Ruiwen Zhao’s research while affiliated with First Affiliated Hospital of China Medical University and other places

Incidence of liver cancer as one of the most common cancers worldwide and become the significant contributor for the mortality among cancer patients. The disease burden, risk factors, and trends in incidence and mortality of liver cancer globally was described subsequently estimated the projections of liver cancer incidence or mortality by 2040. Data regarding age-standardized incidence and mortality rates for liver cancer was obtained from multiple databases, including GLOBOCAN 2020, CI5 volumes I–XI, WHO mortality database, and Global Burden of Disease (GBD)-2019. Concentrating on worldwide variations, this thorough analysis offers insights into patterns of incidence and mortality based on gender and age. Our findings encompass significant indicators, including age-standardized rates (ASRs), average annual percentage change (AAPC), and future projections extending up to the year 2040. Liver cancer holds the sixth position in terms of most frequently diagnosed cancers and stands as the sixth leading cause of cancer-related deaths worldwide in 2020, accounting for 905,677 new cases and 782,000 fatalities. Additionally, liver cancer contributed to 12,528,421 age-standardized disability-adjusted life years (DALYs), with an age-standardized DALYs rate of 161.92 in 2019 worldwide. The age-specific incidence rates exhibited significant variations across different regions, showing a fivefold difference in males and females. A significant increase in incidence was observed in North Europe and Asia, while North African countries reported a higher mortality burden (ASR, 10 per 100,000) compared to developed countries. Since last few years, the incidence and mortality rates have increased and attained Annual Average Percentage Change (AAPC) incidence rate of 7.7 (95% CI 3.9–11.6) for men and the highest AAPC mortality rate of 12.2 (95% CI 9.5–15.0) for women. In 2019, Western Europe emerged as the high-risk region for DALYs related to smoking and alcohol consumption, while high-income North America carried a high risk for DALYs associated with a high body-mass index. The projected trend indicates a surge in new liver cancer incident cases, expected to rise from around 905,347 to an estimated 1,392,474 by 2040. This study described the evidence pertinent to higher incidence trends in liver cancer, particularly among both young and older adults, encompassing males and females, as well as those who are HIV-infected and HBsAg positive. A significant rise in the young population poses a significant public health concern that warrants attention from healthcare professionals to prioritize the promotion of health awareness and the development of effective cancer prevention strategies, particularly in many developing countries.

Background The incidence and mortality of gynaecological cancers can significantly impact women's quality of life and increase the health care burden for organisations globally. The objective of this study was to evaluate global inequalities in the incidence and mortality of gynaecological cancers in 2022, based on The Global Cancer Observatory (GLOBOCAN) 2022 estimates. The future burden of gynaecological cancers (GCs) in 2050 was also projected. Methods Data regarding to the total cases and deaths related to gynaecological cancer, as well as cases and deaths pertaining to different subtypes of GCs, gathered from the GLOBOCAN database for the year 2022. Predictions for the number of cases and deaths in the year 2050 were derived from global demographic projections, categorised by world region and Human Development Index (HDI). Results In 2022, there were 1 473 427 new cases of GCs and 680 372 deaths. The incidence of gynecological cancer reached 30.3 per 100 000, and the mortality rate hit 13.2 per 100 000. The age-standardised incidence of GCs in Eastern Africa is higher than 50 per 100 000, whereas the age-standardised incidence in Northern Africa is 17.1 per 100 000. The highest mortality rates were found in East Africa (ASMR (age-standardised mortality rates) of 35.3 per 100 000) and the lowest in Australia and New Zealand (ASMR of 8.1 per 100 000). These are related to the endemic areas of HIV and HPV. Very High HDI countries had the highest incidence of GCs, with ASIR (age-standardised incidence rates) of 34.8 per 100 000, and low HDI countries had the second highest incidence rate, with an ASIR of 33.0 per 100 000. Eswatini had the highest incidence and mortality (105.4 per 100 000; 71.1 per 100 000) and Yemen the lowest (5.8 per 100 000; 4.4 per 100 000). If the current trends in morbidity and mortality are maintained, number of new cases and deaths from female reproductive tract tumours is projected to increase over the next two decades. Conclusions In 2022, gynaecological cancers accounted for 1 473 427 new cases and 680 372 deaths globally, with significant regional disparities in incidence and mortality rates. The highest rates were observed in Eastern Africa and countries with very high and low HDI, with Eswatini recording the most severe statistics. If current trends continue, the number of new cases and deaths from gynaecological cancers is expected to rise over the next two decades, highlighting the urgent need for effective interventions.

Copper is an important metal micronutrient, required for the balanced growth and normal physiological functions of human organism. Copper-related toxicity and dysbalanced metabolism were associated with the disruption of intracellular respiration and the development of various diseases, including cancer. Notably, copper-induced cell death was defined as cuproptosis which was also observed in malignant cells, representing an attractive anti-cancer instrument. Excess of intracellular copper leads to the aggregation of lipoylation proteins and toxic stress, ultimately resulting in the activation of cell death. Differential expression of cuproptosis-related genes was detected in normal and malignant tissues. Cuproptosis-related genes were also linked to the regulation of oxidative stress, immune cell responses, and composition of tumor microenvironment. Activation of cuproptosis was associated with increased expression of redox-metabolism-regulating genes, such as ferredoxin 1 (FDX1), lipoic acid synthetase (LIAS), lipoyltransferase 1 (LIPT1), dihydrolipoamide dehydrogenase (DLD), drolipoamide S-acetyltransferase (DLAT), pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1), and pyruvate dehydrogenase E1 subunit beta (PDHB)). Accordingly, copper-activated network was suggested as an attractive target in cancer therapy. Mechanisms of cuproptosis and regulation of cuproptosis-related genes in different cancers and tumor microenvironment are discussed in this study. The analysis of current findings indicates that therapeutic regulation of copper signaling, and activation of cuproptosis-related targets may provide an effective tool for the improvement of immunotherapy regimens. Graphical Abstract

Background: There are some reports indicating that carcinoembryonic antigen associated cell adhesion molecule 5 (CEACAM5) can act as a diagnostic indicator or molecular marker for GC, but its upstream regulatory pathway still needs to be explored. microRNAs (miRNAs) regulate gene expression at the translation level and fulfil a crucial role in GC physiologyin, whether miR-3149 in family members can affect GC progression by regulating CEACAM5 is still unclear. Methods: miR-3149 and CEACAM5 expressions in GC tissues and cells (N87, AGS, and HGC-27) were observed by RT-qPCR or Western blot. Intervened the miR-3149 and CEACAM5 expression in GC cells, CCK8, Wound healing, Transwell and flow cytometry assays evaluated cell activity and function separately, while detecting related proteins. Predicted the target of miR-3149 and the expression of CEACAM5 in tumor tissue through bioinformatics analysis and evaluated the correlation between both using Spearman analysis. Verified the targeting relationship between the two through the Luciferase reporter assay. Conducted another rescue experiment on CEACAM5 overexpression to further verify this relationship. Results: In GC tissues and cells, miR-3149 and CEACAM5 expression levels were respectively down-regulated and up-regulated. Transfection of miR-3149 mimics or inhibitors respectively reduced or increased GC cell apoptosis and inhibited or encouraged cell proliferation, migration and invasion, which were shown to be enhanced or inhibited respectively by transfection of OE-CEACAM5/Si-CEACAM5, while their apoptosis rate decreased or increased. miR-3149 could target regulating CEACAM5, and showed an inverse correlation with the expression of CEACAM5. The impacts of miR-3149 mimics on the malignancy progression of GC could be partially reversed by OE-CEACAM5. Conclusion: The results indicate that miR-3149 can downregulate the expression of CEACAM5 to inhibit the malignancy progression, as a GC suppressor,which identify a new miRNA mediated tumor suppressor mechanism in GC.

Background Impact of radiotherapy (RT) for esophageal cancer (EC) patients on the development of secondary head and neck cancer (SHNC) remains equivocal. The objective of this study was to investigate the link between definitive RT used for EC treatment and subsequent SHNC. Methods This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of primary EC patients. Fine-Gray competing risk regression and standardized incidence ratio (SIR) and propensity score matching (PSM) method were used to match SHNC patients with only primary head and neck cancer (HNC) patients. Overall survival (OS) rates were applied by Kaplan-Meier analysis. Results In total, 14,158 EC patients from the SEER database were included, of which 9,239 patients (65.3%) received RT and 4,919 patients (34.7%) received no radiation therapy (NRT). After a 12-month latency period, 110 patients (1.2%) in the RT group and 36 patients (0.7%) in the NRT group experienced the development of SHNC. In individuals with primary EC, there was an increased incidence of SHNC compared to the general US population (SIR = 5.95, 95% confidence interval (CI): 5.15 - 6.84). Specifically, the SIR for SHNC was 8.04 (95% CI: 6.78 - 9.47) in the RT group and 3.51 (95% CI: 2.64 - 4.58) in the NRT group. Patients who developed SHNC after RT exhibited significantly lower OS compared to those after NRT. Following PSM, the OS of patients who developed SHNC after RT remained significantly lower than that of matched patients with only primary HNC. Conclusion An association was discovered between RT for EC and increased long-term risk of SHNC. This work enables radiation oncologists to implement mitigation strategies to reduce the long-term risk of SHNC in patients who have received RT following primary EC.

Objective To evaluate the current status of trial registration on the Chinese Clinical Trial Registry (ChiCTR). Design In this descriptive study, a multi-dimensional grouping analysis was conducted to estimate trends in the annual trial registration, geographical distribution, sources of funding, targeted diseases, and trial subtypes. Setting We have analyzed all clinical trial records (over 30,000) registered on the Chinese Clinical Trial Registry (ChiCTR) from 2007 to 2020 executed in China. Main outcome(s) and measure(s) The main outcome was the baseline characteristics of registered trials. These trials were categorized and analyzed based on geographical distribution, year of implementation, disease type, resource and funding type, trial duration, trial phase, and the type of experimental approach. Results From 2008 to 2017, a consistent upward trend in clinical trial registrations was observed, showing an average annual growth rate of 29.2%. The most significant year-on-year (yoy%) growth in registrations occurred in 2014 (62%) and 2018 (68.5%). Public funding represented the predominant source of funding in the Chinese healthcare system. The top five ChiCTR registration sites for all disease types were highly populated urban regions of China, including Shanghai (5,658 trials, 18%), Beijing (5,127 trials, 16%), Guangdong (3,612 trials, 11%), Sichuan (2,448 trials, 8%), and Jiangsu (2,196 trials, 7%). Trials targeting neoplastic diseases accounted for the largest portion of registrations, followed by cardio/cerebrovascular disease (CCVD) and orthopedic diseases-related trials. The largest proportions of registration trial duration were 1–2 years, less than 1 year, and 2–3 years (at 27.36, 26.71, and 22.46%). In the case of the research phase, the top three types of all the registered trials are exploratory research, post-marketing drugs, and clinical trials of new therapeutic technology. Conclusion and relevance Oncological and cardiovascular diseases receive the highest share of national public funding for medical clinical trial-based research in China. Publicly funded trials represent a major segment of the ChiCTR registry, indicating the dominating role of public governance in this health research sector. Furthermore, the growing number of analyzed records reflect the escalation of clinical research activities in China. The tendency to distribute funding resources toward exceedingly populated areas with the highest incidence of oncological and cardiovascular diseases reveals an aim to reduce the dominating disease burden in the urban conglomerates in China.