Community screening for dementia among older adults in China: a machine learning-based strategy.

BACKGROUND: Dementia is a leading cause of disability in people older than 65 years worldwide. However, diagnosing dementia in its earliest symptomatic stages remains challenging. This study combined specific questions from the AD8 scale with comprehensive health-related characteristics, and used machine learning (ML) to construct diagnostic models of cognitive impairment (CI). METHODS: The study was based on the Shenzhen Healthy Ageing Research (SHARE) project, and we recruited 823 participants aged 65 years and older, who completed a comprehensive health assessment and cognitive function assessments. Permutation importance was used to select features. Five ML models using BalanceCascade were applied to predict CI: a support vector machine (SVM), multilayer perceptron (MLP), AdaBoost, gradient boosting decision tree (GBDT), and logistic regression (LR). An AD8 score ≥ 2 was used to define CI as a baseline. SHapley Additive exPlanations (SHAP) values were used to interpret the results of ML models. RESULTS: The first and sixth items of AD8, platelets, waist circumference, body mass index, carcinoembryonic antigens, age, serum uric acid, white blood cells, abnormal electrocardiogram, heart rate, and sex were selected as predictive features. Compared to the baseline (AUC = 0.65), the MLP showed the highest performance (AUC: 0.83 ± 0.04), followed by AdaBoost (AUC: 0.80 ± 0.04), SVM (AUC: 0.78 ± 0.04), GBDT (0.76 ± 0.04). Furthermore, the accuracy, sensitivity and specificity of four ML models were higher than the baseline. SHAP summary plots based on MLP showed the most influential feature on model decision for positive CI prediction was female sex, followed by older age and lower waist circumference. CONCLUSIONS: The diagnostic models of CI applying ML, especially the MLP, were substantially more effective than the traditional AD8 scale with a score of ≥ 2 points. Our findings may provide new ideas for community dementia screening and to promote such screening while minimizing medical and health resources.

PAX2 mediated upregulation of ESPL1 contributes to cisplatin resistance in bladder cancer through activating the JAK2/STAT3 pathway.

Extra spindle-polar body like 1 (ESPL1) is associated with the development of a variety of cancers, including bladder cancer, and is closely related to chemoresistance. In this study, we aimed to reveal the role of ESPL1 in bladder cancer progression and cisplatin (DDP) resistance. First, ESPL1 was found to be highly expressed in tumor tissues and cells of bladder cancer, and more highly expressed in cisplatin resistant tumor tissues or cells. The binding of PAX2 in ESPL1 promoter region was predicted by Jaspar database and verified by Ch-IP analysis and the luciferase reporter gene assay. Next, cisplatin-resistant T24 cells (T24/DDP) were established and transfected with ESPL1 siRNA (si-ESPL1) or overexpression vector (pcDNA-ESPL1) or co-transfected with PAX2 siRNA (si-PAX2) or overexpression vector (pcDNA-PAX2), and then treated with DDP or AG490, an inhibitor of JAK2. The results showed that silencing ESPL1 significantly reduced T24/DDP cell viability, colony formation and invasion, enhanced sensitivity to DDP, and induced cell apoptosis. Silencing PAX2 decreased ESPL1 expression, enhanced sensitivity to DDP, and induced apoptosis of T24/DDP cells, and inhibited activation of JAK2/STAT3 pathway. Overexpressing ESPL1 reversed the effect of PAX2 silencing on T24/DDP cells, while AG490 counteracted the reversal effect of overexpressing ESPL1. Finally, a xenograft tumor model was established and found that silencing ESPL1 or DDP treatment inhibited tumor growth, while silencing ESPL1 combined with DDP treatment had the best effect. In summary, this study suggested that PAX2-mediated ESPL1 transcriptional activation enhanced cisplatin resistance in bladder cancer by activating JAK2/STAT3 pathway.

An improved RIME optimization algorithm for lung cancer image segmentation.

Lung cancer is a prevalent form of cancer worldwide, necessitating early and accurate diagnosis for successful treatment. Within medical imaging processing, image segmentation plays a vital role in medical diagnosis. This study applies swarm intelligence algorithms to segment lung cancer pathological images at three levels. The original algorithm incorporates the Whales' search prey mechanism and a random mutation strategy, resulting in an improved version named WDRIME, which aims to enhance convergence speed and avoid local optima (LO). Additionally, the study introduces a multilevel image segmentation method for lung cancer based on the improved algorithm. WDRIME's performance is showcased by comparing it to the state-of-the-art algorithms in IEEE CEC2014. To design a framework for lung cancer image segmentation, this paper combines the WDRIME algorithm with the multilevel segmentation method. Evaluation of the segmentation results employs metrics such as PSNR, SSIM, and FSIM. Overall, the analysis confirms that the proposed algorithm supersedes others regarding convergence speed and accuracy. This model signifies a high-quality segmentation method and offers practical support for in-depth exploration of lung cancer pathological images.

Associations between Chinese visceral adiposity index and risks of all-cause and cause-specific mortality: A population-based cohort study.

AIM: To determine the associations between the Chinese visceral adiposity index (CVAI) and the risks of all-cause and cause-specific mortality. MATERIALS AND METHODS: A total of 3 916 214 Chinese adults were enrolled in a nationwide population cohort covering all 31 provinces of mainland China. The CVAI was calculated based on age, body mass index, waist circumference, and triglyceride and high-density lipoprotein cholesterol concentrations. We used a Cox proportional hazards regression model to determine the hazard ratios and 95% confidence intervals (CIs) for risk of mortality associated with different CVAI levels. RESULTS: The median follow-up duration was 3.8 years. A total of 86 158 deaths (34 867 cardiovascular disease [CVD] deaths, 29 884 cancer deaths, and 21 407 deaths due to other causes) were identified. In general, after adjusting for potential confounding factors, a U-shaped relationship between CVAI and all-cause mortality was observed by restricted cubic spline (RCS). Compared with participants in CVAI quartile 1, those in CVAI quartile 4 had a 23.0% (95% CI 20.0%-25.0%) lower risk of cancer death, but a 23.0% (95% CI 19.0-27.0) higher risk of CVD death. In subgroup analysis, a J-shaped and inverted U-shaped relationship for all-cause mortality and cancer mortality was observed in the group aged < 60 years. CONCLUSIONS: The CVAI, an accessible indicator reflecting visceral obesity among Chinese adults, has predictive value for all-cause, CVD, and cancer mortality risks. Moreover, the CVAI carries significance in the field of health economics and secondary prevention. In the future, it could be used for early screening purposes.

Interferon-Gamma-Inducible Protein 16 Inhibits Hepatocellular Carcinoma via Interferon Regulatory Factor 3 on Chemosensitivity.

BACKGROUND AND AIM: Previous reports have suggested IFI16 as a tumor suppressor in hepatocellular carcinoma (HC). Nonetheless, the biological significance of IFI16 and its mechanism concerning resistance to cisplatin (DDP) in HC requires further exploration. METHODS: Samples of tumor and corresponding para-carcinoma tissues were acquired from patients with HC. Furthermore, DDP-resistant cell lines of HC, specifically HCC, Huh7 and Hepatoblastoma, HepG3, were generated by gradually increasing the concentration of DDP. Cell apoptosis and DNA damage were evaluated by utilizing flow cytometry assay and TUNEL staining. The interaction between IFI16 and interferon regulatory factor 3 (IRF3) proteins were analyzed using Co-Immunoprecipitation (Co-IP) assay. In vivo assays were conducted by establishing HC subcutaneous xenograft tumor models. RESULTS: The study found a reduction in IFI16 expression in both HC tissues and DDP-resistant HC cell lines. The binding of IFI16 to IRF3 regulated DNA damage-associated markers in vitro. Overexpression of IFI16 heightened the susceptibility of DDP-induced apoptosis and DNA damage, which was counteracted by IRF3 knockdown, while strengthened by IRF3 overexpression. Moreover, overexpression of IFI16 diminished in vivo DDP-resistant HC tumorigenicity. CONCLUSION: In summary, our findings suggest that IFI16 serves as a tumor suppressor in HC by promoting DNA damage via its interaction with IRF3, thereby reversing DDP resistance.

Fenofibrate inhibits MOXD1 and PDZK1IP1 expression and improves lipid deposition and inflammation in mice with alcoholic fatty liver.

AIMS: Alcoholic liver disease (ALD) can develop into cirrhosis and hepatocellular carcinoma but no specific drugs are available. Fenofibrate is therapeutically effective in ALD, however, the exact mechanism remains unknown. We explored the hub genes of ALD and the role of fenofibrate in ALD. MAIN METHODS: The hub genes of ALD were screened by bioinformatics method, and their functional enrichment, signalling pathways, target genes and their correlation with immune microenvironment and pathogenic genes were analysed. We also analysed the binding affinity of fenofibrate to proteins of hub genes using molecular docking techniques, and the effects on hub gene expression, lipid deposition, oxidative stress and inflammation in the liver of National Institute on Alcohol Abuse and Alcoholism (NIAAA) model mice. The regulatory effects of fenofibrate on MOXD1 and PDZK1P1 were investigated after gene silencing of peroxisome proliferator-activated receptor-α (Ppar-α). KEY FINDINGS: Hub genes identified, including monooxygenase DBH-like 1 (MOXD1), PDZK1-interacting protein 1 (PDZK1IP1) and solute carrier 51 ß (SLC51B), are highly predictive for ALD. Hepatic MOXD1 and PDZK1IP1 expression was elevated in patients with ALD and NIAAA model mice, with no significant difference in SLC51B expression between the groups. Fenofibrate binds tightly to MOXD1 and PDZK1IP1, inhibits their hepatic expression independently of PPAR-α signalling, and ameliorates lipid deposition, oxidative stress and inflammatory responses in NIAAA model mice. SIGNIFICANCE: MOXD1 and PDZK1IP1 are key genes in ALD progression; fenofibrate improves liver damage in NIAAA model mice by downregulating their expression. Our findings provide insight for improving diagnostic and therapeutic strategies for ALD.

Effect of a two-phase tobacco control regulation on incidence from ischemic stroke and hemorrhagic stroke, Shenzhen, China, 2007-2016.

INTRODUCTION: The Shenzhen government is widely considered to be most efficiently implementing smoke-free legislation in China. We evaluated and compared the impact of Shenzhen's two-phase smoke-free regulation on the incidence rates for ischemic and hemorrhagic stroke. METHODS: An interrupted time series design was used to capture immediate and annual incidence changes from 2007 to 2016 for both ischemic and hemorrhagic stroke due to two-phase smoke-free regulation in Shenzhen, China, by using a generalized additive model. The first phase, implemented on 9 March 2010, required five main public places to be smoke-free. In the second phase, the comprehensive law was expanded to the whole city on 1 March 2014. RESULTS: The regulation implementation during phase I was associated with a strong immediate decline in the incidence rate of ischemic stroke (-14.2%, 95% CI: -19.6 - -8.4) and hemorrhagic stroke (-10.1%, 95% CI: -18.2 - -1.2), but without showing the annual changes (p>0.05). Following the implementation of the comprehensive law, the gradual annual effect showed a significant change in ischemic stroke, with a 6.3% (95% CI: 8.9 - -3.6) reduction. Neither the immediate nor gradual decreases in hemorrhagic stroke incidences associated with the comprehensive regulation were statistically significant during phase II (p>0.05). Subgroup analyses indicate that a much larger health effect of the regulation during phase I was greater among those aged ≥65 years than among those aged 35-64 years. CONCLUSIONS: Shenzhen's two-phase smoke-free regulation was well implemented. Even though the regulation did not extend to the whole city, the immediate health benefits on the incidence rates of ischemic stroke and hemorrhagic stroke could be seen. However, the health benefits brought by the implementation of comprehensive smoke-free legislation were attenuated by previous smoke-free regulations in five main public places, which were more evident in hemorrhagic stroke.

Associations Among Multimorbid Conditions in Hospitalized Middle-aged and Older Adults in China: Statistical Analysis of Medical Records.

BACKGROUND: Multimorbidity has become a new challenge for medical systems and public health policy. Understanding the patterns of and associations among multimorbid conditions should be given priority. It may assist with the early detection of multimorbidity and thus improve quality of life in older adults. OBJECTIVE: This study aims to comprehensively analyze and compare associations among multimorbid conditions by age and sex in a large number of middle-aged and older Chinese adults. METHODS: Data from the home pages of inpatient medical records in the Shenzhen National Health Information Platform were evaluated. From January 1, 2017, to December 31, 2018, inpatients aged 50 years and older who had been diagnosed with at least one of 40 conditions were included in this study. Their demographic characteristics (age and sex) and inpatient diagnoses were extracted. Association rule mining, Chi-square tests, and decision tree analyses were combined to identify associations between multiple chronic conditions. RESULTS: In total, 306,264 hospitalized cases with available information on related chronic conditions were included in this study. The prevalence of multimorbidity in the overall population was 76.46%. The combined results of the 3 analyses showed that, in patients aged 50 years to 64 years, lipoprotein metabolism disorder tended to be comorbid with multiple chronic conditions. Gout and lipoprotein metabolism disorder had the strongest association. Among patients aged 65 years or older, there were strong associations between cerebrovascular disease, heart disease, lipoprotein metabolism disorder, and peripheral vascular disease. The strongest associations were observed between senile cataract and glaucoma in men and women. In particular, the association between osteoporosis and malignant tumor was only observed in middle-aged and older men, while the association between anemia and chronic kidney disease was only observed in older women. CONCLUSIONS: Multimorbidity was prevalent among middle-aged and older Chinese individuals. The results of this comprehensive analysis of 4 age-sex subgroups suggested that associations between particular conditions within the sex and age groups occurred more frequently than expected by random chance. This provides evidence for further research on disease clusters and for health care providers to develop different strategies based on age and sex to improve the early identification and treatment of multimorbidity.

The 980 nm diode laser treatment for non-muscle-invasive bladder tumor with en bloc technique: single-center experience.

BACKGROUND: Transurethral resection of the bladder tumor (TURBT) is one of the most established urological procedures for the treatment of the primary non-muscle-invasive bladder cancer (NMIBC). The aim of the study is to evaluate the efficacy and safety of 980 nm diode laser as a treatment for primary NMIBC. METHODS: Eighty-eight patients with NMIBC were treated by en bloc transurethral resection with 980 nm diode laser, and 76 patients were treated by plasmakinetic transurethral resection from May 2016 to July 2019 at the Department of Urology, Tangdu Hospital, Air Force Medical University. The clinical data were collected and compared between the two groups. RESULTS: The bladder irrigation time was shortened in 980 nm diode laser group compared to that of plasmakinetic transurethral resection group (4.1 ± 0.6 vs 13.1 ± 3.1 h, p < 0.001). A total of 13.2% (10/76) patients experienced obturator nerve reflex, and 5.3% (4/76) experienced delayed bleeding in plasmakinetic transurethral resection group, while no obturator nerve reflex and delayed bleeding cases were observed in 980 nm diode laser group (p < 0.05). The postoperative catheterization and hospitalization time showed no significant difference between the two groups. The median follow-up time was 27 months (13-38 months). No significant difference in the recurrence rate was observed between the two groups. CONCLUSIONS: The 980 nm diode laser is an effective and safe tool in transurethral resection of NMIBC using en bloc technique. It has less perioperative complications and shortened bladder irrigation time.

Glycoprotein α-Subunit of Glucosidase II (GIIα) is a novel prognostic biomarker correlated with unfavorable outcome of urothelial carcinoma.

BACKGROUND: Urothelial carcinoma (UC) is among the most prevalent malignancies. The muscle-invasive bladder cancer (MIBC) shows an invasive feature and has poor prognosis, while the non-muscle invasive bladder cancer (NMIBC) shows a better prognosis as compared with the MIBC. However, a significant proportion (10%-30%) of NMIBC cases progress to MIBC. Identification of efficient biomarkers for the prediction of the course of UC remains challenging nowadays. Recently, there is an emerging study showed that post-translational modifications (PTMs) by glycosylation is an important process correlated with tumor angiogenesis, invasion and metastasis. Herein, we reported a data-driven discovery and experimental validation of GANAB, a key regulator of glycosylation, as a novel prognostic marker in UC. METHODS: In the present study, we conducted immunohistochemistry (IHC) assay to evaluate the correlation between the expression levels of GANAB protein and the prognosis of UC in our cohort of 107 samples using whole slide image (WSI) analysis. In vitro experiments using RNAi were also conducted to investigate the biological functions of GANAB in UC cell lines. RESULTS: We observed that positive GANAB protein expression was significantly correlated with poor prognosis of UC in our cohort, with p-value of 0.0017 in Log-rank test. Notably, tumor cells at the invasive front of the tumor margin showed stronger GANAB expression than the tumor cells inside the tumor body in UCs. We further validated that the elevated expression levels of GANAB were significantly correlated with high grade tumors (p-values of 1.72 × 10-10), advanced stages (6.47 × 10-6), and elevated in luminal molecular subtypes. Moreover, knocking-down GANAB using RNAi in UM-UC-3 and T24 cells inhibited cell proliferation and migration in vitro. Knockdown of GANAB resulted in cell cycle arrest at G1 phase. We demonstrated that GANAB mediated HIF1A and ATF6 transcriptional activation in the ER stress signaling, and regulated the gene expression of cell cycle-related transcriptional factors E2F7 and FOXM1. CONCLUSIONS: The elevated expression of GANAB is a novel indicator of poorer prognosis of UC. Our data suggests that GANAB is not only a new and promising prognostic biomarker for UC, but also may provide important cues for the development of PTM-based therapeutics for UC treatment.

Identification of leucine-rich repeat-containing protein 59 (LRRC59) located in the endoplasmic reticulum as a novel prognostic factor for urothelial carcinoma.

BACKGROUND: Urothelial carcinoma (UC) is one of the most common cancers worldwide. The biological heterogeneity of UCs causes considerable difficulties in predicting treatment outcomes and usually leads to clinical mismanagement. The identification of more sensitive and efficient predictive biomarkers is important in the diagnosis and classification of UCs. Herein, we report leucine-rich repeat-containing protein 59 (LRRC59) located in the endoplasmic reticulum as a novel predictive factor and potential therapeutic target for UCs. METHODS: Using whole-slide image analysis in our cohort of 107 UC samples, we performed immunohistochemistry to evaluate the prognostic value of LRRC59 expression in UCs. In vitro experiments using RNAi were conducted to explore the role of LRRC59 in promoting UC cell proliferation and migration. RESULTS: A significant correlation between LRRC59 and unfavorable prognosis of UCs in our cohort was demonstrated. Subsequent clinical analysis also revealed that elevated expression levels of LRRC59 were significantly associated with higher pathological grades and advanced stages of UC. Subsequently, knockdown of LRRC59 in UM-UC-3 and T24 cells using small interfering RNA significantly inhibited cell proliferation and migration, resulting in cell cycle arrest at the G1 phase. Conversely, the overexpression of LRRC59 in UC cells enhanced cell proliferation and migration. An integrated bioinformatics analysis revealed a significant functional network of LRRC59 involving protein misfolding, ER stress, and ubiquitination. Finally, in vitro experiments demonstrated that LRRC59 modulates ER stress signaling. CONCLUSIONS: LRRC59 expression was significantly correlated with UC prognosis. LRRC59 might not only serve as a novel prognostic biomarker for risk stratification of patients with UC but also exhibit as a potential therapeutic target in UC that warrants further investigation.

Prognostic values of preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and lymphocyte- to-monocyte ratio for patients with muscle- invasive bladder cancer undergoing radical cystectomy. / Valor pronóstico del índice neutrófilo-linfocito, plaqueta- linfocito y linfocito-monocito preoperatorio en pacientes con cáncer músculo invasivo de vejiga sometidos a cistectomía radical.

OBJECTIVE: To study the prognosticvalues of preoperative neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) for patients with muscle-invasive bladder cancer (MIBC) undergoing radicalcystectomy. METHODS: The clinical data of 186 MIBC patientsreceiving radical cystectomy from January 2013 toOctober 2015 were collected. Receiver operating characteristic(ROC) curves were plotted based on preoperativeNLR, PLR and LMR as well as survival of patientswithin 5 years after surgery. The NLR, PLR and LMRvalues of patients with different clinicopathologicalcharacteristics were described by frequencies.Recurrence-free survival curve was plotted using theKaplan-Meier method, and survival curves were comparedby the log-rank test. Independent risk factorsfor recurrence were explored by multivariate logistic regression analysis. NLR, PLR and LMR were utilizedto establish the recurrence risk scoring model, and theaccuracy for predicting recurrence was assessed byROC curves. RESULTS: NLR groups had significantly differentpathological grade, T stage, lymph node metastasisand tumor number. The differences in age,pathological grade, T stage, lymph node metastasisand tumor number were significant between PLRgroups. Gender, pathological grade, T stage, lymphnode metastasis, tumor number and tumor sizehad significant differences between LMR groups(Pfree survival rate between NLR≥2.45 andNLRand PLRLMR≥3.72 and LMR33.61%) (Ptumor number, lymph node metastasis, NLR, PLRand LMR were independent risk factors for MIBCpatients. After these factors were included into therecurrence risk scoring model, the area under ROCcurve was 0.821. CONCLUSIONS: Preoperative NLR, PLR and LMRare potential biomarkers for determining the prognosisof MIBC patients, and the combination of independent risk factors may work better for prognosticevaluation.

OBJETIVOS: Estudiar el valor pronósticodel índice neutrófilo-linfocito (INL), plaqueta-linfocito(IPL) y linfocito-monocito (ILM) preoperatorioen pacientes con Cáncer de Vejiga Músculo Invasivo(CVMI) sometidos a cistectomía radical.MÉTODOS: Se analizaron los datos clínicos de 186pacientes con CVMI sometidos a cistectomía desdeEnero 2013 a Octubre 2015. Se ejecutaron curvasReceiver operating characteristics (ROC) basadas enel valor preoperatorio de INL, IPL, ILM así como la supervivenciaa los 5 años de la cirugía. Los valores delos INR, IPL, ILM de los pacientes con diferentes característicasclínicopatológicas se describieron mediantefrecuencias. Se obtuvo una curva de supervivencialibre de recurrencia usando el método de Kaplan-Meier, mientras que las curvas de supervivencias secompararon con el log-rank test. Se exploraron losfactores independientes de recurrencia a través de unanálisis de regresión logística. Se usaron los INL, IPL,ILM para establecer un modelo predictive de riesgo derecurrencia cuya precision fue evaluada con curvasROC. RESULTADOS: Las diferencias fueron significativaspara los grupos INL en cuanto a grado histológico,estadio tumoral, metastasis ganglionares y númerode tumores. Las diferencias en edad, grado histológico,estadio tumoral, metastasis a ganglios linfáticosy número de tumores fueron significativas entre losgrupos IPL. Mientras que en los grupos ILM las diferenciasfueron significativas en género, grado histológico,estadio tumar, metastasis a ganglios linfáticos,número y tamaño tumoral. (Psignificativas en la tasa de recurrencia libre de enfermedaden los grupos INL≥2.45 e INL71.11%), los grupos IPL≥157.3 e IPL77.65%), y los grupos ILM≥3.72 e ILMvs. 33.61%) (Pnúmero de tumores, metastasis ganglionares,INL, IPL, ILM fueron factores de riesgo independientesen pacientes con CVMI. Después de incluir estos factoresen el modelo predictive de riesgo de recurrencia, elárea bajo la curva ROC fue 0.821. CONCLUSIONES: Los INL, IPL, ILM preoperatoriosson potenciales biomarcadores para determinar elpronóstico de pacientes con CVMI. La combinaciónde factores independientes podría mejorar la evaluaciónpronóstica.

Association of the serum transaminase with mortality among the US elderly population.

BACKGROUND AND AIM: Considering the inconsistent findings of research into the associations between serum levels of liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and gamma-glutamyltransferase [GGT]) and mortality among elderly people, we aimed to investigate the associations of ALT, AST, GGT, and De-Ritis ratio (DRR, defined as AST/ALT) and all-cause or cause-specific mortality among the US elderly people using National Health and Nutrition Examination Surveys data. METHODS: We included 6415 elderly participants (≥ 65 years). Exclusion criteria included positive test for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infection at baseline. Multivariable-adjusted Cox regression models calculating hazard ratios (HR) and 95% confidence intervals were developed for each of the liver enzyme measures. RESULTS: All-cause cumulative mortality was 33.8%, of which 23.8% were cardiovascular disease (CVD) deaths, 15.6% were cancer deaths, and 60.6% were other cause deaths. Adjusted Cox models found increased all-cause mortality risk for low ALT (HR: 1.70), low AST (HR: 1.13), high GGT (HR: 1.25), and high DRR (HR: 1.68). Low ALT and high DRR predicted CVD mortality. Low ALT (HR: 1.91), low AST (HR: 1.16), high GGT (HR: 1.40), and high DRR (HR: 1.76) predicted other cause mortality. CONCLUSIONS: Low ALT and high DRR were associated with increased CVD and cancer mortality. All serum liver enzyme measures were associated with all-cause mortality and other cause mortality in the US elderly population. Further studies may validate these findings in other elderly populations.

The Association of Polymorphisms in Base Excision Repair Genes with Ovarian Cancer Susceptibility in Chinese Women: A Two-Center Case-Control Study.

Base excision repair (BER) acts upon the most important mechanism of the DNA repair system, protecting DNA stability and integrity from the mutagenic and cytotoxic effects. Multiple researches have indicated that single-nucleotide polymorphisms (SNPs) in the BER-related gene may be associated with the susceptibility of ovarian cancer. However, the results are controversial. In this two-center case-control study, 19 potentially functional SNPs in six BER-related genes (hOGG1, APE1, PARP1, FEN1, LIG3 and XRCC1) was genotyped in 196 ovarian cancer cases and 272 cancer-free controls. And, their associations with ovarian cancer risk were assessed by unconditional logistic regression analyses. We found that PARP1 rs8679 and hOGG1 rs293795 polymorphisms were associated with a decreased risk of ovarian cancer under dominant model (adjusted OR=0.39, 95% CI=0.17-0.90, P=0.026; and adjusted OR=0.36, 95% CI=0.13-0.99, P=0.049, respectively). Stratification analysis demonstrated that this association was more pronounced in the subgroups of lower BMI and patients with early menarche and serous carcinoma. Moreover, LIG3 rs4796030 AA/AC variant genotypes performed an increased risk of ovarian cancer under recessive model (adjusted OR=1.54, 95% CI=1.01-2.35, P=0.046), especially in the subgroups of higher BMI, early clinic stage and the carcinoma at the left. These results suggested that PARP1, hOGG1 and LIG3 polymorphisms might impact on the risk of ovarian cancer. However, more researches with larger and different ethnic populations are warranted to support our findings.

The prevalence, genotype distribution of human papillomavirus and cervical cytology in Wenzhou, China: a retrospective research of 7391 cases.

BACKGROUND: Human papillomavirus (HPV) infection is the main pathogen of precancerous transformation and finally progress to cervical cancer. It associated with cervical squamous and glandular lesions. However, the genotype distribution of HPV and the relationship between HPV infection and cervical disease are still remind unclear. MATERIAL AND METHODS: A total of 7391 abnormal cervical cytology cases with detailed histological reports and HPV genotypes were collected. The prevalence of HPV infection in squamous epithelial lesions and glandular epithelial lesions were statistically analyzed. RESULT: Around 6958 cytological squamous epithelial lesions and 433 glandular epithelial lesions were enrolled. 79.72% of cytological squamous epithelial lesions and 26.56% of glandular epithelial lesions were HPV infected. The HPV infection rates in squamous cell carcinoma, cervical adenocarcinoma and endometrial adenocarcinoma were 66.67%, 54.17% and 19.72%, respectively. HVP16, 18 and 58 are the most common types in squamous and glandular epithelial lesions. Among the squamous epithelial lesions, women less than 25 years old had the highest HPV infection rate, and majority of multiple infections was found in women >55 years old. The total infection rate of HPV in glandular epithelial lesions was the highest in the 35 to 45 group. Multiple infections peaked in women around 55 years old. CONCLUSION: The prevalence of HPV infection is divergent in different types of cervical cancer. The HPV infections in cervical squamous epithelial lesions tended to be younger. HPV detection is one of the necessary tests for cervical disease screening and should be individualized in an age manner.

Tumor-infiltrating B cell is associated with the control of progression of gastric cancer.

This study aimed to further explore the clinicopathological correlation of B cell infiltration in gastric cancer (GC) and its impact on prognostic. By immunohistochemical method, CD20+ B cells, CD3+ T cells, CD66b+ tumor-associated neutrophils, CD163+ tumor-associated macrophages, and CD57+ natural killer cells were analyzed in consecutive sections of 584 GC tissues and 69 normal adjacent tissues. Kaplan-Meier and Cox regression analyses determined the relationship between clinical relevance or prognosis and B cell infiltration. The correlation between total B cell infiltration and various T cell subtype infiltration in GC tissues from 407 patients in the TCGA data was also analyzed. Kaplan-Meier and Cox regression analyses determined the effects of total B cell infiltration and various B cell subtype infiltration on the prognosis of patients with GC. The infiltration level of CD20+ B cells was positively correlated with that of T cells (risk ratio [RR] = 0.0930), especially CD4+ T cells and CD8+ T cells (P < 0.05). A high level of CD20+ B cell infiltration was significantly associated with low lymph node involvement and low TNM stage (P < 0.05). High levels of CD20+ B cell infiltration were significantly associated with improvements in overall survival and disease-free survival. Univariate Cox regression and multivariate Cox regression analysis showed that CD20+ B cell infiltration was an independent protective factor of prognosis. Higher levels of class-switched memory B cell and plasma cell also reflected better overall survival, and class-switched memory B cell and plasma cell were independent protective factors for prognosis. The findings indicate that B cell infiltration in GC, especially switched memory B cells and plasma cells, has a significant effect on tumor progression and prognosis.

PRRG4 promotes breast cancer metastasis through the recruitment of NEDD4 and downregulation of Robo1.

Metastasis is responsible for the death of most breast cancer patients. Robo1 has been implicated as a tumor suppressor for various cancers including breast cancer. However, it is not well understood how Robo1 expression is regulated during tumorigenesis. In this study, we uncovered that the transmembrane proline rich γ-carboxyglutamic acid protein 4 (PRRG4) promotes breast cancer metastasis by downregulating Robo1. Analysis of mRNA expression data in The Cancer Genome Atlas and immunohistochemistry assay on breast tumor samples showed that PRRG4 expression was higher in breast tumors than in normal breast tissues. Experiments with PRRG4 knockdown and overexpression revealed that PRRG4 promoted migration and invasion of breast cancer cells, and enhanced metastasis in an experimental metastasis model. Mechanistically, we found that PRRG4 via its LPSY and PPPY motifs recruited the E3 ubiquitin ligase NEDD4, which induced ubiquitination and degradation of Robo1, thus contributing to migration and invasion of breast cancer cells. In addition, PRRG4 interacted with and enhanced protein tyrosine kinase Src and FAK activation. Overall, our data support a model that PRRG4 via NEDD4 downregulates the Robo1, resulting in the activation of Src and FAK and promoting breast cancer metastasis. PRRG4 may be a novel target for treating metastatic breast cancer.

Opposing biological functions of the cytoplasm and nucleus DAXX modified by SUMO-2/3 in gastric cancer.

Death domain-associated protein (DAXX) is a complex biological multifunctional protein and is involved in the tumorigenesis and progression of multiple cancers. The accumulation of DAXX in the nucleus is a common phenomenon in tumor cells. However, altering the subcellular localizations of DAXX results in different biological functions, and we also found that its nuclear/cytoplasmic ratio (NCR) was associated with poor prognosis in gastric cancer (GC). In this study, we investigated the effect of cytoplasmic and nuclear DAXX (cDAXX and nDAXX) in GC and the underlying mechanisms. Immunohistochemical detection performed in 323 GC tissues reveled that cDAXX was associated with a better survival, while high nDAXX expression suggested a poorer prognosis outcome. Upregulation of DAXX in the cytoplasm inhibited cell proliferation and promoted apoptosis, whereas downregulation of DAXX in the nucleus displayed opposite effects. Moreover, Transwell assays revealed that DAXX enhanced GC cell migration and invasion. Analysis from the Gene Expression Profile Interactive Analysis (GEPIA) database showed that the expression of DAXX was significantly associated with SUMO-2/3 in GC tissues. Co-immunoprecipitation combined with immunofluorescence analysis indicated that DAXX interacted directly with SUMO-2/3. Subsequently, down-regulating the expression of SUMO-2/3 resulted in altered subcellular localization of DAXX. Bioinformatics analysis showed that RanBP2 may act as SUMO E3 ligase to promote nuclear-plasma transport via combining with RanGAP1. Taken together, our results indicated that DAXX plays opposing roles in GC and suggest a new model whereby cDAXX, nDAXX, and SUMO-2/3 form a molecular network that regulates the subcellular localization of DAXX and thereby modulates its opposing biological effects. Thus, our findings provide a foundation for future studies of DAXX as a novel therapeutic target for patients with GC.

The association of polymorphisms in nucleotide excision repair genes with ovarian cancer susceptibility.

Nucleotide excision repair (NER), the core mechanism of DNA repair pathway, was commonly used to maintain genomic stability and prevent tumorigenesis. Previous investigations have demonstrated that single nucleotide polymorphisms (SNPs) of NER pathway genes were associated with various types of cancer. However, there was no research elucidating the genetic association of entire NER pathway with ovarian cancer susceptibility. Therefore, we conducted genotyping for 17 SNPs of six NER core genes (XPA, XPC, XPG, ERCC1, ERCC2, and ERCC4) in 89 ovarian cancer cases and 356 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to describe the strength of association. The result showed that both ERCC1 rs11615 and XPC rs2228000 were significantly associated with reduced risk of ovarian cancer under dominant genetic model (adjusted OR = 0.35, 95% CI = 0.20-0.61, P=0.0002 and adjusted OR = 0.49, 95% CI = 0.30-0.81, P=0.005 respectively). In addition, XPC rs2228001 and ERCC2 rs238406 had statistically significant association with the increased risk of ovarian cancer under dominant genetic model (adjusted OR = 1.72, 95% CI = 1.02-2.92, P=0.043 and adjusted OR = 2.07, 95% CI = 1.07-4.01, P=0.032 respectively). ERCC1 rs3212986 were related with the increased risk of ovarian cancer under recessive model (adjusted OR = 2.40, 95% CI = 1.30-4.44, P=0.005). In conclusion, our results indicated that ERCC1, XPC and ERCC2 might influence ovarian cancer susceptibility. Further research with large sample size is warranted to validate the reliability and accuracy of our results.

Microstructure and characterization of aluminum-incorporated calcium silicate hydrates (C-S-H) under hydrothermal conditions.

The phase assembly and microstructure of the aluminum-incorporated CaO-SiO2-H2O system, which is technologically important in autoclaved building materials, catalysis and waste management, were investigated using XRD, SEM, FTIR and NMR depending on aluminum addition, reaction temperature and curing time. The content of each phase was obtained using the MAUD program based on the Rietveld refinement. The results revealed that the formation of the tobermorite phase was promoted at Al/(Al + Si) ≤ 0.03, and subsequently retarded by higher aluminum addition, which was corroborated by the presence of more low polymerized and cross-linked (alumino)silicate chains. The phase purity decreased with increasing aluminum addition. Aluminum changed the morphology of tobermorite from plate-like to lath-like and fibrous. About a quarter of the (alumino)silicate chains in the C-S-H structure were linked though a [triple bond, length as m-dash]Si-O-Al[triple bond, length as m-dash] configuration, and this proportion was almost independent of aluminum addition. Furthermore, only Al[4] substituted for silicon in the aluminum incorporated C-S-H, while Al[6] just exited in the hydrogarnet phase. This work is beneficial for understanding the implication on micro-properties of by-products or admixtures containing aluminum in concrete.