[Sinoline inhibits NLRP3 and downstream inflammatory factors to alleviate the arthritis symptoms in adjuvant arthritis rats].

Objective To investigate the anti-inflammatory effects of sinoline on adjuvant arthritis (AA) rats and the changes of NOD like receptor pyrin-domain containing 3 (NLRP3). Methods Wistar rats were randomly divided into control group, AA model group, (100, 200, 400) mg/kg sinomenine group and 100 mg/kg Tripterygium wilfordii group, with 10 rats in each group. Except for the control group, AA model was established by Freund complete adjuvant. 12 days after modeling, control group and model group were given the same amount of normal saline, and other groups were given drugs by intragastric administration, once a day, for consecutive 16 days. Joint conditions of AA rats were evaluated by multiple arthritis and joint swelling. The level of NLRP3 protein in synovial tissues was detected by Western blot, and the expression and distribution of NLRP3 in synovial tissues were detected by immunohistochemical staining. Serum levels of interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor α (TNF-α) were detected by ELISA. Results Compared with the control group, multiple arthritis and joint swelling significantly increased in model group, while those significantly decreased in sinomenine treatment groups and Tripterygium wilfordii group. Decreased expression of NLRP3 protein in synovial tissue was observed, along with the significantly reduced levels of IL-1ß, IL-6 and TNF-α in serum in sinoline treatment groups. Conclusion Sinolin can improve joint inflammation in AA rats by inhibiting NLRP3 and downstream inflammatory factors.

Gender- and age-specific associations of childhood maltreatment with peripheral serum inflammatory cytokines in middle school students.

Background: The impact of childhood maltreatment on multiple inflammatory cytokines among middle school students remains to be elucidated. This study aimed to examine the associations of different types of childhood maltreatment with peripheral serum inflammatory cytokines (interleukin-10, interleukin-1ß, interleukin-6, interleukin-8, and tumor necrosis factor-α) in middle school students, and to explore the differences in these associations between boys and girls and between late (≥15 and<20 years) and early (≥11 and <15 years) adolescence. Methods: A total of 1122 students were recruited from a boarding middle school. Each participant was asked to respond to a detailed questionnaire on childhood maltreatment, from whom one blood sample was drawn via venous blood. Results: In the overall sample there was no association between childhood maltreatment and peripheral serum inflammatory cytokines; (2) emotional abuse was significantly correlated with IL-1ß only in girls (B = -0.16; 95% CI, -0.28~-0.03; p = 0.06); (3) in late adolescence, emotional abuse, emotional neglect, and childhood maltreatment had marked link with IL-8 (B = 0.39; 95%CI, 0.16~0.63; p = 0.01; B =0.20; 95% CI, 0.04~0.37; p = 0.08; B = 0.50; 95% CI, 0.18~0.82; p = 0.01, respectively). Conclusion: These findings also strengthened an inference regarding the effects of childhood maltreatment on inflammation of students in late adolescence.

Patterns of adverse childhood experiences and depressive symptom trajectories in young adults: A longitudinal study of college students in China.

Background: Adverse childhood experiences (ACEs) tend to cluster together in daily life, and most studies focus on the level of depression at certain points, but the dynamic process of depression is often neglected. Thus, research is urgently needed to explore the relationship between ACEs pattern and trajectory of depressive symptom levels at multiple time points in order to provides early targeted interventions to those who are most at risk. Objective: We aimed to explore patterns of ACEs, including types and timing, associated with depression trajectories in college students. Methods: A school-based health survey was used to collect data as part of a longitudinal study in two medical college in Anhui province, China. Questionnaires were issued to 3,662 participants aged 17-22 and recorded details of ACEs (types and timing) and depression. Latent class analysis (LCA) was used to identify "patterns" of ACEs type and timing. Depressive symptom trajectories employed latent class growth analysis (LCGA). Multiple logistic regressions were employed to evaluate the relationships between ACEs patterns and depressive symptom trajectories. Results: We identified five ACEs patterns: "High neglect/emotional abuse/community violence," "High neglect/emotional abuse," "High neglect/family dysfunction," "High neglect," "Low ACEs." We traced three depression trajectories: "High depressive symptom" "Moderate depressive symptom," "Low depressive symptom." "High neglect/emotional abuse/community violence," "High neglect/emotional abuse" and "High neglect/family dysfunction" demonstrated a high risk for "High depressive symptom" and "Moderate depressive symptom." "High neglect" showed a high risk for "Moderate depressive symptom" but not for "High depressive symptom" (P < 0.05). Conclusions: The findings address the need for a comprehensive consideration of exposure to childhood adversity associated with the risk of depression in young adults through identifying more problematic ACEs patterns amongst exposed children.

Mediating Effect of Sleep Disorder Between Low Mental Health Literacy and Depressive Symptoms Among Medical Students: The Roles of Gender and Grade.

OBJECTIVE: In this study, we aimed to disentangle the mediating effect of sleep disorder between mental health literacy (MHL) and depressive symptoms in Chinese medical students, especially focusing on the impact of gender and grade. METHODS: Pooled longitudinal data of 5,504 medical students was collected between November 2019 and June 2020 to assess the MHL, sleep disorder and mental health of medical students in Anhui province, China. Mediation analyses were tested by using bootstrapping procedures. RESULTS: Sleep disorder were negatively correlated with adequate MHL, but positively correlated with depressive symptoms. The relationships between MHL and depressive symptoms were mediated by sleep disorder in total samples and the indirect effect accounted for 13.59% of the total effect. However, the ratio was 20.82% in female students, whereas no mediating effect was found in the male students. Moreover, the ratio was found higher in freshmen (15.11%) than that in sophomores (11.56%). CONCLUSION: Improving the sleep disorder by enhancing MHL is an effective way to reduce depressive symptoms in Chinese medical students. Further investigations elaborately considered by using more gender-balanced population with higher grade and lower level of education.

Mediating effects of parent-child relationship on the association between childhood maltreatment and depressive symptoms among adolescents.

BACKGROUND: Depressive symptoms are the most common mental disorder among adolescents, and its prevalence has been increasing in recent years. Although childhood maltreatment is a contributing factor to depressive symptoms among adolescents, the underlying mechanism of how this factor causes depressive symptoms is unclear. OBJECTIVE: This study aimed to investigate the mediating effects of parent-child relationship on the association between childhood maltreatment and depressive symptoms among adolescents and to identify how sex and only child status affect this association. METHODS: A total of 14,500 middle school students were randomly selected from four cities (Shenzhen, Zhengzhou, Nanchang, and Guiyang) in China. A survey questionnaire was administered to collect information on childhood maltreatment, parent-child relationship, and depressive symptoms. Pearson's correlation analysis was used in analyzing the relationship, Bootstrap method was used to test the mediating effects. A moderated mediation analysis has been used to determine the moderated mediation effect. RESULTS: Childhood maltreatment significantly negatively correlated with parent-child relationship and positively correlated with depressive symptoms (P < 0.001). The indirect effect of parent-child relationship accounted for 20.60% of the total effect between childhood maltreatment and depressive symptoms in all respondents and differed by sex (boys, 17.00%; girls, 25.23%) and only child status (only child, 15.61%; child with siblings, 23.49%). Besides, the indirect effect of the mediation model was moderated by sex and only child status. CONCLUSIONS: Childhood maltreatment increased the risk of depressive symptoms, and this relationship was partially mediated by parent-child relationship, sex and only child status have moderated the indirect relationship. These findings showed efforts aimed at enhancing the parent-child relationship may prevent or reduce the prevalence of depressive symptoms among adolescents, especially in girls and children with siblings.

Inadequate Mental Health Literacy and Insufficient Physical Activity Potentially Increase the Risks of Anxiety and Depressive Symptoms in Chinese College Students.

Objective: The present study aimed to examine the interactive associations between physical activity and mental health literacy with anxiety and depressive symptoms in Chinese college students. Methods: A cross-sectional study was conducted from May to July 2020. A total of 7,512 students were recruited from two medical colleges in Hefei and Anqing city in Anhui Province, China. Physical activity, mental health literacy, anxiety and depressive symptoms were measured by self-reported validated instruments. Analyses were conducted with logistic regression models. Results: The prevalence of anxiety and depressive symptoms was 8.6% and 16.4%, respectively. Insufficient physical activity was significantly associated with depressive symptoms (OR = 1.359, 95%CI 1.184-1.561) and anxiety symptoms (OR = 1.492, 95%CI: 1.237-1.799). Inadequate mental health literacy was significantly associated with depressive symptoms (OR = 3.089, 95%CI: 2.607-3.662) and anxiety symptoms (OR = 3.675, 95%CI: 2.861-4.721). Low physical activity rank (OR = 1.438, 95%CI: 1.151-1.798) was significantly related with depressive symptoms but not anxiety symptoms. The students who had inadequate mental health literacy and insufficient physical activity had the highest risks of depressive symptoms (OR = 5.049, 95% CI: 3.649-6.987) and anxiety symptoms (OR = 5.270, 95% CI: 3.338-8.321). Conclusion: These finding indicated that Chinese college students having insufficient physical activity and inadequate mental health literacy are at risk of exhibiting anxiety and depressive symptoms. Early intervention programs for college students with mental health problems should be considered to enhance their mental health literacy and to increase their physical activities.

Antioxidant and Anti-inflammatory Properties Mediate the Neuroprotective Effects of Hydro-ethanolic Extract of Tiliacora triandra Against Cisplatin-induced Neurotoxicity.

BACKGROUND: Cisplatin (CDDP) is an efficacious anticancer agent used widely in chemotherapy despite its severe side effect related to neurotoxicity. Redox imbalance and inflammatory mechanism have been implicated in the pathophysiology of CDDP-induced neurotoxicity. Herein, we investigated whether Tiliacora triandra (TT) extract could inhibit  CDDP-induced redox-mediated neurotoxicity and behavioural deficit in rats. MATERIALS AND METHODS: CDDP-induced redox-mediated neurotoxicity and behavioral deficit in rats. Rats were administered TT for five consecutive weeks (250 and 500 mg/kg bw), while weekly i.p. injection of CDDP commenced on the second week (2.5 mg/kg bw) of the TT administration. RESULTS: CCDDP caused significant body weight reduction and cognitive diminution as revealed by Morris water maze and Y maze tests. In the CDDP-induced cognitive impairment (CICI) rats, there were remarkable increases in the brain levels of TNF-α, IL-6 and IL-1ß and malondialdehyde (MDA), whereas catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities considerably decreased compared to normal control. The brain acetylcholinesterase (AChE) activity in CDDP control rats was significantly increased compared to the normal control. The expression of caspase-3 and p53 proteins was upregulated by CDDP injection, whereas Bcl2 was downregulated coupled with histopathological alterations in the rat brain. Interestingly, treatment with TT significantly abated neurobehavioral deficits, MDA and cytokine levels and restored CAT, GPx, GSH, SOD, and AChE activities compared to the CDDP control rats. Caspase-3 level as well as Bcl2 and p53 expressions were modulated with alleviated changes in histopathology. CONCLUSION: The findings highlight neuroprotective and cognitive function improvement efficacy of TT against CICI via redox-inflammatory balance and antiapoptotic mechanism in rats.

Interaction of smoking and being bullied on suicidal behaviors: a school-based cross-sectional survey in China.

BACKGROUND: Suicidal behaviors are seriously social issues among adolescents in the world. Exposed to smoking and being bullied are risk factors of suicidal behaviors. The present study was aimed to examine the interaction of smoking and being bullied on suicidal behaviors among Chinese adolescents. METHODS: A total of 18,900 students were involved in the questionnaire study, in four cities of China from November 2017 to January 2018. Suicidal behaviors, smoking, and being bullied were measured by self-reported validated instruments. Chi-square tests and logistic regression were used to analyze the associations of suicidal ideation (SI)/suicidal plan (SP)/suicidal attempt (SA), smoking, and being bullied. RESULTS: The prevalence of smoking, being bullied, SI/SP/SA, were 3.1%, 20.6%, 26.4%, 13.2%, and 5.2% respectively. Interaction analysis indicated that being bullied was associated with a greater increase in the likelihood of suicidal behaviors for adolescents with smoking than for those without smoking. CONCLUSIONS: These finding suggest that smoking exacerbates the association between being bullied and suicidal behaviors. Future research should explore how and why smoking appears to more bully-victims than for those without smoking and how to mitigate it.

Moderating Role of Health Literacy on the Association between Alexithymia and Depressive Symptoms in Middle School Students.

Depression is a common psychological problem in adolescents. At present, few studies have described the moderating role of health literacy on the association between alexithymia and depressive symptoms among adolescents. The purpose of this study was to explore the relation among health literacy, alexithymia, and depressive symptoms and the moderating role of health literacy in middle school students. In December 2017, data were collected from a school in Shenyang by the convenient sampling method using a questionnaire including demographic information, health literacy, alexithymia, and depressive symptoms. A total of 1068 junior and senior high school students were selected as subjects, and 1062 valid questionnaires were retained for analysis. Logistic regression models were used to examine the association between health literacy and alexithymia with depressive symptoms. The prevalence of depressive symptoms was 48.2%, and the prevalence of alexithymia was 17.9%. Low health literacy was significantly associated with depressive symptoms (odds ratio (OR) (95% confidence interval (CI)) = 3.648 (2.493-5.338)). Alexithymia was significantly correlated with depressive symptoms (OR (95% CI) = 3.091 (2.156-4.429)). Low health literacy was related to a greater increase in the risk of depressive symptoms for students with alexithymia (OR (95% CI) = 10.566 (5.175-21.570)). The findings suggest that alexithymia and health literacy are important factors influencing depressive symptoms and health literacy has a moderating role on the association between alexithymia and depressive symptoms. Enhancing health literacy of middle school students with alexithymia may improve their mental health.

Mediating Effects of Specific Types of Coping Styles on the Relationship between Childhood Maltreatment and Depressive Symptoms among Chinese Undergraduates: The Role of Sex.

Although childhood maltreatment is known to be associated with depressive symptoms, few studies have investigated the mediating effect of different types of coping styles on this association. It is unknown whether the impacts vary by sex. We investigated the mediating effects of different coping styles on the relationship between childhood maltreatment and depressive symptoms among Chinese undergraduates, as well as the role of sex in the mediated pathways. A total of 7643 college freshmen and sophomores (5665 females, 1978 males; 4215 freshmen, 3428 sophomores; mean age, 19.67 years) from two colleges in China completed a standard questionnaire on the details of childhood maltreatment, depressive symptoms, and coping styles. Childhood maltreatment was significantly correlated with all coping styles and depressive symptoms studied (p < 0.001). Problem solving, self-blame, help seeking, problem avoidance, and rationalization mediated the relationship between childhood maltreatment and depressive symptoms. The estimated ratio of the effect of childhood maltreatment on the occurrence of depressive symptoms can be explained by the mediation of problem solving, self-blame, help seeking, problem avoidance, and rationalization, which accounted for 15.1%, 25.6%, 7.4%, 1.6% and 1.6% of the total effect, respectively. Sex differences were found to have mediating effects on coping styles in terms of the relationship between childhood maltreatment and depressive symptoms. The findings illustrate the need to focus on coping styles and to employ sex-specific methods to effectively help college students reduce depressive symptoms associated with childhood maltreatment.

Effects of Cyclopamine on the Viability of Articular Chondrocytes in Rats with Adjuvant Arthritis in vitro.

The aim of the present study is to investigate the effect of cyclopamine, a hedgehog signaling pathway inhibitor, on adjuvant arthritis (AA), rat articular chondrocyte viability, and part mechanisms in vitro In this study, an AA rat model was established by Freund's complete adjuvant (FCA). The arthritis index (AI), secondary paw swelling degree, and HE staining were used to evaluate whether the model was successfully established. Chondrocytes of the ankle joint of AA rats were cultured and identified. Cyclopamine (0, 0.03, 0.1, 0.3, 1, 3, 10 and 30 mg/l) was administered to determine chondrocyte viability. Chondrocyte apoptosis was detected by Annexin V-FITC/PI double dye. The expression of hedgehog signaling pathway-related proteins Shh, Ptch1, and Gli1 in chondrocytes was detected by western blotting. The results show that AA was successfully induced by FCA since the AI of AA rats and secondary paw swelling degree increased and the cartilage tissue of the rats' ankle joint was damaged. Thus, the chondrocytes were successfully cultured in vitro following the identification of toluidine blue and type II collagen. Cyclopamine (0.03, 0.1, 0.3, 1, 3, 10 and 30 mg/l) could increase the viability of chondrocytes in vitro and reduce the apoptotic rate of chondrocytes. As compared with the control group, different doses of cyclopamine (0.3, 3 and 10 mg/l) significantly decreased the expression of Shh, Ptch1 and Gli1 proteins in AA chondrocytes. Therefore, an AA rat model was successfully established in the present study and cyclopamine improved the viability and inhibited the apoptosis of chondrocytes. This is an effect that may be associated with the inhibition of the chondrocyte hedgehog signaling pathway.

Nesfatin-1 is a potential diagnostic biomarker for gastric cancer.

The lack of reliable plasma biomarkers limits their use in the diagnosis of gastric cancer (GC). The current study aimed to determine whether plasma nesfatin-1 can be used as a novel non-invasive biomarker for the diagnosis of GC. The levels of nesfatin-1 in 40 patients with GC and 40 healthy individuals, who were selected from the Chaohu Hospital Affiliated to Anhui Medical University, were assessed. ELISA was used for the measurement of plasma nesfatin-1 levels, while immunohistochemistry was applied to determine Ki67 protein expression in GC and normal gastric tissues. The diagnostic value of plasma nesfatin-1 for GC was further assessed using receiver operating characteristic (ROC) curve analysis. The results revealed that, compared with the controls, the mean nesfatin-1 levels in patients with GC were significantly increased. Furthermore, the protein expression of Ki67 in GC tissue was significantly upregulated compared with that in normal gastric tissue. Plasma nesfatin-1 levels were also demonstrated to be correlated with Ki67 protein expression in GC tissues. Additionally, ROC curve analysis indicated the potential diagnostic value of nesfatin-1, and the area under the ROC curve (AUC) for nesfatin-1 was 0.857 (95% confidence interval, 0.769-0.946). At a threshold nesfatin-1 level of 1.075 ng/ml, the optimal sensitivity and specificity were 70.0 and 95.0%, respectively, in discriminating patients with GC from healthy controls. These results indicated that plasma nesfatin-1 may serve as a novel biomarker for the diagnosis of GC and determination of GC cell proliferation.

Mediating Effect of Social Support in the Relationship Between Childhood Abuse and Non-Suicidal Self-Injury Among Chinese Undergraduates: The Role of Only-Child Status.

Previous research has found a relationship between child abuse and non-suicidal self-injury (NSSI). However, few studies have examined the role of social support underlying this association. Moreover, the influence of the only child status on the mediating effect of social support has not been studied yet. The aim of this study was to investigate the mediating role of social support on the association between specific forms of child abuse and NSSI as well as the role of the only child status on the mediated pathways, among undergraduates. A total of 4799 participants were selected from two medical colleges in the Anhui province using stratified cluster sampling. Pearson's correlation analysis was used in analyzing the relationship. Bootstrapping procedures were applied to examine the mediating effects. After adjusting for confounders, the results showed that the mediating effect of social support on the association between childhood abuse and NSSI was not significant in the total sample. However, among only children, the mediating effects of social support between overall childhood abuse, physical abuse, emotional abuse, and NSSI were 9.65%, 14.82%, and 8.12%, respectively. Moreover, the mediating effect of social support from family and relatives was relatively higher than that from other sources. Social support had a mediating effect on the relationship between childhood abuse and NSSI among only-children. The enhancing of social support may contribute to the prevention and control of NSSI for those who were only-children in undergraduates, especially those who have experienced childhood abuse.

Low KISS1 expression predicts poor prognosis for patients with colorectal cancer: A meta-analysis.

KISS1 and KISS1R, a novel pair of metastasis suppressors, are likely to be associated with the prognosis of colorectal cancer (CRC). Here, a meta-analysis was performed to study the role of KISS1 and KISS1R in CRC. Heterogeneity, stability and publication bias were all estimated. Six publications describing a total of 559 CRC patients were included in the present study. Low KISS1 expression predicted 70% higher risk of poor prognosis for general patients (HR, 1.71; 95% CI, 1.28-2.29) and 99% higher risk for East Asian patients (HR, 1.99; 95% CI, 1.46-2.72). Limited evidence indicated that decreased KISS1R expression might predict poor outcome (HR, 2.96; 95% CI, 1.51-5.82). Neither heterogeneity nor publication bias was identified. The current analyses suggest that low KISS1 expression predicts poor overall survival among East Asian patients with CRC. Evidence on other races and KISS1R are still insufficient, and additional studies are required to clarify the risk of CRC associated with KISS1R by race.

Atorvastatin combined with poly-unsaturated fatty acid confers better improvement of dyslipidemia and endothelium function.

BACKGROUND: Atorvastatin and poly-unsaturated fatty acid (PUFA) are beneficial for lipid-modification, whether atorvastatin plus PUFA could confer better improvement on dyslipidemia and endothelium function is unknown. METHODS: Dyslipidemia model of 40 rabbits were produced with atherogenic diet, and thereafter saline, atorvastatin, PUFA, or atorvastatin plus PUFA were prescribed for 1 week. Ten rabbits given normal diet served as the sham group. Parameters of interest including lipid profiles, endothelium function (nitric oxide, NO) and activation (solution vascular-cellular adhesion molecule, (sVCAM) and intracellular adhesion molecule, (sICAM)), markers of inflammation (C-reactive protein, CRP) and oxidation (malondialdehyde, MDA) were compared among groups. RESULTS: There was no significant difference of parameters among groups at the initial. With 1 week of atherogenic diet administration, serum levels of lipid profiles, sVCAM and sICAM, CRP and MDA were significantly increased, accompanying with profound NO reduction, as compared to the sham group. After 1 week of medical intervention, as compared to the control group (saline administration), dyslipidemia and endothelium function were modestly improved with either atorvastatin or PUFA therapy. Nevertheless, these efficacies were further and significantly enhanced with combined therapy when compared to the control group (p<0.005), suggesting that there was synergistic effects of atorvastatin and PUFA co-therapy in rabbits with dyslipidemia. CONCLUSION: Atorvastatin plus PUFA therapy could immediately contribute to better improvement of lipid-modification and endothelium function in rabbits with dyslipidemia.