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Psychoneurological symptom clusters (PNSCs) are common in patients with ovarian cancer and are associated with reduced quality of life, treatment interruption, and poor prognosis. However, effective interventions for PNSCs remain limited. Traditional Chinese medicine may provide comprehensive benefits for symptom management. This study aims to evaluate the efficacy and safety of the TiaoShenZhiAi (TSZA) regimen in alleviating PNSCs in patients with ovarian cancer and to assess its effects on quality of life and survival outcomes. A total of 316 patients with ovarian cancer aged 18 to 70 years with PNSCs will be included and randomly divided into 2 parallel groups. Both groups will receive standard treatment for ovarian cancer as the basic treatment. The intervention group will receive the TSZA regimen, that is, Compound Ciwujia Granules (containing Acanthopanax senticosus and Schisandra chinensis) combined with psychological intervention. The control group will receive a low-dose active control (simulated Compound Ciwujia Granules) combined with psychological intervention. The primary outcome is the remission rate of PNSCs at 3 months. The secondary outcome measures include the Pittsburgh Sleep Quality Index, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 scale, the revised Piper Fatigue Scale, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Quality of Life Scale, the traditional Chinese medicine syndrome scale, sleep quality, sleep diary, and the 1-year survival analysis. In addition, this study also includes a series of exploratory indicators (including functional magnetic resonance imaging, biomarkers of peripheral blood and tumor tissue, proportion of immune cells, cytokine levels, hypothalamic-pituitary-adrenal axis function, and immune gene expression analysis) and safety indicators (including vital signs, liver and kidney function, and electrocardiogram). The study outcomes will be evaluated based on different indicators during the treatment period (baseline and the 1st, 2nd, and 3rd mo of enrollment) and the follow-up period (the 6th, 9th, and 12th mo of enrollment). Data analysis will be conducted using R (version 4.5.3) software. A one-sided P value of <.03 will be considered statistically significant. This study is designed to enroll a total of 316 participants. Participant enrollment is set to commence in October 2025, with no recruitment having occurred as of April 2026. The recruitment period will extend until September 2028 or until the target enrollment is met. Data analysis is scheduled for November 2028, with submission of the trial results to a peer-reviewed journal anticipated by May 2029. This study will evaluate the efficacy of the TSZA regimen in managing PNSCs in patients with ovarian cancer and generate clinical evidence for a new therapeutic option that improves quality of life and alleviates the symptom burden.

Introduction-Aim: According to the World Health Organization, cardiovascular disease and cancer figure among leading causes of death worldwide. This aim of our study was to identify the deadliest cancers in Tunisia and to assess the quality of medical certification related to cancer deaths. We led a descriptive observational study based on data from the national information system on causes of deaths in 2020. Were included all medical death certificates received by the National Institute of Health and related to deaths occurring in 2020. Causes of death were coded according to the International Classification of Diseases (ICD-10). The share of Garbage codes was determined by ANACONDA software. Data entry and analysis, were performed by SPSS software. In total, 45420 deaths were enrolled, including 7001 deaths from cancer, representing 15.1% of all deaths. The sex ratio (Male/Female) was to 1.7 with median age was 67 years &#xb1;0.2. The deadliest cancers were the following cancers: bronchopulmonary (22.8%), colorectal (7.9%), breast (7.4%), prostate (5.9%), liver (4.9%) and pancreas (4.8%). The share of garbage codes was 12%, dominated by cancers with "unspecified primary location" (6.1%), "primary cancers with multiple independent locations" (1.6%), uterine cancer of undefined location (1.3%), "cancer of the digestive tract of undefined location" (1.2%). Our study highlighted the important place of cancer among all deaths in Tunisia. We recommend training of certifying doctors on the rules of good quality certification, and the strengthening of primary prevention by fighting against risk factors and secondary prevention by screening and early diagnosis of cancers.

Metabolic dysfunction-associated steatohepatitis (MASH) is an increasingly significant contributor to primary liver cancer in the Asia-Pacific region, with substantial regional variation. To quantify the burden and temporal trends of MASH-related liver cancer across countries and subregions from 1990 to 2023. Using the Global Burden of Disease (GBD) 2023 dataset, we analysed age-standardized prevalence, deaths, and disability-adjusted life years (DALYs) for MASH-related liver cancer, assessing temporal trends, regional variation and associations with the Socio-demographic Index (SDI). Decomposition analysis estimated the contributions of ageing, population growth and epidemiological changes. In 2023, the high-income Asia-Pacific region had the highest age-standardized prevalence of MASH-related liver cancer (1.19 per 100&#x2009;000), followed by Oceania (0.98 per 100&#x2009;000) and Australasia (0.88 per 100&#x2009;000), with Central Asia the lowest (0.56 per 100&#x2009;000). Across the Asia-Pacific region, prevalence, mortality and DALYs generally increased with SDI, though patterns varied by subregion. The high-income Asia-Pacific region showed a distinct 'increase-peak-decline' pattern in both mortality and DALYs, whereas low- and middle-income regions (i.e., South Asia, South-east Asia and Central Asia) showed steady increases in prevalence. Pacific island nations experienced disproportionately higher DALYs despite their smaller populations. Decomposition analyses showed that ageing and population growth accounted for the largest proportions of the observed changes in East Asia (44.8% and 41.4%, respectively) and South Asia (41.1% and 30.1%, respectively), whereas epidemiological change was the largest contributor in Australasia (58.4%). MASH-related liver cancer is rising across the Asia-Pacific region, with substantial regional variation, underscoring the need for region-specific public health strategies. The burden of liver cancer related to metabolic dysfunction&#x2010;associated steatohepatitis (MASH) has been increasing in the Asia&#x2010;Pacific region over the past decades, with clear differences between countries. While some high&#x2010;income countries have seen improvements in outcomes, many low&#x2010; and middle&#x2010;income countries and Pacific island nations continue to experience a growing disease burden driven by obesity, diabetes and limited access to healthcare. These findings highlight the need for better prevention and early detection strategies to reduce future disease impact.

This study focuses on the vessel normalization window of anlotinib to preliminarily explore the optimal intervention timing for combining anlotinib with whole brain radiotherapy (WBRT) in treating brain metastases from non-small cell lung cancer (NSCLC). We aimed to explore the feasibility of combining anlotinib with WBRT based on the hypothesized vascular normalization window, and to investigate potential associations with intracranial tumor control, iPFS, and quality of life in patients with NSCLC brain metastases. This study was designed as a prospective, non-randomized, single-center cohort study. From Feb 8, 2024, to Sep 30, 2025, a total of 38 patients with NSCLC brain metastases diagnosed by the Department of Oncology, the Fifth Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, were prospectively recruited. Anlotinib was used as the intervention measure in this study. According to whether the patients received anlotinib or not, they were divided into the experimental group (anlotinib combined with WBRT) and the control group (sole WBRT), with 19 patients in each group. In the experimental group, the vascular normalization time window of anlotinib, which is 5 to 7 days, was precisely utilized. The specific medication regimen was to start taking 8&#xa0;mg of anlotinib 5 days before the initiation of WBRT and continue the medication until the end of WBRT. In contrast, the control group received only WBRT. The primary and secondary endpoint indicators of the patients in both groups were followed up regularly. The primary endpoint indicators included the intracranial objective response rate (iORR) and iPFS, while the secondary endpoint indicators included the intracranial disease control rate (iDCR), quality of life, and adverse reactions. The Kaplan-Meier method was used to draw the survival curve.Meanwhile, the clinical characteristics of the patients in both groups, such as gender, age, primary tumor site, T stage, N stage, and the number of brain metastases, were collected. Univariate analysis was used to screen out the prognostic factors that might affect iPFS. Then, the factors with statistical differences (P < 0.10) in the univariate analysis were taken as independent variables, and further Cox multivariate regression analysis was carried out to explore the independent prognostic factors affecting iPFS. The test standard P value was < 0.05. From Feb 8, 2024, to Sep 30, 2025, a total of 38 patients diagnosed with brain metastases from NSCLC by the Oncology Department of the Fifth Affiliated Hospital of Chengdu University of Traditional Chinese Medicine were prospectively recruited and included in the statistical analysis. The median follow-up time was 15.2 months (95% CI: 9.02-21.37). The results showed that the experimental group had better iORR (57.90% vs. 15.79%, P = 0.017) and iDCR (100% vs. 73.68%, P = 0.046) compared to the control group, with statistically differences. Compared with the control group, the experimental group showed a advantage in iPFS (6.7 months vs. 4.27 months, P = 0.038), and the median iPFS was extended by an additional 2.43 months. The results of subgroup analysis showed that the iPFS of patients with &#x2265; 3 brain metastases and patients with < 3 brain metastases were 6.3 months and 6.7 months, respectively, and there was no significant difference between the two groups (P = 0.723). The iPFS was longer in patients with less than 3 metastases than those with more than 3 metastases (11.73 months vs. 3.17 months, P = 0.035). After WBRT, the iPFS of NSCLC patients with brain metastases who received anti-tumor therapy was improved compared with those who did not receive anti-tumor therapy (8.67 months vs. 3.80 months, P = 0.040). In terms of quality of life, the experimental group showed better outcomes in functional status, symptom domains, and overall health compared to the control group over time. Regarding adverse reactions, the main ones included decreased appetite, fatigue, nausea and vomiting, hypertension, Myelosuppression, dizziness, headache, and abnormal liver function indicators. Grade &#x2265; 3 adverse reactions primarily included anemia, agranulocytosis, leukopenia, thrombocytopenia, cognitive impairment and abnormal liver function indicators, most of which were tolerable after symptomatic treatment. Univariate regression analysis of the overall population indicated that antitumor therapy after WBRT (P = 0.078) and the number of organ metastases (P = 0.038) were clinically relevant factors affecting iPFS. Further multivariate Cox regression analysis revealed that antitumor therapy after WBRT (P = 0.047) and the number of organ metastases (P = 0.028) were independent prognostic factors influencing iPFS. In this exploratory cohort, low-dose (8&#xa0;mg) anlotinib administered 5-7 days prior to WBRT was associated with higher iORR, iDCR, and longer iPFS relative to WBRT alone in patients with NSCLC brain metastases. This combination regimen showed a manageable safety profile and trends toward improved quality of life. Subgroup analyses suggested that patients with < 3 organ metastases or those receiving post-WBRT antitumor therapy tended to have prolonged iPFS. Multivariate Cox regression identified post-WBRT antitumor therapy and number of organ metastases as potential independent prognostic factors for iPFS in this cohort. These findings are hypothesis-generating and require validation in larger randomized controlled trials.

The colorectal cancer rates in India are lower than in other Southeast Asian countries, but there is an increasing trend in incidence as well as mortality. We are reporting the results of a large community-based colorectal cancer screening project implemented through a house-to-house survey. Consenting men and women of ages 50 to 75 years were informed about the purpose of the study and the benefits of colorectal cancer screening. They were educated on how to collect stool sample for occult blood test in a sample collection tube. Health visitors collected the stool sample from the study participants on the next day. Samples were tested with CANCHECK-FOBT, which is Conformite Europeenne-approved and is a rapid, qualitative, two-site sandwich immunoassay for the detection of immunochemical fecal occult blood (iFOB) concentration in human feces. Participants with a positive iFOB test (iFOBT) result underwent colonoscopy as an outpatient procedure at the gastroenterologist's clinic. A total of 5,003 participants provided consent, and 4,352 (86.98%) provided the stool sample. iFOBT was positive among 70/4,352 (1.61%) participants, of whom 31 (44.92%) completed the colonoscopy procedure. Five participants were diagnosed with adenomatous polyps, and one participant had colorectal cancer. The detection rate of histologically confirmed colorectal cancer was 0.23 and that of adenomatous polyp was 1.15 per 1,000 screened persons. Although the screen positivity and adenomatous polyps and colorectal cancer detection rates in our study are much lower than the in neighboring Southeast Asian countries, these findings highlight the importance of investing in preventive healthcare in India. This is the first community-based colorectal cancer screening study from India that suggests the feasibility of colorectal cancer screening. There is an urgent need for investment in prevention of common cancers in the Indian population.

Hepatitis B virus (HBV) infection is widespread in Asia. Of the many chronic diseases linked to HBV, among the most important is liver cancer. This study analysed the disease burden of chronic hepatitis B-associated liver cancer in Asia from 1990 to 2021. Data were obtained from the 2021 Global Burden of Disease study. We analyzed incidence, prevalence, deaths and disability-adjusted life years (DALYs) in Asian regions and countries from 1990 to 2021 by age and sex. Data processing and graph construction were performed using RStudio and BioWinford. The Joinpoint regression model was used to analyse the temporal data trends. From 1990 to 2021, the disease burden of hepatitis B-related liver cancer in Asia decreased. A decline was observed in the rates of incidence (AAPC: -0.6), prevalence (AAPC: -0.1), deaths (AAPC: -1.0), and DALYs (AAPC: -1.2), even though their absolute numbers all increased. The number of incidence, prevalence, deaths and DALYs is highest among the middle-aged and older adults, and the highest rate is found among the older adults. Both the number and rate are highest in East Asia. Disease burdens differ by country. The burden of hepatitis B-associated liver cancer in Asia has decreased over the past three decades, but remains non-negligible. Asian countries need to take corresponding measures against hepatitis B.

Patients with gastrointestinal cancers experience a broad range of symptoms, including anxiety, pain, and reduced quality of life. Although immersive virtual reality (IVR) has emerged as a potential intervention, its efficacy specifically in patients with gastrointestinal cancer remains unclear. This systematic review and meta-analysis of randomized controlled trials (RCTs) evaluated the effects of IVR on symptom management in patients with gastrointestinal cancer. Twelve databases and 1 gray literature source were searched from inception to April 30, 2026. RCTs comparing IVR interventions to routine care or nonimmersive alternatives for symptom management in adults (&#x2265;18 years) with gastrointestinal cancer were eligible. Two reviewers independently screened records, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. The evidence certainty was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Random-effects meta-analyses were performed for primary outcomes (anxiety, pain, quality of life) and secondary outcomes (knowledge, length of stay, vital signs, safety). Heterogeneity was explored using subgroup analyses and meta-regression. Fourteen RCTs were included, comprising individuals (N=837) with colorectal, liver, esophageal, gastric, pancreatic, and biliary tract cancers. IVR interventions-including immersive scenes, interactive games, anatomical models, and cognitive behavioral modules-were primarily delivered during perioperative and chemotherapy periods. Meta-analysis showed that IVR significantly reduced anxiety (standardized mean difference [SMD] -0.58, 95% CI -0.95 to -0.20; P=.01; 95% prediction interval [PI] -1.36 to 0.21) and pain (SMD -0.75, 95% CI -1.48 to -0.03; P=.04; 95% PI -2.21 to 0.71). Subgroup analysis revealed that the anxiolytic effect was more pronounced when IVR was administered during active treatment and when single sessions lasted &#x2265;20 minutes. Hospital stay was significantly shorter in the IVR group (mean difference -4.11 days, 95% CI -7.39 to -0.82; P=.03; 95% PI -13.82 to 5.60 days). No significant effects were detected for quality of life, knowledge acquisition, or vital signs. The evidence certainty was moderate to very low, with common limitations including risk of bias and imprecision. This meta-analysis provides evidence that IVR is an effective nonpharmacological adjunct for symptom management in patients with gastrointestinal cancer, significantly reducing anxiety and pain when implemented during active treatment for at least 20 minutes. However, these findings should be interpreted with caution due to moderate to high heterogeneity, substantial risk of bias in the included studies, and low to very low GRADE evidence certainty. While the 95% CIs indicate a statistically significant average effect, the wide 95% PIs suggest that the true effect in future clinical settings may vary considerably, ranging from marked benefit to negligible impact. These results support the integration of IVR into perioperative and chemotherapy care pathways while underscoring the need for larger, more rigorously designed trials to establish definitive conclusions.

Precise and controllable RNA editing presents a powerful therapeutic strategy for oncogene silencing in cancer treatment. Here, we introduce a photothermal-activatable host-guest supramolecular delivery system enabling spatiotemporally regulated expression of CasRx, a compact RNA-guided RNA endonuclease, for targeted survivin mRNA knockdown in hepatocellular carcinoma. The modular platform is constructed through dynamic assembly of &#x3b2;-cyclodextrin-conjugated polydisulfide and adamantane-functionalized conjugated small molecules through host-guest interactions, enabling the integration of photothermal agents into the delivery vectors that can encapsulate the heat-inducible expression of plasmid encoding CasRx. Upon the near-infrared (NIR) laser irradiation, the moieties containing conjugated small molecules can convert light to heat so as to trigger the specific expression of CasRx in tumor tissue, leading to efficient and selective degradation of survivin transcripts. This supramolecular platform integrates the photothermal switch and delivery carriers and precisely controls RNA editing in vivo, avoiding potential systemic toxicity induced by off-target delivery. Our study establishes a programmable and precise RNA regulation platform in vivo by means of supramolecular assembly for safe, tunable, and effective RNA-based cancer therapy.

Liver cancer poses a serious global health burden, with China experiencing particularly high incidence and mortality rates. Treatment complexity and severe side effects often impair patients' quality of life, leading to self-perceived burden (SPB) stemming from care dependency, financial pressure, and emotional distress. This cross-sectional study of 139 patients with liver cancer explored predictors of SPB using multiple linear regression. Results showed that 97.82% of the participants experienced SPB (mean&#x2009;=&#x2009;63.58&#x2009;&#xb1;&#x2009;15.33). Unemployment before illness, chemotherapy, use of confrontation, and fantasy coping strategies were significant predictors of SPB. Findings highlight the urgent need for targeted interventions to alleviate SPB and enhance patients' quality of life.

Early-onset gastrointestinal cancers (EOGIC) are increasingly recognised as an urgent global health concern. We aimed to describe the global incidence patterns of EOGIC in 2022 and evaluate country-level ecological associations with behavioural risk factors. The incident cases and age-standardised incidence rates (ASIRs) of overall EOGIC, early-onset colorectal cancer (EOCRC), early-onset oesophageal cancer, early-onset gallbladder and biliary tract cancer, early-onset liver cancer (EOLC), early-onset pancreatic cancer (EOPC), and early-onset stomach cancer (EOSC) were extracted from the GLOBOCAN 2022 database. We used machine learning and generalised linear regression to screen and quantify the associations of behavioural risk factors and computed the model-based attributable fraction estimates. In 2022, an estimated 465&#x2009;584 new EOGIC cases occurred globally (9.49% of all-age gastrointestinal cancers), with an ASIR&#x2009;=&#x2009;11.50 per 100&#x2009;000 persons. Early-onset colorectal cancer was the highest in both incident cases (n&#x2009;=&#x2009;186&#x2009;840), and ASIR&#x2009;=&#x2009;4.60 per 100&#x2009;000, followed by EOLC and EOSC. High Human Development Index countries (n&#x2009;=&#x2009;205&#x2009;168 incident cases, ASIR&#x2009;=&#x2009;13.20 per 100&#x2009;000) showed highest incidence of EOGIC. The highest number of EOGIC incident cases was in Eastern Asia (n&#x2009;=&#x2009;147&#x2009;677) and the highest ASIR occurred in Australia-New Zealand (ASIR&#x2009;=&#x2009;18.70 per 100&#x2009;000). In the ecological analyses, diet high in red meat and smoking showed the largest attributable fraction estimates for overall EOGIC incidence, at 12.78% and 8.17%, respectively. Smoking also showed comparatively larger estimates for EOCRC (11.29%) and EOPC (23.97%). High alcohol use was associated with nonzero attributable estimates for EOCRC (3.14%), early-onset oesophageal cancer (1.57%), EOLC (7.39%), EOPC (3.75%), and EOSC (6.88%), whereas diet high in sodium showed the largest estimate for EOSC (15.41%). Early-onset gastrointestinal cancer was a significant global health challenge, particularly for EOCRC and in high Human Development Index countries. These findings may help inform surveillance priorities and hypothesis generation for future etiologic research.

Hepatocellular carcinoma (HCC) is a major health concern, highlighting the need for effective surveillance. Republic of Korea's (South Korea's) National Cancer Screening Program (NCSP) uses ultrasound and serum alpha fetoprotein (AFP) tests for high-risk populations, but its performance remains unevaluated. The AFP result is only used when a mass under 1 cm is detected on ultrasound, raising concerns about its appropriateness. We analyzed data from 820,380 participants in Korea's NCSP for HCC between 2018 and 2020, comparing the ultrasound-alone protocol, current criteria, and the modified criteria newly proposed in this study. The current criteria define surveillance positivity as positive ultrasound findings or equivocal findings with elevated AFP, while the modified criteria consider either positive ultrasound findings or elevated AFP. Sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve for detecting HCC with various AFP cutoffs were evaluated. Ultrasound alone had a sensitivity of 44.26% and a specificity of 97.38%. The current criteria achieved a sensitivity of 44.82-46.51% and a specificity of 97.18-97.38% for detecting HCC with various AFP cutoffs ranging from 5 to 100 ng/mL. The AUROC for the modified criteria was 0.8728, significantly higher than that of the current criteria (0.7209, P < 0.001). An AFP cutoff of 7 ng/mL was identified as the optimal threshold based on Youden's index. An AFP cutoff of 7 ng/mL slightly reduced specificity from 97.28% to 92.24%, whereas sensitivity markedly increased from 46.22% to 76.72%. Additionally, an AFP cutoff of 20 ng/mL yielded an increased sensitivity of 63.25% with maintaining specificity of 96.71%. The modified NCSP criteria we proposed, which incorporate AFP more proactively, identified an optimal cutoff for the Korean NCSP by balancing both sensitivity and specificity. This approach may contribute to improving the effectiveness HCC surveillance in the future.

The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100&#x2008;000 population, and age-standardised rates per 100&#x2008;000 population. We estimated 1&#xb7;17 billion (95% uncertainty interval 1&#xb7;06-1&#xb7;31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14&#x2008;210&#xb7;7 cases (12&#x2008;849&#xb7;5-15&#x2008;940&#xb7;1) per 100&#x2008;000 population. These estimates represented a 95&#xb7;5% (75&#xb7;0-121&#xb7;2) increase in prevalent cases and 24&#xb7;2% (11&#xb7;4-41&#xb7;4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070&#xb7;5 DALYs (1519&#xb7;1-2750&#xb7;5) per 100&#x2008;000 population. Mental disorders contributed to 6&#xb7;1% (4&#xb7;8-7&#xb7;6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17&#xb7;3% (14&#xb7;8-20&#xb7;6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239&#xb7;6 [1643&#xb7;7-3014&#xb7;1] per 100&#x2008;000) than among males (1900&#xb7;2 [1399&#xb7;8-2510&#xb7;8] per 100&#x2008;000), and peaked in the 15-19 years age group (2617&#xb7;3 [1850&#xb7;6-3696&#xb7;8] per 100&#x2008;000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302&#xb7;4 (952&#xb7;7-1683&#xb7;7) per 100&#x2008;000 in Viet Nam to 3555&#xb7;8 (2661&#xb7;9-4715&#xb7;0) per 100&#x2008;000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853&#xb7;0 (1352&#xb7;1-2469&#xb7;3) per 100&#x2008;000 for middle SDI to 2184&#xb7;1 (1606&#xb7;1-2890&#xb7;3) per 100&#x2008;000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.

Obesity is not only an important part of metabolic syndrome, but also closely related to the pathogenesis of a variety of malignancies. However, there are differing views on the relationship between obesity and the risk of digestive malignancies. In this context, it is necessary to assess the true cancer risk in people with different obesity states. In the past, some researchers proposed to use the metabolic syndrome severity z score to predict the risk of certain diseases, but since its introduction, there has been a lack of relevant studies in the Chinese population. Based on the Kailuan cohort, the association between metabolic syndrome severity z score and the risk of digestive system malignancy in the Chinese population was explored. In this study, 48,205 participants who had undergone 3 consecutive physical examinations since 2006 were collected. Cumulative metabolic syndrome severity z score (cMets-Z) was calculated using parameters such as fasting blood glucose, total cholesterol, high-density lipoprotein, systolic blood pressure, and body mass index. Participants were categorized into 4 groups based on cMetS-Z (Q1-Q4), and a Cox regression model was used to evaluate the risk of new digestive system malignancies. The mean age of participants was 48.99&#x2005;&#xb1;&#x2005;11.75 years. Over a median follow-up period of 11.03 years, 749 new cases of digestive cancers were identified, including esophageal, gastric, colorectal, liver, bile duct, and pancreatic cancers. Cox proportional hazards modeling revealed adjusted hazard ratios for gastrointestinal cancers in the Q2 to Q4 groups as 1.19 (0.96-1.48), 1.36 (1.08-1.71), and 1.72 (1.33-2.23). In site-specific analyses, we observed that this risk was more pronounced in esophageal cancer. Subgroup analyses showed that cMetS-Z was associated with digestive system malignancies, particularly in male participants with metabolic syndrome. Restricted cubic spline regresion results showed that cMets-Z had a linear relationship with the risk of digestive system tumors. We found that cMetS-Z was associated with an increased risk of gastrointestinal cancer. cMetS-Z can be used as a prospective tool to predict the risk of gastrointestinal malignancies in Chinese people.

Incidental gallbladder cancer (IGBC) is increasingly diagnosed after cholecystectomy performed for presumed benign disease. For T2 and selected T3 tumors, completion radical re-resection with liver resection and regional lymphadenectomy is recommended, but the optimal hepatic extent-nonanatomic wedge resection versus anatomic segment IVb/V resection-remains debated. This narrative review summarizes evidence from IGBC-specific series and registries, international multicenter cohorts, meta-analyses, and contemporary consensus guidelines comparing wedge resection and segment IVb/V resection for T2-T3 gallbladder cancer, with emphasis on oncologic outcomes, perioperative morbidity, and the evolving role of systemic therapy. Across contemporary cohort studies and meta-analyses, margin-negative wedge resection appears to provide long-term oncologic outcomes comparable to segment IVb/V resection for T2 disease, while segment IVb/V is consistently associated with higher perioperative morbidity. Tumor location (T2a vs T2b) may correlate with prognosis, but does not independently mandate greater liver volume when nodal and margin status are considered. In IGBC, outcomes are driven primarily by nodal involvement, residual disease, and margin status rather than by the specific hepatic volume removed. For T3 and other high-risk presentations, large international datasets suggest limited incremental benefit from escalation to major hepatectomy or routine extrahepatic bile duct resection, although bile duct resection is indicated when the cystic duct margin is positive. Neoadjuvant systemic therapy is increasingly considered in selected borderline-resectable or node-positive disease to enable biologic selection and improve the likelihood of achieving an R0 resection with limited hepatic excision. For T2 IGBC, a parenchyma-sparing, margin-negative wedge resection of the gallbladder bed combined with high-quality regional lymphadenectomy appears to provide oncologic outcomes comparable to segment IVb/V resection in most patients. Current evidence does not demonstrate a consistent survival advantage for routine segment IVb/V resection. In T3 and high-risk disease, surgical strategy should prioritize biologic selection and integration of systemic therapy, with hepatic extent tailored to margin requirements rather than routine escalation.

Some cancers are diagnosed late, making them harder to treat. People with an undiagnosed cancer may use over-the-counter medications to manage non-specific cancer-related symptoms that often mimic other more common, easily treatable conditions. Results from the original Cancer Loyalty Card Study (CLOCS) suggest there may be an increase in purchases of pain and indigestion medication 8-9 months before an ovarian cancer diagnosis. We aim to validate the CLOCS findings by exploring whether a significant change in medication purchases could be an indication for early signs of the following cancer types: oesophageal, stomach (gastric), colorectal (bowel), pancreatic, liver, bladder, endometrial, uterine sarcoma, ovarian and vulval, using data collected through store loyalty cards. Using a retrospective case-control design, we aim to recruit 1450 participants with one of the cancers of interest (cases) and 1450 participants without cancer (controls) in the UK who (or whose household members) hold a loyalty card with at least one participating high street retailer. We will use pre-existing loyalty card data to compare past purchase patterns of cases with those of controls. To assess cancer risk in participants and their purchasing patterns, we will collect information on demographic characteristics, health risk factors, lifestyle habits and behaviours, family history of cancer and any symptoms experienced prior to diagnosis (cases) and in the last year prior to study recruitment (controls). In addition, cases will be asked about their cancer diagnosis. CLOCS-2 was reviewed and approved by the East Midlands-Leicester South Research Ethics Committee (23/EM/0224). Study outcomes will be disseminated through peer-reviewed publications, conferences, presentations to the research communities as well as patients and the public, the study website and other social media outlets. NCT06447064, CPMS58679; pre-results.

The rising incidence of liver cirrhosis among women of childbearing age is associated with increased maternal morbidity and potential adverse maternal health outcomes. This study aimed to analyze temporal trends of cirrhosis incidence and project future epidemiological patterns to guide targeted prevention and control strategies. We extracted liver cirrhosis incidence data from the Global Burden of Disease Study 2021, covering 204 countries and territories from 1992 to 2021. The analytical population included females aged 15 to 49 years. Trends across age groups, periods, and birth cohorts were analyzed using the age-period-cohort model. The Bayesian age-period-cohort model was utilized to forecast epidemiological trends through 2030. Between 1992 and 2021, global cirrhosis trends varied by etiology: alcohol-related cases increased (14,566.88-19,340.29) despite declining age-standardized incidence rates (1.22-0.94 per 100,000), while nonalcoholic fatty liver disease-related cirrhosis showed a continuous upward trend in both case counts and age-standardized incidence rate between 1992 and 2021 (reaching 16,095,135.50 cases and 831.02 per 100,000 population in 2021), with projections indicating it may rise to approximately 19.63 million cases (95% uncertainty interval&#x2005;=&#x2005;16.36 million-22.89 million) by 2030. Low socio-demographic index regions bore the highest burden. Projections through 2030 suggest a potential rising global burden, particularly for alcohol-related cases, with divergent trends projected for China (decreasing) and India (increasing). The global incidence of liver cirrhosis among women of childbearing age is rising, in population-level correlation with the growing burden of nonalcoholic fatty liver disease and regional gaps in viral and alcohol-related cirrhosis etiologies. These findings highlight the potential need for region-specific prevention strategies. Limitations include Global Burden of Disease data quality, ecological bias, and insufficient pregnancy-specific data for detailed incidence trend analysis.

Background: Gastric cancer (GC) is characterized by late-stage diagnosis and a lack of reliable non-invasive biomarkers. This study aims to investigate the plasma bile acid (BA) profile to enhance the understanding of GC metabolism and identify potential diagnostic and prognostic tools. Methods: In a case-control design, 62 GC patients (stages I III) and 70 matched controls were recruited. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), the concentrations of 48 metabolites in plasma were measured. Statistical analysis included univariate tests, principal component analysis, and linear discriminant analysis (LDA). Results: GC patients showed a significantly lower CA/CDCA ratio and alterations in secondary and conjugated bile acids, including TLCA, GLCA, TDCA, GDCA, and GUDCA, suggesting involvement of the gut liver microbiome axis. The ability to distinguish between groups was moderate (AUC = 0.731). Furthermore, BA levels were negatively correlated with tumor stage, tumor size, and systemic inflammatory markers (CRP, mGPS), while they were positively correlated with nutritional and hematological markers such as albumin and hemoglobin. Conclusions: Gastric cancer is associated with a distinct circulating BA profile that reflects not only tumor-related metabolic remodeling, but also systemic inflammation, nutritional status, and disease burden. The reduced CA/CDCA ratio and alterations in secondary and conjugated bile acids support the involvement of the gut-liver-microbiome axis in GC biology. Although BA profiling alone showed moderate diagnostic performance, its integration with conventional tumor markers, inflammatory indices, and clinico-pathological parameters may improve multimodal biomarker panels for noninvasive patient stratification, disease assessment, and future prognostic evaluation.

A substantial proportion of cancers are preventable, yet awareness of risk factors and screening remains limited. This study assessed disparities in knowledge of cancer epidemiology, screening, and environmental risk factors between healthcare workers(HCWs) and the general public(GP) in two urban districts of Istanbul, and identified associated sociodemographic and behavioral determinants. A cross-sectional survey was conducted with 309 participants using a structured 42-item questionnaire covering cancer epidemiology (15 items), screening (9), and environmental risk factors(18). Each correct response scored one point. Internal consistency was high (Cronbach's alpha = 0.944). Knowledge levels were analyzed across subgroups. HCWs scored significantly higher than the GP in all domains: epidemiology (7.7 &#xb1; 3.6; 6.4 &#xb1; 2.8), screening (5.2 &#xb1; 2.7; 2.6 &#xb1; 2.1), and environmental risks (12.5 &#xb1; 5.0; 10.7 &#xb1; 5.7). Higher education, better income, and health-promoting behaviors were associated with increased knowledge. Despite this, notable gaps persisted. Breast cancer was widely recognized (86.1% HCWs; 81.9% GP), whereas awareness of lethal cancers like liver cancer was low (12.2% HCWs; 4.6% GP). Screening knowledge varied: HCWs were more aware of breast cancer screening; prostate and lung cancer screening were poorly recognized, particularly by the GP. While radiation risks were commonly known, links between smoking and non-lung cancers were largely unknown. Despite national programs, critical gaps in knowledge persist across all domains, including among HCWs. These disparities, shaped by education, income, and behavior, undermine prevention efforts. Tailored education strategies are needed to improve knowledge, especially environmental cancer literacy, and promote early detection in both groups.

Previous studies and meta-analyses suggest an association between hypertension and tinnitus; however, the influence of hypertension severity and control status remains unclear. We aimed to investigate the association between hypertension and tinnitus in detail using a large, population-based dataset from a rural setting.DesignObservational cross-sectional study.SettingSheshdeh, Fasa, Iran. We analysed data from 9775 individuals in the general population, aged 35-70 years, excluding those with a history of cancer, pregnancy or medical conditions known to cause tinnitus, such as stroke, seizures or multiple sclerosis. Additionally, although the study design aimed to exclude participants using aminoglycosides because of their significant ototoxic effects, no such users were identified during the study period. Hypertension was defined as a systolic blood pressure (SBP) of &#x2265;140&#x2009;mm Hg or a diastolic blood pressure (DBP) of &#x2265;90&#x2009;mm Hg on at least two separate measurements or as current use of antihypertensive medications following a prior diagnosis. These medications included ACE inhibitors, angiotensin receptor blockers, diuretics, aldosterone antagonists and atenolol. Stage I hypertension was classified as an SBP of 140-159&#x2009;mm Hg or a DBP of 90-99&#x2009;mm Hg, while stage II was defined as an SBP of &#x2265;160&#x2009;mm Hg or a DBP of &#x2265;100&#x2009;mm Hg. Controlled blood pressure was defined as values below these thresholds. Tinnitus, assessed by a self-reported questionnaire, was defined as a continuous wheezing sound in the ear persisting for more than 1&#x2009;week. Among participants (4446 males, 5309 females; mean age 48.55 (SD 9.53) years), the prevalence of tinnitus and hypertension was 7.4% and 19.3%, respectively. Hypertension was significantly associated with higher odds of tinnitus (adjusted OR=1.34; 95%&#x2009;CI 1.10 to 1.62). Notably, even participants with controlled hypertension had a 27% increased odds (OR=1.27; 95%&#x2009;CI 1.02 to 1.59) compared with normotensive individuals. The odds were highest in those with uncontrolled grade II hypertension (OR=2.08; 95%&#x2009;CI 1.25 to 3.47), demonstrating a dose-response relationship. Our findings suggest a positive association between hypertension and tinnitus, with odds increasing alongside the severity and poor control of hypertension. Importantly, even controlled hypertension was associated with elevated odds, indicating that tinnitus screening may be warranted in all hypertensive patients, regardless of control status. These results underscore the need for heightened clinical awareness and further research into the pathophysiological mechanisms linking vascular health and auditory symptoms.