Objective To analyze the case distribution, trends and dispute causes in initial verification of occupational disease diagnosis (VODD) in Guangzhou City from 2015 to 2024. Methods A total of 1 006 cases applying for initial VODD in Guangzhou City from 2015 to 2024 were selected as the study subjects using the convenience sampling method. Data on their basic information, disease category distribution, acceptance status, and dispute-related characteristics were collected and analyzed. Results Among the 1 006 VODD application cases, 884 completed the verification process, accounting for 87.9%. Cases withdrawn by applicants, suspended appraisals, and non-accepted applications accounted for 8.7%, 2.3%, and 1.1%, respectively. Among the 884 cases that completed verification, the most prevalent occupational diseases were occupational noise-induced hearing loss, occupational tumors (benzene-induced leukemia), occupational pneumoconiosis, and occupational chronic benzene poisoning, accounting for 77.0%. Cases appraised as occupational diseases accounted for 41.5%, and the proportion showed a decreasing trend over the years (P<0.01). The inconsistency rate between VODD conclusions and occupational disease diagnostic conclusions was 4.4%, mainly attributable to insufficient cooperation during clinical examinations and incomplete submission of required materials. Conclusion The initial VODD in Guangzhou City from 2015 to 2024 demonstrated relatively concentrated disease categories and controllable dispute levels. Clinical examination compliance and standardization of material submission were key factors affecting consistency of appraisal conclusions. It is proposed that effective measures be adopted to rectify existing deficiencies, with the aim of further enhancing the standardization and refinement of VODD practice.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems