Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Objective To explore the expression of serum lipocalin-2(LCN2)and latent transforming growth factor-β binding protein 2(LTBP2)in ovarian cancer patients and their relationship with clinicopathological features and prognosis.Methods A total of 108 ovarian cancer patients treated in Baoji Hospital Affiliated to Xi'an Medical College from February 2020 to December 2021 were included in the ovarian cancer group.Another 108 patients with benign ovarian lesions during the same period were included and labeled as the lesion group,and 108 healthy female volunteers undergoing physical examination were assigned to the control group.ELISA method was used to detect serum LCN2 and LTBP2 levels.The relationship between serum LCN2 and LTBP2 levels and prognosis survival rate in ovarian cancer patients was analyzed using the Kaplan-Meier method.Multivariate Cox regression analysis was performed to identify the risk factors affecting the prognosis of ovarian cancer patients.Results Serum LCN2 and LTBP2 levels increased in the control group,lesion group,and ovarian cancer group in sequence(P<0.05).Among patients with high expression of serum LCN2 and LTBP2,the proportions of FIGO stage Ⅲ-Ⅳ,tumor maximum diameter>3 cm,and postoperative lymph node metastasis were higher than those of FIGO stages Ⅰ-Ⅱ,tumor maximum diameter≤3 cm,and non lymph node metastasis(P<0.05).The median survival time of ovarian cancer patients with high serum LCN2 and LTBP2 expression was lower than that of patients with low expression(Log-rank χ2=5.367、6.305,P<0.05).The survival rate of patients with FIGO stage Ⅲ～Ⅳ,maximum tumor diameter>3 cm,postoperative lymph node metastasis,LCN2 and LTBP2 high expression was lower than that of patients with FIGO stage Ⅰ～Ⅱ,tumor maximum diameter≤3 cm,no postoperative lymph node metastasis,and low LCN2 and LTBP2 expression(P<0.05).FIGO stages Ⅲ-Ⅳ,maximum tumor diameter>3 cm,postoperative lymph node metastasis,high LCN2,and high LTBP2 were independent risk factors affecting the 3-year survival rate of ovarian cancer patients(P<0.05).Conclusion Serum LCN2 and LTBP2 are upregulated in ovarian cancer patients,and are closely related to FIGO staging,tumor maximum diameter,and postoperative lymph node metastasis.They are important factors affecting prognosis and may serve as biomarkers for evaluating prognosis.

Objective To investigate the mechanism of Chonghe soft extract on ulcer wound healing in diabetic rats through protein kinase B(Akt)/mammalian Sirolimus target protein(mTOR)-mediated nucleotides binding oligomeric acid domain-like receptor protein 3(NLRP3)inflammasome inactivation.Methods Thirty six SD rats with diabetic ulcer,which were established by feeding with high glucose and high fat diet and injecting intraperitoneally with streptozocin(STZ)combined with skin defect,were randomly divided into model group,Chonghe soft extract group and growth factor group,with twelve rats in each group.Another twelve SD rats were injected an equal dose of citric acid-sodium citrate buffer solution and used as blank group.The blank group and the model group were not received drug intervention,but the Chonghe soft extract group and the growth factor group were externally applied Chonghe soft extract and growth factor gel,respectively.The wound healing of each group was observed and recorded.After 7 days and 14 days of treatment,the histopathology of wound were observed by HE staining and the number of fibroblasts were counted.The levels of IL-1β,IL-18 and TNF-α in serum were detected by ELISA.The expression of autophagy-related protein Beclin-1 and LC3Ⅱ in granulation tissue was detected by immunohistochemistry.The expression of NLRP3,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),Caspase1,Pro-Caspase1 and Akt/mTOR autophagy pathway-related proteins Akt,p-Akt,mTOR and p-mTOR were detected by Western Blot.Results Compared with the blank control group,the pathological wound repair of the model group was delayed on the 7th day and 14th day,the number of fibroblasts per unit area was decreased(P<0.01).The levels of IL-1β,IL-18 and TNF-α were increased(P<0.01).The expression levels of ASC,Pro-Caspase1,Caspase1,and NLRP3 were increased in the wound tissues(P<0.01),while the expression levels of Beclin-1,LC3-Ⅱ,mTOR,p-mTOR,Akt and p-Akt were decreased in the wound tissues(P<0.01).Compared with the model group,the pathological injury in Chonghe soft extract group and growth factor group was significantly improved on the 7th day and 14th day.The number of fibroblasts per unit area was significantly increased(P<0.01).The levels of IL-1β,IL-18 and TNF-α were significantly decreased(P<0.01).The expression levels of ASC,Pro-Caspase1,Caspase1,and NLRP3 in the wound tissues were decreased(P<0.01),while the expression levels of Beclin-1,LC3-Ⅱ,mTOR,p-mTOR,Akt and p-Akt were increased(P<0.01,P<0.05).Conclusion Chonghe soft extract can reduce inflammatory reaction,promote the generation of fibro,regulate the Akt/mTOR-mediated NLRP3 inflammasome inactivation,improve the level of autophagy in wound,and promote ulcer wound healing in diabetic rats.

To analyze the clinical characteristics and treatment status of atopic dermatitis (AD) in children in the outpatient department of a children's hospital in Beijing from 2015 to 2019. This study used a cross-sectional study method to retrospectively analyze the data of AD patients who visited the Dermatology outpatient department of Beijing Children's Hospital, Capital Medical University, from April 2015 to April 2019. A total of 1 926 AD patients aged 0-17.5 years old living in Beijing and its surrounding areas were included, and the general situation, severity and distribution of AD disease, clinical characteristics and severity of AD, relevant influencing factors of AD onset, AD disease prognosis and treatment status were recorded. SAS 9.4, SPSS19.0, and R software were used for data processing, and descriptive statistical analysis, Chi-square test, Analysis of Variance, and correspondence analysis were used for statistical analysis. The results showed that the male to female ratio of AD patients in children included in this study was 1.4∶1; 79.0% (1 522/1 926), 86.1%(1 658/1 926), 91.3%(1 758/1 926), and 97.3%(1 907/1 926) of AD onset at the age of 6 months, 1 year, 2 years, and 5 years, respectively; mild of AD patients accounted for 13.2% (255/1 926)(SCORAD score 0-24), moderate of AD patients accounted for 50.1%(965/1 926) (SCORAD score 25-50), and severe of AD patients accounted for 36.7% (706/1 926)(SCORAD score>50).The age of severe AD patients were younger than mild and moderate AD patients. The face, head, trunk, and lower limbs were common areas of onset for moderate to severe AD, while the hands, feet, and ears were common areas of onset for severe AD patients. Temperature changes, hot water factors, mental and emotional states, and spring and winter were the main aggravation factors of AD;35.2% (678/1 926) aggravated and 61.8% (1 191/1 926) persistent. The more frequent bathing, the less severity of AD disease (χ²=29.791,P<0.001); 28.0% (520/1 856) of AD patients have no moisturizing habits, which were correlated with the severity of AD disease (χ²=15.908, P<0.05); the proportion of combined treatment medications in children with moderate to severe AD was significantly higher than mild AD patients. In conclusion, the patients with AD who went to specialist clinics were mainly moderate to severe patients and developed disease before the age of 5 years from 2015 to 2019.The severity of AD were mainly moderate to severe, and most of these patients had poor disease control. Traditional treatment plans had limitations. Identifying the clinical characteristics and treatment status of childhood AD would help us to carry out more targeted prevention and management work.
Humans ; Child ; Male ; Female ; Infant, Newborn ; Infant ; Child, Preschool ; Adolescent ; Dermatitis, Atopic/psychology* ; Cross-Sectional Studies ; Retrospective Studies ; Severity of Illness Index ; Hospitals ; Quality of Life

To analyze the clinical characteristics and treatment status of atopic dermatitis (AD) in children in the outpatient department of a children's hospital in Beijing from 2015 to 2019. This study used a cross-sectional study method to retrospectively analyze the data of AD patients who visited the Dermatology outpatient department of Beijing Children's Hospital, Capital Medical University, from April 2015 to April 2019. A total of 1 926 AD patients aged 0-17.5 years old living in Beijing and its surrounding areas were included, and the general situation, severity and distribution of AD disease, clinical characteristics and severity of AD, relevant influencing factors of AD onset, AD disease prognosis and treatment status were recorded. SAS 9.4, SPSS19.0, and R software were used for data processing, and descriptive statistical analysis, Chi-square test, Analysis of Variance, and correspondence analysis were used for statistical analysis. The results showed that the male to female ratio of AD patients in children included in this study was 1.4∶1; 79.0% (1 522/1 926), 86.1%(1 658/1 926), 91.3%(1 758/1 926), and 97.3%(1 907/1 926) of AD onset at the age of 6 months, 1 year, 2 years, and 5 years, respectively; mild of AD patients accounted for 13.2% (255/1 926)(SCORAD score 0-24), moderate of AD patients accounted for 50.1%(965/1 926) (SCORAD score 25-50), and severe of AD patients accounted for 36.7% (706/1 926)(SCORAD score>50).The age of severe AD patients were younger than mild and moderate AD patients. The face, head, trunk, and lower limbs were common areas of onset for moderate to severe AD, while the hands, feet, and ears were common areas of onset for severe AD patients. Temperature changes, hot water factors, mental and emotional states, and spring and winter were the main aggravation factors of AD;35.2% (678/1 926) aggravated and 61.8% (1 191/1 926) persistent. The more frequent bathing, the less severity of AD disease (χ²=29.791,P<0.001); 28.0% (520/1 856) of AD patients have no moisturizing habits, which were correlated with the severity of AD disease (χ²=15.908, P<0.05); the proportion of combined treatment medications in children with moderate to severe AD was significantly higher than mild AD patients. In conclusion, the patients with AD who went to specialist clinics were mainly moderate to severe patients and developed disease before the age of 5 years from 2015 to 2019.The severity of AD were mainly moderate to severe, and most of these patients had poor disease control. Traditional treatment plans had limitations. Identifying the clinical characteristics and treatment status of childhood AD would help us to carry out more targeted prevention and management work.
Humans ; Child ; Male ; Female ; Infant, Newborn ; Infant ; Child, Preschool ; Adolescent ; Dermatitis, Atopic/psychology* ; Cross-Sectional Studies ; Retrospective Studies ; Severity of Illness Index ; Hospitals ; Quality of Life

Objective: To analyze the trends of the age of menarche among Chinese Han girls aged 9 to 18 years from 2010 to 2019. Methods: Data were extracted from the Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019. A total of 253 037 Han girls aged 9 to 18 years with complete data on menarche were selected in this study. They were asked one-on-one about their menstrual status, age and residence information. The median age of menarche was estimated by probability regression. U tests were used to compare the difference in median age at menarche in different years. Results: The median age at menarche (95%CI) among Chinese Han girls was 12.47 (12.09-12.83) years in 2010, 12.17 (11.95-12.38) years in 2014 and 12.05 (10.82-13.08) years in 2019, respectively. Compared with that in 2010, the median age at menarche in 2019 decreased by 0.42 years (U=-77.27, P<0.001). The annual average changes were -0.076 years from 2010 to 2014 (U=-57.19, P<0.001) and -0.023 years from 2014 to 2019 (U=-21.41, P<0.001), respectively. The average annual changes in urban areas in the periods of 2010 to 2014 and 2014 to 2019 were -0.071 years and 0.006 years, respectively, while those in rural areas were -0.082 years and -0.053 years, respectively. The average annual changes in the regions of north, northeast, east, south central, southwest and northwest were -0.064, -0.099, -0.091, -0.080, -0.096 and -0.041 years in the period of 2010 to 2014 and 0.001, -0.040, -0.002, -0.005, -0.043 and -0.081 years in the period of 2014 to 2019. Conclusion: The age of menarche among Chinese Han girls aged 9 to 18 years shows an advanced trend from 2010 to 2019, and the trends in urban and rural areas and different regions have different characteristics.
Female ; Humans ; Menarche ; Probability ; East Asian People ; Child ; Adolescent

Objective: To investigate the association between muscle mass and quality of life in adults in Shaanxi adults. Methods: The data in this analysis were part of the baseline survey of the Regional Ethnic Cohort Study in Northwest China from June 2018 to May 2019 in Shaanxi Province. The participants' quality of life, including physical component summary (PCS) and mental component summary (MCS), was assessed by the 12-Item Short Form Survey, and the Body Fat Determination System measured muscle mass. A logistic regression model with adjustment for confounding factors was established to analyze the association between muscle mass and quality of life in different genders. Further, sensitivity and subgroup analyses were conducted to explore its stability. Finally, a restricted cubic spline was employed to investigate the dose-response relationship between muscle mass and quality of life in different genders. Results: A total of 20 595 participants were included, with an average age of 55.0, and 33.4% were male. After controlling for potential confounders, compared with the Q₁ group, the risk of low PCS was reduced by 20.6% (OR=0.794, 95%CI: 0.681-0.925) and the risk of low MCS was lower reduced by 20.1% (OR=0.799, 95%CI: 0.689-0.926) in female Q₅ groups. Compared with the Q₁ group, the risk of low PCS was reduced by 24.4% (OR=0.756, 95%CI: 0.644-0.888) in the male Q₂ group. However, no significant association between muscle mass and MCS in males has been found. In females, restricted cubic spline analysis showed a significant linear dose-response relationship between muscle mass and PCS and MCS. Conclusions: There is a positive association between muscle mass and quality of life in Shaanxi adults, especially females. With the increase in muscle mass, the physical and mental functions of the population continue to improve.
Humans ; Female ; Adult ; Male ; Quality of Life ; Cohort Studies ; Adipose Tissue ; China ; Muscles

A large number of people would be exposed to irradiation in large-scale nuclear and radiation accidents or nuclear terrorist attacks. Therefore, it is urgent to establish rapid and high-throughput biodosimetry for in triage, providing a basis for emergency management. Imaging flow cytometry (IFC) possesses the high through put advantages of traditional flow cytometry and the sensitivity and specificity of microscope, and has a good application prospect in the research and development of rapid, automated, and high-throughput biological dose estimation technology. This article reviews the application progress of IFC in biodosimetry, and provides a reference for the development of biological dose estimation and detection equipment for large-scale nuclear and radiation accidents.