Estimating disparities of prostate cancer burden and its attributable risk factors for males across the BRICS-plus, 1990-2019: A comparable study of key nations with emerging economies.

BACKGROUNDS: The study aimed to analyze epidemiology burden of male prostate cancer across the BRICS-plus, and identify potential risk factors by assessing the associations with age, period, birth cohorts and sociodemographic index (SDI). METHODS: Data were extracted from the Global Burden of Disease Study 2019. The average annual percent change (AAPC) was calculated to assess long-term trends, and age-period-cohort analysis was used to analyze these three effects on prostate cancer burden. Quantile regression was used to investigate the association between SDI and health outcomes. RESULTS: The higher incidence and mortality were observed in Mercosur and SACU regions, increasing trends were observed in prostate cancer incidence in almost all BRICS-plus countries (AAPC > 0), and EEU's grew by 24.31% (%AAPC range: -0.13-3.03). Mortality had increased in more than half of countries (AAPC > 0), and SACU grew by 1.82% (%AAPC range: 0.62-1.75). Incidence and mortality risk sharply increased with age across all BRICS-plus countries and globally, and the peak was reached in the age group 80-84 years. Rate ratio (RR) of incidence increased with birth cohorts in all BRICS-plus countries except for Kazakhstan where slightly decrease, while mortality RR decreased with birth cohort in most of BRICS-plus countries. SDI presented significantly positive associations with incidence in 50 percentiles. The deaths attributable to smoking declined in most of BRICS-plus nations, and many countries in China-ASEAN-FTA and EEU had higher values. CONCLUSION: Prostate cancer posed a serious public health challenge with an increasing burden among most of BRICS-plus countries. Age had significant effects on prostate cancer burden, and recent birth cohorts suffered from higher incidence risk. SDI presented a positive relationship with incidence, and the smoking-attributable burden was tremendous in China-ASEAN-FTA and EEU region. Secondary prevention should be prioritized in BRICS-plus nations, and health policies targeting important populations should be strengthened based on their characteristics and adaptability.

Changes in disease burden and global inequalities in bladder, kidney and prostate cancers from 1990 to 2019: a comparative analysis based on the global burden of disease study 2019.

BACKGROUND: Bladder, kidney and prostate cancers make significant contributors to cancer burdens. Exploring their cross-country inequalities may inform equitable strategies to meet the 17 sustainable development goals before 2030. METHODS: We analyzed age-standardized disability-adjusted life-years (ASDALY) rates for the three cancers based on Global Burden of Diseases Study 2019. We quantified the inequalities using slope index of inequality (SII, absolute measure) and concentration index (relative measure) associated with national sociodemographic index. RESULTS: Varied ASDALY rates were observed in the three cancers across 204 regions. The SII decreased from 35.15 (95% confidence interval, CI: 29.34 to 39.17) in 1990 to 15.81 (95% CI: 7.99 to 21.79) in 2019 for bladder cancers, from 78.94 (95% CI: 75.97 to 81.31) in 1990 to 59.79 (95% CI: 55.32 to 63.83) in 2019 for kidney cancer, and from 192.27 (95% CI: 137.00 to 241.05) in 1990 to - 103.99 (95% CI: - 183.82 to 51.75) in 2019 for prostate cancer. Moreover, the concentration index changed from 12.44 (95% CI, 11.86 to 12.74) in 1990 to 15.72 (95% CI, 15.14 to 16.01) in 2019 for bladder cancer, from 33.88 (95% CI: 33.35 to 34.17) in 1990 to 31.13 (95% CI: 30.36 to 31.43) in 2019 for kidney cancer, and from 14.61 (95% CI: 13.89 to 14.84) in 1990 to 5.89 (95% CI: 5.16 to 6.26) in 2019 for prostate cancer. Notably, the males presented higher inequality than females in both bladder and kidney cancer from 1990 to 2019. CONCLUSIONS: Different patterns of inequality were observed in the three cancers, necessitating tailored national cancer control strategies to mitigate disparities. Priority interventions for bladder and kidney cancer should target higher socioeconomic regions, whereas interventions for prostate cancer should prioritize the lowest socioeconomic regions. Additionally, addressing higher inequality in males requires more intensive interventions among males from higher socioeconomic regions.

Effectiveness of simulation-based clinical research curriculum for undergraduate medical students - a pre-post intervention study with external control.

BACKGROUND: Simulation is widely utilized in medical education. Exploring the effectiveness of high-fidelity simulation of clinical research within medical education may inform its integration into clinical research training curricula, finally cultivating physician-scientist development. METHODS: Standard teaching scripts for both clinical trial and cross-sectional study simulation were designed. We recruited undergraduates majoring in clinical medicine at 3th grade into a pre-post intervention study. Additionally, a cross-sectional survey randomly selected medical undergraduates at 4th or 5th grade, medical students in master and doctor degree as external controls. Self-assessment scores of knowledge and practice were collected using a 5-point Likert scale. Changes in scores were tested by Wilcoxon signed-rank test and group comparisons were conducted by Dunn's tests with multiple corrections. Multivariable quantile regressions were used to explore factors influencing the changes from baseline. RESULTS: Seventy-eight undergraduates involved the clinical trial simulation and reported improvement of 1.60 (95% CI, 1.48, 1.80, P < 0.001) in knowledge and 1.82 (95% CI, 1.64, 2.00, P < 0.001) in practice score. 83 undergraduates involved in the observational study simulation and reported improvement of 0.96 (95% CI, 0.79, 1.18, P < 0.001) in knowledge and 1.00 (95% CI, 0.79, 1.21, P < 0.001) in practice. All post-intervention scores were significantly higher than those of the three external control groups, P < 0.001. Higher agreement on the importance of clinical research were correlated with greater improvements in scores. Undergraduates in pre-post study showed high confidence in doing a future clinical research. CONCLUSION: Our study provides evidence supporting the integration of simulation into clinical research curriculum for medical students. The importance of clinical research can be emphasized during training to enhance learning effect.

The causal association between smoking, alcohol consumption and risk of bladder cancer: A univariable and multivariable Mendelian randomization study.

Smoking and alcohol consumption are associated with bladder cancer risk in observational studies. We conducted a two-sample univariable and multivariable Mendelian randomization (MR) analysis to determine whether those associations are causal. We used 21, 126, 360, 39 single nucleotide polymorphisms (SNPs) as instrumental variables for number of cigarettes per day, lifetime smoking index, smoking initiation, and drinks per week, respectively. A total of 1115 cases with bladder cancer and 174 006 noncases from FinnGen consortium and 2883 cases with bladder cancer and 417 955 noncases from UK Biobank study were obtained. Genetic predisposition to cigarettes per day, lifetime smoking index and smoking initiation were positively associated with an increased risk of bladder cancer in both the FinnGen and UK Biobank consortium. The summary odds ratio (OR) of bladder cancer was 1.79 (95% confidence interval [CI], 1.31-2.45; P = .0002), 2.38 (95% CI, 1.45-3.88; P = .0005) and 1.91 (95% CI, 1.46-2.50; P = 1.59 × 10-06 ) for one SD increase in the number of cigarettes per day, lifetime smoking index and smoking initiation, respectively. The genetically instrumented number of drinks per week was not associated with bladder cancer (OR = 0.69; 95% CI, 0.44-1.10; P = .1237). Estimates were consistent in multivariable MR analyses by the adjustments of body mass index and education. Our study suggests a causal potential of the association of smoking but not alcohol consumption with bladder cancer according to current evidence.

Spatial and temporal patterns of prostate cancer burden and their association with Socio-Demographic Index in Asia, 1990-2019.

BACKGROUND: Prostate cancer is the second most frequently diagnosed cancer for males worldwide, but the spatial and temporal trends of prostate cancer burden remain unknown in Asia. This study aimed to investigate the changing spatial and temporal trends of incidence, prevalence, mortality, disability-adjusted life year (DALY), and mortality-to-incidence ratio (MIR) of prostate cancer, and their association with the Socio-Demographic Index (SDI) in 48 Asian countries from 1990 to 2019. METHODS: Data were extracted from the Global Health Data Exchange query tool, covering 48 Asian countries from 1990 to 2019. The average annual percent change was calculated to evaluate temporal trends. Spatial autocorrelation analysis was used to obtain spatial patterns, and the association between SDI and prostate cancer burden was estimated using a spatial panel model. RESULTS: In Asia, the age-standardized incidence and prevalence of prostate cancer increased in almost all countries, and its mortality and DALY also increased in over half of the countries. Significantly regional disparities were found in Asia, and the hot spots for incidence, prevalence, mortality, and DALY were all located in Western Asia, the hot spots of percent change also occurred in Western Asia for incidence and DALY. Furthermore, SDI had a positive association with mortality (coef = 2.51, 95% confidence interval [CI]: 2.13-2.90) and negative association with DALY (coef = -14.99, 95% CI: -20.37 to -9.60) and MIR (coef = -0.95, 95%CI: -0.99 to -0.92). CONCLUSIONS: Prostate cancer burden increased rapidly throughout Asia and substantial disparities had persisted between countries. Geographically targeted interventions are needed to reduce the prostate cancer burden throughout Asia and in specific countries.

Causal relationship between obesity, lifestyle factors and risk of benign prostatic hyperplasia: a univariable and multivariable Mendelian randomization study.

BACKGROUND: Obesity (waist circumference, body mass index (BMI)) and lifestyle factors (dietary habits, smoking, alcohol drinking, Sedentary behavior) have been associated with risk of benign prostatic hyperplasia (BPH) in observational studies, but whether these associations are causal is unclear. METHODS: We performed a univariable and multivariable Mendelian randomization study to evaluate these associations. Genetic instruments associated with exposures at the genome-wide significance level (P < 5 × 10-8) were selected from corresponding genome-wide associations studies (n = 216,590 to 1,232,091 individuals). Summary-level data for BPH were obtained from the UK Biobank (14,126 cases and 169,762 non-cases) and FinnGen consortium (13,118 cases and 72,799 non-cases). Results from UK Biobank and FinnGen consortium were combined using fixed-effect meta-analysis. RESULTS: The combined odds ratios (ORs) of BPH were 1.24 (95% confidence interval (CI), 1.07-1.43, P = 0.0045), 1.08 (95% CI 1.01-1.17, P = 0.0175), 0.94 (95% CI 0.67-1.30, P = 0.6891), 1.29 (95% CI 0.88-1.89, P = 0.1922), 1.23 (95% CI 0.85-1.78, P = 0.2623), and 1.04 (95% CI 0.76-1.42, P = 0.8165) for one standard deviation (SD) increase in waist circumference, BMI, and relative carbohydrate, fat, protein and sugar intake, 1.05 (95% CI 0.92-1.20, P = 0.4581) for one SD increase in prevalence of smoking initiation, 1.10 (95% CI 0.96-1.26, P = 0.1725) and 0.84 (95% CI 0.69-1.02, P = 0.0741) for one SD increase of log-transformed smoking per day and drinks per week, and 1.31 (95% CI 1.08-1.58, P = 0.0051) for one SD increase in sedentary behavior. Genetically predicted waist circumference (OR = 1.26, 95% CI 1.11-1.43, P = 0.0004) and sedentary behavior (OR = 1.14, 95% CI 1.05-1.23, P = 0.0021) were associated with BPH after the adjustment of BMI. CONCLUSION: This study supports independent causal roles of high waist circumference, BMI and sedentary behavior in BPH.

The Effect of Cognitive Intervention on Cognitive Function in Older Adults With Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Cognitive intervention includes cognitive stimulation, cognitive training, and cognitive rehabilitation. This systematic review was performed to re-assess the efficacy of cognitive intervention for the patients with Alzheimer's disease (AD). Twenty studies (2012 participants) were eventually included. For global cognitive function, the combined mean difference (MD) in eight studies was 1.67 (95% Confidence Interval: 0.45, 2.89, p = 0.007; Q = 33.28, df = 8, p < 0.0001, τ2 = 2.17, I2 = 76%) for the short term. The pooled standardized mean difference (SMD) of six RCTs was 1.61 (95% Confidence Interval: 0.65, 2.56, p = 0.0009; Q = 127.66, df = 6, p < 0.00001, τ2 = 1.56, I2 = 95%) for the medium term. The pooled SMD of seven studies was 0.79 (95% Confidence Interval: 0.33, 1.25, p = 0.0008; Q = 35.10, df = 7, p < 0.0001, τ2 = 0.33, I2 = 80%) for the long term. For depression, the pooled SMD of two trials was -0.48 (95% Confidence Interval: -0.71, -0.24; p < 0.0001, I2 = 4%) for the short term. Cognitive training may show obvious improvements in global cognitive function whether after short, medium, or long-term interventions and in depression after short term intervention. However, the positive effect of the intervention on general cognitive function or depression did not seem to persist after intervention ended. There is still a lack of reliable and consistent conclusions relevant to the effect of cognitive stimulation and cognitive rehabilitation on observed outcomes, cognitive training for memory or other non-cognitive outcomes. PROSPERO registration number: CRD42019121768.

Emerging photodynamic/sonodynamic therapies for urological cancers: progress and challenges.

Photodynamic therapy (PDT), and sonodynamic therapy (SDT) that developed from PDT, have been studied for decades to treat solid tumors. Compared with other deep tumors, the accessibility of urological tumors (e.g., bladder tumor and prostate tumor) makes them more suitable for PDT/SDT that requires exogenous stimulation. Due to the introduction of nanobiotechnology, emerging photo/sonosensitizers modified with different functional components and improved physicochemical properties have many outstanding advantages in cancer treatment compared with traditional photo/sonosensitizers, such as alleviating hypoxia to improve quantum yield, passive/active tumor targeting to increase drug accumulation, and combination with other therapeutic modalities (e.g., chemotherapy, immunotherapy and targeted therapy) to achieve synergistic therapy. As WST11 (TOOKAD® soluble) is currently clinically approved for the treatment of prostate cancer, emerging photo/sonosensitizers have great potential for clinical translation, which requires multidisciplinary participation and extensive clinical trials. Herein, the latest research advances of newly developed photo/sonosensitizers for the treatment of urological cancers, and the efficacy, as well as potential biological effects, are highlighted. In addition, the clinical status of PDT/SDT for urological cancers is presented, and the optimization of the photo/sonosensitizer development procedure for clinical translation is discussed.

A potential therapeutic strategy for prostatic disease by targeting the oral microbiome.

Nowadays, human microbiome research is rapidly growing and emerging evidence has witnessed the critical role that oral microbiome plays in the process of human health and disease. Oral microbial dysbiosis has been confirmed as a contributory cause for diseases in multiple body systems, ranging from the oral cavity to the gastrointestinal, endocrine, immune, cardiovascular, and even nervous system. As research progressing, oral microbiome-based diagnosis and therapy are proposed and applied, which may represent potential drug targets in systemic diseases. Recent studies have uncovered the possible association between periodontal disease and prostatic disease, suggesting new prevention and therapeutic treatment for the disease by targeting periodontal pathogens. Thus, we performed this review to first explore the association between the oral microbiome and prostatic disease, according to current knowledge based on published articles, and then mainly focus on the underlying molecular and cellular mechanisms and the potential prevention and treatment derived from these mechanistic studies.

STAT1 is a key gene in a gene regulatory network related to immune phenotypes in bladder cancer: An integrative analysis of multi-omics data.

The immunophenotype of bladder cancer plays a pivotal role in the prognosis of cancer, but the effect of different epigenetic factors on different immunophenotypes in bladder tumours remains unclear. This study used multi-omics data analysis to provide molecular basis support for different immune phenotypes. Unsupervised cluster analysis revealed distinct subclusters with higher (subcluster B2) or lower cytotoxic immune phenotypes (subcluster A1) related to PD-L1 and IFNG expression. Mutational landscape analyses showed that the mutation level of TP53 in subcluster B1 was highest than other subclusters, and subcluster B1 had a lower frequency of concurrent mutation than subcluster A2. A total of 2364 differentially expressed genes were identified between subclusters A2 and B1, and the main functions of the up-regulated genes in subcluster B1 were enriched in the activation of T cells and other related pathways. We found that STAT1 was a key gene in a gene regulatory network related to immune phenotypes in bladder cancer. Finally, we constructed a prognostic prediction model by LASSO Cox regression which could distinguish high-risk and low-risk cases significantly. In conclusion, the present study addressed a field synopsis between genetic and epigenetic events in immune phenotypes of bladder cancer.

Secular trends in severe periodontitis incidence, prevalence and disability-adjusted life years in five Asian countries: A comparative study from 1990 to 2017.

AIMS: To investigate secular trends in severe periodontitis incidence, prevalence and disability-adjusted life year (DALY) rates in China, India, Japan, South Korea and Thailand from 1990 to 2017. MATERIALS AND METHODS: Data were obtained from the "Global Burden of Disease Study" 2017. The annual percentage change and average annual percentage change were calculated using Joinpoint regression analysis. The independent age, period and cohort effects were estimated by age-period-cohort analysis. RESULTS: From 1990 to 2017, the overall age-standardized incidence, prevalence and DALY rates increased in China, Japan and India, while decreasing in South Korea and Thailand. The highest incidence, prevalence and DALY rates were in India. By APC analysis, the age effect presented increase in 20-59 years in China, Japan and South Korea, 20-54 years in India and 20-64 years in Thailand; the period effect showed progressive increases in five countries, with the most significant increase shown in China; the cohort effect showed monotonic decreases with birth cohort in five countries. CONCLUSIONS: Severe periodontitis poses a serious burden in Asian countries, especially China and India. We suggest raising people's awareness of periodontal health and providing professional interventions in these countries, especially for high-risk groups, such as younger people aged ≤65 years.

Determinants of successful guideline implementation: a national cross-sectional survey.

BACKGROUND: CPGs are not uniformly successful in improving care and several instances of implementation failure have been reported. Performing a comprehensive assessment of the barriers and enablers is key to developing an informed implementation strategy. Our objective was to investigate determinants of guideline implementation and explore associations of self-reported adherence to guidelines with characteristics of participants in China. METHODS: This is a cross-sectional survey, using multi-stage stratified typical sampling based on China's economic regional divisions (the East, the Middle, the West and the Northeast). 2-5 provinces were selected from each region. 2-3 cities were selected in each province, and secondary and tertiary hospitals from each city were included. We developed a questionnaire underpinned by recommended methods for the design and conduct of self-administered surveys and based on conceptual framework of guideline use, in-depth related literature analysis, guideline development manuals, related behavior change theory. Finally, multivariate analyses were performed using logistic regression to produce adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: The questionnaire consisted of four sections: knowledge of methodology for developing guidelines; barriers to accessing guideline; barriers to guideline implementation; and methods for improving guideline implementation. There were 1732 participants (87.3% response rate) from 51 hospitals. Of these, 77.2% reported to have used guidelines frequently or very frequently. The key barriers to guideline use were lack of education or training (46.2%), and overly simplistic wording or overly broad scope of recommendations (43.8%). Level of adherence to guidelines was associated with geographical regions (the northeast P < 0.001; the west P = 0.02; the middle P < 0.001 compared with the east), hospital grades (P = 0.028), length of practitioners' practice (P = 0.006), education background (Ph.D., P = 0.027; Master, P = 0.002), evidence-based medicine skills acquired in work unit (P = 0.012), and medical specialty of practitioner (General Practice, P = 0.006; Surgery, P = 0.043). CONCLUSION: Despite general acknowledgement of the importance of guidelines, the use of guidelines was not as frequent as might have been expected. To optimize the likelihood of adherence to guidelines, guideline implementation should follow an actively developed dissemination plan incorporating features associated with adherence in our study.

Comparing clinical parameters of abnormal and normal fasting blood glucose in benign prostatic hyperplasia patients.

OBJECTIVE: To investigate the correlation of clinical measurements on normal and abnormal fasting blood glucose (FBG) with benign prostatic hyperplasia (BPH). METHODS: From September 2016 to January 2018, 771 BPH patients were enrolled for further selection. The eligible patients were divided into normal FBG, impaired fasting glucose (IFG), and high risk of type 2 diabetes mellitus (HR-T2DM) groups. Then, relevant parameters were compared among these three groups using Pearson's correlation coefficient. RESULTS: Finally including 443 patients with normal FBG, 113 with IFG and 56 with HR-T2DM. Height, weight, body mass index, smoking status, hemoglobin, serum Na+, serum Cl-, and serum Ca2+ were significantly different between normal and abnormal FBG groups. In IFG/HR-T2DM group, obviously connections were demonstrated for weight with prostate volume (PV), for serum Na+, PV, and serum Cl- with total prostate-specific antigen (t-PSA), for FBG with international prostate symptom score (IPSS). In normal FBG group, significant correlations of age, weight, body mass index, hemoglobin, and serum Ca2+ with PV, of age, systolic blood pressure, PV, and serum Cl- with t-PSA; and of FBG, hemoglobin, and serum Na+ with IPSS were also observed. CONCLUSIONS: Our study suggests that FBG level probably plays an important role in BPH.

The important effect of 5-HTTLPR polymorphism on the risk of depression in patients with coronary heart disease: a meta-analysis.

BACKGROUND: Depression has been recognized as an independent risk factor of coronary heart disease (CHD). Moreover, there is interrelationship of both depression and CHD. However, the potential pathophysiological mechanisms remain unknown. It might be influenced by genetic and environmental factors. According to recent researches, there is potential association between serotonin transporter gene-linked polymorphic region (5-HTTLPR) polymorphism and risk of depression in CHD patients, but the results are still inconclusive. Therefore, we performed this meta-analysis based on unadjusted and adjusted data to ascertain a more precise conclusion. METHODS: We searched relevant articles through PubMed, Embase, Web of Science, Chinese BioMedical Literature (CBM) and Chinese National Knowledge Infrastructure (CNKI) databases up to August 26, 2019. Study selection and data extraction were accomplished by two authors independently. The strength of the correlation was assessed via odds ratios (ORs) with their 95% confidence intervals (95%CIs). RESULTS: This meta-analysis enrolled six observational studies. Based on unadjusted data, there was significant relationship between 5-HTTLPR polymorphism and depression risk in CHD patients under all genetic models (S vs. L: OR = 1.31, 95%CI = 1.07-1.60; SS vs. LL: OR = 1.73, 95%CI = 1.12-2.67; LS vs. LL: OR = 1.47, 95%CI = 1.13-1.92; LS + SS vs. LL: OR = 1.62, 95%CI = 1.25-2.09; SS vs. LL + LS: OR = 1.33, 95%CI = 1.02-1.74). The results of adjusted data further strengthened this relationship (SS vs. LL: OR = 1.89, 95%CI = 1.28-2.80; LS vs. LL: OR = 1.69, 95%CI = 1.14-2.51; LS + SS vs. LL: OR = 1.80, 95%CI = 1.25-2.59). Subgroup analyses based on ethnicity and major depressive disorder revealed similar results to that of the overall analysis. No evidence of publication bias was observed. CONCLUSIONS: Our results suggest that 5-HTTLPR polymorphism may have an important effect on the risk of depression among patients with CHD, and carriers of the S allele of 5-HTTLPR are more vulnerable to depression.

Actinin-4 as a Diagnostic Biomarker in Serum of Breast Cancer Patients.

BACKGROUND alpha-actinin-4 (Actinin-4 or ACTN4), originally identified as an actin-binding protein associated with the biological function of cancer cells, appears to be highly expressed in numerous human epithelial carcinomas, including breast cancer (BC). In the present study we assessed the role of serum ACTN4 as a biomarker for BC diagnosis, as well as the association between ACTN4 levels and clinicopathological features. MATERIAL AND METHODS ACTN4 expression level was measured with quantitative real-time PCR (qRT-PCR) analysis in serum specimens of 128 BC patients and 96 healthy volunteers. χ² testing was conducted to explore the association of ACTN4 levels with clinicopathologic factors. Moreover, the diagnostic value of ACTN4 was analyzed using receiver operating characteristic (ROC) curves. RESULTS Serum ACTN4 level was obviously upregulated in patients with BC compared with healthy controls (P<0.05). High ACTN4 expression was significantly associated with clinical stage (P=0.000), tumor grade (P=0.004), and lymph node status (P=0.024). However, no association was found between ACTN4 expression and age, tumor size, ER status, PR status, or HER-2 status (all P>0.05). The ROC analysis showed that the area under the curve (AUC) of ACTN4 was 0.887 (95%CI: 0.843-0.931), with sensitivity of 80.5% and specificity of 84.4%, and the cutoff value was 1.050. CONCLUSIONS ACTN4 in serum can serve as a clinical predictor in the diagnosis or prediction of clinical outcomes of patients with BC.

Baicalein Inhibits Proliferation of Myeloma U266 Cells by Downregulating IKZF1 and IKZF3.

BACKGROUND Baicalein can suppress the growth of multiple tumors, including multiple myeloma (MM), but the exact mechanisms remains elusive. Here, we investigated the exact mechanisms of the anti-myeloma activity of baicalein. MATERIAL AND METHODS Proliferation and rates of apoptosis of myeloma U266 cells exposed to baicalein were detected. Microarray, polymerase chain reaction (PCR) assay, and Western blot analysis were applied to evaluate the mRNA and protein levels of associated molecules. Survival analysis of IKZF1 and IKZF3 was conducted as well. RESULTS Baicalein suppressed the growth and stimulated apoptosis of myeloma U266 cells in a dose- and time-dependent way. Baicalein increased mRNA level of CRBN, and further studies suggested that baicalein downregulated IKZF1 and IKZF3 on a post-transcriptional level. Although the differences did not reach statistical significance, IKZF1 and IKZF3 were associated with poor overall survival. CONCLUSIONS Our results suggest that baicalein suppresses the growth and promotes apoptosis of myeloma U266 cells through downregulating IKZF1 and IKZF3. Baicalein increased the expression of CRBN, which might exert a reversion effect on resistance of IMiDs. MM patients in IKZF1 and IKZF3 low-expression groups had better overall survival than those in IKZF1 and IKZF3 high-expression groups. Thus, the present results indicate that baicalein might be a therapeutic choice for targeting IKZF1 and IKZF3.

The Clinical Relevance of Fragile Histidine Triad Protein (FHIT) in Patients with Bladder Cancer.

BACKGROUND The present study aimed to investigate the clinical relevance of fragile histidine triad protein (FHIT) in patients with bladder cancer (BC). MATERIAL AND METHODS Three independent BC microarray studies were collected and reanalyzed. The expression of FHIT was evaluated between BC samples and normal bladder tissues. The correlation between the expression of FHIT and clinicopathological features was analyzed using the chi-square test. Log-rank based survival analysis was conducted to detect the survival significance of FHIT in patients with BC. Gene set enrichment analysis (GSEA) was performed to identify the mechanisms. RESULTS FHIT was significantly downregulated in BC cells (p=0.0044). BC patients in the FHIT high expression group had better clinical characteristics (including invasiveness, tumor grade, disease progression, and T staging) than those in the FHIT low expression group (p<0.0001, p<0.0001, p=0.031, p<0.0001, and p=0.056, respectively). Patients in the FHIT high expression group had better cancer-specific survival (p<0.0001) and overall survival (p=0.0008) than those in the FHIT low expression. GSEA results indicated that BC samples in the FHIT low expression group were enriched in interferon alpha response, apoptosis, androgen response, interferon gamma response, heme metabolism, and transforming growth facto r(TGF) beta signaling. CONCLUSIONS FHIT predicts better clinical relevance for patients with BC, which may be a promising therapeutic target.

Endobronchial one-way valves for treatment of persistent air leaks: a systematic review.

Persistent air leak (PAL) is associated with significant morbidity and mortality, prolonged hospitalization and increased health-care costs. It can arise from a number of conditions, including pneumothorax, necrotizing infection, trauma, malignancies, procedural interventions and complications after thoracic surgery. Numerous therapeutic options, including noninvasive and invasive techniques, are available to treat PALs. Recently, endobronchial one-way valves have been used to treat PAL. We conducted a systematic review based on studies retrieved from PubMed, EMbase and Cochrane library. We also did a hand-search in the bibliographies of relevant articles for additional studies. 34 case reports and 10 case series comprising 208 patients were included in our review. Only 4 patients were children, most of the patients were males. The most common underlying disease was COPD, emphysema and cancer. The most remarkable cause was pneumothorax. The upper lobes were the most frequent locations of air leaks. Complete resolution was gained within less than 24 h in majority of patients. Complications were migration or expectoration of valves, moderate oxygen desaturation and infection of related lung. No death related to endobronchial one-way valves implantation has been found. The use of endobronchial one-way valve adds to the armamentarium for non-invasive treatments of challenging PAL, especially those with difficulties of anesthesia, poor condition and high morbidity. Nevertheless, prospective randomized control trials with large sample should be needed to further evaluate the effects and safety of endobronchial one-way valve implantation in the treatment of PAL.

COX-2 rs689466, rs5275, and rs20417 polymorphisms and risk of head and neck squamous cell carcinoma: a meta-analysis of adjusted and unadjusted data.

BACKGROUND: Numerous case-control studies have been performed to investigate the association between three cyclooxygenase-2 (COX-2) polymorphisms (rs20417 (-765G > C), rs689466 (-1195G > A), and rs5275 (8473 T > C)) and the risk of head and neck squamous cell carcinoma (HNSCC). However, the results were inconsistent. Therefore, we conducted this meta-analysis to investigate the association. METHODS: We searched in PubMed, Embase, and Web of Science up to January 20, 2015 (last updated on May 12, 2016). Two independent reviewers extracted the data. Odds ratios (ORs) with their 95 % confidence intervals (CIs) were used to assess the association. All statistical analyses were performed using the Review Manager (RevMan) 5.2 software. RESULTS: Finally 8 case-control studies were included in this meta-analysis. For unadjusted data, an association with increased risk was observed in three genetic models in COX-2 rs689466 polymorphism; however, COX-2 rs5275 and rs20417 polymorphisms were not related to HNSCC risk in this study. The pooled results from adjusted data all revealed non-significant association between these three polymorphisms and risk of HNSCC. We also found a similar result in the subgroup analyses, based on both unadjusted data and adjusted data. CONCLUSION: Current results suggest that COX-2 rs689466, rs5275, and rs20417 polymorphisms are not associated with HNSCC. Further large and well-designed studies are necessary to validate this association.

Aberrant GSTP1 promoter methylation is associated with increased risk and advanced stage of breast cancer: a meta-analysis of 19 case-control studies.

BACKGROUND: Glutathione S-transferase P1 (GSTP1) has been reported to function as a tumor suppressor gene in various types of human cancers. Aberrant methylation of tumor-related genes at the promoter regions can inactivate genes, which is important in the carcinogenesis of breast cancer. However, the role of GSTP1 promoter methylation in the occurrence of breast cancer and its relationship with tumor stage and histological grade has not been fully elucidated. Thus, we carried out a meta-analysis to yield a more accurate association. METHODS: A systematically literature search was made on PubMed, EMBASE and Web of Science databases for eligible studies. The odds ratio (OR) and 95 % confidence interval (95 % CI) were calculated by RevMan 5.2 software. Subgroup and sensitivity analyses were conducted to explore the source of heterogeneity. RESULTS: Eventually, 17 articles involving 19 case-control studies were included in the present meta-analysis. Overall, the pooled results indicated that aberrant GSTP1 promoter methylation was significantly associated with the risk of breast cancer (OR = 7.85, 95 % CI = 5.12-12.01; Caucasians OR = 7.23, 95 % CI = 3.76-13.90 and Asians OR = 11.71, 95 % CI = 5.69-24.07). Furthermore, our results revealed that GSTP1 promoter methylation was more often observed in late-stage breast cancer patients compared with early-stage ones (OR = 1.84, 95 % CI = 1.32-2.58). However, no significant association was identified between GSTP1 promoter methylation and histological grade (OR = 0.74, 95 % CI = 0.43-1.26). CONCLUSIONS: The results indicated that GSTP1 promoter methylation probably plays an important role in breast carcinogenesis, which could serve as an effective biomarker for the diagnosis and monitor of breast cancer.