BACKGROUND: This study delves into the intricate landscape of oral cancer, a global concern with a high incidence in Asian countries. We focus on oral squamous cell carcinoma (OSCC), primarily driven by the consumption of betel nut and its derivatives. OSCC often arises from premalignant lesions like oral submucous fibrosis (OSF). In Pakistan, OSCC is prevalent among men due to various addictive substances, including smokeless tobacco and chewing materials. Mutations in tumor suppressor genes, such as TP53 and p21, play crucial roles in this malignancy\'s development. We also explore the involvement of TUSC3 gene deletion in OSCC and OSF.
METHODS: In this study we investigated demographics, TUSC3 gene expression, deletion analysis, and TP53 and p21 genetic alterations in OSCC and OSF patients (blood and tissue of 50 samples in each condition) who had tobacco derivates usage history. The association analysis was carried out mainly through PCR based genotyping.
RESULTS: The study\'s patient cohort (OSCC and OSF) displayed a wide age range from 13 to 65 years (Mean = 32.96 years). Both conditions were more prevalent in males, with a male-female ratio of approximately 2.5:1. Chewing habits analysis revealed high frequencies of gutka use in both OSF and OSCC patients. TUSC3 expression analysis in OSCC cell lines indicated significant downregulation. Genotyping showed no TUSC3 deletion in OSF cases, but a deletion rate of over 22% in OSCC tissue samples. Analysis supported a significant association of TUSC3 deletion with OSCC development but not with OSF. Polymorphism in p53 exon 4 and p21 (rs1801270) were significantly associated with both OSCC and OSF, adding to their pathogenesis. Our findings further revealed a strong correlation between TUSC3 deletion and the excessive use of tobacco and related products, shedding light on the genetic underpinnings of OSCC development.
CONCLUSIONS: Notably, our study provides a crucial insight into genetic aspects underlying OSCC and OSF in response of addictive consumption of areca nut, betel quid, and tobacco derivatives. A significant association between TUSC3 deletion and OSCC development, along with polymorphisms in TP53 and p21, underscores the importance of further research into the molecular mechanisms driving oral cancer progression for improved diagnosis and treatment outcomes.

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OBJECTIVE: To explore the feasibility of snuff pot arterial pressure measurement for patients undergoing routine elective surgery during anesthesia.
METHODS: A prospective randomized controlled trial was conducted. Patients undergoing elective surgery admitted to the Handan Hospital of Traditional Chinese Medicine from June 1, 2020 to June 1, 2022 were enrolled. Patients who needed arterial pressure measurement for hemodynamic monitoring were randomly divided into routine radial artery puncture group and snuff pot artery puncture group with their informed consent. The patients in the routine radial artery puncture group were placed a catheter at the styloid process of the patient\'s radius to measure pressure. In the snuff pot artery puncture group, the snuff pot artery, that was, the radial fossa on the back of the hand (snuff box), was selected to conduct the snuff pot artery puncture and tube placement for pressure measurement. The indwelling time of arterial puncture catheter, arterial blood pressure, and complications of puncture catheterization of patients in the two groups were observed. Multivariate Logistic regression analysis was used to screen the relevant factors that affect the outcome of arterial catheterization.
RESULTS: Finally, a total of 252 patients were enrolled, of which 130 patients received routine radial artery puncture and 122 patients received snuff pot artery puncture. There was no statistically significant difference in general information such as gender, age, body mass index (BMI), and surgical type of patients between the two groups. There was no significant difference in the indwelling time of artery puncture catheter between the routine radial artery puncture group and the snuff pot artery puncture group (minutes: 3.4±0.3 vs. 3.6±0.3, P > 0.05). The systolic blood pressure (SBP) and the diastolic blood pressure (DBP) measured in the snuff pot artery puncture group were significantly higher than those in the conventional radial artery puncture group [SBP (mmHg, 1 mmHg ≈ 0.133 kPa): 162.3±14.3 vs. 156.6±12.5, DBP (mmHg): 85.3±12.6 vs. 82.9±11.3, both P < 0.05]. There was no statistically significant difference in the incidence of complications such as arterial spasm, arterial occlusion, and pseudoaneurysm formation between the two groups. However, the incidence of hematoma formation in the snuff pot artery puncture group was significantly lower than that in the conventional radial artery puncture group (2.5% vs. 4.6%, P < 0.05). Based on the difficulty of arterial puncture, multivariate Logistic regression analysis showed that gender [odds ratio (OR) = 0.643, 95% confidence interval (95%CI) was 0.525-0.967], age (OR = 2.481, 95%CI was 1.442-4.268) and BMI (OR = 0.786, 95%CI was 0.570-0.825) were related factors that affect the outcome of arterial catheterization during anesthesia in patients undergoing elective surgery (all P < 0.05).
CONCLUSIONS: Catheterization through the snuff pot artery can be a new and feasible alternative to conventional arterial pressure measurement.

The aim was to study whether non-combustible nicotine (Swedish snuff) use in pregnancy is associated with elevated risk of post neonatal mortality, Sudden Infant Death Syndrome (SIDS), and Sudden Unexpected Infant Death (SUID) and to study how cessation before the antenatal booking influenced these risks.
This was a population-based register study of all infants with information on tobacco exposure in early pregnancy born in Sweden 1999-2019, n = 2,061,514. Self-reported tobacco use in early pregnancy was categorized as nonuse, snuff use, and moderate and heavy smoking. Multiple logistic regression models were used to estimate crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs).
Maternal snuff use was associated with increased risks of post neonatal mortality, SIDS, and SUID. The risks of snuff use and moderate smoking were of similar magnitude. Heavy smoking was associated with the highest risks. Cessation of smoking and snuff use before the antenatal booking was associated with lower risks of SIDS and SUID compared to that of continuous usage.
Maternal snuff use was associated with increased risks of post neonatal mortality, SIDS, and SUID. Nicotine is the common substance in cigarette smoke and snuff. These findings support the hypothesis that nicotine contributes to an elevated risk of SIDS.
Maternal snuff use and smoking in early pregnancy were associated with increased risks of post neonatal mortality, SIDS, and SUID. Cessation of smoking and snuff use before the first antenatal visit was associated with reduced risks of SIDS and SUID. The common substance in cigarette smoke and snuff is nicotine. Our findings suggest that nicotine contributes to an elevated risk of SIDS and SUID. The implication of our findings is that all forms of nicotine should be avoided in pregnancy.

OBJECTIVE: To describe the prevalence of smokeless tobacco (SLT) use and number of users by year, in addition to trends in mortality and attributable disease burden in countries of the WHO South-East Asia Region (SEAR), to inform policies for SLT control in the Region.
METHODS: For each SEAR country, we obtained data from Global Adult Tobacco Surveys, WHO STEPwise Approach to NCD Risk Factor Surveillance surveys and Demographic and Health Surveys conducted since 2010 to estimate prevalence of SLT use by country, sex and year. Using data from the World Population Prospects database we estimated the number of users by country. Next, using the results of previous meta-analyses and prevalence results, we estimated the population attributable fractions and attributable mortality and morbidity in terms of annual deaths and disability-adjusted life years lost. We then characterised trends in attributable deaths and disease burden for countries with comparable data.
RESULTS: There were wide differences in SLT use prevalence by country. We estimated that, during 2015-2019, there were 165 803 900 SLT users across SEAR, with 479 466 attributable deaths annually of which India accounted for 79.9% with 383 248. Attributable annual deaths increased in some countries during 2015-2019.
CONCLUSIONS: Annual deaths and disease burden attributable to SLT remain high across SEAR and have only declined modestly in recent years. Effective implementation of all WHO Framework Convention on Tobacco Control measures, addressing both supply-side and demand-side issues, in relation to SLT and areca nut products must be prioritised to ensure reductions in mortality and disease burden are sustained and accelerated.

Smokeless tobacco use is popular in some regions worldwide, but it receives less attention compared to cigarette smoking. We aimed to estimate the recent prevalence of, and trends in, smokeless tobacco use and to examine its associated factors among adolescents aged 12-16 years in 138 countries/territories (hereafter \"countries\") from 1999 to 2019.
Data from the Global Youth Tobacco Survey conducted in 138 countries in 2010-2019 and the National Youth Tobacco Survey conducted in the United States in 2019 were used to calculate the prevalence of current smokeless tobacco use and investigate its associated factors among adolescents aged 12-16 years. We also assessed the trend in the prevalence of smokeless tobacco use in 100 countries that had conducted more than one survey from 1999 to 2019.
The overall prevalence of current smokeless tobacco use was 4.4% (95% confidence interval [CI] 4.0-4.9), with 5.7% (5.1-6.3) for boys, 3.1% (2.6-3.5) for girls, 3.9% (3.5-4.4) for adolescents aged 12-14 years and 5.4% (4.8-5.9) for those aged 15-16 years. The prevalence was highest in the South-East Asian region (6.1%, 4.4-7.7) and lowest in the Western Pacific region (2.0%, 1.7-2.4). The prevalence of smokeless tobacco use decreased in 57 of 100 countries, increased in 32 countries, and remained unchanged in 11 countries. Current cigarette smoking (odds ratio [OR]=2.00, 95% CI=1.68-2.39), other tobacco product use (OR=6.03, 95% CI=4.92-7.40), tobacco advertisement exposure (OR=1.44, 95% CI=1.19-1.74), being offered free tobacco products (OR=2.01, 95% CI=1.66-2.42), and not being taught about dangers of smoking (OR=1.28, 95% CI=1.09-1.50) were all positively associated with current smokeless tobacco use.
Smokeless tobacco use among adolescents remains a public health concern worldwide. Although the prevalence among adolescents decreased in most countries, it remains high especially in the South-East Asian region. More strict and effective strategies and measures are needed to further curb the smokeless tobacco use among adolescents.

BACKGROUND: The impact of smokeless tobacco (SLT) use on the risk of oral cavity cancer (OCC) has been confirmed; however, the sex-based difference in this association remains inconclusive. Therefore, this study aimed to estimate the association between SLT use and OCC risk in women and compared it to that in men.
METHODS: PubMed, Embase, and Cochrane Library databases were systematically searched for eligible studies from their inception up to August 2020. Studies reporting the effect estimates of SLT use on OCC risk in men and women, were eligible for inclusion. The relative risk ratio (RRR) was applied to calculate the sex-based difference in the relationship between SLT use and OCC risk, and pooled analysis was conducted using a random-effects model with inverse variance weighting.
RESULTS: Nineteen studies reporting a total of 6593 OCC cases were included in the final meta-analysis. The pooled relative risk (RR) suggested that SLT use was associated with an increased risk of OCC in both men (RR, 2.94; 95% confidence interval [CI], 2.05-4.20; P < 0.001) and women (RR, 6.39; 95%CI, 3.16-12.93; P < 0.001). Moreover, the SLT-use-related risk of OCC was higher in women than that in men (RRR,1.79; 95%C, 1.21-2.64; P = 0.003). The risk of OCC related to SLT use in women was still significantly higher than that in men (RRR, 1.75; 95%CI, 1.15-2.66; P = 0.008) after excluding indirect comparison results. Finally, a subgroup analysis suggested significant sex-based differences only in individuals who received chewed smokeless products, regardless of the control definition. Pooled analysis of studies with high design quality confirmed the notably higher risk of OCC in women than in men.
CONCLUSIONS: This study found that SLT use was associated with a higher risk of OCC in women than in men. Further large-scale prospective cohort studies should be conducted to verify sex-based differences in the association between use of specific smokeless products and OCC risk.

Tobacco use is a leading preventable cause of morbidity and mortality worldwide. Little is known about recent prevalence and trends in tobacco use among adolescents globally. We aimed to assess the recent global prevalence of tobacco use in young adolescents and the secular trends in prevalence between 1999 and 2018.
We used the most recent Global Youth Tobacco Surveys data on adolescents aged 13-15 years from 143 countries or territories that had done at least one survey between Jan 1, 2010, and Dec 31, 2018, to assess the recent prevalence of tobacco use; and data from 140 countries that had done two or more surveys between Jan 1, 1999, and Dec 31, 2018, to assess the trends in the prevalence of tobacco use.
530 234 adolescents were included from the 143 countries that had done at least one survey between 2010 and 2018. 1 192 312 adolescents were included from the 140 countries that had done two or more surveys between 1999 and 2018. The most recent global prevalence of cigarette smoking was 11·3% (95% CI 10·3-12·3) in boys and 6·1% (5·6-6·6) in girls, based on cigarette smoking on at least 1 day during the past 30 days, 6·0% (5·5-6·6) and 2·6% (2·4-2·9) based on smoking on at least 3 days, and 4·2% (3·8-4·6) and 1·6% (1·4-1·8) based on smoking on at least 6 days. The most recent prevalence of the use of tobacco products other than cigarettes (eg, chewing tobacco, snuff, dip, cigars, cigarillos, pipe, electronic cigarettes) on at least 1 day during the past 30 days was 11·2% (9·9-12·6) in boys and 7·0% (6·4-7·7) in girls. The most recent prevalence of any tobacco use on at least 1 day during the past 30 days was 17·9% (16·1-19·6) in boys and 11·5% (10·5-12·4) in girls. The prevalence of cigarette smoking on at least 1 day during the past 30 days decreased between the first and last surveys in 80 (57·1%) of 140 countries, was unchanged in 39 countries (27·9%), and increased in 21 countries (15·0%). However, the prevalence of the use of tobacco products other than cigarettes was unchanged or increased in 81 (59·1%) of 137 countries.
The global prevalence of tobacco use among adolescents aged 13-15 years was substantial. Although the prevalence of cigarette smoking decreased over time in the majority of countries, the prevalence of the use of other tobacco products increased or did not change in the majority of countries during the past two decades. These findings re-emphasise the need to strengthen tobacco control efforts among young adolescents globally.
Shandong University.

Smokeless tobacco products provide an alternative to cigarettes; however, smokeless tobacco is carcinogenic and harmful to human health. This study evaluated the toxicological effects of snus extracts and cigarette smoke total particulate matter (TPM) on human umbilical vein endothelial cells (HUVECs). Treated cells were examined for cell viability, reactive oxygen species (ROS), apoptosis, and inflammatory cytokines. Moreover, we explored the mechanism of programmed cell death induced by snus. The results showed that snus extracts significantly inhibited cell viability in a dose-dependent manner. ROS was significantly increased in treatment groups, and anti-oxidant treatment could not prevent snus extract-induced cell death. Snus extracts induced apoptosis, DNA damage, activation and cleavage of caspase-3 and caspase-8, pathway-related gene change, and interleukin (IL)-6 and IL-8 release in HUVECs. Snus extracts exposure may induce cytotoxicity, ROS generation, inflammatory cytokines release, and apoptosis or DNA damage through intrinsic and extrinsic pathways in HUVECs.

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