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WHAT IS KNOWN AND OBJECTIVE: Although superseded by other antiviral agents in many Western countries, vidarabine is still widely used in some countries, including China; hence, the extent and appropriateness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.
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Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Antivirais/efeitos adversos , Prescrição Inadequada/estatística & dados numéricos , Vidarabina/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Antivirais/administração & dosagem , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Uso Off-Label/normas , Vidarabina/administração & dosagem , Adulto JovemRESUMO
PURPOSE: Although a series of serious adverse events have continually raised concerns about the potential toxicity of traditional Chinese medicine injections (TCM injections), studies on this subject are still sparse. We conducted a descriptive analysis of a spontaneous reporting system in China to describe the safety profile of TCM injections. METHODS: The safety profile of TCM injections is described by descriptive analysis of 559 066 adverse reports collected from Guangdong Provincial Center for adverse drug reaction (ADR) Monitoring in China during 2003 to 2017. RESULTS: The percentage of new or serious ADRs of TCM injections is much higher than average percentage of China's spontaneous reporting system (SRS) as a whole (48.70% vs <25%). Compared with conventional injections, TCM injections have a slightly lower percentage of serious ADRs (6.02% vs 6.72%) and much higher percentage of unknown (new) ADRs (46.74% vs 24.13%). The gender and age distribution for TCM injections are similar to conventional injections. The reporting rates of ADRs increased with age. Anaphylactic shock and anaphylactoid reaction are high-risk ADRs for TCM injections and, anaphylactic shock is ranked number 1 in causing deaths (50.00%). CONCLUSIONS: There are some differences and similarities on the safety profile between TCM injections and conventional injections. TCM injections have higher risk of adverse effects than any other dosage forms of TCM medications and higher percentage of new or serious adverse effects than conventional injections. A lot of work need to be done to clarify the huge amount of potential unknown adverse effects related to TCM injections.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Medicamentos de Ervas Chinesas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anafilaxia/induzido quimicamente , Anafilaxia/epidemiologia , China/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Injeções , Masculino , Medicina Tradicional Chinesa/efeitos adversos , Pessoa de Meia-Idade , Farmacoepidemiologia , Adulto JovemRESUMO
BACKGROUND: The effectiveness of active pharmacovigilance depends on the specific methods adopted and the work patterns put into place. Over the past few years, much attention has been paid to the importance of implementing such systems in China. However, less has been done to evaluate the state of implementation and future needs of such systems. METHODS: This paper reviews China's recent approaches to active pharmacovigilance by examining: (1) information collected from scientific articles and the websites of the China Food and Drug Administration and the China National Center for Adverse Drug Reaction Monitoring, (2) information available on China's spontaneous reporting systems (SRS) and active pharmacovigilance system, and (3) annual reports and internal reports on this subject. RESULTS: Areas that improved most meaningfully for China's active pharmacovigilance in recent years appear to include: (1) quicker reporting and more intelligent scanning methods for adverse drug reactions (ADRs), (2) the use of pharmacovigilance approaches to mine electronic hospital records, and (3) the development of integrated systems including the China Hospital Pharmacovigilance System and China Sentinel Hospital Alliance Program. CONCLUSION: Not only has the national online SRS system provided a platform for passive pharmacovigilance, it has also become an important platform for various explorations of active pharmacovigilance in China. Quick reporting and intelligent scanning of ADRs, facilitated by automated ADR detection based on electronic hospital records, have accelerated to capabilities for active pharmacovigilance. The outcomes of the programs, such as the China Hospital Pharmacovigilance System and China Sentinel Hospital Alliance Program, usher in a new era for China's active pharmacovigilance. These are particularly important to bridge the information system of sentinel hospitals and ADR research centers, but gaps remain. Thus, much work needs to be done before a high-level active pharmacovigilance system is sufficiently mature to ensure drug safety in the country.
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Sistemas de Notificação de Reações Adversas a Medicamentos , Farmacovigilância , China , Sistemas de Informação Hospitalar , HumanosRESUMO
PURPOSE: The study aims to quantify anaphylaxis signal for combined exposure of benzylpenicilin and qingkailing injection (QI) compared with individual exposure of the two drugs and the background risk based on all other exposures in SRS database. METHODS: Data used in this study were collected during 2003-2014 from China Guangdong Provincial Center of ADR Monitoring. We studied the suspected ADR reports using a case/non-case design. The cases were defined as the reactions coded by WHO-preferred terms of anaphylactic shock or anaphylactoid reaction. Reporting odds ratios (RORs) were used as a measure of disproportionality and were adjusted for age and gender to reduce confounding effects. An observed-to-expected ratio Ω was also used for interaction detection. RESULTS: The crude RORs (95 % CIs) for anaphylaxis in patients who used only benzylpenicillin or QI and those who used the two drugs concomitantly compared with patients who used neither of the two drugs were 2.50 (2.34-2.68), 1.59 (1.46-1.73), and 6.22 (3.34-11.58), respectively. The adjusted RORs (95 % CIs) were 2.48 (2.31-2.65), 1.54 (1.41-1.67), and 6.01 (3.22-11.20), respectively, after being adjusted for age and gender. The measured Ω, Ω0, Ω025, and Ω975 was 1.03, 1.09, 0.14, and 1.71, respectively. CONCLUSIONS: Case reports in the database are suggestive of a safety signal which indicates that an interaction between benzylpenicillin and QI resulting in excess risk of anaphylaxis may occur. SRS databases have a potential for signaling unknown drug-herbal interactions. More effort is needed to expand this potential.
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Sistemas de Notificação de Reações Adversas a Medicamentos , Bases de Dados Factuais , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Interações Ervas-Drogas , Penicilina G/administração & dosagem , Penicilina G/efeitos adversos , Adolescente , Adulto , Idoso , Anafilaxia/induzido quimicamente , Antibacterianos/efeitos adversos , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Injeções , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Clinical indexes are often selected as relevant factors for constructing prognostic models of tongue squamous cell carcinoma (TSCC) patients, while factors related to therapeutic targets are less frequently included. As Apigenin (API) shows anti-tumor properties in many tumors, in this study, we construct a novel prognostic model for TSCC patients based on Apigenin-associated genes through transcriptomic analysis. METHODS: The effect of Apigenin (API) on the cell characteristics of TSCC cells was measured by several phenotype experiments. RNA-seq was executed to ensure differentially expressed genes (DEGs) in squamous cell carcinoma-9 (SCC-9) cells after API treatment. Furthermore, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed to verify the expression of API-related genes. Then, combined with the gene expression data and relevant individual information of TSCC samples acquired from The Cancer Genome Atlas (TCGA), an API-related model was built through Lasso regression and multivariate Cox regression. A receiver operating characteristic (ROC) curve and a nomogram and calibration curve were created to forecast patient outcomes to improve the clinical suitability of the API-related signature. The relationships between the two risk groups and function enrichment, immune infiltration characteristics, and drug susceptibility were analyzed. RESULTS: We demonstrated that API could inhibit the malignant behavior of TSCC cells. Among API-related genes, TSCC cells treated with API, compared to the control group, have higher levels of transmembrane protein 213 (TMEM213) and G protein-coupled receptor 158 (GPR158), and lower levels of caspase 14 (CASP14) and integrin subunit alpha 5 (ITGA5). An 7 API-associated gene model was built through Lasso regression and multivariate Cox regression that could direct TSCC prognostic status and tumor immune cell infiltration. In addition, we acquired 6 potential therapeutic agents for TSCC based on the prognostic model. CONCLUSIONS: Our research suggested the inhibition effect of API on TSCC cells and provided a novel prognostic model combined with therapeutic factors that can guide the prognosis of TSCC and clinical decision-making in TSCC.
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Carcinoma de Células Escamosas , Neoplasias da Língua , Humanos , Neoplasias da Língua/tratamento farmacológico , Neoplasias da Língua/genética , Neoplasias da Língua/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Apigenina/farmacologia , Apigenina/metabolismo , Prognóstico , Língua/metabolismo , Língua/patologiaRESUMO
Background: TP53 mutation is a poor factor for non-small cell lung cancer (NSCLC), while the effect of TP53 on prognosis in epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma (LUAD) with brain metastasis remains elusive and needs further exploration. Methods: We retrospectively analyzed 236 patients and tested for TP53- and EGFR-mutant status in metastasis LUAD patients who had received first-line EGFR-tyrosine kinase inhibitor (TKI) treatment. Survival rates were calculated by the Kaplan-Meier method. Furthermore, univariate and multivariate Cox analyses were performed to identify the independent prognostic factors. Results: There were 114 patients with confirmed non-brain metastasis (NBM), 74 patients with preliminary diagnosis early brain metastasis (EBM), and 48 patients with late brain metastasis (LBM). TP53 and EGFR co-mutations were found in 35/236 patients (14.8%). The median progression-free survival (PFS) and overall survival (OS) in the EGFR mutation and TP53 wild-type group were significantly longer than those in the EGFR and TP53 co-mutation group in all advanced LUAD or NBM. Concurrently, PFS and OS were found to be not significant in EBM and LBM patients. Subgroup analysis revealed longer median PFS and OS in the TP53 wild-type group compared to the TP53 mutant group in L858R patients and not significant in EGFR Exon 19 deletion patients. In LBM patients, the time to brain metastasis in the EGFR mutation and TP53 wild-type group was longer than that in the EGFR and TP53 co-mutation group, and TP53 mutant status was an independent prognostic factor for brain metastasis. The TP53 wild-type group exhibited a higher objective remission rate (ORR) and disease control rate (DCR) than the TP53 mutant group in NBM, EBM, and LBM patients, irrespective of primary lung and brain metastatic lesions. Conclusion: TP53/EGFR co-mutation patients receiving first-line EGFR-TKI treatment had poor prognoses in advanced LUAD, especially with L858R mutation. Moreover, TP53/EGFR co-mutation patients treated with EGFR-TKIs may more easy developed intracranial metastasis.
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Sistemas de Notificação de Reações Adversas a Medicamentos , Antibacterianos , Clindamicina/análogos & derivados , Administração Oral , Adolescente , Adulto , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Clindamicina/administração & dosagem , Clindamicina/efeitos adversos , Clindamicina/uso terapêutico , Feminino , Hematúria/induzido quimicamente , Humanos , Lactente , Recém-Nascido , Injeções Intramusculares , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Background: Lung squamous cell carcinoma (LUSC) has poor survival prognosis and few clinical treatment options. We urgently need to explore new therapeutic drugs in clinical practice. Cepharanthine (CEP) has been shown to have anticancer effects in several tumors, but the mechanism of CEP in treating LUSC has not been reported. Methods: SwissTargetPrediction, PharmMapper, and GeneCards were used to identify targets of CEP and LUSC. Further topological analysis was used to obtain hub genes via Cytoscape. Molecular docking was carried out to verify the combination of CEP with hub targets. Based on bioinformatics, we first analyzed the expression and survival of hub targets in LUSC and further analyzed the correlation between hub targets and cancer stemness, immune cell infiltration, and tumor mutation burden (TMB). Results: A total of 41 targets were identified. Further topological analysis identified 6 hub genes: AURKA, CCNA2, CCNE1, CDK1, CHEK1, and PLK1. Molecular docking analysis showed that CEP had stable binding to all these 6 target proteins. In-depth bioinformatics analysis of these 6 targets showed that high expression of these targets were positively correlated with cancer stemness index and negatively correlated with tumor infiltrating immune cells. In immune subtype analysis, the expressions of these targets were significantly decreased in inflammatory tumors. In addition, we also found that the expressions of these targets were positively correlated with TMB. Conclusion: Based on multidisciplinary analysis, we preliminarily identified potential targets of CEP for LUSC treatment and suggested that CEP may play a role in regulating LUSC stemness.
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Carcinoma de Células Escamosas , Farmacologia em Rede , Humanos , Simulação de Acoplamento Molecular , Biologia Computacional , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , PulmãoRESUMO
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.
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Natural products have been widely considered as an important resource for new drugs or lead compounds. Sinomenine (SIN) and its derivatives exert antitumor activity via regulation of inflammatory mediators. For these reasons we synthesized three series of SIN derivatives (compounds 4 a-i, 7 a-c and 11 a-c) as antitumor agents from this natural product. All compounds were prepared by modification at the C1 and C4 positions of the A ring, the C4 position of the A ring, and the C6 and C7 positions of the C ring, respectively. All the derivatives were subjected to inâ vitro antitumor activity against HeLa, A549, HepG-2, MCF-7 and HT-29â cell lines. To observe the apoptotic induction of SIN derivatives and its mechanism, fluorescent staining and western blot assays were carried out for active compound against MCF-7. Based on the screening results, most of the SIN derivatives showed better antitumor activity than SIN. Some of them were found to possess broad-spectrum antitumor activity. Most notably, 11 c exhibited obvious antitumor activity in both cell lines with IC50 values less than 11â µM. Besides, 11 c induced apoptosis of MCF-7 in a dose-dependent manner. Western blot assay demonstrated that 11 c inhibited IL-6-mediated activation of PI3K/Akt pathway. A docking study revealed that 11 c had stronger binding interaction with the residues of IL-6 than SIN. All these results indicate that 11 c may be a potential anti-breast cancer agent by directly targeting IL-6.
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Antineoplásicos , Fosfatidilinositol 3-Quinases , Antineoplásicos/química , Apoptose , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Interleucina-6 , Células MCF-7 , Estrutura Molecular , Morfinanos , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Relação Estrutura-AtividadeRESUMO
The GTP-binding protein Di-Ras3 (DIRAS3) has been established as a maternally imprinted tumor suppressor gene. Growing evidence has correlated the DIRAS3 gene with tumor progression, but its role in non-small cell lung cancer (NSCLC) is rarely reported. Accordingly, the current study sought to evaluate the role and mechanism of DIRAS3 in NSCLC cell progression. First, we uncovered that DIRAS3 was poorly expressed in NSCLC tissues and cells. Subsequently, we examined the effect of DIRAS3 over-expression or knockdown in different lung cancer cells on their malignant phenotypes, with the help of transwell cell migration and invasion assays, and Western blot analyses. It was found that the over-expression of DIRAS3 inhibited the migration and invasion of A549 cells or H520 cells, whereas knockdown of DIRAS3 led to opposing trends. In addition, over-expression of DIRAS3 attenuated the tumor growth and reduced the number of lung tumor nodules. Mechanistically, DIRAS3 may inhibit the migration and invasion of NSCLC cells by inhibiting the RAS/extracellular-regulated kinase (ERK) signaling pathway. Collectively, our findings indicate that DIRAS3 could serve as a potential therapeutic target biomarker for NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Células A549 , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Humanos , Neoplasias Pulmonares/patologia , Sistema de Sinalização das MAP Quinases/genéticaRESUMO
Background: Compelling evidence indicates that elevated peripheral serum lymphocytes are associated with a favorable prognosis in various cancers. However, the association between serum lymphocytes and glioma is contradictory. In this study, a nomogram was established to predict the diagnosis of glioma-grading through Ki-67 expression and serum lymphocytes. Methods: We performed a retrospective analysis of 239 patients diagnosed with LGG and 178 patients with HGG. Immunohistochemistry was used to determine the Ki-67 expression. Following multivariate logistic regression analysis, a nomogram was established and used to identify the most related factors associated with HGG. The consistency index (C-index), decision curve analysis (DCA), and a calibration curve were used to validate the model. Results: The number of LGG patients with more IDH1/2 mutations and 1p19q co-deletion was greater than that of HGG patients. The multivariate logistic analysis identified Ki-67 expression, serum lymphocyte count, and serum albumin (ALU) as independent risk factors associated with HGG, and these factors were included in a nomogram in the training cohort. In the validation cohort, the nomogram demonstrated good calibration and high consistency (C-index = 0.794). The Spearman correlation analysis revealed a significant association between HGG and serum lymphocyte count (r = -0.238, P <0.001), ALU (r = -0.232, P <0.001), and Ki-67 expression (r = 0.457, P <0.001). Furthermore, the Ki-67 expression was negatively correlated with the serum lymphocyte count (r = -0.244, P <0.05). LGG patients had lower Ki-67 expression and higher serum lymphocytes compared with HGG patients, and a combination of these two variables was significantly higher in HGG patients. Conclusion: The constructed nomogram is capable of predicting the diagnosis of glioma-grade. A decrease in the level of serum lymphocyte count and increased Ki-67 expression in HGG patients indicate that their immunological function is diminished and the tumor is more aggressive.
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BACKGROUND: The safety assessment of ulinastatin can guide clinical practice. The present study aimed to investigate the real-world safety of ulinastatin in China. METHODS: This multicenter study retrospectively analyzed the post-marketing surveillance data of consecutive patients treated with ulinastatin between August 2014 and June 2017 in the general wards and the intensive care units (ICU) of nine hospitals in China. Adverse drug reactions/adverse drug events (ADRs/ADEs) were collected and evaluated in a post-marketing database. RESULTS: A total of 11,252 consecutive patients were included in the study: 7009 ICU patients and 4243 general ward patients. Eleven patients with ADRs/ADEs were observed, including nine ICU patients and two general ward patients. The clinical manifestations were liver dysfunction (n = 5 ICU cases, n = 1 general case), thrombocytopenia (n = 2 ICU cases, n = 1 general case), leukopenia (n = 1 ICU case), and rash (n = 1 ICU case). During the study period, the drug ADR/ADE rate of ulinastatin injection was 0.98 (11/11,252 × 1000). Among the 11,252 valid patients, only 327 received ulinastatin in accordance with the drug specifications. After excluding unreasonable drug use, the calculated ADR rate was 3.06 (1/327 × 1000) (95% confidence interval: 0.0-17.1). In ICU and general ward patients, the use of other drugs combined with ulinastatin was associated with the occurrence of ADRs/ADEs (100% with ADRs/ADEs vs. 0% in controls, P < 0.001). CONCLUSIONS: The incidence of ADRs/ADEs of ulinastatin is < 5. The ADRs/ADEs involved limited organs, mainly the skin, gastrointestinal tract, and blood. In most cases, the ADRs/ADEs gradually alleviated or recovered after drug withdrawal. The inappropriate/off-label use of ulinastatin should be the focus of surveillance.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , China/epidemiologia , Glicoproteínas , Humanos , Marketing , Vigilância de Produtos Comercializados , Estudos RetrospectivosRESUMO
Hepatocellular carcinoma (HCC) is one of the common cancers with a high incidence and mortality. The human replication factor C (RFC) family contains 5 subunits that play an important role in DNA replication and DNA damage repair. RFCs are abnormally expressed in a variety of cancers; some of them are differentially expressed in HCC tissues and related to tumor growth. However, the expression, prognostic value, and effect targets of the whole RFC family in HCC are still unclear. To address these issues, we performed a multidimensional analysis of RFCs in HCC patients by Oncomine, UALCAN, GEPIA, Human protein atlas, Kaplan-Meier plotter, cBioPortal, GeneMANIA, String, and LinkedOmics. mRNA expression of RFCs was significantly increased in HCC tissues. There was a significant correlation between the expression of RFC2/3/4/5 and tumor stage of HCC patients. Besides, high mRNA expression of RFC2/4 was associated with worse overall survival (OS). Moreover, genetic alterations of RFCs were associated with worse OS in HCC patients. We found that genes co-expressed with RFC2/4 were mainly involved in biological processes, such as chromosome segregation, mitotic cell cycle phase transition, and telomere organization and they activated the cell cycle and spliceosome pathways. The gene set is mainly enriched in cancer-related kinases AURKA, ATR, CDK1, PLK1, and CHEK1. E2F family members were the key transcription factors for RFCs. Our results suggest that differentially expressed RFC2 and RFC4 are potential prognostic biomarkers in HCC and may act on E2F transcription factors and some kinase targets to dysregulate the cell cycle pathway. These efforts may provide new research directions for prognostic biomarkers and therapeutic targets in HCC.
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BACKGROUND: This meta-analysis evaluates the difference of sparing organs at risk (OAR) in different position (Prone position and Supine position) with different breathing patterns (Free breathing, FB/Deep inspiration breath hold, DIBH) for breast cancer patients receiving postoperative radiotherapy and provides a useful reference for clinical practice. METHOD: The relevant controlled trials of prone position versus supine position in postoperative radiotherapy for breast cancer were retrieved from the sources of PubMed, Cochrane Library, Embase, Web of Science and ClinicalTrails.gov. The principal outcome of interest was OAR doses (heart dose, left anterior descending coronary artery dose and ipsilateral lung dose) and target coverage. We mainly compared the effects of P-FB (Prone position FB) and S-FB (Supine position FB) and discussed the effects of DIBH combined with different positions on OAR dose in postoperative radiotherapy. We calculated summary standardized mean difference (SMD) and 95% confidence intervals (CI). The meta-analysis was performed using RevMan 5.4 software. RESULTS: The analysis included 751 patients from 19 observational studies. Compared with the S-FB, the P-FB can have lower heart dose, left anterior descending coronary artery (LADCA) dose, and ipsilateral lung dose (ILL) more effectively, and the difference was statistically significant (heart dose, SMDâ=â- 0.51, 95% CI - 0.66 â¼ - 0.36, Pâ<â.00001. LADCA dose, SMDâ=â- 0.58, 95% CI - 0.85 â¼ - 0.31, Pâ<â.0001. ILL dose, SMDâ=â- 2.84, 95% CI - 3.2 â¼ - 2.48, Pâ<â.00001). And there was no significant difference in target coverage between the S-FB and P-FB groups (SMDâ=â- 0.1, 95% CI - 0.57 â¼ 0.36, Pâ=â.66). Moreover, through descriptive analysis, we found that P-DIBH (Prone position DIBH) has better sparing OAR than P-FB and S-DIBH (Supine position DIBH). CONCLUSION: By this meta-analysis, compared with the S-FB we found that implementation of P-FB in postoperative radiotherapy for breast cancer can reduce irradiation of heart dose, LADCA dose and ILL dose, without compromising mean dose of target coverage. Moreover, P-DIBH might become the most promising way for breast cancer patients to undergo radiotherapy.
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Neoplasias da Mama/terapia , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco/efeitos da radiação , Posicionamento do Paciente/métodos , Lesões por Radiação/prevenção & controle , Vasos Coronários/efeitos da radiação , Feminino , Coração/efeitos da radiação , Humanos , Pulmão/efeitos da radiação , Mastectomia , Decúbito Ventral , Lesões por Radiação/etiologia , Radiometria/estatística & dados numéricos , Dosagem Radioterapêutica , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Decúbito DorsalRESUMO
OBJECTIVE: To establish a web-based quantitative signal detection system for adverse drug reactions (ADRs) based on spontaneous reporting to the Guangdong province drug-monitoring database in China. METHODS: Using Microsoft Visual Basic and Active Server Pages programming languages and SQL Server 2000, a web-based system with three software modules was programmed to perform data preparation and association detection, and to generate reports. Information component (IC), the internationally recognized measure of disproportionality for quantitative signal detection, was integrated into the system, and its capacity for signal detection was tested with ADR reports collected from 1 January 2002 to 30 June 2007 in Guangdong. RESULTS: A total of 2,496 associations including known signals were mined from the test database. Signals (e.g., cefradine-induced hematuria) were found early by using the IC analysis. In addition, 291 drug-ADR associations were alerted for the first time in the second quarter of 2007. CONCLUSIONS: The system can be used for the detection of significant associations from the Guangdong drug-monitoring database and could be an extremely useful adjunct to the expert assessment of very large numbers of spontaneously reported ADRs for the first time in China.
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Sistemas de Notificação de Reações Adversas a Medicamentos , Bases de Dados Factuais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Internet , Redes Neurais de Computação , China , Feminino , Humanos , Masculino , Sistemas Computadorizados de Registros Médicos , Processamento de Sinais Assistido por Computador , Design de SoftwareRESUMO
PURPOSE: To examine the concordance of various measures to Bayesian Confidence Propagation Neural Network (BCPNN) measure used by the WHO Collaborating Centre for International Drug Monitoring based on the database of Guangdong province in China. METHODS: The Reporting Odds Ratio (ROR)--1.96 standard errors (SE), Proportional Reporting Ratio (PRR)--21.96 SE, combination chi (2)-PRR measure used by the Medicines and Healthcare Products Regulatory Agency (MHRA) were compared with the IC--2 standard deviations (SDs) with the tested database collected from 1 January 2002 to 30 June 2007 in Guangdong. Additionally, the concordance of the various measures, in respect to the number of reports per combination, was examined. RESULTS: Sensitivity, specificity, positive predictive value and negative predictive value were high in respect to the BCPNN measure when a combination of point and interval estimate was used based on four types of signal detection for the ROR and PRR measures, and the four evaluation indexes increased when A (the number of reports per combination) increased. However the MHRA measure had decreasing sensitivity and increasing specificity with A increasing. CONCLUSIONS: The ROR, PRR and BCPNN measures used are broadly comparable when three or more cases per combination have been collected. The MHRA measure is comparable to the BCPNN when seven or less case per combination have been collected for 'drug-ADR', 'drug category-ADR', 'drug-ADR category' combinations based on the Guangdong database, and the MHRA is unsuitable for detecting signals from 'drug category-ADR category' combinations based on the Guangdong database because of its low sensitivity.
Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Redes Neurais de Computação , Teorema de Bayes , China , Bases de Dados Factuais , Humanos , Sistemas Computadorizados de Registros Médicos , Razão de Chances , Organização Mundial da SaúdeRESUMO
BACKGROUND: Suicidal ideation and attempts are still currently serious problems among adolescents worldwide, and there is evidence that sleep problem may be associated with increased rates of mental disorder. This study aimed to examine the associations between sleep duration and suicidal ideation and attempts among adolescents and to test whether depressive symptoms have moderating effects on the associations. METHODS: A 3-stage, stratified cluster, random sampling method was used to collect data from 20,130 high school students in southeast China. RESULTS: The weighted prevalence of short sleep among Chinese adolescents was 5.6% (95% CI, 5.3-6.0%), and the weighted prevalence of long sleep was 2.7% (95% CI, 2.5-3.0%). The final results demonstrated that short sleep was positively associated with suicidal ideation (AOR=2.28, 95% CI=1.96-2.66) and suicidal attempts (AOR=3.20, 95% CI=2.46-4.16), and long sleep was only significantly associated with suicidal attempts (AOR=2.47, 95% CI=1.70-3.58). Stratification analyses conducted separately for students with and without depressive symptoms demonstrated that depressive symptoms may have moderating effects on the associations between sleep duration and suicidality. LIMITATIONS: Our study sample only included school students, and causal inference could not be examined due to the cross-sectional design. CONCLUSIONS: Sleep duration was associated with suicidal ideation and attempts, and the association between sleep duration and suicidal attempts was U-shaped. These findings support that proper treatments services with the potential to restore adolescent normal sleep would be helpful in preventing suicidality among adolescents.
Assuntos
Comportamento do Adolescente/psicologia , Povo Asiático/psicologia , Depressão/psicologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Ideação Suicida , Tentativa de Suicídio/psicologia , Adolescente , China/epidemiologia , Estudos Transversais , Depressão/complicações , Feminino , Humanos , Masculino , Prevalência , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Estudantes/psicologiaRESUMO
BACKGROUND: The nature of the relationship between the non-medical use of prescription drugs (NMUPD) and suicide has not been clearly elucidated. Some studies have suggested that the relationship between substance use and suicidal ideation may be spurious and could be explained by other variables. METHODS: A school-based cross-sectional study was performed in Guangzhou. A total of 5853 students completed questionnaires and were included in the study. NMUPD, alcohol use, illicit drug use, depressive symptoms, sleep quality, and suicidal behaviors were assessed. The mediating effects of depressive symptoms and sleep quality on the relationship between NMUPD and suicidal behaviors were examined using a structural equation model. RESULTS: In the simple model without mediation, a positive relationship between NMUPD and suicidal behaviors in adolescents was found, which was independent of effects from the use of other substances. Both depressive symptoms and sleep quality were significant mediators of this relationship. CONCLUSION: Public health and educational professionals should survey depressive symptoms and sleep quality and provide interventions when managing suicidal behaviors among adolescents engaging in NMUPD.
Assuntos
Comportamento do Adolescente/psicologia , Povo Asiático/psicologia , Depressão/epidemiologia , Depressão/psicologia , Uso Indevido de Medicamentos sob Prescrição/estatística & dados numéricos , Sono/fisiologia , Ideação Suicida , Adolescente , Povo Asiático/estatística & dados numéricos , Estudos Transversais , Feminino , Humanos , Masculino , Uso Indevido de Medicamentos sob Prescrição/psicologia , Fatores de Risco , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Consumo de Álcool por Menores/psicologia , Adulto JovemRESUMO
AIMS: To test, among Chinese adolescents: (1) whether childhood maltreatment is associated with non-medical use of prescription drugs (NMUPD) and (2) whether there are interaction effects of childhood maltreatment and depressive symptoms on NMUPD. DESIGN: A secondary analysis of the cross-sectional data collected from 7th- and 12th-graders who were sampled using a multi-stage, stratified-cluster, random-sampling method in the 2015 School-based Chinese Adolescents Health Survey (SCAHS). SETTING: Surveys conducted in high schools in six cities of China in 2015. PARTICIPANTS: There were 24 457 students who were invited to participate and 23 039 students' questionnaires were completed and qualified for our survey. MEASUREMENTS: The outcomes comprised self-report of NMUPD (prior 30 days); a history of childhood maltreatment was our main predictor. Other covariates included depressive symptoms, smoking, drinking and demographics. Data were analysed using multi-level regression modelling. FINDINGS: Our final multivariable logistic regression models demonstrated that after adjusting for other variables, physical abuse was associated positively with non-medical use of opioids [adjusted odds ratio (AOR) = 1.13, 95% confidence interval (CI) = 1.10-1.22], sedatives (AOR = 1.11, 95% CI = 1.10-1.21) and any prescription drugs (AOR = 1.13, 95% CI = 1.09-1.20); emotional abuse, sexual abuse and emotional neglect were also associated with an increased risk of opioids, sedatives and any prescription drugs misuse; students who reported that they had experienced childhood physical neglect were more likely to be involved in the non-medical use of sedatives (AOR = 1.08, 95% CI = 1.04-1.12) and any prescription drugs (AOR = 1.06, 95% CI = 1.03-1.10). Additionally, there was no evidence of interaction effects on NMUPD between depressive symptoms and each of physical abuse, emotional abuse, sexual abuse, physical neglect and emotional neglect, respectively. CONCLUSIONS: Maltreatment while a child is associated with an increased risk of non-medical use of prescription drugs (NMUPD) among Chinese adolescents. The interactions of maltreatment while a child and depressive symptoms do not appear to be associated significantly with NMUPD among Chinese adolescents.