Correlation Between Cortical Thickness Abnormalities of the Olfactory Sulcus and Olfactory Identification Disorder and Persistent Auditory Verbal Hallucinations in Chinese Patients With Chronic Schizophrenia.

BACKGROUND AND HYPOTHESIS: Persistent auditory verbal hallucinations (pAVHs) and olfactory identification impairment are common in schizophrenia (SCZ), but the neuroimaging mechanisms underlying both pAVHs and olfactory identification impairment are unclear. This study aimed to investigate whether pAVHs and olfactory identification impairment in SCZ patients are associated with changes in cortical thickness. STUDY DESIGN: In this study, cortical thickness was investigated in 78 SCZ patients with pAVHs (pAVH group), 58 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) using 3T magnetic resonance imaging. The severity of pAVHs was assessed by the Auditory Hallucination Rating Scale. Olfactory identification deficits were assessed using the Odor Stick Identification Test for Japanese (OSIT-J). In addition, the relationship between the severity of pAVHs and olfactory identification disorder and cortical thickness abnormalities was determined. STUDY RESULTS: Significant reductions in cortical thickness were observed in the right medial orbital sulcus (olfactory sulcus) and right orbital sulcus (H-shaped sulcus) in the pAVH group compared to both the non-AVH and HC groups (P < .003, Bonferroni correction). Furthermore, the severity of pAVHs was found to be negatively correlated with the reduction in cortical thickness in the olfactory sulcus and H-shaped sulcus. Additionally, a decrease in cortical thickness in the olfactory sulcus showed a positive correlation with the OSIT-J scores (P < .05, false discovery rate correction). CONCLUSIONS: Cortical thickness abnormalities in the olfactory sulcus may be a common neuroimaging mechanism for pAVHs and olfactory identification deficits in SCZ patients.

Multiple serum anti-glutamate receptor antibody levels in clozapine-treated/naïve patients with treatment-resistant schizophrenia.

BACKGROUND: Glutamatergic function abnormalities have been implicated in the etiology of treatment-resistant schizophrenia (TRS), and the efficacy of clozapine may be attributed to its impact on the glutamate system. Recently, evidence has emerged suggesting the involvement of immune processes and increased prevalence of antineuronal antibodies in TRS. This current study aimed to investigate the levels of multiple anti-glutamate receptor antibodies in TRS and explore the effects of clozapine on these antibody levels. METHODS: Enzyme linked immunosorbent assay (ELISA) was used to measure and compare the levels of anti-glutamate receptor antibodies (NMDAR, AMPAR, mGlur3, mGluR5) in clozapine-treated TRS patients (TRS-C, n = 37), clozapine-naïve TRS patients (TRS-NC, n = 39), and non-TRS patients (nTRS, n = 35). Clinical symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS), while cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). RESULT: The levels of all four glutamate receptor antibodies in TRS-NC were significantly higher than those in nTRS (p < 0.001) and in TRS-C (p < 0.001), and the antibody levels in TRS-C were comparable to those in nTRS. However, no significant associations were observed between antibody levels and symptom severity or cognitive function across all three groups after FDR correction. CONCLUSION: Our findings suggest that TRS may related to increased anti-glutamate receptor antibody levels and provide further evidence that glutamatergic dysfunction and immune processes may contribute to the pathogenesis of TRS. The impact of clozapine on anti-glutamate receptor antibody levels may be a pharmacological mechanism underlying its therapeutic effects.

Preliminary Efficacy of a Cognitive Behavioral Therapy-Based Smartphone App for Smoking Cessation in China: Randomized Controlled Pilot Trial.

BACKGROUND: The overall prevalence of cigarette smokers in China is very high, and China's total cigarette consumption makes up more than 40% of the world's consumption. In view of the lack of smoking cessation services and social support in China and the effectiveness of mobile phone apps for quitting smoking in other countries, we carried out a smartphone app-based smoking cessation trial in China. OBJECTIVE: This study aimed to evaluate the efficacy of a cognitive behavioral therapy (CBT)-based smoking cessation smartphone app among smokers seeking treatment in China. METHODS: We conducted a randomized controlled, web-based pilot clinical trial in China between February 23 and June 27, 2021. Eligible participants were randomly assigned to the smoking cessation app intervention group or the control group in a ratio of 1:1. The intervention group received the CBT smoking cessation intervention using a smartphone app, and the control group received a "thank you" message. The intervention was 4 weeks long, and the patients were followed up for 4 weeks. The primary outcome was self-reported continuous smoking abstinence at week 4 after the quit date. The secondary outcomes included self-reported 7-day point prevalence of smoking abstinence; reduction of the number of cigarettes smoked per day at weeks 1, 2, 3, and 4; and program acceptability. RESULTS: A total of 973 people were recruited to quit smoking, of whom 262 completed basic information, 56 were excluded, and 206 were randomized and included in the final analysis. There were 189 (91.7%) men and 17 (8.3%) women, with an average age of 34.46 (SD 7.53) years and an average daily smoking rate of 15.93 (SD 7.10) cigarettes/day. We found 30 (29.7%) of the 101 participants in the intervention group and 7 (6.7%) of the 105 participants in the control group reported continuous smoking cessation after the quit date at week 4 (odds ratio 5.92, 95% CI 3.78-9.26; P<.001). The 7-day point prevalence abstinence rate of the intervention group varied from 42.6% (43/101) to 46.5% (47/101) after 1, 2, 3, and 4 weeks, while the control group varied from 18.1% (19/105) to 26.7% (28/105). Compared to the control group, continued smokers consumed 1.5-3.0 fewer cigarettes per day in the intervention group. The overall program got positive user feedback with a high satisfaction rate (66/87, 76%) and an average Mobile Application Rating Scale user version score of 3.46. CONCLUSIONS: Our pilot study provided preliminary evidence that the CBT-based smoking cessation smartphone app led to improved smoking quit rates versus control in Chinese smokers. The study demonstrated the CBT-based smartphone app may be an effective and feasible digital treatment model to help smokers quit, which may improve smoking cessation service quality and accessibility in China. TRIAL REGISTRATION: ClinicalTrials.gov NCT04421170; https://clinicaltrials.gov/study/NCT04421170. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2020-041985.

Gender differences in alcohol drinking among adolescents: a school-based survey in China.

BACKGROUND: Alcohol drinking among adolescents is associated with their health development. However, the prevalence of alcohol drinking among adolescents in Southwestern China remains largely unexplored. This study aimed to investigate the prevalence of alcohol drinking, with a particular focus on gender differences, among primary and middle school students in Zigong, a city in Southwestern China. Additionally, we examined the association between alcohol consumption and demographic and family factors. METHODS: A school-based cross-sectional survey was conducted in a city in Southwestern China, encompassing a total of 89 360 students from 132 different ordinary schools, including both primary and middle schools. Participants were recruited through cluster sampling. The Alcohol Use Disorders Identification Test Consumption was employed to assess alcohol consumption. Gender differences in the prevalence of alcohol drinkers across various schools and grades were analysed. Multivariable logistic regression analysis was used to investigate factors associated with hazardous drinking. RESULTS: Out of the 89 360 participants, 19.0% reported alcohol drinking, with 2.1% classified as hazardous drinkers. There was a higher prevalence of alcohol drinking among boys compared with girls, as well as hazardous drinking. There were significant gender disparities in alcohol drinking observed across various schools and grade levels. A notable divergence between boys and girls was observed starting from grade 10, with a rising prevalence of hazardous drinking among boys and a decline among girls. Additionally, older age, male gender and being left-behind children were identified as risk factors for hazardous drinking, while belonging to a nuclear family and having parents who do not drink were protective factors against hazardous drinking. CONCLUSIONS: Alcohol consumption is prevalent among Chinese adolescents, with some even classified as hazardous drinkers. These findings may offer valuable insights for policymakers and caregivers, guiding them in formulating appropriate interventions and support strategies.

Using brain structural neuroimaging measures to predict psychosis onset for individuals at clinical high-risk.

Machine learning approaches using structural magnetic resonance imaging (sMRI) can be informative for disease classification, although their ability to predict psychosis is largely unknown. We created a model with individuals at CHR who developed psychosis later (CHR-PS+) from healthy controls (HCs) that can differentiate each other. We also evaluated whether we could distinguish CHR-PS+ individuals from those who did not develop psychosis later (CHR-PS-) and those with uncertain follow-up status (CHR-UNK). T1-weighted structural brain MRI scans from 1165 individuals at CHR (CHR-PS+, n = 144; CHR-PS-, n = 793; and CHR-UNK, n = 228), and 1029 HCs, were obtained from 21 sites. We used ComBat to harmonize measures of subcortical volume, cortical thickness and surface area data and corrected for non-linear effects of age and sex using a general additive model. CHR-PS+ (n = 120) and HC (n = 799) data from 20 sites served as a training dataset, which we used to build a classifier. The remaining samples were used external validation datasets to evaluate classifier performance (test, independent confirmatory, and independent group [CHR-PS- and CHR-UNK] datasets). The accuracy of the classifier on the training and independent confirmatory datasets was 85% and 73% respectively. Regional cortical surface area measures-including those from the right superior frontal, right superior temporal, and bilateral insular cortices strongly contributed to classifying CHR-PS+ from HC. CHR-PS- and CHR-UNK individuals were more likely to be classified as HC compared to CHR-PS+ (classification rate to HC: CHR-PS+, 30%; CHR-PS-, 73%; CHR-UNK, 80%). We used multisite sMRI to train a classifier to predict psychosis onset in CHR individuals, and it showed promise predicting CHR-PS+ in an independent sample. The results suggest that when considering adolescent brain development, baseline MRI scans for CHR individuals may be helpful to identify their prognosis. Future prospective studies are required about whether the classifier could be actually helpful in the clinical settings.

Fault Diagnosis Methods for an Artillery Loading System Driving Motor in Complex Noisy Environments.

With the development of modern military technology, electrical drive technology has become a power source for modern artillery. In fault monitoring of a driving motor mounted on a piece of artillery, various sensors are susceptible to interference from the complex environment, both inside and outside the artillery itself. In this study, we creatively propose a fault diagnosis model based on an attention mechanism, the AdaBoost method and a wavelet noise reduction network to address the difficulty in obtaining high-quality motor signals in complex noisy interference environments. First, multiple fusion wavelet basis, soft thresholding, and index soft filter optimization were used to train multiple wavelet noise reduction networks that could recover sample signals under different noise conditions. Second, a convolutional neural network (CNN) classification module was added to construct end-to-end classification models that could correctly identify faults. The above basis classification models were then integrated into the AdaBoost method with an improved attention mechanism to develop a fault diagnosis model suitable for complex noisy environments. Finally, two experiments were conducted to validate the proposed method. Under motor signals with varying signal-to-noise ratios (SNRs) noises, the proposed method achieved an average accuracy of 92%, surpassing the conventional method by over 8.5%.

Workplace violence inflicted by patients or their family members/visitors and its relationship with suicidal ideation among undergraduate medical students during clinical training in China.

BACKGROUND: Workplace violence in healthcare settings is a significant public concern that profoundly impacts healthcare workers. However, there is a dearth of knowledge regarding the prevalence of workplace violence and its correlation with suicidal ideation among undergraduate medical students in China during their clinical training. The objective of this study was to evaluate the prevalence of workplace violence inflicted by patients or their family members/visitors and to assess its association with suicidal ideation among undergraduate medical students. METHOD: The snowballing sampling technique was used to recruit Chinese medical students. A question designed by the research team was used to ask medical students about their encounters with workplace violence. Students' basic demographic information and mental distresses (learning burnout, depression symptoms, anxiety symptoms, alcohol abuse/dependence, excessive daytime sleepiness and history of mental disorders) were also assessed. As appropriate, the data were analysed using descriptive statistics, chi-square tests, independent-sample t-tests and multiple logistic regression. RESULTS: Out of the 1402 undergraduate medical students who participated, 493 (35.2%) reported having experienced workplace violence inflicted by patients or their family members/visitors, of which 394 (28.1%) were verbal abuse, 14 (1.0%) were physical aggression, and 85 (6.1%) were suffered from both verbal abuse and physical aggression. Furthermore, students exposed to workplace violence were more likely to report suicidal ideation and had a higher prevalence of learning burnout, depression symptoms, anxiety symptoms, alcohol abuse/dependence and excessive daytime sleepiness. Depression symptoms, history of mental disorders, learning burnout and having a partner were significantly associated with suicidal ideation in this population. CONCLUSION: The prevalence of workplace violence inflicted by patients or their family members/visitors was high among undergraduate medical students in China. This may be associated with their mental distress and suicidal ideation. Consequently, it is crucial to strengthen workplace safety measures and promptly implement interventions to mitigate the potentially serious consequences.

Workplace violence was common among Chinese undergraduate medical students during clinical training and may be associated with suicidal ideation, learning burnout, depression symptoms, anxiety symptoms, alcohol abuse/dependence and excessive daytime sleepiness.Depression symptoms, history of mental disorders, learning burnout and having a partner were significantly associated with suicidal ideation among undergraduate medical students exposed to workplace violence.

Screening for osteoporosis based on IQon spectral CT virtual low monoenergetic images: Comparison with conventional 120 kVp images.

Objectives: To explore the differences between low kiloelectron volt (keV) virtual monoenergetic images (VMIs) using IQon spectral CT and conventional CT (120 kVp) in the diagnosis of osteoporosis. Methods: This retrospective study included 317 patients who underwent IQon spectral CT and dual-energy X-ray absorptiometry (DXA) examination. Commercial deep learning-based software was used for the fully automated extraction of the CT values of the first to fourth lumbar vertebrae (L1-L4) from two different low-keV levels (including 40/70 keV) VMIs and conventional 120 kVp images. The DXA examination results served as the standard of reference (normal [T-score ≥ -1], osteopenia [-2.5 < T-score < -1], and osteoporosis [T-score < -2.5]). Osteoporosis diagnosis models were constructed using machine learning classifiers (logistic regression, support vector machine, random forest, XGBoost, and multilayer perceptron) based on the average CT values of L1-L4. The area under the receiver operating characteristic curve (AUC) and DeLong test were performed to compare differences in the performance of the osteoporosis diagnosis model between virtual low-keV VMIs and standard 120 kVp images. Results: Random forest-based prediction model obtained good overall performance among all classifiers, and macro/micro average AUC values of 0.820/840, 0.834/853, and 0.831/852 were obtained based on 40/70 keV and 120 kVp images, respectively. The model presented no significant difference between low-keV VMIs and standard 120 kVp images for the diagnosis of osteoporosis (p > 0.05). Conclusions: The performance of the osteoporosis diagnosis model using IQon spectral CT simulating the low tube voltage scanning condition (less than 120 kVp) was also satisfactory. Bone density screening evaluation can be performed with a combination of low-dose lung scanning CT, greatly reducing the radiation dose without affecting the diagnosis.

Gender differences in alcohol abuse/dependence among medical undergraduates during the post-COVID­19 pandemic period (October 20, 2020-April 5, 2021) in China.

BACKGROUND: This study aimed to assess the prevalence and the gender-specific risk factors of alcohol abuse/dependence among medical undergraduates during the post-COVID­19 pandemic period in China. METHOD: The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) was used to identify respondents with alcohol abuse/dependence. A questionnaire on basic demographics and mental distresses (learning burnout, depression symptoms, anxiety symptoms, excessive daytime sleepiness, and history of mental disorders) was used. The logistic regression model was used to explore the associations between the above characteristics and alcohol abuse/dependence. RESULTS: A total of 3,412 medical undergraduates were included in the analysis. Males showed a higher prevalence of alcohol abuse/dependence than females (16.6% vs 7.4%, p < 0.001). Alcohol abuse/dependence was associated with learning burnout (OR: 2.168, p < 0.001) and having a partner (OR: 1.788 p = 0.001) among female medical undergraduates. Among male medical undergraduates, excessive daytime sleepiness (OR: 1.788 p = 0.001) and older age (OR: 1.788, p = 0.001) were independently associated with alcohol abuse/dependence. CONCLUSION: Alcohol abuse/dependence was common among medical undergraduates during the post-COVID­19 pandemic period. Substantial gender differences in the prevalence and risk factors of alcohol abuse/dependence were found among medical undergraduates in this study, which highlighted the need for timely gender-specific screening and interventions. However, the cross-sectional design adopted in this study has limited the examination of causality, thus further longitudinal studies are warranted.

Evaluation of microcirculation in asymptomatic cerebral infarction with multi-parameter imaging of spectral CT.

OBJECTIVE: To investigate the role of spectral CT multiparametric imaging in the evaluation of cerebral microcirculatory perfusion. METHODS: The imaging data of 145 patients with asymptomatic cerebral infarction confirmed by MR were retrospectively analyzed, and all cases underwent head CTA and cranial CT perfusion imaging (CTP) on double-layer detector spectral CT. Single energy level images (MonoE45 keV), iodine density maps, and effective atomic number maps were reconstructed based on spectral CTA data, and CT values, iodine density values, and effective atomic number values were measured in the infarcted area, healthy control area, centrum semiovale and posterior limb of the internal capsule, respectively; perfusion values, such as cerebral blood volume (CBV) values, cerebral blood flow (CBF) values, time to peak (TTP) values, and mean passage time, were measured in the above-mentioned areas on CTP images. (TTP) values, and mean time to passage (MTT) values. CT values, iodine density values, effective atomic number values, and perfused CBV, CBF, TTP, and MTT values were compared between the infarcted area and the healthy side, the center of the hemianopia, and the posterior limb of the internal capsule. The role of spectral CT parameters and perfusion parameters in the evaluation of asymptomatic cerebral infarction was analyzed. RESULTS: CT values, iodine density values, and effective atomic number values were statistically different between the infarcted area and the healthy side; CT values, iodine density values, and effective atomic number values were not statistically different between the infarcted side and the healthy side of the hemispheric centrum and the posterior limb of the internal capsule; CBV and CBF were statistically different between the infarcted side and the healthy side, and MTT and TTP were not statistically different. There were statistically significant differences in TTP between the infarcted area and the healthy side of the hemiaxial center, and no statistically significant differences in CBV, CBF, and MTT. There were no statistical differences in CBV, CBF, TTP, and MTT in the inner capsule area. ROC curve analysis of spectral CT-related parameters and CT perfusion parameters for the diagnosis of asymptomatic cerebral infarction: area under the curve of MonoE 45Kv 0.71, area under the curve of iodine density values 0.76, area under the curve of effective atomic number values 0.74; area under the curve of CBV value 0.64, area under the curve of CBF value 0.61, area under the curve of MTT value 0.50, The area under the TTP curve was 0.52. The area under the ROC curve of the multivariate logistic regression model based on spectral parameters is 0.76, which is higher than that of the logistic regression model with perfusion parameters (P < 0.05). CONCLUSION: Spectral CT can better demonstrate small intracranial ischemic lesions, and iodine density values have a better evaluation of microcirculation in asymptomatic cerebral infarcts.

Determination of the cutoff point for Smartphone Application-Based Addiction Scale for adolescents: a latent profile analysis.

BACKGROUNDS: The Smartphone Application-Based Addiction Scale (SABAS) is a validated 6-item measurement tool for assessing problematic smartphone use (PSU). However, the absence of established cutoff points for SABAS hinders its utilities. This study aimed to determine the optimal cutoff point for SABAS through latent profile analysis (LPA) and receiver operating characteristic curve (ROC) analyses among 63, 205. Chinese adolescents. Additionally, the study explored whether PSU screening with SABAS could effectively capture problematic social media use (PSMU) and internet gaming disorder (IGD). METHOD: We recruited 63,205. adolescents using cluster sampling. Validated questionnaires were used to assess PSMU, IGD, and mental health (depression, anxiety, sleep disturbances, well-being, resilience, and externalizing and internalizing problems). RESULTS: LPA identified a 3-class model for PSU, including low-risk users (38.6%, n = 24,388.), middle-risk users (42.5%, n = 26,885.), and high-risk users (18.9%, n = 11,932.). High-risk users were regarded as "PSU cases" in ROC analysis, which demonstrated an optimal cut-off point of 23 (sensitivity: 98.1%, specificity: 96.8%). According to the cutoff point, 21.1% (n = 13,317.) were identified as PSU. PSU adolescents displayed higher PSMU, IGD, and worse mental health. PSU screening effectively captured IGD (sensitivity: 86.8%, specificity: 84.5%) and PSMU (sensitivity: 84.5%, specificity: 80.2%). CONCLUSION: A potential ideal threshold for utilizing SABAS to identify PSU could be 23 (out of 36). Employing SABAS as a screening tool for PSU holds the potential to reliably pinpoint both IGD and PSMU.

Nicotine Decreases Nerve Regeneration and Pain Behaviors via PTEN and Downstream Inflammation-Related Pathway in Two Rat Nerve Injury Models.

Neuropathic pain is stubborn and associated with the peripheral nerve regeneration process. Nicotine has been found to reduce pain, but whether it is involved in the regulation of nerve regeneration and the underlying mechanism are unknown. In this study, we examined the mechanical allodynia thermal hyperalgesia together with the peripheral nerve regeneration after nicotine exposure in two rat neuropathic pain models. In the spinal nerve ligation model, in which anatomic nerve regeneration can be easily observed, nicotine reduced anatomic measures of regeneration as well as expression of regeneration marker growth-associated protein 43 (GAP43). In the tibial nerve crush model, nicotine treatment significantly suppressed GAP43 expression and functional reinnervation as measured by myelinated action potential and electromyography of gastrocnemius. In both models, nicotine treatment reduced macrophage density in the sensory ganglia and peripheral nerve. These effects of nicotine were reversed by the selective α7 nicotinic acetylcholine receptor (nAChR) blocker methyllycaconitine. In addition, nicotine significantly elevated expression of PTEN (the phosphatase and tensin homolog deleted on chromosome 10), a key player in both regeneration and pain. Pharmacological interference of PTEN could regulate GAP43 expression, pain-related behaviors, and macrophage infiltration in a nicotine-treated nerve crush model. Our results reveal that nicotine and its α7-nAChR regulate both peripheral nerve regeneration process and pain though PTEN and the downstream inflammation-related pathway.

Prevalence and associated factors of depressive and anxiety symptoms among Chinese secondary school students.

BACKGROUND: Depressive and anxiety symptoms affect about one-fourth of Chinese secondary school students. However, the prevalence and correlates of mental distress among secondary school students from Western China remain largely unexplored. This study aimed to examine the prevalence and associations of depressive and anxiety symptoms with demographic, family, school, life, and behavior factors in a large, representative sample of secondary school students in Zigong, a city in Western China. METHODS: Secondary school students were recruited using cluster sampling. The 9-item Patient Health Questionnaire, the 7-item Generalized Anxiety Disorder Questionnaire, Multidimensional Peer-Victimization Scale, the Pittsburgh Sleep Quality Index, and Nine-Item Internet Gaming Disorder Scale-Short Form were used. Descriptive statistic was used to describe the sociodemographic characteristics of participants. The clustering effect was adjusted by the "survey" package of R to calculate weighted prevalence. Univariate and multivariate logistic regression were used to explore associated factors of depression and anxiety, respectively. RESULTS: A total of 63,205 participants were involved, in which the weighted prevalence of depression in all subjects was 23.0% (95% CI: 19.6- 27.0%), and the weighted prevalence of anxiety was 13.9% (95% CI: 11.2- 17.0%). Logistic regression results showed girls, being single-child, non-nuclear family, peer bullying, sleep disturbance, and internet gaming disorder symptoms were positively associated with depressive and anxiety symptoms. CONCLUSION: Depressive and anxiety symptoms were prevalent among secondary school students in Western China. Our results can guide policy strategies for the assessment, prevention, and intervention of psychological status among Chinese secondary school students.

Exosome and exosomal contents in schizophrenia.

Schizophrenia (SCZ) is a severe mental disorder that affects approximately 1% general population worldwide and poses a considerable burden to society. Despite decades of research, its etiology remains unclear, and diagnosis remains challenging due to its heterogeneous symptoms. Exosomes play a crucial role in intercellular communication, and their contents, including nucleotides, proteins and metabolites, have been linked to various diseases. Recent studies have implicated exosome abnormalities in the pathogenesis of schizophrenia. In this review, we discuss the current understanding of the relationship between exosomes and schizophrenia, focusing on the role of exosomal contents in this disease. We summarize recent findings and provide insights into the potential use of exosomes as biomarkers for the diagnosis and treatment of schizophrenia.

Sex differences in the association of treatment-resistant schizophrenia and serum interleukin-6 levels.

BACKGROUND: Low-grade inflammation and altered inflammatory markers have been observed in treatment-resistant schizophrenia (TRS). Interleukin-6 (IL-6) is one of the pro-inflammatory cytokines linked with TRS and receives increasing attention. Previous studies showed that patients with TRS might have higher IL-6 levels compared with healthy individuals and treatment-responsive patients. Besides, emerging evidence has suggested that there are sex differences in the associations between IL-6 levels and various illnesses, including chronic hepatitis C, metabolic syndrome, etc.; however, there is limited study on TRS. In this present study, we aimed to compare the serum IL-6 levels of TRS and partially responsive schizophrenia (PRS) and explore potential sex differences in the association of TRS and IL-6 levels. METHODS: The study population consisted of a total of 90 patients with schizophrenia: 64 TRS patients (45.3% males and 54.7% females) and 26 PRS patients (46.2% males and 53.8% females). We measured serum IL-6 levels using enzyme-linked immunosorbent assay (ELISA) and analyzed them separately by gender, controlling for confounders (age, education, medication, body mass index, and PANSS scores) rigorously. RESULT: The results showed that patients with TRS had higher serum IL-6 levels than patients with PRS (p = 0.002). In females, IL-6 levels increased significantly in the TRS group compared with the PRS group (p = 0.005). And a positive correlation tendency was observed between IL-6 levels and PANSS general sub-scores (r = 0.31, p = 0.039), although this correlation was not significant after correcting for multiple comparisons. Whereas, there were no differences in IL-6 levels between the TRS and PRS (p = 0.124) in males. CONCLUSION: Our findings provided evidence supporting the hypothesis that the inflammatory response system (IRS) may play a role in the pathogenesis of TRS in a sex-dependent manner. In addition, sex differences in the immune dysfunction of individuals with schizophrenia cannot be neglected, and inflammation in male and female TRS should be discussed separately.

Efficacy of WeChat-based online smoking cessation intervention ('WeChat WeQuit') in China: a randomised controlled trial.

Background: China has approximately 300 million current smokers, and smoking cessation services are limited. This study aimed to assess the efficacy of a Cognitive Behavioral Theory-based smoking cessation intervention ('WeChat WeQuit') via the most popular social media platform in China, WeChat. Methods: A parallel, single-blind, two-arm randomised controlled trial was conducted via WeChat between March 19, 2020 and November 16, 2022. Chinese-speaking adult smokers (n = 2000) willing to quit within one month were recruited and randomised in a 1:1 ratio. The intervention group (n = 1005) received the 'WeChat WeQuit' program and the control group (n = 955) received control messages for 14 weeks (2-week prequit and 12-week postquit). Participants were followed up to 26 weeks after the quit date. The primary outcome was self-reported continuous smoking abstinence rate, biochemically validated at 26 weeks. The secondary outcomes were self-reported 7-day and continuous abstinence rates at 6 months. All analyses were by intention to treat. The trial is registered at ClinicalTrials.gov (NCT03169686). Findings: By intention-to-treat analysis, the biochemically verified 26-week continuous abstinence rate was 11.94% in the intervention group and 2.81% in the control group (OR = 4.68, 95% CI: 3.07-7.13, p < 0.0001). The self-reported 7-day abstinence rates ranged from 39.70% at week 1-32.04% at week 26 for the intervention group and 14.17%-11.86% in the control group for weeks 1 and 26, respectively; the self-reported continuous abstinence rates at weeks 1 and 26 ranged from 34.33% to 24.28% and 9.65% to 6.13% in the intervention group and the control group respectively (all p < 0.0001). Participants with low nicotine dependence or previous quit attempts were more likely to successfully quit smoking. Interpretation: The 'WeChat WeQuit' intervention significantly increased smoking abstinence rates at 6 months and should be considered for treatment-seeking smokers in China. Funding: The research is supported by the Natural Science Foundation of Hunan Province (2020JJ4794, YLiao), the K.C. Wong Postdoctoral Fellowship for YLiao to study at King's College London, and China Medical Board (CMB) Open Competition Program (grant no. 15-226, 22-485, YLiao).

Cross-talks between gut microbiota and tobacco smoking: a two-sample Mendelian randomization study.

BACKGROUND: Considerable evidence has been reported that tobacco use could cause alterations in gut microbiota composition. The microbiota-gut-brain axis also in turn hinted at a possible contribution of the gut microbiota to smoking. However, population-level studies with a higher evidence level for causality are lacking. METHODS: This study utilized the summary-level data of respective genome-wide association study (GWAS) for 211 gut microbial taxa and five smoking phenotypes to reveal the causal association between the gut microbiota and tobacco smoking. Two-sample bidirectional Mendelian randomization (MR) design was deployed and comprehensively sensitive analyses were followed to validate the robustness of results. We further performed multivariable MR to evaluate the effect of neurotransmitter-associated metabolites on observed associations. RESULTS: Our univariable MR results confirmed the effects of smoking on three taxa (Intestinimonas, Catenibacterium, and Ruminococcaceae, observed from previous studies) with boosted evidence level and identified another 13 taxa which may be causally affected by tobacco smoking. As for the other direction, we revealed that smoking behaviors could be potential consequence of specific taxa abundance. Combining with existing observational evidence, we provided novel insights regarding a positive feedback loop of smoking through Actinobacteria and indicated a potential mechanism for the link between parental smoking and early smoking initiation of their children driven by Bifidobacterium. The multivariable MR results suggested that neurotransmitter-associated metabolites (tryptophan and tyrosine, also supported by previous studies) probably played a role in the action pathway from the gut microbiota to smoking, especially for Actinobacteria and Peptococcus. CONCLUSIONS: In summary, the current study suggested the role of the specific gut microbes on the risk for cigarette smoking (likely involving alterations in metabolites) and in turn smoking on specific gut microbes. Our findings highlighted the hazards of tobacco use for gut flora dysbiosis and shed light on the potential role of specific gut microbiota for smoking behaviors.

Differences in olfactory dysfunction and its relationship with cognitive function in schizophrenia patients with and without auditory verbal hallucinations.

Olfactory discrimination dysfunction has been observed in patients with schizophrenia (SCZ), but its relationship with cognitive function has not been clarified. The purpose of this study was to examine the differences in olfactory identification function in SCZ patients with and without auditory verbal hallucinations (AVHs) and its relationship with cognitive function. Olfactory identification function was measured in 80 SCZ patients with AVHs, 57 SCZ patients without AVHs, and 87 healthy controls (HC). Clinical symptom scores and neuropsychological measures were also administered to all corresponding subjects. Compared to HC, SCZ patients showed significant deficits in olfactory identification and cognitive function, but there were no differences in olfactory identification dysfunction and cognitive dysfunction between the two subgroups. In the non-AVHs subgroup only, poorer Olfactory Stick Identification Test for Japanese (OSIT-J) scores were significantly and positively correlated with total and delayed recall (Bonferroni correction, p < 0.002). Stepwise regression analysis revealed that factors affecting olfactory identification impairment differed in the two SCZ patient subgroups. In conclusion, this study highlights the commonality of olfactory identification dysfunction in SCZ patients and the importance of olfactory assessment of different subtypes of SCZ patients.

Factors Influencing the Level of Depression and Anxiety of Community-Dwelling Patients with Schizophrenia in China during the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) poses a huge challenge to global public health. People with schizophrenia living in communities urgently need effective interventions to help them adjust to life and work, but they have not received enough attention. This study aims to assess the prevalence of anxiety and depression symptoms in community-dwelling patients with schizophrenia in China during the epidemic and to explore the possible influencing factors. METHODS: Using a cross-sectional survey, we collected 15,165 questionnaires. Assessments included demographic information, concern about COVID-19-related information, sleep status, anxiety and depressive symptoms, and accompanying illnesses. The 7-item Generalized Anxiety Disorder (GAD-7) and the 9-item Patient Health Questionnaire (PHQ-9) were used to evaluate depression and anxiety levels. Group comparison was conducted by t-test, ANOVA, or chi-square test wherever suitable, with Bonferroni pairwise correction. Multivariate logistic regression was performed to identify predictors for anxiety and depression. RESULTS: 16.9% of patients had at least moderate anxiety, and 34.9% had at least moderate depression. T-test showed that females scored higher on GAD-7 and PHQ-9 than males, and patients without accompanying long-standing diseases, who were not concerned about COVID-19, had lower GAD-7 and PHQ-9 scores. ANOVA showed that participants aged from 30 to 39, with higher education scored higher on GAD-7, and patients with better sleep, and having less concern about COVID-19, had lower GAD-7 and PHQ-9 scores. Regression analysis indicated that participant ages of 30-39 and 40-49 positively predicted anxiety, whereas patient ages of 30-39 years positively predicted depression. Patients with poor sleep, accompanying diseases, and concern about the COVID-19 pandemic were more likely to experience anxiety and depression. CONCLUSION: During the pandemic, Chinese community-dwelling patients with schizophrenia had high rates of anxiety and depression. These patients deserve clinical attention and psychological intervention, especially those with risk factors.