ABSTRACT
BACKGROUND AND OBJECTIVE: Nicotine metabolic ratio (NMR) has been associated with nicotine metabolism and smoking characteristics. However, there are few studies on the potential association between NMR and smoking cessation efficacy in smokers with chronic obstructive pulmonary disease (COPD) in China or elsewhere. METHODS: This study was a stratified block randomized controlled trial for smoking cessation in Chinese smokers with COPD. NMR was used as a stratification factor; slow metabolizers were defined as those with NMR <0.31, and normal metabolizers as those with NMR ≥0.31. Participants were randomly assigned to the varenicline or bupropion group. Follow-up visits were conducted at 1, 2, 4, 6, 9, 12 and 24 weeks. RESULTS: Two hundred twenty-four participants were recruited and analysed from February 2019 to June 2022. In normal metabolizers, the 9-12 weeks continuous abstinence rate of varenicline (43.1%) was higher than in bupropion (23.5%) (OR = 2.47, 95% CI 1.05-5.78, p = 0.038). There was no significant difference in abstinence rates between treatment groups in slow metabolizers (54.1% vs. 45.9%, OR = 1.39, 95% CI 0.68-2.83, p = 0.366). For slow metabolizers, the total score of side effects in the varenicline group was significantly higher than the bupropion group (p = 0.048), while there was no significant difference in side effects between groups for normal metabolizers (p = 0.360). CONCLUSION: Varenicline showed better efficacy than bupropion in normal metabolizers, and bupropion showed equivalent efficacy in slow metabolizers with less side effects. According to our study, NMR provides a better justification for both scientific research and tailoring optimal pharmacotherapy for smoking cessation among smokers in COPD.
Subject(s)
Bupropion , Nicotine , Pulmonary Disease, Chronic Obstructive , Smoking Cessation Agents , Smoking Cessation , Varenicline , Humans , Varenicline/therapeutic use , Bupropion/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/metabolism , Male , Female , Smoking Cessation/methods , Middle Aged , Smoking Cessation Agents/therapeutic use , Treatment Outcome , Aged , China/epidemiology , SmokersABSTRACT
The catalytic asymmetric synthesis of P-chiral phosphorus compounds is an important way to construct P-chiral ligands. Herein, we report a new strategy that adopts the pyridinyl moiety as the coordinating group in the cobalt-catalysed asymmetric nucleophilic addition/alkylation of secondary phosphine oxides. A series of tertiary phosphine oxides were generated with up to 99 % yield and 99.5 % ee, and with broad functional-group tolerance. Mechanistic studies reveal that (R)-secondary phosphine oxides preferentially interact with the cobalt catalysts to produce P-stereogenic compounds.
ABSTRACT
BACKGROUND/AIMS: Human leukocyte antigen-G (HLA-G) plays an important role in inhibiting natural killer (NK) cell function and promoting immune escape. However, the specific mechanism of HLA-G on NK in gastric cancer (GC) remains not well understood. This study investigated the expression of HLA-G in GC and the role of HLA-G-effected NK cells in GC progression. METHODS: HLA-G expression in GC tissues obtained from 49 patients with GC was analyzed by immunohistochemistry and western blot. The number of tumor-infiltrating NK cells and the expression of their surface receptors were analyzed by immunohistochemistry and flow cytometry, respectively. The effect of HLA-G on NK cell proliferation was examined by Cell Counting Kit-8 (CCK8) assay. LDH release assay was used to evaluate the effect of HLA-G on the cytotoxic activity of NK cells, and the levels of IFN-γ and TNF-α in the co-cultured supernatant were detected by ELISA. Mice bearing a xenograft tumor model were used to examine the effect of HLA-G on the anti-tumor effect of NK cells. RESULTS: HLA-G positive expression was detected in most of the GC tissues, and was correlated with the adverse prognosis of the disease. The expression of HLA-G was negatively associated with the number of tumor-infiltrating NK cells. Furthermore, GC cell lines with overexpressed HLA-G revealed their ability to inhibit the cell proliferation and cytotoxic activity of NK-92MI cells, and reduce the secretion of IFN-γ and TNF-α through immunoglobulin-like transcript 2 (ILT2). Finally, this in vivo experiment was able to prove that HLA-G can inhibit the anti-tumor effect of NK cells through ILT2. CONCLUSION: The expression of HLA-G was strongly correlated with the adverse prognosis of GC. The reason may be that it inhibits the proliferation and cytotoxic activity of infiltrating NK cells through ILT2.
Subject(s)
Antigens, CD/metabolism , HLA-G Antigens/metabolism , Killer Cells, Natural/immunology , Leukocyte Immunoglobulin-like Receptor B1/metabolism , Stomach Neoplasms/pathology , Aged , Animals , Antigens, CD/genetics , Cell Line, Tumor , Cell Proliferation , Coculture Techniques , Disease-Free Survival , Female , HLA-G Antigens/genetics , Humans , Interferon-gamma/analysis , Interferon-gamma/metabolism , Killer Cells, Natural/metabolism , Leukocyte Immunoglobulin-like Receptor B1/genetics , Lymphocyte Activation/immunology , Male , Mice, Inbred NOD , Mice, SCID , Middle Aged , Prognosis , Receptors, KIR2DL4/genetics , Receptors, KIR2DL4/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/mortality , Transplantation, Heterologous , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/metabolismABSTRACT
BACKGROUND: The prevalence of cigarette smoking among women is significantly different from that of men, however, cigarette use by women is little known. The study aims to describe cigarette use prevalence and patterns among Chinese females by age and province. METHODS: This study was based on the 2018 China Health Literacy Survey (2018 CHLS), a nationally representative cross-sectional study, and our analysis included 43,319 female participants aged 20-69 with valid data. The prevalence of cigarette use was estimated overall by sociodemographic factors and weighted based on the census population data. The logistic regression model was conducted to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the risk factors associated with cigarette use and dependency. RESULTS: In China, the estimated female current cigarette use prevalence was 1.85%, with over half of the population suffering from tobacco dependence (7.34 million). Jilin Province has the highest cigarette prevalence among women (10.59%), while Fujian Province has the lowest (0.27%). Participants over 60 years old (aOR=1.61, 95%CI=1.20-2.14), single (aOR=1.54, 95%CI=1.07-2.21), with primary education (aOR=1.93, 95%CI=1.47-2.52) were more likely to smoke. The age of smoking initiation among women intergenerational advanced, and compared to the cigarette users without tobacco dependence, those who have tobacco dependence start smoking earlier in all age groups (25.69 years vs. 19.36 years, p<0.001). CONCLUSIONS: The cigarette use prevalence among Chinese women was 1.85%, and there are significant differences among provinces. We noted a trend of women initiating smoking at increasingly younger ages, particularly among those with tobacco dependence.
Subject(s)
Cigarette Smoking , Humans , Female , Middle Aged , Adult , China/epidemiology , Prevalence , Cigarette Smoking/epidemiology , Cigarette Smoking/trends , Aged , Cross-Sectional Studies , Young Adult , Health Literacy , Tobacco Use Disorder/epidemiology , Age Factors , Health Surveys , East Asian PeopleABSTRACT
Background: Tobacco cessation is proven to be the most effective and cost-effective strategy for smokers to reduce their risk of smoking-related disease and premature death. Providing effective, efficient, safe, and patient-centred tobacco cessation treatment to reach those who need them is a significant challenge. To date, only a few nationwide studies in China have assessed the overall clinical care practice and treatment outcome of tobacco cessation. Methods: This a prospective, nationwide, multicenter, cohort study covering all Eastern China, Northwest China, Central China, North China, Southwest China, Northeast China, and South China. Participants who were current smokers aged 18-85 years attending clinic for smoking cessation were included. All the participants were treated with 3-month cessation treatment and followed up for 3 months. Data were collected prospectively using online system. The primary outcome was 7-day point abstinence rate at 24 weeks, validated biochemically by an expired carbon monoxide level of less than 10 ppm. The participants lost to follow-up or not providing validation were included as non-abstainers. Findings: A representative sample of 3557 participants were recruited and 2943 participants were included into this analysis. These participants had mean age of 53.05 years, and 94.8% were males, with 75.8% showing symptoms of tobacco dependence. A total of 965 (32.8%) participants were treated with Bupropion + behavioural counselling, followed by 935 (31.8%) with behavioural counselling, 778 (26.4%) with Varenicline + behavioural counselling, 135 (4.6%) with alternative treatments + behavioural counselling, and 130 (4.4%) with nicotine replacement therapy (NRT) + behavioural counselling. After 3-month treatment and 3-month follow-up, 21.74% of the participants quit smoking at 24 weeks. In the multivariable-adjusted analyses, quitting smoking was significantly associated with female, higher socioeconomic status, poor health condition, different treatment received, and less smoking intensity. The tobacco cessation treatment varied widely across different areas of China. In particular, the areas with higher usage of cessation medication were associated with better cessation treatment outcome. Interpretation: The CNTCCS is the first large-scale nationwide cohort study of smoking cessation in China. Rich data collected from this prospective cohort study provided the opportunity to evaluate the clinical practice of tobacco cessation treatment in China. Funding: Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), Heilongjiang Provincial Science and Technology Key Program (2022ZXJ03C02), and National Key R&D Program of China (grant no. 2017YFC1309400).
ABSTRACT
Objective: To clarify the extent to which smokers in the general population experience tobacco withdrawal symptoms and whether such experience differs in those who continue to smoke and those who stopped smoking. Methods: We included relevant questions in the nationally-representative China Health Literacy Survey (CHLS) conducted in 2018-2019. Among 87,028 participants, there were 22,115 ever-smokers aged 20-69 years who provided information on their smoking history and their experience of tobacco withdrawal symptoms. Multivariate logistic regressions were conducted to explore the association between withdrawal symptoms and other variables. Results: Among ever-smokers, there were 19,643 (88.8%) current smokers and 2,472 (11.2%) ex-smokers. Among current smokers, 61.3% reported having tried to quit smoking in the past. Overall, 61.1% of current smokers reported experiencing withdrawal symptoms: 69.9% of those who tried to quit smoking in the past and 47.5% of those who did not. A lower proportion of ex-smokers experienced withdrawal symptoms (46.3%) and the difference remained significant after controlling for demographic characteristics (OR = 1.76, 95% CI 1.62-1.93, P < 0.001). The most commonly reported withdrawal symptoms in both current smokers and ex-smokers were craving, restlessness and anxiety. In the multivariable-adjusted analyses, those who experienced withdrawal symptoms when they tried to quit smoking (OR: 2.05, 95% CI: 1.86-2.27) were less likely to successfully quit. Conclusions: The clinical picture of the tobacco withdrawal syndrome is the same in current smokers and in ex-smokers, but ex-smokers are less likely to have experienced it. The experience of discomfort when unable to smoke is common and seems likely to be a major factor contributing to maintaining smoking behavior not just among individuals seeking help with quitting smoking, but among smokers generally.
ABSTRACT
Background: Tobacco dependence is the key barrier to successful smoking cessation. However, little is known about its prevalence, sociodemographic characteristics and determinants. We aimed to estimate the prevalence, associated factors and burden of tobacco dependence in China. Methods: During 2018-2019, the nationally representative 2018 China Health Literacy Survey (2018 CHLS) invited 87,708 participants to participate using a multistage stratified sampling method from 31 provinces (or equivalent) in mainland China, and 84,839 participants aged 20-69 with valid data were included in the analysis. We diagnosed tobacco dependence based on international criteria (ICD-10, DSM-4) and tailored to Chinese population according to China Clinical Guideline for Tobacco Cessation (2015 version). The prevalence of tobacco dependence was estimated overall and by sociodemographic factors. The Logistic regression was conducted to estimate odds ratios (OR) and 95% confidence intervals (CIs) for tobacco dependence and success of smoking cessation (being ex-smokers), with different levels of adjustment. These were used to estimate the total number of adults who were tobacco dependent in China. Findings: In China, the estimated prevalence of current smoking was 25.1%, significantly higher in men than in women (47.6% vs 1.9%). The prevalence of current smoking varied approximately 3-fold (12.9% to 37.9%) across 31 provinces of China. Among general population aged 20-69 years, the prevalence of tobacco dependence was 13.1% (95% CI:12.2-14.1). Among current smokers, the prevalence of tobacco dependence was 49.7% (46.5-52.9%), with no difference between men and women (49.7% vs 50.8%). The prevalence of tobacco dependence was associated significantly with smoking intensity, defined by pack-years (1.62 [1.54-1.70] per 10 pack-years), cigarettes smoked per day (2.01 [1.78, 2.27] per 10 cigarettes), and smoking starting age (0.93 [0.90, 0.97] per 5 years). Given smoking intensity, the prevalence of tobacco dependence also varied by age, gender, certain socioeconomic status and regions. Compared with those without tobacco dependence, ever smokers with tobacco dependence were less likely to be ex-smokers (2.88, 2.59-3.21). In China, 183.5 (170.4-197.4) million adults (177.5 million were men) were tobacco dependent in 2018. Interpretation: In China, tobacco dependence is highly prevalent, with approximately half of current smokers being addictive, highlighting the need for coordinated effort to improve awareness, diagnosis and treatment of tobacco dependence. Funding: Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), National Key R&D Program of China (grant no 2017YFC1309400), and National Natural Science Foundation of China (grant no 81720108001). Note: Chinese translation of abstract is available in appendix section.