Biological effects and mechanism of ß-amyloid aggregation inhibition by penetrable recombinant human HspB5-ACD structural domain protein.

Alzheimer's disease (AD) is a global medical challenge. Studies have shown that neurotoxicity caused by pathological aggregation of ß-amyloid (Aß) is an important factor leading to AD. Therefore, inhibiting the pathological aggregation of Aß is the key to treating AD. The recombinant human HspB5-ACD structural domain protein (AHspB5) prepared by our group in the previous period has been shown to have anti-amyloid aggregation effects, but its inability to penetrate biological membranes has limited its development. In this study, we prepared a recombinant fusion protein (T-AHspB5) of TAT and AHspB5. In vitro experiments showed that T-AHspB5 inhibited the formation of Aß1-42 protofibrils and had the ability to penetrate the blood-brain barrier; in cellular experiments, T-AHspB5 prevented Aß1-42-induced oxidative stress damage, apoptosis, and inflammatory responses in neuronal cells, and its mechanism of action was related to microglia activation and mitochondria-dependent apoptotic pathway. In animal experiments, T-AHspB5 improved memory and cognitive dysfunction and inhibited pathological changes of AD in APP/PS1 mice. In conclusion, this paper is expected to reveal the intervention mechanism and biological effect of T-AHspB5 on pathological aggregation of Aß1-42, provide a new pathway for the treatment of AD, and lay the foundation for the future development and application of T-AHspB5.

Functional modification of recombinant brain-derived neurotrophic factor and its protective effect against neurotoxicity.

Brain-derived neurotrophic factor (BDNF) is a neurotrophic protein that promotes neuronal survival, increases neurotransmitter synthesis, and has potential therapeutic effects in neurodegenerative and psychiatric diseases, but its drug development has been limited by the fact that recombinant proteins of BDNF are unstable and do not penetrate the blood-brain barrier (BBB). In this study, we fused a TAT membrane-penetrating peptide with BDNF to express a recombinant protein (TBDNF), which was then PEG-modified to P-TBDNF. Protein characterization showed that P-TBDNF significantly improved the stability of the recombinant protein and possessed the ability to penetrate the BBB, and in cellular experiments, P-TBDNF prevented MPTP-induced nerve cell oxidative stress damage, apoptosis and inflammatory response, and its mechanism of action was closely related to the activation of tyrosine kinase B (TrkB) receptor and inhibition of microglia activation. In animal experiments, P-TBDNF improved motor and cognitive deficits in MPTP mice and inhibited pathological changes in Parkinson's disease (PD). In conclusion, this paper is expected to reveal the mechanism of action of P-TBDNF in inhibiting neurotoxicity, provide a new way for treating PD, and lay the foundation for the future development of recombinant P-TBDNF.

Isolation and purification of Eleutherococcus sessiliflorus (Rupr. & Maxim.) S. Y. Hu peptides and study of their antioxidant effects and mechanisms.

Oxidative stress is a state of imbalance between oxidant and antioxidant effects in the body, which is closely associated with aging and many diseases. Therefore, the development of antioxidants has become urgent. In this study, we isolated three polypeptides, G-6-Y, P-8-R, and F-10-W, from Eleutherococcus sessiliflorus (Rupr. & Maxim.) S. Y. Hu (E. sessiliflorus), based on the antioxidant and anti-aging properties of Eleutherococcus, and screened the most powerful free radical scavenging peptide P-8-R. Ultraviolet B (UVB)-induced oxidative stress damage in the skin was established to test the efficacy of P-8-R. In cellular experiments, P-8-R not only prevented oxidative stress damage in HaCaT cells, reduced intracellular reactive oxygen species levels, and inhibited the overexpression of matrix metalloproteinases but also inhibited apoptosis via the mitochondria-dependent apoptotic pathway; in animal experiments, P-8-R was able to prevent oxidative stress damage in the skin and reduce skin collagen loss by inhibiting the overexpression of MMPs to prevent mouse skin aging. In conclusion, the present study contributes to an in-depth understanding of the active compounds of Eleutherococcus, which is of great significance for the pharmacodynamic mechanism and industrial development of Eleutherococcus, and P-8-R is likely to become a potential antioxidant and anti-aging drug or skin care cosmetic in the future.

Recombinant human HspB5-ACD structural domain inhibits neurotoxicity by regulating pathological α-Syn aggregation.

The treatment of Parkinson's disease is a global medical challenge. α-Synuclein (α-Syn) is the causative protein in Parkinson's disease and is closely linked to its progression. Therefore, inhibiting the pathological aggregation of α-Syn and its neurotoxicity is essential for the treatment of Parkinson's disease. In this study, α-Syn and recombinant human HspB5-ACD structural domain protein (AHspB5) were produced using the BL21(DE3) E. coli prokaryotic expression system, and then the role and mechanism of AHspB5 in inhibiting the pathological aggregation of α-Syn and its neurotoxicity were investigated. As a result, we expressed α-Syn and AHspB5 proteins and characterised the proteins. In vitro experiments showed that AHspB5 could inhibit the formation of α-Syn oligomers and fibrils; in cellular experiments, AHspB5 could prevent α-Syn-induced neuronal cell dysfunction, oxidative stress damage and apoptosis, and its mechanism of action was related to the TH-DA pathway and mitochondria-dependent apoptotic pathway; in animal experiments, AHspB5 could inhibit behavioural abnormalities, oxidative stress damage and loss of dopaminergic neurons. In conclusion, this work is expected to elucidate the mechanism and biological effects of AHspB5 on the pathological aggregation of α-Syn, providing a new pathway for the treatment of Parkinson's disease and laying the foundation for recombinant AHspB5.

PEG-modified nano liposomes co-deliver Apigenin and RAGE-siRNA to protect myocardial ischemia injury.

Ischemic heart disease (IHD) is a cardiac disorder in which myocardial damage occurs as a result of myocardial ischemia and hypoxia. Evidence suggests that oxidative stress and inflammatory responses are critical in the development of myocardial ischemia. Therefore, the combination of antioxidant and anti-inflammatory applications is an effective strategy to combat ischemic heart disease. In this paper, polyethylene glycol (PEG)-modified cationic liposomes were used as carriers to deliver apigenin (Apn) with small interfering RNA (siRNA) targeting the receptor for glycosylation end products (RAGE) (siRAGE) into cardiomyocytes to prevent myocardial ischemic injury through antioxidant and anti-inflammatory effects. Our results showed that we successfully prepared cationic PEG liposomes loaded with Apn and siRAGE (P-CLP-A/R) with normal appearance and morphology, particle size and Zeta potential, and good encapsulation rate, drug loading and in vitro release degree. In vitro, P-CLP-A/R was able to prevent oxidative stress injury in H9C2 cells, downregulate the expression of RAGE, reduce the secretion of cellular inflammatory factors and inhibit apoptosis through the RAGE/NF-κB pathway; In vivo, P-CLP-A/R was able to prevent arrhythmia and myocardial pathological injury, and reduce apoptosis and the area of necrotic myocardium in rats. In conclusion, P-CLP-A/R has a protective effect on myocardial ischemic injury and is expected to be a potential drug for the prevention of ischemic heart disease in the future.

Anti-photoaging effect and mechanism of flexible liposomes co-loaded with apigenin and doxycycline.

Prolonged exposure to UV light can lead to photo-ageing of the skin. Therefore, the development and application of anti-photoaging drugs is urgent. In this study, we co-loaded apigenin (Apn) and doxycycline (Doc), a broad-spectrum inhibitor of matrix metalloproteinases (MMPs), into flexible liposomes to exert anti-photoaging effects by combating oxidative stress, anti-inflammation, reducing the activation of MMPs and preventing collagen loss. The results showed that we prepared a flexible liposome (A/D-FLip) containing Apn and Doc. Its appearance, particle size and Zeta potential were normal and it had good encapsulation efficiency, drug loading, in vitro release and transdermal efficiency. In cellular experiments, A/D-FLip could inhibit oxidative stress damage, reduce inflammatory factors and decrease the activation of MMPs in Human immortalized keratinocytes (HaCaT) cells; in animal experiments, A/D-FLip could inhibit skin damage and reduce skin collagen loss by decreasing the activation of MMPs, thus inhibiting skin photoaging in mice. In conclusion, A/D-FLip has good anti-photoaging effects and it has the potential to become an effective skin care product or drug against UV damage and skin photoaging in the future.

Single Gold Nanostars Achieve Inherent Cascade Catalytic and Near-Infrared Photothermal Activities for Efficient Tumor Therapy.

Gold nanoparticles (Au NPs) used as photosensitizers for photothermal therapy (PTT) have attracted extensive attention. However, limited tissue penetration of light seriously hinders the practical application, causing Au NPs to be combined with multiple theranostic agents to improve the treatment effect. Herein, we fabricate one potent gold nanostars (GNS) that can unify the dual nanozyme activities and photothermal property, achieving effective synergistic cascade catalytic and photothermal therapy. Notably, GNS is prepared by a green and facile one-step synthesis method using biodegradable poly(γ-glutamic acid) as a medium. The single GNS exhibits inherent dual nanozyme activities, glucose oxidase- and peroxidase-like activities, which not only convert glucose of tumor tissue into hydrogen peroxide (H2O2) but also catalyze H2O2 to produce the amount of toxic hydroxyl radicals (•OH), leading to an amplified cascade catalytic therapy. Moreover, the cascade catalytic activity of GNS is enhanced 1.4-fold in the photothermal effect. Finally, the GNS can achieve photoacoustic imaging-guided efficient synergistic cascade catalytic and photothermal therapy with a high antitumor rate of 97.0%. This simple but multifunctional GNS could provide a new strategy facilitating the practical treatment application of single Au NPs.

The Factor Structure and Measurement Invariance of the Coping Inventory for Stressful Situations in a Sexual Minority Population.

Coping strategies have been studied as protective factors against stress for individuals. However, the psychometric properties of the most widely used coping self-report questionnaires, the Coping Inventory for Stressful Situations (CISS-21), have not been examined in a sexual minority population (men and women that identify as lesbian, gay, or bisexual or LGB). In this study, we conducted exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) simultaneously to assess the factor structure of the CISS-21 questionnaire in LGBs. Also, we tested the measurement invariance of CISS across sex and sexual identity in the LGB sample (N = 2850, 52.00% woman, mean age = 32.46 years). The results show that a four-factor structure consisting of task-oriented coping (TOC), emotion-oriented coping (EOC), distraction-oriented coping (DOC), and social diversion-oriented coping (SOC) explained the data best. The results also show acceptable internal consistency reliability, convergent validity, and discriminant validity. Subsequently, multi-group analyses established measurement invariance across sex and sexual identity. These results indicate that the CISS-21 could be used as a simple, reliable, and valid scale for measuring coping strategies in LGBs, and that it allows valid score comparisons from different sex and sexual identity groups.

Sexual orientation and sleep problem among Chinese college students: Mediating roles of interpersonal problems and depressive symptoms.

BACKGROUND: This study aimed to investigate disparities in sleep quality between sexual minority and heterosexual college students, and to examine the serial multiple mediation effects of interpersonal relationships and depressive symptoms on sexual minority disparities in sleep quality. We also explored the sex differences in the mediating effects. METHODS: Data were drawn from the 2019 School-based Chinese College Students Health Survey using a multi-stage, stratified-cluster, random-sampling method to examine the risk factors of sleep disparities and the mediation effects. Measures included sexual orientation, perceived interpersonal relationships (i.e., family, teachers, and peer relationship), depressive symptoms, sleep quality, and other covariates. RESULTS: Of all the college students in the analysis, 95.8% were heterosexual, 4.2% were sexual minorities. In the adjusted model without mediation, sexual minority students were at a higher risk of poor sleep quality (P < 0.001). Serial multiple mediation analysis revealed that: both interpersonal relationships and depressive symptoms mediated the link between sexual orientation and sleep quality; a serial indirect pathway (i.e., sexual orientation â†’ interpersonal relationships â†’ depressive symptoms â†’ sleep quality) existed. Moreover, the serial indirect pathway might be moderated by sex. LIMITATIONS: Causal inference is limited due to the cross-sectional design. CONCLUSIONS: Interventions to prevent or manage sleep disorders of sexual minority college students may yield better results if they consider the effects of improving interpersonal relationships and depression symptoms comprehensively than targeting sleep problems alone.

Childhood maltreatment predicts subsequent anxiety symptoms among Chinese adolescents: the role of the tendency of coping styles.

Childhood maltreatment may have an influence on anxiety symptoms and coping styles. This longitudinal study aimed to estimate the prospective associations between different types of childhood maltreatment and anxiety symptoms among Chinese adolescents, with a particular focus on investigating whether these associations vary by the tendency of coping styles. Data were from the Longitudinal Study of Adolescents' Mental and Behavioral Well-being Research. The baseline sample included 1957 participants (response rate: 99.03%) and followed up at 1-year later (n = 1836, retention rate: 93.8%). Anxiety symptoms, childhood maltreatment, the tendency of coping styles, morning cortisol level, depressive symptoms, self-esteem, and other demographics were measured. Overall, the mean age of the baseline students was 13.6 (SD: 1.5) years. The final results showed that childhood emotional abuse (unstandardized ß-estimate = 0.13, 95% CI = 0.07-0.18), physical abuse (unstandardized ß-estimate = 0.08, 95% CI = 0.01-0.16), and sexual abuse (unstandardized ß-estimate = 0.17, 95% CI = 0.04-0.29) were positively associated with anxiety symptoms at follow-up after adjusting for significant covariates at baseline. Additionally, the stratified analyses demonstrated that only among students with negative coping styles, childhood emotional abuse, physical abuse, and sexual abuse were associated with subsequent anxiety symptoms; the differences between the positive and negative coping style strata were significant (P < 0.05). Childhood maltreatment appears to be a predictor of anxiety symptoms among adolescents, and the tendency of coping styles may have a moderating role in these longitudinal associations. The efforts to prevent anxiety symptoms are recommended to be focused on adolescents with the experience of childhood maltreatment and negative coping styles.

Role of IgE-FcεR1 in Pathological Cardiac Remodeling and Dysfunction.

BACKGROUND: Immunoglobulin E (IgE) belongs to a class of immunoglobulins involved in immune response to specific allergens. However, the roles of IgE and IgE receptor (FcεR1) in pathological cardiac remodeling and heart failure are unknown. METHODS: Serum IgE levels and cardiac FcεR1 expression were assessed in diseased hearts from human and mouse. The role of FcεR1 signaling in pathological cardiac remodeling was explored in vivo by FcεR1 genetic depletion, anti-IgE antibodies, and bone marrow transplantation. The roles of the IgE-FcεR1 pathway were further evaluated in vitro in primary cultured rat cardiomyocytes and cardiac fibroblasts (CFs). RNA sequencing and bioinformatic analyses were used to identify biochemical changes and signaling pathways that are regulated by IgE/FcεR1. RESULTS: Serum IgE levels were significantly elevated in patients with heart failure as well as in 2 mouse cardiac disease models induced by chronic pressure overload via transverse aortic constriction and chronic angiotensin II infusion. Interestingly, FcεR1 expression levels were also significantly upregulated in failing hearts from human and mouse. Blockade of the IgE-FcεR1 pathway by FcεR1 knockout alleviated transverse aortic constriction- or angiotensin II-induced pathological cardiac remodeling or dysfunction. Anti-IgE antibodies (including the clinical drug omalizumab) also significantly alleviated angiotensin II-induced cardiac remodeling. Bone marrow transplantation experiments indicated that IgE-induced cardiac remodeling was mediated through non-bone marrow-derived cells. FcεR1 was found to be expressed in both cardiomyocytes and CFs. In cultured rat cardiomyocytes, IgE-induced cardiomyocyte hypertrophy and hypertrophic marker expression were abolished by depleting FcεR1. In cultured rat CFs, IgE-induced CF activation and matrix protein production were also blocked by FcεR1 deficiency. RNA sequencing and signaling pathway analyses revealed that transforming growth factor-ß may be a critical mediator, and blocking transforming growth factor-ß indeed alleviated IgE-induced cardiomyocyte hypertrophy and cardiac fibroblast activation in vitro. CONCLUSIONS: Our findings suggest that IgE induction plays a causative role in pathological cardiac remodeling, at least partially via the activation of IgE-FcεR1 signaling in cardiomyocytes and CFs. Therapeutic strategies targeting the IgE-FcεR1 axis may be effective for managing IgE-mediated cardiac remodeling.

Association of sexual minority status, gender nonconformity with childhood victimization and adulthood depressive symptoms: A path analysis.

BACKGROUND: Sexual minority status and childhood gender nonconformity have been associated with elevated risks of childhood adversities and poorer mental health. OBJECTIVE: To explore how abuse and bullying explain the disparities in the associations of sexual minority status and childhood gender nonconformity with adulthood depressive symptoms in men. PARTICIPANTS AND SETTING: We conducted a cross-sectional study using a self-report questionnaire among Chinese adult men (18-35 years) who were identified as heterosexual (n = 873) and sexual minority (n = 858) in Guangzhou from 2017 to 2019. METHODS: Structural equation modeling (SEM) were conducted for path analysis. RESULTS: The levels of exposure to childhood maltreatment were higher in sexual minorities than in straight men, and sexual minority status predicted an increased risk of depressive symptoms via childhood maltreatment (indirect effect: ß = 0.026, p = 0.004). Meanwhile, childhood gender nonconformity predicted higher depressive symptoms via both family (indirect effect: ß = 0.042, p < 0.001) and school (indirect effect: ß = 0.028, p < 0.001) victimization, and there was a direct effect (ß = 0.154, p < 0.001) of gender nonconformity on depressive symptoms. CONCLUSION: Sexual minority status and gender nonconformity are indicators of men's increased risk of childhood victimization and adulthood depressive symptoms. As a result, intervention based on both family and school dimensions needs to be developed.

The Longitudinal Association between Sleep Duration and Suicidal Behavior among Chinese Adolescents: The Role of Nonmedical Use of Prescription Drug.

OBJECTIVE/BACKGROUND: Abnormal sleep and nonmedical use of prescription drugs are known to be factors associated with suicidal behavior, but the nature of the association between weekday sleep duration and suicidal behavior has not been elucidated. Nonmedical use of prescription drugs may play a mediator role in the association mentioned above. PARTICIPANTS: There were a total of 3,273 high school students interviewed at baseline with a response rate of 96.8% and followed up at one year (retention rate, 96.1%). The mean (SD) age of the students was 13.7 (1.0) years. METHODS: Data were drawn from the longitudinal data of the School-based Chinese Adolescents Health Survey. A total of 12 high schools were selected in Guangzhou. Suicidal behavior, weekday sleep duration, and nonmedical use of prescription drugs were measured. RESULTS: Sleeping < 7 hours/day at time 0 was positively associated with suicidal ideation (Adjusted odds ratio [AOR] = 1.51, 95% CI = 1.21-1.89) and suicide attempts (AOR = 2.35, 95% CI = 1.02-5.38) at time 1. The mediation analyses showed that baseline opioids misuse or sedatives misuse partially mediated the associations of baseline short weekday sleep duration with suicidal ideation and suicide attempts at one-year follow-up. CONCLUSIONS: Baseline short weekday sleep duration was positively associated with subsequent suicidal ideation and suicide attempts, and nonmedical use of opioids or sedatives partially mediated the associations mentioned above. Suicidal behavior can be prevented, short weekday sleep duration and nonmedical use of prescription drugs may be risk factors for suicidal behavior, and the respective roles of these factors are needed to be better understood.

Association Among Maltreatment, Bullying and Mental Health, Risk Behavior and Sexual Attraction in Chinese Students.

OBJECTIVE: To identify the association between sexual attraction, childhood maltreatment and bullying victimization, and mental and behavioral health problems among Chinese adolescents. METHODS: A cross-sectional study among Chinese high school students by multistage stratified cluster sampling was conducted using a self-reported questionnaire. Participants who were same- or both-sex attracted were identified as sexual minorities, and those who were opposite-sex attracted were identified as heterosexuals. Childhood maltreatment was assessed as physical, emotional, and sexual abuse, and bullying was assessed as traditional and cyberbullying. Psychological distress was assessed as depressive and anxiety symptoms, and self-destructive behavior was assessed as suicidal behavior and nonsuicidal self-injury. Logistic regression and path analysis were conducted to analyze the data. RESULTS: There were 1360 sexual minority and 15,020 heterosexual respondents. Sexual minority status was associated with increased risk of maltreatment (adjusted odds ratio [AOR] range: 1.25-2.46) and bullying (AOR range: 1.38-1.77) victimization, and a series of health problems (AOR range: 1.85-3.69). Furthermore, childhood maltreatment could partially explain the association of sexual minority status with psychological distress (indirect effect: ß = 0.026 for boys; ß = 0.086 for girls) and self-destructive behavior (ß = 0.056 for boys; ß = 0.125 for girls), and bullying could partially explain the association between sexual minority status and psychological distress (ß = 0.040 for boys; ß = 0.031 for girls). CONCLUSIONS: Sexual minority adolescents were more likely than heterosexuals to experience different forms of childhood victimization, which may put them at higher risk for mental and behavioral health problems. Interventions based on both family and school are essential.

Screen-Printed High-Performance Flexible Electrothermal Films Based on Three-Dimensional Intercalation Graphene Nanosheets/MWCNT/Carbon Black Composite.

A liquid-phase stripping method was used to strip the graphite under the action of mechanical shear force to prepare graphene nanosheets (GNSs) on a large scale. Given the multicomponent composite conductive particles formed by GNSs with acid-treated MWCNTs (f-MWCNTs) and carbon black (CB), the three-dimensional (3D) intercalation electrothermal composite of GNSs/MWCNTs/CB with excellent conductivity and mechanical properties was prepared with water-based acrylic resin as a connector. Carbon particles (16.97 wt %) are found in the composite and the sheet resistance (Rs) is only 4 Ω sq-1 as f-MWCNTs and CB intercalations form a more stable 3D conducting medium between the GNSs. The flexible electrothermal film (2.5 cm × 2.5 cm) printed with the 3D intercalation GNSs/MWCNTs/CB composite had a saturation temperature (Ts) of 175 °C with an input of 3 V and lower power consumption (249.87 cm2 W-1). It only takes 10 s to reach Ts and the electrical performance is still intact under the pressure of 1 × 105 kPa. After being bent 2500 times (bending radius is 5 mm), the electrothermal performance of the flexible electrothermal film remained stable.

Gender differences in the associations between types of childhood maltreatment and sleep disturbance among Chinese adolescents.

BACKGROUND: To explore the association between different types of childhood maltreatment and sleep disturbance among Chinese adolescents, with a particular focus on gender differences. METHODS: A cross-sectional study was conducted in 7 randomly selected provinces of China via the 2015 School-Based Chinese Adolescents Health Survey. Questionnaires from 153,547 students were completed and were eligible for this study. The Chinese Version of the Pittsburgh Sleep Quality Index (CPSQI) and Childhood Trauma Questionnaire-Short Form (CTQ-SF) were used to assess sleep disturbance and childhood maltreatment, respectively. RESULTS: The prevalence of sleep disturbance among adolescents in China was 21.6%. A significantly increased risk of sleep disturbance was associated with physical abuse (aOR=1.22, 95% CI=1.21-1.24), emotional abuse (aOR=1.15, 95% CI=1.14-1.15), sexual abuse (aOR=1.16, 95% CI=1.15-1.18), physical neglect (aOR=1.04, 95% CI=1.03-1.05), and emotional neglect (aOR=1.03, 95% CI=1.02-1.03). A significant dose-response relationship was found between cumulative childhood maltreatment experiences and sleep disturbance. The interaction terms (between physical abuse/emotional abuse/sexual abuse/physical neglect/emotional neglect/number of childhood traumas and gender) were significantly associated with sleep disturbance. Further stratification analyses by gender showed that girls who reported experiencing one or more of these five types of childhood maltreatment had a higher risk of sleep disturbance than boys. LIMITATIONS: The study only included school students, and the cross-sectional design limited our ability to make causal inferences. CONCLUSIONS: The study findings suggest that childhood maltreatment increases the risk of sleep disturbance in adolescents. Furthermore, exposure to single and multiple types of childhood maltreatment predicts lower sleep quality in girls.

Associations of Substance Use Behaviors With Suicidal Ideation and Suicide Attempts Among US and Chinese Adolescents.

Background: Adolescence has been described as a period of increased health risk-taking behaviors. Given the variety of cultural contexts, healthcare systems, and public health policies in different regions, the present study aimed to determine whether there are similar or different associations of substance use behaviors with suicidal ideation and suicide attempts among US and Chinese adolescents. Methods: This study included a total of 14,765 US adolescents from the 2017 National Youth Risk Behavior Surveillance System (YRBSS) and 24,345 Chinese adolescents from the 2017 School-based Chinese Adolescents Health Survey (SCAHS). Results: The proportions of suicidal ideation and suicide attempts were 17.4 and 5.7% among US adolescents, which were higher than those among Chinese adolescents (suicidal ideation: 13.7% and suicide attempts: 2.7%). Among Chinese adolescents, the most common substance use behavior was "alcohol use (55.4%)," followed by "cigarette use (11.6%)." Among US adolescents, the most popular substance was alcohol (ever used: 55.9%), followed by marijuana (ever used: 34.6%). Moreover, alcohol use was significantly related to suicidal ideation/suicide attempts only in Chinese adolescents [suicidal ideation: Adjusted odds ratio (AOR) = 1.88, 95% CI = 1.71~2.06; suicide attempts: AOR = 2.12, 95% CI = 1.71~2.63], and marijuana use was associated with suicidal ideation and suicide attempts only in the US adolescent group (suicidal ideation: AOR = 1.23, 95% CI = 1.06~1.44; suicide attempts: AOR = 1.51, 95% CI = 1.21~1.87). Moreover, although the associations of prescription pain medication use with suicide attempts were significant in both Chinese and US adolescent groups, the adjusted associations were stronger in Chinese adolescents than in US adolescents (Chinese adolescents: AOR = 3.97, 95% CI = 2.76~5.72; US adolescents: AOR = 1.76, 95% CI = 1.43~2.16; P < 0.05). Conclusions: The associations of alcohol use with suicidal ideation and suicide attempts were only significant in Chinese adolescents. Marijuana use was associated with suicidal ideation and suicide attempts only in the US adolescent group. Although the associations of prescription pain medication use with suicide attempts were significant in both Chinese and US adolescent groups, the adjusted associations were significantly stronger for Chinese adolescents. These findings might be related to the differences in cultural contexts, healthcare systems, and public health policies in the two different countries.

Effect of Sex on the Association Between Nonmedical Use of Opioids and Sleep Disturbance Among Chinese Adolescents: A Cross-Sectional Study.

Sleep disturbance and non-medical prescription opioid use (NMPOU) are currently growing public health concerns, and sex differences may result in differential exposure to frequency of NMPOU or sleep disturbance. This study aimed to explore the association between the frequency of lifetime or past-year NMPOU and sleep disturbance and to evaluate whether there was any sex difference in this association among Chinese adolescents. A cross-sectional study was performed in seven randomly selected Chinese provinces through the 2015 School-Based Chinese Adolescents Health Survey. A total of 159,640 adolescents were invited to participate and among them, 148,687 adolescents' questionnaires were completed and qualified for this study (response rate: 93.14%). All analyses were performed for boys and girls separately. There were significant sex differences in the prevalence of lifetime or past-year opioid misuse and sleep disturbance (p < 0.05). Among girls, frequent lifetime NMPOU (adjusted odds ratio [aOR] = 2.09, 95% CI = 1.80-2.44) and past-year NMPOU (aOR = 2.16, 95% CI = 1.68-2.77) were positively associated with sleep disturbance. Among boys, these associations were also statistically significant, while the magnitudes of associations between frequent lifetime NMPOU or past-year NMPOU and sleep disturbance were greater in girls than those in boys. There is a significant sex difference in the prevalence of lifetime or past-year NMPOU and sleep disturbance. Furthermore, exposure to more frequent lifetime or past-year NMPOU is associated with a greater risk of sleep disturbance, especially among girls. Taking into account the sex difference for lifetime or past-year NMPOU may help to decrease the risk of sleep disturbance.

Association between nonmedical use of opioids or sedatives and suicidal behavior among Chinese adolescents: An analysis of sex differences.

OBJECTIVE: The rising rate of suicidal behavior among adolescents is a growing concern, and sex differences may induce differential exposure to prescription drug misuse or suicidal behavior. We estimated, among Chinese adolescents, (1) the prevalence of nonmedical use of prescription drugs, suicidal ideation and suicide attempts; (2) whether nonmedical use of prescription drugs was independently associated with suicidal ideation and suicide attempts; and (3) whether there were sex differences in the associations. METHODS: This was a secondary analysis of the data drawn from the 2015 National School-based Chinese Adolescents Health Survey. A total of 94,911 students completed questionnaires and qualified for our survey (response rate: 93.7%). All analyses were conducted separately for boys and girls. RESULTS: There were significant sex differences in the prevalence of opioid or sedative misuse, and the sources and reasons for nonmedical use of prescription drugs ( p < 0.05). The prevalence of suicidal ideation or suicide attempts was significantly higher in girls than in boys (suicidal ideation: 17.9% among girls vs 14.1% among boys; suicide attempts: 3.5% among girls vs 2.7% among boys). Among girls, frequent use of opioids was associated with an increased risk of suicidal ideation (adjusted odds ratio = 1.84, 95% confidence interval = [1.57, 2.17]) and suicide attempts (adjusted odds ratio = 2.96, 95% confidence interval = [2.34, 3.74]), and frequent use of sedatives was also positively associated with suicidal ideation (adjusted odds ratio = 2.23, 95% confidence interval = [1.91, 2.60]) and suicide attempts (adjusted odds ratio = 4.02, 95% confidence interval = [3.25, 4.99]). These associations were also statistically significant in boys, but the magnitudes of adjusted odds ratios for the associations between frequent use of opioids and sedatives and suicidal behavior were greater in girls than boys. CONCLUSION: There exist significant sex differences in the prevalence rates of nonmedical use of prescription drugs and suicidal behavior, and the child's sex plays a role in the association between nonmedical use of prescription drugs and suicidal behavior. The significant sex differences found above may provide a basis for early identification of adolescents at high risk of suicidal behavior.

Influence of andrographolide on the pharmacokinetics of warfarin in rats.

CONTEXT: Andrographolide and warfarin are often used together in clinics in China. However, the herb-drug interaction between andrographolide and warfarin is still unknown. OBJECTIVE: This study investigates the herb-drug interaction between andrographolide and warfarin in vivo and in vitro. MATERIALS AND METHODS: A sensitive and reliable LC-MS/MS method was developed for the determination of warfarin in male Sprague-Dawley rats plasma, and then the pharmacokinetics of orally administered warfarin (0.5 mg/kg) with or without andrographolide (30 mg/kg/day for 7 days) pretreatment was investigated. In addition, Sprague-Dawley rat liver microsomes incubation systems were used to support the in vivo pharmacokinetic data and investigate its potential mechanism. RESULTS: The method validation results showed that a sensitive and reliable LC-MS/MS method was developed for the determination of warfarin in rat plasma samples. The pharmacokinetic results indicated that co-administration of andrographolide could increase the systemic exposure of warfarin significantly, including area under the curve (118.92 ± 18.08 vs. 60.58 ± 9.46 µg × h/mL), maximum plasma concentration (3.32 ± 0.41 vs. 2.35 ± 0.25 µg/mL) and t1/2 (22.73 ± 3.28 vs. 14.27 ± 2.67 h). Additionally, the metabolic stability of warfarin increased from 23.5 ± 4.7 to 38.7 ± 6.1 min with the pretreatment of andrographolide, and the difference was significant (p < 0.05). DISCUSSION AND CONCLUSION: In conclusion, andrographolide could increase the systemic exposure of warfarin in rats when andrographolide and warfarin were co-administered, and possibly by slowing down the metabolism of warfarin in rat liver by inhibiting the activity of CYP3A4 or CYP2C9.