1.Gallstones, cholecystectomy, and cancer risk: an observational and Mendelian randomization study.
Yuanyue ZHU ; Linhui SHEN ; Yanan HUO ; Qin WAN ; Yingfen QIN ; Ruying HU ; Lixin SHI ; Qing SU ; Xuefeng YU ; Li YAN ; Guijun QIN ; Xulei TANG ; Gang CHEN ; Yu XU ; Tiange WANG ; Zhiyun ZHAO ; Zhengnan GAO ; Guixia WANG ; Feixia SHEN ; Xuejiang GU ; Zuojie LUO ; Li CHEN ; Qiang LI ; Zhen YE ; Yinfei ZHANG ; Chao LIU ; Youmin WANG ; Shengli WU ; Tao YANG ; Huacong DENG ; Lulu CHEN ; Tianshu ZENG ; Jiajun ZHAO ; Yiming MU ; Weiqing WANG ; Guang NING ; Jieli LU ; Min XU ; Yufang BI ; Weiguo HU
Frontiers of Medicine 2025;19(1):79-89
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
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Mendelian Randomization Analysis
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Gallstones/complications*
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Female
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Male
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Cholecystectomy/statistics & numerical data*
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Middle Aged
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Risk Factors
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Aged
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Adult
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Neoplasms/etiology*
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Stomach Neoplasms/epidemiology*
2.Investigations into the Mechanism of Phycocyanin in Modulating the Wip1/p53 Pathway to Induce Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells
Yun-Xi JIA ; Da HUO ; Chao YAO ; Min LI ; Fu-Ling LIU ; Hong YUAN ; Hui-Ting XUE ; Rui-Ping HU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(5):741-752
Hepatocellular carcinoma(HCC)is difficult to detect in its early stages and current treatment methods are associated with significant side effects and a high risk of developing drug resistance.This study aims to investigate the effect of phycocyanin(PC)on the apoptosis of human HCC HepG2 cells and its potential mechanism.HepG2 cells were treated with PC at concentrations of 0.1,0.25,0.5,1,2.5,5,and 10 μg/mL for 12 h,and with 10 μg/mL PC and 2.5 μmol/L Wip1 inhibitor(Wip1i)alone or in combination for 12 and 24 h,respectively.Cell proliferation levels were assessed using the CCK-8 cell proliferation-toxicity assay kit.Apoptosis levels were measured by Annexin V-FITC/Propidium Iodide double staining combined with flow cytometry.TMT(Tandem Mass Tag)proteomics quantitative technol-ogy was applied to analyze differential protein expression.Western blotting was used to detect the expres-sion levels of Wip1,p53,and phosphorylated-p53(Ser15)proteins.The CCK-8 assay revealed that PC effectively inhibited HepG2 cell proliferation in a concentration-dependent manner,with a half-maximal inhibitory concentration(IC50)of 19.37 μg/mL.Flow cytometry results showed that PC significantly in-duced apoptosis,with an apoptosis rate of 30.40%.Quantitative proteomics analysis indicated that PC induced activation of the p53 pathway.The CCK-8 assay showed that Wip1i enhanced the cytotoxic effect of PC on HepG2 cells.Western blotting confirmed that PC inhibited Wip1 expression,induced p53 pro-tein phosphorylation,and promoted the expression of total p53 protein.Additionally,Wip1i further en-hanced PC-mediated activation of the p53 pathway,increasing the expression of p53 and pP53(S15).In conclusion,PC may induce apoptosis by inhibiting the activity of the p53 negative regulator Wip1,thereby promoting apoptosis through the Wip1/p53 pathway.
3.Correlation between serum 25-hydroxyvitamin D levels and 24-h urinary calcium excretion and hypercalciuria in Chinese adults
Li SHEN ; Hao ZHANG ; Qi LU ; Shanshan LI ; Chao GAO ; Yazhao MEI ; Hua YUE ; Xiangtian YU ; Qi YAO ; Yanan HUO ; Yuhong ZENG ; Yin JIANG ; Zhongjian XIE ; Aijun CHAO ; Xiaolan JIN ; Li MAO ; Zhenlin ZHANG
Chinese Journal of Internal Medicine 2025;64(4):318-324
Objective:To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and 24-h urinary calcium excretion (24-h UCaE) and hypercalciuria in Chinese adults.Methods:This cross-sectional study was conducted from March 2022 to March 2023 in nine cities in China and included 1 239 residents. Demographic characteristics were collected through questionnaires and physical examinations, fasting blood samples were assessed for bone metabolism indicators, and 24-h urine samples were used to determine the 24-h UCaE. Multiple linear regression analysis was used to explore the relationship between serum 25(OH)D and 24-h UCaE and bone metabolism indexes. The relationship between serum 25(OH)D and hypercalciuria was analyzed using a multiple logistic regression model combined with restricted cubic spline modeling.Results:The mean participant age was (47.9±18.1) years, of which 453 (36.6%) were male. The percentages of vitamin D sufficiency, insufficiency, and deficiency were 7.6% (94/1 239), 29.0% (359/1 239), and 63.4% (786/1 239), respectively. The multiple linear regression model showed that after adjusting for the covariates the 24-h UCaE gradually increased with higher levels of 25(OH)D ( P overall <0.001, P nonlinear <0.001). The logistic regression analysis revealed that compared with the vitamin D deficient group, the OR for the prevalence of hypercalciuria in the vitamin D sufficient and vitamin D insufficient groups were 3.290 (95% CI 1.745 to 6.202) and 3.742 (95% CI 2.458 to 5.697), respectively. The results of the restricted cubic spline modeling showed a positive nonlinear relationship between 25(OH)D and the prevalence of hypercalciuria ( P overall <0.001, P nonlinear <0.001). The prevalence of hypercalciuria increased when 25(OH)D was >17.00 μg/L and peaked at 26.71 μg/L, after which there was a decreasing trend in the prevalence of hypercalciuria with increasing 25(OH)D. Conclusion:Associations between serum 25(OH)D levels and urinary calcium excretion and the prevalence of hypercalciuria were observed in the Chinese adult population.
4.Erratum: Author correction to "Generation of αGal-enhanced bifunctional tumor vaccine" Acta Pharm Sin B 12 (2022) 3177-3186.
Jian HE ; Yu HUO ; Zhikun ZHANG ; Yiqun LUO ; Xiuli LIU ; Qiaoying CHEN ; Pan WU ; Wei SHI ; Tao WU ; Chao TANG ; Huixue WANG ; Lan LI ; Xiyu LIU ; Yong HUANG ; Yongxiang ZHAO ; Lu GAN ; Bing WANG ; Liping ZHONG
Acta Pharmaceutica Sinica B 2025;15(2):1207-1207
[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].
5.Clinical efficacy of robot-assisted spinal endoscopic lumbar interbody fusion for the treatment of sin-gle-segment lumbar spinal stenosis
Chao CHEN ; Rongrui HU ; Zhiming HUO
Chinese Journal of Spine and Spinal Cord 2025;35(4):359-365
Objectives:To investigate the clinical efficacy of robot-assisted(RA)unilateral biportal endoscopic lumbar interbody fusion(UBE-LIF)in the treatment of single-level lumbar spinal stenosis(LSS).Methods:A retrospective analysis was conducted on the clinical data of 90 patients with LSS admitted to the Spine De-partment of Foshan Hospital of Traditional Chinese Medicine from August 2023 to February 2024.The pa-tients were divided into an observation group(42 patients,treated with RA-UBE-LIF)and a control group(48 patients,treated with UBE-LIF).The patients' baseline information and clinical data were collected,including age,gender,duration of illness,and lesion segments.The number of fluoroscopic exposures,operative time,intraoperative blood loss,postoperative drainage volume,length of hospital stay,screw placement accuracy(based on the Gertzbein criteria),and the occurrence of complications were compared between the two groups.The visual analogue scale(VAS)score and Oswestry disability index(ODI)were used to quantitatively assess the improvement in back and leg pain and the recovery of lumbar function in patients before surgery and at 1 week,3 months,and 6 months postoperatively.Results:All the patients successfully completed the surgery and were followed up for a period ranging from 6 to 12 months.Compared with the control group,the obser-vation group had significantly fewer fluoroscopic exposures(4.40±0.83 vs 9.92±1.62),less intraoperative blood loss(90.76±13.27mL vs 121.21±16.75mL),postoperative drainage volume(75.93±14.43mL vs 93.02±17.04mL),and length of hospital stay(4.43±1.52d vs 7.19±1.79d)(all P<0.05).There was no significant difference in oper-ative time between the two groups(118.24±8.91min vs 120.67±10.43min)(P>0.05).The accuracy rate of RA percutaneous screw placement in the observation group was 97.62%,which was significantly different from that of the control group(89.58%)(P<0.05).The complication rate in the observation group was 2.38%,which was not significantly different from that of the control group(6.25%)(P>0.05).The VAS scores for back and leg pain and ODI of both groups at each postoperative time point were significantly lower than those at the previ-ous time point(P<0.05).There were no significant differences between the two groups preoperatively(P>0.05),but the improvements in VAS scores and ODI at each postoperative time point(1 week,3 months,6 months)were better in the observation group compared to the control group(P<0.05).Conclusions:Orthopedic RA-UBE-LIF for the treatment of LSS is accurate and safe,which has satisfactory therapeutic effects.
6.Clinical efficacy of robot-assisted spinal endoscopic lumbar interbody fusion for the treatment of sin-gle-segment lumbar spinal stenosis
Chao CHEN ; Rongrui HU ; Zhiming HUO
Chinese Journal of Spine and Spinal Cord 2025;35(4):359-365
Objectives:To investigate the clinical efficacy of robot-assisted(RA)unilateral biportal endoscopic lumbar interbody fusion(UBE-LIF)in the treatment of single-level lumbar spinal stenosis(LSS).Methods:A retrospective analysis was conducted on the clinical data of 90 patients with LSS admitted to the Spine De-partment of Foshan Hospital of Traditional Chinese Medicine from August 2023 to February 2024.The pa-tients were divided into an observation group(42 patients,treated with RA-UBE-LIF)and a control group(48 patients,treated with UBE-LIF).The patients' baseline information and clinical data were collected,including age,gender,duration of illness,and lesion segments.The number of fluoroscopic exposures,operative time,intraoperative blood loss,postoperative drainage volume,length of hospital stay,screw placement accuracy(based on the Gertzbein criteria),and the occurrence of complications were compared between the two groups.The visual analogue scale(VAS)score and Oswestry disability index(ODI)were used to quantitatively assess the improvement in back and leg pain and the recovery of lumbar function in patients before surgery and at 1 week,3 months,and 6 months postoperatively.Results:All the patients successfully completed the surgery and were followed up for a period ranging from 6 to 12 months.Compared with the control group,the obser-vation group had significantly fewer fluoroscopic exposures(4.40±0.83 vs 9.92±1.62),less intraoperative blood loss(90.76±13.27mL vs 121.21±16.75mL),postoperative drainage volume(75.93±14.43mL vs 93.02±17.04mL),and length of hospital stay(4.43±1.52d vs 7.19±1.79d)(all P<0.05).There was no significant difference in oper-ative time between the two groups(118.24±8.91min vs 120.67±10.43min)(P>0.05).The accuracy rate of RA percutaneous screw placement in the observation group was 97.62%,which was significantly different from that of the control group(89.58%)(P<0.05).The complication rate in the observation group was 2.38%,which was not significantly different from that of the control group(6.25%)(P>0.05).The VAS scores for back and leg pain and ODI of both groups at each postoperative time point were significantly lower than those at the previ-ous time point(P<0.05).There were no significant differences between the two groups preoperatively(P>0.05),but the improvements in VAS scores and ODI at each postoperative time point(1 week,3 months,6 months)were better in the observation group compared to the control group(P<0.05).Conclusions:Orthopedic RA-UBE-LIF for the treatment of LSS is accurate and safe,which has satisfactory therapeutic effects.
7.Investigations into the Mechanism of Phycocyanin in Modulating the Wip1/p53 Pathway to Induce Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells
Yun-Xi JIA ; Da HUO ; Chao YAO ; Min LI ; Fu-Ling LIU ; Hong YUAN ; Hui-Ting XUE ; Rui-Ping HU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(5):741-752
Hepatocellular carcinoma(HCC)is difficult to detect in its early stages and current treatment methods are associated with significant side effects and a high risk of developing drug resistance.This study aims to investigate the effect of phycocyanin(PC)on the apoptosis of human HCC HepG2 cells and its potential mechanism.HepG2 cells were treated with PC at concentrations of 0.1,0.25,0.5,1,2.5,5,and 10 μg/mL for 12 h,and with 10 μg/mL PC and 2.5 μmol/L Wip1 inhibitor(Wip1i)alone or in combination for 12 and 24 h,respectively.Cell proliferation levels were assessed using the CCK-8 cell proliferation-toxicity assay kit.Apoptosis levels were measured by Annexin V-FITC/Propidium Iodide double staining combined with flow cytometry.TMT(Tandem Mass Tag)proteomics quantitative technol-ogy was applied to analyze differential protein expression.Western blotting was used to detect the expres-sion levels of Wip1,p53,and phosphorylated-p53(Ser15)proteins.The CCK-8 assay revealed that PC effectively inhibited HepG2 cell proliferation in a concentration-dependent manner,with a half-maximal inhibitory concentration(IC50)of 19.37 μg/mL.Flow cytometry results showed that PC significantly in-duced apoptosis,with an apoptosis rate of 30.40%.Quantitative proteomics analysis indicated that PC induced activation of the p53 pathway.The CCK-8 assay showed that Wip1i enhanced the cytotoxic effect of PC on HepG2 cells.Western blotting confirmed that PC inhibited Wip1 expression,induced p53 pro-tein phosphorylation,and promoted the expression of total p53 protein.Additionally,Wip1i further en-hanced PC-mediated activation of the p53 pathway,increasing the expression of p53 and pP53(S15).In conclusion,PC may induce apoptosis by inhibiting the activity of the p53 negative regulator Wip1,thereby promoting apoptosis through the Wip1/p53 pathway.
8.Correlation between serum 25-hydroxyvitamin D levels and 24-h urinary calcium excretion and hypercalciuria in Chinese adults
Li SHEN ; Hao ZHANG ; Qi LU ; Shanshan LI ; Chao GAO ; Yazhao MEI ; Hua YUE ; Xiangtian YU ; Qi YAO ; Yanan HUO ; Yuhong ZENG ; Yin JIANG ; Zhongjian XIE ; Aijun CHAO ; Xiaolan JIN ; Li MAO ; Zhenlin ZHANG
Chinese Journal of Internal Medicine 2025;64(4):318-324
Objective:To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and 24-h urinary calcium excretion (24-h UCaE) and hypercalciuria in Chinese adults.Methods:This cross-sectional study was conducted from March 2022 to March 2023 in nine cities in China and included 1 239 residents. Demographic characteristics were collected through questionnaires and physical examinations, fasting blood samples were assessed for bone metabolism indicators, and 24-h urine samples were used to determine the 24-h UCaE. Multiple linear regression analysis was used to explore the relationship between serum 25(OH)D and 24-h UCaE and bone metabolism indexes. The relationship between serum 25(OH)D and hypercalciuria was analyzed using a multiple logistic regression model combined with restricted cubic spline modeling.Results:The mean participant age was (47.9±18.1) years, of which 453 (36.6%) were male. The percentages of vitamin D sufficiency, insufficiency, and deficiency were 7.6% (94/1 239), 29.0% (359/1 239), and 63.4% (786/1 239), respectively. The multiple linear regression model showed that after adjusting for the covariates the 24-h UCaE gradually increased with higher levels of 25(OH)D ( P overall <0.001, P nonlinear <0.001). The logistic regression analysis revealed that compared with the vitamin D deficient group, the OR for the prevalence of hypercalciuria in the vitamin D sufficient and vitamin D insufficient groups were 3.290 (95% CI 1.745 to 6.202) and 3.742 (95% CI 2.458 to 5.697), respectively. The results of the restricted cubic spline modeling showed a positive nonlinear relationship between 25(OH)D and the prevalence of hypercalciuria ( P overall <0.001, P nonlinear <0.001). The prevalence of hypercalciuria increased when 25(OH)D was >17.00 μg/L and peaked at 26.71 μg/L, after which there was a decreasing trend in the prevalence of hypercalciuria with increasing 25(OH)D. Conclusion:Associations between serum 25(OH)D levels and urinary calcium excretion and the prevalence of hypercalciuria were observed in the Chinese adult population.
9.Novel 18F-FES PET/CT in Non-invasive Functional Diagnosis of Delayed Lung Metastasis Presented with Horner Syndrome in a Metastatic Breast Cancer Patient
Ru YAO ; Zhixin HAO ; Yang QU ; Chao ZHANG ; Weijia LI ; Jie LANG ; Bo PAN ; Yidong ZHOU ; Qiang SUN ; Li HUO
Medical Journal of Peking Union Medical College Hospital 2024;15(3):702-707
Hormonal receptor positive human epidermal receptor 2 negative (HR+/HER2-) is the commonest molecular subtype of breast cancer (BC). Patients with HR+/HER2- BC may manifest clinically a late recurrence whose BC metastasizes 10-15 years post-operatively. We report one case who presented with pulmonary mass in upper lobe of lung and Horner syndrome 16 years after BC surgery. FDG PET/CT suggested pulmonary malignancy but could not differentiate between primary or metastatic cancer when invasive biopsy was quite risky. Novel 18F-FES PET/CT facilitated the non-invasive functional diagnosis of estrogen-receptor positive (ER+) pulmonary metastasis of BC, and the patient experienced partial response (PR) after CDK4/6 inhibitor and aromatase inhibitor as endocrine therapy. This article reviews the diagnosis and treatment process of this case, to provide guidance for non-invasive global evaluation of ER status among metastatic HR+/HER2- BC patients with 18F-FES PET/CT.
10.Endovascular treatment for symptomatic non-acute long-segment occlusion of the internal carotid artery: comparison with drug therapy
Yue ZHU ; Chao HOU ; Shuxian HUO ; Qin YIN ; Xianjun HUANG ; Wen SUN ; Guodong XIAO ; Yong YANG ; Hongbing CHEN ; Min LI ; Mingyang DU ; Ruidong YE
International Journal of Cerebrovascular Diseases 2024;32(8):576-584
Objective:To investigate the clinical outcome of endovascular treatment vs. drug treatment in patients with symptomatic non-acute long-segment occlusion of the internal carotid artery. Methods:Based on prospective cohort registration research data, patients with symptomatic non-acute long-segment occlusion of internal carotid artery were retrospectively included. They were divided into a drug treatment group and an endovascular treatment group according to the actual treatment received. The latter was further divided into a successful recanalization group and an unsuccessful recanalization group. The endpoint events included ipsilateral ischemic stroke, any stroke, and all-cause death. Multivariate logistic regression analysis was used to compare the endpoint events between groups during the perioprocedural period (within 30 days), and multivariate Cox proportional hazards model was use to compare the endpoint events between the groups during the long-term follow-up. Results:A total of 684 patients were included, of which 570 (83.33%) were male, median aged 63 years (interquartile range, 56-70 years). Three hundred and fifty-three patients (51.6%) received drug treatment; 331 (48.4%) received endovascular treatment, of which 161 (48.6%) had successful recanalization. The median follow-up time was 1 223 days (interquartile range, 646.5-2 082 days), with 109 patients (15.9%) experiencing stroke recurrence events (including 87 ipsilateral ischemic stroke) and 78 (11.4%) experiencing all-cause mortality. The risk of any stroke during the perioprocedural period in the successful recanalization group was significantly higher than that in the drug treatment group (odds ratio 3.679, 95% confidence interval 1.038-13.036; P=0.044), but the risk of ipsilateral ischemic stroke recurrence (risk ratio 0.347, 95% confidence interval 0.152-0.791; P=0.012) and all-cause mortality (risk ratio 0.239, 95% confidence interval 0.093-0.618; P=0.003) during the long-term follow-up were significantly lower than those in the drug treatment group. Conclusions:In patients with symptomatic non-acute long-segment occlusion of the internal carotid artery, endovascular treatment can increase the risk of stroke recurrence within 30 days, but successful recanalization can reduce the risks of long-term ipsilateral ischemic stroke recurrence and all-cause mortality.

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