1.Recommendations for Standardized Reporting of Systematic Reviews and Meta-Analysis of Animal Experiments
Qingyong ZHENG ; Donghua YANG ; Zhichao MA ; Ziyu ZHOU ; Yang LU ; Jingyu WANG ; Lina XING ; Yingying KANG ; Li DU ; Chunxiang ZHAO ; Baoshan DI ; Jinhui TIAN
Laboratory Animal and Comparative Medicine 2025;45(4):496-507
Animal experiments are an essential component of life sciences and medical research. However, the external validity and reliability of individual animal studies are frequently challenged by inherent limitations such as small sample sizes, high design heterogeneity, and poor reproducibility, which impede the effective translation of research findings into clinical practice. Systematic reviews and meta-analysis represent a key methodology for integrating existing evidence and enhancing the robustness of conclusions. Currently, however, the application of systematic reviews and meta-analysis in the field of animal experiments lacks standardized guidelines for their conduct and reporting, resulting in inconsistent quality and, to some extent, diminishing their evidence value. To address this issue, this paper aims to systematically delineate the reporting process for systematic reviews and meta-analysis of animal experiments and to propose a set of standardized recommendations that are both scientific and practical. The article's scope encompasses the entire process, from the preliminary preparatory phase [including formulating the population, intervention, comparison and outcome (PICO) question, assessing feasibility, and protocol pre-registration] to the key writing points for each section of the main report. In the core methods section, the paper elaborates on how to implement literature searches, establish eligibility criteria, perform data extraction, and assess the risk of bias, based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement, in conjunction with relevant guidelines and tools such as Animal Research: Reporting of in Vivo Experiments (ARRIVE) and a risk of bias assessment tool developed by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). For the presentation of results, strategies are proposed for clear and transparent display using flow diagrams and tables of characteristics. The discussion section places particular emphasis on how to scientifically interpret pooled effects, thoroughly analyze sources of heterogeneity, evaluate the impact of publication bias, and cautiously discuss the validity and limitations of extrapolating findings from animal studies to clinical settings. Furthermore, this paper recommends adopting the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to comprehensively grade the quality of evidence. Through a modular analysis of the entire reporting process, this paper aims to provide researchers in the field with a clear and practical guide, thereby promoting the standardized development of systematic reviews and meta-analysis of animal experiments and enhancing their application value in scientific decision-making and translational medicine.
2.Huaier alleviates acute pancreatitis in mice by reducing ROS-induced pyroptosis in acinar cells
Mengyuan GONG ; Bo ZHANG ; Ze’en ZHU ; Qingyong MA ; Zheng WU ; Zheng WANG ; Weikun QIAN
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(2):183-191
【Objective】 To investigate the therapeutic effect of Huaier on acute pancreatitis (AP) and its potential mechanism. 【Methods】 A mouse model of cerulean-induced AP was used to verify the therapeutic effect of Huaier in vivo. HE staining and immunohistochemical staining were used to evaluate the histopathological changes of the pancreas, and transmission electron microscopy was used to observe the pyroptosis morphology of the pancreas. In vitro, 266-6 cell line was used as the experimental carrier to verify the protective effect of Huaier on acinar cells. Electron microscopy and Western blotting were used to evaluate the pyroptosis level of acinar cells, and ROS fluorescence probe was used to detect the oxidative stress state of acinar cells. 【Results】 Huaier significantly alleviated the severity of AP in mice. HE staining of pancreas showed that necrosis and inflammatory cell infiltration were reduced, and the level of serum amylase was decreased. Immunohistochemical staining and Western blotting showed that Huaier effectively inhibited the expressions of pyroptosis-related molecules such as NLRP3 and GSDMD in pancreatic tissue. Electron microscopy showed that Huaier could reduce the pyroptosis level of pancreatic acinar cells under inflammatory state. In addition, the level of ROS in acinar cells was significantly reduced after the intervention of Huaier, and ROS-mediated pyroptosis of acinar cells could be effectively inhibited by Huaier. 【Conclusion】 Huaier can effectively reduce the severity of AP by inhibiting ROS-mediated pyroptosis of acinar cells.
3.Risk factors for acute pancreatitis in long-term drinking participants: a longitudinal UK Biobank-based study
Jinpeng ZHAO ; Yifei MA ; Qingyong MA ; Zheng WU ; Zheng WANG ; Xue YANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(2):192-199
【Objective】 To examine risk factors for acute pancreatitis (AP) in individuals with chronic alcohol consumption habits. 【Methods】 The study incorporated participants from the initial survey (2006-2010) and subsequent follow-ups (2014+) taken from the UK Biobank database, with the observation period ending on November 30, 2022. During this period, 176 individuals were newly diagnosed with AP, while 59,512 remained unaffected. Vital characteristics of the target population, such as their medical histories, surgical experiences and dietary patterns, were collected during the enrolment phase (2006-2010). The Cox proportional hazard model was employed to ascertain whether these characteristics were potent risk factors for AP. Concurrently, a subgroup from the target population with documented drinking behavior was selected. The multivariate Cox proportional hazard model was utilized to analyze the relationship of the established factors, variances in alcohol consumption, and increased alcohol intake (Δ) with the onset of AP, and whether the additional alcohol intake served as a risk factor. 【Results】 Multivariate analysis revealed that consumption quantity of cooked vegetables inversely correlated with AP risk (HR=0.44, 0.39, 0.42 and 0.41 for one, two, three and four+ tablespoons per day, respectively, as compared to non-consumers). Coffee consumption (2-3 cups per day) also reduced AP risk (HR=0.45 for 2 cups/day; HR=0.39 for 3 cups/day as compared to non-coffee drinkers). However, those with biliary disease without cholecystectomy exhibited a marked increase in AP risk (HR=7.82), which reduced albeit remained elevated for those with biliary disease post-cholecystectomy (HR=2.15). Subgroup analysis showed minimal impact of alcohol intake levels on AP incidence. Yet, increased alcohol consumption (Δ of 1 bottle/week) was linked to a heightened AP risk (HR=1.05, 95% CI:1.02-1.09, P<0.05). 【Conclusion】 Among longstanding alcohol consumers, a diet rich in cooked vegetables and moderate coffee consumption offers protective effects against AP. Conversely, biliary disease (particularly without cholecystectomy) and elevated alcohol intake present considerable risk factors for the development of this condition.
4.Pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy in the treatment of chronic pancreatitis: initial experience in 11 cases
Shuai WU ; Wanxing DUAN ; Xue YANG ; Wanzhen WEI ; Qingyong MA ; Zheng WANG ; Zheng WU
Chinese Journal of Surgery 2024;62(5):412-418
Objective:To investigate the surgical strategy for chronic pancreatitis complicated with suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas.Methods:This is a retrospective cohort study. Clinical data from 11 patients with chronic pancreatitis who underwent pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy(PD-L) were retrospectively collected(PD-L group) from the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi′an Jiaotong University between December 2021 and September 2023. All patients were male with an age of (49.0±11.2) years(range:32 to 70 years). Their primary preoperative diagnoses included pancreatic lesions, chronic pancreatitis, pancreatolithiasis, and dilatation of the pancreatic duct. Data from 248 patients who underwent pancreaticoduodenectomy(PD) during the same period were retrospectively collected(PD group). There were 157 males and 91 females in the PD group, with an age of (61.5±10.8) years(range:27 to 82 years). Among them, 87 cases were diagnosed as pancreatic cancer or chronic pancreatitis. The propensity score matching method was used to reduce confounding bias between the two groups. The caliper value of 0.1 was used and the 1∶4 nearest neighbor matching method was used for the matching. Comparisons between the two groups were made using the independent sample t test, Mann-Whitney U test or χ2 test,respectively. Results:After complete excision of the specimen during pancreaticoduodenectomy, the key surgical step of PD-L was longitudinal pancreaticojejunostomy in the remaining pancreas. Intraoperative blood loss in the PD-L group was lower than that in the PD group [ M(IQR)](300(200)ml vs. 500(500)ml, respectively; P<0.05). Similarly, hospitalization days(21.0(7.0)days vs. 25.0(8.5)days) and postoperative hospitalization days(13.0(8.0)days vs. 17.0(5.0) days) were also lower in the PD-L group compared to the PD group ( P<0.05). There were no significant differences in the operation time and postoperative complication rate between the two groups( P>0.05). In the PD-L group, the postoperative follow-up time was 5(5)months(range: 3 to 21 months). One case was lost for follow-up. Abdominal pain was relieved in 10 patients. Additionally, abdominal distension and steatosis were alleviated in 8 cases. Furthermore, 5 cases of diabetes mellitus showed improved control of HbA1c and fasting blood glucose levels after surgery. Conclusions:PD-L treatment can be used to treat chronic pancreatitis complicated by suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas. PD-L also has advantages in removing stones from the pancreatic duct and evaporation of pancreatic fluid. However, due to the single-center design and the small sample size of this study, further practice and long-term follow-up are still necessary.
5.Advances and Challenges in the Research of Integration Methods of Animal Experimental Evidence
Qingyong ZHENG ; Tengfei LI ; Jianguo XU ; Yongjia ZHOU ; Zhichao MA ; Na WANG ; Molan LI ; Wenjing YANG ; Peirun WU ; Haidong WANG ; Jinhui TIAN
Laboratory Animal and Comparative Medicine 2024;44(5):567-576
Integrating evidence from animal experiments is a critical component of biomedical research, providing essential prior information for in-depth investigations of disease mechanisms and new drug development. Animal models have played an irreplaceable role in simulating human diseases. However, the integration of evidence from animal experiments has faced numerous challenges, including insufficient emphasis, significant heterogeneity in study designs, high publication bias, and discrepancies with clinical research practices. This paper first identifies existing issues in the original research evidence from animal experiments, such as the selection and applicability of animal models, considerations in the design of experimental studies, and factors influencing the translation of animal experimental evidence. It then discusses various methods for integrating this evidence, including systematic review and meta-analysis, overview of systematic review/umbrella review, scoping review, and evidence mapping, while highlighting recent advancements in their application. Finally, the paper addresses the main challenges currently encountered in the integration of evidence from animal experiments and proposes targeted improvement strategies aimed at enhancing the efficiency of translating research outcomes into clinical practice and promoting the advancement of evidence-based medicine. By continuously optimizing original experimental research protocols and evidence integration practices, this work aims to establish a more efficient and scientific environment for the synthesis of evidence from animal experiments, ultimately contributing to clinical trials and human health.
6.Pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy in the treatment of chronic pancreatitis: initial experience in 11 cases
Shuai WU ; Wanxing DUAN ; Xue YANG ; Wanzhen WEI ; Qingyong MA ; Zheng WANG ; Zheng WU
Chinese Journal of Surgery 2024;62(5):412-418
Objective:To investigate the surgical strategy for chronic pancreatitis complicated with suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas.Methods:This is a retrospective cohort study. Clinical data from 11 patients with chronic pancreatitis who underwent pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy(PD-L) were retrospectively collected(PD-L group) from the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi′an Jiaotong University between December 2021 and September 2023. All patients were male with an age of (49.0±11.2) years(range:32 to 70 years). Their primary preoperative diagnoses included pancreatic lesions, chronic pancreatitis, pancreatolithiasis, and dilatation of the pancreatic duct. Data from 248 patients who underwent pancreaticoduodenectomy(PD) during the same period were retrospectively collected(PD group). There were 157 males and 91 females in the PD group, with an age of (61.5±10.8) years(range:27 to 82 years). Among them, 87 cases were diagnosed as pancreatic cancer or chronic pancreatitis. The propensity score matching method was used to reduce confounding bias between the two groups. The caliper value of 0.1 was used and the 1∶4 nearest neighbor matching method was used for the matching. Comparisons between the two groups were made using the independent sample t test, Mann-Whitney U test or χ2 test,respectively. Results:After complete excision of the specimen during pancreaticoduodenectomy, the key surgical step of PD-L was longitudinal pancreaticojejunostomy in the remaining pancreas. Intraoperative blood loss in the PD-L group was lower than that in the PD group [ M(IQR)](300(200)ml vs. 500(500)ml, respectively; P<0.05). Similarly, hospitalization days(21.0(7.0)days vs. 25.0(8.5)days) and postoperative hospitalization days(13.0(8.0)days vs. 17.0(5.0) days) were also lower in the PD-L group compared to the PD group ( P<0.05). There were no significant differences in the operation time and postoperative complication rate between the two groups( P>0.05). In the PD-L group, the postoperative follow-up time was 5(5)months(range: 3 to 21 months). One case was lost for follow-up. Abdominal pain was relieved in 10 patients. Additionally, abdominal distension and steatosis were alleviated in 8 cases. Furthermore, 5 cases of diabetes mellitus showed improved control of HbA1c and fasting blood glucose levels after surgery. Conclusions:PD-L treatment can be used to treat chronic pancreatitis complicated by suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas. PD-L also has advantages in removing stones from the pancreatic duct and evaporation of pancreatic fluid. However, due to the single-center design and the small sample size of this study, further practice and long-term follow-up are still necessary.
7.Application of new surgical clinical classification and staging of myasthenia gravis in the perioperative period
Yonghui ZHANG ; Wenqiang MA ; Yuwei HUANG ; Zhiwen ZHANG ; Meng WANG ; Chenshuo SHI ; Xinzheng CUI ; Qingyong ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(06):853-857
Objective To exploring the effectiveness of perioperative application of new surgical clinical classification and staging for myasthenia gravis (MG) in reducing the incidence of postoperative myasthenic crisis (MC). Methods The clinical data of patients with generalized MG admitted to the Comprehensive Treatment Center for Myasthenia Gravis of Henan Provincial People’s Hospital from January 2018 to June 2022 were retrospectively analyzed, who were scored with myasthenia gravis-activities of daily living (MG-ADL) score and quantification of the myasthenia gravis (QMG) score at the first visit, 1 day before surgery, and 3 days after surgery. The patients were divided into a group A (typeⅡ) and a group B (typeⅢ+Ⅳ+Ⅴ) by the new surgical clinical classification and staging of MG according to the disease progression process, and all patients underwent expanded thoracoscopic thymus (tumor) resection after medication and other interventions to control symptoms in remission or stability. The incidence of MC and the efficiency rate after surgery were analyzed. The normal distribution method and percentile method were used to calculate the unilateral 95% reference range of the QMG score and MG-ADL score. Results Finally 126 patients were enrolled, including 62 males and 64 females, aged 13-71 years, with an average age of 46.00±13.00 years. There were 95 patients in the group A and 31 patients in the group B, and the differences of the preoperative baseline data between the two groups were not statistically significant (P>0.05). The incidence of postoperative MC was 1.05% (1/95) in the group A and 3.23%(1/31) in the group B (P>0.05). The effective one-sided 95% reference range of the QMG score and MG-ADL score 1 day before surgery was 0-7.75 and 0-5.00, and there was no postoperative death in both groups. Conclusion The new surgical clinical classification and staging of MG can guide the timing of surgery, which can benefit patients undergoing surgery for MG and greatly reduce the incidence of postoperative MC.
8.Drug resistance factors in postoperative gemcitabine chemotherapy after radical resection of pancreatic cancer
Shuai WU ; Jiaqiang REN ; Hanxue WU ; Feng XUE ; Jiantao MO ; Zheng WANG ; Qingyong MA ; Zheng WU
Chinese Journal of Digestive Surgery 2023;22(5):616-622
Objective:To investigate the drug resistance factors in postoperative gemci-tabine chemotherapy after radical resection of pancreatic cancer.Methods:The retrospective case-control study was constructed. The clinicopathological data of 255 patients with pancreatic cancer who were firstly admitted to the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi ′an Jiaotong University from January 2018 to June 2021 were collected. There were 140 males and 115 females, aged (59±10)years. All patients underwent radical resection of pancreatic cancer and received postoperative gemcitabine-based adjuvant chemotherapy. Observation indicators: (1) follow-up; (2) postoperative chemotherapy; (3) drug resistance and changing of regimen; (4) factors influencing postoperative chemotherapy resistance. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and compari-son between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the Pearson chi-square test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model with forward method. Kaplan-Meier method was used to draw survival curve, and Log-Rank test was used for survival analysis. Results:(1) Follow-up. All 255 patients were followed up for 18.6(16.7,21.4)months. The median survival time of 255 patients was 18.2[95% confidence interval ( CI) as 15.8-20.6]months. (2) Postoperative chemotherapy. Of the 255 patients, there were 5 cases receiving postoperative chemotherapy as gemcitabine monotherapy, 167 cases receiving postoperative chemotherapy as the AG combination (gemcitabine plus albumin-bound paclitaxel), 74 cases receiving postoperative chemotherapy as the GS combination (gemcitabine plus S-1) and 9 cases receiving postoperative chemotherapy as the GP combination (gemcitabine plus platinum). (3) Drug resistance and changing of regimen. Of the 255 patients, 81 cases completed the course of postoperative chemotherapy and evaluation. Of the 81 patients, there were 18 cases with no recurrence or metastasis of tumor, 10 cases with tumor local recurrence, 40 cases with tumor lymph node metastasis or distant metas-tasis, 3 cases with tumor local recurrence combined with distant metastasis, 10 cases with elevation of CA19-9. Of the 81 patients, 18 cases responded to chemotherapy, 63 cases underwent resistant to chemotherapy, including 11 cases with primary resistance and 52 cases with acquired resistance. The 63 patients with chemotherapy resistance underwent changing of regimen. (4) Factors influencing postoperative chemotherapy resistance. Results of multivariate analysis showed that chemotherapy cycle<6 is an independent risk factor for postoperative chemotherapy resistance in patients ( hazard ratio=17.18, 95% CI as 2.07-142.28, P<0.05). Conclusion:Adjuvant chemotherapy cycle <6 is an independent risk factor for postoperative chemotherapy resistance for gemcitabine based chemo-therapy in pancreatic cancer patients receiving radical resection.
9.Clinical characteristics analysis of acute pancreatitis
Qiqi WANG ; Yali CHENG ; Cancan ZHOU ; Mengyuan GONG ; Haonan LIU ; Zheng WANG ; Qingyong MA ; Zheng WU
Chinese Journal of Digestive Surgery 2023;22(S1):38-43
Objective:To analyze the clinical characteristics of acute pancreatitis.Methods:The retrospective case-control study was conducted. The clinical data of 558 patients with acute pancreatitis who were admitted to The First Affiliated Hospital of Xi′an Jiaotong University from June 2015 to June 2023 were collected. There were 352 males and 206 females, aged (46±15)years. Observation indicators: (1) general situations of acute pancreatitis patients; (2) etiology of acute pancreatitis patients; (3) severity of acute pancreatitis patients; (4) chronic diseases in acute pan-creatitis patients; (5) complications in acute pancreatitis patients; (6) subgroup analysis of patients with recurrent acute pancreatitis. Measurement data with normal distribution 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), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Bonferroni correction was used for pairwise comparison. Results:(1) General situations of acute pancreatitis patients. There were significant differences in gender, age, total duration of hospital stay, smoking, and alcohol consumption between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (2) Etiology of acute pancreatitis patients. There were significant differences in gallstones and hyperlipidemia between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (3) Severity of acute pancreatitis patients. Of the 443 patients with first episode of acute pancreatitis and 115 patients with recurrent acute pancreatitis, cases with mild acute pancreatitis, cases with moderate-severe acute pancreatitis, cases with severe acute pan-creatitis were 320 and 83, 24 and 9, 99 and 23, showing no significant difference between them ( P>0.05). (4) Chronic diseases in acute pancreatitis patients. There were significant differences in com-plication as hyperlipidemia, fatty liver and diabetes between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (5) Complications in acute pancrea-titis patients. There was no significant difference in terms of acute necrotic collection, acute peripan-creatic fluid accumulation, walled-off necrosis, pancreatic pseudocyst, infectious pancreatic necrosis, systemic inflammatory response syndrome, respiratory system complications, circulatory system complications, renal complications, sepsis, abdominal compartment syndrome, or pancreatic ence-phalopathy between the first episode of acute pancreatitis patients and the recurrent acute pancrea-titis patients ( P>0.05). (6) Subgroup analysis of patients with recurrent acute pancreatitis. ① Combination with chronic diseases. Of the 115 patients with recurrent acute pancreatitis, cases with mild acute pancreatitis, cases with moderate-severe acute pancreatitis, cases with severe acute pancreatitis were 83, 9, 23, and there were 25, 8, 11 cases of them with hyperlipidemia, respectively, showing a significant difference among them ( P<0.05). ② Complications. Of the 115 patients with recurrent acute pancreatitis, there were 44 cases with hyperlipidemia and 71 cases without hyper-lipidemia, and there were significant differences in acute peripancreatic fluid accumulation and renal complications between them ( P<0.05). Conclusions:Recurrent acute pancreatitis is more common in males. Compared with first episode of acute pancreatitis, cases with recurrent acute pancreatitis usually have younger age, shorter total duration of hospital stay, higher proportion of smoking and drinking. The etiology of recurrent acute pancreatitis is composed of lower levels of biliary diseases and higher levels of hyperlipidemia. Patients with recurrent acute pancreatitis have higher proportion of comorbidities as hyperlipidemia, fatty liver and diabetes. There was no signifi-cant difference in the incidence of complications between first episode of acute pancreatitis and recurrent acute pancreatitis. Compared with recurrent acute pancreatitis patients without concomi-tant hyperlipidemia, recurrent acute pancreatitis patients with concomitant hyperlipidemia are more prone to acute peripancreatic fluid accumulation and renal complications.
10.Epidemiological trends and major risk attribution analysis of pancreatic cancer in China, Japan and South Korea from 1990 to 2019
Yifei MA ; Hairong HE ; Tian'ao YAN ; Jiachun DING ; Ze'en ZHU ; Zheng WU ; Qingyong MA ; Zheng WANG
Chinese Journal of Digestive Surgery 2022;21(4):507-519
Objective:To analyze the epidemiological trends and major risk attribution of pancreatic cancer in China, Japan and South Korea from 1990 to 2019.Methods:The descriptive epidemiological method was conducted. The overall incidence rate, mortality rate, age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of pancreatic cancer in China, Japan and South Korea from 1990 to 2019 were collected from the Global Burden of Disease (GBD) Database. Age-standardized rates were calculated based on the worldwide standardized population structure provided by GBD Database 2019. Observation indicators: (1) incidence and motality of pancreatic cancer in China, Japan and South Korea in 2019; (2) age-period-cohort model analysis of incidence and mortality rates of pancreatic cancer in China, Japan and South Korea from 1990 to 2019; (3) trends of ASIR and ASMR of pancreatic cancer in China, Japan and South Korea from 1990 to 2019; (4) trends of major risk attribution of pancreatic cancer related death in China, Japan and South Korea from 1990 to 2019. Count data were represented as absolute numbers, percentages and ratios. Joinpoint V.4.7.0.0 software was used to calculate the annual percentage change (APC), the average annual percentage change (AAPC) of incidence and mortality rates of pancreatic cancer in different time periods and 95% confidence interval (95% CI). The age-period-cohort model in STATA V.15.0 software was used to analyze the influence of different ages, periods and birth cohorts on the risk of onset and death of pancreatic cancer after controlling the other two variables, with the risk effect size described as relative risk (95% CI). Results:(1) Incidence and motality of pancreatic cancer in China, Japan and South Korea in 2019. In 2019, the incidence rate of pancreatic cancer in China increased from 0.07/100,000 among 15-19 years old to 64.01/100,000 among 85-89 years old, with increasing from 0.09/100,000 to 94.71/100,000 in males and from 0.04/100,000 to 47.47/100,000 in females. The mortality rate of pancreatic cancer in China increased from 0.04/100,000 among 15-19 years old to 79.58/100,000 among 85-89 years old, with increasing from 0.05/100,000 to 116.50/100,000 in males and from 0.03/100,000 to 59.69/100,000 in females. The incidence rate of pancreatic cancer in Japan increased from 0.03/100,000 among 15-19 years old to 162.26/100,000 among 85-89 years old, with increasing from 0.03/100,000 to 177.67/100,000 in males and from 0.04/100,000 to 153.67/100,000 in females. The mortality rate of pancreatic cancer in Japan increased from 0.02/100,000 among 15-19 years old to 154.88/100,000 among 85-89 years old, with increasing from 0.02/100,000 to 170.93/100,000 in males and from 0.02/100,000 to 145.94/100,000 in females. The incidence rate of pancreatic cancer in South Korea increased from 0.04/100,000 among 15-19 years old to 136.78/100,000 among 85-89 years old, with increasing from 0.03/100,000 to 153.78/100,000 in males and from 0.04/100,000 to 129.73/100,000 in females. The mortality rate of pancreatic cancer in South Korea increased from 0.02/100,000 among 15-19 years old to 135.98/100,000 among 85-89 years old, with increasing from 0.02/100,000 to 156.21/100,000 in males and from 0.02/100,000 to 127.59/100,000 in females. The peak incidence and mortality of pancreatic cancer in China were found in males aged 65-69 years, and the overall incidence and mortality of males in different age groups were higher than those of females in the same age group. In Japan, the peak incidence of pancreatic cancer occurred in females aged 80-84 years and the peak mortality occurred in males aged 75-79 years. The morbidity and mortality of males aged <80 years were higher than those of females in the same age group, while the morbidity and mortality of males aged ≥80 years were lower than those of females in the same age group. In South Korea, the peak incidence of pancreatic cancer occurred in females aged 80-84 years, and the peak mortality occurred in males aged 70-74 years. The morbidity and mortality of males aged <75 years were higher than those of females in the same age group, while the morbidity and mortality of males aged ≥75 years were lower than those of females in the same age group. (2) Age-period-cohort model analysis of incidence and mortality rates of pancreatic cancer in China, Japan and South Korea from 1990 to 2019. Age effect: after adjustment for the period and cohort effects, the risk of incidence and mortality rates of pancreatic cancer in both males and females of China, Japan and South Korea increased with age, which is more obvious in females than males, and more obvious in Japanese than Chinese and Korean populations. Period effect: after adjustment for age and cohort effects, the risk of incidence and mortality rates of pancreatic cancer in both males and females of China, Japan and South Korea increased from 1990 to 2019, with the period effect more significant in the Chinese population. Cohort effect: after adjustment for age and period effects, the risk of morbidity and mortality rates of pancreatic cancer decreased with the passage of birth cohort in China, Japan and South Korea. (3) Trends of ASIR and ASMR of pancreatic cancer in China, Japan and South Korea from 1990 to 2019. The ASIR and ASMR of pancreatic cancer in China increased yearly from 1990 to 2019, and the ASIR and ASMR in 2019 were 1.82 times and 1.79 times those in 1990, respectively. The ASIR and ASMR of pancreatic cancer in Japan showed a slowly increasing trend, and the ASIR and ASMR in 2019 were 1.09 times and 1.05 times those in 1990, respectively. The ASIR and ASMR of pancreatic cancer in South Korea increased firstly, then decreased, and slowly increased. From 1990 to 2019, the AAPC of ASIR of pancreatic cancer in China was 2.08% (95% CI as 1.91% to 2.24%, P<0.05) and AAPC of ASMR was 2.02% (95% CI as 1.86% to 2.19%, P<0.05). The AAPC of ASIR of pancreatic cancer in Japan was 0.28% (95% CI as 0.15% to 0.42%, P<0.05) and AAPC of ASMR was 0.13% (95% CI as 0.03% to 0.24%, P<0.05). The AAPC of ASIR of pancreatic cancer in South Korea was 0.50% (95% CI as 0.21% to 0.80%, P<0.05) and AAPC of ASMR was 0.15% (95% CI as -0.10% to 0.40%, P>0.05). (4) Trends of major risk attribution of pancreatic cancer related death in China, Japan and South Korea from 1990 to 2019. The main risk factors for pancreatic cancer related death in China, Japan and South Korea from 1990 to 2019 were smoking, high fasting glucose and high body mass index (BMI). The trend of pancreatic cancer related death, mainly attributed to smoking, showed that the proportion of Chinese males increased from 31.4% in 1990 to 34.1% in 2000, then decreased to 31.1% in 2015, and then showed a slow increase to 31.7% in 2019. The proportion of Chinese females increased from 6.7% in 1990 to 10.4% in 2005 and then dropped to 8.7% in 2019. The proportion of Japanese males decreased from 38.8% in 1990 to 26.9% in 2019 and the proportion of Japanese females decreased from 20.9% in 1990 to 14.8% in 2019. The proportion of South Korean males decreased from 37.5% in 1990 to 30.3% in 2019 and the proportion of South Korean females decreased from 12.6% in 1990 to 10.0% in 2019. The trend of pancreatic cancer related death proportion, mainly attributed to high fasting blood glucose, showed that the proportion of Chinese males increased from 5.9% in 1990 to 7.1% in 2019 and the propor-tion of Chinese females increased from 6.2% in 1990 to 6.8% in 2019. The proportion of Japanese males increased from 7.0% in 1990 to 7.7% in 2019 and the proportion of females increased from 5.0% in 1990 to 5.5% in 2019. The proportion of South Korean males increased from 6.8% in 1990 to 9.7% in 2019 and the proportion of females increased from 6.1% in 1990 to 8.2% in 2019. The trend of pancreatic cancer related deaths proportion, attributed mainly to high BMI, showed that the proportion of Chinese males increased from 1.3% in 1990 to 3.0% in 2019 and the proportion of females increased from 2.1% in 1990 to 4.3% in 2019. The proportion of Japanese males increased from 2.0% in 1990 to 2.4% in 2019 and the proportion of females increased from 3.1% in 1990 to 3.4% in 2019. The proportion of South Korean males increased from 1.9% in 1990 to 3.1% in 2019 and the proportion of females increased from 3.4% in 1990 to 4.3% in 2019. Conclusions:The incidence of pancreatic cancer in China may continue to rise but to be stable in Japan and South Korea. The incidence of pancreatic cancer in females, especially elderly women, needs more attention. Smoking remains the most critical risk factor for pancreatic cancer. More attention should also be paid to the increased risk of pancreatic cancer associated with high BMI and high fasting plasma glucose.

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