1.Mechanism of circRNA_0076631 mediated diabetic retinopathy by regulating pyroptosis
Yanyan ZHANG ; Yanyan WANG ; Xueli SHAO ; Quanyong YI ; Yahui XI
International Eye Science 2025;25(3):351-358
AIM: To investigate the role of pyroptosis in the development of diabetic retinopathy(DR)and to explore the regulatory mechanism by which circular RNA(circRNA)and its targeted microRNA(miRNA)mediate pyroptosis in DR, providing new therapeutic targets and strategies for the prevention and treatment of DR.METHODS: A streptozotocin(STZ)-induced model of type 1 diabetes in SD rats was established. The expression of circRNA_0076631, miR-214, and pyroptosis-related factors were measured in retinal tissues. CCK-8 and tube formation assays were used to detect the effect of different concentration of glucose on cell proliferation and angiogenic abilities of human retinal microvascular endothelial cells(HRMECs). The expression levels of circRNA_0076631, miR-214, and pyroptosis-related markers were evaluated through qRT-PCR and Western blot analysis, with additional experiments conducted following circRNA_0076631 knockdown to assess its effect on pyroptosis markers. Previous bioinformatics analysis and luciferase reporter assays identified a shared binding site among circRNA_0076631, miR-214, and caspase-1. To clarify the interaction between these molecules, co-transfection experiments using circRNA_0076631 inhibitors(ASO-circRNA_0076631), miR-214 overexpression transfection reagent, and miR-214 inhibitors(AMO-miR-214)were conducted to elucidate the regulatory pathway involved in DR.RESULTS: Both the diabetic rat model and D-glucose-treated HRMECs showed significantly elevated expression of circRNA_0076631 and pyroptosis-related factors(NLRP3, caspase-1, and IL-1β), while miR-214 expression was reduced(all P<0.05). The mRNA expression of pyroptosis-related factors caspase-1 was reduced after the overexpression of miR-214, and it was upregulated after the inhibition of miR-214(all P<0.05). Knockdown of circRNA_0076631 reduced the mRNA expression of pyroptosis markers caspase-1(P<0.05). Co-transfection experiments revealed that the inhibition circRNA_0076631 suppressed pyroptosis(all P<0.05), but this suppression was reversed upon co-transfection with miR-214 inhibitors, leading to increased mRNA expression of the pyroptosis marker caspase-1(all P<0.05).CONCLUSION: The circRNA_0076631 and pyroptosis play critical roles in the pathogenesis of DR, and circRNA_0076631 may regulate pyroptosis by modulating miR-214, which in turn influences the expression of caspase-1 in the pyroptosis signaling pathway, thereby contributing to DR progression. The circRNA_0076631 may serve as a novel therapeutic target, providing new insights for the prevention and treatment of DR.
2.Mechanism of circRNA_0076631 mediated diabetic retinopathy by regulating pyroptosis
Yanyan ZHANG ; Yanyan WANG ; Xueli SHAO ; Quanyong YI ; Yahui XI
International Eye Science 2025;25(3):351-358
AIM: To investigate the role of pyroptosis in the development of diabetic retinopathy(DR)and to explore the regulatory mechanism by which circular RNA(circRNA)and its targeted microRNA(miRNA)mediate pyroptosis in DR, providing new therapeutic targets and strategies for the prevention and treatment of DR.METHODS: A streptozotocin(STZ)-induced model of type 1 diabetes in SD rats was established. The expression of circRNA_0076631, miR-214, and pyroptosis-related factors were measured in retinal tissues. CCK-8 and tube formation assays were used to detect the effect of different concentration of glucose on cell proliferation and angiogenic abilities of human retinal microvascular endothelial cells(HRMECs). The expression levels of circRNA_0076631, miR-214, and pyroptosis-related markers were evaluated through qRT-PCR and Western blot analysis, with additional experiments conducted following circRNA_0076631 knockdown to assess its effect on pyroptosis markers. Previous bioinformatics analysis and luciferase reporter assays identified a shared binding site among circRNA_0076631, miR-214, and caspase-1. To clarify the interaction between these molecules, co-transfection experiments using circRNA_0076631 inhibitors(ASO-circRNA_0076631), miR-214 overexpression transfection reagent, and miR-214 inhibitors(AMO-miR-214)were conducted to elucidate the regulatory pathway involved in DR.RESULTS: Both the diabetic rat model and D-glucose-treated HRMECs showed significantly elevated expression of circRNA_0076631 and pyroptosis-related factors(NLRP3, caspase-1, and IL-1β), while miR-214 expression was reduced(all P<0.05). The mRNA expression of pyroptosis-related factors caspase-1 was reduced after the overexpression of miR-214, and it was upregulated after the inhibition of miR-214(all P<0.05). Knockdown of circRNA_0076631 reduced the mRNA expression of pyroptosis markers caspase-1(P<0.05). Co-transfection experiments revealed that the inhibition circRNA_0076631 suppressed pyroptosis(all P<0.05), but this suppression was reversed upon co-transfection with miR-214 inhibitors, leading to increased mRNA expression of the pyroptosis marker caspase-1(all P<0.05).CONCLUSION: The circRNA_0076631 and pyroptosis play critical roles in the pathogenesis of DR, and circRNA_0076631 may regulate pyroptosis by modulating miR-214, which in turn influences the expression of caspase-1 in the pyroptosis signaling pathway, thereby contributing to DR progression. The circRNA_0076631 may serve as a novel therapeutic target, providing new insights for the prevention and treatment of DR.
3.Application of deep learning with multimodal data in glaucoma diagnosis and severity grading
Chaoxu QIAN ; Lingxiang ZHOU ; Xueli FENG ; Xi CHEN ; Wenyan YANG ; Sanli YI ; Hua ZHONG
Chinese Journal of Experimental Ophthalmology 2024;42(12):1149-1154
Objective:To develop a deep learning model based on multimodal data for glaucoma diagnosis and severity assessment.Methods:A diagnostic test was conducted.A total of 145 normal eyes from 86 participants and 507 eyes with primary open-angle glaucoma from 314 participants were collected at the First Affiliated Hospital of Kunming Medical University from June to December in 2023.Fundus photographs and visual field data were obtained, and glaucoma eyes were divided into three groups based on the mean deviation value of the visual field, namely mild group (154 eyes), moderate group (113 eyes), and severe group (240 eyes).Three convolutional neural network (CNN) models, including DenseNet 121, ResNet 50 and VGG 19, were used to build an artificial intelligence (AI) model.The impact of single-modal and multimodal data on the classification results was evaluated, and the most appropriate CNN network architecture for multimodal data was identified.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of The First Affiliated Hospital of Kunming Medical University (No.2023L93).Written informed consent was obtained from each subject.Results:A total of 652 eyes had both fundus photographs and visual field test results.Images were randomly assigned to training and test datasets in a 4∶1 ratio by using computer random number method.AI models built with different CNN models showed high accuracy, with DenseNet 121 outperforming ResNet 50 and VGG 19 on various effectiveness measures.In the single-modal algorithm using fundus photographs, single-modal algorithm using visual field tests, and multimodal algorithm combining fundus photographs and visual field data, the area under the curve for early glaucoma detection was 0.87, 0.93 and 0.95, respectively.Conclusions:The use of multimodal data enables the development of a highly accurate tool for the glaucoma diagnosis and severity grading.
4.Research progress of circrna and atherosclerotic ischemic stroke
Chunling PAN ; Xueli YI ; Li SU ; Shengshan YUAN ; Guijiang WEI
The Journal of Practical Medicine 2024;40(12):1755-1761
Stroke is one of the main diseases endangering the health and life of the middle-aged and elderly,and in recent years it shows a younger trend.It has the characteristics of high incidence,mortality and disability rate.Atherosclerosis is the main intervention target for stroke prevention and treatment.CircRNA is highly expressed in the cerebrovascular system and plays an important regulatory role in the pathogenesis of ischemia-reperfusion and ischemic stroke.This paper reviews the mechanism of circRNA and miRNA molecular network in the pathophysiological process of atherosclerosis,ischemic stroke and ischemia-reperfusion injury,so as to provide theoretical support for the application of circRNA in gene diagnosis and drug treatment of atherosclerotic ischemic stroke.
5.Correlation between serum HBV RNA and duration of treatment with nucleos(t)ide analogues in patients with chronic hepatitis B
Xueli FAN ; Aiqin ZHAN ; Yi AN ; Liyan TIAN
Journal of Clinical Hepatology 2024;40(1):58-63
ObjectiveTo investigate the serum level of HBV RNA in untreated or treatment-experienced patients with chronic hepatitis B (CHB) and the correlation between serum HBV RNA level and the duration of antiviral therapy with nucleos(t)ide analogues (NAs). MethodsA total of 300 patients with CHB who attended Department of Infectious Diseases in The First Affiliated Hospital of Shihezi University School of Medicine from February to July, 2022, were enrolled as subjects. Related clinical data were collected, and according to the duration of antiviral therapy, they were divided into untreated group with 73 patients, treatment duration ≤1 year group with 91 patients, and treatment duration >1 year group with 136 patients. Serum HBV RNA load, HBV DNA load, and HBsAg concentration were measured for all patients. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups, further pairwise comparison using Bonferroni method; the chi-square test was used for comparison of categorical data; a Spearman correlation analysis was used to investigate the degree of correlation between various indicators. ResultsThe positive rate of HBeAg was 18.3%, and among the patients with negative HBV DNA, the patients with positive HBV RNA accounted for 44.1% (86/195). There was a significant difference in the distribution of the serum levels of HBV RNA, HBV DNA, and HBsAg between the positive HBeAg group and the negative HBeAg group (Z=10.740, 6.300, and 7.280, all P<0.05). There was a significant difference in the distribution of DNA level between the untreated group and the treatment duration ≤1 year group (P<0.05); there was a significant difference in the distribution of HBV RNA and HBV DNA levels between the untreated group and the treatment duration >1 year group (P<0.05); there was a significant difference in the distribution of HBV RNA, HBV DNA, and HBsAg levels between the treatment duration ≤1 year group and the treatment duration >1 year group (P<0.05). The correlation analysis between the duration of antiviral therapy and the levels of HBV RNA, HBV DNA, and HBsAg showed that the duration of antiviral therapy had an extremely weak negative correlation with the levels of HBV RNA and HBsAg (r=-0.247 and -0.138, both P<0.05) and a strong negative correlation with the level of HBV DNA (r=-0.771, P<0.001). There was a low degree of correlation between the serum level of HBV RNA and the serum levels of HBV DNA and HBsAg (r=0.360 and 0.442, both P<0.001). Further stratified analysis showed that in the untreated group, there was a strong positive correlation between HBV RNA and HBV DNA (r=0.752, P<0.001) and a moderate positive correlation between HBV RNA and HBsAg (r=0.559, P<0.001); in the treatment duration ≤1 year group, there was a low degree of positive correlation between HBV RNA and HBV DNA/HBsAg (r=0.396 and r=0.388, both P<0.001); in the treatment duration >1 year group, there was a low degree of positive correlation between HBV RNA and HBsAg (r=0.352, P<0.001). ConclusionSerum HBV RNA is negatively correlated with the duration of treatment with NAs, and the correlation of HBV RNA with HBV DNA and HBsAg gradually decreases with the increase in the duration of treatment. Therefore, it can be used as a supplementary indicator for monitoring the level of virologic response in CHB patients to a certain extent, with a relatively high accuracy in reflecting the level of viral replication in untreated patients.
6.Effect of Gehua Jiejiu Dizhi Decoction on energy metabolism in liver tissue of alcoholic liver disease mice
Rui LIU ; Xu YI ; Xueli WU ; Shuoshi WANG ; Diancheng HE ; Shaowei YOU
Journal of Beijing University of Traditional Chinese Medicine 2024;47(5):662-671
Objective To detect the level of related indexes of energy metabolism in liver tissue of alcoholic liver disease(ALD)mice,and to explore the intervention effect of Gehua Jiejiu Dizhi Decoction.Methods Forty male C57BL/6J mice were randomly divided into the normal control group,the model group,the Gehua Jiejiu Dizhi Decoction high-dose group(4.94 g/kg),the Gehua Jiejiu Dizhi Decoction low-dose group(2.47 g/kg),and the resveratrol group(0.40 g/kg),with 8 mice in each group.Except the normal control group,the mice in other groups were fed with Lieber-DeCarli control liquid diet for five days,followed by Lieber-DeCarli alcohol liquid diet for ten days,and on the 16th day,the mice were given 31.5%alcohol solution through gavage to establish the ALD model.From the second day after modeling,the rats in the intervention groups were given the corresponding drugs by gavage once a day for nine consecutive days.Hematoxylin and eosin staining and oil red O staining were used to observe the liver steatosis in liver tissue.The activities of Na+K+-ATPase and Ca2+Mg2+-ATPase,and the contents of succinate dehydrogenase(SDH)and hepatic glycogen in liver tissue were detected using spectrophotometry.The contents of ATP,ADP,AMP,the AMP/ATP value,total adenosine pool(TAN)content,and energy charge(EC)in liver tissue were detected by reversed phase high performance liquid chromatography method.The mRNA expressions of NAD dependent deacetylase Sirtuin-1(SIRT1)and AMP-activated protein kinase(AMPK)α2 in liver tissue were detected by real-time PCR.The protein expressions of SIRT1,AMPKα2,and AMPKβ1 in liver tissue were detected by Western blotting.Results Compared with the normal control group,the model group mice showed significant hepatic steatosis,significantly decreased Ca2+Mg2+-ATPase activity and SDH content in liver tissue,significantly increased hepatic glycogen content,significantly decreased EC and AMP/ATP value,significantly increased ATP,ADP,AMP,and TAN content,significantly decreased mRNA expressions of SIRT1 and AMPKα2,significantly increased protein expression of AMPKβ1(P<0.05).Compared with the model group,the Gehua Jiejiu Dizhi Decoction high-and low-dose groups significantly reduced liver tissue steatosis,and the activity of Na+K+-ATPase in liver tissue was significantly reduced,the EC and the mRNA expressions of SIRT1 and AMPKα2 were increased(P<0.05);the activity of Ca2+Mg2+-ATPase,SDH and ATP contents were increased in the Gehua Jiejiu Dizhi Decoction low-dose group(P<0.05);the AMP/ATP value was increased in the Gehua Jiejiu Dizhi Decoction high-dose group(P<0.05);and the protein expression of SIRT1 was increased in the the Gehua Jiejiu Dizhi Decoction high-and low-dose groups and the resveratrol group(P<0.05);the protein expression of AMPKα2 in the Gehua Jiejiu Dizhi Decoction low-dose group and the resveratrol group was increased(P<0.05).Compared with the Gehua Jiejiu Dizhi Decoction high-dose group,the Gehua Jiejiu Dizhi Decoction low-dose group and the resveratrol group showed a significant increase in ATP,TAN contents,and EC in liver tissue,while the AMP/ATP value decreased(P<0.05);mRNA expressionin of AMPKα2 in the Gehua Jiejiu Dizhi Decoction low-dose group was decreased(P<0.05);and the protein expressions of SIRT1 and AMPKα2 in the resveratrol group were increased(P<0.05).Compared with the Gehua Jiejiu Dizhi Decoction low-dose group,the protein expression of AMPKβ1 was decreased in the resveratrol group(P<0.05).Conclusion The changes of energy metabolism caused by chronic alcohol intake may be related to the occurrence of ALD,and the intervention of Gehua Jiejiu Dizhi Decoction can improve the abnormal energy metabolism in the liver of ALD mice.
7.A survey on the current situation of serum vitamin A and vitamin D levels among children aged 2-<7 years of 20 cities in China
Qionghui WU ; Qian CHEN ; Ting YANG ; Jie CHEN ; Li CHEN ; Xueli XIANG ; Feiyong JIA ; Lijie WU ; Yan HAO ; Ling LI ; Jie ZHANG ; Xiaoyan KE ; Mingji YI ; Qi HONG ; Jinjin CHEN ; Shuanfeng FANG ; Yichao WANG ; Qi WANG ; Tingyu LI
Chinese Journal of Pediatrics 2024;62(3):231-238
Objective:To investigate serum vitamin A and vitamin D status in children aged 2-<7 years in 20 cities in China.Methods:A cross-sectional study was conducted. A total of 2 924 healthy children aged 2-<7 years were recruited from September 2018 to September 2019 from 20 cities in China, categorized by age groups of 2-<3 years, 3-<5 years, and 5-<7 years. The demographic and economic characteristics and health-related information of the enrolled children were investigated. Body weight and height were measured by professional staff members. The serum vitamin A and vitamin D levels were detected by high-performance liquid chromatography-tandem mass spectrometry. Chi-square test and Logistic regression were applied to analyze the association between vitamin A and vitamin D deficiency and insufficiency as well as their underlying impact factors.Results:The age of the 2 924 enrolled children was 4.33 (3.42, 5.17) years. There were 1 726 males (59.03%) and 1 198 females (40.97%). The prevalences of vitamin A and vitamin D deficiency in enrolled children were 2.19% (64/2 924) and 3.52% (103/2 924), respectively, and the insufficiency rates were 29.27% (856/2 924) and 22.20% (649/2 924), respectively. Children with both vitamin A and vitamin D deficiencies or insufficiencies were found in 10.50% (307/2 924) of cases. Both vitamin A ( χ2=7.91 and 8.06, both P=0.005) and vitamin D ( χ2=71.35 and 115.10, both P<0.001) insufficiency rates were higher in children aged 3-<5 and 5-<7 years than those in children aged 2-<3 years. Vitamin A and vitamin D supplementation in the last 3 months was a protective factor for vitamin A and D deficiency and insufficiency, respectively ( OR=0.68 and 0.22, 95% CI 0.49-0.95 and 0.13-0.40, both P<0.05). The rates of vitamin A and D insufficiency was higher in children with annual household incomes <60 000 RMB than in those with annual household incomes ≥60 000 RMB ( χ2=34.11 and 10.43, both P<0.01). Northwest and Southwest had the highest rates of vitamin A and vitamin D insufficiency in children aged 2-<7 yeas, respectively ( χ2=93.22 and 202.54, both P<0.001). Conclusions:Among 20 cities in China, children aged 2-<7 years experience high rates of vitamin A and vitamin D insufficiency, which are affected by age, family economic level, vitamin A and vitamin D supplementation, and regional economic level. The current results suggest that high level of attention should be paid to vitamin A and vitamin D nutritional status of preschool children.
8.Efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit
Jun NI ; Huisheng CHEN ; Guofang CHEN ; Yong JI ; Fei YI ; Zhuobo ZHANG ; Yi YANG ; Jin WU ; Xueli CAI ; Bei SHAO ; Jianfeng WANG ; Yafang LIU ; Deqin GENG ; Xinhui QU ; Xiaohong LI ; Yan WEI ; Jianping DING ; Hua LYU ; Yining HUANG ; Yonghua HUANG ; Bo XIAO ; Tao GONG ; Liying CUI
Chinese Journal of Neurology 2022;55(5):474-480
Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.
9.Treatment of diabetic foot with antibiotic bone cement combined with delayed lateral supramolleolar perforator fascial flap
Ping HUANG ; Xiaofang YU ; Jiarui YOU ; Jinmei HE ; Guojun DU ; Yi LIU ; Xueli LI ; Junjie QUAN
Chinese Journal of Microsurgery 2022;45(2):128-132
Objective:To explore the clinical effect of antibiotic bone cement combined with delayed lateral supramolleolar perforator fascial flap in the treatment of diabetic foot(DF).Methods:From April 2020 to July 2021, a total of 6 patients with DF were treated with antibiotic bone cement combined with delayed lateral supramolleolar perforator fascial flap. The patients were 5 males and 1 female, aged from 45 to 67 years old with an average of 56.2 years old. The wounds were all located in dorsal foot, 4 in right foot and 2 in the left. The wound area was 2.4 cm×5.0 cm-6.5 cm×10.0 cm. The depth of wound were: 3 cases up to tendon layer, and 3 cases up to metatarsal bone. Two of the wound were complicated with metatarsal osteomyelitis. The wounds at Wagner grade 3 in 4 patients and grade 4 in 2 patients. The flap size was 3.0 cm×6.0 cm-8.0 cm×11.0 cm. All of the wounds were repaired with delayed supramolleolar perforator fascia flap after debridement, application of antibiotic bone cement and fumigation with Sanhuang decoction(a traditional Chinese medicine). The affected limbs were externally fixed with plaster and raised after surgery, and the colour, temperature, tension and capillary reaction of the flaps were closely observed. Stitches were removed 2 weeks after surgery and rehabilitation of the affected limb was performed. Regular follow-up was made postoperatively. The appearance of flaps and the scar of donor and recipient sites were observed. The foot and ankle function were evaluated by the American Orthopaedic Association foot and Ankle Surgery(AOFAS) score scale.Results:Six cases of DF had no recurrence of wound infection. All flaps survived well. The average follow-up time was 6(3-14) months. The postoperative follow-up revealed satisfactory appearance of the flap, only linear scars remained in the donor and recipient sites. The function of foot and ankle recovered well with full weight-bearing and normal walk. AOFAS scores ranged from 81 to 95.Conclusion:It is an effective method to treat DF by applying antibiotic bone cement combined with delayed superior lateral malleolus perforator fascial flap. The operation is simple, safe and can cut down the time of treatment, quickly control the wound infection. It deserves further trials.
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.

Result Analysis
Print
Save
E-mail