ObjectiveTo investigate the associations of multiple glycolipid metabolic indicators and their cumulative abnormality burden with incident colorectal cancer risk in a general population-based prospective cohort, and to examine the mediating role of glycolipid metabolic abnormalities in the relationships between smoking, alcohol consumption, physical activity, and colorectal cancer incidence. MethodsA total of 17 897 eligible participants recruited from the Taizhou Cohort between 2011 and 2014 were included. Cox proportional hazards regression models were used to assess the associations of conventional and derived glycolipid indicators, as well as a glycolipid abnormality index constructed from total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and insulin, with incident colorectal cancer risk. Restricted cubic spline models were applied to evaluate dose-response relationships for major indicators. Receiver operating characteristic curves were generated to compare predictive performance across indicators. Mediation analyses were conducted to assess the mediating effects of the glycolipid abnormality index on the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence. ResultsDuring a median follow-up of 11.2 years, 102 incident colorectal cancer cases were identified, with an incidence density of 51.2 per 100 000 person-years. After adjustment for potential confounders, Cox proportional hazards regression analyses showed that decreased high-density lipoprotein cholesterol was associated with a 1.74-fold higher risk of colorectal cancer (HR=1.74, 95%CI: 1.03‒2.95), elevated low-density lipoprotein cholesterol was associated with a 1.78-fold higher risk (HR=1.78, 95%CI: 1.05‒3.02), and abnormal fasting plasma glucose was associated with a 1.86-fold higher risk (HR=1.86, 95%CI: 1.15‒3.02). Triglycerides and fasting plasma glucose showed an approximately linear increasing association with colorectal cancer risk in multivariable restricted cubic spline models. The glycolipid abnormality index showed a clear gradient association with colorectal cancer risk; participants with three or more abnormal indicators had a 3.08-fold higher risk than those without abnormalities (HR=3.08, 95%CI: 1.60‒5.92). The area under the curve was 0.795, higher than that of individual glycolipid indicators and other combined indices, and gender-stratified analyses showed generally consistent patterns. Glycolipid metabolic abnormalities partially mediated the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence, with mediation proportions of 8.33%, 9.45%, and 9.04%, respectively. ConclusionGlycolipid metabolic abnormalities are associated with an increased risk of incident colorectal cancer. The glycolipid abnormality index shows an increasing relationship with colorectal cancer risk and demonstrates better discrimination, and it partially mediates the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence in the overall population.

After more than ten years of development, retinal organoid (RO) based on pluripotent stem cells can highly simulate the development process of human retina, provide insight into the mechanism of retinal development and provide new treatments for retinal diseases.At present, RO has been widely used in the research of the mechanism and treatment of retinal diseases, especially in retinitis pigmentosa (RP).This review summarizes the methods of preparing RO from human pluripotent stem cells, and elaborates the mechanism and therapeutic application of RO-RP disease model in different mutated genes such as PRPF31, RPGR, CRB1, RP2, IMPG2, NR2E3, USH2A, PDE6B and TRNT1, as well as the research progress of RO in drug screening, drug toxicity testing, gene therapy and cell therapy, and discusses the research and application challenges of RO.

Objective:To summarize the prenatal ultrasound features of fetal cleidocranial dysplasia (CCD) and provide references for clinical consultation.Methods:A retrospective analysis was conducted on the prenatal ultrasound features, genetic testing results, and prognosis of a CCD fetus diagnosed at Qingdao Women and Children's Hospital in June 2023. Relevant literature on CCD was retrieved from the CNKI, Yiigle, Wanfang, and PubMed databases including cases confirmed by genetic testing or postnatal clinical phenotype and imaging with relatively complete prenatal ultrasound information. The prenatal ultrasound features of CCD fetuses were summarized using descriptive statistical analysis.Results:(1) In this case, prenatal ultrasound at 25 weeks of gestation indicated widened cranial sutures with clear near-field intracranial structures, absence of the nasal bone, shortened and rigid bilateral clavicles, and mildly shortened bilateral femurs and humeri. Chromosomal karyotyping and chromosomal microarray analysis showed no abnormalities, but whole exome sequencing detected a RUNX2 gene mutation, leading to a diagnosis of CCD combined with the ultrasound phenotype. At 36 weeks of gestation, the mother experienced premature rupture of membranes and delivered a male infant vaginally. Bedside X-rays indicated bilateral wet lungs and bilateral clavicular dysplasia in the newborn. Telephone follow-up at 9 months showed no abnormalities in growth and development. (2) Literature review: Thirteen cases from 13 articles were included, along with this case, totaling 14 CCD fetuses. The main ultrasound phenotypes of CCD fetuses were clavicular dysplasia (12/14), incomplete cranial ossification (10/14), absence of the nasal bone (8/14), and shortening of the femur (12/14). Other ultrasound phenotypes included scapular dysplasia, short ribs, and increased interocular distance. Conclusion:Clavicular dysplasia and incomplete cranial ossification are the most specific signs of fetal CCD, while absence of the nasal bone and mild femoral shortening are secondary features of CCD.