Novel Prognostic Model Construction of Tongue Squamous Cell Carcinoma Based on Apigenin-Associated Genes.

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.

The prognosis of TP53 and EGFR co-mutation in patients with advanced lung adenocarcinoma and intracranial metastasis treated with EGFR-TKIs.

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.

Effect of Cepharanthine on the Stemness of Lung Squamous Cell Carcinoma Based on Network Pharmacology and Bioinformatics.

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.

Based on clinical Ki-67 expression and serum infiltrating lymphocytes related nomogram for predicting the diagnosis of glioma-grading.

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.

Real-world safety of ulinastatin: a post-marketing surveillance of 11,252 patients in China.

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.

Sinomenine Derivatives: Synthesis, Antitumor Activity, and Apoptotic Induction in MCF-7 Cells via IL-6/PI3K/Akt/NF-κB Signaling Pathway.

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 in vitro antitumor activity against HeLa, A549, HepG-2, MCF-7 and HT-29 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 11 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.

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.

GTP-binding protein Di-RAS3 diminishes the migration and invasion of non-small cell lung cancer by inhibiting the RAS/extracellular-regulated kinase pathway.

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.

Prone position versus supine position in postoperative radiotherapy for breast cancer: A meta-analysis.

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, SMD = - 0.51, 95% CI - 0.66 ∼ - 0.36, P < .00001. LADCA dose, SMD = - 0.58, 95% CI - 0.85 ∼ - 0.31, P < .0001. ILL dose, SMD = - 2.84, 95% CI - 3.2 ∼ - 2.48, P < .00001). And there was no significant difference in target coverage between the S-FB and P-FB groups (SMD = - 0.1, 95% CI - 0.57 ∼ 0.36, P = .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.

Exploration of Prognostic Biomarkers among Replication Factor C Family in the Hepatocellular Carcinoma.

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.

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.

Safety profile of traditional Chinese herbal injection: An analysis of a spontaneous reporting system in China.

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.

Active pharmacovigilance in China: recent development and future perspectives.

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.

The mediating effects of depressive symptoms and sleep quality on the relationship between the non-medical use of prescription drugs and suicidal behaviors among Chinese adolescents.

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.

Associations between childhood maltreatment and non-medical use of prescription drugs among Chinese adolescents.

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.

Association between sleep duration, suicidal ideation, and suicidal attempts among Chinese adolescents: The moderating role of depressive symptoms.

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.

Alcohol use and alcohol-related problems among adolescents in China: A large-scale cross-sectional study.

Alcohol misuse among adolescents is a common issue worldwide and is an emerging problem in China. This study aimed to investigate the prevalence of alcohol drinking and alcohol-related problems among Chinese adolescents and to explore their risk factors and connections.A cross-sectional study using an anonymous questionnaire was conducted among junior and senior high school students between 2010 and 2012. Data on self-reported alcohol use, alcohol-related problems, school factors, family factors, and psychosocial factors were collected. Descriptive analyses were made of the proportions of sociodemographics, family, school, and psychosocial factors. Multilevel logistic regression models were conducted to analyze the risk factors for alcohol drinking and alcohol-related problems.Of the 105,752 students who ranged in age from 9 to 21 years, the prevalence of current drinking among students was 7.3%, and 13.2% students reported having alcohol-related problems. Male students were 1.78 (95% confidence interval [CI] = 1.69-1.87) times more likely to be involved in current drinking and 1.86 (95% CI = 1.79-1.93) times more likely to have alcohol-related problems. Higher grade level students were at a higher risk of current drinking (adjusted odds ratio [AOR] = 1.09, 95% CI = 1.05-1.13) and having alcohol-related problems (AOR = 1.43, 95% CI = 1.42-1.58). Older students were more likely to report current drinking (AOR = 1.06, 95% CI = 1.04-1.17) and having alcohol-related problems (AOR = 1.83, 95% CI = 1.82-1.85). Having poor classmate relations (AOR = 1.28, 95% CI = 1.03-1.37), having poor relationships with teachers (AOR = 1.08, 95% CI = 1.00-1.16), and below average academic achievement (AOR = 1.50, 95% CI = 1.41-1.59) were positively associated with current drinking. Moreover, students with suicidal ideation were at a higher risk of current drinking (AOR = 1.70, 95% CI = 1.61-1.81) and having alcohol-related problems (AOR = 2.08, 95% CI = 1.98-2.16). Having higher Center for Epidemiology Scale for Depression scores was positively associated with current drinking (AOR = 1.09, 95% CI = 1.05-1.11) and having alcohol-related problems (AOR = 1.08, 95% CI = 1.06-1.18).Alcohol drinking and alcohol-related problems among Chinese adolescents are major public health problems, and effective preventive programs will require full consideration of the individual, social, and environmental factors that facilitate and prevent alcohol use.

Association Between Nonmedical Use of Prescription Drugs and Suicidal Behavior Among Adolescents.

IMPORTANCE: Suicidal behavior is a leading cause of injury and death worldwide, and previous cross-sectional studies have demonstrated that nonmedical use of prescription drugs (NMUPD) was associated with suicidality. However, there is not any study in China having examined the longitudinal relationships between NMUPD, suicidal ideation, and suicidal attempts, as well as explored the potential mediating effects of depressive symptoms. OBJECTIVE: To determine whether baseline NMUPD was associated with subsequent suicidal ideation and attempts while controlling for depressive symptoms and to determine whether the increased risks were mediated by depressive symptoms. DESIGN, SETTING, AND PARTICIPANTS: In this longitudinal study, a total of 3273 students in randomly selected schools in Guangzhou were surveyed from 2009 to 2010 (response rate, 96.8%) and followed up at 1 year (2011-2012; retention rate, 96.1%). The dates of data analysis were October 9, 2015, to October 15, 2015; additional data analysis occurred March 23, 2016, to March 29, 2016. MAIN OUTCOMES AND MEASURES: Suicidal ideation, suicidal attempts, NMUPD, depressive symptoms, and alcohol-related problems. RESULTS: Overall, 3273 adolescents (mean [SD] age, 13.7 [1.0] years) were recruited for this study. The final results showed that after controlling for sociodemographic information (including sex, age, household socioeconomic status, and living arrangements), baseline depressive symptoms, baseline alcohol-related problems, baseline suicidal ideation, and baseline suicidal attempts, baseline opioids misuse (adjusted odds ratio [AOR], 2.31; 95% CI, 1.30-4.11), sedatives misuse (AOR, 4.46; 95% CI, 1.54-7.94), and nonmedical use of any prescription drug (AOR, 1.97; 95% CI, 1.21-3.23) were positively associated with suicidal ideation at follow-up. Additionally, baseline opioid misuse (AOR, 3.39; 95% CI, 1.33-5.63) and nonmedical use of any prescription drug (AOR, 2.91; 95% CI, 1.26-3.71) were also associated with subsequent suicidal attempts after controlling for sex, age, household socioeconomic status, living arrangements, depressive symptoms, alcohol-related problems, suicidal ideation, and suicidal attempts at baseline. There were significant standardized indirect effects of baseline opioids misuse on subsequent suicidal ideation (standardized ß estimate = 0.020; 95% CI, 0.010-0.030) and suicidal attempts (standardized ß estimate = 0.009; 95% CI, 0.004-0.015) through depressive symptoms; the standardized indirect effect of baseline sedatives misuse on subsequent suicidal ideation through depressive symptoms was also significant (standardized ß estimate = 0.016; 95% CI, 0.005-0.026). CONCLUSIONS AND RELEVANCE: In this study, NMUPD at baseline was associated with subsequent suicidal ideation and attempts. These findings support that proper surveillance systems with the potential to reduce adolescent suicidality should be established to control and supervise suicidality and NMUPD among Chinese adolescents.

The prevalences of and association between nonmedical prescription opioid use and poor sleep among Chinese high school students.

The purpose of this study was to investigate the prevalences of and association between nonmedical prescription opioid use (NMPOU) and sleep quality among Chinese high school students. A cross-sectional study was conducted in Chongqing high school students in 2012, and questionnaires from 18,686 students were completed and eligible for this study. Demographic and NMPOU information was collected using a self-administered questionnaire. The Chinese Pittsburgh Sleep Quality index (CPSQI) was used to assess the occurrence of poor sleep. Among the total sample, 18.0% were classified as poor sleepers (27.4% of the subjects with past-month NMPOU), and the prevalences of lifetime, past-year and past-month NMPOU were 14.6, 4.6 and 2.8% across the entire sample, respectively. The most commonly used medicine was licorice tablets with morphine (9.1, 2.5 and 1.5% for lifetime, past-year and past-month, respectively), followed by cough syrup with codeine, Percocet, diphenoxylate and tramadol. After adjustment for potential confounders, the association between past-month NMPOU and poor sleep remained significant (AOR = 1.47, 95% CI 1.17 to 1.85). Programs aimed at decreasing NMPOU should also pay attention to sleep quality among adolescents.