BACKGROUND: People are exposed to metals in various ways during their daily lives. However, the association between metal exposure and gallstones remains unclear.
OBJECTIVE: To investigate the relationship between serum elemental concentrations and the risk of gallstones.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.

UNASSIGNED: Prior research suggests polyunsaturated fatty acids (PUFA) may prevent gallstones, but evidence on saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) is limited. This study aims to explore the associations between fatty acids and gallstones using a large sample of American population and Mendelian randomization (MR) methods.
UNASSIGNED: The cross-sectional study involved 6,629 participants from the National Health and Nutrition Examination Survey (NHANES) 2017-2020. Logistic regression and restricted cubic spline (RCS) analysis were conducted after stratifying by gender subgroups. Two-sample MR analysis was used to explore the causal relationship between fatty acids and gallstones without confounding factors.
UNASSIGNED: In females, higher SFA intake was positively associated with gallstone risk, while higher intake of n-3 and n-6 PUFA was negatively associated. No significant associations were found in males. No nonlinear correlations were found in any group by RCS analysis. MR analysis indicated that SFA, n-3, and n-6 PUFA could reduce gallstone risk.
UNASSIGNED: The influence of dietary fatty acid composition on gallstone development differs by gender, providing insights into dietary prevention and treatment of gallstones.

BACKGROUND: The chronic digestive condition gallstones is quite common around the world, the development of which is closely related to oxidative stress, inflammatory response and abnormalities of lipid metabolism. In the last few years, as a novel biomarker of lipid metabolism, the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has garnered significant interest. However, its relationship with gallstones has not been studied yet.
METHODS: 3,772 people, all under 50, were included in this study, and their full data came from the National Health and Nutrition Examination Survey (NHANES) database for the years 2017-2020. Information on gallstones was obtained through self-reported questionnaires. Smoothed curve fitting multifactorial logistic regression was utilized to evaluate the connection of NHHR with gallstone formation incidence. Subsequently, subgroup analysis and interaction tests were applied. Finally, to create a prediction model, logistic regression and feature screening by last absolute shrinkage and selection operator (LASSO) were used. The resulting model was displayed using a nomogram.
RESULTS: In multivariate logistic regression that accounted for all factors, there was a 77% increase in the likelihood of gallstones for every unit rise in lnNHHR (OR 1.77 [CI 1.11-2.83]). Following NHHR stratification, the Q4 NHHR level was substantially more linked to the risk of gallstones than the Q1 level (OR 1.86 [CI 1.04-3.32]). This correlation was stronger in women, people under 35, smokers, abstainers from alcohol, non-Hispanic White people, those with excessively high cholesterol, people with COPD, and people without diabetes. After feature screening, a predictive model and visualized nomogram for gallstones were constructed with an AUC of 0.785 (CI 0.745-0.819), which was assessed by DCA to be clinically important.
CONCLUSIONS: In the group of people ≤ 50 years of age, elevated NHHR levels were substantially linked to a higher incidence of gallstones. This correlation was stronger in several specific groups such as females, under 35 years of age, smokers, and so on. Predictive models constructed using the NHHR have potential clinical value in assessing gallstone formation.

BACKGROUND: The incidence of gallstones is high in Qinghai Province. However, the molecular mechanisms underlying the development of gallstones remain unclear.
METHODS: In this study, we collected urine samples from 30 patients with gallstones and 30 healthy controls. The urine samples were analysed using multi-omics platforms. Proteomics analysis was conducted using data-independent acquisition, whereas metabolomics analysis was performed using liquid chromatography-mass spectrometry (LC-MS).
RESULTS: Among the patients with gallstones, we identified 49 down-regulated and 185 up-regulated differentially expressed proteins as well as 195 up-regulated and 189 down-regulated differentially expressed metabolites. Six pathways were significantly enriched: glycosaminoglycan degradation, arginine and proline metabolism, histidine metabolism, pantothenate and coenzyme A biosynthesis, drug metabolism-other enzymes, and the pentose phosphate pathway. Notably, 10 differentially expressed proteins and metabolites showed excellent predictive performance and were selected as potential biomarkers.
CONCLUSIONS: The findings of our metabolomics and proteomics analyses provide new insights into novel biomarkers for patients with cholelithiasis in high-altitude areas.

UNASSIGNED: Morphologic changes in the gallbladder and gallstones are common in cirrhotic patients, but their associations with outcomes of cirrhotic patients are unclear.
UNASSIGNED: We retrospectively enrolled 206 cirrhotic patients and measured their gallbladder length and width, gallbladder wall thickness, presence of gallstones, and gallstones\' length and width in axial contrast-enhanced computed tomography (CT) images. X-tile software was utilized to calculate the optimal cutoff values of these parameters for evaluating survival and hepatic decompensation events in the cirrhosis group. Their associations with survival were explored by Cox regression analyses and Kaplan-Meier curve analyses. Their associations with hepatic decompensation events were evaluated by competing risk analyses and Nelson-Aalen cumulative risk curve analyses where death was a competing event.
UNASSIGNED: Cirrhotic patients with gallbladder length < 72 mm had a significantly higher cumulative survival rate than those with a length of ≥ 72 mm (P = 0.049 by log-rank test), but gallbladder width, gallbladder wall thickness, presence of gallstones, and gallstones\' length and width were not significantly associated with survival (P = 0.10, P = 0.14, P = 0.97, P = 0.73, and P = 0.73 by log-rank tests, respectively). Cirrhotic patients with gallbladder wall thickness < 3.4 mm had a significantly lower cumulative rate of hepatic decompensation events than those with a wall thickness of ≥ 3.4 mm (P = 0.02 by Gray\'s test), but gallbladder length and width, presence of gallstones, and gallstones\' length and width were not significantly associated with hepatic decompensation events (P = 0.15, P = 0.15, P = 0.54, P = 0.76, and P = 0.54 by Gray\'s tests, respectively).
UNASSIGNED: Changes in gallbladder length and gallbladder wall thickness, rather than gallstone parameters, may be in parallel with the long-term outcomes of cirrhotic patients.

BACKGROUND: Gallstone, a common digestive disorder, poses a significant public health burden. Concurrently, depression is acknowledged as a health risk. However, limited information exists on depression\'s impact on gallstone formation. This study investigates depression\'s causal effect on gallstone risk.
METHODS: Using National Health and Nutrition Examination Survey (NHANES) data, we conducted an observational study. The severity of depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Multivariable logistic regression and subgroup analyses explored the correlation between depression and gallstone risk. Mendelian Randomization (MR) analysis, leveraging Genome-Wide Association Studies (GWAS) data, reduced observational bias and elucidated causality. Inverse Variance Weighting (IVW) was the primary method, with sensitivity analyses validating results.
RESULTS: In the observational study (7707 participants), gallstone risk was elevated in mild (OR: 1.58, 95 % CI 1.31-1.90, P < 0.001), moderate (OR: 2.07, 95 % CI 1.59-2.67, P < 0.001), and severe (OR: 2.41, 95 % CI 1.70-3.34, P < 0.001) depression groups (P for trend <0.001). Subgroup analyses revealed a stronger association in those under 65, females, non-Hispanic Black, individuals with obesity, smokers, and those with college education or higher. Mendelian Randomization indicated a causal link between genetically predicted depression and higher cholelithiasis risk (OR: 2.06, 95 % CI 1.34-3.17, P = 0.001), validated through sensitivity analyses and multi-cohort verification.
CONCLUSIONS: Depression independently increases gallstone risk, particularly in those under 65, females, non-Hispanic Black, individuals with obesity, smokers, and those with college education or higher. Further validation is needed through multi-center, prospective cohort studies.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are novel inflammatory indicators that can be used to predict the severity and prognosis of various diseases. We categorize acute pancreatitis by etiology into acute biliary pancreatitis (ABP) and hypertriglyceridemia-induced acute pancreatitis (HTGP).
OBJECTIVE: To investigate the clinical significance of NLR and PLR in assessing persistent organ failure (POF) in HTGP and ABP.
METHODS: A total of 1450 patients diagnosed with acute pancreatitis (AP) for the first time at Shanxi Bethune Hospital between January 2012 and January 2023 were enrolled. The patients were categorized into two groups according to the etiology of AP: ABP in 530 patients and HTGP in 241 patients. We collected and compared the clinical data of the patients, including NLR, PLR, and AP prognostic scoring systems, within 48 h of hospital admission.
RESULTS: The NLR (9.1 vs 6.9, P < 0.001) and PLR (203.1 vs 160.5, P < 0.001) were significantly higher in the ABP group than in the HTGP group. In the HTGP group, both NLR and PLR were significantly increased in patients with severe AP and those with a SOFA score ≥ 3. Likewise, in the ABP group, NLR and PLR were significantly elevated in patients with severe AP, modified computed tomography severity index score ≥ 4, Japanese Severity Score ≥ 3, and modified Marshall score ≥ 2. Moreover, NLR and PLR showed predictive value for the development of POF in both the ABP and HTGP groups.
CONCLUSIONS: NLR and PLR vary between ABP and HTGP, are strongly associated with AP prognostic scoring systems, and have predictive potential for the occurrence of POF in both ABP and HTGP.

BACKGROUND: Studies have indicated that monocyte-to-high-density lipoprotein cholesterol ratio (MHR) can be a reliable indicator of various diseases. However, the association between MHR and gallstone prevalence remains unclear. Therefore, this study aimed to explore any potential association between MHR and gallstone prevalence.
METHODS: This study used data from the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020. MHR was calculated as the monocyte count ratio to high-density lipoprotein cholesterol levels. Multiple logistic regression models, Cochran-Armitage trend test, and subgroup analyses were used to examine the association between MHR and gallstones.
RESULTS: This study included 5907 participants, of whom 636 (10.77%) were gallstone formers. The study participants had a mean age of 50.78 ± 17.33 years. After accounting for multiple covariables, the multiple logistic regression model showed a positive linear association between MHR and gallstone odds. The subgroup analyses and interaction testing results revealed that the association between MHR and gallstones was statistically different across strata, including sex, smoking, asthma, and hypertension.
CONCLUSIONS: Gallstone prevalence positively associated with elevated MHR, indicating that MHR can be employed as a clinical indicator to assess gallstone prevalence.

UNASSIGNED:  Gallstone disease is one of the most common gastrointestinal disorders. Despite extensive research exploring the risk factors associated with gallstones, the association between depressive symptoms and gallstones remains inadequately understood. This study aimed to assess the association between depressive symptoms and the prevalence of gallstones among adults in the United States.
UNASSIGNED: In this study, a cross-sectional design utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2017 to 2020. The assessment of depressive symptoms was conducted through the utilization of the Patient Health Questionnaire-9 (PHQ-9), which assigns total scores ranging from 0 to 27. Participants with PHQ-9 scores equal to or exceeding 10 were categorized as having clinically relevant depressive symptoms. Multivariable adjusted logistic regression and subgroup analysis were used to assess the association between depressive symptoms and gallstone prevalence.
UNASSIGNED: A total of 7,797 participants aged 20 years or older were enrolled in this study, of whom 835 had a self-reported history of gallstones. After multiple adjustments, each one-point increase in PHQ-9 scores was associated with a 5 % increase in the risk of gallstones (odds ratio [OR], 1.05; 95 % confidence interval [CI], 1.03, 1.07, P < 0.001). Compared to individuals with PHQ-9 scores < 10, participants with PHQ-9 total scores ≥ 10 exhibited a 79 % higher risk of gallstones (OR = 1.79, 95 % CI: 1.43, 2.23, P < 0.001).
UNASSIGNED: Depressive symptoms were associated with an elevated prevalence of gallstones. However, it is important to note that further validation through prospective cohort studies is warranted to confirm this finding.

UNASSIGNED: Gallstone disease (GS) is an important risk factor for Gallbladder cancer (GBC). However, the mechanisms of the progression of GS to GBC remain unclear. Long non-coding RNA (lncRNA), modulates DNA/RNA/proteins at epigenetic, pre-transcriptional, transcriptional and posttranscriptional levels, and plays a potential therapeutic role in various diseases. This study aims to identify lncRNAs that have a potential impact on GS-promoted GBC progression.
UNASSIGNED: Six GBC patients without GS, six normal gallbladder tissues, nine gallstones and nine GBC patients with GS were admitted to our hospital. The next-generation RNA-sequencing was performed to analyze differentially expressed (DE) lncRNA and messenger RNA (mRNA) in four groups. Then overlapping and specific molecular signatures were analyzed. We identified 29 co-DEGs and 500 co-DElncRNAs related to gallstone or GBC. The intersection and concatenation of co-DEGs and co-DElncRNA functionally involved in focal adhesion, Transcriptional misregulation in cancers, Protein digestion and absorption, and ECM-receptor interaction signaling pathways may contribute to the development of gallbladder cancer. Further exploration is necessary for early diagnosis and the potential treatment of GBC. FXYD2, MPZL1 and PAH were observed in both co-DEGs and co-DElncRNA and validated by qRT-PCR.
UNASSIGNED: Our data identified a series of DEGs and DElncRNAs, which were involved in the progression of GBC and GS-related metabolism pathways. Compared to GBC, the GS profile was more similar to para-tumor tissues in transcriptome level and lower risk of cancer. Further exploration is necessary from GBC patients with different periods of follow-up gallstone.