LncRNA HOTAIRM1 promotes radioresistance in nasopharyngeal carcinoma by modulating FTO acetylation-dependent alternative splicing of CD44.

BACKGROUND: Radiotherapy is the primary treatment for patients with nasopharyngeal carcinoma (NPC); however, almost 20% of patients experience treatment failure due to radioresistance. Therefore, understanding the mechanisms of radioresistance is imperative. HOTAIRM1 is deregulated in various human cancers, yet its role in NPC radioresistance are largely unclear. METHODS: This study investigated the association between HOTAIRM1 and radioresistance using CCK8, flow cytometry, and comet assays. Additionally, xenograft mice and patient-derived xenografts (PDX) models were employed to elucidate the biological functions of HOTAIRM1, and transcriptomic RNA sequencing was utilized to identify its target genes. RESULTS: Our study revealed an upregulation of HOTAIRM1 levels in radioresistant NPC cell lines and tissues. Furthermore, a positive correlation was noted between high HOTAIRM1 expression and increased NPC cell proliferation, reduced apoptosis, G2/M cell cycle arrest, and diminished cellular DNA damage following radiotherapy. HOTAIRM1 modulates the acetylation and stability of the FTO protein, and inhibiting FTO elevates the m6A methylation level of CD44 precursor transcripts in NPC cells. Additionally, silencing the m6A reading protein YTHDC1 was found to increase the expression of CD44V. HOTAIRM1 enhances NPC cell resistance to ferroptosis and irradiation through the HOTAIRM1-FTO-YTHDC1-CD44 axis. Mechanistically, HOTAIRM1 interacts with the FTO protein and induces m6A demethylation of the CD44 transcript. The absence of m6A modification in the CD44 transcript prevents its recognition by YTHDC1, resulting in the transition from CD44S to CD44V. An abundance of CD44V suppresses ferroptosis induced by irradiation and contributes to NPC radioresistance. CONCLUSIONS: In conclusion, the results in this study support the idea that HOTAIRM1 stimulates CD44 alternative splicing via FTO-mediated demethylation, thereby attenuating ferroptosis induced by irradiation and promoting NPC radioresistance.

Global, regional, and national burden of early-onset gastric cancer.

OBJECTIVE: The burden of gastric cancer (GC) across different age groups needs updating. We determined the GC global, regional, and national burden profiles and changes in incidence for 3 sequential 5-year intervals from 2003 to 2017. METHODS: The latest incidence and mortality estimates of GC from 185 countries and regions were extracted from the GLOBOCAN 2022 database. The 5-year interval age-standardised incidence rates (ASIRs) were evaluated using cancer registry data from volumes X-XII of the Cancer Incidence in Five Continents (CI5). Correlation analysis was used to evaluate the relationship between ASIR or the age-standardised mortality rate (ASMR) and the Human Development Index (HDI). RESULTS: There was an estimated global 968,000 new GC cases and 660,000 deaths in 2022, with male predominance. GC ASIRs and ASMRs were 9.2 and 6.1 per 100,000 persons, respectively. East Asia had the highest burden, with 53.8% of cases and 48.2% of deaths among all geographic regions. There was a significant correlation between ASIR and HDI. Over three 5-year intervals from 2003 to 2017, the incidence of GC notably decreased in most countries but peaked at 2008-2012 in New Zealand, Turkey, and South Africa. Several countries in Europe, Oceania, and America suggest an increasingly concerning trend among younger individuals, especially females. CONCLUSIONS: GC is a significant health issue, especially among males and in geographic regions with an HDI, such as eastern Asia. While the incidence of GC is decreasing in many countries due to prevention efforts and improved treatments, a rising trend persists among younger individuals. Comprehensive prevention strategies tailored to different age patterns are clearly needed.

Recent developments in immunotherapy for gastrointestinal tract cancers.

The past few decades have witnessed the rise of immunotherapy for Gastrointestinal (GI) tract cancers. The role of immune checkpoint inhibitors (ICIs), particularly programmed death protein 1 (PD-1) and PD ligand-1 antibodies, has become increasingly pivotal in the treatment of advanced and perioperative GI tract cancers. Currently, anti-PD-1 plus chemotherapy is considered as first-line regimen for unselected advanced gastric/gastroesophageal junction adenocarcinoma (G/GEJC), mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC), and advanced esophageal cancer (EC). In addition, the encouraging performance of claudin18.2-redirected chimeric antigen receptor T-cell (CAR-T) therapy in later-line GI tract cancers brings new hope for cell therapy in solid tumour treatment. Nevertheless, immunotherapy for GI tumour remains yet precise, and researchers are dedicated to further maximising and optimising the efficacy. This review summarises the important research, latest progress, and future directions of immunotherapy for GI tract cancers including EC, G/GEJC, and CRC.

Personalized starting age of gastric cancer screening based on individuals' risk profiles: a population-based prospective study.

BACKGROUND: The current recommended starting age for gastric cancer (GC) lacks unified guideline and individualized criteria. We aimed to determine risk-stratified starting age for GC screening in China based on individuals' risk profiles, and develop an online calculator for clinical application. METHODS: In this multi-center population-based prospective study, we divided participants enrolled during 2015-2017 (n = 59,771, aged 40-69) into screened and unscreened groups and observed them for primary endpoints-GC occurrence, all-cause and GC-specific deaths. The median follow-up was 6.07 years. To determine the reference starting age, the effectiveness of GC screening was assessed by age-groups after propensity-score-matching. Further, we categorized the calculated individual risk scores (using well-established risk factors) by quantiles. Subsequently, we used age-specific 10-year cumulative risk curves to estimate the risk-stratified starting age-when the individual's risk level matches reference starting age risk threshold. RESULTS: During follow-up, 475 GC cases, 182 GC deaths and 1,860 all-cause deaths occurred. All-cause and GC-specific mortality decreased among screened individuals aged ≥45 and 50-59 years, respectively. Thus, the average population (reference) starting age was set as 50 years. The 10-year cumulative risk of GC in average population aged 50 was 1.147%. We stratified the starting age using eight risk factors, and categorized participants as low-, medium-, and high-risk individuals, whose risk-stratified starting age was 58, 50, and 46, respectively. CONCLUSION: While high-risk individuals warrant 3-5 years earlier GC screening than average population (age 50), low-risk individuals can tolerate delayed screening. Our online, personalized starting-age calculator will help risk-adapted GC screening (https://web.consultech.com.cn/gastric/#/).

Attributable liver cancer deaths and disability-adjusted life years in China and worldwide: profiles and changing trends.

OBJECTIVE: Liver cancer is a major health concern globally and in China. This analysis investigated deaths and disability-adjusted life years (DALYs) with respect to etiologies and risk factors for liver cancer in China and worldwide. METHODS: Global and China-specific data were collected on liver cancer deaths, DALYs, and age-standardized rates (ASRs) from the Global Burden of Disease Study 2019 database. Liver cancer etiologies were classified into five groups and risk factors were categorized into three levels. Each proportion of liver cancer burden was calculated in different geographic regions. The joinpoint regression model were used to assess the trends from 1990-2019. RESULTS: Liver cancer accounted for 484,577 deaths worldwide in 2019 with an ASR of 5.9 per 100,000 population. China had an elevated liver cancer death ASR in 2019 and males had an ASR 1.7 times the global rate. The global ASR for DALYs peaked at 75-79 years of age but peaked earlier in China. Hepatitis B virus was the prominent etiology globally (39.5%) and in China (62.5%), followed by hepatitis C virus and alcohol consumption. In high sociodemographic index countries, non-alcoholic steatohepatitis has gained an increasing contribution as an etiologic factor. The liver cancer burden due to various etiologies has decreased globally in both genders. However, metabolic risk factors, particularly obesity, have had a growing contribution to the liver cancer burden, especially among males. CONCLUSIONS: Despite an overall decreasing trend in the liver cancer burden in China and worldwide, there has been a rising contribution from metabolic risk factors, highlighting the importance of implementing targeted prevention and control strategies that address regional and gender disparities.

Psychological Status and Warfarin Therapy in Patients after Valve Replacement during the COVID-19 Pandemic: A Cross-sectional Study.

OBJECTIVE: The standardization of warfarin anticoagulant therapy is the key to lifelong treatment for patients after heart valve replacement. The present study explored the possible risk factors for anxiety and depression during the coronavirus disease 2019 (COVID-19) pandemic and analyzed the influence of psychological state on medication safety. METHODS: Eligible patients received a web-based questionnaire survey via the Wenjuanxing platform during outpatient visits. Depression was evaluated by the Self-Rating Depression Scale (SDS). Anxiety was evaluated by the Self-Rating Anxiety Scale (SAS). Medication adherence was evaluated by the Morisky scale. RESULTS: A total of 309 patients (aged 52.2±11.4 years) were included in the present study. The SDS score of all included patients was 36.9±9.4 points, of which 11 (3.6%) patients were diagnosed as having depression. The SAS score of all included patients was 43.1±9.3 points, of which 71 (23%) patients were diagnosed as having anxiety. Seven patients (2.3%) had both anxiety and depression. Logistic regression analysis revealed that only monthly income was an independent influencing factor for depression. Regarding anxiety, patients who underwent repeated operations had a 2.264-fold greater risk, and patients who received combination medication had a 2.140-fold greater risk. More bleeding events and coagulation disorders could be observed in patients with anxiety, depression or both. When anxiety occurred, patients showed worse medication adherence. However, depression had no significant effect on medication adherence. CONCLUSION: During the COVID-19 pandemic, the detection rate of mental illnesses such as anxiety and depression was high, which seriously affected the medication safety of warfarin. Analysis of its influencing factors will provide a reference for further standardized regulation of warfarin anticoagulant therapy after valve replacement.

Esophageal cancer global burden profiles, trends, and contributors.

OBJECTIVE: This study aimed to provide a comprehensive overview of the global burden of esophageal cancer (EC) and determine the temporal trends and factors influencing changes in the global burden. METHODS: The latest incidence and mortality data for EC worldwide were obtained from GLOBALCAN 2022. The mortality and disability-adjusted life years (DALYs) rates for EC from 1990-2019 were sourced from the 2019 Global Burden of Diseases. Trends in EC mortality and DALYs attributable to 11 risk factors or clusters of risk were analyzed using the joinpoint regression model. The trends in age-related EC burden were assessed using a decomposition approach. RESULTS: An estimated 511,054 new cases of EC were diagnosed in 2022 with 445,391 deaths worldwide. Approximately 75% of cases and deaths occurred in Asia. Nearly 50% of global EC deaths and DALYs were attributed to tobacco use in men in 2019, while 20% were attributed to high body mass index (BMI) in women. From 1990-2019, EC deaths and DALYs attributable to almost all risk factors had declining trends, while EC deaths and DALYs attributed to high BMI in men had upward trends. The age-related EC burden exhibited an upward trend driven by population growth and aging, which contributed to 307.4 thousand deaths and 7.2 million DALYs due to EC. CONCLUSIONS: The EC burden remains substantial worldwide. Effective tobacco and obesity control measures are critical for addressing the risk-attributable burden of EC. Population growth and aging pose challenges for EC prevention and control efforts.

Chronic venous disease of lower limbs in young men at high-altitude: A cross-sectional survey.

OBJECTIVES: The aim of this study was to understand the prevalence of chronic venous disease (CVD) of lower limbs in young men at high-altitude in Xizang, and to provide prevention measures. METHODS: The convenient sampling method was used to conduct a questionnaire survey among males aged 18 to 40 above an altitude of 3000 meters in Xizang in April 2023. The contents of the questionnaire included basic information, symptoms of CVD of lower limbs, protection status and training needs. Multivariate logistic regression model was calculated to evaluate the risk factors for CVD. RESULTS: A total of 350 survey questionnaires were received, and 326 valid samples were collected. The prevalence of CVD of lower limbs (C1-C6) was 37.42% (95%CI: 32.17%-42.68%), the ratio of C0 to C5 were 62.58%, 27.30%, 3.07%, 4.60%, 2.15% and 0.31%, respectively, no one reached C6. The top three symptoms of CVD were lower limb fatigue (18.10%), heaviness (15.34%) and pain (13.19%). 46.01% of respondents were unaware of CVD, and 12.88% of respondents did not have any protective measures of CVD. Multivariate logistic regression showed that age (OR = 1.076, 95%CI: 1.018-1.137, p = .009), preference for spicy food (OR = 1.747, 95%CI: 1.083-2.818, p = .022), unbalanced diet (OR = 1.877, 95%CI: 1.049-3.358, p = .034) and physical exercise (OR 0.610, 95%CI: 0.377-0.986, p = .044) were the independent risk factors for CVD. CONCLUSIONS: This study provided data on the prevalence of CVD in young men at high-altitude and the risk factors for CVD. The findings of this study may facilitate the development of individualized clinical assessments and targeted prevention programs.

Clinical Analysis of Myocardial Injury in Highlanders with Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is a prevalent adverse cardiovascular event at high-altitude environments. Prolonged exposure to high altitudes may result in myocardial injury, which is associated with poor clinical outcomes. This study aims to investigate the clinical characteristics of myocardial injury in patients with PH at high altitude. Methods: Consecutive patients admitted to a general tertiary hospital at the altitude of 3,650 m were selected into this retrospective study. Clinical and biochemical data were collected, as well as based on cardiac troponin I (cTnI) and echocardiography, patients were divided into myocardial injury group and non-myocardial injury group. Results: A total of 231 patients were enrolled, among whom 29 (12.6%) had myocardial injury. We found that body mass index, left ventricular end-diastolic dimension, and serum level of creatine kinase-MB (CK-MB) in myocardial injury group were significantly higher than non-myocardial injury group. Spearman correlation analysis revealed that cTnI has a significant positive correlation with CK-MB and lactic dehydrogenase instead of aspartate aminotransferase. A receiver operating characteristic curve was drawn to demonstrate that CK-MB could significantly predict the occurrence of myocardial injury with an area under the curve of 0.749, and a level of 3.035 (sensitivity = 59.3%, specificity = 90.5%) was optimal cutoff value. Conclusion: The incidence of myocardial injury in highlanders with PH is significant. CK-MB, as a convenient and efficient marker, has been found to be closely associated with cTnI and plays a predictive role in the occurrence of myocardial injury with PH in individuals exposed to high altitude.

The cardiovascular system at high altitude: A bibliometric and visualization analysis.

BACKGROUND: When exposed to high-altitude environments, the cardiovascular system undergoes various changes, the performance and mechanisms of which remain controversial. AIM: To summarize the latest research advancements and hot research points in the cardiovascular system at high altitude by conducting a bibliometric and visualization analysis. METHODS: The literature was systematically retrieved and filtered using the Web of Science Core Collection of Science Citation Index Expanded. A visualization analysis of the identified publications was conducted employing CiteSpace and VOSviewer. RESULTS: A total of 1674 publications were included in the study, with an observed annual increase in the number of publications spanning from 1990 to 2022. The United States of America emerged as the predominant contributor, while Universidad Peruana Cayetano Heredia stood out as the institution with the highest publication output. Notably, Jean-Paul Richalet demonstrated the highest productivity among researchers focusing on the cardiovascular system at high altitude. Furthermore, Peter Bärtsch emerged as the author with the highest number of cited articles. Keyword analysis identified hypoxia, exercise, acclimatization, acute and chronic mountain sickness, pulmonary hypertension, metabolism, and echocardiography as the primary research hot research points and emerging directions in the study of the cardiovascular system at high altitude. CONCLUSION: Over the past 32 years, research on the cardiovascular system in high-altitude regions has been steadily increasing. Future research in this field may focus on areas such as hypoxia adaptation, metabolism, and cardiopulmonary exercise. Strengthening interdisciplinary and multi-team collaborations will facilitate further exploration of the pathophysiological mechanisms underlying cardiovascular changes in high-altitude environments and provide a theoretical basis for standardized disease diagnosis and treatment.

The current infection with Helicobacter pylori and association with upper gastrointestinal lesions and risk of upper gastrointestinal cancer: Insights from multicenter population-based cohort study.

The relationship between Helicobacter pylori (H. pylori) infection and upper gastrointestinal (UGI) cancers is complex. This multicenter, population-based cohort study conducted in seven areas in China aimed to assess the correlation between current H. pylori infection and the severity of UGI lesions, as well as its association with the risk of gastric cancer (GC) and esophageal cancer (EC). From 2015 to 2017, 27,085 participants (aged 40-69) completed a standardized questionnaire, and underwent a 13C-urea breath test. Then a subset underwent UGI endoscopy to assess the UGI lesion detection rates. All individuals were followed up until December 2021 to calculate the hazard ratios (HRs) for UGI cancers. H. pylori infection prevalence was 45.9%, and among endoscopy participants, 22.2% had gastric lesions, 19.2% had esophageal lesions. Higher detection rates of gastric lesions were noted in the H. pylori-positive population across all lesion severity levels. Over a median follow-up of 6.3 years, 104 EC and 179 GC cases were observed, including 103 non-cardia gastric cancer (NCGC) cases and 76 cardia gastric cancer (CGC) cases. H. pylori-infected individuals exhibited a 1.78-fold increased risk of GC (HR 1.78, 95% confidence interval [CI] 1.32-2.40) but no significant increase in EC risk (HR 1.07, 95% CI 0.73-1.57). Notably, there was a higher risk for both NCGC and CGC in H. pylori-infected individuals. This population-based cohort study provides valuable evidence supporting the association between current H. pylori infection and the risk of both NCGC and CGC. These findings contribute to the empirical basis for risk stratification and recommendations for UGI cancer screening.

Features of thromboelastogram in populations exposed to or transferring from high altitude.

Background: Thromboelastogram (TEG) is an effective indicator that monitors the dynamic changes of blood coagulation in real-time. It still remains controversial about the performance and influence of coagulation at high altitude. The present study intends to describe comprehensively the clinical features of TEG in populations exposed to or transferring from high altitude. Methods: Two groups were recruited in the present study. Group A included young males who worked at high-altitude (4888 m or 5418 m) areas for some time, while Group B included young males who had recently returned from high-altitude (4888 m or 5418 m) areas. Medical examinations were performed using portable devices. Spearman's test was used to evaluate the correlations between thromboelastogram (TEG) variables and other variables. Logistic regression analysis was used to analyze the factors affecting various abnormal TEG variables. Results: A total of 51 adult males were included in the two groups. Significantly increased reaction time (R) and decreased maximum amplitude (MA) were found in group B (P < 0.05). No significant differences were observed in the comparisons of K and angle between the two groups. Various TEG variables were identified to be correlated with different coagulation and biochemical variables. Logistic regression analysis demonstrated that abnormal R was independently associated with direct bilirubin, and abnormal K was independently associated with the platelet count in Group A (P < 0.05). However, none of the factors were independently associated with abnormal TEG variables in Group B. Conclusion: Populations exposed to or transferring from high altitudes are characterized by different TEG characteristics. Our findings give a comprehensive description of the complex interaction between TEG indexes, coagulation dynamics, and hematological parameters, which can help guide the development of appropriate medical approaches tailored to the unique needs of these populations.

Benefits and harms of polygenic risk scores in organised cancer screening programmes: a cost-effectiveness analysis.

Background: While polygenic risk scores (PRS) could enable the streamlining of organised cancer screening programmes, its current discriminative ability is limited. We conducted a cost-effectiveness analysis to trade-off the benefits and harms of PRS-stratified cancer screening in China. Methods: The validated National Cancer Center (NCC) modelling framework for six cancers (lung, liver, breast, gastric, colorectum, and oesophagus) was used to simulate cancer incidence, progression, stage-specific cancer detection, and risk of death. We estimated the number of cancer deaths averted, quality-adjusted life-years (QALY) gained, number needed to screen (NNS), overdiagnosis, and incremental cost-effectiveness ratio (ICER) of one-time PRS-stratified screening strategy (screening 25% of PRS-defined high-risk population) for a birth cohort at age 60 in 2025, compared with unstratified screening strategy (screening 25% of general population) and no screening strategy. We applied lifetime horizon, societal perspective, and 3% discount rate. An ICER less than $18,364 per QALY gained is considered cost-effective. Findings: One-time cancer screening for population aged 60 was the most cost-effective strategy compared to screening at other ages. Compared with an unstratified screening strategy, the PRS-stratified screening strategy averted more cancer deaths (61,237 vs. 40,329), had a lower NNS to prevent one death (307 vs. 451), had a slightly higher overdiagnosis (14.1% vs. 13.8%), and associated with an additional 130,045 QALYs at an additional cost of $1942 million, over a lifetime horizon. The ICER for all six cancers combined was $14,930 per QALY gained, with the ICER varying from $7928 in colorectal cancer to $39,068 in liver cancer. ICER estimates were sensitive to changes in risk threshold and cost of PRS tools. Interpretation: PRS-stratified screening strategy modestly improves clinical benefit and cost-effectiveness of organised cancer screening programmes. Reducing the costs of polygenic risk stratification is needed before PRS implementation. Funding: The Chinese Academy of Medical Sciences, the Jing-jin-ji Special Projects for Basic Research Cooperation, and the Sanming Project of the Medicine in Shenzhen.

ZNF148 inhibits HBV replication by downregulating RXRα transcription.

BACKGROUND: Progressive hepatitis B virus (HBV) infection can result in cirrhosis, hepatocellular cancer, and chronic hepatitis. While antiviral drugs that are now on the market are efficient in controlling HBV infection, finding a functional cure is still quite difficult. Identifying host factors involved in regulating the HBV life cycle will contribute to the development of new antiviral strategies. Zinc finger proteins have a significant function in HBV replication, according to earlier studies. Zinc finger protein 148 (ZNF148), a zinc finger transcription factor, regulates the expression of various genes by specifically binding to GC-rich sequences within promoter regions. The function of ZNF148 in HBV replication was investigated in this study. METHODS: HepG2-Na+/taurocholate cotransporting polypeptide (HepG2-NTCP) cells and Huh7 cells were used to evaluate the function of ZNF148 in vitro. Northern blotting and real-time PCR were used to quantify the amount of viral RNA. Southern blotting and real-time PCR were used to quantify the amount of viral DNA. Viral protein levels were elevated, according to the Western blot results. Dual-luciferase reporter assays were used to examine the transcriptional activity of viral promoters. ZNF148's impact on HBV in vivo was investigated using an established rcccDNA mouse model. RESULTS: ZNF148 overexpression significantly decreased the levels of HBV RNAs and HBV core DNA in HBV-infected HepG2-NTCP cells and Huh7 cells expressing prcccDNA. Silencing ZNF148 exhibited the opposite effects in both cell lines. Furthermore, ZNF148 inhibited the activity of HBV ENII/Cp and the transcriptional activity of cccDNA. Mechanistic studies revealed that ZNF148 attenuated retinoid X receptor alpha (RXRα) expression by binding to the RXRα promoter sequence. RXRα binding site mutation or RXRα overexpression abolished the suppressive effect of ZNF148 on HBV replication. The inhibitory effect of ZNF148 was also observed in the rcccDNA mouse model. CONCLUSIONS: ZNF148 inhibited HBV replication by downregulating RXRα transcription. Our findings reveal that ZNF148 may be a new target for anti-HBV strategies.

Cancer statistics for young adults aged 20 to 49 years in China from 2000 to 2017: a population-based registry study.

An increasing cancer incidence among adults younger than 50 years has been reported for several types of cancer in multiple countries. We aimed to report cancer profiles and trends among young adults in China. Data from the China Cancer Registry Annual Report were used to estimate incidence and mortality among young adults (ages 20-49 years) in China in 2017, and an age-period-cohort model was employed to estimate the average annual percent change (AAPC) in incidence and mortality from 2000 to 2017. All 25 cancer types were grouped into obesity- or overweight-associated cancers (12 cancer types) and additional cancers (13 cancer types). In 2017, there were 681,178 new cases and 214,591 cancer deaths among young adults in China. Among young adults, the most common cancers were thyroid, breast, cervical, liver, lung, and colorectal cancer, and the leading causes of cancer deaths were liver, lung, cervical, stomach, breast, and colorectal cancer. From 2000 to 2017, the cancer incidence increased for all cancers combined among young adults, with the highest AAPC (1.46%) for adults aged 20-24 years, while cancer mortality decreased, with the highest AAPC (-1.63%) for those aged 35-39 years. In conclusion, the cancer incidence in China has increased among young adults, while cancer mortality has decreased for nearly all ages. Cancer control measures, such as obesity control and appropriate screening, may contribute to reducing the increasing cancer burden among young adults.

Lung cancer burden and trends from 2000 to 2018 in China: Comparison between China and the United States.

Objective: This study aims to provide an analysis of the current status and trends of lung cancer incidence and mortality rates in China, comparing trends with those in the United States (U.S.). Methods: Data on lung cancer incidence and mortality rates spanning 2000 to 2018 were extracted from the China Cancer Registry Annual Report and the Surveillance, Epidemiology, and End Results database for China and the U.S., respectively. Crude incidence and mortality rates were calculated by sex and age, with age-standardized incidence rates (ASIR) and mortality rates (ASMR) calculated using the Segi-Doll world standard population. Trend analyses employed Joinpoint regression models to determine average annual percentage change (AAPC). The study also assessed the proportion of new cases and deaths by sex and age. Results: In 2018, the ASIR of lung cancer for males in China was 50.72 per 100,000 and the ASMR was 39.69 per 100,000, the ASIR for females was 26.25 per 100,000 and the ASMR was 15.24 per 100,000. Both ASIR and ASMR were higher in males and the highest in the population aged 65 years and older, with the lowest among those aged 20-49 years. In China, female ASIR demonstrated an increasing trend (AAPC: 1.16%), while ASMR decreased in both sexes (AAPCs: -0.48% for males, -1.00% for females). The U.S. exhibited decreasing trends in both ASIR and ASMR across sexes and age groups. Conclusions: The study identified an increasing trend in lung cancer incidence among females and a decreasing mortality trend in both sexes in China. These trends are likely linked to factors such as smoking prevalence, advancements in cancer screening, and improved medical care. The findings underscore the need for tailored lung cancer prevention measures in China, particularly the reinforcement of anti-smoking policies.

A high-throughput screening approach to discover potential colorectal cancer chemotherapeutics: Repurposing drugs to disrupt 14-3-3 protein-BAD interactions.

Inducing apoptosis in different types of cancer cells is an effective therapeutic strategy. However, the success of existing chemotherapeutics can be compromised by tumor cell resistance and systemic off-target effects. Therefore, the discovery of pro-apoptotic compounds with minimal systemic side-effects is crucial. 14-3-3 proteins are molecular scaffolds that serve as important regulators of cell survival. Our previous study demonstrated that 14-3-3ζ can sequester BAD, a pro-apoptotic member of the BCL-2 protein family, in the cytoplasm and prevent its translocation to mitochondria to inhibit the induction of apoptosis. Despite being a critical mechanism of cell survival, it is unclear whether disrupting 14-3-3 protein:BAD interactions could be harnessed as a chemotherapeutic approach. Herein, we established a BRET-based high-throughput drug screening approach (Z'-score= 0.52) capable of identifying molecules that can disrupt 14-3-3ζ:BAD interactions. An FDA-approved drug library containing 1971 compounds was used for screening, and the capacity of identified hits to induce cell death was examined in NIH3T3-fibroblasts and colorectal cancer cell lines, HT-29 and Caco-2. Our in vitro results suggest that terfenadine, penfluridol, and lomitapide could be potentially repurposed for treating colorectal cancer. Moreover, our screening method demonstrates the feasibility of identifying pro-apoptotic agents that can be applied towards conditions where aberrant cell growth or function are key determinants of disease pathogenesis.

Trends in high-risk rates and screening rates for the population-based cancer screening program on esophageal, stomach and liver cancer in China, 2010-2016.

Background: A population-based cancer screening program in rural China, targeting three types of cancer that are most prevalent in these areas, including esophageal, stomach, and liver cancer was awarded by the government in China since 2007. A two-step design with cancer risk assessment based on questionnaire interview and HBsAg test strip and subsequent clinical intervention for high-risk populations was adopted with free of charge at the local hospitals designated in the program. The participate rate including high-risk rates and screening rates was important to find appropriate strategies to improve the overall awareness of the program. Methods: Data from the cancer screening program between 2010 and 2016 were used to calculate higher rate (high-risk population/ participants recruited) and screening rate (participants received screening/ high-risk population). Results: From 2010 to 2016, 1,637,429 residents were recruited in the program and filled the questionnaires, 350,646 (21.4%) for esophagus cancer, 273,715 (16.7%) for stomach cancer and 1,013,068 (61.9%) for liver cancer. 471,974 participants were assessed as high-risk population including 114,786 (24.3%) high risk for esophagus cancer, 161,809 (34.3%) high risk for stomach cancer and 195,379 (41.4%) high risk for liver cancer, respectively. 249,185 (52.8%) participants who were assessed as high risk received clinical screening. There were 64,710 (26.0%) for esophagus cancer screening, 71,365 (28.6%) for stomach cancer screening and 113,110 (45.4%) for liver cancer screening, respectively. Conclusion: Our findings will provide important references for designing effective population-based screening strategies to enhance the screening acceptance by health action plan in the future.