Gallstones affect a significant proportion of U.S. adults and can cause serious complications. We aimed to investigate the association between gallstone disease and common metabolic disorders in a nationally representative sample in the United States.

We analyzed data from the National Health and Nutrition Examination Survey (NHANES) collected from 2017 to 2020. We included 6164 participants meeting the eligibility criteria, which represented 171 407 370 participants. The associations between gallstone disease and six metabolic disorders were analyzed using multivariate logistic regression analyses, accounting for potential confounding factors. Subgroup analyses were conducted by age, gender, and race.

Altogether 10.9% of participants had gallstone disease, with prevalence increasing with age (mean age with vs. without gallstones: 56.435 years vs. 46.896 years, p < 0.001) and a female predominance (75.1% vs. 24.9%, p < 0.001). Non-alcoholic fatty liver disease (NAFLD), obesity, hypertension, and diabetes mellitus were significantly associated with an increased risk of gallstone formation, with adjusted odds ratios (OR) of 1.523 (95% confidence interval [CI] 1.180-1.965, p = 0.002), 1.733 (95% CI 1.265-2.374, p = 0.001), 1.466 (95% CI 1.203-1.785, p = 0.001), and 1.522 (95% CI 1.165-1.989, p = 0.003), respectively. These associations were more pronounced in individuals under 60 years of age and in females. No significant associations were observed with hyperlipidemia or hyperuricemia.

Gallstone disease is significantly associated with obesity, NAFLD, diabetes mellitus, and hypertension, with stronger associations found in younger individuals and females. Sensitivity analyses confirmed the robustness of these findings.

Numerous risk factors are linked to gallbladder stone disease (GBSD). Nonetheless, the relationship between Clonorchis sinensis (C. sinensis) and this condition remains to be clarified.

The antibody against C. sinensis in serum and the glucose, triglyceride, and cholesterol levels were investigated in 220 patients with GBSD and 251 controls. Bile components were analysed in patients with gallbladder polyps (GP, n = 18), gallstones (GS, n = 265), and GS combined with C. sinensis infection (GSI, n = 243). Additionally, the gallbladder ejection fraction (%E), residual gallbladder volume (RGV) at 1 h after a fatty meal, and fasting gallbladder volume (FGV) were compared among the GP (n = 43), GS (n = 311), and GSI (n = 277) groups.

The results indicated positive antibody against C. sinensis (OR: 1.759, 95% CI: 1.163-2.662) and hyperglycaemia (glucose concentration ≥ 6.10 mmol/L, OR: 2.263, 95% CI: 1.227-4.172) were risk factors for GBSD. There were more non-cholesterol stones in GSI patients (216/241, 89.6%) than in GS patients (137/281, 48.8%) (P < 0.0001). Microscopic observations revealed that mucus containing glycogen coated the C. sinensis eggs and the proportion of dead eggs gradually increased in bile, sediment, and stones alongside rising calcium salt content. Total bile acid and cholesterol concentrations were lower in GSI patients than in GP patients or GS patients (P < 0.05). Moreover, increased FGV and RGV and decreased %E were observed in GSI patients compared with GP patients (P < 0.001).

The formation of non-cholesterol gallstones in populations residing in endemic areas is related to the deposition, death, and calcification of eggs in the gallbladder, changes in bile components, and decreased gallbladder motility caused by C. sinensis infection.

Gallstones are a prevalent condition that can lead to significant morbidity and healthcare costs. Relative fat mass (RFM), as a potential marker of body fat distribution, may offer insights beyond traditional metrics like body mass index (BMI) and waist circumference. This study aims to investigate the association between RFM and gallstone prevalence in the U.S. population.

The study cohort comprised 6,881 participants obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 2017 and 2020. Participants were stratified into quartiles (Q1-Q4) based on their RFM. To evaluate the associations, multivariable logistic regression analyses were employed to assess odds ratios (OR) for gallstone risk across different quartiles of RFM. Additionally, restricted cubic spline analysis was conducted to ascertain the relationship trend while subgroup analyses examined interactions based on age, sex, race, education level, and lifestyle factors.

The analysis revealed significant associations for participants within the higher RFM quartiles (Q3 and Q4), with ORs of 2.58 (95% CI: 1.65, 4.04) and 6.30 (95% CI: 3.63, 10.93), respectively, compared to Q1. The findings consistently indicated that RFM, particularly in Q4, is a strong predictor of gallstone risk, demonstrating superior predictive performance relative to waist circumference and BMI, as evidenced by an AUC of 0.702.

Elevated RFM is a noteworthy predictor of gallstone risk in the studied population, suggesting its potential utility in clinical risk assessment frameworks. Future research should focus on elucidating the underlying mechanisms driving this association and exploring RFM's applicability as a pragmatic tool in clinical practice for gallstone risk stratification.

Cholesterol synthesis and gallstone formation are promoted by trimethylamine-N-oxide (TMAO), a derivative of trimethylamine, which is a metabolite of gut microbiota. However, the underlying mechanisms of TMAO-induced lithogenesis remain incompletely understood. This study aimed to explore the specific molecular mechanisms through which TMAO promotes gallstone formation.

Enzyme-linked immunosorbent assays were used to compare serum concentrations of TMAO, apolipoprotein A4 (APOA4), and proprotein convertase subtilisin/kexin type 9 (PCSK9) between patients with cholelithiasis and normal controls. A murine model of TMAO-induced cholelithiasis was employed, incorporating assays of gallstone weight and bile cholesterol content, along with RNA sequencing of murine hepatic tissue. A TMAO-induced AML12 hepatocyte line was constructed and transfected with targeted small interfering RNAs and overexpression plasmids. In vivo and in vitro experiments were performed to determine the expression and regulation of genes related to cholesterol metabolism.

Serum TMAO and PCSK9 levels were elevated, whereas APOA4 levels were reduced in patients with cholelithiasis. Furthermore, our murine model demonstrated that TMAO upregulated hepatic expression of PCSK9, 3-hydroxy-3-methylglutaryl-CoA reductase, and ATP-binding cassette sub-family G member 5/8, while reducing APOA4 expression, thereby modulating cholesterol metabolism and promoting lithogenesis. PCSK9 and APOA4 were identified as key regulatory genes in the cholesterol metabolic pathway. PCSK9 knockdown increased APOA4 expression, while APOA4 overexpression led to reduced PCSK9 expression.

TMAO upregulated hepatic PCSK9 expression and reduced APOA4 expression, initiating a feedback loop that dysregulated cholesterol metabolism and promoted lithogenesis.

The Cardiometabolic Index (CMI), a composite marker integrating lipid profiles (triglycerides-to-HDL-C ratio) and abdominal obesity (waist-to-height ratio), we aimed to assess its association with gallstone prevalence.

We analyzed data from 2,692 participants in the NHANES 2017-2020 dataset. Gallstones were identified through self-reported data, which may introduce bias in the diagnosis. This limitation should be considered when interpreting the results. Logistic regression modelling, smoothed curve fitting and threshold effect analysis assessed the association between CMI and gallstones.

Higher CMI was significantly associated with an increased risk of gallstones (OR = 1.90, 95% CI: 1.37-2.62, P < 0.0001). A threshold effect was observed at CMI = 0.85, below which risk increased significantly (OR = 2.62, 95% CI:1.34-5.12, P = 0.0049), but became non-significant above this value. The association was stronger in women.

Our findings support the use of CMI as a potential predictive marker for gallstone risk, suggesting its integration into clinical assessments for early detection and prevention.

Numerous cohort studies have consistently shown a significant link between obesity and an increased risk of gallstones. However, body mass index (BMI) alone may not fully capture the complexity of obesity. This study aimed to analyze the associations between different obesity indexes and the incidence of gallstones, using a competing risk model.

A total of 459,523 UK Biobank participants without gallstones at baseline were analyzed. Cox proportional hazards models, competing risk models, and restricted cubic spline were performed to assess the longitudinal associations between 11 obesity indexes including a body shape index (ABSI), body adiposity index (BAI), body roundness index (BRI), conicity index (ConI), cardiometabolic index (CMI), hip circumference (HC), visceral adiposity index (VAI), lipid accumulation product (LAP), waist circumference (WC), waist-to-height ratio (WHtR), and waist-to-hip ratio (WHR) apart from BMI and gallstone occurrence risk, respectively.

Over a follow-up period of 12.54 years, a total of 14,951 participants developed gallstones. After adjusting for confounding factors, competing risk regression analyses revealed that BMI, BRI, BAI, confidence interval, CMI, HC, LAP, VAI, WC, and WHtR were all positively associated with an increased risk of gallstones. ABSI and WHR showed a "J-shaped" association with the incidence of gallstones, suggesting a nonlinear relationship. Sensitivity analyses confirmed the consistency of the results even after excluding participants who developed gallstones within 1 year of follow-up.

Different dimensions of obesity are all significantly associated with an increased risk of gallstones. These findings highlight the importance of managing obesity, including both overall body weight and abdominal fat, to prevent the occurrence of gallstones.

With the gradual improvement of living standards, the incidence of gallstones is getting higher and higher, and cholesterol gallstones (CG) are the most prevalent subtype. Therefore, we urgently need a better way to treat gallstones.

This study aimed to evaluate the effects of resveratrol (Res) on cholesterol gallstone formation and explore its underlying mechanisms, focusing on its modulation of hepatic peroxisome proliferator-activated receptor γ (PPAR-γ) expression, bile cholesterol saturation, and hepatic cholesterol metabolism.

Thirty-two male C57BL/6 mice were randomly divided into four groups: control, model, ursodeoxycholic acid (UDCA), and Res groups. Res (100 mg/kg/day) and UDCA (100 mg/kg/day) were administered via gavage for 5 weeks. Gallbladder bile, liver, and gallbladder tissues were collected for bile cholesterol crystal analysis, bile lipid profiling, and histopathological examination. Protein expression levels of PPARγ and scavenger receptor class B type I (SR-BI) were analyzed using Western blotting and immunohistochemistry.

Mice fed on a high fat diet resulted in larger gallbladder (about 2 times in both long and width diameters compared to control group) and CG formation, while resveratrol treatment significantly reduced gallstone formation, improved gallbladder dilatation, and declined cholestasis symptoms. Res suppressed hepatic inflammation by downregulating the receptor for advanced glycation end products (RAGE) expression and inhibiting the synthesis of proinflammatory factors. Res alleviated liver lipid deposition. It also enhanced PPARγ and SR-BI expression, promoting cholesterol efflux and lowering cholesterol levels, thereby preventing CG formation in mice.

Resveratrol demonstrates significant potential as a therapeutic agent for the prevention and treatment of cholesterol gallstone disease (CGD) by modulating hepatic cholesterol metabolism, reducing bile cholesterol saturation, and alleviating hepatic inflammation. Further studies are warranted to explore its clinical applicability in humans.

While dietary factors are known to influence gallstone development, the specific relationships between comprehensive dietary quality indicators and gallstone risk remain poorly understood. This study aimed to explore the association between dietary quality indicators and gallstones using data from the 2017 to 2020 US National Health and Nutrition Examination Survey (NHANES).

A total of 6,623 US adults were extracted from the 2017-2020 NHANES, of which 734 participants self-reported having gallstones. Dietary quality indicators were assessed using 24-hour dietary recall data. We used multivariate logistic regression analysis to evaluate the association between dietary quality indicators and the likelihood of gallstones. To delineate the non-linear relationships and threshold effects, we utilized a restricted cubic spline (RCS) regression model. Subgroup analyses were also performed.

After adjusting for sex, age, race, education, poverty-to-income ratio, body mass index, large weight loss, alcohol use, smoking, physical activity, diabetes, hypertension, heart failure, coronary heart disease, angina pectoris, heart attack, total calories, total cholesterol, estrogen use, antihyperglycemic drug use, statin use, and glucocorticosteroid use (Model 4), a higher Dietary Inflammatory Index (DII) and lower Alternative Healthy Eating Index (AHEI), Healthy Eating Index (HEI-2020), Dietary Approaches to Stop Hypertension (DASH), and Mediterranean Diet (MED) were all significantly associated with gallstones. Further RCS analysis revealed a nonlinear relationship between the DII and gallstones, with a threshold value of 1.842. Above this threshold, for each unit increase in the DII score, the odds of developing gallstones increased by 27.5%. Subgroup analysis demonstrated that this association was consistent across all subgroups.

Participants with gallstones exhibited poor dietary habits. Adopting a diet that reduces inflammation and supports overall health may help lower the risk of gallstone development, with potential implications for dietary recommendations in clinical practice.

Asymptomatic gallbladder and biliary tract calculus may make into symptomatic disease or bring anxiety for patients. The formation of gallstones was associated with genetic risk factors and metabolic abnormalities. Genome-wide association studies (GWAS) data of 1400 plasma metabolites (PMs) and 91 circulating inflammatory cytokines (CICs) were obtained from the GWAS catalog, while the GWAS data of calculus of gallbladder without cholecystitis and calculus of bile duct without cholangitis or cholecystitis were retrieved from the IEU OpenGWAS project. The causalities from PMs or CICs to asymptomatic bile duct or cholecyst calculus were explored by 2-sample Mendelian randomization (MR) analysis. Furthermore, the MR analyses were implemented from the identified PMs to CICs. Following the false discovery rate adjustment, the significant causalities, including 6 CICs and 5 PMs on asymptomatic biliary stone and 5 CICs and 48 PMs on asymptomatic gallstone, were identified. Fibroblast growth factor 19 (FGF-19) and aspartate/mannose ratio were the common protective factors of asymptomatic biliary tract calculus, while Monocyte chemoattractant protein 2 (CCL-2) may serve as a disease-promoting agent. Moreover, Bilirubin degradation product, C17H18N2O4 (1) levels, and Bilirubin (Z,Z)/etiocholanolone glucuronide ratio were associated with FGF-19 level, while aspartate/mannose ratio was related to TNF-related apoptosis-inducing ligand level. Based on MR analysis, we identified the multiple PMs and CICs, especially FGF-19, which may affect the formation of gallbladder and biliary tract calculus. Moreover, the partial CICs could be the downstream mediator of PMs related to asymptomatic gallbladder and biliary tract calculus. These results contributed to supporting previous studies and provided evidence for disease prevention or management.

The Inflammatory Load Index (IBI) and Body Roundness Index (BRI) were employed to evaluate the systemic inflammatory status and body fat. This study aims to elucidate the association between IBI and the prevalence of gallstones, as well as to analyze the mediating role of BRI in this association.

Data from the National Health and Nutrition Examination Survey (NHANES) (2017-2020) were utilized in our cross-sectional study. A total of 2598 participants aged ≥ 20 years were enrolled. The Boruta algorithm, a supervised classification feature selection method, is leveraged to identify the confounding variables most strongly associated with the prevalence of gallstones. Weighted multivariate logistic regression, restricted cubic splines (RCS), and subgroup analyses were employed to investigate the association between IBI and gallstones, assess the presence of a linear association, and evaluate the effect of IBI on gallstone risk across different populations. Finally, the mediating effect of BRI was examined.

In the fully adjusted model, when IBI was in the highest tertile, each unit increase in IBI (corresponding to an increase of 1 in the natural logarithm of IBI) was linked to a 110.8% higher prevalence of gallstones (OR = 2.108, 95% CI: 1.109-4.005; P = 0.028). The odds ratio for gallstones increased with higher IBI levels across unadjusted, partially adjusted, and fully adjusted models (P for trend < 0.05). This positive association was confirmed to be linear by the RCS curve (P for nonlinear = 0.887). Subgroup analysis indicated that the risk of gallstones was significantly elevated in individuals aged ≥ 60, females, and those with a Poverty-to-Income Ratio (PIR) ≥ 2 (P < 0.05). Mediation analysis revealed that IBI had a significant indirect effect on gallstone prevalence through BRI, with an effect size of 0.0129 (95% CI: 0.0121-0.0136; P < 0.001), and the mediation contributed to 33.24% of the total effect.

This study demonstrates a significant linear positive relation of IBI to gallstone prevalence. Furthermore, BRI mediates the effect of IBI on gallstone risk. These findings provide a more precise inflammatory marker for gallstone prevention and treatment.

Not applicable.

Cholesterol gallstone is a disease with high incidence and quality of life. This study aimed to investigate the function of exosome-derived miRNA in gallstone formation and its related molecular mechanism. Exosomes were extracted and isolated from patients with gallbladder stones and age- and gender-matched healthy controls, and exosomal miRNA expression was compared between the two groups. The function of exosomal miR-107 in gallstone formation was evaluated using a lithogenic fed-induced gallstone mouse model. We used a dual luciferase reporter assay to identify the miR-107 target gene. Expression of BSEP and CYP7A1 were detected using Western Blot and immunohistochemical staining to ascertain the role of miR-107 in bile acid transport and cholesterol synthesis. Bile acids, phospholipids, cholesterol and triglycerides were determined with the kit, and cholesterol saturation index was calculated. Liver cholesterol transport-related genes, phospholipid transport-related genes, liver bile salt transport-related genes, sodium-dependent bile acid transporters and organic solute transporters were detected by q-PCR. Exosomal miR-107 high expression was significant in people with gallstones. Inhibitor of miR-107 reduced lithogenic diet-induced gallstone formation in mice. MiR-107 directly inhibited caveolin-1 expression. Inhibition of caveolin-1 reduced the BSEP function. After treatment of miR-107 inhibitor, the expression of BSEP and CYP7A1 was significantly increased compared with gallbladder stones model, but the concentration of bile acid in gallbladder was significantly decreased. miR-107 altered biliary and liver lipid profiles and increased biliary cholesterol saturation index (CSI). Inhibited miR-107 promoted liver homeostasis-related cholesterol and the expression of bile acid transporters. This study revealed that exosome-derived miR-107 promoted gallstone progression by regulating the hepatobiliary cholesterol secretion pathway through targeting caveolin-1.

NXT629, a PPAR-alpha antagonist, exerts widespread effects in many diseases; however, its function and relevant mechanism in cholesterol gallstones (CG) remain largely unknown.

Male C57BL/6 J mice were fed a regular diet or lithogenic diet (LD), followed by treatment with intraperitoneal injection of NXT629. H&E staining was performed to analyze hepatic pathological changes, and Oil red O staining was conducted to detect lipid accumulation. Concentrations of total cholesterol (TC), triglyceride (TG), phospholipids (PL), total bile acids (TBA), and cholesterol saturation index (CSI) in both bile and serum were analyzed using commercially available kits. The mRNA expressions of ABCG5/8, CYP7A1, CYP7B1, PPAR-α, and ABCB11 in mouse liver tissues were measured by qRT-PCR assay. Overexpression of glycerol-3-phosphate acyltransferase mitochondrial (GPAM) was constructed to investigate the molecular mechanism of NXT629 in CG.

NXT629 could prevent the formation of cholesterol gallstones (CG) and improve lipid metabolic disorders in mice fed a lithogenic diet (LD). Treatment with NXT629 significantly reduced the levels of ABCG5, ABCG8, and ABCB11, while increasing the levels of CYP7A1 and CYP7B1 in the LD group. Additionally, NXT629 treatment downregulated GPAM expression in hepatic tissue from LD-fed mice. Overexpression of GPAM partially counteracted the beneficial effects of NXT629 on CG formation, lipid metabolic disorders, and lipid-related gene expressions.

NXT629 can inhibit CG formation, improve lipid metabolism disorders and cholesterol homeostasis by inhibiting GPAM expression, suggesting that NXT629 may serve as a potential therapeutic strategy for cholesterol stones prevention and treatment.

Cholesterol gallstones (CGS) still lack effective noninvasive treatment. The etiology of experimentally proven cholesterol stones remains underexplored. This cross-sectional study aims to comprehensively evaluate potential biomarkers in patients with gallstones and assess the effects of microbiome-targeted interventions in mice. Microbiome taxonomic profiling was conducted on 191 samples via V3-V4 16S rRNA sequencing. Next, 60 samples (30 age- and sex-matched CGS patients and 30 controls) were selected for metagenomic sequencing and fecal metabolite profiling via liquid chromatography-mass spectrometry. Microbiome and metabolite characterizations were performed to identify potential biomarkers for CGS. Eight-week-old male C57BL/6J mice were given a lithogenic diet for 8 weeks to promote gallstone development. The causal relationship was examined through monocolonization in antibiotics-treated mice. The effects of short-chain fatty acids such as sodium butyrate, sodium acetate (NaA), sodium propionate, and fructooligosaccharides (FOS) on lithogenic diet-induced gallstones were investigated in mice. Gut microbiota and metabolites exhibited distinct characteristics, and selected biomarkers demonstrated good diagnostic performance in distinguishing CGS patients from healthy controls. Multi-omics data indicated associations between CGS and pathways involving butanoate and propanoate metabolism, fatty acid biosynthesis and degradation pathways, taurine and hypotaurine metabolism, and glyoxylate and dicarboxylate metabolism. The incidence of gallstones was significantly higher in the Clostridium glycyrrhizinilyticum group compared to the control group in mice. The grade of experimental gallstones in control mice was significantly higher than in mice treated with NaA and FOS. FOS could completely inhibit the formation of gallstones in mice. This study characterized gut microbiome and metabolome alterations in CGS. C. glycyrrhizinilyticum contributed to gallstone formation in mice. Supplementing with FOS could serve as a potential approach for managing CGS by altering the composition and functionality of gut microbiota.

Epoxyeicosatrienoic acids (EETs) are closely associated with lipoprotein metabolism, and changes in lipid profiles potentially affect their levels and functions. Given the alterations in lipid metabolism after cholecystectomy, this study aimed to investigate the levels of four EET regioisomers (free and esterified) and lipid profiles in patients with cholelithiasis after laparoscopic cholecystectomy (LC) and explore correlations between these parameters.

This prospective study involved 40 patients with symptomatic cholelithiasis who underwent LC. Plasma EETs and serum total cholesterol, triglyceride, high-density lipoprotein (HDL), very low-density lipoprotein, low-density lipoprotein, and body mass index (BMI) values were determined preoperatively and after 6 months of LC.

After LC, triglyceride and very low-density lipoprotein levels increased while TC decreased. BMI values increased significantly after the operation. Despite plasma EET levels decreasing remarkably after surgery, this change did not reach statistical significance. A significant correlation was observed between preoperative levels of 8,9- and 11,12-EET and pre-and post-operative HDL. There was a significant negative correlation between the EET levels measured before and after surgery and the change in BMI values.

In this study, we observed significant changes in lipid profile 6 months after LC. While HDL, low-density lipoprotein, and EET levels showed a decreasing trend post-surgery, this change was not statistically significant. This trend and their significant correlations may indicate a complex relationship between HDL and EET metabolism. In addition, the negative correlation between EET levels and BMI changes highlights the need for further research to elucidate the metabolic impact and weight regulation of EETs after LC.

Gallbladder and biliary diseases (GABD) represent prevalent disorders of the digestive system.

Data on age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life years (DALYs) rate (ASDR) were extracted from the Global Burden of Disease (GBD) 2021 study. The estimated annual percentage change (EAPC) was utilized to quantify temporal trends in GABD. Age-period-cohort analysis was conducted to determine the effects attributable to age, period, and birth cohort. Additionally, we projected global trends to 2035.

Globally, GABD incident cases, mortality cases, and DALYs increased by 60.11%, 71.71%, and 56.90%, respectively. However, all corresponding age-standardized rates (ASRs) demonstrated overall downward trends with estimated annual percentage changes (EAPC) of -0.32 (-0.38 to -0.26), -0.95 (-1.08 to -0.83), and - 0.69 (-0.74 to -0.65), respectively. The number of incident cases was higher in females than in males across all age groups. The age effect indicated that older individuals had higher age-specific incidence and death rates. Both period and cohort effects showed declining risk across incidence and mortality. The ASIR and ASMR of GABD are projected to continue decreasing over the next 15 years.

GABD continue to pose a significant global public health challenge, particularly affecting women and the elderly population. Consequently, the implementation of effective interventions to mitigate the GABD burden is of paramount importance.

The neutrophil percentage to albumin ratio (NPAR) is an emerging, costimulatory indicator of inflammation that is associated with a variety of diseases, such as non-alcoholic fatty liver disease, liver fibrosis, stroke, and cardiovascular disease. However, the relationship between NPAR and gallstones (GS) has not yet been explored. Therefore, this study aimed to evaluate the association of the NPAR with the odds of GS and the age of patients at the time of their first GS surgery.

Participants were selected from the National Health and Nutrition Examination Survey (NHANES) in the United States, a nationally representative survey. Logistic regression analysis and dose-response curve were performed to analyze the relationship between NPAR and the prevalence of GS. Multiple linear regression analysis and dose-response curve were used to analyze the association between NPAR and the age of patients at the time of their first GS surgery. Subgroup analyses further explored the relationships between NPAR and age, sex, race, body mass index, hypertension, and diabetes.

In total, 7805 adults aged > 20 years were included in this study, of whom 838 had a history of GS. After adjusting for all potential confounders, each 1-unit increase in NPAR was found to be associated with a 4% increase in the prevalence of GS (odds ratio (OR): 1.04, 95% confidence interval (CI): 1.02, 1.07) and an advancement in the age of the patient at the time of the first GS surgery by 0.35 years (β = - 0.35, 95% CI: - 0.68, - 0.02). Dose-response curves further confirmed that NPAR was positively associated with the prevalence of GS and negatively associated with the age of patients at the time of their first GS surgery. The results of the subgroup analyses suggested that after adjusting for all potential confounders, the positive association of NPAR with the prevalence of GS was more pronounced in the 40-59-year-old (OR: 1.07, 95% CI: 1.02, 1.12), male (OR: 1.07, 95% CI: 1.02, 1.12), non-Hispanic Black (OR: 1.06, 95% CI: 1.01, 1.12), non-hypertensive (OR: 1.06, 95% CI: 1.02, 1.10), and non-diabetic populations (OR=: 1.05, 95% CI: 1.02, 1.08).

The higher the NPAR, the higher the prevalence of GS, and the earlier the age of the patient at the time of the first GS surgery. Due to the nature of cross-sectional study, it is not possible to determine a causal relationship between them.

Gallstones are a prevalent health issue, with established risk factors such as diet body mass index (BMI) and physical activity. However, the role of Life's Essential 8 (LE8), a composite measure of health behaviors and biological markers, in predicting gallstone risk remains unclear. This study aims to examine the association between LE8 scores and gallstone prevalence in a U.S. adult population.

A cross-sectional analysis was conducted on 2836 adults. LE8 scores were categorized into tertiles, and multivariable logistic regression models assessed the relationship between LE8 and gallstones, with additional nonlinear assessment using restricted cubic spline analysis.

Gallstones prevalence was 10.37%, decreasing with higher LE8 scores. The multivariable analysis showed participants in higher LE8 tertiles had significantly lower gallstone risks compared to the lowest tertile. The spline analysis confirmed a significant nonlinear inverse association between LE8 and gallstone risk.

Higher LE8 scores correlate with a lower prevalence of gallstones, suggesting the potential of LE8 as a predictor of gallstone risk. This emphasizes the value of promoting LE8 components in public health initiatives to reduce gallstone prevalence and medical burden.

Cholelithiasis areis a common digestive system disorder, with cholesterol gallstones being the most prevalent type. Gallstones lead to many severe complications, posing a significant burden on global healthcare systems. Many studies have shown associations between biliary microbiota, gallbladder immune microenvironment, and gallstone formation. However, the specific immune mechanisms underlying the cholesterol gallstone formation have not been fully elucidated.

In this study, gallbladderand bile samples from 8 asymptomatic patients with cholelithiasis undergoing cholecystectomy and 11 healthy liver transplant donors were collected for tissue transcriptome sequencing and differential analysis. Male C57BL/6J mice were fed a normal or lithogenic diet for 6 weeks. Starting from the third week, lipopolysaccharide (LPS) or specific regulators were injected intraperitoneally once a week for a total of 3 times. Enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, Western blot, immunohistochemistry, and immunofluorescence were employed for quantitative, qualitative or localization analysis of LPS, neutrophil extracellular traps (NETs), inflammatory factors, proteins, and mRNAs using samples collected from mice.

In patients with cholelithiasis, the gallbladder mechanical barrier is impaired, resulting in an immune-activated state. LPS induces damage to the gallbladder mucosal mechanical barrier through the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) signaling pathway. Furthermore, it stimulates the continuous production of NETs through the TLR4/Phosphoinositide 3-kinase (PI3K)/Protein kinase B (Akt) signaling pathway, aggravating the formation of gallstones.

With the biliary dysbiosis, excessive LPS can invade the submucosa of the gallbladder, leading to chronic inflammation that recruits neutrophils to form NETs, which are ultimately expelled into bile, thereby promoting the formation of gallstones.

This article delved into the comprehensive study by Jiang et al, which meticulously examined the bidirectional relationships among gallstone disease, non-alcoholic fatty liver disease, and kidney stone disease through a multicenter study, systematic review, and meta-analysis. The study provides significant evidence supporting these associations, offering valuable insights into the etiology and potential prevention strategies for these interconnected conditions. The clinical significance of these bidirectional relationships is profound, as they underscore the importance of recognizing these conditions not only as isolated diseases but as part of a complex network that can influence each other. These results highlight the critical need for thorough screening and personalized prevention strategies for individuals with these interconnected conditions. Explicit implications for prevention strategies and early screening practices are crucial, as they can lead to early detection and intervention, significantly altering disease progression and outcomes. Furthermore, identifying potential therapeutic targets within these shared pathways may enhance treatment efficacy and patient outcomes, making this research highly relevant to clinical practice. By comprehending the common pathophysiological mechanisms and applying specific interventions, healthcare professionals can greatly enhance patient care and lessen the impact of these widespread diseases on global health.

Both gallstone disease and sleep disorders are important public health problems. Few studies to date have investigated the associations between sleep and gallstone disease in humans. This study aimed to assess whether sleep factors (sleep time, sleep amounts, trouble sleeping) were associated with gallstone disease in the United States adults.

This was a population-based cross-sectional study of US adults, which included data of participants aged over 20 years from the National Health and Nutrition Examination Survey (NHANES) gathered between 2017 and March 2020. The assessment of gallstone disease and sleep factors was based on self-reported data. We used sample-weighted logistic regression and restricted cubic spline models to explore the associations between sleep factors and gallstone disease. Subgroup analyses were conducted to assess the interaction between trouble sleeping and interacting factors.

The prevalence of gallstone disease was 11% among the 9,210 adult participants. Going to bed late on weekdays (OR, 1.41; 95% CI, 1.15 to 1.74) and weekends (OR, 1.43; 95% CI, 1.14 to 1.78), and short sleep duration on weekdays (OR, 1.29; 95% CI, 1.00 to 1.68) were factors associated with increased risk of gallstone disease, and we detected dose-response associations with the restricted cubic spline model (RCS) models, after adjusting for confounders. Presenting trouble sleeping was associated with increased risk of gallstone disease (OR, 1.52; 95% CI, 1.03 to 2.23) and the association was influenced by the presence of thyroid disease (P for interaction = 0.037).

Our study results indicate that going to bed late, short sleep duration, and trouble sleeping were associated with increased risk of gallstone disease in a nationally representative sample of adults in the US.

People are exposed to metals in various ways during their daily lives. However, the association between metal exposure and gallstones remains unclear.

To investigate the relationship between serum elemental concentrations and the risk of gallstones.

Participants (n = 4204) were drawn from the Henan Rural Cohort. Gallstone diagnosis was based on abdominal ultrasound reports during follow-up. Baseline serum elemental concentrations were measured using inductively coupled plasma mass spectrometry. The relationship between serum elemental levels and gallstones was evaluated using robust Poisson regression, restricted cubic spline (RCS), quantile g-computation (Qgcomp), grouped weighted quantile sum (GWQS) and Bayesian kernel machine regression (BKMR).

121 individuals were diagnosed with gallstone (incidence rate of 2.88 %). In robust Poisson regression, after adjusting for confounding factors, the highest quartile of arsenic concentration compared to the lowest quartile had a 1.90 times higher relative risk (RR) [95 % confidence interval (CI): 1.05, 3.44]. Conversely, the highest quartile of zinc concentration compared to the lowest quartile had a 0.50 times lower RR (95 % CI: 0.28, 0.89). RCS showed an approximately "S"-shaped nonlinear relationship between serum arsenic levels and gallstones, with increasing arsenic concentration leading to a higher risk of gallstones; however, the risk plateaued when arsenic concentration exceeded 0.62 μg/L. Both the Qgcomp and GWQS indicated that arsenic plays a significant role in increasing the risk of gallstones, whereas zinc plays a significant role in reducing the risk of gallstones. BKMR showed that raising arsenic exposure from the 25th to the 75th percentile increased the risk of gallstones, while raising serum zinc concentration reduced it.

Higher serum arsenic concentration increases the risk of gallstones, whereas higher zinc concentration may reduce the risk. Effective prevention of gallstones may require further reduction of arsenic exposure and appropriate increases in zinc intake.

High-sensitivity C-reactive protein (hs-CRP), a classical indicator of inflammation, holds significant clinical value in various diseases. The relationship between hs-CRP and gallstones, however, remains poorly studied at present. The relationship between hs-CRP and gallstones will be investigated in this study.

Data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) were analyzed, focusing on participants aged 20 years and older who provided complete hs-CRP and gallstone information. Due to the skewed distribution of hs-CRP, the data were log-transformed [Log (hs-CRP)] to achieve normalization. Logistic regression analysis, subgroup analysis, and smoothed fitted curves were applied to determine the relationship between Log (hs-CRP) and the presence of gallstones.

The study included 4,484 participants with an average Log (hs-CRP) of 1.18 ± 0.74. The prevalence of gallstones was 11.15%, increasing with higher Log (hs-CRP) levels (quartile 1: 8.31%; quartile 2: 8.76%; quartile 3: 11.98%; quartile 4: 16.36%; p < 0.0001). Adjusting for all covariates in Model 3, each 10-fold increase in hs-CRP [corresponding to a one-unit increase in log10 (hs-CRP)] corresponded to a 29% increased odds of gallstones prevalence [1.29 (1.12-1.49)]. The smoothed fitted curve showed a positive linear relationship between Log (hs-CRP) and gallstones prevalence. The results of subgroup analyses exhibited a more pronounced positive correlation in the 20-40 age group [1.70 (1.33, 2.16)], compared to those aged 40-60 years [1.22 (1.01, 1.48)], and 60-80 years [1.14 (0.98, 1.34)].

Higher Log (hs-CRP) levels are linked to a greater prevalence of gallstones. We still need to carry out further large prospective research to explore the causal relationship of this association.

Nonalcoholic fatty liver disease (NAFLD) and gallstones are generally seen together, and many of the risk factors for fatty liver and gallstones are common and similar. Therefore, this study aims to investigate the relationship between NAFLD and gallstones.

This case-control study was conducted in patients referred to Imam Khomeini and Golestan hospitals of Ahvaz University of Medical Sciences in 2023, whose ultrasound showed fatty liver. Patients who were diagnosed with NAFLD by ultrasound were considered as the case group, and patients who did not have diagnostic findings of fatty liver in ultrasound were considered as the control group. Finally, the information recorded in the checklists was statistically analyzed using SPSS version 26 (SPSS Inc.).

Three hundred patients were included in our study, 150 as cases and 150 as controls. There was no significant difference between the groups in terms of gender and age (gender P-value: 0.817/age P-value: 0.102). A statistically significant relationship was found between obesity, diabetes mellitus (DM), the presence of gallstones, and NAFLD (weight p-value < 0.001/DM p-value < 0.001/gallstones P-value: 0.03). In addition, based on binary logistic regression analysis, the presence of gallstones increases the odds of NAFLD by 2.33 times (P-value: 0.035). Furthermore, having DM and increasing each BMI unit increases the odds of NAFLD by 16 times and 30%, respectively (BMI p-value < 0.001/DM p-value < 0.001).

Based on the results of our study, gallstones are an important risk factor for NAFLD. The possible mechanisms are the existence of common risk factors between gallstones and NAFLD and the reduction of motility and flow of bile in the bile ducts with the presence of gallstones.

To explore the pathogenesis of different subtypes of gallstones in high-altitude populations from a molecular perspective.

We collected bile samples from 20 cholesterol gallstone disease (CGD) patients and 20 pigment gallstone disease (PGD) patients. Proteomics analysis was performed by LC/MS DIA, while metabolomics analysis was performed by UPLC- Q-TOF/MS.

We identified 154 up-regulated and 196 down-regulated differentially expressed proteins, which were significantly enriched in neurodegenerative diseases, energy metabolism, amino acid metabolism etc. In metabolomics analysis, 20 up-regulated and 63 down-regulated differentially expressed metabolites were identified, and they were significantly enriched in vitamin B6 metabolism. Three pathways of integrated proteomics and metabolomics were significantly enriched: porphyrin and chlorophyll metabolism, riboflavin metabolism and aminoacyl-tRNA biosynthesis. Remarkably, 7 differentially expressed proteins and metabolites showed excellent predictive performance and were selected as potential biomarkers.

The findings of our metabolomics and proteomics analyses help to elucidate the underlying mechanisms of gallstone formation in high-altitude populations.

Questions remain about the association among cholecystectomy, cardiovascular disease, all-cause and cause-specific mortality. We performed a systematic review and meta-analysis to clarify these associations.

PubMed, Web of Science, Embase, and Cochrane Library databases were searched up to February 2024. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a DerSimonian-Laird random effects model.

We screened 16,595 articles and included 14 studies. No significant association was found between cholecystectomy and cardiovascular disease (CVD), with RR being 1.03 (95% CI [0.77-1.37], p = 0.848, I 2 = 99.6%), even in results with high heterogenous studies excluded (RR 1.20, 95% CI [0.97-1.49], p = 0.095, I 2 = 77.7%). Same result was proved in its subtype, coronary heart disease (RR 1.06, 95% CI [0.84-1.33], p = 0.633, I2 = 96.6%). Cholecystectomy increased CVD risk compared with healthy controls without gallstones (RR 1.19, 95% CI [1.05-1.35], p = 0.007, I 2 = 83.3%) and lowered CVD risk compared with gallstone carriers (RR 0.62, 95% CI [0.57-0.67], p < 0.001, I 2 = 82.1%). As for mortality, increase in the risk for all-cause (RR 1.17, 95% CI [1.03-1.34], p = 0.020, I 2 = 51.6%) and cardiovascular (RR 1.24, 95% CI [1.06-1.47], p = 0.009, I 2 = 20.7%) mortality, but not for cancer mortality (RR 1.18, 95% CI [0.95-1.47], p = 0.131, I 2 = 0.0%), were observed after cholecystectomy.

Cholecystectomy may not be associated with the overall development of CVD, as well as CHD. Cholecystectomized patients showed increased CVD risk compared with healthy controls without gallstones, but decreased CVD risk compared with gallstone patients. Increased risk for all-cause and cardiovascular, but not cancer mortality was observed following cholecystectomy.

The aim of the research was to look into the connection between the occurrence of gallstones in adult US citizens and lipid accumulation products (LAP).

We conducted a cross-sectional study of 3,582 U.S. adults with relevant indicators collected from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) database. Multifactorial logistic regression was used to investigate the linear relationship between LAP and gallstone incidence, while smoothed curve fitting was used to describe the nonlinear relationship, and subgroup and interaction analyses were used to evaluate the potential differences between groups.

Among the 3582 participants aged ≥ 20 years included, there was a positive association between LAP and gallstones. Following adjustments for all covariates, the likelihood of getting gallstones rose by 29% for each unit rise in log2-LAP (OR = 1.29, 95% CI: 1.13‒1.49). Compared to those in the lowest tertile, those in the highest LAP tertile had a significantly higher risk of developing gallstones (OR = 1.97, 95% CI: 1.31‒2.95). Subgroup analyses indicated that the association between LAP and gallstones was not affected by the stratification of the variables examined.

Gallstones and LAP exhibited a positive association in our investigation, indicating that LAP may be utilized as a clinical indicator to determine the occurrence of gallstones.

Gallstones represent a prevalent health issue globally, resulting in significant annual healthcare costs. While tobacco exposure is recognized for its association with numerous diseases, its correlation with gallstones remains contentious. Serum cotinine, a metabolite of nicotine, serves as a widely utilized indicator for assessing tobacco exposure. Crucially, no research has yet examined the association between serum cotinine levels and the gallstones.

This study is designed as a cross-sectional analysis, utilizing data from the NHANES public database. The relationship between serum cotinine levels and gallstones was analyzed using multinomial logistic regression models and smooth curve fitting. Subgroup analyses and interaction tests were performed to examine the potential contributions of different populations and covariates to the findings.

A total of 5,856 participants were included in this study. After adjusting for relevant covariates, the multiple logistic regression model results indicated that for each unit increase in serum cotinine concentration above 0.29 ng/mL, there was a 29% increase in the prevalence of gallstones. Furthermore, smooth curve fitting analysis revealed a positive correlation between these variables. These findings underscore the impact of tobacco exposure on gallstone prevalence.

This study demonstrates a positive correlation between tobacco exposure, as measured by serum cotinine levels, and the prevalence of gallstones, thus adding to the body of existing research on this relationship.

Metabolic abnormalities in the body increase the risk of gallbladder stones and their complications, which brings a great economic and social burden. The relationship between different types and amounts of metabolic abnormalities and gallstone risk in different sexes is poorly documented and controversial.

Based on the baseline survey data of the Chinese Multi-Ethnic Cohort (CMEC) study, 4,075 Chinese adults aged 30-79 years with complete abdominal ultrasound results and metabolic index data. Logistic regression model was used to evaluate the correlation between five metabolic abnormalities and gallstones, and to explore the gender difference.

The detection rate of gallbladder stones was found to be 7.0%, with a higher rate in women (8.6%) than in men (4.1%). Logistic results showed adjustment odds ratio (ORs) and 95% confidence interval (95% CI) of dysglycemia + hypertension + central obesity in 3 metabolic combinations was 4.459 (1.653, 12.029). The four metabolic combinations, dysglycemia + dyslipidemia + hypertension + central obesity, dysglycemia + dyslipidemia + hypertension + abnormal blood uric acid and dysglycemia + dyslipidemia + central obesity + abnormal blood uric acid adjusted OR and 95%CI were 3.342 (1.459, 7.659), 5.439 (1.555, 19.018) and 2.971 (1.187, 7.435), respectively. Gender-stratified analysis found that "any three or more metabolic abnormalities and their components were associated with gallstone risk, more significantly in women.

Different types and amounts of five metabolic abnormalities were associated with the risk of gallstone development, and the differences were more significant in women than men.

Majority of dietary intake in United States adults comes from ultraprocessed foods (UPFs), which have been linked to several adverse health outcomes. Gallstone disease is highly prevalent and constitutes a significant burden to the United States health system but remains understudied.

This study aimed to investigate the association between UPF consumption and incident gallstone disease risk.

In this analysis, 44,149 males in the Health Professionals' Follow-up Study (HPFS: 1986-2022), 71,145 females in the Nurses' Health Study (NHS: 1986-2021), and 90,932 females in the NHS II (1991-2021) were prospectively followed. Dietary intake was quadrennially assessed with semiquantitative food frequency questionnaires and used to identify UPFs. The primary outcome was defined as cholecystectomy. Cox proportional hazards model was used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).

Baseline median age was 54 y in HPFS, 53 y in NHS, and 36 y in NHS II. We identified 32,374 incident gallstone disease cases over 5,077,059 person-years. Participants in the highest UPF quintile had a higher incidence of gallstone disease than those in the lowest quintile (aHR: 1.29; 95% CI: 1.24, 1.36; P < 0.001). Incremental risk of incident gallstone disease was 2.8% per daily serving (95% CI: 2.4%, 3.2%; P < 0.001). This risk was driven by sugar-sweetened beverages and artificially sweetened beverages on UPF subgroup analyses. The proportion of risk mediated by obesity was 12.8% (95% CI: 7.7%, 20.5%; P < 0.001) in HPFS, 14.3% (95% CI: 10.4%, 19.4%; P < 0.001) in NHS, and 39.4% (95% CI: 31.2%, 48.1%; P < 0.001) in NHS II. The partial population attributable risk was estimated at 15.9% (95% CI: 13.4%, 18.3%).

UPF consumption is associated with a higher risk of gallstone disease, particularly consumption of sugar-sweetened beverages and artificially sweetened beverages. A substantial proportion of this risk is potentially mediated by obesity in younger females.

Gallstone disease affects ≥40 million people in the USA and accounts for health costs of ≥$4 billion a year. Risk factors such as obesity and metabolic syndrome are well established. However, data are limited on relevant metabolomic alterations that could offer mechanistic and predictive insights into gallstone disease. This study prospectively identifies and externally validates circulating prediagnostic metabolites associated with incident gallstone disease.

Female participants in Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II) who were free of known gallstones (N=9960) were prospectively followed up after baseline metabolomic profiling with liquid chromatography-tandem mass spectrometry. Multivariable logistic regression and enrichment analysis were used to identify metabolites and metabolite groups associated with incident gallstone disease at PFDR<0.05. Findings were validated in 1866 female participants in the Women's Health Initiative and a comparative analysis was performed with 2178 male participants in the Health Professionals Follow-up Study.

After multivariate adjustment for lifestyle and putative risk factors, we identified and externally validated 17 metabolites associated with incident gallstone disease in women-nine triacylglycerols (TAGs) and diacylglycerols (DAGs) were positively associated, while eight plasmalogens and cholesterol ester (CE) were negatively associated. Enrichment analysis in male and female cohorts revealed positive class associations with DAGs, TAGs (≤56 carbon atoms and ≤3 double bonds) and de novo TAG biosynthesis pathways, as well as inverse associations with CEs.

This study highlights several metabolites (TAGs, DAGs, plasmalogens and CE) that could be implicated in the aetiopathogenesis of gallstone disease and serve as clinically relevant markers.

This study used data from the National Health and Nutrition Examination Survey (NHANES) to investigate the relationship between the triglyceride-glucose (TyG) index and gallstones. We evaluated the data collected between 2017 to 2020. To evaluate the relationship between TyG index and gallstones, logistic regression analysis, basic characteristics of participants, subgroup analysis, and smooth curve fitting were utilized. The study included 3870 participants over the age of 20 years, 403 of whom reported gallstones, with a prevalence rate of 10.4%. After adjusting for all confounding factors, the risk of gallstones increased by 41% for each unit increase in the TyG index (OR 1.41, 95% CI 1.07, 1.86). The smooth curve fitting also showed a positive correlation between the TyG index and gallstones. Subgroup analysis revealed a significant positive relationship between the TyG index and the risk of gallstones in those aged < 50 years, women, individuals with total cholesterol levels > 200 mg/dL, individuals with body mass index (BMI) > 25, and individuals without diabetes. The risk of gallstones is positively correlated with a higher TyG index. Thus, the TyG index can be used as a predictor of the risk of gallstones.

The association between nonobese/lean nonalcoholic fatty liver disease (NAFLD) and gallstone formation remains unclear. We aimed to assess whether NAFLD is an independent risk factor for gallstones, even in nonobese or lean individuals.

We analyzed 265 353 asymptomatic adults who underwent abdominal ultrasonography. The risk of gallstone was assessed on the basis of obesity and NAFLD status.

The overall prevalence rates of NAFLD and gallstones were 27.1% and 2.6%, respectively. The prevalence rates of NAFLD among the 195 204 nonobese and 136 194 lean participants were 14.7% and 7.4%, respectively. Individuals with NAFLD had a significantly increased risk of gallstones (adjusted odds ratio [OR], 1.23; 95% confidence interval [CI], 1.14-1.32). Moreover, NAFLD significantly increased the risk of gallstone (adjusted OR, 1.29; 95% CI, 1.17-1.41) among nonobese individuals. Lean individuals with NAFLD also exhibited a significantly increased risk of gallstones (adjusted OR, 1.20; 95% CI, 1.03-1.40). Furthermore, these findings remained consistent even in nonobese and lean individuals without insulin resistance.

Nonobese/lean NAFLD is an independent risk factor for gallstone formation, suggesting its role in gallstone pathogenesis, regardless of obesity status. Therefore, when hepatic steatosis is detected on abdominal ultrasonography, a more thorough evaluation of the gallstones may be necessary, even in nonobese or lean individuals.

The incidence of gallbladder diseases is as high as 20%, but whether gallbladder diseases contribute to hepatic disorders remains unknown.

Here, we established an animal model of gallbladder dysfunction and assessed the role of a diseased gallbladder in cholestasis-induced hepatic fibrosis (CIHF).

Mice with smooth muscle-specific deletion of Mypt1, the gene encoding the main regulatory subunit of myosin light chain phosphatase (myosin phosphatase target subunit 1 [MYPT1]), had apparent dysfunction of gallbladder motility. This dysfunction was evidenced by abnormal contractile responses, namely, inhibited cholecystokinin 8-mediated contraction and nitric oxide-resistant relaxation. As a consequence, the gallbladder displayed impaired bile filling and biliary tract dilation comparable to the alterations in CIHF. Interestingly, the mutant animals also displayed CIHF features, including necrotic loci by the age of 1 month and subsequently exhibited progressive fibrosis and hyperplastic/dilated bile ducts. This pathological progression was similar to the phenotypes of the animal model with bile duct ligation and patients with CIHF. The characteristic biomarker of CIHF, serum alkaline phosphatase activity, was also elevated in the mice. Moreover, we observed that the myosin phosphatase target subunit 1 protein level was able to be regulated by several reagents, including lipopolysaccharide, exemplifying the risk factors for gallbladder dysfunction and hence CIHF.

We propose that gallbladder dysfunction caused by myosin phosphatase target subunit 1 ablation is sufficient to induce CIHF in mice, resulting in impairment of the bile transport system.

Cholesterol stones affect a certain subpopulation of children. Concerns have been raised on the impact of gallbladder surgery on the growth of children and adolescents.

To study the population characteristics, clinical features, treatment, and prognosis of gallstones in children.

The clinical data of 44 children with gallstones admitted to The First Affiliated Hospital of Naval Medical University from August 2009 to August 2021 were collected, the children were followed up by telephone to monitor their prognoses. The follow-up ended in August 2023. The shortest follow-up time was 2 years and 6 months, whereas the longest was 13 years and 11 months. The population characteristics, general clinical characteristics, and treatments were retrospectively analyzed. The children were divided according to whether they underwent surgical gallbladder removal into an operation group (n = 28) and a non-operation group (n = 16), The effects of surgical gallbladder resection on the growth and development of children were analyzed.

The male-female ratio in the population was 6:5 and 84.09% of the children had onset in adolescence. Furthermore, 29.55% of the children were overweight or obese. The study identified 26 cases with metabolic abnormalities, 9 with hemolytic anemia, and 4 with choledochal cyst. Of the population, 68.18% had recurrent symptomatic cholecystolithiasis. Surgical treatment accounted for 63.64%, with laparoscopic cholecystectomy accounting for 71.43% of surgical treatment. No significant differences were observed in symptoms and complications between the surgery and non-surgery groups. Furthermore, no significant differences were found between the two groups in the attainment of genetic height target and the rightward shift of height curve during follow-up.

The sex characteristics of gallstones in children were not observed. Most gallstones occurred in adolescents and rarely in young children. A considerable proportion of children have inborn causes, which are often concurrent with metabolic abnormalities and hemolytic anemia. Most children had recurrent symptomatic gallstones. Surgical treatment, especially laparoscopic cholecystectomy, is still the main treatment for gallstones in children. Surgical treatment did not affect the growth and development of children who underwent gallstone removal.

A total of 300 research participants-200 consecutive patients diagnosed with dyslipidemia (100 statin (+), treated for at least five years, and 100 statin (-)) and 100 healthy controls-were included in this observational study. The aim of the study was to deliver insights into the relationship between the long-term use of statins for dyslipidemia and gallstone disease (GSD), as well as insights into the background particularities of the gut microbiota. All study participants underwent clinical examination, laboratory workups, stool microbiology/stool 16S r RNA, next-generation sequencing, and abdominal ultrasound/CT exams. Results: The research participants presented with similarities related to age, gender, and location. Patients displayed comparable heredity for GSs, metabolic issues, and related co-morbidities. Gut dysbiosis (DB) was present in 54% of the statin (-) patients vs. 35% of the statin (+) patients (p = 0.0070). GSs were present in 14% of patients in the statin (-) group vs. 5% of patients in the statin (+) group (p = 0.0304). Severe dysbiosis, with a significant reduction in biodiversity, an increase in LPS (+) bacteria, and a notable decrease in mucin-degrading bacteria, mucosa-protective bacteria, and butyrate-producing bacteria were observed in the statin (-) group. Strong positive correlations between GSD and diabetes/impaired glucose tolerance (r = 0.3368, p = 0.0006), obesity (r = 0.3923, p < 0.0001), nonalcoholic fatty liver disease (r = 0.3219, p = 0.0011), and DB (r = 0.7343, p < 0.0001), as well as significant negative correlations between GSD and alcohol use (r = -0.2305, p = 0.0211), were observed. The multiple regression equation demonstrated that only DB (95% CI: 0.3163 to 0.5670; p < 0.0001) and obesity (95% CI: 0.01431 to 0.2578; p = 0.0289) were independent risk factors predicting GSD in the group of patients treated with statins. Conclusion: The long-term use of statins in dyslipidemic patients was associated with a low risk of developing GSs. The gut microbiota associated with a long-term use of statins in dyslipidemic patients was characterized by a low risk of developing an imbalance of various functional bacteria and alterations in the metabolic microbiota. DB and obesity were found to be independent risk factors predicting GSD in statin (+) patients.

Exposure to a mixture of environmental chemicals may cause gallstone, but the evidence remains equivocal. The current study aims to investigate the association between phthalate metabolites and gallstones, and to explore their mediators.

Data from the National Health and Nutrition Examination Survey 2017-2018 on U.S. adults (≥20 years) were analyzed to explore the association between phthalate metabolites and gallstones by employed survey-weighted logistic regression, restricted cubic spline (RCS), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR). Mediation analyses examined the role of oxidative stress markers, inflammatory markers, metabolic syndrome, body composition, diabetes, and insulin.

The current study included 1,384 participants, representing 200.6 million U.S. adults. Our results indicated a significant association between phthalate metabolites, particularly high molecular weight metabolites such as Di(2-ethylhexyl) phthalate (DEHP) and 1,2-Cyclohexane dicarboxylic acid diisononyl ester (DINCH), and gallstones. Furthermore, mediation analyses indicated that phthalate metabolites may play a role in the development of gallstones by influencing insulin secretion. Subgroup analyses did not reveal significant interaction.

The association between exposure to phthalates and the occurrence of gallstones, potentially mediated by hyperinsulinemia from a nationally representative epidemiological perspective. These insights contribute to a better understanding of the potential health implications of plasticizers, emphasizing the need for proactive management measures.

Gallstone disease is a common health problem worldwide. The role of the gut microbiota in gallstone pathogenesis remains obscure. Our aim was to evaluate the association and crosstalk between gut microbiota, gut metabolomic, and metabolic parameters in cholesterol gallstone patients, pigmented gallstone patients, and controls.

We collected stool samples from healthy individuals and patients with gallstones in our hospital from March 2019 to February 2021. 16s rRNA sequencing was performed, followed by differential abundance analyses. Measurement of bile acids and short-chain fatty acids was conducted via targeted metabolomics.

Thirty healthy individuals and 20 gallstone patients were recruited. The intergroup difference of microbial composition was significant between control and gallstone patients. The control group had more abundant Faecalibacterium , Prevotella 9 , and Bacteroides plebeius DSM 17135 . The cholesterol stones group had higher Desulfovibrionaceae and Bacteroides uniformis than the other two groups, while the pigment stone group had more abundant Escherichia-Shigella . In the analysis of metabolites, only n-butyric acid had a significantly higher concentration in the controls than in the gallstone group ( p < 0.01). The level of 3α-hydroxy-12 ketolithocholic acid, deoxycholic acid, and cholic acid showed no intergroup differences but was correlated to the serum cholesterol level and bacterial richness and evenness.

Our study revealed the key taxa that can discriminate between individuals with or without gallstones. We also identified metabolites that are possibly associated with metabolic parameter and bacterial diversity. However, the correlation of the metabolites to certain clusters of bacteria should be analyzed in a larger cohort.