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Background: Bladder urothelial carcinoma (BLCA) is the most common malignant tumor of the urinary system. Ferroptosis is a new type of programmed cell death that is iron-dependent and different from apoptosis, cell necrosis, and autophagy. Studies have indicated that many genes are involved in regulating ferroptosis or markers of ferroptosis. However, the value of genes related to ferroptosis in BLCA remains unclear.Methods: We comprehensively evaluated the differences in ferroptosis genes in patients with BLCA and control samples based on public databases, including mRNA expression, mutations, and copy number variations. The ferroptosis gene expression profile was used for consistent clustering to obtain ferr.clusterA and ferrclusterB. An analysis of differences between groups was performed to obtain ferroptosis-related gene, and then consistent clustering was performed to obtain ferr.gene.cluster A and ferr.gene.clusterB. Subsequently, the random forest algorithm was used to reduce dimensionality, Cox analysis was used to screen characteristic genes, principal component analysis was performed, and the ferroptosis score was constructed to quantify the ferroptosis expression of a single sample.Results: According to the ferroptosis score, the samples could be divided into two groups with significant differences in prognosis, which proves that the ferroptosis expression pattern in a single tumor can predict the prognostic response of patients.Conclusion: In summary, ferroptosis-related genes are significantly related to the progression of BLCA.

Periodontitis has been proposed as a novel risk factor of genitourinary cancers: although periodontitis and genitourinary cancers are two totally distinct types of disorders, epidemiological and clinical studies, have established associations between them. Dysbiosis of oral microbiota has already been established as a major factor contributing to periodontitis. Recent emerging epidemiological evidence and the detection of oral microbiota in genitourinary organs indicate the presence of an oral-genitourinary axis and oral microbiota may be involved in the pathogenesis of genitourinary cancers. Therefore, oral microbiota provides the bridge between periodontitis and genitourinary cancers. We have carried out this narrative review which summarizes epidemiological studies exploring the association between periodontitis and genitourinary cancers. We have also highlighted the current evidence demonstrating the capacity of oral microbiota to regulate almost all hallmarks of cancer, and proposed the potential mechanisms of oral microbiota in the development of genitourinary cancers.

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.

BackgroundUrinary tract infections (UTIs) are some of the most common infections worldwide and consume a lot of medical resources every year. However, there were a lack of available data on its incidence and disease burden. We armed to investigate incidence, mortality, and disability adjusted life-years (DALYs) of urinary tract infections (UTIs) from 1990 to 2017.MethodsWe extracted data from the Global Burden of Disease Study 2017, then calculated estimated annual percentage changes (EAPC) of age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALYs rate at global, national, regional, and socio-demographic index (SDI) level.ResultsFrom 1990 to 2017, the globally incident cases (+52.09%), death cases (+140.10%), and DALYs (+69.65%) of UTIs all increased. The ASIR, ASDR, and age-standardized DALYs rate showed upward trends with the EAPC of +0.10 (95%CI: 0.07 to 0.12), +0.72 (95%CI: 0.65-0.78), and +0.06 (95%CI: -0.05 to 0.16), respectively. The ASIR decreased only in the high-middle SDI quantile (-0.26, 95%CI: -0.3 to -0.23). United Arab Emirates had the largest increase of DALYs (+835.04%), but Bulgaria had the largest decrease (-80.74%). EAPC for incidence and mortality were below 0 mainly in Europe and East Asia. In 2017, the incident cases (+3.44 times), the deaths (+1.31 times), and DALYs (+1.21 times) were all higher in females than males. The incident cases were mainly concentrated in 15-49 years old; DALYs and mortality were higher in over 80 age groups.Conclusions Globally, the burden of UTIs increased from 1990 to 2017, especially in females; however, distinct varies were observed in different regions and countries. The infants and elders are easier to die when they suffer from UTIs.

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 P = 0.02; the middle P 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.

The incidence of chronic aging-associated diseases, especially cardiovascular and prostatic diseases, is increasing with the aging of society. Evidence indicates that cardiovascular diseases usually coexist with prostatic diseases or increase its risk, while the pathological mechanisms of these diseases are unknown. Oxidative stress plays an important role in the development of both cardiovascular and prostatic diseases. The levels of oxidative stress biomarkers are higher in patients with cardiovascular diseases, and these also contribute to the development of prostatic diseases, suggesting cardiovascular diseases may increase the risk of prostatic diseases via oxidative stress. This review summarizes the role of oxidative stress in cardiovascular and prostatic diseases and also focuses on the main shared pathways underlying these diseases, in order to provide potential prevention and treatment targets.

ObjectiveWe aimed to systematically identify the possible risk factors responsible for severe cases.MethodsWe searched PubMed, Embase, Web of science and Cochrane Library for epidemiological studies of confirmed COVID-19, which include information about clinical characteristics and severity of patients’ disease. We analyzed the potential associations between clinical characteristics and severe cases.ResultsWe identified a total of 41 eligible studies including 21060 patients with COVID-19. Severe cases were potentially associated with advanced age (Standard Mean Difference (SMD) = 1.73, 95% CI: 1.34–2.12), male gender (Odds Ratio (OR) = 1.51, 95% CI:1.33–1.71), obesity (OR = 1.89, 95% CI: 1.44–2.46), history of smoking (OR = 1.40, 95% CI:1.06–1.85), hypertension (OR = 2.42, 95% CI: 2.03–2.88), diabetes (OR = 2.40, 95% CI: 1.98–2.91), coronary heart disease (OR: 2.87, 95% CI: 2.22–3.71), chronic kidney disease (CKD) (OR = 2.97, 95% CI: 1.63–5.41), cerebrovascular disease(OR = 2.47, 95% CI: 1.54–3.97), chronic obstructive pulmonary disease (COPD) (OR = 2.88, 95% CI: 1.89–4.38), malignancy (OR = 2.60, 95% CI: 2.00–3.40), and chronic liver disease (OR = 1.51, 95% CI: 1.06–2.17). Acute respiratory distress syndrome (ARDS) (OR = 39.59, 95% CI: 19.99–78.41), shock (OR = 21.50, 95% CI: 10.49–44.06) and acute kidney injury (AKI) (OR = 8.84, 95% CI: 4.34–18.00) were most likely to prevent recovery. In summary, patients with severe conditions had a higher rate of comorbidities and complications than patients with non-severe conditions.ConclusionPatients who were male, with advanced age, obesity, a history of smoking, hypertension, diabetes, malignancy, coronary heart disease, hypertension, chronic liver disease, COPD, or CKD are more likely to develop severe COVID-19 symptoms. ARDS, shock and AKI were thought to be the main hinderances to recovery.

Background The American Joint Committee on Cancer (AJCC) 8th tumor-node-metastasis (TNM) classification for colorectal cancer (CRC) has limited ability to predict prognosis. Methods We included 45 379 eligible stage I-III CRC patients from the Surveillance, Epidemiology, and End Results Program. Patients were randomly assigned individually to a training (n = 31 772) or an internal validation cohort (n = 13 607). External validation was performed in 10 902 additional patients. Patients were divided according to T and N stage permutations. Survival analyses were conducted by a Cox proportional hazard model and Kaplan-Meier analysis, with T1N0 as the reference. Area under receiver operating characteristic curve and Akaike information criteria were applied for prognostic discrimination and model fitting, respectively. Clinical benefits were further assessed by decision curve analyses. Results We created a modified TNM (mTNM) classification: stages I (T1-2N0-1a); IIA (T1N1b, T2N1b, T3N0); IIB (T1-2N2a-2b, T3N1a-1b, T4aN0); IIC (T3N2a, T4aN1a-2a, T4bN0); IIIA (T3N2b, T4bN1a); IIIB (T4aN2b, T4bN1b); and IIIC (T4bN2a-2b). In the internal validation cohort, compared with the AJCC 8th TNM classification, the mTNM classification showed superior prognostic discrimination (area under receiver operating characteristic curve = 0.675 vs 0.667, respectively; 2-sided P Conclusions The mTNM classification provides better prognostic discrimination than AJCC 8th TNM classification, with good applicability in various populations and settings, to help better stratify stage I-III CRC patients into prognostic groups.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued “A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)”; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

Background: Many traditional survival analyses and restricted mean survival time (RMST) based analyses have been proposed for dealing with right censored time-to-event data. It is necessary to sort out the conditions and relationship among these methods for instruction. Comparison between hazard ratio (HR) and RMST in a study may promote appropriate understanding and application of the two effect measures.Method : Traditional survival analyses and RMST-based analyses were integrated into a flowchart and applied for univariable and multivariable analyses, RMST-based analyses included group comparison for difference in RMST, pseudo-value (PV) regressions, inverse probability of censoring probability (IPCW) regressions with group-specific weights and individual weights with homogeneity of censoring mechanism assumption. 4405 osteosarcomas were captured from Surveillance, Epidemiology and End Results Program Database. HR and difference in RMST (survival time lost or gain, STL or STG) were considered as effect measures and the effect of all included covariates on overall survival were reported for comparison. The relationship between difference in RMST and HR were explored when proportional hazard (PH) assumption was and was not met, respectively. Results: In group comparison and univariable regressions, using difference in RMST calculated by Kaplan-Meier methods as reference, PV regressions (R2=0.99) and IPCW regressions with group-specific weights (R2=1.00) provided more consistent estimation on difference in RMST than IPCW with individual weights (R2=0.09). In multivariable analysis, age (HR:1.03, STL: 3.86 months), diagnosis in 1970~1980s (HR:1.39 STL:27.49 months), metastasis (HR:4.47, STL: 202 months), surgery (HR:0.58, SLG:35.55 months) and radiation (HR:1.46, SLT:44.65 months) met PH assumption and were main independent factors for overall survival. In both univariable and multivariable variables, a robust negative logarithmic linear relationship between HRs estimated by Cox regression and differences in RMST by pseudo-value regressions was only observed when PH assumption was hold. Conclusion: The flowchart may be intuitive and helpful to instruct appropriate use of RMST based and traditional methods. PH assumption and homogeneity of censoring mechanism assumption will determine the appropriate selection of these method. HR and difference in RMST can be reported comprehensively.

Background: Given these verity of pulmonary heart disease and the wide utilization of Chinese herbal injections, this network meta-analysis was devised to assess the comparative efficacy of seven Chinese herbal injections (Ciwujia injection, Dazhuhongjingtan injection, Huangqi injection, Shenfu injection, Shengmai injection, Shenmai injection, and Shenqi Fuzheng injection) that were combined with Western medicines in the treatment of pulmonary heart disease. Methods: A literature search was performed in PubMed, Cochrane Library, EMBASE, Chinese Biological Medicine Database, China National Knowledge Infrastructure, Wanfang Database, and the Chinese Scientific Journal Database from their inception to July14, 2019. This network meta-analysis was conducted in accordance with a priori eligibility criteria and methodological quality recommendations. Data analysis was performed with WinBUGS 1.4.3 and Stata 13.0 software focusing on clinical effectiveness rate, arterial blood gas analysis, haemorheology and haemodynamic indexes and right ventricular dimensions. In addition to the odds ratio or mean difference in various outcomes, the ranking probability of interventions calculated by the surface under the cumulative ranking area curve was demonstrated. The surface under the cumulative ranking area was equal to the rank of the intervention and was aimed to assess the best intervention. Results: Ultimately, 118 randomized controlled trials including 10,085 patients were included. Integrating the outcome results, all eligible Chinese herbal injections plus Western medicines were superior to Western medicines alone, especially Shenfu injection+ Western medicines, Shenmai injection+ Western medicines,and Shenqi Fuzheng injection+ Western medicines. Regarding safety, the drip rate was an essential element for clinicians to consider during treatment. Conclusions: In conclusion, Shenfu injection+ Western medicines, Shenmai injection+ Western medicines and Shenqi Fuzheng injection+ Western medicines may be potential optimal treatments for pulmonary heart disease. A larger sample size and high-quality randomized controlled trials are needed to confirm and support this network meta-analysis.

Panic abandonment of household pets during the COVID-19 pandemic is not justified.

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.

Background The clinical presentation of SARS‐CoV‐2‐infected pneumonia (COVID‐19) resembles that of other etiologies of community‐acquired pneumonia (CAP). We aimed to identify clinical laboratory features to distinguish COVID‐19 from CAP. Methods We compared the hematological and biochemical features of 84 patients with COVID‐19 at hospital admission and 221 patients with CAP. Parameters independently predictive of COVID‐19 were calculated by multivariate logistic regression. The receiver operating characteristic (ROC) curves were generated and the area under the ROC curve (AUC) was measured to evaluate the discriminative ability. Results Most hematological and biochemical indexes of patients with COVID‐19 were significantly different from patients with CAP. Nine laboratory parameters were identified to be predictive of a diagnosis of COVID‐19. The AUCs demonstrated good discriminatory ability for red cell distribution width (RDW) with an AUC of 0.87 and hemoglobin with an AUC of 0.81. Red blood cell, albumin, eosinophil, hematocrit, alkaline phosphatase, and mean platelet volume had fair discriminatory ability. Combinations of any two parameters performed better than did the RDW alone. Conclusions Routine laboratory examinations may be helpful for the diagnosis of COVID‐19. Application of laboratory tests may help to optimize the use of isolation rooms for patients when they present with unexplained febrile respiratory illnesses.

When reporting the results of clinical studies, some researchers may choose the five-number summary (including the sample median, the first and third quartiles, and the minimum and maximum values) rather than the sample mean and standard deviation (SD), particularly for skewed data. For these studies, when included in a meta-analysis, it is often desired to convert the five-number summary back to the sample mean and SD. For this purpose, several methods have been proposed in the recent literature and they are increasingly used nowadays. In this article, we propose to further advance the literature by developing a smoothly weighted estimator for the sample SD that fully utilizes the sample size information. For ease of implementation, we also derive an approximation formula for the optimal weight, as well as a shortcut formula for the sample SD. Numerical results show that our new estimator provides a more accurate estimate for normal data and also performs favorably for non-normal data. Together with the optimal sample mean estimator in Luo et al., our new methods have dramatically improved the existing methods for data transformation, and they are capable to serve as "rules of thumb" in meta-analysis for studies reported with the five-number summary. Finally for practical use, an Excel spreadsheet and an online calculator are also provided for implementing our optimal estimators.

BackgroundThe clinical presentation of 2019 Novel Coronavirus (2019-nCov) infected pneumonia (NCIP) resembles that of other etiologies of community-acquired pneumonia (CAP). We aimed to identify clinical laboratory features to distinguish NCIP from CAP.MethodsWe compared the ability of the hematological and biochemical features of 84 patients with NCIP at hospital admission and 316 patients with CAP. Parameters independently predictive of NCIP were calculated by multivariate logistic regression. The receiver operating characteristic (ROC) curves were generated and the area under the ROC curve (AUC) was measured to evaluate the discriminative ability.ResultsMost hematological and biochemical indexes of patients with NCIP were significantly different from patients with CAP. Nine laboratory parameters were identified to be highly predictive of a diagnosis of NCIP by multivariate analysis. The AUCs demonstrated good discriminatory ability for red cell distribution width (RDW) with an AUC of 0.88 and Hemoglobin (HGB) with an AUC of 0.82. Red blood cell (RBC), albumin (ALB), eosinophil (EO), hematocrit (HCT), alkaline phosphatase (ALP), and white blood cell (WBC) had fair discriminatory ability. Combinations of any two parameters performed better than did the RDW alone.ConclusionsRoutine laboratory examinations may be helpful for the diagnosis of NCIP. Application of laboratory tests may help to optimize the use of isolation rooms for patients when they present with unexplained febrile respiratory illnesses.

To investigate the correlation between number of retrieved lymph nodes (rLNs) and prognosis and further ascertain the optimal number of rLNs with a beneficial survival impact in patients with pN0 colon cancer.The Surveillance, Epidemiology, and End Results (SEER) database was searched for pN0 colon cancer cases. X-Tile software and Kaplan-Meier survival analysis were applied to determine the optimal number of rLNs based on the minimal probability (P) value and the largest χA total of 6269 pN0 colon cancer patients who underwent surgical therapy were finally included for analysis. Harvest of at least 18 lymph nodes was determined as the optimal rLN number. This cut-off rLN value ( 18 versus ≥ 18) was identified as an independent prognostic factor (P 0.001) of overall survival via multivariate analysis. Similar findings were obtained in patients with retrieval of at least 12 lymph nodes (18 rLNs ≥ 12 versus rLNs ≥ 18) stratified into several groups.The number of rLNs was identified as an independent prognostic factor for pN0 colon cancer. Retrieval of at least 18 lymph nodes was associated with favorable prognosis in patients with pN0 colon cancer, and should, therefore, be regarded as an alternative cut-off value for survival analysis.

Methodological quality (risk of bias) assessment is an important step before study initiation usage. Therefore, accurately judging study type is the first priority, and the choosing proper tool is also important. In this review, we introduced methodological quality assessment tools for randomized controlled trial (including individual and cluster), animal study, non-randomized interventional studies (including follow-up study, controlled before-and-after study, before-after/ pre-post study, uncontrolled longitudinal study, interrupted time series study), cohort study, case-control study, cross-sectional study (including analytical and descriptive), observational case series and case reports, comparative effectiveness research, diagnostic study, health economic evaluation, prediction study (including predictor finding study, prediction model impact study, prognostic prediction model study), qualitative study, outcome measurement instruments (including patient - reported outcome measure development, content validity, structural validity, internal consistency, cross-cultural validity/ measurement invariance, reliability, measurement error, criterion validity, hypotheses testing for construct validity, and responsiveness), systematic review and meta-analysis, and clinical practice guideline. The readers of our review can distinguish the types of medical studies and choose appropriate tools. In one word, comprehensively mastering relevant knowledge and implementing more practices are basic requirements for correctly assessing the methodological quality.

Background Hazard ratio is considered as an appropriate effect measure of time-to-event data. However, hazard ratio is only valid when proportional hazards (PH) assumption is met. The use of the restricted mean survival time (RMST) is proposed and recommended without limitation of PH assumption. Method 4405 osteosarcomas were captured from Surveillance, Epidemiology and End Results Program Database. Traditional survival analyses and RMST-based analyses were integrated into a flowchart and applied for univariable and multivariable analyses, using hazard ratio (HR) and difference in RMST (survival time lost or gain, STL or STG) as effect measures. The relationship between difference in RMST and HR were explored when PH assumption was and was not met, respectively. Results In univariable analyses, using difference in RMST calculated by Kaplan-Meier methods as reference, pseudo-value regressions (R2=0.99) and inverse probability of censoring probability (IPCW) regressions with group-specific weights (R2=1.00) provided more consistent estimation on difference in RMST than IPCW with individual weights (R2=0.09). In multivariable analysis, age (HR:1.03, STL: 3.86 months), diagnosis in 1970~1980s (HR:1.39 STL:27.49 months), metastasis (HR:4.47, STL: 202 months), surgery (HR:0.58, SLG:35.55 months) and radiation (HR:1.46, SLT:44.65 months), met PH assumption and were main independent factors for overall survival. In both univariable and multivariable variables, a robust negative logarithmic linear relationship between HRs estimated by Cox regression and differences in RMST by pseudo-value regressions was only observed when PH assumption was hold (Difference in RMST = -109.3✕ln (HR) - 0.83, R² = 0.97, and Difference = -127.7✕ln (HR) – 9.49, R² = 0.93, respectively.) Conclusion The flowchart will be intuitive and helpful to instruct appropriate use of RMST based and traditional methods. RMST-based methods provided an absolute effect measure to inspect effects of covariates on survival time and promote evidence communication with HR. Difference in RMST should be reported with hazard ratio routinely.

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

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.

Background Accumulating evidence has confirmed the potential prognostic value of LVI in patients with cancers. This aim of the current study was to clarify the potential relationship between LVI and lymph node metastasis, establish predictive clinicopathologic prognostic factors for LVI and lymph node metastasis, and determine the prognostic significance of LVI for patients younger than 70 years with resected gastric cancer. Methods Overall survival rates were calculated using Kaplan-Meier analysis. Differences in proportions of patients were tested with the χ 2 test. Univariate and multivariate analyses were applied to identify independent prognostic factors. Logistic regression analysis was employed to identify the risk factors predicting the presence of LVI and LN metastasis. Results Univariate analysis led to the identification of tumor size, LVI and pN stage as factors significantly correlated with prognosis. Multivariate analysis demonstrated that tumor size, LVI, pN stage, and number of LNs retrieved are independent prognostic factors for the entire population. Logistic regression analysis proved that LVI and pT stage were significantly associated with LN metastasis. Conclusion LVI is an independent prognostic factor predicting LN metastasis and a strongly independent predictor of survival for patients with resected gastric cancer. We recommend that LVI should be taken into account as an important adjuvant prognostic factor, specially for pN0 cases with inadequate LNs retrieved. And the maximum number of LNs possible should be retrieved for optimal staging, especially for patients with higher cT stage.

// Yan Yan 1, * , Ai-Ping Deng 2, * , Wen Chen 3, * , Yu-Hua Ming 1 , Xian-Tao Zeng 1 and Wei-Dong Leng 1 1 Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China 2 Department of Neurosurgery, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China 3 Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China * These authors contributed equally to this work Correspondence to: Wei-Dong Leng, email: lengtaihe@163.com Keywords: human 8-oxoguanine glycosylase 1, hOGG1, polymorphism, head and neck squamous cell carcinoma, meta-analysis Received: March 27, 2017 Accepted: August 28, 2017 Published: January 06, 2018 ABSTRACT Background: The human 8-oxoguanine glycosylase 1 ( hOGG1 ) Ser326Cys polymorphism has been involved in the risk of head and neck squamous cell carcinoma (HNSCC), but the results of published studies on this topic still inconsistent. Results: Finally 11 qualified publications with 13 independent case-control studies were yielded. Overall, we observed significant differences in CysCys vs. SerSer [odds ratio (OR) = 1.55, 95% confidence interval (95% CI) = 1.01–2.38] and CysCys vs. SerCys+SerSer (OR = 1.42, 95% CI = 1.005–1.99) genetic models. Sensitivity analyses showed the results were not robust, cumulative meta-analyses and trial sequential analysis indicated the results didn't not need more studies to identification. Subgroup analyses showed there was a significant association in Caucasian, laryngeal squamous cell carcinoma, studies agreement with Hardy-Weinberg equilibrium, and alcohol drinkers subgroups under the corresponding contrasts. In addition, the results of Egger’s test were contradictory. Materials and Methods: All eligible studies were searched from the online databases including PubMed, Web of Science, China Knowledge Resource Integrated Database, and Wanfang databases up to February 10, 2017. After study selection and data extraction, the meta-analysis was performed using STATA 12.0 software and TSA software version 0.9 Beta. Conclusions: Our meta-analysis results indicated that hOGG1 Ser326Cys polymorphism may be associated with increased risk of HNSCC, especially in Caucasians, alcohol drinkers and the patients with laryngeal squamous cell carcinoma.

Assess the efficacy and safety of Broncho-Vaxom in pediatric recurrent respiratory tract infections (RRTIs).Published randomized controlled trials (RCTs) of Broncho-Vaxom for pediatric RRTI were searched using PubMed, Embase, Cochrane Library, CBM, CNKI, WanFang Data, and VIP databases up to January 2017. Risk of bias was evaluated in accordance to the guidelines of the Cochrane collaboration and the level of evidence was graded according to the GRADE.53 RCTs involving 4851 pediatric patients were included in this meta-analysis. It showed that Broncho-Vaxom was positively correlated with a reduction in the frequency of respiratory infection [MD=-2.33, 95% CI (-2.75, -1.90), P0.00001] compared to the control group. The Broncho-Vaxom group was more effective than control groups in relation to the duration of antibiotics course, infections, fever, cough, and wheezing, increasing serum immunoglobulin levels (IgG, IgA or IgM), and T-lymphocytes subtype (CD3+, CD4+, or CD8+). However, Broncho-Vaxom had higher adverse event rates [RR=1.39, 95% CI (1.02, 1.88), P=0.04]; these were not serious and did not influence the treatment course.Broncho-Vaxom shows a good efficacy for pediatric RRTIs on the basis of routine therapy (e.g. anti-infection and antiviral therapy). However, the level of evidence was low and more international multicenter clinical trials are needed to explore the efficacy and safety of Broncho-Vaxom.

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.

The present study was conducted to investigate the prognosis and survival of patients with locally advanced gastric cancer who underwent distal subtotal gastrectomy with modified D2 (D1+) and D2 lymphadenectomy, under 70 years of age. The five-year overall survival rates of 390 patients were compared between those receiving D1+ and D2 lymphadenectomy. Univariate and multivariate analyses were used to identify factors that correlated with prognosis and lymph node metastasis. Tumor size (P=0.039), pT stage (P=0.011), pN stage (P

// Cheng Fang 1, 2 , Yue Cao 2 , Xiaoping Liu 2 , Xian-Tao Zeng 2 and Yirong Li 1 1 Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China 2 Center for Evidence-Based and Translation Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China Correspondence to: Yirong Li, email: liyirong838@163.com Keywords: serum tumor markers, CA125, breast cancer, clinicopathological features, molecular subtype Received: March 09, 2017 Accepted: June 11, 2017 Published: July 12, 2017 ABSTRACT Detection of serum tumor markers has been developed as a non-invasive tool to assess treatment efficiency in different types of cancer. This study aims to investigate the role of preoperative serum tumor markers (CEA, CA125 and CA15-3) in the management of breast cancer, and their relationships with patients’ clinicopathological parameters as well as different molecular subtypes. Altogether, 151 patients with invasive breast cancer and 180 control subjects with benign breast diseases were enrolled in this study. In the present study, preoperative serum levels of CEA, CA125 and CA15-3 were significantly higher in patients with breast cancer than controls subjects. Moreover, late-stage cancer patients exhibited significantly higher levels of CEA, CA125 and CA15-3 compared with early-stage ones. Statistical analysis indicated that elevated CA125 and CA15-3 levels were obviously related to patients with larger tumor diameter (>5cm) and lymph node metastasis. Furthermore, our results showed that the preoperative serum levels of CA125 exhibited statistical differences among various molecular subtypes, with the most frequent elevations occurring in the triple-negative tumors. In summary, our study indicated that the preoperative serum levels of CEA, CA125 and CA15-3 might be more efficient for monitoring advanced tumors than early diagnosis. High preoperative CA125 levels may reflect tumor burden and are associated with aggressive molecular subtype, suggesting that it can be used to predict poor outcome and prognosis of breast cancer patients.

// Xiao-Bing Ni 1, * , Cheng Jia 2, * , He-Dong Yu 1, * , Yan-Qin Li 1 , Xian-Tao Zeng 1 and Wei-Dong Leng 1 1 Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China 2 Department of Orthodontics, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, China * These authors contributed equally to this work Correspondence to: Wei-Dong Leng, email: lengtaihe@163.com Keywords: interleukin-8, periodontitis, periodontal diseases, meta-analysis, polymorphism Received: February 14, 2017 Accepted: March 09, 2017 Published: April 07, 2017 ABSTRACT Background: Associations between interleukin-8 (IL-8) gene polymorphisms and periodontitis susceptibility have been investigated in many published studies, but the conclusions are still inconsistent. Therefore, we performed this systematic review and meta-analysis to review which polymorphisms have been researched and to obtain a precise result of the same polymorphism from different studies. Results: Finally 10 publications involving 1938 patients and 1569 controls were yielded, including 12 polymorphisms. Six studies investigated rs4073 polymorphism; two focused on rs2227306 and rs2227307; two referred to rs2227532 and T-738A; one detected rs2230054, rs1126579 and rs1126580; one inspected A2767T, T 1 1722T 2 and C1633T, and one for rs2234671 polymorphism. Of them, IL-8 C1633T and rs1126580 polymorphisms showed positive association while the other ten polymorphisms revealed negative results. Materials and methods: A comprehensive literature search from PubMed, Web of Science, and Chinese National Knowledge Infrastructure was conducted for all potentially relevant studies published before January 2, 2017. Two authors selected the studies and extracted data. The pooled analysis was conducted using the RevMan 5.1 software if a polymorphism was reported by two or more studies. Conclusions: Based on current evidence, the IL-8 rs4073, A2767T, T 1 1722T 2 , rs2234671, rs2230054, rs1126579, rs2227306, rs2227307, rs2227532, and T-738A polymorphisms were not associated with periodontitis susceptibility; the IL-8 C1633T and rs1126580 polymorphisms were associated with increased risk of periodontitis.

// Xin-Jun Su 1,* , Xian-Tao Zeng 1,2,3,* , Cheng Fang 2 , Tong-Zu Liu 1 and Xing-Huan Wang 1,2,3 1 Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China 2 Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China 3 Department of Evidence-Based Medicine and Clinical Epidemiology, The Second Clinical College, Wuhan University, Wuhan, China * These authors have contributed equally to this work Correspondence to: Xing-Huan Wang, email: // Keywords : PSA, polymorphism, BPH, meta-analysis Received : January 02, 2017 Accepted : February 08, 2017 Published : February 16, 2017 Abstract Inconsistency between reported findings on the association of prostate specific antigen ( PSA ) gene -158G/A polymorphism with benign prostatic hyperplasia (BPH) susceptibility need a meta-analysis to obtain a more accurate conclusion. A systematic search was conducted in electronic databases for the collection of eligible studies on PSA -158G/A polymorphism and BPH susceptibility. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were then calculated. 7 case-control studies with 758 cases and 752 controls were included into the present meta-analysis. The analysis results showed no significant relationship between PSA -158G/A polymorphism and BPH susceptibility in total analysis. Interestingly, after subgroup analyses based on ethnicity and source of control, the polymorphism reduced the susceptibility of BPH in Caucasian group (AA vs . GG: OR=0.47, 95% CI=0.25-0.89; allele A vs . allele G: OR=0.68, 95% CI=0.49-0.93), but it increased the disease susceptibility in Asian (AA vs . GG: OR=1.63, 95% CI=1.02-2.60; allele A vs . allele G: OR=1.37, 95% CI=1.03-1.83) and population-based (AA vs . GG: OR=2.39, 95% CI=1.07-5.38; allele A vs . allele G: OR=1.83, 95% CI=1.26-2.65) groups. PSA -158G/A polymorphism may be an inhibitor to the incidence of BPH in Caucasians, but it is likely to be a susceptible factor in Asians.

// Jie Liu 1, 2, * , Guo-Zheng Yu 3, * , Xiao-Ke Cheng 4, * , Xiao-Dong Li 4, 5 , Xian-Tao Zeng 6 and Xue-Qun Ren 1, 4 1 Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China 2 Nursing Department, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China 3 Department of General Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi 435000, Hubei Province, China 4 Center for Evidence-Based Medicine, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China 5 Department of Urology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China 6 Center for Evidence-Based and Translation Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China * These authors have contributed equally to this work Correspondence to: Xue-Qun Ren, email: renxuequn001@163.com Keywords: hepatocellular carcinoma, LGR5, leucine-rich repeat-containing G-protein coupled receptor 5, metastasis, epithelial-mesenchymal transition Received: December 01, 2016 Accepted: January 06, 2017 Published: February 07, 2017 ABSTRACT The purpose of the present study was to investigate the prognostic value of Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) in hepatocellular carcinoma (HCC) and its role in promoting HCC metastasis. The expression level of LGR5 in liver tumor tissues and adjacent non-tumor tissues were detected adopting immunohistochemistry (IHC), real-time PCR (RT-PCR) and western blot assays. Chi-square test was used to evaluate the correlation between LGR5 expression and clinicopathological characteristics. In addition, we assessed the relationship between LGR5 and two epithelial-mesenchymal transition (EMT) markers (E-cadherin and N-cadherin) in HCC tissues and cell lines. Our results showed that the expression of LGR5 was significantly higher in liver tumor tissues than in adjacent non-tumor tissues. Moreover, up-regulated LGR5 was associated with larger tumor diameter (>5cm, P=0.001), higher TNM stage (P=0.021), increased recurrence (P=0.023) and growing metastasis (P=0.030). Besides, we found that the expression level of LGR5 was correlated with E-cadherin and N-cadherin. In conclusion, up-regulated LGR5 in HCC patients is associated with malignant clinicopathological characteristics. LGR5 may promote HCC metastasis through inducting EMT process, and thus can be regarded as a candidate biomarker for prognosis and as a target in therapy.

Background. Previous studies have revealed that gene polymorphisms of inflammatory factors may influence the development or progression of periodontitis, a main cause of tooth loss in adults; however, due to limitations of individual studies, inconsistent findings were reported.Objective. To meta-analytically investigate the relationship between periodontitis and the Interleukin-4 (IL-4) and Interleukin-4 receptor (IL-4R) gene polymorphisms.Methods. Databases were searched for relevant case-control studies. After study selection based on the predefined selection criteria, methodological quality assessment and data extraction were conducted independently by two reviewers, before subsequent statistical analyses.Results. 37 studies involving 4,385 patients and 5,168 controls were included. All the studied IL-4 polymorphisms were not significantly associated with periodontitis, except the -33C/T (CT versus CC: OR = 0.50, 95% CI = 0.28–0.88) associated with reduced AgP susceptibility. Positive association was found between IL-4R Q551 polymorphism and periodontitis susceptibility in three genetic models (R versus Q: OR = 1.59, 95% CI = 1.14–2.22; QR versus QQ: OR = 1.84, 95% CI = 1.21–2.80; RR + QR versus QQ: OR = 1.82, 95% CI = 1.22–2.72).Conclusions. A positive association exists between the IL-4R Q551R polymorphism and occurrence of CP. The IL-4 -33 CT genotype is negatively associated with the occurrence of AgP.

Background Synthetic thymic peptides (sTPs) are used with chemotherapy to treat non-small cell lung cancer (NSCLC). In this study, we have performed a systematic review and meta-analysis of published trials to confirm the clinical efficacy and safety of sTPs, and determine the optimal types, usages, and sTP/chemotherapy combinations to produce the desired responses. Materials and methods We collected all studies regarding combined sTP therapy and chemotherapy for NSCLC from the Chinese and English databases (up to October 2018). Bias risk was evaluated for each. Data for meta-analysis was extracted using a pre-designed form. Evidence quality was rated using the Grading of Recommendations Assessment, Development and Evaluation approach. Results We included 27 randomized controlled trials containing 1925 patients, most with unclear bias risk. Combining sTPs with chemotherapy significantly increased the objective response rate [1.28, (1.13 to 1.45)], disease control rate [1.10, (1.01 to 1.18)], quality of life (QOL) [2.05, (1.62, 2.60)], and 1-year overall survival rate [1.43, (1.15 to 1.78)], with decreased risks of neutropenia, thrombocytopenia, and gastrointestinal reactions. Optimal conditions included treatment in combination with gemcitabine or navelbine and cisplatin, twice a week, with one 3-week cycle. In these conditions, thymosin α1 improved both antitumor immunity and tumor response. Most results had good robustness, and their quality ranged from moderate to very low. Conclusions The results suggest that treatment with sTPs, especially thymosin α1, and concomitant chemotherapy is beneficial to the patient, and provide evidence for optimal treatment regimens that may increase patient QOL and survival.

To investigate the correlation of clinical measurements on normal and abnormal fasting blood glucose (FBG) with benign prostatic hyperplasia (BPH).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.Finally including 443 patients with normal FBG, 113 with IFG and 56 with HR-T2DM. Height, weight, body mass index, smoking status, hemoglobin, serum NaOur study suggests that FBG level probably plays an important role in BPH.

Periodontal disease is linked to a number of systemic diseases such as cardiovascular diseases and diabetes mellitus. Recent evidence has suggested periodontal disease might be associated with lung cancer. However, their precise relationship is yet to be explored. Hence, this study aims to investigate the association of periodontal disease and risk of incident lung cancer using a meta-analytic approach.PubMed, Scopus, and ScienceDirect were searched up to June 10, 2015. Cohort and nested case-control studies investigating risk of lung cancer in patients with periodontal disease were included. Hazard ratios (HRs) were calculated, as were their 95% confidence intervals (CIs) using a fixed-effect inverse-variance model. Statistical heterogeneity was explored using the Q test as well as the I(2) statistic. Publication bias was assessed by visual inspection of funnel plots symmetry and Egger's test.Five cohort studies were included, involving 321,420 participants in this meta-analysis. Summary estimates based on adjusted data showed that periodontal disease was associated with a significant risk of lung cancer (HR = 1.24, 95% CI = 1.13 to 1.36; I(2) = 30%). No publication bias was detected. Subgroup analysis indicated that the association of periodontal disease and lung cancer remained significant in the female population.Evidence from cohort studies suggests that patients with periodontal disease are at increased risk of developing lung cancer.

Xiang-Yu Meng,1,* Yi Liao,2,* Xiao-Ping Liu,3 Sheng Li,1 Ming-Jun Shi,4 Xian-Tao Zeng11Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China; 2Department of Oncology, Nanfang Hospital, Southern Medical University, GuangZhou Province, People’s Republic of China; 3Department of Hematology and Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China; 4Institut Curie, Paris Sciences etLettres Research University, LeCentre National de la Recherche Scientifique, Les Unités Mixtes de Recherche 144, F-75005, Paris, France*These authors contributed equally tothis workObjective: To evaluate the efficacy and safety of cisplatin-based concurrent chemoradiotherapy (DDP-CCRT) in patients with high-risk cervical carcinoma (CC) compared with exclusive radiotherapy (RT).Materials and methods: Databases were searched for randomized controlled trials (RCTs) and cohort studies comparing DDP-CCRT with RT alone. Risk of bias assessment for RCTs was performed using the Cochrane Collaboration’s tool, and the Newcastle–Ottawa quality scale was used to perform quality assessment for cohort studies. Meta-analysis was conducted using Review Manager 5 and Stata 12.0 software.Results: Finally, eight RCTs and three cohort studies containing 2,130 subjects were included. Analysis on total failures revealed a statistically significant difference in favor of DDP-CCRT (risk ratio =0.77, 95% confidence intervals [CIs]: 0.67–0.89). No significant heterogeneity was detected for pooled analysis concerning overall survival; the result of which demonstrated the superiority of DDP-CCRT over RT alone (hazard ratio =0.68, 95% CI: 0.57–0.80), and stable and established accumulative effects were observed in cumulative meta-analysis. Similar results were observed for progression-free survival (hazard ratio =0.63, 95% CI: 0.50–0.76). In terms of treatment-related Grade 3 and 4 adverse events, our pooled analysis with a fixed-effects model showed significantly enhanced toxicity in the DDP-CCRT group compared with that in the RT group (odds ratio =3.13, 95% CI: 2.37–4.13).Conclusion: Solid and stable beneficial effects are associated with DDP-CCRT, and its superiority over comparative RT in patients with high-risk CC is confirmed. DDP-CCRT should be considered one of the frontline treatment options for high-risk CC patients without contraindications. However, enhanced toxicity associated with DDP-CCRT should never be ignored.Keywords: cervical carcinoma, concurrent chemoradiotherapy, meta-analysis, cisplatin, radiotherapy, survival

The association between periodontal disease and carotid atherosclerosis has been evaluated primarily in single-center studies, and whether periodontal disease is an independent risk factor of carotid atherosclerosis remains uncertain. This meta-analysis aimed to evaluate the association between periodontal disease and carotid atherosclerosis.We searched PubMed and Embase for relevant observational studies up to February 20, 2015. Two authors independently extracted data from included studies, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for overall and subgroup meta-analyses. Statistical heterogeneity was assessed by the chi-squared test (P0.1 for statistical significance) and quantified by the I(2) statistic. Data analysis was conducted using the Comprehensive Meta-Analysis (CMA) software.Fifteen observational studies involving 17,330 participants were included in the meta-analysis. The overall pooled result showed that periodontal disease was associated with carotid atherosclerosis (OR: 1.27, 95% CI: 1.14-1.41; P0.001) but statistical heterogeneity was substantial (I(2)=78.90%). Subgroup analysis of adjusted smoking and diabetes mellitus showed borderline significance (OR: 1.08; 95% CI: 1.00-1.18; P=0.05). Sensitivity and cumulative analyses both indicated that our results were robust.Findings of our meta-analysis indicated that the presence of periodontal disease was associated with carotid atherosclerosis; however, further large-scale, well-conducted clinical studies are needed to explore the precise risk of developing carotid atherosclerosis in patients with periodontal disease.

BACKGROUND The aim of this study was to investigate the association between cyclooxygenase-2 (COX-2) rs689466 (-1195 GA) polymorphism and susceptibility to head and neck squamous cell carcinoma (HNSCC) by performing a meta-analysis. MATERIAL AND METHODS PubMed and Embase were searched for relevant cohort and case-control studies up to 13 March 2015. After data extraction and methodological quality assessment for eligible studies, the overall, subgroup, sensitivity, and cumulative meta-analyses were conducted using the Comprehensive Meta-Analysis software (version 2.2). RESULTS Finally, 5 case-control studies involving 1564 HNSCC patients and 2346 healthy controls were included. For overall population, the results of 3 genetic models showed significant association, while the other 2 presented negative association [A vs. G: OR=0.97-1.09, 95%CI=0.97-1.09; AA vs. GG: OR=1.26, 95%CI=1.01-1.57; AA vs. GA: OR=1.21, 95%CI=1.01-1.45); AA vs. (GG+GA): OR=1.20, 95%CI=1.01-1.43; (AA+GA) vs. GG: OR=0.98, 95%CI=0.84-1.15]. Publication bias was not assessed due to the limited number of included studies. CONCLUSIONS This meta-analysis indicated that COX-2 rs689466 polymorphism might be associated with increased susceptibility to HNSCC. We also suggest performing more relevant studies in order to enlarge the sample size and obtain more precise results.

Introduction Bupleuri Radix and Curcumae Radix are two Chinese herbal medicines which commonly used in the treatment of hepatitis C. The present study identified the active compounds and significant pathways of Bupleuri Radix/Curcumae Radix medicine pair based on network pharmacology. Methods This study adopted the method of network pharmacology. Additionally, molecular docking simulation and cluster analysis was conducted for further analysis. Results The results showed that Bupleuri Radix/Curcumae Radix medicine pair may influence the progression of hepatitis C through the 16 common targets, including MMP1, CXCL10, BCL2, MMP9, PIK3CG, IL10, LDLR, CASP3, EGF, EGFR, BCL2L1, RAF1, IL6, APOB, MMP2 and CASP8. The components related to them were quercetin, naringenin, kaempferol, beta-sitosterol and isorhamnetin. GO function enrichment indicated that the targets was most related to negative regulation of apoptotic process, response to glucocorticoid and identical protein binding. Ten pathways were related to the treatment of hepatitis C through KEGG pathway enrichment analysis. Clustering analysis suggests that the targets were mainly enriched in the regulation of the process of apoptosis and lipoprotein and cholesterol metabolism. As a validation, the compounds had good binding activity to the targets. Conclusion Bupleuri Radix/Curcumae Radix medicine pair may have an effect on the procedure of programmed death and apoptosis and lipid metabolism. PIK3CG, BCL2, CASP3, MMP1 and CASP8 may play a key role in the treatment of hepatitis C. The two medicines may work on those targets and have an effect on hepatitis C.

Background: There is still a dispute over an issue of the clinical pathology and prognostic of programmed cell death ligand 1 (PD-L1) in hepatocellular carcinoma (HCC) patients. Here, we undertook this meta-analysis to survey the conceivable role of PD-L1 in HCC.Method: We searched databases like MEDLINE, EMBASE, and Google Scholar for relevant studies published in English up to February 13, 2018. We implemented the appraisal of the eligible studies according to the choice criterion. We used Hazard ratio (HR) and its 95% confidence interval (95% CI) to evaluate the prognostic role of PD-L1 for overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS). Odds ratio (OR) and the corresponding 95% CI were calculated to evaluate the connection between PD-L1 and clinicopathological features. Publication bias was tested.Results: 13 studies, which published range from 2009 to 2017 were contained in this meta-analysis, involving 1,843 patients with HCC. The results indicated that high PD-L1 could predict shorter OS (HR = 1.57, 95% CI: 1.09-2.27, P < 0.00001) as well as poorer DFS (HR = 2.07, 95% CI: 1.20-3.58, P = 0.009). Additionally, high PD-L1 expression was correlated to liver cirrhosis (OR = 1.66, 95% CI: 1.10-2.50, P = 0.02), poorer tumor Barcelona Clinical Liver Cancer (BCLC) stage (OR = 0.30, 95% CI: 0.10-0.88, P = 0.03) and portal vein invasion (OR = 1.96, 95% CI: 1.04-3.68, P = 0.04), but had no correlation with age, gender, tumor size, number of tumors, AFP, vascular invasion, HBVs-Ag, Anti-HCV, differentiation or TNM stage. Besides, no significant publication bias was found among these identified studies.Conclusion: The meta-analysis suggested that PD-L1 overexpression could foresee worse OS and DFS in HCC. Moreover, the PD-L1 expression has to bear on liver cirrhosis, portal vein invasion, and BCLC stage.

Background and objective Promoter status of O6-methylguanine-DNA methyltransferase (MGMT) has been widely established as a clinically relevant factor in glioblastoma (GBM) patients. However, in addition to varied therapy schedule, the prognosis of GBM patients is also affected by variations of age, race, primary or recurrent tumor. This study comprehensively investigated the association between MGMT promoter status and prognosis in overall GBM patients and in different GBM subtype including new diagnosed patients, recurrent patients and elderly patients. Methods A comprehensive search was performed using PubMed, EMBASE, Cochrane databases to identify literatures (published from January 1, 2005 to April 1, 2017) that evaluated the associations between MGMT promoter methylation and prognosis of GBM patients. Results Totally, 66 studies including 7,886 patients met the inclusion criteria. Overall GBM patients with a methylated status of MGMT receiving temozolomide (TMZ)-containing treatment had better overall survival (OS) and progression-free survival (PFS) [OS: hazard ratio (HR) = 0.46, 95% confidence interval (CI): 0.41–0.52, p

Objectives: TP53 is an important tumor suppressor gene to maintain genomic integrity, and its mutations increase the susceptibility to oral carcinoma. Previous published studies have reported the relation of TP53 codon 72 polymorphism with the risk of oral carcinoma, but the results remain controversial and inconclusive. Methods: We therefore utilized meta-analysis based on a comprehensive search in PubMed, EMBASE, and Google of Scholar databases up to August 19, 2017. Results: Total 3,525 cases and 3,712 controls from 21 case-control studies were selected. We found no significant association between TP53 codon 72 polymorphism and oral carcinoma susceptibility in all genetic contrast models, including subgroup analysis based on control source and ethnicity. Furthermore, TP53 codon 72 polymorphism was not significant associated with oral carcinoma susceptibility in tobacco or alcohol use, and HPV infection status. Our results were confirmed by sensitivity analysis and no publication bias was found. Conclusions: Taken together, our data indicate that TP53 codon 72 polymorphism is not associated with the susceptibility to oral carcinoma.

Bladder cancer and benign prostatic hyperplasia have been two very common diseases among the elderly men, especially with the aging of the population in the world. We have designed a study to investigate the clinical effect of interventional therapy for plasmakinetic resection of the prostate and plasmakinetic resection of the bladder, which is called "BPSC" (The bladder cancer and benign prostatic hyperplasia study in Chinese population). The BPSC is not only a specific study, it is made up of many studies. In this article, we introduced the research background, source, name, study framework, study management and further direction of BPSC project. We hope this process will contribute to the growth of the database through sharing data and enriching the evidence of bladder cancer and benign prostatic hyperplasia in the Chinese population, thereby finally improving the accessibility of these important findings for doctors, researchers, and patients.

Objective. DC-CIK therapy included DC-CIK cells and Ag-DC-CIK cells. To further confirm whether DC-CIK reconstructs the antitumor immunity and improves the tumor responses and reveals its optimal usage and combination with chemotherapy, we systematically reevaluated all the related studies.Materials and Methods. All studies about DC-CIK plus chemotherapy for NSCLC were collected from the published and ongoing database as CBM, CNKI, VIP, Wanfang, ISI, Embase, MEDLINE, CENTRAL, WHO-ICTRP, Chi-CTR, and US clinical trials (established on June 2017). We evaluated their methodological bias risk according to the Cochrane evaluation handbook of RCTs (5.1.0), extracted data following the predesigned data extraction form, and synthesized the data using meta-analysis.Results. We included 28 RCTs (phase IV) with 2242 patients, but most trials had unclear bias risk. The SMD and 95% CI of meta-analysis for CD3+T cells, CD3+CD4+T cells, CD3+CD8+T cells, CD4+/CD8+T cell ratio, CIK cells, NK cells, and Treg cells were as follows: 1.85 (1.39 to 2.31), 0.87 (0.65 to 1.10), 1.04 (0.58 to 1.50), 0.75 (0.27 to 1.22), 3.87 (2.48 to 5.25), 1.51 (0.99 to 2.03), and −2.31(−3.84 to −0.79). The RR and 95% CI of meta-analysis for ORR and DCR were as follows: 1.38 (1.24 to 1.54) and 1.27 (1.20 to 1.34). All differences were statistically significant between DC-CIK plus chemotherapy and chemotherapy alone. Subgroup analysis showed that only DC-CIK cells could increase the CD3+T cells, CD3+CD4+T cells, CD3+CD8+T cells, and CD4+/CD8+T cell ratio. In treatment with one cycle or two cycles and combination with NP or GP, DC-CIK could increase the CD4+/CD8+T cell ratio. All results had good stability.Conclusions. DC-CIK therapy can simultaneously improve the antitumor immunity and tumor responses. DC-CIK therapy, especially DC-CIK cells, can improve antitumor immunity through increasing the T lymphocyte subsets, CIK cell, and NK cells in peripheral blood. The one cycle to two cycles may be optimal cycle, and the NP or GP may be optimal combination.

Objective: To discover the correlation of clinical and physiological measures for benign prostatic hyperplasia in hypertensive and normotensive patients. Methods: From September 2016 to October 2017, 435 patients were enrolled for further selection. The parameters evaluated for eligible patients included prostate volume, systolic blood pressure, diastolic blood pressure, international prostate symptom score, etc. Then the eligible patients were divided into two groups according to hypertension condition, and the clinical and physiological parameters were compared between two groups. The Pearson's correlation coefficient was used to test the linearity of the relationships of these clinical and physiological components with prostate volume, total prostate specific antigen, and international prostate symptom score. Results: Finally, 350 patients were involved in this study, including 117 with hypertension and 233 without hypertension. Weight, body mass index, systolic blood pressure, and diastolic blood pressure were significantly different between the hypertension and normotension groups. In the normotension group, there were positive correlations between weight, body mass index, age, and prostate volume; between fasting blood sugar, systolic blood pressure, diastolic blood pressure, and total prostate specific antigen; between fasting blood sugar and international prostate symptom score. In the hypertension group, there were positive correlations between age and total prostate specific antigen and international prostate symptom score; between weight and prostate volume; between systolic blood pressure and total prostate specific antigen. Conclusion: This study indicated that there might be no significant association between hypertension and prostate volume.

s Objective Cytokine-induced killer cells (CIK) therapy is the most commonly used cellular immunotherapy. The CIK plus radiotherapy was clinically used in a wide range of treatment, but the efficacy of their combination against lung cancer is not clear yet. Therefore, we systematically evaluated all the related studies to reveal the combination's clinical efficacy and safety in lung cancer. Materials and methods We collected all the studies about CIK plus radiotherapy for lung cancer in Medline, Embase, Web of Science (ISI), China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang Database, China Biological Medicine Database (CBM) and Cochrane Central Register of Controlled Trials (CENTRAL), Chinese clinical trial registry (Chi-CTR), WHO International Clinical Trials Registry Platform (WHO-ICTRP) and US-clinical trials (March 2017). We evaluated their bias risk according to the Cochrane evaluation handbook of randomized controlled trials (RCTs), extracted all the data, and synthesized the data using meta analysis. Results We included 16 RCTs involving 1197 patients with lung cancer, and most trials had unclear risk of bias. Meta-analysis showed that CIK therapy could increase the objective response rate (ORR) (1.32, 1.21 to 1.44), the disease control rate (DCR) (1.13, 1.04 to 1.23), the 1-year overall survival (OS) rate (1.38, 1.16 to 1.63) and the 2-year OS rate (1.23, 1.11 to 1.35). DCs-CIK cells increased the 3-year OS rate (1.66, 1.20 to 2.29). DCs-CIK therapy could increase the CD3+T cells (2.27, 1.47 to 3.06), CD4+T cells (1.28, 0.74 to 1.81), NK cells (2.04, 0.74 to 3.33) and CD4+/CD8+ T cells ratio (1.20, 0.64 to 1.76) and decrease the CD8+T cells (−0.84, −1.60 to −0.08). CIK plus radiotherapy had lower risk of leukopenia (0.85, 0.76 to 0.95) and higher risk of fever (5.50, 2.71 to 11.17) than that of radiotherapy alone. Subgroup analysis showed that CIK plus radiotherapy, mainly three dimensional conformal radiotherapy (3D-CRT) could increase the ORR, DCR, 1- and 2- year OS rate in non-small cell lung cancer (NSCLC), and only DCR in small cell lung cancer (SCLC). Compared with CIK plus pure radiotherapy, except for the ORR, DCR, 1-year OS rate, CIK plus chemoradiotherapy could still increase the 2-year OS rate. DCs-CIK could increase the ORR, DCR, 1- and 2-year OS rate, CIK cells could only increase the ORR and the 1-year OS rate. Conclusions CIK plus radiotherapy can improve the clinical response, OS and PFS in lung cancer. It may have low risk of leukopenia and high risk of fever. CIK plus chemoradiotherapy, mainly 3D-CRT can improve the clinical response, OS and PFS in NSCLC. DCs-CIK cells can improve the 1-, 2- and 3-year OS rate, and the 1- and 2-year PFS rate, and CIK cells only improve the 1-year OS rate. DCs-CIK cells can repair the antitumor immunity.