Drug-Related Deaths in China: An Analysis of a Spontaneous Reporting System.

Background: Adverse drug reactions with an outcome of death represent the most serious consequences and are inherently important for pharmacovigilance. The nature and characteristics of drug-related deaths are to a large extent unknown in the Chinese population. This study aims to characterize drug-related deaths by analysis of individual case safety reports (ICSRs) with an outcome of death in China. Methods: The characteristics of death ICSRs were analyzed by descriptive statistics of a large multi-provincial pharmacovigilance database in China. Results: There were 1,731 ICSRs with an outcome of death, representing 0.95% of all serious cases and 0.05% of all reported ICSRs. Most death ICSRs (78.57%) were reported by medical institutions. Only 16.00% of death ICSRs were reported by manufacturers or distributors. The reporting rate of death ICSRs in the age group of 0-4 years was significantly higher than patients aged 5-64 years. Patients aged over 64 years had the highest reporting rate of death ICSRs. Male patients generally had a higher reporting rate of death ICSRs than female patients. However, the reporting rate of female patients exceeded that of male patients in the age group of 20-34 years. Among 3,861 drugs implicated, ceftriaxone sodium with 146 (3.78%) records of death ranked first. Dexamethasone with 131 (3.39%) records of death ranked second. Qingkailing, an injectable traditional Chinese medicine with 75 (1.94%) records of death, ranked the fifth most frequently implicated medicine. Conclusion: Young children and elderly patients have a higher risk of drug-related deaths than patients aged 5-64 years. Female patients generally have a lower risk of drug-related deaths than male patients. However, female patients of reproductive age (aged 20-34 years) have a higher risk of drug-related deaths than male patients, hinting that physiological changes and drug uses for child bearing, giving birth, or birth control may significantly increase the risk of death for female patients aged 20-34 years. This paper suggests more research on the safe use of drugs for young children, elderly patients, and female patients of reproductive ages. Pharmacovigilance databases can be valuable resources for comprehensive understanding of drug-related problems.

Association between common cardiovascular drugs and depression.

OBJECTIVE: Cardiovascular diseases are associated with an increased risk of depression, but it remains unclear whether treatment with cardiovascular agents decreases or increases this risk. The effects of drugs on individual usage are also often unknown. This review aimed to examine the correlation between depression and common cardiovascular drugs, develop more potent interventions for depression in cardiovascular patients, and further research on the bio-behavioural mechanisms linking cardiovascular drugs to depression. DATA SOURCES: The data in this review were obtained from articles included in PubMed, EMBASE, and Web of Science. STUDY SELECTION: Clinical trials, observational studies, review literature, and guidelines about depression and cardiovascular drugs were selected for the article. RESULTS: We systematically investigated whether the seven most used cardiovascular drugs were associated with altered risk of incident depression in this literature review. Statins have been proven to have antidepressant effects. Some studies believe angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARB) can exert an antidepressant influence by acting on the renin-angiotensin system, but further clinical trials are needed to confirm this. Beta-blockers have previously been associated with depression, but the current study found no significant association between beta blockers and the risk of depression. Aspirin may have antidepressant effects by suppressing the immune response, but its role as an antidepressant remains controversial. calcium channel blockers (CCBs) can regulate nerve signal transduction by adjusting calcium channels, but whether this effect is beneficial or harmful to depression remains unclear. Finally, some cases have reported that nitrates and diuretics are associated with depression, but the current clinical evidence is insufficient. CONCLUSIONS: Statins have been proven to have antidepressant effect, and the antidepressant effects of ACEIs/ARB and aspirin are still controversial. CCBs are associated with depression, but it is unclear whether it is beneficial or harmful. No association has been found with ß-blockers, diuretics, and nitrates.

A multi-institutional retrospective study of hyperthermic plus intravesical chemotherapy versus intravesical chemotherapy treatment alone in intermediate and high risk nonmuscle-invasive bladder cancer.

Objective: To compare the efficacy and safety of hyperthermic intravesical chemotherapy (HIVEC) and intravesical chemotherapy (IVEC) in patients with intermediate and high risk nonmuscle-invasive bladder cancer (NMIBC) after transurethral resection. Methods: We included 560 patients diagnosed with primary or recurrent NMIBC between April 2009 and December 2015 at 1 of 6 tertiary centers. We matched 364 intermediate or high risk cases and divided them into 2 groups: the HIVEC+IVEC group [chemohyperthermia (CHT) composed of 3 consecutive sessions followed by intravesical instillation without hyperthermia] and the IVEC group (intravesical instillation without hyperthermia). The data were recorded in the database. The primary endpoint was 2-year recurrence-free survival (RFS) in all NMIBC patients (n = 364), whereas the secondary endpoints were the assessment of radical cystectomy (RC) and 5-year overall survival (OS). Results: There was a significant difference in the 2-year RFS between the two groups in all patients (n = 364; HIVEC+IVEC: 82.42% vs. IVEC: 74.18%, P = 0.038). Compared with the IVEC group, the HIVEC+IVEC group had a lower incidence of RC (P = 0.0274). However, the 5-year OS was the same between the 2 groups (P = 0.1434). Adverse events (AEs) occurred in 32.7% of all patients, but none of the events was serious (grades 3-4). No difference in the incidence or severity of AEs between each treatment modality was observed. Conclusions: This retrospective study showed that HIVEC+IVEC had a higher 2-year RFS and a lower incidence of RC than IVEC therapy in intermediate and high risk NMIBC patients. Both treatments were well-tolerated in a similar manner.

Coronavirus Disease 2019 Related Clinical Studies: A Cross-Sectional Analysis.

OBJECTIVE: The quality and rationality of many recently registered clinical studies related to coronavirus disease 2019 (COVID-19) needs to be assessed. Hence, this study aims to evaluate the current status of COVID-19 related registered clinical trial. METHODS: We did an electronic search of COVID-19 related clinical studies registered between December 1, 2019 and February 21, 2020 (updated to May 28, 2020) from the ClinicalTrials.gov, and collected registration information, study details, recruitment status, characteristics of the subjects, and relevant information about the trial implementation process. RESULTS: A total of 1,706 studies were included 10.0% of which (n=171) were from France, 943 (55.3%) used an interventional design, and 600 (35.2%) used an observational design. Most of studies (73.6%) aimed to recruit fewer than 500 people. Interferon was the main prevention program, and antiviral drugs were the main treatment program. Hydroxychloroquine and chloroquine (230/943, 24.4%) were widely studied. Some registered clinical trials are incomplete in content, and 37.4% of the 1,706 studies may have had insufficient sample size. CONCLUSION: The quality of COVID-19 related studies needs to be improved by strengthening the registration process and improving the quality of clinical study protocols so that these clinical studies can provide high-quality clinical evidence related to COVID-19.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version).

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.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: an evidence-based clinical practice guideline (updated version)

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 COVID19 patients

Gaining insight into irrational off-label use of vidarabine through analysis of a spontaneous reporting system in China.

WHAT IS KNOWN AND OBJECTIVE: Although superseded by other antiviral agents in many Western countries, vidarabine is still widely used in some countries, including China; hence, the extent and appropriateness of vidarabine prescriptions in children require better characterization. This study examined the rationale, extent, and health risks associated with irrational off-label vidarabine use in China. METHODS: Data used in the study were extracted from a multi-provincial joint adverse drug reactions monitoring platform from 2002 to 2018. Descriptive statistics were used to analyse the characteristics of individual case safety reports (ICSRs) related to vidarabine use. RESULTS AND DISCUSSION: Among 2772 individual ICSRs related to vidarabine, 2223 (80.19%) cases occurred in patients aged 0-9. In all patients, the median age and interquartile range were 2 (0-6). Although most adverse events were mild, five deaths were recorded, all in children below 7 years of age. Paediatric use is the most prominent off-label use of vidarabine. Additionally, several other irrational off-label uses were identified, including 218 (7.86%) cases of overdosing and numerous applications beyond the approved indications, dosages, routes of administration, and solvents. WHAT IS NEW AND CONCLUSION: Data indicate that vidarabine was mainly prescribed for suspected common viral infections in paediatric patients, demonstrating serious inappropriate off-label uses. The problem was further complicated by the lack of sufficient information regarding safety, efficacy, and dosing regimens in children, as well as by several additional risk factors such as inappropriate solvents, routes of administration, and overdose. In the case of children, the physicians' lack of understanding of antiviral activities and compassionate prescriptions were mainly responsible for drug overuse. The health risks associated with the paediatric use of vidarabine in China require greater attention and further investigation.

A convenient clinical nomogram for predicting the cancer-specific survival of individual patients with small-intestine adenocarcinoma.

BACKGROUND: The objective of this study was to develop a practical nomogram for predicting the cancer-specific survival (CSS) of patients with small-intestine adenocarcinoma. METHODS: Patients diagnosed with small-intestine adenocarcinoma between 2010 and 2015 were selected for inclusion in this study from the Surveillance, Epidemiology, and End Results (SEER) database. The selected patients were randomly divided into the training and validation cohorts at a ratio of 7:3. The predictors of CSS were identified by applying both forward and backward stepwise selection methods in a Cox regression model. The performance of the nomogram was measured by the concordance index (C-index), the area under receiver operating characteristic curve (AUC), calibration plots, the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), and decision-curve analysis (DCA). RESULTS: Multivariate Cox regression indicated that factors including age at diagnosis, sex, marital status, insurance status, histology grade, SEER stage, surgery status, T stage, and N stage were independent covariates associated with CSS. These factors were used to construct a predictive model, which was built and virtualized by a nomogram. The C-index of the constructed nomogram was 0.850. The AUC values indicated that the established nomogram displayed better discrimination performance than did the seventh edition of the American Joint Committee on Cancer TNM staging system in predicting CSS. The IDI and NRI also showed that the nomogram exhibited superior performance in both the training and validation cohorts. Furthermore, the calibrated nomogram predicted survival rates that closely corresponded to actual survival rates, while the DCA demonstrated the considerable clinical usefulness of the nomogram. CONCLUSION: We have constructed a nomogram for predicting the CSS of small-intestine adenocarcinoma patients. This prognostic model may improve the ability of clinicians to predict survival in individual patients and provide them with treatment recommendations.

Developments, Evolution, and Implications of National Diagnostic Criteria for COVID-19 in China.

Recently WHO has characterized COVID-19 as a pandemic. Diagnosing the disease accurately and decreasing misdiagnoses and missed diagnoses is very important for management. Therefore, we have analyzed the seven versions of China's national guidelines to examine how the diagnostic criteria roadmap has developed and evolved, in order to share our experience worldwide. In this article, we present the developments from the first to seventh versions, involving changes of case classification, changes to "suspected case," changes in "confirmed case," changes in clinical classifications, changes in "severe case," and unchanged criteria. We have also discussed the reasons and implications for these changes and are looking forward to providing suggestions for worldwide understanding and management of this pandemic. A nucleic acid test is currently accepted as the gold standard method to confirm diagnosis. In addition, imaging examination and epidemiological history should also be considered as auxiliary diagnosis methods.

LncRNA CASC15 promotes tumour progression through SOX4/Wnt/ß-catenin signalling pathway in hepatocellular carcinoma.

Objective: The present study aimed to investigate the function of lncRNA CASC15 (cancer susceptibility candidate 15) in hepatocellular carcinoma (HCC), as well as its regulatory roles in SOX4 expression and Wnt/ß-catenin pathway.Methods: Quantitative real-time polymerase chain reaction (QRT-PCR) method was used to detect the relative expression of CASC15 mRNA in HCC tissues. Protein detection was performed by western blot. Luciferase assay was used to confirm the potential target of CASC15 in HCC. Cell proliferation, migration and invasion, as well as apoptosis were analyzed using MTT, transwell assays and flow cytometry in vitro, respectively.Results: The expression of CASC15 was significantly increased in HCC tissues (p < .001) and showed positive correlation with tumour size (p = .016), TNM stage (p = .018) and metastasis (p = .021). The knockdown of CASC15 could obviously inhibit HCC cell proliferation, migration and invasion and promote cell apoptosis in vitro (p < .05 for all). Furthermore, the protein levels of SOX4, ß-catenin, Cyclin D1 and c-Myc also exhibited decreased trends after CASC15 inhibition. Luciferase assay confirmed that SOX4 might be a targeted gene of CASC15 in HCC.Conclusion: In HCC, CASC15 may activate the Wnt/ß-catenin pathway via enhancing the expression of SOX4, thus promote tumour progression.

Updating the diagnostic criteria of COVID-19 "suspected case" and "confirmed case" is necessary.

On 6 February 2020, our team had published a rapid advice guideline for diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infection, and this guideline provided our experience and make well reference for fighting against this pandemic worldwide. However, the coronavirus disease 2019 (COVID-19) is a new disease, our awareness and knowledge are gradually increasing based on the ongoing research findings and clinical practice experience; hence, the strategies of diagnosis and treatment are also continually updated. In this letter, we answered one comment on our guideline and provided the newest diagnostic criteria of "suspected case" and "confirmed case" according to the latest Diagnosis and Treatment Guidelines for COVID-19 (seventh version) that issued by the National Health Committee of the People's Republic of China.

A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version).

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

Nomogram for predicting the survival of gastric adenocarcinoma patients who receive surgery and chemotherapy.

BACKGROUND: Surgery is the only way to cure gastric adenocarcinoma (GAC), and chemotherapy is the basic adjuvant management for GAC. A significant prognostic nomogram for predicting the respective disease-specific survival (DSS) rates of GAC patients who receive surgery and chemotherapy has not been established. OBJECTIVE: We were planning to establish a survival nomogram model for GAC patients who receive surgery and chemotherapy. METHODS: We identified 5764 GAC patients who had received surgery and chemotherapy from the record of Surveillance, Epidemiology, and End Results (SEER) database. About 70% (n = 4034) of the chosen GAC patients were randomly assigned to the training set, and the rest of the included ones (n = 1729) were assigned to the external validation set. A prognostic nomogram was constructed by the training set and the predictive accuracy of it was validated by the validation set. RESULTS: Based on the outcome of a multivariate analysis of candidate factors, a nomogram was developed that encompassed age at diagnosis, number of regional lymph nodes examined after surgery, number of positive regional lymph nodes, sex, race, grade, derived AJCC stage, summary stage, and radiotherapy status. The C-index (Harrell's concordance index) of the nomogram model was some larger than that of the traditional seventh AJCC staging system (0.707 vs 0.661). Calibration plots of the constructed nomogram displayed that the probability of DSS commendably accord with the survival rate. Integrated discrimination improvement (IDI) revealed obvious increase and categorical net reclassification improvement (NRI) showed visible enhancement. IDI for 3-, 5- and 10- year DSS were 0.058, 0.059 and 0.058, respectively (P > 0.05), and NRI for 3-, 5- and 10- year DSS were 0.380 (95% CI = 0.316-0.470), 0.407 (95% CI = 0.350-0.505), and 0.413 (95% CI = 0.336-0.519), respectively. Decision curve analysis (DCA) proved that the constructed nomogram was preferable to the AJCC staging system. CONCLUSION: The constructed nomogram supplies more credible DSS predictions for GAC patients who receive surgery and chemotherapy in the general population. According to validation, the new nomogram will be beneficial in facilitating individualized survival predictions and useful when performing clinical decision-making for GAC patients who receive surgery and chemotherapy.

Identification of key genes for predicting colorectal cancer prognosis by integrated bioinformatics analysis.

Colorectal cancer (CRC) is a life-threatening disease with a poor prognosis. Therefore, it is crucial to identify molecular prognostic biomarkers for CRC. The present study aimed to identify potential key genes that could be used to predict the prognosis of patients with CRC. Three CRC microarray datasets (GSE20916, GSE73360 and GSE44861) were downloaded from the Gene Expression Omnibus (GEO) database, and one dataset was obtained from The Cancer Genome Atlas (TCGA) database. The three GEO datasets were analyzed to detect differentially expressed genes (DEGs) using the BRB-ArrayTools software. Functional and pathway enrichment analyses of these DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery tool. A protein-protein interaction (PPI) network of DEGs was constructed, hub genes were extracted, and modules of the PPI network were analyzed. To investigate the prognostic values of the hub genes in CRC, data from the CRC datasets of TCGA were used to perform the survival analyses based on the sample splitting method and Cox regression model. Correlation among the hub genes was evaluated using Spearman's correlation analysis. In the three GEO datasets, a total of 105 common DEGs were identified, including 51 down- and 54 up-regulated genes in CRC compared with normal colorectal tissues. A PPI network consisting of 100 DEGs and 551 edges was constructed, and 44 nodes were identified as hub genes. Among these 44 genes, the four hub genes TIMP metallopeptidase inhibitor 1 (TIMP1), solute carrier family 4 member 4 (SLC4A4), aldo-keto reductase family 1 member B10 (AKR1B10) and ATP binding cassette subfamily E member 1 (ABCE1) were associated with overall survival (OS) in patients with CRC. Three significant modules were extracted from the PPI network. The hub gene TIMP1 was present in Module 1, ABCE1 was involved in Module 2 and SLC4A4 was identified in Module 3. Univariate analysis revealed that TIMP1, SLC4A4, AKR1B10 and ABCE1 were associated with the OS of patients with CRC. Multivariate analysis demonstrated that SLC4A4 may be an independent prognostic factor associated with OS. Furthermore, the results from correlation analysis revealed that there was no correlation between TIMP1, SLC4A4 and ABCE1, whereas AKR1B10 was positively correlated with SLC4A4. In conclusion, the four key genes TIMP1, SLC4A4, AKR1B10 and ABCE1 associated with the OS of patients with CRC were identified by integrated bioinformatics analysis. These key genes may be used as prognostic biomarkers to predict the survival of patients with CRC, and may therefore represent novel therapeutic targets for CRC.

Insurance status is related to overall survival in patients with small intestine adenocarcinoma: A population-based study.

BACKGROUND: Our goal was to investigate the effect of insurance status on the overall survival (OS) in cases of small intestine adenocarcinoma. METHODS: The SEER (Surveillance, Epidemiology, and End Results) database was used to identify 3822 patients who were diagnosed with small intestine adenocarcinoma between 2007 and 2015. The proportional hazard ASSUMPTION was evaluated by proportional-hazards assumption test and Schoenfeld residual test. The Kaplan-Meier method and Cox proportional-hazards regression analysis were performed to evaluate the association between insurance status and OS. RESULTS: We found that the insurance status at the time of diagnosis affected OS at the population level, both in those aged <65 and ≥65 years. Cox multivariate analysis of patients aged <65 years revealed that the hazard of death was greater in the Medicaid group (hazard ratio [HR] = 1.641, 95% confidence interval [CI] = 1.299-2.073, P < 0.001] and uninsured group (HR = 1.472, 95% CI = 1.095-1.979, P = 0.010) compared with the insured group, while the OS did not differ significantly between the Medicaid and uninsured groups. Similarly, the hazard of death among patients aged ≥65 years was higher in the Medicaid than the insured group (HR = 1.403, 95% CI = 1.136-1.733, P = 0.002). CONCLUSION: Our results suggest that patients with small intestine adenocarcinoma with insurance coverage have a significantly better OS than patients who have Medicaid or are uninsured, while the OS does not differ between Medicaid and uninsured patients.

Nomograms for predicting long-term overall survival and cancer-specific survival in patients with primary urethral carcinoma: a population-based study.

BACKGROUND: Our aim was to identify the independent prognostic factors in patients with primary urethral carcinoma (PUC) and to predict their overall survival (OS) and cancer-specific survival (CSS) at 3, 5, and 8 years. METHODS: Patients with PUC identified in the Surveillance, Epidemiology, and End Results (SEER) database were divided into training and validation cohorts. Nomograms were constructed based on the results of Cox regression analysis. The predictive performance of each nomogram was evaluated using the consistency index (C-index), the area under the receiver operating characteristics curve (AUC), and calibration plots. Decision-curve analysis (DCA) was used to test the clinical value of the predictive models. RESULTS: Our study screened 822 patients with PUC. Multivariate analysis showed that the age at diagnosis, race, histology, American Joint Committee on Cancer (AJCC) stage, and surgery status were independent prognostic factors for CSS and age at diagnosis, race, histology, AJCC stage, surgery status, and chemotherapy for OS (all P < 0.05). We used these prognostic factors to construct nomograms. The C-indexes for OS and CSS were 0.713 and 0.741 in training cohorts and 0.714 and 0.738 in validation cohorts, respectively. The AUC and calibration plots demonstrated the good performance of both nomograms. The DCA indicated the presence of clinical net benefits in both the training and validation cohorts. CONCLUSION: We developed and validated nomograms for predicting OS and CSS in patients with PUC, which can help clinicians make treatment decisions.

Downregulation of Wnt3 Suppresses Colorectal Cancer Development Through Inhibiting Cell Proliferation and Migration.

The aberrant expression of Wnt3 has linked to several types of human malignancies. However, it is not known for its role in tumorigenesis of colorectal cancer (CRC). Herein, we show that Wnt3 is upregulated in human CRC tissues and is essential for the CRC progression. Knockdown of Wnt3 in human CRC cells delayed tumor formation in nude mouse xenografts through silencing of canonical Wnt pathway and glycolysis. We further found that silencing of Wnt3 enhanced the sensitivity of CRC cells to cisplatin through inducing apoptotic cell death. Taken together, it demonstrates that Wnt3 is a novel clinical biomarker for the detection of CRC and plays an important role in colorectal tumorigenesis. Therefore, downregulation of Wnt3 will be a valuable strategy in CRC treatment.

Effect of marital status on duodenal adenocarcinoma survival: A Surveillance Epidemiology and End Results population analysis.

Numerous studies have shown that marital status may be a prognostic factor in various malignancies, but little is known about its effect on duodenal adenocarcinoma. The aim of the present study was to determine the association between marital status and survival in patients with duodenal adenocarcinoma. The Surveillance, Epidemiology and End Results database was utilized to analyze 2,018 patients who had been diagnosed with duodenal adenocarcinoma between January 2004 and December 2015. Kaplan-Meier and Cox regression analyses were also used to determine the impact of marital status on overall survival (OS) and cause-specific survival (CSS). The 5-year OS rate was higher in married patients (32.6%) compared with unmarried (26.8%) patients (P<0.001), as was the 5-year CSS rate (38.8 vs. 33.7%; P<0.001). Multivariate analysis demonstrated that marital status was an independent prognostic factor for duodenal adenocarcinoma, with married patients having improved OS (P<0.001) and CSS (P=0.001) compared with unmarried patients. Subgroup analysis showed that marital status played a role in the survival of patients at American Joint Committee on Cancer Tumor-Node-Metastasis stage I, but not of patients at stages II, III or IV. The survival outcomes for duodenal adenocarcinoma are improved in married patients compared with those in unmarried patients. Therefore, attention should be paid to the impact of social factors and socio-economic factors on unmarried patients, in order to improve their survival outcomes.

Serotonin Transporter (5-HTT) Gene Polymorphisms and Susceptibility to Chronic Periodontitis: A Case-Control Study.

Objective: The current study is aimed at exploring the relationship between chronic periodontitis and serotonin transporter (5-HTT) gene polymorphisms (rs6354 and rs12449783) in the Chinese Han population. Methods: This study included a total of 120 patients with chronic periodontitis and 125 healthy control subjects. The 5-HTT gene (rs6354 and rs12449783) was genotyped using oral mucosal tissue with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Linkage disequilibrium was examined using Haploview. Genotype and allele frequencies were compared between the cases and controls using a χ2 test. Results: Genotype distribution of the 5-HTT gene polymorphisms rs6354 and rs12449783 in the control group conformed to Hardy-Weinberg equilibrium. The frequency of the AC genotype, the AC + CC genotype and C allele of the 5-HTT rs6354 polymorphism was higher in cases (P < 0.05) vs. the healthy control. The adjusted odds ratio (OR) was 1.910 (95%CI = 1.049-3.476) for the AC genotype, 2.026 (95%CI = 1.115-3.680) for the AC+CC genotype, and 1.875 for the C allele (95%CI = 1.089-3.228. Such an association was particularly strong in women for the AC genotype (OR = 2.167, 95%CI = 1.034-4.542). The genotype and allele frequencies of rs12449783 did not differ between the cases and controls. Haplotype C-C (rs6354-rs12449783) was also more frequent in the cases (OR = 2.372, 95%CI = 1.154-4.875, P = 0.016). Conclusion: Chronic periodontitis is associated with the 5-HTT gene rs6354 polymorphism, as well as rs6354/rs12449783 interaction.

ZNF281 Regulates Cell Proliferation, Migration and Invasion in Colorectal Cancer through Wnt/ß-Catenin Signaling.

BACKGROUND/AIMS: Zinc Finger Protein 281 (ZNF281) was recently identified as a novel oncogene in several human carcinomas. However, the clinical significance of ZNF281 in colorectal cancer (CRC) and the molecular mechanisms by which ZNF281 promotes the growth and metastasis of CRC remain unknown. METHODS: ZNF281 expression in CRC tissues was assessed, and the outcomes were analyzed to determine the clinical importance of ZNF281 expression. Cell Transwell assays and a wound healing assay were performed to assess the effects of ZNF281 on CRC cell migration and invasion in vitro. Western blotting was applied to analyze the potential mechanisms. RESULTS: ZNF281 mRNA and protein levels were significantly increased in CRC tissues compared with normal colon tissues, and high ZNF281 expression was associated with advanced T stage, N stage, TNM stage and differentiation. Therefore, ZNF281 expression might be an independent prognostic indicator in CRC patients. Moreover, knockdown of ZNF281 expression suppressed cell proliferation, migration and invasion by inhibiting the Wnt/ß-catenin pathway. CONCLUSION: Our study indicates that ZNF281 plays a critical role in the progression and metastasis of CRC and could represent a potential therapeutic target for CRC.