This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective To study the changes and significance of plasma atrial natriuretic peptide (ANP),endothehn-1 (ET-1),von Willebrand factor (vWF) levels in newborns with persistent pulmonary hypertension (PPHN) after the treatment of sildenafil.Methods Sixty-six cases with PPHN group and 40 cases with non-PPHN (control group) were enrolled.PPHN group was in the treatment of sildenafil.Collected the blood when before the treatment of sildenafil and 3,7 d after treatment,respectively.Arterial blood gas were done and pulmonary arterial systolic pressure (PASP) was measured before treatment and 3,7 d after treatment,and by the same time recording pulse oxygen saturation (SpO2).Plasma ANP,ET-1,vWF levels were measured by ELISA method.Results The levels of PASP,SpO2 arterial partial pressure of oxygen (PaO2),arterial partial pressure of carbon dioxide (PaCO2) and plasma ANP,ET-1,vWF in PPHN group before treatment [(66.5 ± 13.4)mm Hg (1 mm Hg =0.133 kPa),0.726 ±0.531,(46.3 ±7.2)mm Hg,(59.2 ± 7.4) mm Hg,(272.6 ± 20.3)ng/L,(221.3 ± 24.3) ng/L,(142.5 ± 20.3)％] compared with controlgroup [(25.0±6.2) mm Hg,0.896 ± 0.767,(88.3 ±7.6) mm Hg,(41.1 ±6.1) mm Hg,(68.4 ± 7.9) ng/L,(39.8 ± 6.5) ng/L,(95.3 ± 18.5)％] were statistically significant(P ＜ 0.05).Their levels in PPHN group 3 dafter treatment[(48.3 ± 3.2) mm Hg,0.841 ± 0.416,(73.6 ± 9.3)mm Hg,(50.5 ± 7.2) mm Hg,(102.6 ±20.3) ng/L,(79.6 ± 15.2) ng/L,(103.6 ± 14.1)％] were significantly improved,there was significantdifference compared with before treatment and control group(P ＜ 0.05).Their levels in PPHN group 7 d aftertreatment [(25.2 ± 3.6) mm Hg,0.882 ± 0.724,(85.4 ± 7.4) mm Hg,(40.2 ± 6.4) mm Hg,(64.4 ± 3.6)ng/L,(37.3 ± 5.4)ng/L,(92.9 ± 11.7)％] were significantly improved,there was significant difference compared with 3 d after treatment (P ＜ 0.05),the difference was no statistically significant compared with control group (P＞ 0.05).Linear correlation analysis showed that ANP,ET-1,vWF and PASP,PaCO2 were significantly positively correlated (P ＜ 0.01),ANP,ET-1,vWF and SpO2,PaO2 were significantly negatively correlated (P＜ 0.01).On the basis of cardiac ultrasound monitoring PASP,ANP evaluation of the efficacy of sildenafil sensitivity was 82.2％,specificity was 83.4％ ;ET-1 was 86.4％ and 87.6％; vWF was 85.1％ and 84.7％.Conclusion ANP,ET-1,vWF may play an important role in the mechanism of the treatment of PPHN by sildenafil,and could be used as an objective index to evaluate the effect of sildenafil on PPHN.