1.Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma
Yang LIU ; Fan PENG ; Siyuan WANG ; Huanmin JIAO ; Kaixiang ZHOU ; Wenjie GUO ; Shanshan GUO ; Miao DANG ; Huanqin ZHANG ; Weizheng ZHOU ; Xu GUO ; Jinliang XING
Clinical and Molecular Hepatology 2025;31(1):196-212
		                        		
		                        			 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. 
		                        		
		                        		
		                        		
		                        	
2.Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma
Yang LIU ; Fan PENG ; Siyuan WANG ; Huanmin JIAO ; Kaixiang ZHOU ; Wenjie GUO ; Shanshan GUO ; Miao DANG ; Huanqin ZHANG ; Weizheng ZHOU ; Xu GUO ; Jinliang XING
Clinical and Molecular Hepatology 2025;31(1):196-212
		                        		
		                        			 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. 
		                        		
		                        		
		                        		
		                        	
3.Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma
Yang LIU ; Fan PENG ; Siyuan WANG ; Huanmin JIAO ; Kaixiang ZHOU ; Wenjie GUO ; Shanshan GUO ; Miao DANG ; Huanqin ZHANG ; Weizheng ZHOU ; Xu GUO ; Jinliang XING
Clinical and Molecular Hepatology 2025;31(1):196-212
		                        		
		                        			 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. 
		                        		
		                        		
		                        		
		                        	
4.Current status of book publishing in the field of biological weapons defense in China
Xuechun WANG ; Jiajun DU ; Xixiaoxue ZHANG ; Ting KAN ; Wenjun WU ; Yu MA ; Shanshan YANG ; Shengshu WANG ; Yao HE ; Miao LIU
Shanghai Journal of Preventive Medicine 2024;36(7):673-678
		                        		
		                        			
		                        			ObjectiveTo provide scientific support for the compilation of high-quality anti-nuclear, biological, and chemical (NBC) medical textbooks in China by retrieving books in the field of biological weapons defense in China, summarizing the publication time and distribution of publishing institutions, and categorizing content and key points of related books. MethodsRelevant subject terms in the field of biological weapons defense were searched through the official website of China National Digital Library and other websites, up until December 31, 2023, and were limited to books. Topic analysis was conducted on the introductions and contents of the books using the latent Dirichlet allocation (LDA) model. The number of topics was determined based on perplexity, and topics were identified according to the intertopic distance map, followed by a qualitative description of the core content of each topic. ResultsA total of 104 books were included in this study, among which four were identified as higher educational textbooks. The volume of publications increased during the periods 2002‒2004 and 2020‒2023. Research institutions accounted for the highest percentage of publishers (37.78%), and 56.67% of the publishers were military institutions. The study identified six topics: "distribution, defense, and response to biological weapons", "category, diagnosis, and treatment of biological warfare agents", "response to biological public health emergencies", "status of nuclear, biological, and chemical weapons internationally", "biosafety risk management and prevention and control", and "technologies and equipment related to biological hazard identification". ConclusionThere are few books in the field of biological weapons defense in China and the content is relatively outdated. In the future, the preparation of teaching materials should be aimed at practical emergency handling techniques for biological weapons, enhance the emphasis on biological weapons detection and biological warfare early warning, improve the fundamental theories at different training levels, and timely update the current research status in the field. 
		                        		
		                        		
		                        		
		                        	
5.Effects of cognition-related lifestyles on early cognitive decline in community older adults in China
Haowei LI ; Shige QI ; Shengshu WANG ; Shanshan YANG ; Shimin CHEN ; Rongrong LI ; Xuehang LI ; Shaohua LIU ; Junhan YANG ; Huaihao LI ; Yinghui BAO ; Yueting SHI ; Zhihui WANG ; Yao HE ; Miao LIU
Chinese Journal of Epidemiology 2024;45(1):63-70
		                        		
		                        			
		                        			Objective:To investigate the distribution characteristics of cognition-related lifestyles of elderly in communities and explore the integrated effects on early cognitive decline.Methods:The participants were from the Project of Prevention and Intervention of Neurodegenerative Disease for Elderly in China. A total of 2 537 older adults aged ≥60 years without dementia in the 2015 baseline survey and the 2017 follow-up survey were included. The information about their cognition-related lifestyles, including physical exercise, social interaction, leisure activity, sleep quality, smoking status, and alcohol consumption, were collected through questionnaire survey and the integrated scores were calculated. Multivariate logistic regression analysis was used to assess the association between integrated cognition-related lifestyle score and early cognitive decline.Results:In the 2 537 older adults surveyed, 28.7% had score of 5-6, while only 4.8% had high scores for all 6 healthy lifestyles. Significant differences in healthy lifestyle factor distributions were observed between men and women. Multivariate logistic regression model showed that the risks for early cognitive decline in the older adults who had lifestyle score of 4 and 5-6 were lower than that in those with lifestyle score of 0-3 ( OR=0.683, 95% CI: 0.457-1.019; OR=0.623, 95% CI: 0.398-0.976; trend P=0.030). In the women, the risks for early cognitive decline was lower in groups with score of 4 and 5-6 than in group with score of 0-3 ( OR=0.491, 95% CI: 0.297-0.812; OR=0.556, 95% CI: 0.332-0.929; trend P=0.024). Conclusion:Cognition-related healthy lifestyles are associated with significantly lower risk for early cognitive decline in the elderly, especially in women.
		                        		
		                        		
		                        		
		                        	
6.Potential applications of a compartment model in the prevention and control of emerging respiratory infectious diseases in military camps
Xuechun WANG ; Xixiaoxue ZHANG ; Shanshan YANG ; Miao LIU
Military Medical Sciences 2024;48(9):686-689
		                        		
		                        			
		                        			Military camps are characterized by compact space and high personnel density,which increases the risk of emerging respiratory infectious diseases and makes prevention and control difficult.One effective solution is to use a compartment model for early warning,prediction of epidemic outbreaks,and for optimization of precautions.Given the strong similarities in the transmission of emerging respiratory infectious diseases across military camps and communities,this article summarizes the cases where compartment models have been used both at home and abroad,constructs a susceptible-exposed-infectious-removed model and a susceptible-exposed-infectious-quarantined-removed model,and simulates the prediction of trends and selection of prevention and control measures in typical military camp scenarios after the outbreak of an epidemic in hopes of providing references for the prevention and control of emerging respiratory infectious diseases and for the construction of a regional intelligent early warning platform in military camps.
		                        		
		                        		
		                        		
		                        	
7.Experimental animal studies on skin irritation with Shexiang Anhe hemorrhoid ointment and hemorrhoidal proximity models
Xinghao ZHU ; Qingjia REN ; Ga ZHUO ; Shanshan LI ; Zongyao WU ; Mingsan MIAO ; Dongmei QI
Acta Laboratorium Animalis Scientia Sinica 2024;32(9):1114-1121
		                        		
		                        			
		                        			Objective To investigate the acute toxicity,irritation,and other effects of Shexiang Anhe hemorrhoid ointment on hemorrhoid-phased model rats by examining the TLR4/p38 MAPK/NF-κB signaling pathway.Methods Sixteen New Zealand rabbits were randomly divided into an intact skin Shexiang Anhe hemorrhoid ointment group,intact skin control group,broken skin Shexiang Anhe hemorrhoid ointment group,and broken skin control group,with four rabbits in each group.In the experimental group,20 g of Shexiang Anhe hemorrhoid ointment(1 g/mL)was evenly applied to an area on the rabbits depleted of hair,and an equal volume of solvent(mixture of glycerol,lanolin,and water)was evenly applied to the area on the backs of the rabbits in the control group once a day for 14 days.Another 40 rats were taken and randomly divided into a normal group,model group,Maillard group,and hemorrhoid cream group,with 10 animals in each group.The cream was applied once a day for 14 days.The acute toxicity of the cream in the intact and broken skin of rabbits was observed by hematoxylin and eosin staining and other method after treatment.In situ photographs were taken of the perianal tissues of rats with hemorrhoids to observe the efficacy of Shexiang Anhe hemorrhoid ointment,and the length and width of the ulcers were measured with vernier calipers to calculate the area.Quantitative real time polymerase chain reaction was used to detect the expression of TLR4,p38 MAPK,and NF-κB mRNA in the perianal tissues of the rats.Results Compared with rabbits in the control groups with intact or broken skin,rabbits in the administered group showed no significant difference in body mass.The mean values for the irritation evaluation points for Shexiang Anhe hemorrhoid ointment on rabbits with broken skin for 1 h,24 h,48 h,and 72 h were 1.5,1,0.5,and 0.25,respectively,showing there was no obvious skin irritation.In the hemorrhoidal rats,Shexiang Anhe hemorrhoid ointment treatment significantly reduced hemorrhoid symptoms after 14 days administration;the ulcer area was significantly smaller(P<0.05)and TLR4,p38 MAPK,and NF-κB mRNA levels were significantly lower compared with the findings in the model group(P<0.05).Conclusions Shexiang Anhe hemorrhoid ointment is a safe topical treatment with minimal acute toxicity and irritation to the skin and achieved good efficacy in the treatment of hemorrhoidal rats.Its mechanism of action may be related to the inhibition of the TLR4/p38 MAPK/NF-κB signaling pathway.
		                        		
		                        		
		                        		
		                        	
8.Serum miR-15a and MIF levels and their relationship with adverse maternal and infant outcomes in patients with gestational diabetes mellitus
Chen ZHANG ; Aiwen MIAO ; Shanshan LI ; Gaoxiang HUO ; Shuxia WU
International Journal of Laboratory Medicine 2024;45(16):1973-1978
		                        		
		                        			
		                        			Objective To investigate the serum micro-ribonucleic acid-15a(miR-15a)and macrophage mi-gration inhibitory factor(MIF)levels and their relationship with adverse maternal and infant outcomes in pa-tients with gestational diabetes mellitus(GDM).Methods From January 2020 to December 2022,106 patients with GDM who underwent prenatal examination and gave birth in the Hengshui Fourth People's Hospital were selected as the experimental group.Another 106 healthy women who underwent pregnancy examination and delivered in a hospital during the same period were selected as the control group.Detection of serum miR-15a level by real-time fluorescent quantitative polymerase chain reaction and serum MIF levels were detected by enzyme-linked immunosorbent assay.Serum MIF and miR-15a levels were compared between the two groups,and the relationship between miR-15a and MIF levels and adverse maternal and infant outcomes in GDM patients was analyzed by multivariate Logistic regression.Results The serum levels of miR-15a and MIF in the experimental group were higher than those in the control group,the difference was statistically sig-nificant(P<0.05).The age of patients with adverse maternal and infant outcomes in the experimental group was>35 years old,the pre-pregnancy body mass index was>24 kg/m2,the proportion of patients with ad-verse pregnancy history,poor blood glucose control and serum MIF and miR-15a levels were higher than those with good maternal and infant outcomes in the experimental group,and the differences were statistically sig-nificant(P<0.05).Multivariate Logistic regression analysis showed that age>35 years old,pre-pregnancy body mass index>24 kg/m2,adverse pregnancy history,poor blood glucose control and serum miR-15a and MIF were all risk factors for adverse maternal and infant outcomes in the experimental group(P<0.05).Conclusion Serum miR-15a and MIF levels are abnormally elevated in GDM patients,and serum miR-15a and MIF levels are closely related to adverse maternal and infant outcomes.
		                        		
		                        		
		                        		
		                        	
9.Application of indocyanine green angiography in repair of facial soft tissue defect using superficial temporal artery based forehead flap.
Mengqi ZHOU ; Yuanbo LIU ; Xiaoye RAN ; Shan ZHU ; Shanshan LI ; Zixiang CHEN ; Tinglu HAN ; Shengyang JIN ; Miao WANG ; Mengqing ZANG
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(10):1259-1265
		                        		
		                        			OBJECTIVE:
		                        			To explore the feasibility of using indocyanine green angiography in mapping the superficial temporal vessels and assisting design and harvesting of the superficial temporal artery based forehead flap.
		                        		
		                        			METHODS:
		                        			A clinical data of 14 patients with facial soft tissue defects repaired with superficial temporal artery based forehead flaps between October 2015 and November 2022 was retrospectively analyzed. There were 9 males and 5 females with a median age of 9.5 years (range, 3-38 years). The forehead flaps were used to reconstruct facial soft tissue defects following excision of facial scar (8 cases) or congenital melanocyte nevus (6 cases). The size of defects ranged from 3 cm×2 cm to 24 cm×9 cm. Before operation, the indocyanine green angiography was used to map the superficial temporal artery and vein, and to analyze the relationship of the arteries and veins. The forehead flaps with unilateral superficial temporal fascia as the pedicle was transferred to repair the small facial defect in 2 cases. The facial pedicle contained the frontal branch of the superficial temporal artery and 2 cm of the superficial temporal fascia around the vessel, and the tiny accompanying vein of the frontal branch of the superficial temporal artery was used as the outflow of the flap. The forehead flaps with the skin pedicle including bilateral or unilateral superficial temporal fascia and the overlying skin was pre-expanded and transferred to repair the large facial defect in 12 cases. The skin pedicle contained the frontal branch of superficial temporal artery and one of main branches of superficial temporal vein. Among the 12 cases, the frontal branch of superficial temporal vein was used as the outflow in 4 cases, and the parietal branch was used as the outflow in 8 cases. The size of the flaps ranged from 3 cm×2 cm to 30 cm×13 cm. The skin pedicles were divided at 3 weeks after the flap transfer.
		                        		
		                        			RESULTS:
		                        			Indocyanine green angiography could clearly showed the course and branching of the superficial temporal artery and vein. Individual differences existed in the location where the frontal branch of the superficial temporal artery entered the forehead. The superficial temporal vein had great variability and did not follow the artery. One patient had expander-related complication, which resulted in 3-cm flap necrosis. The necrotic tissue was debrided and repaired with skin grafting. The other flaps totally survived and the incisions healed by first intention. All patients were followed up 2-24 months, with a median of 11.5 months. The color, texture, and thickness of the flaps matched well with those of recipient sites. Hypertrophic scar was not observed in recipient or donor site. All patients were satisfied with the reconstructive outcomes.
		                        		
		                        			CONCLUSION
		                        			Indocyanine green angiography can clearly visualize the course and the branches of the superficial temporal arteries and veins, which can help surgeons understand the position, distribution, and concomitant relationship of the superficial temporal vessels, and make a rational surgical plan of the forehead flap.
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Child, Preschool
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Young Adult
		                        			;
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Temporal Arteries/surgery*
		                        			;
		                        		
		                        			Indocyanine Green
		                        			;
		                        		
		                        			Forehead/surgery*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Skin Transplantation
		                        			;
		                        		
		                        			Angiography
		                        			;
		                        		
		                        			Soft Tissue Injuries/surgery*
		                        			;
		                        		
		                        			Perforator Flap/blood supply*
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
10.Characteristics of changes in the demand for emergency medical services due to epidemics of sudden acute respiratory infectious diseases—Data analysis of pre hospital first aid during the period of optimizing the implementation of COVID-19 prevention and control measures in Zhejiang Province
Wenwei CAI ; Xiaoyan MIAO ; Zhiwen WU ; Jin FU ; Aili SHI ; Shanshan CHEN
Chinese Journal of Emergency Medicine 2023;32(11):1476-1480
		                        		
		                        			
		                        			Objective:To study characteristics of changes in the demand for emergency medical services during epidemic prevention and control "10 new measures" in Zhejiang province.Methods:The data of 26 emergency centers connected to the provincial integration platform of Zhejiang Province (hereinafter referred to as "provincial platform" ) were retrospectively analyzed, and the data were collected from one week before the implementation of "10 new measures" to the sixth week after implementation (December 1, 2022 to January 18, 2023). The collected information included: the number of 120 calls and ambulance services, the types of disease, age composition of patients, performance of emergency medical services.Results:From the second week of the implementation of "10 new measures" (December 15 to 21, 2022), the number of 120 calls and ambulance services were increased rapidly, and the peak occurred in the third week of implementation (December 21 to 28, 2022). Among the types of diseases, the number and proportion of patients with abnormal symptoms and respiratory diseases increased significantly, reaching the highest peak in the third week (December 21 to 28, 2022) and the fourth week (December 29, 2022 to January 4, 2023) of implementation, respectively. After the second week of implementation, the number of elderly patients aged 71 to 100 increased significantly, reaching a peak in the fourth week (December 29, 2022 to January 4, 2023), accounting for 60.76% of the total. During the epidemic period, the quality control indicators such as emergency dispatch time, ambulance dispatch time and medical treatment all fluctuated, but the changes were not significant.Conclusions:During the implementation of epidemic prevention and control "10 new measures", there were obvious characteristic changes in the demand for pre-hospital emergency in Zhejiang Province, but the quality of pre-hospital emergency medical was basically stable.
		                        		
		                        		
		                        		
		                        	
            
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