1.Mortality and years of life lost of residents with viral hepatitis among in Pudong New Area of Shanghai in 2003 - 2023
Sen WANG ; Lianghong SUN ; Caixia HU ; Hua CHEN ; Xiaobin QU ; Jiayi SHENG ; Siyue HAN ; Caoyi XUE ; Yichen CHEN
Journal of Public Health and Preventive Medicine 2026;37(1):53-57
Objective To analyze the characteristics of viral hepatitis mortality and life loss among residents in Pudong New Area from 2003 to 2023, and to provide a basis for related prevention and control work. Methods Viral hepatitis mortality data were obtained from the Pudong New Area mortality monitoring system. The crude mortality rate (CMR), standardized mortality rate (SMR), potential years of life lost (PYLL), average years of life lost (AYLL), and standardized potential years of life lost (SPYLL) were calculated to analyze viral hepatitis deaths. The average annual change (AAPC) and annual percentage change (APC) of the mortality rate were calculated by Joinpoint regression analysis to analyze the trend of mortality. Results The CMR and SMR of viral hepatitis among residents in Pudong New Area from 2003 to 2023 were 3.89/100000 and 1.98/100000, respectively. Both CMR and SMR of viral hepatitis showed a decreasing trend over time (CMR:APC=-5.476, t=-13.581, P<0.001; SMR:APC=- 7.624, t= -21.253, P<0.001). The CMR for males was 4.75/100000 and the SMR for males was 2.65/100000; the CMR for females was 3.04/100000 and the SMR for females was 1.32/100000, with a higher mortality rate for males than for females(ZCME=12.094,P<0.001; ZSMR=-14.718,P<0.001). Deaths were concentrated in the age groups of 45-64 years old and 65 years old and above, accounting for 91.62% of the total deaths. The PYLL of deaths due to viral hepatitis among residents in Pudong New Area from 2003 to 2023 was 26912 person-years, with a PYLLR of 0.45% and an AYLL of 8.88 years per person. Conclusion The mortality rate of viral hepatitis among the residents of Pudong New Area in 2003-2023 shows a decreasing trend over time. The mortality rate of males is higher than that of females, and the deaths of middle-aged and elderly people account for a large proportion of the total deaths. Chronic hepatitis B is the main cause of death.
2.Inhibitory effect of pterostilbene on high glucose-mediated endothelial-to-mesenchymal transition in human retinal microvascular endothelial cells
Xiaolan* WANG ; Hanyi* YANG ; Yimeng ZHANG ; Sida LIU ; Chengming CHEN ; Tingke XIE ; Yixuan CHEN ; Jiayi NING ; Jing HAN
International Eye Science 2025;25(3):359-364
AIM: To investigate the potential inhibitory effect of pterostilbene on the endothelial-to-mesenchymal transition(EndMT)induced by high glucose conditions in human retinal microvascular endothelial cells(HRMECs).METHODS: The optimal concentration of pterostilbene for treating HRMECs was determined using the CCK-8 assay, with 12.5 and 25 μmol/L concentrations selected for subsequent experiments. Four experimental groups were established: control group, high glucose group, high glucose combined with 12.5 μmol/L pterostilbene treatment group, and high glucose combined with 25 μmol/L pterostilbene treatment group. The expression levels of HDAC7 and EndMT-associated markers were detected via Western blot analysis. Cell migration ability was assessed using Transwell migration assays and scratch wound healing tests, while vasculogenic capability was evaluated through tube formation assays.RESULTS: The CCK-8 assay revealed that pterostilbene at a concentration of 22.07 μmol/L inhibited 50% of cell viability in HRMECs. Western blot analysis demonstrated that compared with the control group, the expression levels of HDAC7, ZEB1, Vimentin, and Snail were significantly upregulated in HRMECs cultured in high glucose(all P<0.01), while the expressions of VE-cadherin and CD31 were significantly reduced(all P<0.01). Compared to the high glucose group, the treatment with 12.5 and 25 μmol/L pterostilbene significantly reduced the expression of HDAC7, ZEB1, Vimentin, and Snail under high glucose conditions(all P<0.01). Notably, 25 μmol/L pterostilbene enhanced the expression of VE-cadherin and CD31(all P<0.01). Scratch wound healing tests revealed that HRMECs treated with high glucose exhibited a significantly increased cell migration rate compared to the control group(P<0.05), while the application of 25 μmol/L pterostilbene significantly suppressed HRMECs migration under high glucose conditions(P<0.01). Transwell migration assays demonstrated that the cell migration rate in the high glucose group was significantly higher than that in the control group(P<0.01), with cell migration rate markedly reduced following treatment with both of 12.5 and 25 μmol/L pterostilbene(all P<0.01). The tube formation assay revealed that the ability of HRMECs to form tubular structures was significantly enhanced under high glucose conditions(P<0.01), and both 12.5 and 25 μmol/L of pterostilbene effectively inhibited this effect(all P<0.01).CONCLUSION: Pterostilbene can inhibit HDAC7 expression, suppress EndMT-mediated migration of HRMECs, and impair tube formation under high-glucose conditions.
3.Inhibitory effect of pterostilbene on high glucose-mediated endothelial-to-mesenchymal transition in human retinal microvascular endothelial cells
Xiaolan* WANG ; Hanyi* YANG ; Yimeng ZHANG ; Sida LIU ; Chengming CHEN ; Tingke XIE ; Yixuan CHEN ; Jiayi NING ; Jing HAN
International Eye Science 2025;25(3):359-364
AIM: To investigate the potential inhibitory effect of pterostilbene on the endothelial-to-mesenchymal transition(EndMT)induced by high glucose conditions in human retinal microvascular endothelial cells(HRMECs).METHODS: The optimal concentration of pterostilbene for treating HRMECs was determined using the CCK-8 assay, with 12.5 and 25 μmol/L concentrations selected for subsequent experiments. Four experimental groups were established: control group, high glucose group, high glucose combined with 12.5 μmol/L pterostilbene treatment group, and high glucose combined with 25 μmol/L pterostilbene treatment group. The expression levels of HDAC7 and EndMT-associated markers were detected via Western blot analysis. Cell migration ability was assessed using Transwell migration assays and scratch wound healing tests, while vasculogenic capability was evaluated through tube formation assays.RESULTS: The CCK-8 assay revealed that pterostilbene at a concentration of 22.07 μmol/L inhibited 50% of cell viability in HRMECs. Western blot analysis demonstrated that compared with the control group, the expression levels of HDAC7, ZEB1, Vimentin, and Snail were significantly upregulated in HRMECs cultured in high glucose(all P<0.01), while the expressions of VE-cadherin and CD31 were significantly reduced(all P<0.01). Compared to the high glucose group, the treatment with 12.5 and 25 μmol/L pterostilbene significantly reduced the expression of HDAC7, ZEB1, Vimentin, and Snail under high glucose conditions(all P<0.01). Notably, 25 μmol/L pterostilbene enhanced the expression of VE-cadherin and CD31(all P<0.01). Scratch wound healing tests revealed that HRMECs treated with high glucose exhibited a significantly increased cell migration rate compared to the control group(P<0.05), while the application of 25 μmol/L pterostilbene significantly suppressed HRMECs migration under high glucose conditions(P<0.01). Transwell migration assays demonstrated that the cell migration rate in the high glucose group was significantly higher than that in the control group(P<0.01), with cell migration rate markedly reduced following treatment with both of 12.5 and 25 μmol/L pterostilbene(all P<0.01). The tube formation assay revealed that the ability of HRMECs to form tubular structures was significantly enhanced under high glucose conditions(P<0.01), and both 12.5 and 25 μmol/L of pterostilbene effectively inhibited this effect(all P<0.01).CONCLUSION: Pterostilbene can inhibit HDAC7 expression, suppress EndMT-mediated migration of HRMECs, and impair tube formation under high-glucose conditions.
4.Preparation of zinc and nitrogen modified titanium dioxide nanoparticles/mesoporous alumina composite resin and its performance evaluation
Rong HAN ; Zhimin ZHANG ; Yuanhang ZHAO ; Jiayi WANG ; Wenjun TANG ; Hong ZHANG
Journal of Jilin University(Medicine Edition) 2025;51(4):904-913
Objective:To prepare novel dental composite resins using zinc(Zn)-and nitrogen(N)-modified titanium dioxide(TiO?)nanoparticles(NPs)and mesoporous alumina(Al?O?,r type,20 mm)NPs as reinforcing fillers,systematically evaluating their antibacterial activity,mechanical strength,basic performance,and biosafety to obtain the dental composite resins with excellent antibacterial activity and mechanical strength.Methods:Zn-N-TiO? NPs and mesoporous Al?O? NPs were added into a resin matrix at varying mass ratios to prepare five composite resins:control group(no filler),group 0(Zn-N-TiO?∶Al?O?=1∶0),group 1(Zn-N-TiO?∶Al?O?=1∶1),group 2(Zn-N-TiO?∶Al?O?=1∶2),and group 3(Zn-N-TiO?∶Al?O?=1∶3).Plate colony counting method was used to detect the number of adhered bacteria on composite resin surfaces in various groups and calculate the antibacterial rate;scanning electron microscope(SEM)was used to observe the morphology of adhered bacteria in various groups;universal testing machine was used to measure flexural strength(FS)and elastic modulus(EM)of composite resins in various groups;SEM was used to observe fracture surface morphology of composite resins in various groups;microhardness tester was used to determine Vickers microhardness of the composite resins in various groups;Fourier transform infrared spectroscope was used to detect double bond conversion rate(DC)after 20 s photocuring and calculate curing depth;water contact angle meter was used to measure water contact angle(WCA),water sorption property(WSP),and water solubility level(WSL)of composite resins in various groups;cell counting kit-8(CCK-8)method was used to evaluate relative growth rate(RGR)of the mouse fibroblast L-929 cells cultured in composite resin extracts on days 1,3,and 5 and determine in vitro cytotoxicity grade.Results:The plate colony counting results showed that compared with control group,the colony counts on agar plates in the other groups were significantly reduced,with group 1 showing the lowest count.The SEM images results showed densely distributed and morphologically intact Streptococcus mutans in control group;small clusters of bacteria with depressed cell membranes in group 0 and group 3;sparsely distributed bacteria with obvious membrane shrinkage and cytoplasmic leakage in group 1 and group 2.No statistically significant difference in colony counts was found between group 1 and group 2(P>0.05),but both were lower than the other groups(P<0.05).All the composite resins in experimental groups exhibited>85%antibacterial rates,with group 1 and group 2 exceeding 99%.The composite resins in group 0 showed the lowest FS.With addition of mesoporous Al?O?,the FS of the composite resin in group 1 and group 2 were significantly increased,with the composite resin in group 2 showing the highest FS among all groups.Although the FS of the composite resin in group 3 was lower than that in group 2,but it remained higher than other groups(P<0.05).The SEM images results showed that in control group,the smooth-surfaced sillicon dioxide(SiO?)particles exhibited clear fracture interfaces with resin matrix,with>50%particle exposure;the composite resin in group 0 showed similar morphology and large Zn-N-TiO? agglomerates with tight filler-matrix bonding;the composite resin in group 1,2,and 3 showed resin adhesion to SiO? surfaces(<50%particle exposure)and uneven fracture surfaces.Fractured SiO? spheres were observed in group 2.Filler distribution was uniform in group 1 and group 2,while the minor NP agglomeration occurred in group 3.The composite resin in control group showed the lowest EM.The EM was significantly improved in experimental groups,with group 3 having the highest value.Group 0 exhibited the lowest Vickers microhardness,showing statistically significant differences among other groups(P<0.05).The Vickers microhardness of the composite resion was gradually increased with the rising of Al?O? content.The resins in group 2 and group 3 achieved>45 HV hardness,representing increases of 29.73%and 33.82%compared with control group,and 51.34%and 56.28%compared with group 0.No significant differences in DC of the composite resin were found among groups(P>0.05).The depth of cure for all composite resin groups exceeded 4 mm,with no significance differences observed between various groups(P>0.05).The composite resin in group 0 showed the smallest WCA.The hydrophobicity of the composite resion was increased with the rising of Al?O? content,but all the WCA values remained<80°.The composite resin in group 3 had the largest WCA without statistical significance compared with group 2(P>0.05).Filler incorporation reduced the water sorption/solubility.The composite resin in the CCK-8 assay results showed the composite resins in all groups had RGR>75%,meeting in vitro safety standards.Conclusion:Reinforcing fillers impart superior antibacterial activity and mechanical properties to composite resins.Under experimental conditions,group 2 composite resin achieves optimal comprehensive performance in antibacterial efficacy and mechanical strength,demonstrating promising clinical application potential.
5.Influence of cytoplasmic strings during blastocyst expansion on embryonic development and pregnancy outcome
Jiahong ZHU ; Jiayi ZOU ; Jiang WANG ; Shun XIONG ; Guoning HUANG ; Wei HAN ; Yang GAO
Journal of Chongqing Medical University 2025;50(5):688-693
Objective:To investigate the influence of inner cell mass and trophectoderm cytoplasmic strings during blastocyst expan-sion on embryonic development and pregnancy outcome.Methods:A retrospective cohort analysis was performed for the clinical data of patients who received pre-implantation genetic testing for aneuploidy(PGT-A)and underwent single blastocyst transplantation in our hospital from June 2019 to December 2021.A total of 530 patients were enrolled,and genetic testing was performed for 2132 blasto-cysts.According to the presence or absence of cytoplasmic strings during blastocyst expansion,the blastocysts were divided into cyto-plasmic strings(+)group with 534 blastocysts and cytoplasmic strings(-)group with 1598 blastocysts,and quality and PGT-A results were compared between the two groups.After the transfer of euploid blastocysts,pregnancy outcome was compared between the 115 blastocysts with cytoplasmic strings and the 415 blastocysts without cytoplasmic strings.Results:The rates of cytoplasmic strings(+)in the high-,average-,and low-quality blastocyst groups were 30.19%,24.62%,and 12.63%,respectively.The correlation analysis showed a correlation coefficient of-0.115(P<0.001)between embryo quality and the rate of cytoplasmic strings(+).There was no sig-nificant difference in euploidy rate between the two groups(45.3%vs.44.6%).There were no significant differences between the euploid blastocysts with cytoplasmic strings and those without cytoplasmic strings in implantation rate(72.17%vs.66.02%,P=0.213),miscarriage rate(14.46%vs.12.77%,P=0.691),and live birth rate(61.74%vs.57.59%,P=0.424).Conclusion:The presence of cyto-plasmic strings is associated with the morphological quality of blas-tocysts,while it has no impact on embryo ploidy or clinical outcome after euploid embryo transfer.Further research is needed to confirm the impact of cytoplasmic strings on embryonic development.
6.Establishment of a CD8+T cell exhaustion model in vitro
Lingmin ZENG ; Dingyi LU ; Jiayi CHEN ; Haoqian ZHANG ; Jun GAO ; Qiuying HAN ; Xin PAN
Military Medical Sciences 2025;49(4):265-272
Objective To establish a stable in vitro model of CD8+T cell exhaustion.Methods CD8+T cells were isolated and purified from the spleens of ovalbumin-specific CD8+T cell receptor(OT-I)transgenic mice and subjected to chronic antigen stimulation to induce exhaustion in vitro.Flow cytometry was employed to evaluate the expressions of exhaustion markers,secretion of effector cytokines,and transcription factor profiles in CD8+T cells.Exhausted and effector(non-exhausted)CD8+T cells were co-cultured with tumor cells before tumor cell viability was measured to assess the cytotoxic potential of CD8+T cells.Additionally,N-acetyl-L-cysteine(N-AC)was used as a positive control during exhaustion induction to validate the model.Results Chronic stimulation resulted in a significant upregulation of inhibitory receptors,including programmed cell death protein 1(PD-1),T cell immunoglobulin and mucin domain-containing protein 3(TIM-3),T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motifdomain(TIGIT),and lymphocyte activation gene 3(LAG-3).Concurrently,the secretion of key effector cytokines such as tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)was markedly reduced.Exhausted CD8+T cells exhibited diminished cytotoxicity against tumor cells compared to effector CD8+T cells.Notably,treatment with N-AC effectively restored the function of exhausted CD8+T cells and enhanced their anti-tumor activity.Conclusion This study has established an effective in vitro model for CD8+T cell exhaustion.The use of N-AC demonstrates its potential to restore functionality in exhausted CD8+T cells,underscoring the reliability and utility of this model for investigating the anti-tumor potential of exhausted T cells.
7.Single-center clinical analysis of laparoscopic pancreaticoduodenectomy and laparoscopic total pancreatectomy for treating pancreatic cancer
Mengqing SUN ; Xuesong BAI ; Jiayi LI ; Xiaodong HE ; Xianlin HAN
Chinese Journal of Pancreatology 2024;24(1):11-16
Objective:To analyze the safety and therapeutic efficacy of laparoscopic pancreaticoduodenectomy (LPD) and laparoscopic total pancreatectomy (LTP) in the treatment of pancreatic cancer.Methods:Clinical data of 87 patients with pancreatic head and neck cancer who underwent LPD or LTP in the Department of General Surgery at Peking Union Medical College Hospital from December 2018 to August 2023 were retrospectively analyzed. The surgical approach, operative time, intraoperative blood loss volume, conversion rate to open surgery, perioperative mortality, re-operative rate, rate of major postoperative complications, postoperative hospital stay, number of lymph nodes harvested, tumor pathological stage, R 0 resection rate, initiation of postoperative chemotherapy and survival outcomes were recorded. The follow-up period extended until September 2023. Results:Among the 87 patients, 78(89.7%) underwent LPD and 9(10.3%) underwent LTP. PV-SMV vascular resection and reconstruction was performed in 16 cases (18.4%), and 11 cases totally underwent laparoscopy. Five cases (5.7%) required conversion to open surgery. The mean operative time was 279.8±74.0 minutes, and the mean intraoperative blood loss volume was 520.1±743.2 ml. The overall length of hospital stay was 15.9±6.3 days, with a mean postoperative hospital stay of 11.5±6.0 days. The rate of major postoperative complications was 19.5%, including 4 cases (4.6%) of postoperative bile leakage, 6 cases (6.9%) of postoperative gastric emptying disorders, and 3 cases (3.4%) of postoperative bleeding. There was one case (1.1%) with secondary surgery and one case (1.1%) with perioperative death. Among LPD patients, 5 cases (6.4%) had postoperative grade B or higher pancreatic fistula. Advanced age (≥70 years) did not increase the incidence of perioperative complications. All patients achieved R 0 resection. The mean number of lymph nodes harvested was 25.9±11.4. The median time to initiation of postoperative chemotherapy was 2.13±1.43 months. The median overall survival was 16 months. Conclusions:In a high-volume center for pancreatic diseases, LPD and LTP are safe and feasible for the treatment of pancreatic cancer, which could achieve satisfactory anti-tumor efficacy and improve patients' prognosis.
8.Transcriptomic and cellular decoding of scaffolds-induced suture mesenchyme regeneration
Wu JIAYI ; Li FEIFEI ; Yu PENG ; Yu CHANGHAO ; Han CHUYI ; Wang YITIAN ; Yu FANYUAN ; Ye LING
International Journal of Oral Science 2024;16(2):306-321
Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal regeneration.Despite extensive studies on mineralized parenchymal tissue rebuilding,regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances yet.Current knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic damage.But to date,the absence of promising therapeutic biomaterials/scaffolds remains.The reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of scaffolds.To address these issues,in this study,we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial scaffolds.Our data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses.A feasible scaffold,polylactic acid electrospinning membrane(PLA),was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center,meanwhile supporting proper osteointegration with defect bony edges.Especially,transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were deciphered.This study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing,offering clinicians potential choices for regenerating such complicated injuries.
9.Efficacy of Lenvatinib Combined with Anti–PD-1 Antibodies Plus Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective, Multicenter Study
Xiangye OU ; Junyi WU ; Jiayi WU ; Yangkai FU ; Zhenxin ZENG ; Shuqun LI ; Yinan LI ; Deyi LIU ; Han LI ; Bin LI ; Jianyin ZHOU ; Shaowu ZHUANG ; Shuqun CHENG ; Zhibo ZHANG ; Kai WANG ; Shuang QU ; Maolin YAN
Cancer Research and Treatment 2024;56(4):1207-1218
Purpose:
The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti–programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT.
Materials and Methods:
This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles.
Results:
During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively.
Conclusion
Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.
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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