1.Critical role of mitochondrial dynamics in chronic respiratory diseases and new therapeutic directions.
Xiaomei WANG ; Ziming ZHU ; Haocheng JIA ; Xueyi LU ; Yingze ZHANG ; Yingxin ZHU ; Jinzheng WANG ; Yanfang WANG ; Rubin TAN ; Jinxiang YUAN
Chinese Medical Journal 2025;138(15):1783-1793
Chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) are both chronic progressive respiratory diseases that cannot be completely cured. COPD is characterized by irreversible airflow limitation, chronic airway inflammation, and gradual decline in lung function, whereas PH is characterized by pulmonary vasoconstriction, remodeling, and infiltration of inflammatory cells. These diseases have similar pathological features, such as vascular hyperplasia, arteriolar contraction, and inflammatory infiltration. Despite these well-documented observations, the exact mechanisms underlying the occurrence and development of COPD and PH remain unclear. Evidence that mitochondrial dynamics imbalance is one major factor in the development of COPD and PH. Mitochondrial dynamics is precisely regulated by mitochondrial fusion proteins and fission proteins. When mitochondrial dynamics equilibrium is disrupted, it causes mitochondrial and even cell morphological dysfunction. Mitochondrial dynamics participates in various pathological processes for heart and lung disease. Mitochondrial dynamics may be different in the early and late stages of COPD and PH. In the early stages of the disease, mitochondrial fusion increases, inhibiting fission, and thereby compensatorily increasing adenosine triphosphate (ATP) production. With the development of the disease, mitochondria decompensation causes excessive fission. Mitochondrial dynamics is involved in the development of COPD and PH in a spatiotemporal manner. Based on this understanding, treatment strategies for mitochondrial dynamics abnormalities may be different at different stages of COPD and PH disease. This article will provide new ideas for the potential treatment of related diseases.
Humans
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Mitochondrial Dynamics/physiology*
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Pulmonary Disease, Chronic Obstructive/metabolism*
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Hypertension, Pulmonary/metabolism*
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Mitochondria/metabolism*
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Animals
2.A controlled study on the efficacy of combined indoor light therapy for depression and its effects on physiological indicators
Li YANG ; Ruojia REN ; Wenting LU ; Tianyu ZHAO ; Shijie GUO ; Bufan LIU ; Fanfan HUANG ; Huan CHEN ; Na JIN ; Yuehang XU ; Quan LIN ; Xueyi WANG
Chinese Journal of Psychiatry 2025;58(3):211-219
Objective:To investigate the efficacy of lightroom therapy on depressive mood and sleep problems in patients with depression, and the potential effects on physiological indices related to circadian rhythms.Methods:From October 2021 to July 2023, 54 patients with acute-phase depression hospitalized in the Mental Health Center of the First Hospital of Hebei Medical University were recruited. The participants were randomly assigned to either medication combined with the bright light therapy group (bright light group, n=36) or medication combined with the dim light therapy group (dim light group, n=18). Both groups received light therapy for 2 weeks, at 10 000 lx in the bright light group and 300 lx in the dim light group. Both groups received 30 minutes of light therapy from 7:30-8:00 a.m daily over two weeks, followed up for 1 week post-treatment. The Hamilton Depression Rating Scale (HAMD 17) was used to assess patients′ depressive symptoms, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess patients′ sleep quality at baseline, at the end of every week. The 32-Item Hypomania Checklist (HCL-32) was used at the end of week 2 to assess the risk of manic switching after treatment. Daily measurements of body temperature, heart rate, and blood pressure were taken before and after light therapy, along with recording adverse events related to the therapy. Paired t- tests were used to compare changes in physiological indicators before and after treatment, and repeated measures ANOVA was applied to compare clinical symptom changes between the two groups. Results:Thirty-one and fifteen patients completed this study in the bright light and dim light groups, respectively, with no statistically significant difference in dropout rates( P>0.05). There were significant interaction effects between the time and group for HAMD 17 and PSQI score( F=5.51,4.11, both P<0.05). Both groups showed significant reductions in HAMD 17 and PSQI scores at baseline, week 1, week 2, and week 3 ( P<0.001). In the bright light group, body temperature increased significantly post-treatment on days 1-4, day 7, and day 12 (all P<0.05). Heart rate elevated on day 5 ( P<0.05).Systolic blood pressure decreased on days 4, 5, 11, and 12 compared to the pre-treatment baseline(all P<0.05). In the dim light group, systolic blood pressure increased on day 11 ( P<0.05). Diastolic blood pressure in the bright light group decreased on days 1, 5, and 6( P<0.05). No serious adverse events, vision loss, ocular structural changes occurred in either group. No hypomania or mania episodes were observed. The incidence of adverse events did not differ significantly ( P>0.05). Conclusion:Medication combined with indoor bright light is more effective than the combination of dim light for depressive symptoms and sleep problems in patients with depression. Patients receiving bright light also may exhibit a higher body temperature, accelerated heart rate, and reduced blood pressure.
3.A controlled study on the efficacy of combined indoor light therapy for depression and its effects on physiological indicators
Li YANG ; Ruojia REN ; Wenting LU ; Tianyu ZHAO ; Shijie GUO ; Bufan LIU ; Fanfan HUANG ; Huan CHEN ; Na JIN ; Yuehang XU ; Quan LIN ; Xueyi WANG
Chinese Journal of Psychiatry 2025;58(3):211-219
Objective:To investigate the efficacy of lightroom therapy on depressive mood and sleep problems in patients with depression, and the potential effects on physiological indices related to circadian rhythms.Methods:From October 2021 to July 2023, 54 patients with acute-phase depression hospitalized in the Mental Health Center of the First Hospital of Hebei Medical University were recruited. The participants were randomly assigned to either medication combined with the bright light therapy group (bright light group, n=36) or medication combined with the dim light therapy group (dim light group, n=18). Both groups received light therapy for 2 weeks, at 10 000 lx in the bright light group and 300 lx in the dim light group. Both groups received 30 minutes of light therapy from 7:30-8:00 a.m daily over two weeks, followed up for 1 week post-treatment. The Hamilton Depression Rating Scale (HAMD 17) was used to assess patients′ depressive symptoms, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess patients′ sleep quality at baseline, at the end of every week. The 32-Item Hypomania Checklist (HCL-32) was used at the end of week 2 to assess the risk of manic switching after treatment. Daily measurements of body temperature, heart rate, and blood pressure were taken before and after light therapy, along with recording adverse events related to the therapy. Paired t- tests were used to compare changes in physiological indicators before and after treatment, and repeated measures ANOVA was applied to compare clinical symptom changes between the two groups. Results:Thirty-one and fifteen patients completed this study in the bright light and dim light groups, respectively, with no statistically significant difference in dropout rates( P>0.05). There were significant interaction effects between the time and group for HAMD 17 and PSQI score( F=5.51,4.11, both P<0.05). Both groups showed significant reductions in HAMD 17 and PSQI scores at baseline, week 1, week 2, and week 3 ( P<0.001). In the bright light group, body temperature increased significantly post-treatment on days 1-4, day 7, and day 12 (all P<0.05). Heart rate elevated on day 5 ( P<0.05).Systolic blood pressure decreased on days 4, 5, 11, and 12 compared to the pre-treatment baseline(all P<0.05). In the dim light group, systolic blood pressure increased on day 11 ( P<0.05). Diastolic blood pressure in the bright light group decreased on days 1, 5, and 6( P<0.05). No serious adverse events, vision loss, ocular structural changes occurred in either group. No hypomania or mania episodes were observed. The incidence of adverse events did not differ significantly ( P>0.05). Conclusion:Medication combined with indoor bright light is more effective than the combination of dim light for depressive symptoms and sleep problems in patients with depression. Patients receiving bright light also may exhibit a higher body temperature, accelerated heart rate, and reduced blood pressure.
4.Mechanism of Ginkgo flavone aglycone in alleviating doxorubicin-induced cardiotoxicity based on transcriptomics and proteomics
Yujie TU ; Ying CAI ; Xueyi CHENG ; Jia SUN ; Jie PAN ; Chunhua LIU ; Yongjun LI ; Yong HUANG ; Lin ZHENG ; Yuan LU
China Pharmacy 2024;35(21):2596-2602
OBJECTIVE To investigate the mechanism by which Ginkgo flavone aglycone (GA) reduces the cardiotoxicity of doxorubicin (DOX) based on transcriptomics and proteomics. METHODS Thirty-six mice were randomly assigned to control group (CON group, tail vein injection of equal volume of physiological saline every other day+daily intragastric administration of an equal volume of physiological saline), DOX group (tail vein injection of 3 mg/kg DOX every other day), and GDOX group (daily intragastric administration of 100 mg/kg GA+tail vein injection of 3 mg/kg DOX every other day), with 12 mice in each group. The administration of drugs/physiological saline was continued for 15 days. Mouse heart tissues were collected for RNA-Seq transcriptomic sequencing and 4D-Label-free quantitative proteomic analysis to screen differentially expressed genes and proteins, which were then subjected to Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. The expression levels of Apelin peptide (Apelin), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) mRNA and protein in mouse heart tissues, as well as the phosphorylation levels of PI3K and Akt proteins, were verified. H9c2 cardiomyocytes were divided into control group (CON group), DOX group (2 μmol/L), and GDOX group (2 μg/mL GA+2 μmol/L DOX) to determine cell viability and the levels of key glycolytic substances in the cells. RESULTS Six common pathways were identified from transcriptomics and proteomics, including the Apelin signaling pathway, the PI3K-Akt signaling pathway, and insulin resistance. Among them, the Apelin and PI3K-Akt signaling pathways were the most enriched in terms of gene numbers. Target validation experiments showed that compared to the CON group, the relative expression of Apelin, PI3K and Akt mRNA and protein levels, as well as the phosphorylation levels of PI3K and Akt proteins, were significantly decreased in the DOX group (P<0.05 or P<0.01). The relative expression of Apelin, PI3K and Akt mRNA and the phosphorylation levels of PI3K and Akt proteins were significantly increased in the GDOX group as compared with the DOX group (P<0.05 or P<0.01). Cellular experiments indicated that compared to the CON group, cell viability in the DOX group was significantly decreased (P<0.05), the relative uptake of glucose and the relative production of pyruvate and lactate were significantly increased (P<0.05), and the relative production of ATP was significantly reduced (P<0.05). Compared to the DOX group, cell viability in the GDOX group was significantly increased (P< 0.05), and the relative production of pyruvate and lactate was significantly reduced (P<0.05). CONCLUSIONS GA may alleviate DOX-induced cardiotoxicity by upregulating the mRNA and protein expression of Apelin, PI3K, and Akt in heart tissues, and regulating glycolytic processes.
5.Infiltration of neutrophil extracellular traps promotes activation of ure-thral fibroblasts and scar formation after urethral trauma
Yehui CHEN ; Yicheng XU ; Zhongtian RUAN ; Tingting LIN ; Xueyi XUE ; Ning XU
Chinese Journal of Pathophysiology 2024;40(1):103-109
AIM:This study was performed to investigate the impact of neutrophil extracellular traps(NETs)on scar formation following urethral trauma.METHODS:(1)Clinical samples were derived from patients of Department of Urology,The First Affiliated Hospital of Fujian Medical University,from June 2021 to December 2022.Levels of NETs in the blood and urine were compared between patients with urethral trauma(n=20)and those without urethral trauma(controls,n=20).The relationship between NETs and scar formation was analyzed.(2)Urethral fibroblasts were isolated from urethral scar tissues,and neutrophils were induced to produce NETs in vitro.The urethral fibroblasts were treated with normal saline,0.5 mg/L NETs,or 1.5 mg/L NETs to investigate the effects of NETs on activation and collagen syn-thesis of urethral fibroblasts.Additionally,a rabbit model of urethral trauma was established and the animals were dioided into four groups to explore the therapeutic potential of deoxyribonuclease I(DNase I)in preventing urethral scar forma-tion:control,operation + transforming growth factor-β1(TGF-β1),operation + normal saline,and operation+DNase I.RESULTS:The level of NETs in urine increased after urethral trauma(P<0.05),but the level of NETs in blood did not change(P>0.05).In the animal models,the urethral scar became more severe as the level of NETs in the urine increased(P<0.05).At the cellular level,NETs promoted the viability,migration,and collagen synthesis of urethral fibroblasts(P<0.05)..Additionally,urethral injection of DNase I after trauma reduced the level of NETs and inhibited the formation of urethral scar tissue in the animal models(P<0.05).CONCLUSION:Infiltration of NETs promotes activation of urethral fibroblasts and scar formation after urethral trauma.
6.Construction of prognostic nomogram based on clinicopathological characteristics and epithelial-stromal interaction 1 expression for clear cell renal cell carcinoma
Zeng CHENGLONG ; Wu XIAOHUI ; Lin BOHAN ; Qiu QIANREN-SHUN ; Zheng QINGSHUI ; Xu NING ; Xue XUEYI ; Chen SHAOHAO
Chinese Journal of Clinical Oncology 2024;51(12):595-601
Objective:To construct a prognostic nomogram based on epithelial-stromal interaction protein 1(EPSTI1)and predict the pro-gnosis of clear cell renal cell carcinoma(ccRCC).Methods:A retrospective analysis was performed from January 2012 to December 2015 at The First Affiliated Hospital of Fujian Medical University,on 221 patients with ccRCC who underwent surgical treatment in our center and 533 patients with ccRCC in The Cancer Genome Atlas(TCGA)database.Immunohistochemical(IHC)staining was performed on adjacent nor-mal and cancerous tissues to analyze the expression level of EPSTI1 and its correlation with clinicopathological characteristics.Kaplan-Meier survival analysis was performed for the overall survival(OS)and disease-free survival(DFS)of patients with high and low EPSTI1 expression levels.Univariate and multivariate Cox proportional hazards models were used to analyze the prognostic factors for OS,and a nomogram model was constructed and verified.Results:The IHC scores and mRNA expression levels of EPSTI1 were significantly higher in ccRCC tissues than in normal tissues(all P<0.001).EPSTI1 was expressed at higher levels in cancer tissues at higher T stages(P=0.036,P=0.006).The EPSTI1 protein expression level was related to the maximum tumor diameter and TNM stage(P=0.002,P=0.032,respectively).The OS and DFS were higher in the low-EPSTI1-expression group than the high-EPSTI1-expression group(P=0.046,P=0.003,P=0.001).Univariate and multivariate Cox regression analyses showed that a high EPSTI1 protein expression level,WHO/ISUP grade,and AJCC/TNM stage were independent risk factors for poor prognosis(P=0.009,P=0.039,P<0.001).The prognostic nomogram model constructed based on the above variables was su-perior to the AJCC/TNM stage in predicting the 5-year OS,and the calibration curve showed that the predicted value of the model was con-sistent with the actual value.Conclusions:The nomographic model based on EPSTI1,AJCC/TNM staging and WHO/ISUP staging has a strong predictive ability for the prognosis of renal clear cell carcinoma.
7.Study on the efficacy and safety of light room therapy as an adjunctive treatment for depression
Ruojia REN ; Wenting LU ; Yuanyuan GAO ; Na LI ; Li YANG ; Tianyu ZHAO ; Shijie GUO ; Fanfan HUANG ; Bufan LIU ; Quan LIN ; Yuehang XU ; Na JIN ; Xi YANG ; Xueyi WANG
Chinese Journal of Nervous and Mental Diseases 2023;49(12):720-726
Objective To explore whether indoor light-assisted therapy can rapidly improve depression and anxiety symptoms in patients with depression,as well as the safety of indoor-light-assisted therapy.Methods From September 2021 to December 2022,patients with depression were recruited from the Mental Health Center of the First Hospital of Hebei Medical University.According to the random number table method,patients were divided into test group and control group.The test group was treated with light therapy 30 minutes from 7:30 am to 8:00 am daily for 2 weeks in addition to antidepressant therapy.Antidepressant therapy was continued after completion of light therapy and patients were followed up for 2 weeks.The control group was treated with regular antidepressants throughout the four-week trial.Hamilton depression scale(HAMD17)and the Hamilton anxiety scale(HAMA)were used to assess the clinical symptoms at the baseline and the end of every week of treatment.Safety was evaluated using patient adverse events,anterior segment photography and visual testing.Results A total of 80 patients were enrolled,including 40 in the test group and 40 in the control group.The data of dropped were processed for missing values and then included in the statistical analysis.At the 1st(20.0%vs.0.0%)and 2nd(45.0%vs.17.5%)weekend of treatment,the response rate in the test group was significantly higher than that in the control group.There was an interaction between the time point and the group in HAMD17 total score(F=9.66,P<0.01).The scores of HAMD17 at the end of every week in the test group were significantly lower than that in the control group(P<0.05).There were significant differences in the reduction rate of total score in HAMD17[33.3%(25.0%,43.3%)vs.13.9%(9.9%,19.8%)]and HAMA[22.4%(16.5%,35.3%)vs.14.2%(4.4%,26.9%)]between the two groups(P<0.05).Incidences of adverse effect were not significantly different between the two groups(12.5%vs.10.0%,P=1.00).There were no severe adverse events or mania was reported in the test group and the eye examination showed no abnormality.Conclusion Compared with antidepressant therapy alone,indoor light therapy combined with antidepressant can quickly improve depression and anxiety symptoms in patients with depression,shorten the duration of depression treatment,and has good safety.
8.An exploratory randomised controlled study on the efficacy and safety of deep transcranial magnetic stimulation in the treatment of depression
Li YANG ; Ruojia REN ; Wenting LU ; Tianyu ZHAO ; Shijie GUO ; Bufan LIU ; Fanfan HUANG ; Huan CHEN ; Na JIN ; Quan LIN ; Yuehang XU ; Xueyi WANG
Chinese Journal of Psychiatry 2023;56(3):161-166
Objective:To investigate the efficacy and safety of deep transcranial magnetic stimulation (dTMS) as an adjunctive treatment for depression.Methods:From May 2021 to June 2022, 56 patients aged 18-60 who met the diagnostic criteria in the International Classification of Diseases (ICD-10) for depression were recruited from the Mental Health Center of the First Hospital of Hebei Medical University.According to the random number table method, they were divided into dTMS combined with the drug treatment group (dTMS group, n=28), and the repetitive transcranial magnetic stimulation(rTMS) combined with the drug treatment group (rTMS group, n=28). Both groups received dTMS or rTMS based on drug therapy, 5 times weekly for 2 weeks in total. At the baseline and the end of 2nd week of treatment, the Hamilton Depression Rating Scale (HAMD 17) and Hamilton Anxiety Rating Scale (HAMA) were used to assess patients′ depression and anxiety symptoms, and the 32-Item Hypomania Checklist (HCL-32) was used to assess the risk of mania after treatment.The reductions on HAMD 17 and HAMA were the primary assessment, and the treatment response rate in HAMD 17, adverse events and the risk of switching to mania were also assessed. The efficacy was compared between the two groups by using independent samples t-test and chi-square test. Results:There was no significant difference in baseline HAMD 17 and HAMA scores between the two groups ( P>0.05). At the end of 2nd week of the treatment, The HAMD 17 reduction and the reduction rate were higher in the dTMS group than in the rTMS group( t=3.27, P=0.02; t=2.11, P=0.04). The HAMA reduction and the reduction rate showed a trend favouring the dTMS group, but the difference was insignificant ( t=1.03, P=0.31; t=0.76, P=0.45). The treatment response rates on the HAMD 17 assessment were 52.2%(12/23) and 38.5% (10/26) in the dTMS and rTMS groups, respectively. However, the difference was not statistically significant (χ 2=0.93, P=0.34). The overall incidence of adverse events was 14.3% (4/28) in the dTMS group and 7.1% (2/28) in the rTMS group, with no significant differences between the two groups (χ 2=0.19, P=0.67). All subjective discomforts during the treatment automatically resolved within three days, and no mania was reported. Conclusion:As the adjunctive treatment, both TMS protocols are safe and effective in relieving the depressive and anxious symptoms of depressive disorder, and the adjunctive dTMS seems better in treating depressive symptoms than rTMS.
9.An exploratory randomised controlled study on the efficacy and safety of deep transcranial magnetic stimulation in the treatment of depression
Li YANG ; Ruojia REN ; Wenting LU ; Tianyu ZHAO ; Shijie GUO ; Bufan LIU ; Fanfan HUANG ; Huan CHEN ; Na JIN ; Quan LIN ; Yuehang XU ; Xueyi WANG
Chinese Journal of Psychiatry 2023;56(3):161-166
Objective:To investigate the efficacy and safety of deep transcranial magnetic stimulation (dTMS) as an adjunctive treatment for depression.Methods:From May 2021 to June 2022, 56 patients aged 18-60 who met the diagnostic criteria in the International Classification of Diseases (ICD-10) for depression were recruited from the Mental Health Center of the First Hospital of Hebei Medical University.According to the random number table method, they were divided into dTMS combined with the drug treatment group (dTMS group, n=28), and the repetitive transcranial magnetic stimulation(rTMS) combined with the drug treatment group (rTMS group, n=28). Both groups received dTMS or rTMS based on drug therapy, 5 times weekly for 2 weeks in total. At the baseline and the end of 2nd week of treatment, the Hamilton Depression Rating Scale (HAMD 17) and Hamilton Anxiety Rating Scale (HAMA) were used to assess patients′ depression and anxiety symptoms, and the 32-Item Hypomania Checklist (HCL-32) was used to assess the risk of mania after treatment.The reductions on HAMD 17 and HAMA were the primary assessment, and the treatment response rate in HAMD 17, adverse events and the risk of switching to mania were also assessed. The efficacy was compared between the two groups by using independent samples t-test and chi-square test. Results:There was no significant difference in baseline HAMD 17 and HAMA scores between the two groups ( P>0.05). At the end of 2nd week of the treatment, The HAMD 17 reduction and the reduction rate were higher in the dTMS group than in the rTMS group( t=3.27, P=0.02; t=2.11, P=0.04). The HAMA reduction and the reduction rate showed a trend favouring the dTMS group, but the difference was insignificant ( t=1.03, P=0.31; t=0.76, P=0.45). The treatment response rates on the HAMD 17 assessment were 52.2%(12/23) and 38.5% (10/26) in the dTMS and rTMS groups, respectively. However, the difference was not statistically significant (χ 2=0.93, P=0.34). The overall incidence of adverse events was 14.3% (4/28) in the dTMS group and 7.1% (2/28) in the rTMS group, with no significant differences between the two groups (χ 2=0.19, P=0.67). All subjective discomforts during the treatment automatically resolved within three days, and no mania was reported. Conclusion:As the adjunctive treatment, both TMS protocols are safe and effective in relieving the depressive and anxious symptoms of depressive disorder, and the adjunctive dTMS seems better in treating depressive symptoms than rTMS.
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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