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 Cases withdrawn by applicants, suspended appraisals, and non-accepted applications accounted for 8.7%, 2.3%, and 1.1%, respectively.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.

Objective To investigate the consistency and diagnostic efficacy of 1.5T and 3.0T MRI in the kidney clear cell likeli-hood score(ccLS)v2.0.Methods A retrospective collection was conducted on the data of 176 pathologically confirmed small renal mass(SRM).Two radiologists independently scored the MRI images using the ccLS v2.0.The Kappa test was used to assess inter-observer consistency,and receiver operating characteristic(ROC)curves were plotted to analyze the diagnostic efficacy.The area under the curve(AUC),sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NP V)were calculated.Results The inter-observer consistency for ccLS v2.0 score was good for 1.5T MRI and excellent for 3.0T MRI(Kappa values were 0.754 and 0.836,respectively).On 1.5T MRI examination,a ccLS≥4 points was identified as the optimal threshold,with AUC of 0.935 and 0.923 for the two radiologists,sensitivities of 92.45％and 88.68％,and specificities of 88.00％and 92.00％,respec-tively.For 3.0T MRI examination,using the same threshold,the AUC were 0.933 and 0.901,with sensitivities of 91.43％and 90.00％,and specificities of 78.57％and 78.57％for both radiologists.Conclusion The ccLS v2.0 demonstrates good consistency across high and low field intensity MRI,and a threshold of ccLS≥4 pionts provides high diagnostic efficacy for clear cell renal cell carcinoma(ccRCC).

Objective To investigate the value of predicting microsatellite instability(MSI)status in endometrial cancer based on whole-tumor apparent diffusion coefficient(ADC)histogram.Methods The data of 131 endometrial cancer patients who underwent preoperative MRI examination and were confirmed by pathology were retrospectively analyzed.According to the pathological immu-nohistochemical results,they were divided into microsatellite stability(MSS)group(103 cases)and MSI group(28 cases).The whole-tumor volume of interest(VOI)was outlined using ITK-SNAP software,and ADC histogram analysis was performed using uAI Research Portal software.The t-test or Mann-Whitney U-test were used to compare the differences between the two groups,and multifactorial logistic regression analysis was used to screen independent predictors for the above parameters with differences.The area under the curve(AUC),sensitivity and specificity were calculated using the receiver operating characteristic(ROC)curve.Results The ADC histogram parameters that were statistically significant between groups were ADC10th,ADC90th,ADCmaximum,ADCmedian,ADCmean,ADCrange,ADCinterquartile range,ADCuniformity,ADCvariance,ADCenergy,ADCentropy,ADCtotal energy,ADCroot mean square,ADCmean absolute deviation,ADCrobust mean absolute deviation,all the above parameters were significantly smaller in the MSI group than in the MSS group.Further multifactorial logistic regression analysis results showed that ADCmedian[odds ratio(OR)=1.019,P=0.020]and ADCroot mean square(OR=0.977,P=0.005)were independent predictors of the MSI status in endometrial cancer.The results of ROC curve showed that the AUC of ADCmedian and ADCroot mean square for predicting MSI status were 0.699 and 0.731,respectively,and the AUC of combining the two parameters to predict MSI status was 0.760,with a sensitivity of 57.14%and a specificity of 86.41%.Conclusion The parameters of ADCmedian and ADCroot mean square based on whole-tumor ADC histogram can be used to predict the MSI status of endometrial cancer,and the combined use of these two parameters helps to improve the efficacy of predicting MSI.

Objective To investigate the consistency and diagnostic efficacy of 1.5T and 3.0T MRI in the kidney clear cell likeli-hood score(ccLS)v2.0.Methods A retrospective collection was conducted on the data of 176 pathologically confirmed small renal mass(SRM).Two radiologists independently scored the MRI images using the ccLS v2.0.The Kappa test was used to assess inter-observer consistency,and receiver operating characteristic(ROC)curves were plotted to analyze the diagnostic efficacy.The area under the curve(AUC),sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NP V)were calculated.Results The inter-observer consistency for ccLS v2.0 score was good for 1.5T MRI and excellent for 3.0T MRI(Kappa values were 0.754 and 0.836,respectively).On 1.5T MRI examination,a ccLS≥4 points was identified as the optimal threshold,with AUC of 0.935 and 0.923 for the two radiologists,sensitivities of 92.45％and 88.68％,and specificities of 88.00％and 92.00％,respec-tively.For 3.0T MRI examination,using the same threshold,the AUC were 0.933 and 0.901,with sensitivities of 91.43％and 90.00％,and specificities of 78.57％and 78.57％for both radiologists.Conclusion The ccLS v2.0 demonstrates good consistency across high and low field intensity MRI,and a threshold of ccLS≥4 pionts provides high diagnostic efficacy for clear cell renal cell carcinoma(ccRCC).

Objective To investigate the value of predicting microsatellite instability(MSI)status in endometrial cancer based on whole-tumor apparent diffusion coefficient(ADC)histogram.Methods The data of 131 endometrial cancer patients who underwent preoperative MRI examination and were confirmed by pathology were retrospectively analyzed.According to the pathological immu-nohistochemical results,they were divided into microsatellite stability(MSS)group(103 cases)and MSI group(28 cases).The whole-tumor volume of interest(VOI)was outlined using ITK-SNAP software,and ADC histogram analysis was performed using uAI Research Portal software.The t-test or Mann-Whitney U-test were used to compare the differences between the two groups,and multifactorial logistic regression analysis was used to screen independent predictors for the above parameters with differences.The area under the curve(AUC),sensitivity and specificity were calculated using the receiver operating characteristic(ROC)curve.Results The ADC histogram parameters that were statistically significant between groups were ADC10th,ADC90th,ADCmaximum,ADCmedian,ADCmean,ADCrange,ADCinterquartile range,ADCuniformity,ADCvariance,ADCenergy,ADCentropy,ADCtotal energy,ADCroot mean square,ADCmean absolute deviation,ADCrobust mean absolute deviation,all the above parameters were significantly smaller in the MSI group than in the MSS group.Further multifactorial logistic regression analysis results showed that ADCmedian[odds ratio(OR)=1.019,P=0.020]and ADCroot mean square(OR=0.977,P=0.005)were independent predictors of the MSI status in endometrial cancer.The results of ROC curve showed that the AUC of ADCmedian and ADCroot mean square for predicting MSI status were 0.699 and 0.731,respectively,and the AUC of combining the two parameters to predict MSI status was 0.760,with a sensitivity of 57.14%and a specificity of 86.41%.Conclusion The parameters of ADCmedian and ADCroot mean square based on whole-tumor ADC histogram can be used to predict the MSI status of endometrial cancer,and the combined use of these two parameters helps to improve the efficacy of predicting MSI.

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