1.Metabolic profiling of lung cancer cells with acquired resistance to sotorasib
Peichen ZOU ; Hongyu LIU ; AIHEMAITI·AYINAZHAER ; Liang ZHU ; Yabin TANG ; Huimin LEI
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(2):138-149
Objective·To explore the metabolic profiling and metabolic reprogramming patterns of lung cancer cells with acquired resistance to sotorasib,a specific inhibitor to KRAS.Methods·The H2122 and H358 lung cancer cell models with acquired resistance to sotorasib(H2122-SR and H358-SR cells)were established and validated by CCK-8 assay.Ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS)was employed to acquire the metabolic profiling of the resistant lung cancer cells and their homologous parental cells.Untargeted metabolomics studies and metabolic characterizations were conducted with multi-dimensional methods,including principal component analysis(PCA)and partial least squares-discriminant analysis(PLS-DA),to identify differential metabolites associated with acquired resistance to sotorasib.Then these differential metabolites were subjected to pathway enrichment analysis.Heatmap analysis was used to compare the changes in metabolites in major differential metabolic pathways between the resistant and parental cells.Results·The cell models of H2122 and H358 with acquired resistance were successfully constructed,with half-maximal inhibitory concentrations(IC50)of sotorasib being 50 times higher than those of the parental cells.Besides,the metabolic profiling was significantly different between the resistant and parental cells.A total of 48 differential metabolites were identified between H2122-SR and H2122 cells.The top 10 differential metabolites,ranked by VIP values,were uridine,xanthylic acid,indole-3-carboxylic acid,nicotinic acid,xanthosine,xanthine,N-methylnicotinamide,hypoxanthine,trigonelline,and galactonic acid.Between H358-SR and H358 cells,a total of 79 differential metabolites were identified.The top 10 differential metabolites,ranked by VIP values,were glutathione,xanthosine,2-ketoglutaric acid,carboxyethyl lysine,thymidine,purine,riboflavin,3-indoleacrylic acid,indole-3-pyruvic acid,and dihydrouracil.The differential metabolites in the two lung cancer cell lines mainly participated in purine metabolism and glycolysis/gluconeogenesis,and purine metabolism was the most significantly altered metabolic pathway.Heatmap analysis showed that many metabolites in the purine metabolism were elevated in the sotorasib-resistant cells.Conclusion·The lung cancer cells with acquired resistance to sotorasib show enhanced purine metabolism.
2.Metabolic profiling of lung cancer cells with acquired resistance to sotorasib
Peichen ZOU ; Hongyu LIU ; AIHEMAITI·AYINAZHAER ; Liang ZHU ; Yabin TANG ; Huimin LEI
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(2):138-149
Objective·To explore the metabolic profiling and metabolic reprogramming patterns of lung cancer cells with acquired resistance to sotorasib,a specific inhibitor to KRAS.Methods·The H2122 and H358 lung cancer cell models with acquired resistance to sotorasib(H2122-SR and H358-SR cells)were established and validated by CCK-8 assay.Ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS)was employed to acquire the metabolic profiling of the resistant lung cancer cells and their homologous parental cells.Untargeted metabolomics studies and metabolic characterizations were conducted with multi-dimensional methods,including principal component analysis(PCA)and partial least squares-discriminant analysis(PLS-DA),to identify differential metabolites associated with acquired resistance to sotorasib.Then these differential metabolites were subjected to pathway enrichment analysis.Heatmap analysis was used to compare the changes in metabolites in major differential metabolic pathways between the resistant and parental cells.Results·The cell models of H2122 and H358 with acquired resistance were successfully constructed,with half-maximal inhibitory concentrations(IC50)of sotorasib being 50 times higher than those of the parental cells.Besides,the metabolic profiling was significantly different between the resistant and parental cells.A total of 48 differential metabolites were identified between H2122-SR and H2122 cells.The top 10 differential metabolites,ranked by VIP values,were uridine,xanthylic acid,indole-3-carboxylic acid,nicotinic acid,xanthosine,xanthine,N-methylnicotinamide,hypoxanthine,trigonelline,and galactonic acid.Between H358-SR and H358 cells,a total of 79 differential metabolites were identified.The top 10 differential metabolites,ranked by VIP values,were glutathione,xanthosine,2-ketoglutaric acid,carboxyethyl lysine,thymidine,purine,riboflavin,3-indoleacrylic acid,indole-3-pyruvic acid,and dihydrouracil.The differential metabolites in the two lung cancer cell lines mainly participated in purine metabolism and glycolysis/gluconeogenesis,and purine metabolism was the most significantly altered metabolic pathway.Heatmap analysis showed that many metabolites in the purine metabolism were elevated in the sotorasib-resistant cells.Conclusion·The lung cancer cells with acquired resistance to sotorasib show enhanced purine metabolism.
3.Study on the value of 24 h urinary aldosterone measurement by liquid chromatography-tandem mass spectrometry in the subtype classification of primary aldosteronism
Hongyu PU ; Lu TAN ; Jia TANG ; Tao CHEN ; Mingxi ZOU ; Yuchun ZHU ; Sikui SHEN ; Haoming TIAN ; Yan REN
Chinese Journal of Endocrinology and Metabolism 2025;41(5):387-393
Objective:To investigate the value of 24 h urinary aldosterone(24 h-UAC) measurement by liquid chromatography-tandem mass spectrometry(LC-MS/MS) in the subtype classification of primary aldosteronism(PA).Methods:A total of 86 patients with PA, including 51 with unilateral primary aldosteronism(UPA) and 35 with bilateral primary aldosteronism(BPA), were enrolled in the Department of Endocrinology and Metabolism at West China Hospital between January 2018 and December 2022. Plasma aldosterone concentration(PAC), plasma renin concentration(PRC) and 24 h-UAC were measured by LC-MS/MS. 24-hour urinary electrolytes and 24-hour urinary creatinine(24 h-UCR) were also measured. The diagnostic value of 24 h-UAC in PA subtype classification was evaluated using receiver operating characteristic(ROC) curve analysis. Multivariate logistic regression analysis was conducted with PA subtypes as the dependent variable(UPA=1, BPA=0) to establish a diagnostic model for differentiating unilateral from bilateral lesions, and its performance was compared with published Chinese classification models. Results:There were no statistical differences between the UPA and BPA groups in terms of age, gender, BMI, systolic and diastolic blood pressure, 24 h urinary potassium, sodium, chloride, 24 h-UCR and PRC( P<0.05). The lowest plasma potassium level was significantly lower in the UPA group than in the BPA group, while PAC, 24 h-UAC, aldosterone-renin ratio(ARR), and 24 h-UAC/UCR were significantly higher( P<0.05). The detection rate of typical adenomas on imaging also showed a significant difference between the two groups( P<0.05). The area under the ROC curve(AUC) of 24 h-UAC for differentiating UPA from BPA was 0.829(95% CI 0.733-0.902), with an optimal cut-off value of 15.4 μg/24 h, yielding a sensitivity of 68.63% and a specificity of 88.57%( P<0.001). At a cut-off value of 24.5 μg/24 h, specificity reached 100%, with a sensitivity of 27.45%. Multivariate analysis indicated that a combined model incorporating 24 h-UAC, the lowest plasma potassium level, and imaging findings of typical adenomas significantly improved diagnostic accuracy for PA subtyping, achieving a specificity of 91.43%. Compared with the existing Chinese modified Küpers scoring model and CONPASS prediction model, this model demonstrated higher diagnostic efficiency, a lower missed diagnosis rate, and a misdiagnosis rate intermediate between the two. Conclusion:The 24 h-UAC in UPA patients is significantly higher than in BPA patients, making it a valuable marker for PA subtype classification. A predictive model combining 24 h-UAC, the lowest plasma potassium level, and imaging evidence of typical adenomas demonstrated high diagnostic accuracy for PA subtype classification and may provide valuable guidance for clinical decision-making.
4.Study on the value of 24 h urinary aldosterone measurement by liquid chromatography-tandem mass spectrometry in the subtype classification of primary aldosteronism
Hongyu PU ; Lu TAN ; Jia TANG ; Tao CHEN ; Mingxi ZOU ; Yuchun ZHU ; Sikui SHEN ; Haoming TIAN ; Yan REN
Chinese Journal of Endocrinology and Metabolism 2025;41(5):387-393
Objective:To investigate the value of 24 h urinary aldosterone(24 h-UAC) measurement by liquid chromatography-tandem mass spectrometry(LC-MS/MS) in the subtype classification of primary aldosteronism(PA).Methods:A total of 86 patients with PA, including 51 with unilateral primary aldosteronism(UPA) and 35 with bilateral primary aldosteronism(BPA), were enrolled in the Department of Endocrinology and Metabolism at West China Hospital between January 2018 and December 2022. Plasma aldosterone concentration(PAC), plasma renin concentration(PRC) and 24 h-UAC were measured by LC-MS/MS. 24-hour urinary electrolytes and 24-hour urinary creatinine(24 h-UCR) were also measured. The diagnostic value of 24 h-UAC in PA subtype classification was evaluated using receiver operating characteristic(ROC) curve analysis. Multivariate logistic regression analysis was conducted with PA subtypes as the dependent variable(UPA=1, BPA=0) to establish a diagnostic model for differentiating unilateral from bilateral lesions, and its performance was compared with published Chinese classification models. Results:There were no statistical differences between the UPA and BPA groups in terms of age, gender, BMI, systolic and diastolic blood pressure, 24 h urinary potassium, sodium, chloride, 24 h-UCR and PRC( P<0.05). The lowest plasma potassium level was significantly lower in the UPA group than in the BPA group, while PAC, 24 h-UAC, aldosterone-renin ratio(ARR), and 24 h-UAC/UCR were significantly higher( P<0.05). The detection rate of typical adenomas on imaging also showed a significant difference between the two groups( P<0.05). The area under the ROC curve(AUC) of 24 h-UAC for differentiating UPA from BPA was 0.829(95% CI 0.733-0.902), with an optimal cut-off value of 15.4 μg/24 h, yielding a sensitivity of 68.63% and a specificity of 88.57%( P<0.001). At a cut-off value of 24.5 μg/24 h, specificity reached 100%, with a sensitivity of 27.45%. Multivariate analysis indicated that a combined model incorporating 24 h-UAC, the lowest plasma potassium level, and imaging findings of typical adenomas significantly improved diagnostic accuracy for PA subtyping, achieving a specificity of 91.43%. Compared with the existing Chinese modified Küpers scoring model and CONPASS prediction model, this model demonstrated higher diagnostic efficiency, a lower missed diagnosis rate, and a misdiagnosis rate intermediate between the two. Conclusion:The 24 h-UAC in UPA patients is significantly higher than in BPA patients, making it a valuable marker for PA subtype classification. A predictive model combining 24 h-UAC, the lowest plasma potassium level, and imaging evidence of typical adenomas demonstrated high diagnostic accuracy for PA subtype classification and may provide valuable guidance for clinical decision-making.
5.Effect of Xiaoxuming decoction on OGD/R-induced synaptic plasticity in HT22 cells
Manman WANG ; Rui LAN ; Yong ZHANG ; Xueqin FU ; Xuhuan ZOU ; Weiwei WANG ; Hongyu LI ; Chen TANG ; Shuang LIU
Chinese Journal of Pathophysiology 2024;40(1):126-133
AIM:To explore the protective effect of Xiaoxuming decoction(XXMD)on synaptic plasticity in the context of cerebral ischemia-reperfusion injury following ischemic stroke.METHODS:An oxygen-glucose depriva-tion/reoxygenation(OGD/R)model was employed in vitro using mouse hippocampal neurons(HT22 cells)to simulate ischemia-reperfusion injury.Cell viability was assessed using a CCK-8 assay to determine the optimal XXMD concentra-tion.The HT22 cells were divided into two groups:control and model(OGD/R).Cellular morphological changes were ob-served using an inverted microscope.The levels of IL-1β,IL-6 and TNF-α in the supernatant were quantified by ELISA.Ultrastructural changes were examined by transmission electron microscopy.Immunofluorescence staining was used to de-tect neuron markers NeuN and synaptic proteins NF200 and MAP2.The protein levels of NF200 and MAP2 were analyzed by Western blot.RESULTS:The highest cell survival rate occurred at an XXMD concentration of 100 mg/L(P<0.05).Compared with control group,the cells in model group exhibited round shape and shrinkage,mitochondrial swelling or vacuolization,and a marked decrease in survival rate.There were significant increases in IL-1β,IL-6 and TNF-α levels(P<0.05).Immunofluorescence intensity and protein levels of NeuN,NF200 and MAP2 were notably reduced(P<0.05).Treatment with XXMD improved cell morphology,ultrastructure and survival rate(P<0.05),and decreased in-flammatory factor levels(P<0.05).Compared with model group,the cells in OGD/R+XXMD group showed significantly increased immunofluorescence intensity and protein levels of NeuN,NF200 and MAP2(P<0.05).CONCLUSION:Xiaoxuming decoction may mitigate OGD/R-induced injury,potentially by inhibiting inflammatory responses and enhanc-ing synaptic plasticity.
6.Mechanism of astragaloside IV promoting bone marrow EPCs mobilization in diabetic ulcer rats
Luyao ZHANG ; Shimin CAI ; Xi ZHANG ; Xiaoqin SONG ; Xiaoling ZOU ; Yuting XIAO ; Ying YANG ; Yang WEI ; Hongyu HUANG ; Wu XIONG
Journal of Chinese Physician 2024;26(3):376-381
Objective:To investigate the effect of astragaloside IV (AS-IV) regulating the signal axis of stromal cell-derived factor-1α (SDF-1α)/CXC chemokine receptor 4 (CXCR4) on the mobilization of bone marrow endothelial progenitor cells (EPCs) to peripheral blood in diabetes skin ulcer (DSU) rats.Methods:Twenty four SPF grade male Sprague Dawley (SD) rats were selected to make the model of type 2 diabetes rats by intraperitoneal injection of 30 mg/kg 1% (plastid ratio) streptozotocin, and then round full-thickness skin with a diameter of 2 cm was cut on both sides of the waist and back to make the skin ulcer model of diabetes rats. After that, they were randomly divided into AS-IV group (50 mg/kg AS-IV), blocker group (50 mg/kg AS-IV+ 5 mg/kg AMD3100) and model group. At the same time, a blank group ( n=8) was set up, The drug was administered via intraperitoneal injection, and the model group and blank group were treated with 0.9% NaCl of equal volume. On the 10th day, peripheral blood, femoral bone marrow, and wound neovascularization tissues of rats were collected. The number of EPCs in peripheral blood of each group of rats was measured by flow cytometry, and the protein expression of SDF-1α and CXCR4 in peripheral blood, femoral bone marrow, and wound neovascularization tissues of rats was detected by enzyme-linked immunosorbent assay (ELISA); At the same time, the wound healing rates of each group were tested. Results:On the 10th and 21st day after modeling, the wound healing rate of each group of rats was compared. The blank group healed the fastest, while the model group healed the slowest. The AS-IV group had better healing than the model group and the blocker group, and the difference was statistically significant (all P<0.05). On the 10th day after modeling, the positive rates of peripheral blood EPCs in the white group, AS-IV group, and blocker group were significantly higher than those in the model group (all P<0.05), while the positive rates of peripheral blood EPCs in the blocker group were significantly lower than those in the AS-IV group (all P<0.05). On the 10th day after modeling, the protein expression of SDF-1α and CXCR4 in the wound, serum, and bone marrow of the model group was the lowest, while the protein expression in the blank group was the highest (all P<0.05). The protein expression of SDF-1α and CXCR4 in the wound, serum, bone marrow of the AS-IV group was significantly higher than that of the blocker group and model group, and the difference was statistically significant (all P<0.05). Conclusions:Astragaloside IV can promote the mobilization and migration of endothelial progenitor cells from bone marrow to peripheral blood in diabetes ulcer rats by regulating SDF-1α/CXCR4 signal axis, and can participate in angiogenesis of diabetes ulcer wounds as seed cells to promote the healing of diabetes skin ulcers.
8.Research advances in acute pancreatitis-associated ascites fluid
Zhangpeng WANG ; Jun WU ; Guangxu JING ; Xuyang WANG ; Hong ZOU ; Hongyu SUN ; Lijun TANG
Journal of Clinical Hepatology 2023;39(5):1227-1233
Acute pancreatitis-associated ascites fluid (PAAF) is a common complication in patients with acute pancreatitis (AP) and is closely associated with the severity of AP, the development of local and systemic complications, and prognosis. PAAF may originate from the leakage of abdominal blood vessels, lymphatic vessels, and pancreatic duct. Recent studies have found that early removal of PAAF by abdominal paracentesis drainage can help to reduce systemic inflammation and alleviate pancreatitis-associated organ injury, thereby improving the conditions of patients with severe AP and reducing mortality. However, it is still not completely clear how PAAF aggravates systemic inflammatory response, participates in pancreatic injury and damage of distal organs, and leads to the aggravation of disease conditions in patients with AP. Therefore, this article gives an overview of PAAF and summarizes related studies in recent years, so as to provide directions for exploring the pathophysiological process and treatment of AP.
9.Research on the Development of Antigen Immunoassay Technology Based on Patent Information
ZOU Yue ; YOU Jin ; QIAO Zhiwei ; LI Yang ; LI Hongyu
Chinese Journal of Modern Applied Pharmacy 2023;40(13):1858-1868
OBJECTIVE To analyze technical and legal information of patents in the field of antigen immunoassay technology, and to provide advice to related enterprises on R&D direction and patent layout. METHODS Using patent analysis means combined with data visualization presentation, the R&D trends and research hotspots in the field of immunoassays of Abbott, Wondfo Bio, BGI Genomics and other related companies were systematically analyzed. RESULTS Abbott's patent layout in the field of immunoassay was more comprehensive and occupied a dominant position in international competition. Although the immunoassay technologies of Chinese enterprises had their own expertise, the industrial layout and the comprehensiveness of patent layout were weak. CONCLUSION Chinese enterprises should strengthen interdisciplinary research and strive for breakthroughs in the direction of cutting-edge technologies such as multiplex multi-pathogen high-throughput detection, magnetic particle chemiluminescence detection and microfluidic chip detection, as well as choosing appropriate patent protection strategies considering their own characteristics.
10.Epidemiological characteristics, diagnosis, treatment and prognosis of gallbladder cancer in China: a report of 6 159 cases
Xuheng SUN ; Yijun WANG ; Wei ZHANG ; Yajun GENG ; Yongsheng LI ; Tai REN ; Maolan LI ; Xu'an WANG ; Xiangsong WU ; Wenguang WU ; Wei CHEN ; Tao CHEN ; Min HE ; Hui WANG ; Linhua YANG ; Lu ZOU ; Peng PU ; Mingjie YANG ; Zhaonan LIU ; Wenqi TAO ; Jiayi FENG ; Ziheng JIA ; Zhiyuan ZHENG ; Lijing ZHONG ; Yuanying QIAN ; Ping DONG ; Xuefeng WANG ; Jun GU ; Lianxin LIU ; Yeben QIAN ; Jianfeng GU ; Yong LIU ; Yunfu CUI ; Bei SUN ; Bing LI ; Chenghao SHAO ; Xiaoqing JIANG ; Qiang MA ; Jinfang ZHENG ; Changjun LIU ; Hong CAO ; Xiaoliang CHEN ; Qiyun LI ; Lin WANG ; Kunhua WANG ; Lei ZHANG ; Linhui ZHENG ; Chunfu ZHU ; Hongyu CAI ; Jingyu CAO ; Haihong ZHU ; Jun LIU ; Xueyi DANG ; Jiansheng LIU ; Xueli ZHANG ; Junming XU ; Zhewei FEI ; Xiaoping YANG ; Jiahua YANG ; Zaiyang ZHANG ; Xulin WANG ; Yi WANG ; Jihui HAO ; Qiyu ZHANG ; Huihan JIN ; Chang LIU ; Wei HAN ; Jun YAN ; Buqiang WU ; Chaoliu DAI ; Wencai LYU ; Zhiwei QUAN ; Shuyou PENG ; Wei GONG ; Yingbin LIU
Chinese Journal of Digestive Surgery 2022;21(1):114-128
Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.


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