Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China

BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively.METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected.The incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were measured.Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD.RESULTS A total of 83.13%of participants with MAFLD had normal ALT levels.The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group.Compared with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,respectively.CONCLUSION Most participants with MAFLD had normal ALT levels.Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.

Who should be screened for colorectal cancer and how can it be prevented more effectively?

In this editorial,we comment on the article published by Agatsuma et al in a recent issue of the World J Gastroenterol(2024;30:1368-1376).We firmly concur with Agatsuma et al regarding the vital significance of colorectal cancer(CRC)screening as a public health strategy to diminish disease burden.Individuals exposed to risk factors for CRC,those with comorbid conditions,and those with limited health literacy should undergo screening.However,we believe that more regular screenings should be accompanied by a greater focus on primary prevention(PP)of CRC.CRC remains a significant global health challenge,and its incidence is strongly linked to age,lifestyle,and socioeconomic factors.It is particularly noteworthy that the majority of CRC patients are diagnosed outside of established screening pathways and frequently at an advanced stage of the disease,and the majority of patients possess inadequate or even nonexistent knowledge regarding CRC,which significantly impacts the prognosis and imposes a substantial economic burden.This study revealed that CRC identified during hospital visits for comorbid conditions was typically diagnosed at an earlier stage than detected via symptomatic pathways.Remarkably,early incidental detection of CRC aligns closely with the timing of discovery through routine cancer screenings.This suggests that by adopting more inclusive screening protocols that combine opportunistic testing with traditional screening methods,health care systems can create a more comprehensive safety net for individuals at risk of CRC.However,before maximizing the health benefits of screening programs,it is essential to make additional efforts prior to screening,such as raising awareness via public education,risk assessment,and personalized recommendations,enhancing the knowledge and skills of health care professionals,optimizing the accessibility and convenience of screening processes,ensuring the quality and safety of screening services,strengthening follow-up and support systems,and providing policy support and financial investment.The establishment of a comprehensive screening system often requires substantial investment in human,material,and financial resources,which can be challenging to achieve in regions with limited health care resources.Strengthening PP strategies can reduce the disease burden by targeting the cause,representing a more cost-effective and impactful approach.Establishing a comprehensive cancer PP service platform that integrates authoritative public education on malignant tumor PP,individualized malignant tumor risk assessment,and self-health management assistance accessible to the entire population will significantly enhance the overall effectiveness of CRC PP strategies.

An ROS-Responsive Antioxidative Macromolecular Prodrug of Caffeate for Uveitis Treatment

Uveitis is a sophisticated syndrome showing a high relevance with reactive oxygen species(ROS).Herein,an ROS-responsive PEGylated polypeptide based macromolecular prodrug of herbaceous antioxidant ethyl caffeate(EC)is designed via phenylboronic esters with improved solubility for the alleviation of uveitis.The antioxidative 4-hydroxybenzyl alcohol(HBA)and EC can be released from the macromolecular EC prodrug under the stimulation of ROS,which can effectively protect cells against oxidative stress-induced injury in an ROS-depletion way.The antioxidative and protective effects of the macromolecular EC prodrug in vivo are further verified in a uveitis mouse model.Overall,this work not only provides a handy method to synthesize a phenylboronic ester-bearing EC prodrug which is highly sensitive to pathological ROS,but also depicts a promising future to apply macromolecular antioxidative prodrugs in the treatment of uveitis as well as other ROS-related diseases.