Selective disrupted gray matter volume covariance of amygdala subregions in schizophrenia.

Objective: Although extensive structural and functional abnormalities have been reported in schizophrenia, the gray matter volume (GMV) covariance of the amygdala remain unknown. The amygdala contains several subregions with different connection patterns and functions, but it is unclear whether the GMV covariance of these subregions are selectively affected in schizophrenia. Methods: To address this issue, we compared the GMV covariance of each amygdala subregion between 807 schizophrenia patients and 845 healthy controls from 11 centers. The amygdala was segmented into nine subregions using FreeSurfer (v7.1.1), including the lateral (La), basal (Ba), accessory-basal (AB), anterior-amygdaloid-area (AAA), central (Ce), medial (Me), cortical (Co), corticoamygdaloid-transition (CAT), and paralaminar (PL) nucleus. We developed an operational combat harmonization model for 11 centers, subsequently employing a voxel-wise general linear model to investigate the differences in GMV covariance between schizophrenia patients and healthy controls across these subregions and the entire brain, while adjusting for age, sex and TIV. Results: Our findings revealed that five amygdala subregions of schizophrenia patients, including bilateral AAA, CAT, and right Ba, demonstrated significantly increased GMV covariance with the hippocampus, striatum, orbitofrontal cortex, and so on (permutation test, P< 0.05, corrected). These findings could be replicated in most centers. Rigorous correlation analysis failed to identify relationships between the altered GMV covariance with positive and negative symptom scale, duration of illness, and antipsychotic medication measure. Conclusion: Our research is the first to discover selectively impaired GMV covariance patterns of amygdala subregion in a large multicenter sample size of patients with schizophrenia.

Improvement of social functioning in patients with first-episode schizophrenia using blonanserin treatment: a prospective, multi-centre, single-arm clinical trial.

Objectives: This clinical trial primarily aimed to investigate the effects of blonanserin on social functioning in patients with first-episode schizophrenia. Methods: In this prospective, multi-centre, single-arm clinical trial study, blonanserin (flexible oral dose ranging from 8mg to 24mg per day) was given 26 weeks. Outcome measures included the Personal and Social Performance (PSP) scale for evaluating social functioning, the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) for measuring neurocognitive performance, and the Positive and Negative Syndrome Scale (PANSS) for assessing symptom severity. The primary endpoint was social function improvement evaluated by PSP scale at the end of blonanserin treatment. And the secondary endpoint was to validate the efficacy and neurocognitive effects of blonanserin. Adverse drug reactions (ADRs) were also recorded and analysed. Results: A total of 96 patients with first-episode schizophrenia were recruited and proceeded to analysis. Fifty-one participants (53.1%) completed the PSP scale measurements at baseline and week 26. Following 26 weeks of blonanserin treatment, all outcome measurements demonstrated significant improvement during the follow-up period. Notably, PSP scores exhibited a continuous increase up to 68.1% ± 103.7% at the end of the treatment (46.6 ± 14.6 at baseline, 69.4 ± 17.4 at week 26, p<0.001), indicating positive effects on social functioning that were already noticeable by week 8. Conclusion: Blonanserin treatment exhibited favourable effects on social functioning in individuals with first-episode schizophrenia. The results suggest that blonanserin was effective treatment options for patients with schizophrenia encountering functional impairments.

Influence of Various Flame Temperatures of the Gun Propellant on the Effectiveness of the Erosion Inhibitor and Relevant Mechanisms.

The development of high energy gun propellants faces significant challenges in terms of erosion, partly due to the inadequate effectiveness of erosion inhibitors. In this paper, the influence of quite different flame temperature of five gun-propellants on erosion-reducing efficiency of four representative inhibitors materials (talc/TiO2/ PDMS/Paraffin) were studied in vented erosion vessel tester. From aspects of morphologies and element compositions of erode steel samples, as well as the pressure and heat generated by propellant burning, the relevant erosion-reducing processes and mechanisms were discussed. The results indicated that erosion inhibitors should be appropriately selected according to the type of gun propellant. The erosion of gun propellants having extremely high flame temperature of 3810 K were hardly reduced using talc, TiO2, and PDMS inhibitors, which can generate numerous solid particles aggravating the melt-wipe process. While paraffin exhibits a uniquely positive erosion-reducing efficiency for the gun propellant having a flame temperature of 3810 K, that was attributed to the mitigated melt-wipe process. The inference was further supported by the high-volume cooling gas, resulting from the higher burning pressure of propellants loading with paraffin and excellent heat absorption capacity of paraffin tested with propellants having higher propellant flame temperature. The obtained results indicated that the factors of flame temperature of gun propellants should be taken into the design and composition optimization of an effective inhibitor. This work could provide potential reference for the development of future novel inhibitors, which serves as high energy gun propellants.

Safety and effectiveness of lurasidone in the treatment of Chinese schizophrenia patients: An interim analysis of post-marketing surveillance.

BACKGROUND: Schizophrenia is a psychiatric disorder characterized by chronic or recurrent symptoms. Lurasidone was licensed in China in 2019 for the treatment of adult schizophrenia in adults with a maximum dose of 80 mg/d. However, post-market surveillance (PMS) with an adequate sample size is required for further validation of the drug's safety profile and effectiveness. AIM: To conduct PMS in real-world clinical settings and evaluate the safety and effectiveness of lurasidone in the Chinese population. METHODS: A prospective, multicenter, open-label, 12-wk surveillance was conducted in mainland China. All patients with schizophrenia from 10 sites who had begun medication with lurasidone between September 2019 and August 2022 were eligible for enrollment. Safety assessments included adverse events (AEs), adverse drug reactions (ADRs), extrapyramidal symptoms (EPS), akathisia, use of EPS drugs, weight gain, and laboratory values as metabolic parameters and the QTc interval. The effectiveness was assessed using the brief psychiatric rating scale (BPRS) from baseline to the end of treatment. RESULTS: A total of 965 patients were enrolled in the full analysis set and 894 in the safety set in this interim analysis. The average daily dose was 61.7 ± 19.08 mg (mean ± SD) during the treatment. AEs and ADRs were experienced by 101 patients (11.3%) and 78 patients (8.7%), respectively, which were mostly mild. EPS occurred in 25 individuals with a 2.8% incidence, including akathisia in 20 individuals (2.2%). Moreover, 59 patients received drugs for treating EPS during the treatment, with an incidence of 6.6% which dropped to 5.4% at the end of the treatment. The average weight change was 0.20 ± 2.36 kg (P = 0.01687) with 0.8% of patients showing a weight gain of ≥ 7% at week 12 compared with that at the baseline. The mean values of metabolic parameters and the QTc interval at baseline and week 12 were within normal ranges. The mean changes in total BPRS scores were -8.9 ± 9.76 (n = 959), -13.5 ± 12.29 (n = 959), and -16.8 ± 13.97 (n = 959) after 2/4, 6/8, and 12 wk, respectively (P < 0.001 for each visit compared with the baseline) using the last-observation-carried-forward method. CONCLUSION: The interim analysis of the PMS of adult patients with schizophrenia demonstrate the safety and effectiveness of lurasidone in the Chinese population. No new safety or efficacy concerns were identified.

Safety and effectiveness of oral blonanserin for schizophrenia in adolescents in China: Data from a 12-week post-marketing surveillance

Background and objectives Blonanserin is a second-generation antipsychotic (SGA)for the treatment of schizophrenia and has been approved for use in Japan, South Korea and China. This analysis aimed to evaluate the effectiveness and safety of blonanserin in Chinese adolescent patients, using data from a post-marketing surveillance of blonanserin started in September 2018. Methods A 12-week, prospective, multi-center, open-label post-marketing surveillance was conducted. Patients in this analysis were stratified by age. Results 78 patients with schizophrenia aged < 18 years were included. The incidence of adverse drug reactions in adolescent patients was 33.3% significantly higher than patients over 40 years old. After 12-week treatment, 8.1% of adolescent patients had a weight gain ≥ 7%, and it was not significantly different from other age groups. Mean Brief Psychiatric Rating Scale (BPRS) total score was significantly reduced at week 12, and the decline of anergia score and thought disturbance score of adolescent patients was significantly greater than in adults. Conclusions Blonanserin was well tolerated and effective in the treatment of schizophrenia in Chinese adolescent patients in real-world clinical practice. Blonanserin might be a reasonable choice for the treatment of schizophrenia in adolescent patients. (AU)

Low-frequency repetitive transcranial magnetic stimulation over the right orbitofrontal cortex for patients with first-episode schizophrenia: A randomized, double-blind, sham-controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) has been used in the treatment of patients with schizophrenia. The conventional targets of rTMS treatment are the dorsolateral prefrontal cortex (DLPFC) and temporoparietal cortex (TPC). However, the efficacy of these two treatment strategies was quite heterogeneous. Structural and functional abnormalities of the orbitofrontal cortex (OFC) in schizophrenia are closely related to negative symptoms. We sought to determine whether 1 Hz rTMS over the right OFC is effective in treating patients with first-episode schizophrenia. In this study, eighty-nine patients with drug-naïve, first-episode schizophrenia were randomly divided into the rTMS (n = 47) or sham stimulation (n = 42) groups, with both groups receiving twenty sessions of 1 Hz rTMS treatment. The PANSS was assessed at baseline, day 10, and day 20, and MATRICS Consensus Cognitive Battery (MCCB) was implemented to assess the cognitive impairment at baseline and day 20. Results showed that patients in the active rTMS group had more improvement in clinical symptoms and cognitive deficits than patients in sham group at day 20. In conclusion, 1 Hz rTMS over OFC can improve psychotic symptoms and cognitive functions in schizophrenic patients. Our study provides a new alternative for the treatment of negative symptoms and cognitive deficits in schizophrenia.

Safety and effectiveness of oral medium to high dose blonanserin in patients with schizophrenia: subgroup analysis from a prospective, multicenter, post-marketing surveillance study in mainland China.

BACKGROUND: Blonanserin (BNS) had been undergoing post-market surveillance (PMS) since September 2018. Using the surveillance data, we did this analysis to assess the safety and effectiveness of different doses of BNS to explore a sufficient dose range of BNS in Chinese patients with schizophrenia (SZ). METHODS: A 12-week, prospective, observational, single-arm, multicenter, open-label PMS was conducted. In this analysis, we divided the patients from PMS into low, medium to high, and high dose groups based on the dose of BNS they received, with medium to high dose group being the focus. The Brief Psychiatric Rating Scale (BPRS) scores at week 2 or 4, 6 or 8, and 12 were calculated to evaluate the effectiveness of BNS in improving psychiatric symptoms. The safety of BNS was reported as the incidence of adverse drug reactions. RESULTS: 364 patients were included in the medium to high dose group, of which 321 completed the surveillance, with a dropout rate of 11.8%. The mean daily dose was 15.1 ± 1.92 mg. The BPRS total score was 50.1 ± 11.95 at baseline and decreased to 26.6 ± 7.43 at 12 weeks (P < 0.001). When compared with other groups, the median to high dose group achieved significantly more reduction in BPRS score at week 12 (P = 0.004 versus low dose and P = 0.033 versus higher dose). Extrapyramidal symptoms [EPS (46.4%)] were the most common adverse reactions in the medium to high group. The average weight gain during the surveillance was 0.5 ± 2.56 kg and prolactin elevation occurred in 2.2% patients. Most adverse reactions were mild. CONCLUSIONS: BNS at medium to high doses (mean 15.1 mg/d) significantly improved symptoms of SZ and was well-tolerated. Most ADRs were mild, and the likelihood of causing metabolic side effects and prolactin elevations was low. Medium to high dose of BNS is a more potent treatment choice for SZ. TRIAL REGISTRATION NUMBER: ChiCTR2100048734. Date of registration: 2021/07/15 (retrospectively registered).

Recent Advances in Polyoxometalate Based Nanoplatforms Mediated Reactive Oxygen Species Cancer Therapy.

The potential of reactive oxygen species (ROS) cancer therapy in tumor treatment has been greatly enhanced by the introduction of catalytically superior polyoxometalate (POM)-based nanoplatforms, mainly composed of atomic clusters consisting of pre-transition metals and oxygen. These nanoplatforms have unique advantages, such as Fenton activity at neutral pH, induction of cellular ferroptosis instead of just apoptosis, and sensitivity to external field stimulation. However, there are also inevitable challenges such as neutralization of ROS by the antioxidant system of the tumor microenvironment (TME), hypoxia, and limited hydrogen peroxide concentrations. This review article aims to provide an overview of recent research advancements in POM-based nanoplatforms for ROS therapy from the perspective of chemical reactions and biological processes, addressing endogenous and exogenous factors that affect the antitumor efficacy. Endogenous factors include the mechanism of ROS generation by POM, the impact of pH and antioxidant systems on POM, and the various manners of tumor cell death. Exogenous stimuli mainly include light, heat, X-rays, and electricity. The article analyzes the specific mechanisms of action of each influencing factor in the first two sections, concluding with the limitations of the present study and some possible directions for future research.

Kinect-based objective assessment for early frailty identification in patients with Parkinson's disease.

BACKGROUND: Frailty is common in Parkinson's disease (PD) and increases vulnerability to adverse outcomes. Early detection of this syndrome aids in early intervention. AIMS: To objectively identify frailty at an early stage during routine motor tasks in PD patients using a Kinect-based system. METHODS: PD patients were recruited and assessed with the Fried criteria to determine their frailty status. Each participant was recorded performing the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) extremity tasks with a Kinect-based system. Statistically significant kinematic parameters were selected to discriminate the pre-frail from the non-frail group. RESULTS: Of the fifty-two participants, twenty were non-frail and thirty-two were pre-frail. Decreased frequency in finger tapping (P = 0.005), hand grasping (P = 0.002), toe tapping (P = 0.002), and leg agility (P = 0.019) alongside reduced hand grasping speed (P = 0.030), lifting (P < 0.001) and falling speed (P < 0.001) in leg agility were observed in the pre-frail group. Amplitude in leg agility (P = 0.048) and amplitude decrement rate (P = 0.046) in hand grasping showed marginally significant differences between two groups. Moderate discriminative values were found in frequency and speed of the extremity tasks to identify pre-frailty with sensitivity, specificity, and area under the curve (AUC) in the range of 45.00-85.00%, 68.75-100%, and 0.701-0.836, respectively. The combination of frequency and speed in extremity tasks showed moderate to high discriminatory ability, with AUC of 0.775 (95% CI 0.637-0.913, P < 0.001) for upper limb tasks and 0.909 (95% CI 0.832-0.987, P < 0.001) for lower limb tasks. When combining these features in both upper and lower limb tasks, the AUC increased to 0.942 (95% CI 0.886-0.999, P < 0.001). CONCLUSIONS: Our findings demonstrated the promise of utilizing Kinect-based kinematic data from MDS-UPDRS III tasks as early indicators of frailty in PD patients.

Genome-wide DNA methylation analysis in families with multiple individuals diagnosed with schizophrenia and intellectual disability.

OBJECTIVES: Schizophrenia (SZ) and intellectual disability (ID) are both included in the continuum of neurodevelopmental disorders (NDDs). DNA methylation is known to be important in the occurrence of NDDs. The family study is conducive to eliminate the effects of relative epigenetic backgrounds, and to screen for differentially methylated positions (DMPs) and regions (DMRs) that are truly associated with NDDs. METHODS: Four monozygotic twin families were recruited, and both twin individuals suffered from NDDs (either SZ, ID, or SZ plus ID). Genome-wide methylation analysis was performed in all samples and each family. DMPs and DMRs between NDD patients and unaffected individuals were identified. Functional and pathway enrichment analyses were performed on the annotated genes. RESULTS: Two significant DMPs annotated to CYP2E1 were found in all samples. In Family One, 1476 DMPs mapped to 880 genes, and 162 DMRs overlapping with 153 unique genes were recognised. Our results suggested that the altered methylation levels of FYN, STAT3, RAC1, and NR4A2 were associated with the development of SZ and ID. Neurodevelopment and the immune system may participate in the occurrence of SZ and ID. CONCLUSIONS: Our findings suggested that DNA methylation participated in the development of NDDs by affecting neurodevelopment and the immune system.

The safety and efficacy of sequential intramuscular/oral ziprasidone treatment of acute episode in patients with schizophrenia: a multicenter, open-labeled study.

BACKGROUND: Ziprasidone mesylate injection is an atypical antipsychotic drug which is recently approved in China. In combination with its oral formulation, sequential therapy with ziprasidone brings new interventions to patients with agitation in the acute phase of schizophrenia. The purpose of this 7-day multicenter study conducted in China was to evaluate the efficacy and safety of ziprasidone sequential treatment through intramuscular/oral routes in agitated patients with schizophrenia. METHODS: A total of 95 patients were enrolled from three centers in this study. The study duration was 7 days. In the first 3 days, subjects were administered an intramuscular injection of ziprasidone 10-40 mg daily and started sequentially with oral ziprasidone 40-80 mg at dinner (or lunch) from the day of the last intramuscular injection. In the following 4 days, according to the severity of the symptoms and the drug response, 120-160 mg of ziprasidone was orally administered daily. In total, six visits were scheduled to assess the Positive and Negative Syndrome Scale (PANSS), the Behavioral Activity Rating Scale (BARS), the Clinical Global Impression of Severity (CGI-S), and Improvement (CGI-I) scores throughout the procedure. Lastly, adverse events were recorded during treatment. RESULTS: Out of the 95 patients that were enrolled, 83 cases were effectively completed. Visits 3, 4, 6, PANSS, and PANSS-excited component (PANSS-EC) subscale points, and Visit 2-Visit 6 viewpoints, BARS scale points, and baseline scores denote a progressive downward trend (P < 0.001). In this study, 62 adverse events were reported. The most common adverse events were extrapyramidal symptoms (EPS) (23 cases) and excessive sedation(10 cases), and 13 cases of prolonged QTc interval were reported. CONCLUSIONS: Ziprasidone IM demonstrated significant and rapid reduction in agitation, and sequential oral formulation keep stability and continuation of the treatment can further ensure efficacy. Ziprasidone sequential therapy may provide a new approach to acute agitation in schizophrenic patients. TRIAL REGISTRATION: The Chinese Clinical Trials Registry; URL: https://www.chictr.org.cn : ChiCTR-OIC-16007970.

The Effect of Shear on the Properties of an Associated Polymer Solution for Oil Displacement.

Polymer flooding is one of the techniques used to enhance oil recovery from depleted hydrocarbon reservoirs. Although this technology is popular for this application, the shearing effect in the injection process causes poor performance, which is an obstacle to meeting the needs of the formation. An experimental evaluation of the rheological properties, viscoelasticity, hydrodynamic size, static adsorption, and seepage characteristics of the associated polymer solution before and after shearing was conducted to determine the influence of shearing on the polymer solution. The results show that the effect of shear on the polymer was irreversible, and the properties of the polymer solution damaged by shear were attenuated. After the critical associating concentration, the associated polymer can recover its solution properties through hydrophobic association, which can improve the shear resistance of the polymer solution and make its own rheological law and reduce the viscoelastic change. Although the hydrodynamic size, viscoelasticity, and adsorption capacity of the polymer solution after shear failure decreased, strong flow resistance during porous media seepage and mobility control was achieved. Improving the shear resistance of the polymer solution by increasing the intermolecular force is proposed to develop new polymer systems for subsequent oil displacement.

Effectiveness and safety of blonanserin in young and middle-aged female patients with schizophrenia: data from a post-marketing surveillance.

BACKGROUND: A post-marketing surveillance of blonanserin has been ongoing since September 2018. The aim of this study was to assess the effectiveness and safety of oral blonanserin in Chinese young and middle-aged female patients with schizophrenia in real clinical settings, using the data from the post-marketing surveillance. METHODS: A 12-week, prospective, multi-center, open-label, post-marketing surveillance was conducted. Female patients aged 18-40 years were included in this analysis. The Brief Psychiatric Rating Scale (BPRS) was used to evaluate the effectiveness of blonanserin in improving psychiatric symptoms. The incidence of adverse drug reactions (ADRs) such as of extrapyramidal symptoms (EPS), prolactin elevation and the weight gain were used to evaluate the safety profile of blonanserin. RESULTS: A total of 392 patients were included both in the safety and full analysis sets, 311 patients completed the surveillance protocol. The BPRS total score was 48.8 ± 14.11 at the baseline, decreasing to 25.5 ± 7.56 at 12 weeks (P < 0.001, compared with baseline). EPS (20.2%) including akathisia, tremor, dystonia, and parkinsonism were found as the most frequent ADRs. The mean weight gain was 0.27 ± 2.5 kg at 12 weeks from the baseline. Four cases (1%) of prolactin elevation were observed during the period of surveillance. CONCLUSION: Blonanserin significantly improved the symptoms of schizophrenia in female patients aged 18-40 years; the drug was well tolerated and had a low tendency to cause metabolic side effects, including prolactin elevation in these patients. Blonanserin might be a reasonable drug for the treatment of schizophrenia in young and middle-aged female patients.

Safety and Effectiveness of Blonanserin in Chinese Patients with Schizophrenia: An Interim Analysis of a 12-Week Open-Label Prospective Multi-Center Post-marketing Surveillance.

Schizophrenia is an unexplained, complex and serious mental illness. Blonanserin (BNS) is a new antipsychotic drug widely used in the treatment of schizophrenia. However, large-scale clinical studies have not been conducted in China. A multi-center, prospective, open-label, 12-week surveillance was carried out to evaluate the safety and effectiveness of BNS in patients with schizophrenia in China. Safety assessments included adverse drug reactions (ADRs), extrapyramidal symptoms (EPS), akathisia, concomitant medications for EPS by the end of treatment, and the changes in body weight from baseline by the end of treatment. The effectiveness was evaluated by the Brief Psychiatric Rating Scale (BPRS). From September 2018 to May 2020, of the 1,060 patients enrolled, 1,018 were included in the full analysis set (FAS) and safety set (SS), respectively. ADRs were developed in 205 patients among the included, the incidence being 20.1%. ADRs of EPS occurred in 169 patients, the incidence being 16.6%, ADRs of akathisia occurred in 90 patients, the incidence being 8.8%; concomitant therapeutic and prophylactic agents for EPS accounts for 19.2%; 4.0% of patients had a ≥7% increase in body weight from baseline at 12 weeks after initiating treatment. Using the last-observation-carried-forward (LOCF) method, the changes in total BPRS scores were -11.2 ± 10.17 (N = 1,018), -16.8 ± 12.69 (N = 1,018) and -20.6 ± 13.99 (N = 1,018) after 2/4, 6/8, or 12 weeks, respectively. 53.5% (545/1,018) patients showed response to blonanserin treatment in week 12. The post-marketing surveillance results of BNS demonstrates safety profile and effectiveness of the drug.

High PSQI score is associated with the development of dyskinesia in Parkinson's disease.

Dyskinesia is one of the most disabling motor complications in Parkinson's Disease (PD). Sleep is crucial to keep neural circuit homeostasis, and PD patients often suffer from sleep disturbance. However, few prospective studies have been conducted to investigate the association of sleep quality with dyskinesia in PD. The objective of the current study is to investigate the association between sleep quality and dyskinesia and build a prediction model for dyskinesia in PD. We prospectively followed a group of PD patients without dyskinesia at baseline for a maximum of 36 months. Univariable and multivariable Cox regression with stepwise variable selection was used to investigate risk factors for dyskinesia. The performance of the model was assessed by the time-dependent area under the receiver-operating characteristic curve (AUC). At the end of follow-up, 32.8% of patients developed dyskinesia. Patients with bad sleep quality had a significantly higher proportion of dyskinesia compared with those with good sleep quality (48.1% vs. 20.6%, p = 0.023). Multivariable Cox regression selected duration of PD, sleep quality, cognition, mood, and levodopa dose. Notably, high Pittsburgh sleep quality index (PSQI) score was independently associated with an increased risk of dyskinesia (HR = 2.96, 95% CI 1.05-8.35, p = 0.041). The model achieved a good discriminative ability, with the highest AUC being 0.83 at 35 months. Our results indicated that high PSQI score may increase the risk of developing dyskinesia in PD, implying that therapeutic intervention targeting improving sleep quality may be a promising approach to prevent or delay the development of dyskinesia in PD.

The Chinese Brief Cognitive Test: Normative Data Stratified by Gender, Age and Education.

The aim of this study was to develop a brief version of cognitive assessment test for evaluating the efficacy of treatments targeting cognitive impairments in Chinese schizophrenia patients, to examine its reliability, and establish normative data. Stratified according to age, gender, and educational level, healthy adult subjects were recruited from fifteen institutions in seven administrative regions of China and 723 valid samples were obtained, of which 50 were retested. Generalized Linear Models were conducted to analyze the effects of age, sex, and education. There was no significant difference between genders, while significant effects were demonstrated respectively among age and education on the normative data of C-BCT. The Cronbach α of C-BCT is 0.75, and the test-retest reliability (ICC) ranged from 0.62 to 0.76. Normative data of C-BCT were generated by gender, age and education, and the effects of these demographic factors were analyzed. It revealed good internal consistency and test-retest reliability of C-BCT.

Protocol for a Pragmatic Trial of Pharmacotherapy Options Following Unsatisfactory Initial Treatment in OCD (PROCEED).

Background: Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacotherapy for obsessive-compulsive disorder (OCD), but a large proportion of patients do not achieve remission after an adequate SSRI trial. To the best of our knowledge, there have been no well-powered randomized controlled trials (RCTs) of sequenced pharmacotherapy using pragmatic research designs. China provides a unique context for undertaking such a trial that will recruit the largest treatment-naïve participants and systematically compare the efficacy of different sequenced pharmacotherapy. Methods: A pragmatic research design will be adopted, with n = 1,600 treatment-naïve OCD patients initially treated for sertraline for 12 weeks, and with non-remitters then randomized to 5 different augmentation or switching pharmacotherapy options for another 12 weeks. The 5 arms will include: (1) treatment with higher than usual doses of sertraline, (2) switch to fluvoxamine, (3) switch to venlafaxine, (4) augmentation with memantine, and (5) augmentation with aripiprazole. Discussion: China is uniquely positioned to recruit sufficiently large sample sizes of treatment-naïve OCD patients to compare different pharmacotherapy options; data from the proposed trial promises to help inform current clinical practice guidelines by providing important information about optimal pharmacotherapy choice for those who demonstrate no response or response but no remission to first line pharmacotherapy. Trial Registration: The trail was registered on 27 August 2020 in ClinicalTrials.gov (https://register.clinicaltrials.gov/) (NCT04539951).

The cost of obsessive-compulsive disorder (OCD) in China: a multi-center cross-sectional survey based on hospitals.

BACKGROUND: Obsessive-compulsive disorder (OCD) is considered a very debilitating disorder with severe loss of quality of life and income. AIMS: This study estimates the quality of life and economic consequences of OCD in China. METHODS: The research team interviewed 639 patients with OCD in 13 hospitals in 12 cities in China. The direct method was used to get the direct cost of OCD. Indirect costs associated with OCD were estimated using the human capital approach. Linear regression analysis was conducted for quality of life and generalised linear model analysis was conducted for total cost. Sensitivity analysis was used to analyse the uncertainty of total cost. RESULTS: The mean quality of life score for OCD was 52.78 (20.46). The annual total cost of OCD per capita was 24 503.78 (95% CI: 22 621.53 to 26 386.03) renminbi (RMB) (US$3465.88 (95% CI: US$3199.65 to US$3732.11)). The annual cost of OCD in China was estimated to be 37.74 billion (95% CI: 34.95 billion to 40.53 billion) RMB (equal to US$5.34 billion (95% CI: US$4.94 billion to US$5.73 billion)). Sensitivity analysis showed that the total annual cost of OCD in China was between 23.15 billion RMB (US$3.27 billion) and 370.00 billion RMB (US$52.33 billion). Worse social function status, more psychiatric symptoms and higher Yale Brown Obsessive-Compulsive Scale (Y-BOCS) score were associated with worse quality of life. The numbers of clinic visits and hospitalisations, socioeconomic status, education, Y-BOCS scores and age were found to be significantly associated with total cost. CONCLUSIONS: OCD is associated with low quality of life and high costs in China. The findings call for concerted efforts to improve services for patients with OCD.Improvements may include early detection and diagnosis, the provision of evidence-based treatments and relapse prevention strategies.

Biomimetic-Inspired One-Step Strategy for Improvement of Interfacial Interactions in Cellulose Nanofibers by Modification of the Surface of Nitramine Explosives.

Recently, a burgeoning category of biocompatible botanically derived nanomaterial cellulose nanofibers (CNFs) has captured tremendous attention on account of its entangled nanostructured network, natural abundance, and outstanding mechanical properties. Biomimetically inspired by the superior properties of CNFs, this paper examined them as the coating material to cover cyclotrimethylenetrinitramine (RDX), cyclotetramethylenetetranitramine (HMX), and hexanitrohexaazaisowurtzitane (CL-20) via a facile water suspension method and the ultrasonic technology. The core-shell structure and the composition of energetic crystal@CNF were examined through scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy analyses. The obtained outcomes demonstrated that the dispersibility of the CNF enhanced favorably upon covering the surface of explosive crystals; the interfacial contact ability between CNFs and energetic crystals was also manifested to be increased, which could be ascribed to the interfacial interaction of hydrogen bonds and the electrostatic force of self-assembly. In addition, the stable crystalloid construction of ß-HMX and ε-CL-20 has been preserved positively in the preparation process. In comparison with raw explosives, the thermal stability and sensitivity performances of the core-shell structure composites were outstanding. Accordingly, this work demonstrated the rewarding application of coating CNFs uniformly on the surface of energetic crystals, ulteriorly offering a potential fabrication strategy for the embellishment of high-explosive crystals.

Mutually exclusive substrate selection strategy by human m3C RNA transferases METTL2A and METTL6.

tRNAs harbor the most diverse posttranscriptional modifications. The 3-methylcytidine (m3C) is widely distributed at position C32 (m3C32) of eukaryotic tRNAThr and tRNASer species. m3C32 is decorated by the single methyltransferase Trm140 in budding yeasts; however, two (Trm140 and Trm141 in fission yeasts) or three enzymes (METTL2A, METTL2B and METTL6 in mammals) are involved in its biogenesis. The rationale for the existence of multiple m3C32 methyltransferases and their substrate discrimination mechanism is hitherto unknown. Here, we revealed that both METTL2A and METTL2B are expressed in vivo. We purified human METTL2A, METTL2B, and METTL6 to high homogeneity. We successfully reconstituted m3C32 modification activity for tRNAThr by METT2A and for tRNASer(GCU) by METTL6, assisted by seryl-tRNA synthetase (SerRS) in vitro. Compared with METTL2A, METTL2B exhibited dramatically lower activity in vitro. Both G35 and t6A at position 37 (t6A37) are necessary but insufficient prerequisites for tRNAThr m3C32 formation, while the anticodon loop and the long variable arm, but not t6A37, are key determinants for tRNASer(GCU) m3C32 biogenesis, likely being recognized synergistically by METTL6 and SerRS, respectively. Finally, we proposed a mutually exclusive substrate selection model to ensure correct discrimination among multiple tRNAs by multiple m3C32 methyltransferases.