Guangdong Pan’s research while affiliated with Guangxi University of Chinese Medicine and other places

Background The global burden of non-alcoholic steatohepatitis (NASH)-related liver cancer (NRLC) is increasing, making NASH the fastest-growing cause of liver cancer worldwide. This study presents a comprehensive analysis of NRLC burden at the global, regional, and national levels, further categorized by age, sex, and sociodemographic index (SDI). Method Data on NRLC from the Global Burden of Disease, Injuries, and Risk Factors (GBD) study 2021 were downloaded at global, regional, and national levels. The numbers and age-standardized rates (ASRs) of incidence, mortality, and disability-adjusted life years (DALYs) were analyzed to quantify the global burden of NRLC. Additionally, percentage changes in ASRs were used to identify trends in NRLC from 1990 to 2021. Results Globally, both the number of cases and ASRs for NRLC increased between 1990 and 2021. In 2021, there were 42,291 new cases, 40,925 deaths, and 995,475 DALYs attributed to NRLC. East Asia, South Asia, and Southeast Asia reported the highest absolute case numbers, while Western, Southern, and Eastern Sub-Saharan Africa exhibited the highest ASRs. From 1990 to 2021, Australasia, Southern Latin America, and High-income North America showed the most significant increases in NRLC incidence. Nationally, Mongolia, Gambia, and Mozambique exhibited the highest ASR in 2021.The greatest percentage increases in ASIR occurred in Australia, the United Kingdom, and New Zealand between 1990 and 2021. NRLC incidence rates were higher in men and increased with age, peaking at 80–89 years. Similar patterns were observed for NRLC-related deaths and DALYs. Regionally, ASRs initially declined but then increased as SDI rose. At the national level, ASRs consistently decreased with higher SDI. Conclusion This study highlights the substantial burden of NRLC at global, regional, and national levels. Males and older individuals bear a higher disease burden, and considerable variation exists across different regions and countries. These findings provide critical insights for formulating effective strategies to prevent and manage NRLC.

Background Branched-chain amino acid metabolism is involved in the pathogenesis of various liver diseases. In this study, we investigate the potential role of branched-chain amino acid metabolism-related genes in the pathogenesis of hepatic ischemia reperfusion (HIRI). Methods The gene Expression profiles of HIRI were obtained from the Gene Expression Omnibu database. To determine the differential expression of branched-chain amino acid metabolism-related genes between HIRI and normal tissues. Then, the GO and KEGG analyses were performed, and the protein-protein interaction network was constructed. Next, the random forest and LASSO algorithms were used to screen hub genes, and machine learning techniques were used to build diagnostic models. immunoinfiltration was analyzed in both HIRI patients and controls and the ceRNA network was established. Finally, quantitative real-time PCR was used to verify the expression of hub gene. Results Based on data set GSE23649, three central DEGs (SLC7A5, SLC1A5, SLC43A2) were determined by the intersection of three machine learning algorithms and used to establish a nomogram that yielded a high predictive performance (area under the curve 0.733−0.922). In the external GSE15480 dataset, AUC value for three key genes is as high as 1.000. Further analysis of nomogram, decision curve and calibration curve also confirme the predictive efficacy of diagnosis. GSEA and GSVA suggest that these three marker genes were involved in multiple pathways associated with HIRI progression. Immunoinfiltration analysis suggest that the proportion of macrophages, neutrophils, aDCs, Treg, and Th1 cells in HIRI group is higher than that in control group, with statistical significance(P<0.05). The ceRNA network demonstrates the complex regulatory relationships among the three hub genes and these mRNA levels were further confirmed in mouse HIRI liver samples. Conclusions Our study have provided a comprehensive understanding of the association between branched-chain amino acid and HIRI, may provide potential target for HIRI treatment and diagnosis. And provide new insights into the mechanisms of HIRI. Graphical Abstract

Background and Aims Acute hepatitis E (AHE) is still a public health issue worldwide. Here, we report the global burden of AHE in 204 countries and territories from 1990 to 2019 by age, sex and socio‐demographic index (SDI), and predict the future trends to 2030. Methods Data on AHE were collected from the Global Burden of Diseases, Injuries and Risk Factors Study 2019. The average annual percentage change (AAPC) and joinpoint analysis were used to determine the burden trend. Results In 2019, there were 19.47 million (95% UI, 16.04 to 23.37 million) incident cases of AHE globally, with a 19% increase since 1990. Age‐standardized rate (ASR) of disability‐adjusted life years (DALYs), prevalent and incident cases declined from 1990 to 2019. In 2019, the ASR of incidence, prevalence and DALYs due to HEV infection were highest in the same regions of South Asia for both sexes. Southern Sub‐Saharan Africa presented the highest increases in the ASR for incidence of HEV infection in both males (AAPC = .25) and females (AAPC = .24) from 1990 to 2019. Incident cases are higher in males than females before 55–59 years old. The SDI values were negatively correlated with the age‐standardized DALYs. Between 2019 and 2030, the ASR for incidence and prevalence of HEV for both sexes showed an increasing trend. Conclusions Although the overall ASR of AHE decreased, the burden of AHE remains an underappreciated problem for society. The findings may provide useful information for policymakers to develop appropriate strategies aimed at reducing the burden of AHE.

Background Appendicitis is the most common abdominal surgical emergency worldwide, and its burden has been changing. We report the level and trends of appendicitis prevalence, and incidence; and years lived with disability (YLD) in 204 countries and territories from 1990 to 2019, based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods The numbers and age-standardized prevalence, incidence, and YLD rates per 100,000 population of appendicitis were estimated across regions and countries by age, sex, and sociodemographic index (SDI). All the estimates were reported with 95% uncertainty intervals (UIs). Results Globally, the age-standardized prevalence and incidence rates of appendicitis in 2019 were 8.7 (95% UI 6.9 to 11.0) and 229.9 (95% UI 180.9 to 291.0) per 100,000 population, with increases of 20.8% (95% UI 18.9 to 23.0%) and 20.5% (95% UI 18.7 to 22.8%) from 1990 to 2019, respectively. Additionally, the age-standardized YLDs rate was 2.7 (95% UI 1.8 to 3.9) in 2019, with an increase of 20.4% (95% UI 16.2 to 25.1%) from 1990 to 2019. In 2019, the age-standardized prevalence, incidence, and YLD rates peaked in the 15-to-19-year age groups in both male and female individuals. However, no statistically significant differences were observed between the male and female individuals in all groups. Ethiopia, India, and Nigeria showed the largest increases in the age-standardized prevalence rate between 1990 and 2019. Generally, positive associations were found between the age-standardized YLD rates and SDI at the regional and national levels. Conclusions Appendicitis remains a major public health challenge globally. Increasing awareness of appendicitis and its risk factors and the importance of early diagnosis and treatment is warranted to reduce its the burden.

Background: Hepatitis is a major public health challenge and a leading cause of death worldwide. We aimed to study the cause-specific incidence and temporal trends of acute viral hepatitis(AVH). Methods: Data on AVH etiologies were available from the Global Burden of Disease study 2019. Estimated annual percentage change (EAPC) was used to quantify temporal trend in AVH age-standardized incidence rates (ASIRs) by region, sex, and etiology. Results: From 1990 to 2019, the global incidence of AVH increased by 8.02%, from 244,350,063 in 1990 to 263,951,645 in 2019, with an average decreasing ASIR of 0.52% (95%CI -0.58% to -0.45%) annually. The ASIR of AVH due to hepatitis B virus (HBV) decreased, while those of hepatitis A (HAV), hepatitis C (HCV), and hepatitis E (HEV) remained stable, with EAPCs(95%CI) of -1.47 (-1.58 to -1.36), 0 (-0.09 to 0.09), -0.35(-0.83 to -0.13), and -0.16(-0.41 to 0.09), respectively. Although the number of new AVH cases increased in the Low sociodemographic index (SDI), Low-middle SDI regions, the ASIRs decreased in all 5 SDI regions. Globally, HAV and HBV are the leading causes of acute hepatitis. The EAPC is significantly associated with a baseline ASIR of less than 5,500 per 100,000 population (ρ=-0.44), and with the 2019 human development index(HDI) (ρ=0.16) for AVH. Conclusions: Although the ASIR of AVH showed a generally decreasing trend, the burden of AVH remains a major public health challenge globally. The findings may be helpful for policymakers in establishing appropriate policies to reduce the viral hepatitis burden.

Background Liver cancer is one of the most common cancers worldwide. We aimed to report the burden of liver cancer at the global, regional, and national levels in 204 countries from 1990 to 2019, stratified by etiology, sex, age, and sociodemographic index (SDI). Methods Data of mortality, incidence, and disability-adjusted life years (DALYs) of liver cancer and its etiology were available from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2019. The trends in the liver cancer burden were assessed by the annual percentage change. All estimates are presented as numbers and age-standardized rates (ASRs) per 100,000 population, with uncertainty intervals (UIs). Results Globally, 484,577 (95% UI 444,091–525,798) mortalities, 534,364 (486,550–588,639) incident cases, and 12,528,422 (11,400,671–13,687,675) disability-adjusted life years (DALYs) due to liver cancer occurred in 2019. The ASRs were 5.95 (5.44–6.44), 6.51 (5.95–7.16), and 151.08 (137.53–164.8) per 100,000 population for the mortalities, incidences, and DALYs, respectively. From 1990 to 2019, the numbers increased, whereas the ASRs decreased. Hepatitis B and Hepatitis C are the major causes of liver cancer mortality. The liver cancer mortality in 2019 increased with age, peaking at 65–69 and 70–74 age group in males and females, respectively, and the number was higher in males than in females. Generally, there were nonlinear associations between the ASR and SDIs values at the regional and national levels. China had the highest numbers of mortalities, incident cases, and DALYs, whereas Mongolia has the highest ASR in 2019. Conclusion Liver cancer remains a major public health issue worldwide, but etiological and geographical variations exist. It is necessary to increase awareness of the population regarding liver cancer, its etiologies and the importance of early detection, and diagnosis and treatment.

Background Recent randomized controlled trials revealed the combination of gemcitabine and capecitabine (GemCap) regime shows promising efficacy in pancreatic cancer patients. Here, we conducted a meta-analysis to compare the efficacy and safety of gemcitabine (Gem) with GemCap for pancreatic cancer. Methods The database of MEDLINE (PubMed), EMBASE, Cochrane Central Controster of Controlled Trials, Web of Science was searched for relevant randomized controlled trials before 8 April, 2020. The outcomes were overall survival (OS), 12-month survival rate, progress free survival (PFS), partial response rate (PRR), objective response rate (ORR), and Grade 3/4 toxicities. Results Five randomized controlled trials involving 1879 patients were included in this study. The results showed that GemCap significantly improves the OS (hazard ratio = 1.15, 95% CI: 1.037-1.276, P = .008), PFS (hazard ratio = 1.211, 95% CI 1.09-1.344, P = 0), PRR (relative risk (RR) = 0.649, 95% CI 0.488-0.862, P = .003), ORR (RR = 0.605, 95% CI 0.458-0.799, P = 0), and the overall toxicity (RR = 0.708, 95% CI 0.620-0.808, P = .000) compared to Gem alone. However, no significant difference was found in 12-month survival. Conclusions Despite a higher incidence of Grade 3/4 toxicity, GemCap was associated with better outcomes of OS, PFS, PRR, ORR, as compared with Gem, which is likely to become a promising therapy for pancreatic cancer.

Background The global burden of gallbladder and biliary tract cancer (GBTC) is increasing. A comprehensive evaluation of the burden is crucial to improve strategies for GBTC prevention and treatment. Methods The incidence rates, mortality, and disability‐adjusted life years (DALYs) of GBTC from 1990 to 2017 were extracted from the Global Burden of Diseases Study (GBD) 2017. Estimated annual percent changes (EAPCs) were calculated to quantify GBTC trends during the study period. Results Globally, there were 210,878 new cases, 173,974 deaths, and 3,483,046 DALYs because of GBTC in 2017. GBTC incidence increased by 76%, mortality increased by 65%, and DALYs increased by 52% from 1990 to 2017. In addition, relatively higher Socio‐Demographic Index regions had greater incidence and death rates but greatly decreased age‐standardized incidence rate (ASIR) and age‐standardized death rate (ASDR). At the national level, Chile had the highest ASIR (10.38 per 100,000 population) and the highest ASDR (10.43 per 100,000 population) in 2017. The largest increases in ASIR (EAPC, 3.38) and ASDR (EAPC, 3.39) were observed in Georgia. Nonlinear associations were observed between the ASDR, the Socio‐Demographic Index, and DALYs at the 21 GBD regional levels and at the national level. The proportions of GBTC age‐standardized deaths and DALYs attributable to high body mass index were 15.4% and 16%, respectively. Conclusions GBTC remains a major health burden worldwide. These findings are expected to prompt policymakers to establish a cost‐effective method for the early diagnosis, prevention, and treatment of GBTC, reducing its modifiable risk factors and reversing its increasing trends. Lay Summary Although the rates of age‐standardized incidence, death, and disability‐adjusted life‐years for gallbladder and biliary tract cancer decreased from 1990 to 2017, the numbers of these measures increased. Nonlinear associations existed between the age‐standardized death rate, the Socio‐Demographic Index, and disability‐adjusted life‐years at the 21 regional and national levels in the Global Burden of Disease Study.

Background Pancreatitis is a critical public health problem, and the burden of pancreatitis is increasing. We report the rates and trends of the prevalence, incidence, and years lived with disability (YLDs) for pancreatitis at the global, regional, and national levels in 195 countries and territories from 1990 to 2017, stratified by sex, age, and sociodemographic index (SDI). Methods Data on pancreatitis were available from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Numbers and age-standardized prevalence, incidence, and YLDs’ rates per 100,000 population were estimated through a systematic analysis of modeled data from the 2017 GBD study. Both acute and chronic pancreatitis are being modeled separately in the GBD 2017; however, our data show acute and chronic pancreatitis together. Estimates were reported with uncertainty intervals (UIs). Results Globally, in 2017, the age-standardized rates were 76.2 (95% UIs 68.9 to 83.4), 20.6 (19.2 to 22.1), and 4.5 (2.3 to 7.6) per 100,000 population for the point prevalence, incidence, and YLDs, respectively. From 1990 to 2017, the percent changes in the age-standardized prevalence and YLDs rates increased, whereas the age-standardized incidence rate decreased. The global prevalence increased with age up to 60–64 years and 44–49 years in females and males, respectively, and then decreased, with no significant difference between females and males. The global prevalence rate increased with age, peaking in the 95+ age group, with no difference between sexes. Generally, positive correlation between age-standardized YLDs and SDIs at the regional and national levels was observed. Slovakia (297.7 [273.4 to 325.3]), Belgium (274.3 [242.6 to 306.5]), and Poland (266.7 [248.2 to 284.4]) had the highest age-standardized prevalence rates in 2017. Taiwan (Province of China) (104.2% [94.8 to 115.2%]), Maldives (72.4% [66.5 to 79.2%]), and Iceland (64.8% [57.2 to 72.9%]) had the largest increases in age-standardized prevalence rates from 1990 to 2017. Conclusions Pancreatitis is a major public health issue worldwide. The age-standardized prevalence and YLDs rates increased, but the age-standardized incidence rate decreased from 1990 to 2017. Improving the quality of pancreatitis health data in all regions and countries is strongly recommended for better monitoring the burden of pancreatitis.