Widespread reductions in cortical thickness following ketamine abuse.

BACKGROUND: Esketamine is a version of ketamine that has been approved for treatment-resistant depression, but our previous studies showed a link between non-medical use of ketamine and brain structural and functional alterations, including dorsal prefrontal grey matter reduction among chronic ketamine users. In this study, we sought to determine cortical thickness abnormalities following long-term, non-medical use of ketamine. METHODS: We acquired structural brain images for patients with ketamine use disorder and drug-free healthy controls. We used FreeSurfer software to measure cortical thickness for 68 brain regions. We compared cortical thickness between the 2 groups using analysis of covariance with covariates of age, gender, educational level, smoking, drinking, and whole-brain mean cortical thickness. RESULTS: We included images from 95 patients with ketamine use disorder and 169 controls. Compared with healthy controls, patients with ketamine use disorder had widespread decreased cortical thickness, with the most extensive reductions in the frontal (including the dorsolateral prefrontal cortex) and parietal (including the precuneus) lobes. Increased cortical thickness was not observed among ketamine users relative to comparison participants. Estimated total lifetime ketamine consumption was correlated with reductions in the right inferior parietal and the right rostral middle frontal cortical thickness. LIMITATIONS: We conducted a retrospective cross-sectional study, but longitudinal studies are needed to further validate decreased cortical thickness after nonmedical use of ketamine. CONCLUSION: This study provided evidence that, compared with healthy controls, chronic ketamine users have widespread reductions in cortical thickness. Our study underscores the importance of the long-term effects of ketamine on brain structure and serves as a reference for the antidepressant use of ketamine.

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.

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.

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.

Preparation of PEGylated nedaplatin liposomes with sustained release behavior for enhancing the antitumor efficacy of non-small cell lung cancer.

Nedaplatin (NDP) plays an important role in the chemotherapies of non-small cell lung cancer (NSCLC). However, dose-limiting toxicities such as myelosuppression and drug resistance restrict its clinical application. Herein, we intended to overcome these defects by developing a PEGylated liposomal formulation encapsulated NDP (NDP-LPs). For the first time, we found the incompatibility between NDP and natural phospholipids such as egg phosphatidylcholine (EPC) using the high-performance liquid chromatography (HPLC) method. The orthogonal experimental design was applied to optimize the conditions for preparing NDP-LPs, with encapsulation efficiency (EE) as the evaluation indicator. The physicochemical properties of optimized NDP-LPs were further characterized, including particle size, zeta potential, EE, drug release profiles, and so on. Results showed that a significantly sustained-release profile of NDP-LPs was observed and the releasing time of NDP could reach as long as 8 days. At the cellular level, NDP encapsulated in the PEGylated liposomes enhanced its cellular uptake and possessed potent cytotoxic activity. After intravenous injection, NDP-LPs could accumulate at tumor sites and effectivelyinhibit tumor growth of mice without obvious adverse effects. In conclusion, our results demonstrated that PEGylated liposomes could serve as a promising carrier to enhance the therapeutic effects of NDP.

Predictors of long-term abstinence in a randomized controlled trial of smoking cessation by mobile phone text messaging ('Happy Quit') in China.

INTRODUCTION: The mobile phone-based text messaging intervention ('Happy Quit') is a minimal and effective intervention with very wide reach; thus, it has the possibility of a population impact on quitting rates. Obtaining information on predictors of long-term quit rates is crucial for developing and implementing more effective mobile-based interventions. The study aimed to explore the predictors of long-term abstinence following the 'Happy Quit' intervention. METHODS: This study is a secondary analysis of a randomized controlled trial (RCT) that compared 12-week text messaging intervention ('Happy Quit') versus control intervention with follow-up at 24 weeks, in China. Only participants who had biochemically verified continuous smoking abstinence at 24 weeks were followed up at 52 weeks after the quit date. This predictor regression analysis is for those who were biochemically verified continuous 52-week quitters (n=67) compared with the other participants (n=1302) in the RCT. RESULTS: Of the 69 smokers who were continuously abstinent at 24 weeks, 97.1% (n=67) remained continuously abstinent at 52 weeks. The biochemically verified long-term (52 weeks or 1year) quit rate was 6.3% in the intervention group (60/958), 1.7% in the control group (7/411) (OR=3.677; 95% CI: 1.67-8.11, p<0.001). Multivariable regression analysis revealed that only smoked ≤10 cigarettes per day (compared with >10 cigarettes per day) was the only predictor for long-term abstinence. CONCLUSIONS: This study suggests that individuals who are light smokers might get the most benefit from the text messaging intervention ('Happy Quit') in China.

Emotional State of Chinese Healthcare Workers During COVID-19 Pandemic.

Objective: Anti-epidemic work against coronavirus disease (COVID) has become routine work in China. Our study was intended to investigate the emotional and psychological state of healthcare workers and look for the association between sociodemographic factors/profession-related condition and emotional state. Methods: A cross-sectional survey was conducted online among healthcare workers from various backgrounds. Symptoms of anxiety and depression were assessed by the Chinese versions of the seven-item Generalized Anxiety Disorder (GAD-7) and the nine-item Patient Health Questionnaire (PHQ-9), respectively. Supplementary questions (Supplementary Material) were recorded to describe the participants' information about workplace violence, profession, and attitude related to the COVID pandemic. Wherever suitable, independent t-test, and one-way ANOVA were performed to detect group differences of GAD-7 and PHQ-9 total scores after grouping by sociodemographic variables, respectively, such as age, gender, marital status, educational level, after-tax income, department category, job title, experience of workplace violence, and anti-epidemic participation. Multiple linear regression analyses (stepwise method) were utilized in order to look for the potential associated factors of GAD-7 and PHQ-9 total scores. Results: A total of 2,139 questionnaires with valid response were completed. Approximately 86.44% of participants had minimal symptoms of anxiety, 11.08% mild, 1.59% moderate, and 0.89% severe. Meanwhile, 81.34% had minimal symptoms of depression, 14.07% mild, 2.90% moderate, 1.17% moderately severe, and 0.51% severe. Student's t-test showed that participants with female gender, with experience of workplace violence scored higher on both GAD-7 and PHQ-9, and participants with experience of anti-epidemic front-line work during pandemic scored lower on both GAD-7 and PHQ-9. ANOVA showed that participants aging from 31 to 40, with higher educational level, with middle level of annual after-tax income, with department of internal medicine or surgery, or with middle level of job title scored higher on both GAD-7 and PHQ-9. Regression analyses showed that female gender, high job title, and the experience of workplace violence positively were associated with anxiety or depression. Doctoral education, department (other vs. psychiatry), job enthusiasm, and professional self-identity were negatively associated with anxiety or depression. Additionally, psychological support was negatively associated with depression. Conclusion: As the epidemic prevention and control against COVID-19 become normalized in China, emotional state of healthcare workers deserves extensive attention. Our study revealed that gender, educational level, department category, job title, the experience of workplace violence, job enthusiasm, and professional self-identity are the most important influencing factors of physician's anxiety and depression. Self-tailored psychological intervention should be based on the predisposing factors above to mentally prepare healthcare workers for this long-lasting battle against COVID-19.

Attitudes towards smoking and COVID-19, and changes in smoking behaviors before and after the outbreak of COVID-19: A nationwide cross-sectional survey study in China.

INTRODUCTION: China has more than 300 million current smokers. There is a controversy over smokers' risk of COVID-19 infection. Smoking is a risk factor for COVID-19 disease progression, and the outbreak of COVID-19 may change people's smoking behaviors. This study assessed people's attitudes towards 'smoking and COVID-19' and changes of smoking behaviors before and after the outbreak of COVID-19. METHODS: A cross-sectional web survey of 11009 adults in China was conducted between 7 May and 3 August 2020. Attitudes towards 'smoking and COVID-19' were compared among non-smokers (n=8837), ex-smokers (n=399) and current smokers (n=1773), and changes in smoking behaviors before and after the outbreak of COVID-19 were assessed among current smokers. RESULTS: Fewer current smokers (26.2%) agreed with the statement that 'Current smokers are more likely than ex-smokers or non-smokers to contract COVID-19' compared with non-smokers (53%) or ex-smokers (41.4%); fewer current smokers (55.9%) agreed with the statement 'If contracted, current smokers are more likely than ex-smokers or non-smokers to risk disease progression' compared with non-smokers (75.5%) or ex-smokers (68.7%). There were no changes in cigarettes smoked per day (mean ± SD: 13.3 ± 9.55 vs 13.4 ± 9.69, p=0.414), percentage of daily smokers (70.8% vs 71.1%, p=0.882) and percentage of smokers with motivation to quit (intend to quit within the next 6 months, 9.4% vs 10.9%, p=0.148) before and after the outbreak of COVID-19. CONCLUSIONS: The survey found that fewer current smokers agreed that smoking is a risk-factor for COVID-19 compared with non-smokers or ex-smokers. Among current smokers, there were no changes in their cigarette consumption and motivation to quit before and after the outbreak of COVID-19. More efforts are needed to educate smokers about the health risks of smoking, as well as efforts to promote their motivation to quit.

Impact of cigarette package warnings on attitudes towards sharing and gifting cigarettes in China: a nationwide study of smokers and non-smokers.

BACKGROUND: Sharing and gifting cigarettes are common in China. These social practices promote cigarette consumption, and consequently may reduce quit rates in China. This study investigated sharing and gifting cigarettes, and the relationship of observing pictorial health warnings to attitudes towards sharing and gifting cigarettes in China. METHODS: We conducted an online nationwide cross-sectional study of 9818 adults in China. Experiences of sharing and gifting cigarettes, and attitudes towards sharing and gifting cigarettes before and after viewing text and pictorial health warnings on the packages were assessed, and compared between smokers and non-smokers. RESULTS: Most current smokers reported experiences of sharing (97%) and gifting (around 90%) cigarettes. Less than half of non-smokers reported sharing cigarettes and receiving gifted cigarettes, but over half (61.4%) gave cigarettes as a gift to others. More than half of non-smokers but less than 10% of smokers disagreed with sharing and gifting cigarettes. After observing both text and pictorial health warnings on the packages, disagreement with sharing and gifting cigarettes increased by more than 10 percentage points among both smokers and non-smokers. CONCLUSION: Having pictorial health warnings on cigarette packages may reduce sharing and gifting cigarettes in China.

Serum IL-6 and procalcitonin are two promising novel biomarkers for evaluating the severity of COVID-19 patients.

ABSTRACT: To evaluate the development of coronavirus disease 2019 (COVID-19), the roles of interleukin 6 (IL-6) and procalcitonin (PCT) were assessed to diagnose severe COVID-19.Between January and February 2020, 100 consecutive patients with confirmed COVID-19 were included and divided into common (n = 56), severe (n = 28), and critical (n = 16) groups.IL-6 and PCT levels were assayed and compared among groups. IL-6 levels were significantly different among groups (common, 23.93±9.64 pg/mL; severe, 69.22 ±â€Š22.98 pg/mL; critical, 160.34 ±â€Š26.15 pg/mL; P < .05), and there was also a significant difference in the levels of PCT among groups (common, 0.23 ±â€Š0.13 ng/mL; severe, 0.38 ±â€Š0.16 ng/mL; critical, 0.73 ±â€Š0.36 ng/mL; P < .05). Further analysis showed that patients in the critical group had the highest levels of IL-6 and PCT, and those in the common group had the lowest levels (all P < .05).IL-6 and PCT are associated with the severity of COVID-19, and thus have potential value in the diagnosis of COVID-19.

Development of quantum dot-based fluorescence lateral flow immunoassay strip for rapid and quantitative detection of serum interleukin-6.

BACKGROUND: Interleukin-6 (IL-6) is an inflammatory factor that increases rapidly in response to infectious diseases including sepsis. The aim of this study is to develop a quantum dot (QD)-based fluorescence lateral flow immunoassay (LFIA) strip that can rapidly and accurately detect IL-6 levels. METHODS: QD-based LFIA strips were fabricated by conjugating CdSe/ZnS QDs to the IL-6 antibody. Performance verification and clinical sample analysis were carried out to evaluate the newly developed strip. RESULTS: QD-based LFIA strips were successfully fabricated. The test strip's linear range was 10-4000 pg/ml, with a linear correlation coefficient of R2  ≥ .959. The sensitivity of the test strip was 1.995 pg/ml. The recovery rate was 95.72%-102.63%, indicating satisfying accuracy. The coefficient of variation (CV) of the intra-assay was 2.148%-3.903%, while the inter-assay was 2.412%-5.293%, verifying the strip's high precision. The cross-reaction rates with various interleukins (IL-1α, IL-1ß, IL-2, IL-4, and IL-8) and interferon-γ (IFN-γ) were all <0.1%. When the strip was placed in a 50°C oven for 1, 2, 3, and 4 weeks, the test results were not significantly altered compared to storage at room temperature. Furthermore, 200 clinical serum samples were analyzed to compare the strip with the Beckman chemiluminescence immunoassay (CLIA) kit, which revealed a high correlation (n = 200, R2  = .9971) for the detection of IL-6. CONCLUSIONS: The QD-based test strip can rapidly and quantitatively detect IL-6 levels, thus meeting the requirement of point-of-care test (POCT) and showing excellent clinical prospects.

Efficacy of cognitive behavioural therapy-based smartphone app for smoking cessation in China: a study protocol of a randomised controlled trial.

INTRODUCTION: A number of smartphone apps have been proved to be effective in assisting smoking cessation in many countries, but little is known about the effectiveness of smartphone apps that assist in smoking cessation in China. This study aims to evaluate the efficacy of cognitive behavioural therapy (CBT)-based cigarette smoking cessation smartphone app for treatment-seeking smokers in China. METHODS AND ANALYSIS: In this remote control, randomised controlled trial, the participants will be randomised and allocated in 1:1 ratio to smoking cessation app intervention group or to control group. Participants will receive a 12-week intervention (treatment group will receive CBT-based cigarette smoking cessation smartphone app intervention and control group will receive text messaging-based control intervention) with follow-up at week 26. The primary outcome includes biologically verified continuous smoking abstinence at week 26 after the quit date. The main secondary outcomes include 7-hour point prevalence smoking abstinence at weeks 1, 2, 3, 4, 8, 12, 16, 20 and 26, self-reported continuous smoking abstinence at weeks 4, 8, 12, 16, 20 and 26 after the quit date. About 1200 smokers with willingness to make a quit attempt within a month from January 2021 to August 2021 or until the recruitment process is complete will be recruited. The final 26-week follow-up will be completed in August 2022. The trial results will be available by the end of 2022. All analyses will be done on an intention-to-treat basis. Based on the previous studies, we hypothesised that this CBT-based app will be an effective, feasible and accessible smoking cessation app in China. ETHICS AND DISSEMINATION: Ethical approval was obtained from the ethics committee of Sir Run Run Shaw Hospital, an affiliate of Zhejiang University, Medical College (number: 20200129-33). Study results will be disseminated via research conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04421170.

Effectiveness of the WeChat-based smoking cessation intervention ('WeChat WeQuit' program) in China: study protocol for a randomized controlled trial.

BACKGROUND AND AIMS: Since its first release in 2011, WeChat (Chinese pinyin: Wei Xin) has been widely used to promote health. As the most popular all-in-one social media application providing free instant messaging, voice, text, pictures, videos and location information exchange via smartphone, WeChat holds promise for delivering smoking cessation services to a large number of people at low unit cost in China, a country with more than 300 million smokers. This protocol is for a study that aims to assess the efficacy of a WeChat-based smoking cessation intervention ('WeChat WeQuit') for treatment-seeking smokers in China. DESIGN: In this two-arm randomized controlled trial (RCT), the control group will receive only a digital version of a booklet of 'Happy Quit'. The intervention group will also receive the 2 weeks pre- and 12 weeks post-quit 'WeChat WeQuit' intervention. Both groups will be followed-up to 26 weeks (6 months) after quit day. SETTING: This on-line trial has no restrictions on setting or location. PARTICIPANTS: Chinese-speaking current smokers (have smoked ≥100 cigarettes in their life-time and currently smoke cigarettes) aged 18+ years willing to make a quit attempt within 1 month (n = 2000) will be recruited by on- and off-line advertising. Potential participants will register their interest by sending WeChat messages or text messages, or making a voice call. MEASUREMENTS: The primary outcome measure is self-reported 26-week continuous smoking abstinence with biological verification [test by clinic visit: expired carbon monoxide concentration <10 parts per million (p.p.m.) or by mailing cotinine urine dipsticks: urine cotinine <200 ng/ml]. Secondary outcome measures include: 7-day point prevalence abstinence at weeks 1, 4, 8, 12, 16, 20 and 26 after-quit day; self-reported 12-week continuous smoking abstinence and 26-week continuous smoking abstinence; reductions in number of cigarettes smoked per day; and rates of participation in and completion of the smoking-cessation program. CONCLUSIONS: If the 'WeChat WeQuit' program is found to be effective, it will be an accessible, affordable and widely implementable intervention to help cigarette smokers to quit. The potential public health impact of its expansion into underserved regions or communities is considerable.

Feasibility and Acceptability of a Cognitive Behavioral Therapy-Based Smartphone App for Smoking Cessation in China: A Single-Group Cohort Study.

Background: Previous research has suggested that mobile phone applications (apps) may potentially increase quit rates. The purpose of this single-group cohort study sought to examine the feasibility and acceptability of a novel smartphone-based smoking cessation app designed for smoking cessation in China: smoking quit rate. Methods: A total of 180 smokers from two cities of mainland China with willingness to make a quit attempt were invited to this smoking cessation app program, a cognitive behavioral theory (CBT)-based smoking cessation intervention via a smartphone app. Participants received 37- to 44-day intervention (including 7- to 14-day pre-quit preparation and 33-day intervention from quit date). Feasibility and acceptability of the program, and smoking status were assessed at baseline stage (initial installation), pre-quit stage, and post-quit stage (days 7, 15, and 33 after quit date). Results: A total of 163 (90.6%) participants completed the study. Among them, 76-89% of the participants logged into the app ≥1 time per day across stages (at baseline, during pre-quit stage, and on days 7, 15, and 33 of post-quit stage); approximately 90% of the participants were satisfied with the app across stages. A significant rise in self-reported overall satisfaction with the app is observed from baseline (93% at Time 1) to the end of the program (98% at Time 2, 33 days after quit date) (p = 0.021). Participants who believed/agreed this app can help them to quit smoking significantly increased from 69% at baseline to 97% at day 33 after quit date (p < 0.001). Participants were satisfied with most (80-90%) of the features, especially the information feature. Intention-to-treat analysis showed that the percentage of 33-day self-reported continuous prevalence abstinence was 63.9%, and 7-day point prevalence abstinence rate was 81.7, 87.2, and 77.8% on days 7, 15, and 33 after quit date, respectively. Conclusions: This study demonstrated the feasibility and acceptability of the smartphone app intervention for smoking cessation and introduced a new digital treatment model, which is expected to overcome barriers facing accessing traditional in-person smoking cessation services and extend nationwide smoking cessation services in China.

Development of a highly thermostable immunoassay based on a nanobody-alkaline phosphatase fusion protein for carcinoembryonic antigen detection.

Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM-5) assays are employed in routine clinical settings to diagnose tumor. We selected two nanobodies with high-affinity to CEACAM-5, termed Nb11C12 and Nb2D5, using phage-display technology. The Nb2D5 fused with calf intestinal alkaline phosphatase (CAP), human placental alkaline phosphatase (HAP), or Pyrococcus abyssi alkaline phosphatase (PAP) were expressed in human embryonic kidney (HEK293) cells. The enzymatic activity of Nb2D5-HAP fusion protein was the best and remained stable at 60 °C for 7 days. The affinity of Nb2D5-HAP fusion protein to CEACAM-5 reached 42 pM. A chemiluminescent enzyme immunoassay (CLEIA) based on Nb2D5-HAP fusion protein was established for quantitative CEACAM-5 assay in clinical settings. The CLEIA exhibited a wide linear range of 0.31-640 ng/mL toward CEACAM-5, with a limit of detection (LOD) of 0.85 ng/mL. No cross-reactivity occurred with CEACAM-1, CEACAM-3, CEACAM-6, or CEACAM-8, and no interference was observed with rheumatoid factors. The CLEIA based on Nb2D5-HAP fusion protein was stable for 8 weeks at 37 °C and 50% relative humidity. The CLEIA developed from Nb2D5-HAP fusion protein had much better stability and linearity with similar reproducibility compared with the enzyme-linked immunosorbent assay developed from conventional monoclonal antibodies, which have been widely used in clinics over the past several decades. Graphical abstract.

Sleep quality in cigarette smokers and nonsmokers: findings from the general population in central China.

BACKGROUND: Sleep problems are common in the general population. Cigarette smoking is common in the general population of China. Examinations of the prevalence of poor sleep quality among Chinese smokers and nonsmokers are still lacking. This study was designed to examine sleep quality and sleep disturbances among cigarette smokers and nonsmokers in the general population in central China. METHODS: In this population-based sampling project, we used a multi-stage sampling method to recruit survey participants from September 2012 to October 2012 in rural and urban areas of Hunan province, China. A total of 27,300 subjects were sampled from the general population and 26,282 completed the self-report of cigarette smoking characteristics. Cigarette smoker was defined as having smoked ≥100 cigarette in a lifetime and smoked during the last 28 days. Cigarette smoking characteristics were obtained from smokers, including cigarettes per day, years of smoking, quit attempts, and smoking cravings. The Pittsburgh Sleep Quality Index (PSQI) was applied to assess quality of sleep and sleep disturbances (PSQI score > 5). RESULTS: Significantly more smokers than nonsmokers demonstrated poor sleep quality and sleep disturbances. Among smokers, linear regression analyses showed that poor sleep was inversely associated with cigarettes per day, and positively associated with years of smoking, quit attempts, and smoking craving. Logistic regression analysis showed that quit attempts and smoking cravings were associated with higher odds of sleep disturbances. CONCLUSIONS: Sleep disturbances were more prevalent among cigarette smokers than nonsmokers. Smokers also varied in sleep problems on the basis of the characteristics of their smoking. Smokers should be informed about the link between cigarette smoking and poor sleep quality, and should be advised that one of several important health benefits from smoking cessation could be the improvement of sleep quality. Sleep therapy should be recommended as an adjunctive treatment for smoking cessation.

Effectiveness of a text-messaging-based smoking cessation intervention ("Happy Quit") for smoking cessation in China: A randomized controlled trial.

BACKGROUND: China has the highest global prevalence of cigarette smokers, accounting for more than 40% of the total cigarette consumption in the world. Considering the shortage of smoking cessation services in China, and the acceptability, feasibility, and efficacy of mobile-phone-based text messaging interventions for quitting smoking in other countries, we conducted a mobile-phone-based smoking cessation study in China. METHODS AND FINDINGS: We conducted a randomized controlled trial in China across 30 cities and provinces from August 17, 2016, to May 27, 2017. Adult smokers aged 18 years and older with the intention to quit smoking were recruited and randomized to a 12-week high-frequency messaging (HFM) or low-frequency messaging (LFM) intervention ("Happy Quit") or to a control group in a 5:2:3 ratio. The control group received only text messages unrelated to quitting. The primary outcome was biochemically verified continuous smoking abstinence at 24 weeks. Secondary outcomes included (1) self-reported 7-day point prevalence of abstinence (i.e., not even a puff of smoke, for the last 7 days) at 1, 4, 8, 12, 16, 20, and 24 weeks; (2) self-reported continuous abstinence at 4, 12, and 24 weeks; and (3) self-reported average number of cigarettes smoked per day. A total of 1,369 participants received 12 weeks of intervention or control text messages with continued follow-up for 12 weeks. The baseline characteristics of participants among the HFM (n = 674), LFM (n = 284), and control (n = 411) groups were similar. The study sample included 1,295 (94.6%) men; participants had a mean age of 38.1 (SD 9.79) years and smoked an average of 20.1 (SD 9.19) cigarettes per day. We included the participants in an intention-to-treat analysis. Biochemically verified continuous smoking abstinence at 24 weeks occurred in 44/674 participants in the HFM group (6.5%), 17/284 participants in the LFM group (6.0%), and 8/411 participants (1.9%) in the control group; participants in both the HFM (odds ratio [OR] = 3.51, 95% CI 1.64-7.55, p < 0.001) and the LFM (OR = 3.21, 95% CI 1.36-7.54], p = 0.002) intervention groups were more likely to quit smoking than those in the control group. However, there was no difference in quit rate between the HFM and LFM interventions. We also found that the 7-day point quit rate from week 1 to week 24 ranged from approximately 10% to more than 26% with the intervention and from less than 4% to nearly 12% without the intervention. Those who continued as smokers in the HFM group smoked 1 to 3 fewer cigarettes per day than those in the LFM group over the 24 weeks of trial. Among study limitations, the participants were able to use other smoking cessation services (although very few participants reported using them), cotinine tests can only detect smoking status for a few days, and the proportion of quitters was small. CONCLUSIONS: Our findings demonstrate that a mobile-phone-based text messaging intervention (Happy Quit), with either high- or low-frequency messaging, led to smoking cessation in the present study, albeit in a low proportion of smokers, and can therefore be considered for use in large-scale intervention efforts in China. Mobile-phone-based interventions could be paired with other smoking cessation services for treatment-seeking smokers in China. TRIAL REGISTRATION: ClinicalTrials.gov NCT02693626.

Cue-Induced Brain Activation in Chronic Ketamine-Dependent Subjects, Cigarette Smokers, and Healthy Controls: A Task Functional Magnetic Resonance Imaging Study.

BACKGROUND: Observations of drug-related cues may induce craving in drug-dependent patients, prompting compulsive drug-seeking behavior. Sexual dysfunction is common in drug users. The aim of the study was to examine regional brain activation to drug (ketamine, cigarette smoking) associated cues and natural (sexual) rewards. METHODS: A sample of 129 [40 ketamine use smokers (KUS), 45 non-ketamine use smokers (NKUS) and 44 non-ketamine use non-smoking healthy controls (HC)] participants underwent functional magnetic resonance imaging (fMRI) while viewing ketamine use related, smoking and sexual films. RESULTS: We found that KUS showed significant increased activation in anterior cingulate cortex and precuneus in response to ketamine cues. Ketamine users (KUS) showed lower activation in cerebellum and middle temporal cortex compared with non-ketamine users (NKUS and HC) in response to sexual cues. Smokers (KUS and NKUS) showed higher activation in the right precentral frontal cortex in response to smoking cues. Non-ketamine users (NKUS and HC) showed significantly increased activation of cerebellum and middle temporal cortex while viewing sexual cues. CONCLUSION: These findings clearly show the engagement of distinct neural circuitry for drug-related stimuli in chronic ketamine users. While smokers (both KUS and NKUS) showed overlapping differences in activation for smoking cues, the former group showed a specific neural response to relevant (i.e., ketamine-related) cues. In particular, the heightened response in anterior cingulate cortex may have important implications for how attentionally salient such cues are in this group. Ketamine users (KUS) showed lower activation in response to sexual cues may partly reflect the neural basis of sexual dysfunction.