Discovery of novel osthole derivatives exerting anti-inflammatory effect on DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice.

The modification based on natural products is a practical way to find anti-inflammatory drugs. In this study, 26 osthole derivatives were synthesized, and their anti-inflammatory properties were evaluated. The preliminary activity study revealed that most osthole derivatives could effectively inhibit inflammatory cytokines IL-6 secretion in LPS stimulated mouse macrophages J774A.1. Compound 7m exhibited the most effective anti-inflammatory activity (RAW264.7 IL-6 IC50: 4.57 µM, 32 times more active than osthole) in vitro with no significant influence on cell proliferation. Additionally, the mechanistic analysis demonstrated that compound 7m could block MAPK signal transduction by inhibiting the phosphorylation of JNK and p38, thereby inhibiting the release of inflammatory cytokines. Moreover, in vivo functional investigations revealed that 7m could substantially reduce DSS-induced ulcerative colitis and LPS-induced acute lung injury, with good therapeutic effects. The pharmacokinetics and acute toxicity experiments proved the safety and reliability of 7min vivo. Overall, Compound 7m could further be studied as potential anti-inflammatory candidate.

Adjunctive repetitive transcranial magnetic stimulation for adolescents with first-episode major depressive disorder: a meta-analysis.

Objective: This meta-analysis of randomized clinical trials (RCTs) was conducted to explore the therapeutic effects, tolerability and safety of repetitive transcranial magnetic stimulation (rTMS) as an adjunct treatment in adolescents with first-episode major depressive disorder (FE-MDD). Methods: RCTs examining the efficacy, tolerability and safety of adjunctive rTMS for adolescents with FE-MDD were included. Data were extracted by three independent authors and synthesized using RevMan 5.3 software with a random effects model. Results: A total of six RCTs involving 562 adolescents with FE-MDD were included. Adjunctive rTMS was superior in improving depressive symptoms over the control group [standardized mean difference (SMD) = -1.50, 95% confidence interval (CI): -2.16, -0.84; I2 = 89%, p < 0.00001] in adolescents with FE-MDD. A sensitivity analysis and two subgroup analyses also confirmed the significant findings. Adolescents with FE-MDD treated with rTMS had significantly greater response [risk ratio (RR) = 1.35, 95% CI: 1.04, 1.76; I2 = 56%, p = 0.03] and remission (RR = 1.35, 95% CI: 1.03, 1.77; I2 = 0%, p = 0.03) over the control group. All-cause discontinuations were similar between the two groups (RR = 0.79, 95% CI: 0.32, 1.93; I2 = 0%, p = 0.60). No significant differences were found regarding adverse events, including headache, loss of appetite, dizziness and nausea (p = 0.14-0.82). Four out of six RCTs (66.7%), showed that adjunctive rTMS was more efficacious over the control group in improving neurocognitive function (all p < 0.05). Conclusion: Adjunctive rTMS appears to be a beneficial strategy in improving depressive symptoms and neurocognitive function in adolescents with FE-MDD. Higher quality RCTs with larger sample sizes and longer follow-up periods are warranted in the future.

Adjunctive tDCS for treatment-refractory auditory hallucinations in schizophrenia: A meta-analysis of randomized, double-blinded, sham-controlled studies.

OBJECTIVE: Treatment-refractory auditory hallucinations (TRAH) in schizophrenia often do not improve with pharmacotherapy. We performed a meta-analysis of randomized, double-blind, sham-controlled clinical trials (RCTs) that systematically examined the therapeutic effects and tolerability of adjunctive active versus sham active transcranial direct current stimulation (tDCS) for auditory hallucinations as measured by the Auditory Hallucination Rating Scale (AHRS) in schizophrenia patients with TRAH. METHODS: Relevant data were extracted, checked and analyzed using the Review Manager, Version 5.3 by three independent investigators. RESULTS: Eight double-blind RCTs covering 329 schizophrenia patients (168 in active tDCS group, 161 in sham tDCS group) were included. Although no advantage of active tDCS on auditory hallucinations [7 RCTs, n = 224; standardized mean difference (SMD): - 0.33 (95% confidence interval (CI): - 0.71, 0.05), P = 0.09; I2 = 46%] was found compared to sham, subgroup analyses revealed that active tDCS with twice-daily stimulation [6 RCTs, n = 198; SMD: - 0.42 (95%CI: -0.82, -0.02), P = 0.04; I2 = 44%] and active tDCS with ≥ 10 stimulation sessions [6 RCTs, n = 198; SMD: - 0.42 (95%CI: -0.82, -0.02), P = 0.04; I2 = 44%] showed a significantly better therapeutic effect than sham in improving auditory hallucinations symptoms. Meta-analyses of total psychopathology and discontinuation due to any reason were not significantly different between the active and sham tDCS groups. CONCLUSION: This meta-analysis demonstrated that the effects of tDCS for auditory hallucinations symptoms were influenced by the tDCS parameters. Twice-daily stimulation and ≥ 10 stimulation sessions may be needed to improve auditory hallucinations symptoms in schizophrenia with TRAH.

Comparative effectiveness of repeated ketamine infusions in treating anhedonia in bipolar and unipolar depression.

OBJECTIVES: Anhedonia is a common, persistent, and disabling phenomenon in patients with major depressive disorder (MDD) and bipolar depression (BD). This study was conducted to investigate the comparative effectiveness of repeated ketamine infusions in treating anhedonia in Chinese individuals suffering from MDD and BD. METHODS: Ninety-seven individuals suffering from MDD (n = 77) or BD (n = 20) were treated with six intravenous infusions of ketamine (0.5 mg/kg) administered over 40 min. Anhedonia was measured through the Montgomery-Åsberg Depression Rating Scale (MADRS). The antianhedonic response and remission were defined as ≥ 50% and ≥ 75% reduction in MADRS anhedonia subscale score one day after the sixth infusion, respectively. RESULTS: Anti-anhedonic response and remission rates after the sixth ketamine infusion were 48.5% (95% confidence interval =  38.3%-58.6%) and 30.9% (95% confidence interval = 21.6%-40.3%), respectively. When compared to baseline, a significant reduction in the MADRS anhedonia subscale score was observed at 4 h after the first infusion and was maintained with repeated infusions at any time point (all Ps < 0.05). The anti-anhedonic effect of ketamine did not differ between the MDD and BD groups. CONCLUSION: This preliminary study found that repeated ketamine infusions appeared to be effective at rapidly ameliorating anhedonia, with similar efficacy in MDD and BD.

Adjunctive multi-session transcranial direct current stimulation for neurocognitive dysfunction in schizophrenia: A meta-analysis.

Findings of multi-session transcranial direct current stimulation (tDCS) as an adjunctive treatment of neurocognitive dysfunction in schizophrenia have been inconsistent. This meta-analysis of randomized controlled trials (RCTs) investigated the neurocognitive effects of adjunctive multi-session tDCS for schizophrenia. Twelve RCTs covering 418 schizophrenia patients were included and analyzed in this meta-analysis. The RevMan software (Version 5.3) was used to calculate risk ratios (RRs) and standardized mean differences (SMDs) with their 95% confidence intervals (CIs). Adjunctive tDCS outperformed the comparator in improving working memory deficits (SMD = 0.34, 95% CI: 0.03, 0.65; I2 = 52%; p = 0.03), but no significant effects were found in other cognitive domains. No group differences were found with regard to total psychopathology measured by the Brief Psychiatric Rating Scale and the Positive and Negative Symptom Scale (SMD =-0.29, 95%CI: -0.61, 0.03; I2 = 50%, p = 0.07) and discontinuation due to any reason (RR=0.80, 95%CI: 0.39, 1.66; I2 = 9%, p = 0.56). Adjunctive tDCS appears to have a significant therapeutic effect improving the working memory deficits in schizophrenia.

Workplace Violence in County Hospitals in Eastern China: Risk Factors and Hospital Attitudes.

Workplace violence (WPV) against health workers is a public concern worldwide. Yet little is known about WPV in Chinese county level hospitals and its risk factors. The current study aimed to examine the prevalence of and the risk factors of WPV in county hospitals. A total of 1,388 health workers were interviewed in eight county hospitals in four counties of Zhejiang Province. Results indicated that 7.8% of participants suffered physical attacks and 21.2% suffered physical threats, 51.6% experienced or witnessed Yi Nao (medical disturbance created by gangs using extreme means to obtain compensation from a hospital) at least once in the past year. Physical attacks were seen significantly more in physicians (10.9%) than in nurses (5.9%). Physicians were threatened at 27.1%, followed by nurses at 20.2%. Compared with general medicine, health workers working in emergency were significantly more likely to suffer physical attacks (odds ratio [OR] = 2.7, 95% confidence interval [CI] = [1.4, 5.2], p < .01) and WPV (physical attacks or threats; OR =2.5, 95% CI = [1.6, 4.1], p < .001). Being encouraged to tolerate WPV was correlated with physical attacks (OR = 6.1, 95% CI = [3.5, 10.4], p < .001) and WPV (OR = 6.7, 95% CI = [4.6, 9.8], p < .001). Health workers in county hospitals were vulnerable to encounter WPV. This highlights the need for a focused systematic prevention concerning health workers' safety and governmental regulations and the need for hospitals to encourage their employees to report the WPV.

A cross-sectional study of antibiotic misuse among Chinese children in developed and less developed provinces.

INTRODUCTION: Antimicrobial resistance is a global health crisis and primarily caused by antibiotic misuse. Antibiotic misuse among children is particularly concerning, and its prevalence may vary from region to region in China with different development levels. METHODOLOGY: Zhejiang and Shaanxi were selected to represent developed and less developed provinces in China, respectively. Data of 2924 parents in Zhejiang and 3355 parents in Shaanxi whose children were 0-13 years old were collected through multi-stage stratified cluster random sampling and a self-administrated questionnaire. Chi-square tests and logistic regression models were used for statistical analysis. RESULTS: Compared to parents in Zhejiang, those in Shaanxi were more likely to keep antibiotics for children at home, to engage in self-medication with antibiotics for children, and to make their children take antibiotics prophylactically. While there were no significant provincial differences between parents' requests for antibiotics during pediatric consultations, parents in Shaanxi province were more likely to receive prescribed antibiotics. CONCLUSIONS: Children in less developed provinces face higher risks of antibiotic misuse at home as well as when attending medical practitioners. Comprehensive educational interventions are required to improve antibiotic use for children all over China but particularly in less developed provinces such as Shaanxi. Furthermore, non-prescription sales and over-prescribing of antibiotics should be reduced by targeted strategies.

Influence of leftover antibiotics on self-medication with antibiotics for children: a cross-sectional study from three Chinese provinces.

OBJECTIVES: To investigate leftover antibiotics and their influence on self-medication with antibiotics (SMA) for Chinese children, and further explore the different influences of leftovers from two main sources: previous prescriptions and pharmaceutical purchases. DESIGN: A cross-sectional questionnaire study. SETTING: The participants were approached through kindergartens and primary schools as well as in vaccination clinics. PARTICIPANTS: A total of 9526 parents from three Chinese provinces whose children were aged 0-13 years completed the survey. OUTCOME MEASURES: The prevalence of keeping antibiotics at home for children and the proportion of leftover antibiotics from two main sources were measured by a self-administrated questionnaire. Logistic regression models were established to examine the association between keeping antibiotics at home and SMA for children, specifically the risks of leftovers from two main sources. RESULTS: Overall, 4580 (48.1%) reported keeping antibiotics at home for children. Among those who had leftovers, 2891 (63.1%) reported that their leftovers came from previous prescriptions and 1619 (35.3%) reported that their leftovers came from pharmaceutical purchases. Mothers, older age of child, higher household income, higher education level and medical background were significantly associated with keeping antibiotics at home. Keeping antibiotics at home was significantly associated with SMA for children (adjusted OR=4.91, 95% CI 3.84 to 6.28). Particularly, compared with parents who did not keep antibiotics at home, parents who kept leftover antibiotics from previous prescriptions and those whose leftovers came from pharmaceutical purchases were 3.80 (95% CI 2.89 to 5.00) and 6.45 (95% CI 4.89 to 8.51) times more likely to engage in SMA for children, respectively. CONCLUSIONS: Keeping antibiotics at home for children was pervasive in China. Most leftovers came from previous prescriptions, while those from pharmacies had a higher risk of SMA for children.

Cognition Impairment Prior to Errors of Working Memory Based on Event-Related Potential.

Cognitive impairment contributes to errors in different tasks. Poor attention and poor cognitive control are the two neural mechanisms for performance errors. A few studies have been conducted on the error mechanism of working memory. It is unclear whether the changes in memory updating, attention, and cognitive control can cause errors and, if so, whether they can be probed at the same time in one single task. Therefore, this study analyzed event-related potentials in a two-back working memory task. A total of 40 male participants finished the task. The differences between the error and the correct trials in amplitudes and latencies of N1, P2, N2, and P3 were analyzed. The P2 and P3 amplitudes decreased significantly in the error trials, while the N2 amplitude increased. The results showed that impaired attention, poor memory updating, and impaired cognitive control were consistently associated with the error in working memory. Furthermore, the results suggested that monitoring the neurophysiological characteristics associated with attention and cognitive control was important for studying the error mechanism and error prediction. The results also suggested that the P3 and N2 amplitudes could be used as indexes for error foreshadowing.

The Misconception of Antibiotic Equal to an Anti-Inflammatory Drug Promoting Antibiotic Misuse among Chinese University Students.

Massive misuse of antibiotics is one of the most important reasons for antimicrobial resistance (AMR). Misconceptions of antibiotics contribute to antibiotic misuse behaviors. This study aims to examine whether university students hold the misconception that AntibioticisaXiaoyanyao (literally means anti-inflammatory drug in Chinese), and association between this misconception and antibiotic misuse behaviors. A cross-sectional study was conducted among university students using the cluster random sampling method in six universities of six regions in China (one university per region). The Chi-square test was used to assess the relationship between the misconception and antibiotic misuse behaviors. Logistic regression was conducted to identify the risk factors for antibiotic misuse behaviors. 11,192 of university students completed the entire questionnaire. There were 3882 (34.7%) students who were considered to have the misconception. Female students were more likely to have the misconception compared with males (36.7% vs. 32.6%, P < 0.001). Those students with a background of social science/humanities were more likely to have the misconception compared with those from science and medicine (44.1% vs. 30.3% vs. 20.1%, P < 0.001). Students came from rural areas compared with those from urban areas (37.5% vs. 32.5%, P < 0.001) were more likely to have the misconception. Students who had the misconception were 1.51 (95% CI 1.21⁻1.89, P < 0.001) times, 1.34 (95% CI 1.21⁻1.48, P < 0.001) times, and 1.36 (95% CI 1.24⁻1.50, P < 0.001) times more likely to report self-medication, request to obtain antibiotics, and take antibiotics prophylactically than those who did not have this misconception, respectively. The high proportion of university students' misconception on AntibioticisaXiaoyanyao is worth more attention. Effective health education and interventions need to be promoted among university students and the whole population.

The Neuro Patterns Prior to Error Responses in Long-Lasting Working Memory Task: An Event-Related Potential Study.

Few studies exist regarding the mechanism prior to response by which cognitive impairment may induce error in a single long-lasting task. The present study intends to clarify the changes in cognition at the electrophysiological level. Changes in amplitude and latency of N1, P2, N2, and P3 components of event-related potentials (ERPs) were analyzed for error and correct trials during normal and fatigue. Twenty-nine participants had to perform a 2-back working memory (WM) task for 100 min. The first 10 min and the last 10 min of the task were used as the normal state and fatigue state of the participant, respectively. EEG data were obtained from the first 10-min period and the final 10-min period. The results revealed smaller P3 and P2 amplitudes and longer P2 and N2 latency in the final 10-min which was after a long-lasting time task. Moreover, smaller P3 and P2 amplitudes but larger N2 amplitudes were observed in error trials for both states. Our results indicated that: (1) long lasting involvement in a cognitive task had a detrimental effect on attention, memory updating and cognitive control; and (2) impaired attention, impairments in memory updating and cognitive control were related to task errors. Our results imply that several impaired cognitive processes were consistently associated with the error and the altered ERP represents the neural patterns prior to error response in mental fatigue state.

Antibiotic misuse among university students in developed and less developed regions of China: a cross-sectional survey.

BACKGROUND: Antimicrobial resistance (AMR) is a great threat to public health. The primary cause of AMR is human antibiotic misuse. Little is known about regional differences of antibiotic misuse behaviours in China. OBJECTIVES: To explore the antibiotic misuse behaviours among university students in western and eastern China and find out the regional differences. METHODS: Participants were recruited from universities in less developed Guizhou Province and developed Zhejiang Province using a cluster random sampling method. A self-administered questionnaire was designed to collect data, and the χ2 test and logistic regression were adopted to assess the associations between region and antibiotic misuse behaviours. RESULTS: A total of 2073 university students from Guizhou and 1922 from Zhejiang completed questionnaires. Students in Guizhou had lower household income, parents' education, and urban residence proportion than those in Zhejiang. Compared with those in Zhejiang, students in Guizhou had higher antibiotic use prescribed by doctors (79.8% vs 56.2%) and self-medication with antibiotics (33.0% vs 16.1%). Students in Guizhou were more likely to buy over-the-counter antibiotics without prescriptions (73.9% vs 63.4%), ask for antibiotics from doctors (21.4% vs 15.6%), and use antibiotics prophylactically (29.9% vs 15.7%). Adjusted models showed that the less developed region was significantly associated with higher antibiotic misuse behaviours. CONCLUSIONS: Misuse of antibiotics by well-educated young adults was very high in two regions but most serious in the less developed one. Campaigns are urgently needed to promote appropriate antibiotic use especially in less developed regions.

Defects of Gamma Oscillations in Auditory Steady-State Evoked Potential of Schizophrenia.

BACKGROUND: Patients with schizophrenia have many cognitive deficits. Gamma oscillations exist in the human brain and are closely related to neurocognition. Auditory Steady-State Responses (ASSRs) is an electroneurophysiological index that could reflect gamma oscillations. It was found that the energy evoked by 40 Hz ASSRs in schizophrenic patients was significantly lower than that in healthy subjects. However, the correlation between ASSRs phase index and clinical symptoms and neurocognitive deficits has yet to be systematically studied. The purpose of this study was to investigate the dysfunction of neural activity of gamma rhythmdys function and its association with clinical symptoms and neurocognition in patients with schizophrenia. AIMS: To compare and verify the difference in energy and phase coherence of 20 Hz and 40 Hz ASSRs between schizophrenia and healthy participants, and to explore the correlation between schizophrenia ASSRs and neurocognitive deficits. METHOD: Auditory steady-state evoked potentials by repeated auditory stimuli in 24 patients with schizophrenia and 30 healthy controls were recorded. The Positive and Negative Syndrome Scale (PANSS) was used to assess the clinical symptoms of the patients. MATRICS Consensus Cognitive Battery (MCCB) was used for the assessment of neurocognitive function. The correlation between indices, such as ASSRs energy, phase locking factor and phase coherence, and clinical and cognitive assessment was also systematically compared between two groups. RESULTS: Compared with the control group, the patient group had differences in cognitive domains including information processing speed (t=-2.39, p=0.021), attention/vigilance (t=-2.36, p=0.023), verbal learning (t=-3.11, p=0.003), and reasoning and problem solving (t=-2.60, p=0.012). The energy of 40 Hz ASSRs in the patient group was significantly lower than that in the control group (t=-2.291, p=0.032), and their phase locking factor and inter-trial phase coherence index were lower than control group (t=-3.017, p=0.004 and t=3.131, p=0.003), which was also significantly correlated to reasoning and problem solving function deficits. CONCLUSION: Patients with schizophrenia had defects in multiple cognitive domains, and their 40 Hz ASSRs energy was low. Specifically, their phase locking characteristics and phase coherence were poor, which was to some extent related to reasoning ability and thinking disorder.

Effect of adjunctive ranitidine for antipsychotic-induced weight gain: A systematic review of randomized placebo-controlled trials.

This study was a meta-analysis of randomized controlled trials (RCTs) of ranitidine as an adjunct for antipsychotic-induced weight gain in patients with schizophrenia. RCTs reporting weight gain or metabolic side effects in patients with schizophrenia were included. Case reports/series, non-randomized or observational studies, reviews, and meta-analyses were excluded. The primary outcome measures were body mass index (BMI) (kg/m2) and body weight (kg). Four RCTs with five study arms were identified and analyzed. Compared with the control group, adjunctive ranitidine was associated with marginally significant reductions in BMI and body weight. After removing an outlier study for BMI, the effect of ranitidine remained significant. Adjunctive ranitidine outperformed the placebo in the negative symptom score of the Positive and Negative Syndrome Scale. Although ranitidine was associated with less frequent drowsiness, other adverse events were similar between the two groups. Adjunctive ranitidine appears to be an effective and safe option for reducing antipsychotic-induced weight gain and improving negative symptoms in patients with schizophrenia. Larger RCTs are warranted to confirm these findings. Trial registration PROSPERO: CRD42016039735.

Adjunctive Melatonin for Tardive Dyskinesia in Patients with Schizophrenia: A Meta-Analysis.

BACKGROUND: Tardive dyskinesia (TD) is characterized by abnormal and involuntary movements. Importantly, TD could cause considerable personal suffering and social and physical disabilities. AIMS: This meta-analysis based on randomized controlled trials (RCTs) systematically assessed the therapeutic effect and tolerability of melatonin for TD in schizophrenia. METHODS: A computerized and systematical search of both Chinese (Wanfang Data, Chinese National Knowledge Infrastructure (CNKI), SINOMED) and English (PubMed, PsycINFO, Embase, Cochrane Library databases) databases, from their inception until June 8, 2017, was conducted by two independent authors. The severity of TD symptoms were the primary outcome measure and analyzed using a random effects model by the Review Manager (RevMan) Version 5.3. Quality evaluation of included RCTs was conducted using the Cochrane risk of bias and Jadad scale. The GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system recommendation grading method was used to assess the overall quality level of meta-analytic outcomes. RESULTS: Four RCTs (n=130) were identified and analyzed. Three RCTs used double blind and 1 RCT used masked assessors using the Cochrane risk of bias, and 3 RCTs were rated as high quality based on Jadad scale. Compared with the control group, adjunctive melatonin was superior in reducing the severity of TD as measured by the Abnormal Involuntary Movement Scale (AIMS) (4 RCTs, n=130, weighted mean difference (WMD): -1.52 (95% confidence intervals (CI): -3.24, 0.20), p=0.08; I2 =0%) although the improvement did not reach a significant level. The overall evidence quality of the improvement of TD symptoms, according to GRADE approach, was rated as "Low". The data on the ADRs and cognitive effect were limited. CONCLUSIONS: This meta-analysis shows that melatonin has potential for improving TD symptoms in schizophrenia. Future higher quality and larger RCTs are warranted to confirm the findings.