Sex disparities in global burden of gallbladder and biliary tract cancer: analysis of Global Burden of Disease study from 2010 to 2019.

BACKGROUND AND AIM: The global burden of gallbladder and biliary tract cancer (GBTC) has been on the rise, making it a major public health concern. We aim to comprehensively analyze sex disparities in the temporal trends of GBTC incidence, mortality, and disability-adjusted life years (DALYs) regionally and globally from 2010 to 2019. METHODS: Age-standardized rates of GBTC incidence, death, and DALYs were analyzed utilizing the Global Burden of Disease study 2019. RESULTS: From 2010 to 2019, the estimated annual percent change (APC) of the age-standardized incidence rates (ASIRs) and age-standardized disability-adjusted life years (ASDALYs) due to GBTC globally decreased in both sexes (males, APC: -0.80%; APC: -1.00%) and (females, APC: -0.89%; APC: -0.96%). At the same time, age-standardized death rates (ASDRs) decreased only in males (APC: -0.82%) and remained stable in females. By regions, ASIRs and ASDR increased in both sexes only in Southeast Asia (SEA) but decreased in the other regions. All regions had decreased ASDALYs except for an increase in ASDALYs for females only in the SEA region (APC: 0.41%), and males have a stable trend. CONCLUSIONS: Our study reveals substantial geographic variance in the burden of GBTC, specifically in the SEA region. Therefore, localized interventional methodologies must be undertaken to effectively address this global burden from GBTC.

Epidemiology of gastrointestinal cancers: a systematic analysis from the Global Burden of Disease Study 2021.

BACKGROUND: Gastrointestinal cancers comprise nearly one-third of global mortality from cancer, yet the comprehensive global burden of these cancers remains uninvestigated. OBJECTIVE: We aimed to assess the global, regional and national burden of gastrointestinal cancers. DESIGNS: Data on oesophagus, gastric, colorectal, liver, pancreas and biliary tract cancers were extracted from the Global Burden of Disease 2021 database. Age-standardised incidence rate (ASIR) and age-standardised death rate (ASDR) were calculated by sex, region and Sociodemographic Index (SDI). RESULTS: In 2021, there were 5.26 million incidences and 3.70 million deaths from gastrointestinal cancer. The greatest burden is from colorectal, followed by gastric, oesophageal, pancreatic, liver and biliary tract cancer. We noted geographical and socioeconomic differences in ASIR and ASDR across all types of cancers. From 2000 to 2021, ASIR increased for colorectal cancer (annual percent change (APC): 0.10%, 95% CI 0.05% to 0.14%), pancreatic cancer (APC: 0.27%, 95% CI 0.14% to 0.41%), and liver cancer from metabolic dysfunction-associated steatotic liver disease (APC: 0.62%, 95% CI 0.58% to 0.67%) and alcohol-related liver disease (APC: 0.26%, 95% CI 0.22% to 0.30%). ASDR increased for pancreatic cancer (APC: 0.18%, 95% CI 0.02% to 0.34%). Higher SDI countries had higher incidence rates for most types of gastrointestinal cancer. CONCLUSIONS: Although the ASIR of oesophageal, gastric and biliary tract cancer has decreased, the ASIR still increased in colorectal, pancreatic and liver cancer from steatotic liver disease. Public policies are important for controlling gastrointestinal cancers-most importantly, reducing alcohol consumption, hepatitis B immunisation and tackling the burden of metabolic diseases.

Changes in the epidemiological trends of primary liver cancer in the Asia-Pacific region.

Primary liver cancer is the third leading cause of cancer-related mortality. The increasing prevalence of metabolic syndrome and alcohol consumption, along with the existing burden of viral hepatitis, could significantly heighten the impact of primary liver cancer. However, the specific effects of these factors in the Asia-Pacific region, which comprises more than half of the global population, remain largely unexplored. This study aims to analyze the epidemiology of primary liver cancer in the Asia-Pacific region. We evaluated regional and national data from the Global Burden of Disease study spanning 2010 to 2019 to assess the age-standardized incidence, mortality, and disability-adjusted life years associated with primary liver cancer in the Asia-Pacific region. During the study period, there were an estimated 364,700 new cases of primary liver cancer and 324,100 deaths, accounting for 68 and 67% of the global totals, respectively. Upward trends were observed in the age-standardized incidence rates of primary liver cancer due to metabolic dysfunction-associated fatty liver disease (MASLD) and alcohol-associated liver disease (ALD) in the Asia-Pacific region, as well as an increase in primary liver cancer from Hepatitis B virus infection in the Western Pacific region. Notably, approximately 17% of new cases occurred in individuals aged 15-49 years. Despite an overall decline in the burden of primary liver cancer in the Asia-Pacific region over the past decade, increases in incidence were noted for several etiologies, including MASLD and ALD. However, viral hepatitis remains the leading cause, responsible for over 60% of the total burden. These findings underscore the urgent need for comprehensive strategies to address the rising burden of primary liver cancer in the Asia-Pacific region.

Reactive Oxygen Species-Mediated Mitophagy and Cell Apoptosis are Involved in the Toxicity of Aluminum Chloride Exposure in GC-2spd.

Aluminum chloride is an inorganic polymeric coagulant commonly found in daily life and various materials. Although male reproductive toxicity has been associated with AlCl3 exposure, the underlying mechanism remains unclear. This study aimed to examine the impact of AlCl3 exposure on mitophagy and mitochondrial apoptosis in testicular tissue and mouse spermatocytes. Reactive oxygen species (ROS) and ATP levels were measured in GC-2spd after AlCl3 exposure using a multifunctional enzyme labeler. The changes in mitochondrial membrane potential (MMP) and TUNEL were observed through confocal laser microscopy, and the expression of proteins associated with mitophagy and apoptosis was analyzed using Western blot. Our results demonstrated that AlCl3 exposure disrupted mitophagy and increased apoptosis-related protein expression in testicular tissues. In the in vitro experiments, AlCl3 exposure induced ROS production, suppressed cell viability and ATP production, and caused a decrease in MMP, leading to mitophagy and cell apoptosis in GC-2spd cells. Intervention with N-acetylcysteine (NAC) reduced ROS production and partially restored mitochondrial function, thereby reversing the resulting mitophagy and cell apoptosis. Our findings provide evidence that ROS-mediated mitophagy and cell apoptosis play a crucial role in the toxicity of AlCl3 exposure in GC-2spd. These results contribute to the understanding of male reproductive toxicity caused by AlCl3 exposure and offer a foundation for future research in this area.

Associations of serum estradiol level, serum estrogen receptor-alpha level, and estrogen receptor-alpha polymorphism with male infertility: A retrospective study.

ABSTRACT: Estradiol regulates spermatogenesis partly via estrogen receptor-alpha (ESRα). This study aimed to analyze the associations of serum estradiol level, serum ESRα level, and ESRα gene polymorphisms with sperm quality.This retrospective study included infertile men attending the Reproductive Center, Affiliated Hospital of Youjiang Medical University for Nationalities, and a control group without a history of fertility (October, 2016 to March, 2017). Data regarding sperm quality, serum levels of estradiol and ESRα, and rs2234693C/T genotype were extracted from the medical records. Pearson/Spearman correlations (as appropriate) between estradiol level, ESRα level, and sperm quality parameters were evaluated.The analysis included 215 men with infertility and 83 healthy controls. The infertile group had higher serum levels of estradiol (147.57 ±â€Š35.3 vs 129.62 ±â€Š49.11 pg/mL, P < .05) and ESRα (3.02 ±â€Š2.62 vs 1.33 ±â€Š0.56 pg/mL, P < .05) than the control group. For the infertile group, serum estradiol level was negatively correlated with sperm concentration, percentage of progressively motile sperm, and percentage of sperm with normal morphology (r = 0.309, 0.211, and 0.246, respectively; all P < .05). Serum estradiol and ESRα levels were lower in infertile men with normozoospermia than in those with azoospermia, oligozoospermia, mild azoospermia, or malformed spermatozoa (all P < .05). Sperm concentration, percentage of progressively motile sperm, serum ESRα level, and serum estradiol level did not differ significantly among the rs2234693 CC, CT, and TT genotypes.Elevated serum levels of estradiol and possibly ESRα might have a negative impact on sperm quality and fertility, whereas single nucleotide polymorphisms at rs2234693 of the ESRα gene had little or no effect.

[Impacts of aluminum on sperm quality and sperm mitochondria in male rats].

OBJECTIVE: To study the impacts of aluminum chloride (AlCl3) on the sperm quality, sperm mitochondrial membrane potential (MMP) and sperm mitochondrial membrane permeability transition pore (MPTP) function of male rats, and the possible mechanisms of AlCl3 inducing the declination of sperm quality. METHODS: According to the median lethal dose (LD50) of AlCl3・6H2O in drinking water, we randomly assigned 96 male Wistar rats weighing 180－200 g to four groups of equal number and fed them with AlCl3 aqueous drinking water at 256.72 mg/kg/d (1/5 LD50, high-dose group), 128.36 mg/kg/d (1/10 LD50, medium-dose group), 64.18 mg/kg/d (1/20 LD50, low-dose group) and 0 mg/kg/d (control group), respectively, all for 16 weeks. Then, we examined the quality of the epididymal sperm of the rats, observed the morphology of the sperm mitochondria under the transmission electron microscope, and determined the MMP level of the sperm mitochondria and the function of the MPTP by flow cytometry. RESULTS: The percentage of progressively motile sperm was significantly decreased in the low-, medium- and high-dose AlCl3 groups as compared with that in the control group (ï¼»46.49 ± 5.37ï¼½%, ï¼»33.50 ± 8.75ï¼½% and ï¼»16.94 ± 5.00ï¼½% vs ï¼»66.28 ± 5.68ï¼½%, P < 0.01), that of dead sperm was remarkably increased (ï¼»19.73 ± 5.57ï¼½%, ï¼»35.80 ± 5.90ï¼½% and ï¼»55.19 ± 4.97ï¼½% vs ï¼»12.71 ± 4.84ï¼½%, P < 0.01), and so was that of morphologically abnormal sperm (ï¼»19.06 ± 2.44ï¼½%, ï¼»23.78 ± 3.29ï¼½% and ï¼»32.06 ± 4.65ï¼½% vs ï¼»14.56 ± 1.62ï¼½%, P < 0.01). Sperm mitochondrial swelling was aggravated in the AlCl3-exposed rats in a dose-dependent manner. The sperm MMP level was significantly lower in the low-, medium- and high-dose AlCl3 groups than in the control (ï¼»60.88 ± 7.37ï¼½%, ï¼»51.54 ± 6.12ï¼½% and ï¼»37.70 ± 7.44ï¼½% vs ï¼»74.35±4.67ï¼½%, P < 0.01), with a negative correlation to the dose of AlCl3 (rs = －0.819, P < 0.01), while the pathologically open MPTP was markedly higher in the former three than in the latter group (ï¼»27.80 ± 5.74ï¼½%, ï¼»36.58 ± 6.67ï¼½% and ï¼»64.95 ± 8.07ï¼½% vs ï¼»15.37 ± 7.13ï¼½%, P < 0.01), with a positive correlation to the dose of AlCl3 (rs = 0.867, P < 0.01). CONCLUSIONS: Exposure to aluminum can cause sperm mitochondrial swelling, decrease the sperm MMP level, induce pathological opening of the MPTP, and consequently reduce sperm quality in male rats.