient strain. The results unraveled that pfk1Δpck1Δ strain significantly suppressed the ROS level and restored the RLS of pck1Δ strain. Taken together, our data suggested that PCK1 deficiency enhanced the ROS level and shortened the RLS of S. cerevisiae via PFK1.

The -271 G>A polymorphism of kinase insert domain-containing receptor gene regulates its transcription level in patients with non-small cell lung cancer.

BACKGROUND: Kinase insert domain-containing receptor (KDR) plays a critical role in the metastasis of cancer and is used as a molecular target in cancer therapy. We investigated the characteristics of the -271 G>A polymorphism of the KDR gene to gain information that may benefit the development of individualized therapies for patients with non-small cell lung cancer (NSCLC). METHODS: The -271 G>A polymorphism of the KDR gene in 106 lung cancer patients and 203 healthy control individuals was analyzed by polymerase chain reaction (PCR) and DNA sequencing methods. Real-time quantitative PCR and immunohistochemical methods were used to evaluate KDR mRNA and protein expression levels, respectively, in frozen tumor specimens. RESULTS: The -271 G>A polymorphism was associated with the mRNA expression level of the KDR gene in tumor tissues (t = 2.178, P = 0.032, independent samples t-test). Compared with the AG/GG genotype, the AA genotype was associated with higher KDR mRNA expression in tumor tissues. We found no relationship between the genotype and the KDR protein expression level and no significant difference in the distribution of the KDR gene polymorphism genotypes between lung cancer patients and the control group (chi2 = 1.269, P = 0.264, Fisher's exact test). CONCLUSION: This study is the first to show that the -271 G>A polymorphism of the KDR gene may be a functional polymorphism related to the regulation of gene transcription. These findings may have important implications for therapies targeting KDR in patients with NSCLC.

A meta-analysis and bioinformatics exploration of the diagnostic value and molecular mechanism of miR-193a-5p in lung cancer.

Lung cancer is a leading cause of mortality worldwide and despite recent improvements in lung cancer treatments patient mortality remains high. miR-193a-5p serves a crucial role in the initiation and development of cancer; it is necessary to understand the underlying molecular mechanisms of miR-193a-5p in lung cancer, which may enable the development of improved clinical diagnoses and therapies. The present study investigated the diagnostic value of peripheral blood and tissue miR-193a-5p expression using a microarray meta-analysis. Peripheral blood miR-193a-5p was revealed to be upregulated in patients with lung cancer. The pooled area under the curve (AUC) was 0.67, with a sensitivity and specificity of 0.74 and 0.56, respectively. Conversely, the peripheral tissue miR-193a-5p expression in patients with lung cancer was significantly downregulated. The pooled AUC was 0.83, and the sensitivity and specificity were 0.65 and 0.89, respectively. Through bioinformatics analysis, three Kyoto Encyclopedia of Genes and Genomes (KEGG) terms, pathways in cancer, prostate cancer and RIG-I-like receptor signaling pathway, were identified as associated with miR-193a-5p in lung cancer. In addition, in lung cancer, six key miR-193a-5p target genes, receptor tyrosine-protein kinase erbB-2 (ERBB2), nuclear cap-binding protein subunit 2 (NCBP2), collagen α-1(I) chain (COL1A1), roprotein convertase subtilisin/kexin type 9 (PCSK9), casein kinase II subunit α (CSNK2A1) and nucleolar transcription factor 1 (UBTF), were identified, five of which were significantly upregulated (ERBB2, NCBP2, COL1A1, CSNK2A1 and UBTF). The protein expression of ERBB2, NCBP2, COL1A1, CSNK2A1 and UBTF was also upregulated. NCBP2 and CSNK2A1 were negatively correlated with miR-193a-5p. The results demonstrated that miR-193a-5p exhibited opposite expression patterns in peripheral blood and tissue. Upregulated peripheral blood miR-193a-5p and downregulated tissue miR-193a-5p may be promising diagnostic biomarkers in lung cancer. In addition, the KEGG terms pathways in cancer, prostate cancer and RIG-I-like receptor signaling pathway may suggest which pathways serve vital roles in lung cancer by regulating miR-193a-5p. In addition, six genes, ERBB2, COL1A1, PCSK9, UBTF and particularly NCBP2 and CSNK2A1, may be key target genes of miR-193a-5p in lung cancer.

The clinical value of miR-193a-3p in non-small cell lung cancer and its potential molecular mechanism explored in silico using RNA-sequencing and microarray data.

miR-193a-3p is a tumor-related miRNA playing an essential role in tumorigenesis and progression of non-small cell lung cancer (NSCLC). The objective of the present study was to investigate the relationship between miR-193a-3p expression and clinical value and to further explore the potential signaling of miR-193a-3p in the carcinogenesis of NSCLC. RNA-sequencing and microarray data were collected from the databases GEO, ArrayExpress and The Cancer Genome Atlas (TCGA). Furthermore, in silico assessments were performed to analyze the prospective pathways and networks of the target genes of miR-193a-3p. In total, 453 cases of NSCLC patients and 476 normal controls were included in blood samples, while 920 cases of NSCLC patients and 406 normal controls were included in tissue samples. The pooled positive likelihood ratio, the pooled negative likelihood ratio and the pooled diagnostic odds ratio were calculated to reflect the diagnostic value of miR-193a-3p in blood and tissue samples. Moreover, the areas under the curve of the summary receiver operating characteristic curve of blood and tissue were 0.64 and 0.79, respectively. In addition, we found a lower level of miR-193a in NSCLC tissues than in non-cancerous controls based on TCGA. A gene ontology (GO) enrichment analysis demonstrated that miR-193a-3p could be related to key signaling pathways in NSCLC. Also, several vital pathways were illustrated by KEGG. Lower expression of miR-193a-3p in tissue samples of NSCLC may be associated with tumorigenesis and be a predictor of deterioration of NSCLC patients, and pathway analysis revealed crucial signaling pathways correlated with the incidence and progress of NSCLC.

KDR expression is associated with the stage and cigarette smoking of the patients with lung cancer.

PURPOSE: Kinase insert domain-containing receptor (KDR) is one of the molecular targets used in cancer therapy. We studied the KDR expression characteristics and the relationship with the clinical parameters of the patients with lung cancer, to give the basic evidence and clue for tailoring therapy. METHODS: Reverse transcriptase and real-time PCR were used to evaluate the KDR mRNA expression levels in 222 tissue samples (106 tumor tissues, 106 matched normal tissues obtained from the same patients with lung cancer, and 10 normal lung specimens from individuals without lung cancer). The KDR mRNA expression level and clinical parameters were analyzed by paired-sample t test, ANOVA and linear regression, respectively. The Kaplan-Meier method and the log-rank test were used for survival analysis. Expression of KDR protein was also examined immunohistochemically in 15 tumor samples and 15 matched normal lung specimens. RESULTS: The KDR mRNA expression levels were significantly higher in normal tissues (mean 4.50 +/- 0.51) than that in the carcinoma tissues (mean 4.12 +/- 0.50, P < 0.0005). KDR expression in tumor tissues is associated with the histological status, tumor stage, cigarette smoking, and N stage of the patients with lung cancer (P < 0.05) analyzed by using ANOVA methods. Multivariate analysis showed that tumor stages and cigarette smoking status were the two most important independent predictors for the KDR expression levels in tumor tissues (R = 0.415, R (2) = 0.172, F = 10.694, P < 0.0005). Tumors with KDR mRNA expression levels above the mean had a shorter survival (466 +/- 313 days) than did patients with KDR expression levels below the mean (671 +/- 264 days), whereas Kaplan-Meier analysis and log-rank test showed no significant difference in the overall survival between the patients (P = 0.2055). All the 15 normal lung tissues detected showed scale 2 KDR immunostaining. The intensity of immunostaining for KDR in tumor specimens varied from negative (scale 0) to strongest (scale 3) staining. CONCLUSIONS: Locally advanced and non-cigarette smoking patients with lung cancer may be the two valuable surrogate markers for KDR mRNA higher levels. Non-squamous lung cancer, N 2 stage may be the secondary markers for that. The KDR expression level in normal lung tissue is stable, but varied in tumor tissues. Targeting KDR therapy in lung cancer might considerate these clinical and KDR expression information. Further confirmation study must be needed.

[Gefitinib target treatment in non-small cell lung cancer].

OBJECTIVE: To evaluate the efficacy, target population and influencing factors of Gefitinib in patients with non-small-cell lung cancer (NSCLC) pretreated with platinum. METHODS: Patients with NSCLC who had been previously treated with at least one course of platinum based chemotherapy received 250 mg oral doses of Gefitinib once daily till disease progression. Response rate, progression free survival, overall survival and toxicity profile were analyzed. Kaplan-Meier method was used to analyze the survival rate. Cox regression was used to define the predictive factors. RESULTS: A hundred and fifteen patients were enrolled into the study from July 2001 to May 2005. The follow-up was ended on Sep. 30, 2006. Median follow up time was 30 months. The compliance rate was 100%. The median symptom improving time was 8 days. Complete response rate was 4.3% (5/115), partial response 39.1% (45/115), stable disease 27.0% (31/115) and progressive disease 29.6% (34/115). Response rate was 43.5% (50/115). Disease control rate was 70.4% (81/115). The median progression-free survival and median overall survival were 8 and 11 months, respectively. One and two-year progression-free survival rates and overall survival rates were 32.2% (events 78), 5.6% (events 103) and 41.7% (death 67), 21.5% (death 87) respectively; 3-year overall survival 12.3% (death 93). Adenocarcinoma was the only predictor for therapeutic effect in the Cox model (P = 0.004). The primary failure to gefitinib was due to brain metastasis (39.4%, 28/71). Grade III skin toxicity was found in 5.2% (6/115) patients. CONCLUSION: Gefitinib is the drug of choice for patients with heavily pretreated stage III(B) and IV adenocarcinoma of NSCLC with safe and accepted toxicity profile.