Objective:To analyze the changes of DNA methylation in peripheral blood mononuclear cells (PBMC) of patients with hepatocellular carcinoma (HCC) and to evaluate the clinical value of a combined model based on FSIP1 gene methylation on the early diagnosis of HCC.Methods:This is a case-control study. From May 2023 to September 2024, 183 HCC patients and 155 healthy controls were collected in Qilu Hospital of Shandong University. The selected study subjects were divided into three cohorts: 14 HCC patients and 39 healthy controls formed the discovery cohort, a screening cohort consisted of 36 HCC patients and 39 healthy controls, 133 HCC patients and 77 healthy controls were included in the model construction cohort. 935k methylation chip analysis was used to identify specific differentially methylated sites in peripheral blood PBMC of the discovery cohort. The absolute value of the average methylation level difference between HCC group and healthy control group (|Δβ|) and P value were calculated. Then targeted bisulfite sequencing was used to verify the differentially methylated sites in the screening cohort. Finally, based on MethylTarget methylation sequencing technology, differential methylation sites were further verified in model construction cohort (divided into training set and validation set, training set consisted of 99 HCC patients and 57 healthy controls; validation set consisted of 34 HCC patients and 20 healthy controls). HCC early diagnosis model was constructed by random forest algorithm combined with clinical parameters and the diagnostic performance of the model was evaluated by receiver operating characteristic (ROC) curve in the validation set. Results:The total of 7 249 differentially methylated sites between HCC patients and healthy controls in discovery cohort were selected under the rule of |Δβ|≥0.06 and P<0.01. Among them, the cg02155073 site located on FSIP1 was hypermethylated in PBMC of HCC patients in the screening cohort and model cohort ( P<0.001). The AUC of HCC early diagnosis model (FmAP) based on FSIPI in the validation set was 0.967 (95% CI 0.924-1.000); sensitivity was 88%, specificity was 95%. The model had good diagnostic efficacy for patients with early HCC, stage Ⅰ-Ⅱ HCC AUC was 0.958 (95% CI 0.898-1.000). The FmAP model also had diagnostic value for tumor size <2 cm HCC and AFP negative HCC, with AUC of 0.955 (95% CI 0.898-1.000) and 0.964 (95% CI 0.934-0.994).The sensitivity were 92% and 93% and specificity both were 84%. Conclusion:The FmAP model based on FSIP1 gene methylation has good clinical value for the early diagnosis of hepatocellular carcinoma.

Objective:To analyze the changes of DNA methylation in peripheral blood mononuclear cells (PBMC) of patients with hepatocellular carcinoma (HCC) and to evaluate the clinical value of a combined model based on FSIP1 gene methylation on the early diagnosis of HCC.Methods:This is a case-control study. From May 2023 to September 2024, 183 HCC patients and 155 healthy controls were collected in Qilu Hospital of Shandong University. The selected study subjects were divided into three cohorts: 14 HCC patients and 39 healthy controls formed the discovery cohort, a screening cohort consisted of 36 HCC patients and 39 healthy controls, 133 HCC patients and 77 healthy controls were included in the model construction cohort. 935k methylation chip analysis was used to identify specific differentially methylated sites in peripheral blood PBMC of the discovery cohort. The absolute value of the average methylation level difference between HCC group and healthy control group (|Δβ|) and P value were calculated. Then targeted bisulfite sequencing was used to verify the differentially methylated sites in the screening cohort. Finally, based on MethylTarget methylation sequencing technology, differential methylation sites were further verified in model construction cohort (divided into training set and validation set, training set consisted of 99 HCC patients and 57 healthy controls; validation set consisted of 34 HCC patients and 20 healthy controls). HCC early diagnosis model was constructed by random forest algorithm combined with clinical parameters and the diagnostic performance of the model was evaluated by receiver operating characteristic (ROC) curve in the validation set. Results:The total of 7 249 differentially methylated sites between HCC patients and healthy controls in discovery cohort were selected under the rule of |Δβ|≥0.06 and P<0.01. Among them, the cg02155073 site located on FSIP1 was hypermethylated in PBMC of HCC patients in the screening cohort and model cohort ( P<0.001). The AUC of HCC early diagnosis model (FmAP) based on FSIPI in the validation set was 0.967 (95% CI 0.924-1.000); sensitivity was 88%, specificity was 95%. The model had good diagnostic efficacy for patients with early HCC, stage Ⅰ-Ⅱ HCC AUC was 0.958 (95% CI 0.898-1.000). The FmAP model also had diagnostic value for tumor size <2 cm HCC and AFP negative HCC, with AUC of 0.955 (95% CI 0.898-1.000) and 0.964 (95% CI 0.934-0.994).The sensitivity were 92% and 93% and specificity both were 84%. Conclusion:The FmAP model based on FSIP1 gene methylation has good clinical value for the early diagnosis of hepatocellular carcinoma.

Objective:To determine the diagnostic accuracy and prognosis of fetal congenital heart disease (CHD) detected by ultrasound at 11-13 weeks gestation.Methods:Fetuses at 11 to 13 + 6 weeks gestation in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2015 and December 2022 were prospectively collected. Standrardized ultrasound was used to examine the fetuses. For the suspected fetal CHD, the section of cardiac ultrasound was improved as far as possible, and ultrasonic results, prenatal diagnosis, pathological anatomy and pregnancy outcome were followed up. Results:A total of 539 cases of CHD were detected in 72 242 fetuses with mixed risk in the first trimester, the incidence was 0.75% (539/72 242). The incidence of CHD in the fetuses with positive soft markers was 9.20% (287/3 118), and the incidence of multiple fetal malformations was 16.22% (235/1 449). The diagnostic accordance rate of complex CHD was 97.42%. For complex CHD, the sensitivity, specificity, false positive rate and false negative rate of first-trimester ultrasound were 90.41%, 99.98%, 0.02%, 9.59%. Combined with the results of this study, the abnormal section model of complex CHD was recommended. A total of 252 cases underwent staining chromosomal microarray or gene sequencing, of which 42.46% (107/252) were positive.Conclusions:Standardized ultrasound examination has a very high detection rate for fetal CHD in the first trimester. Transverse scanning of the heart can significantly improve the display of gray scale cardiac section, and reference to the cardiac section pattern map is beneficial to the early diagnosis of fetal CHD.

Objective:To analyze the detection of non-alcoholic fatty liver disease (NAFLD) and the multiple corresponding relationships of its risk factors in a middle-aged and young adult population undergoing health check-ups.Methods:This study was a cross-sectional study conducted on 15 423 individuals aged between 18 and 59 who underwent health check-ups at the Health Management Center of Henan Provincial Hospital of Traditional Chinese Medicine from January to December 2021. Relevant health examination data was collected, including basic information (age, gender, past medical history, smoking and alcohol consumption), physical examination, laboratory indicators such as blood lipids and blood glucose, and abdominal ultrasound results. The chi-square test was used to compare the prevalence of NAFLD among different characteristics of the population, and multiple correspondence analysis was employed for statistical analysis of related influencing factors.Results:A total of 5 859 cases of NAFLD were detected in this study, with a detection rate of 37.99%. The detection rate of NAFLD gradually increased with age ( χ2=828.841, P<0.001) and body mass index (BMI) ( χ2=1 889.809, P<0.001). The detection rates of NAFLD were higher in individuals with hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, low high-density lipoprotein cholesterolemia, high low-density lipoprotein cholesterolemia, and hyperuricemia compared to those without these conditions ( χ2 value was 1 223.673, 364.808, 444.074, 2 436.765, 1 323.736, 591.478, and 943.069, respectively, all P<0.001). Multiple correspondence analysis revealed that NAFLD was closely related to hypertension, hypertriglyceridemia, diabetes, hyperuricemia, overweight, obesity, and the age group of 45-49 years. Correspondence analysis graphs for males and females showed associations between NAFLD and hypertension, hypertriglyceridemia, hyperuricemia, overweight, and obesity. In males, NAFLD was closely related to the age group of 35-49 years, while in females, it was closely associated with the age group of 45-49 years and diabetes. Conclusions:The detection rate of non-alcoholic fatty liver disease is relatively high in middle-aged and young adult populations. Males, those who are overweight or obese, and individuals with hypertension, diabetes, hyperuricemia, or abnormal blood lipids are more susceptible to non-alcoholic fatty liver disease.

Objective:To investigate the value of ultrasonography in diagnosis of transposition of great arteries of the fetus at 11-13 + 6 weeks gestation. Methods:A prospective study was conducted on fetuses screened by ultrasound in the first trimester in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2015 and March 2022. Fetal heart structure was screened by three-section screening method. Fetuses with suspected transposition of the great arteries at 11-13 + 6 weeks gestation underwent followed-up ultrasound examination, chromosome and gene test results. The ultrasound characteristics and prognosis pregnancy outcomes were summarized. Results:Twenty-one cases of transposition of the great arteries were detected by ultrasonography, including complete transposition of great arteries (20 cases) and congenitaly corrected transposition of the great arteries (1 case). Two cases were miss diagnosed. Twenty-one cases showed parallel signs of two major arteries on grayscale outflow section at 11-13 + 6 weeks gestation. There were 6 cases with aneuploid ultrasonographic soft markers abnormality, 2 cases with extracardiac malformation. Chromosome and microarray analysis were performed in 13 cases. 4 cases with chromosomal abnormality. Four cases of chromosomal abnormalities were associated with ultrasonographic soft markers abnormality, and 1 case with extracardiac malformation.In the 23 cases, 20 cases were induced, 1 miscarried, and 2 delivered to term. Among the fetuses delivered at term, 1 case died before neonatal operation and 1 case survived. Conclusions:Standardized ultrasound scan at 11-13 + 6 weeks has high accuracy in diagnosis of transposition of the great arteries. And the incidence of chromosomal abnormality is high with ultrasonographic soft markers abnormality or extracardiac malformation.

Objective : To investigate the efficacy of standardized allergen subcutaneous immunotherapy (SCIT) in children with asthma sensitized to single dust mite allergens versus multiple allergens and to assess the safety of SCIT. Methods : 62 children with confirmed allergic asthma who received standardized allergen SCIT were retro⁃ spectively analyzed and divided into the monosensitized group (dust mite results≥ + + + ) and the polysensitized group (dust mite results ≥ + + + combined with other positive allergens) according to the results of skin pricktest , we observed the changes of pulmonary function , medication score and visual analog scale (VAS) scores , children asthma control test (C - ACT) scores , asthma control questionnaire (ACQ) scores before and after treatment in both groupsand compared the efficacy of the two groups. The incidence of local and systemic adverse effects was recorded during treatment in all children to assess the safety of SCIT. Results : Standardized allergen SCIT treatmentimproved lung function parameters , medication scores and VAS scores , C ⁃ACT scores , ACQ scores in both the monosensitized and polysensitized groups , with statistically significant differences before and after treatment (P < 0. 05) . In comparison between the two groups , lung function parameters [forced expiratory flow at 50% vital capacity(FEF50% ) , maximum midexpiratory flow(MMEF)] , medication scores , C ⁃ACT scores and ACQ scores improved significantly in the monosensitized group compared with the polysensitized group after treatment ( P <0. 001) . 62 patients received a total of 2 606 injections during the treatment of SCIT , 6 children had a total of 10 local adverse reactions and 3 children had 3 mild to moderate systemic adverse reactions , with an incidence of 0. 38% for local adverse reactions and 0. 12% for systemic adverse reactions. Conclusion The children with asthma in both the monosensitized group and polysensitized group achieved significant and safe clinical outcomes under standardized allergen SCIT. The children in the monosensitized group had more obvious clinical effects than the polysensitized group under standardized allergen SCIT.

Objective:To investigate the value of atrioventricular valve regurgitation in predicting atrioventricular septal defect (AVSD) in the first trimester.Methods:Fetuses were examined prospectively by ultrasound at 11-13 + 6 weeks in Maternity & Child Healthcare Hospital of Guangxi Zhuang Autonomous Region between February 2016 and February 2021. Congenital heart disease was screened and atrioventricular valve regurgitation was observed in fetuses of gestational age 11 to 13 + 6 weeks using color Doppler in four-chamber view and three vessels and trachea view. Results:Totally 43 549 fetuses of gestational age 11 to 13 + 6 weeks were screened by echocardiography, of whom 37 cases were screened out with AVSD, including complete atrioventricular septal defect (31 cases), partial atrioventricular septal defect(3 cases) and intermediate atrioventricular septal defect(1 cases), 2 cases were misdiagnosed, and ultrasonic scanning in the second trimester found 2 missed cases of intermediate atrioventricular septal defect. Atrioventricular valve regurgitation was observed in 91.89% of atrioventricular septal defects (34/37) in the first trimester, 59.46% (22/37) nuchal translucency greater than 95th percentile, 29.73% (11/37) absence of nasal bone, 32.43% (12/37) ductus venosus A wave inversion, and 40.54% (15/37) had tricuspid regurgitation. The sensitivity of common atrioventricular valve regurgitation in predicting atrioventricular septal defect is better than other ultrasonic indexes. Conclusions:Atrioventricular regurgitation can be used as a clue to predict atrioventricular septal defect in the first trimester, which is beneficial to detect atrioventricular septal defect in the first trimester.

Objective:To investigate the prognostic value of serum levels of miR-320 in sepsis children complicated with acute kidney injury (AKI).Methods:A total of 158 sepsis children with complicated with AKI who were admitted to Hainan Women and Children′s Medical Center from January 2017 to June 2019 were divided into survival group (105 cases) and death group (53 cases) according to their 28-day survival.Serum levels of miR-320, neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and serum creatinine (Scr) were detected in the two groups.Multivariate Logistic regression was used to analyze the risk factors of death in children with sepsis complicated with AKI.The receiver operating characteristic curve (ROC) was drawn to analyze the value of serum levels of miR-320, NGAL, KIM-1 and Scr in predicting the death of children with sepsis complicated with AKI.The correlation between serum levels of miR-320 and NGAL, KIM-1 and Scr was analyzed using Pearson correlation analysis. Results:The serum levels of miR-320 (1.28±0.47 vs. 0.54±0.12), NGAL [(537.40±48.26) mg/L vs. (285.60±29.40) mg/L], KIM-1 [(26.80±5.72) μg/ L vs. (16.35±3.17) μg/L] and Scr[(573.70±105.46) μmol/L vs. (390.64±74.38) μmol/L] in the death group were significantly higher than those in the survival group (all P<0.001). Multivariate Logistic regression analysis showed that serum levels of miR-320 ( OR=2.280, 95% CI: 1.483-4.380), NGAL ( OR=2.753, 95% CI: 1.826-5.227), KIM-1 ( OR=1.985, 95% CI: 1.274-3.518) and Scr ( OR=1.714, 95% CI: 1.105-2.986) were independent risk factors for death in sepsis children with AKI (all P<0.001). ROC curve analysis showed that the area under the curve (0.952, 95% CI: 0.894-0.990) of serum miR-320, NGAL, KIM-1 and Scr levels combined to predict the death of children with sepsis and AKI was the largest, with a high sensitivity and specificity of 95.8% and 90.6%.Correlation analysis showed that the expression level of serum miR-320 in the death group was positively correlated with NGAL, KIM-1 and Scr ( r=0.874, 0.830, 0.702, all P<0.01). Conclusions:Serum levels of miR-320 are significantly increased in sepsis children with AKI, which is an independent risk factor for death in sepsis children with AKI.The combination of NGAL, KIM-1 and Scr levels has important value in predicting the prognosis of children with AKI.

Objective:To explore the current status and influencing factors of self-management of depression in community residents, so as to provide clues and basis for promoting the mental health of community residents.Methods:From June to August 2020, the residents of a community in Jining city in Shandong Province were selected as the survey objects, and 458 permanent residents were selected by simple random sampling method. The self-designed general data questionnaire, Depression Self-management Scale, General Self-Efficacy Scale (GSES) , Simple Coping Style Questionnaire (SCSQ) and Social Support Rating Scale (SSRS) were used to conduct cross-sectional survey, and structural equation was used to analyze the influencing factors of depression self-management of community residents. A total of 458 questionnaires were sent out and 443 were effectively received, with the effective recovery rate of 96.72%.Results:The depression self-management score of 443 community residents was (32.72±5.72) , GSES score was (23.47±5.12) , score of positive coping in SCSQ (2.07±0.51) , score of negative coping in SCSQ was (1.14±0.43) and total score of SSRS (32.89±3.43) . The structural equation model showed that the total effects of self-efficacy, positive coping, negative coping and social support on self-management of depression in community residents were respectively 0.45, 0.42, -0.52 and 0.37 ( P<0.05) . Conclusions:The depression self-management level of community residents is directly or indirectly affected by self-efficacy, coping styles and social support. When conducting mental health publicity and education in the community, it should be based on improving the self-efficacy of residents, coping styles and the level of social support to choose effective methods and content of publicity and education to promote the improvement of the self-management level of individual depression.

Objective:To summarize the genetic diagnosis of two fetuses with clinically suspected Bardet-Biedl syndrome (BBS) and to provide information for genetic counseling and prenatal diagnosis of BBS.Methods:Case one had prenatal care on October 2018 in Shenzhen Maternity and Child Healthcare Hospital and was clinically suspected of fetal BBS as bilateral renal parenchyma echo enhancement as well as polydactyly (six toes on each foot) were shown on ultrasonic examination at 18 +1 gestational weeks. Case two was another suspected fetal BBS for enlarged kidneys with echo enhancement as well as polydactyly (six fingers and toes on each hand and foot) on ultrasonic examination at 26 +4 gestational weeks on August 2016 and the parent requested for termination. Parents of both cases requested for genetic analysis. Amniotic fluid sample was obtained in case one at 19 +6 weeks through amniocentesis, and umbilical cord specimen of case two and peripheral blood samples of the parents were collected. Genetic analysis of the fetuses and their parents was performed using exon capture and next-generation sequencing and the results were validated using Sanger sequencing. Results:Case one carried paternally inherited c.718G>A (p.Gly240Ser) (possible pathogenic) mutation and maternally inherited c.497C>A(p.Ala166Asp) (possible pathogenic) mutation in BBS7 gene. While one paternally inherited mutation c.1002delT(p.N335Ifs*47) (pathogenic) and one maternally inherited heterozygous mutation c.728G>A (p.Cys243Tyr) (possible pathogenic) were identified in BBS7 gene of case two. The three unreported missense mutations were predicted to be harmful by bioinformatics software and the mutation sites were conservative after comparing with multiple species-based protein sequences. Conclusions:Enlarged kidneys with echo enhancement and polydactyly may indicated a BBS fetus caused by BBS7 gene mutation. Whole exome sequencing could provide relevant information for prenatal diagnosis and genetic counseling in these cases.