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 investigate iodine content in drinking water and clarify the distribution characteristics of iodine in water in Shaanxi Province.Methods A cross-sectional survey method was used to collect water samples from administrative villages in the province.Two tap water samples were taken from the centralized water supply villages,and 10％samples were taken from the decentralized water supply villages.Water iodine was detected by arsenic cerium catalytic spectrophotometry.Water iodine areas were divided according to national standards:＜40 μg/L was iodine deficiency area,40-100 μg/L was iodine adequate area,＞100 μg/L was high iodine area.According to the ecological regionification scheme of the Chinese Academy of Sciences,Shaanxi Province was divided into three types:the central and eastern Inner Mongolia Platea-Loess Plateau ecological region,the Fenwei Basin ecological region,and the Qinba Mountains ecological region.SPSS 25.0 was used for statistical analysis.Results The median of water iodine in Shaanxi Province was 6.66 μg/L.The survey of water iodine content was conducted in 22 848 administrative villages,1 309 townships,112 counties and 14 municipalities in the whole province.The median water iodine was less than 40 μg/L in 91.75％(20 963/22 848)of the administrative villages,between 40 and 100 μg/L in 7.40％(1 691/22 848)of the administrative villages,and more than 100 μg/L in 0.85％(194/22 848)of the administrative villages.The median of water iodine in the central and eastern Inner Mongolia Platea-Lose Plateau ecological zone,the Fenwei Basin ecological zone,and Qinba Mountains ecological zone was 12.35,8.88,and 2.00 μg/L,respectively,and the differences among different ecological zones were statistically significant(H=6 616.23,P＜0.001).The median of water iodine of centralized and decentralized water supply was 6.72 and 6.21 μg/L,respectively,and differences between different water supply methods were statistically significant(Z=5.638,P＜0.01).Conclusion The overall external environment of Shaanxi Province is iodine deficient,and most of the administrative villages are iodine deficient areas.There are a certain proportion of high iodine water source areas and suitable iodine areas.

Objective To investigate the effects of acteoside in a rat model on of diabetic nephropathy(DN)and high-glucose-induced glomerular mesangial cells(GMCs),focusing on the role of acteoside in the silent information regulator 1(SIRT1)/nuclear factor eryth-roid 2-related factor 2(Nrf2)signaling pathway.Methods GMCs were cultured under normal glucose conditions or stimulated with high glucose.Fibrosis,oxidative stress,SIRT1 and Nrf2 protein expression,and mitochondrial structure were assessed in four groups:normal glucose,high glucose,high glucose+acteoside,and high glucose+acteoside+SIRT1 inhibitor(hsa62).DN was induced in rats via intraperitoneal streptozotocin injection,and animals were divided into control,model,and acteoside-treated groups.Pathological kidney changes,blood glucose changes,renal function indices,and protein expression of SIRT1 and Nrf2 were evaluated.Results Compared with controls,DN model rats showed significantly elevated fasting blood glucose,serum creatinine,blood urea nitrogen,and 24-h urinary protein levels of rats in the model group were significantly increased(P＜0.01).GMCs exhibited increased fibrosis,oxidative stress,and mitochondrial damage.Acteoside treatment significantly improved all measured parameters(P＜0.01);and mitigated mitochondrial injury.In vitro,acteoside reduced high-glucose-induced fibrosis and oxidative stress in GMCs,effects that were reversed by SIRT1 inhibition.Western blotting confirmed upregulation of SIRT1 and Nrf2 expression in both treated rat kidney tissues and GMCs(P＜0.01).Conclusion Acteoside alleviates glomerular fibrosis and oxidative stress in DN by activating the SIRT1/Nrf2 signaling pathway,suggesting its potential therapeutic agent for DN.

Objective To evaluate the cost-effectiveness of low-dose steroid combined with tacrolimus or cyclophosphamide in treating adult idiopathic membranous nephropathy(IMN).Methods A prospective cohort design was used to collect clinical data on IMN patients admitted to the Affiliated Hospital of Hebei University from December 2018 to April 2022.The patients were divided into the exposure group(low-dose steroid combined with tacrolimus)and control group(low-dose steroid combined with cyclophosphamide)according to the treatment regimen.Propensity score matching was employed to balance the baseline characteristics between the two groups.The total response rate was taken as the effect index,cost-effectiveness analysis was conducted by using the decision tree model,and single factor sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the cost-effectiveness analysis results.Results A total of 112 patients with IMN were included.After propensity score matching,46 patients were included in the exposed and control groups,respectively.The total remission rate of the exposure group was 84.78％,with the cost of 13,352.64 yuan and the cost-effectiveness ratio of 157.50.In the control group,the total remission rate was 80.43％,the cost was 8,154.18 yuan,and the cost-effectiveness ratio was 101.38.The incremental cost-effectiveness ratio of the two groups was 1 195.05,and the sensitivity analysis results were consistent with those of the cost-effectiveness analysis.Conclusion The two treatment schemes have their own advantages in the treatment of IMN.The cost-effectiveness ratio of low-dose hormone combined with tacrolimus is relatively higher,and the combination of low-dose hormone with cyclophosphamide is more economical.Both schemes have certain clinical promotion value..

Objective To explore the relationship between IgA nephropathy(IgAN)and intestinal flora and mucosal immune response disorder based on the theory of"intestinal-kidney axis",and to summarize and enumerate the measures of Chinese and Western medicine in the treatment of IgAN by regulating intestinal flora,mucosal immune response and improving intestinal microecology.Methods Through literature search,the changes of intestinal flora between healthy people and IgAN patients and their effects on intestinal mucosal immunity were compared and analyzed,and then the relationship between different intestinal flora and IgAN was summarized.Results This paper summarizes that different floras including Firmicutes,Escherichia coli,Bifidobacterium and Enterococcus faecalis are closely related to the occurrence and development of IgAN.Conclusions Intestinal flora imbalance can negatively regulate IgAN,regulate intestinal flora and improve intestinal microecological environment,which may become a new target for the treatment of IgAN.

AIM:To investigate the therapeutic effects and potential mechanism of pachymic acid(PA)on li-popolysaccharide(LPS)-induced acute kidney injury(AKI)in mice.METHODS:(1)Genes related to AKI were screened using the DAVID database.Core genes were identified by intersecting related genes and analyzed using Cyto-scape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed through the DAVID database for the cross-targets.Molecular docking and activity assays were conducted on the primary core targets.(2)A total of 100 C57BL/6J mice were randomly divided into five groups:normal control(NC),model(LPS),solvent control(LPS+DMSO),and treatment groups(LPS+PA-10 and LPS+PA-20),with 20 mice in each group.The LPS-AKI model was established by intraperitoneal injection of 18 mg/kg LPS.The treatment groups received 10 mg/kg and 20 mg/kg PA,respectively,and the solvent control group was administered an equivalent dose of DMSO.Mice were euthanized 24 h after injection.Serum was collected for biochemical analysis,and Western blot was used to detect neutro-phil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),caspase-3,cleaved caspase-3,interleu-kin-1β(IL-1β),and monocyte chemoattractant protein-1(MCP-1)protein expression.RT-qPCR was employed to detect inflammatory factor mRNA levels.Molecular docking was used to simulate the optimal binding site of PA to caspase-3.En-zyme activity assays were performed to assess caspase protein activity,and renal lesions were observed via hematoxylin and eosin(HE)staining.Apoptosis was detected by TUNEL staining.RESULTS:(1)Thirty-one potential targets of PA against AKI were identified through network pharmacology.GO and KEGG enrichment analyses indicated that these tar-gets were primarily involved in immune response,inflammatory processes,apoptosis and survival,angiogenesis and hemo-dynamics,oxidative stress,and endoplasmic reticulum stress.Key targets included CASP3(caspase-3),PTGS2,BCL2,CCL2,and CYP219.(2)PA treatment improved renal function and reduced tubular epithelial injury.It significantly de-creased NGAL,KIM-1,and cleaved caspase-3 protein levels,as well as inflammatory factors TNF-α,IL-1β,and MCP-1 mRNA and protein expression.PA also reduced apoptosis of renal tubular epithelial cells.Enzyme activity assays and mo-lecular docking revealed that PA exerted its anti-apoptotic effect by directly binding to caspase-3,thereby inhibiting its ac-tivation by caspase-8.CONCLUSION:PA demonstrated a therapeutic effect in LPS-AKI,potentially through the inhibi-tion of inflammatory factor synthesis and release,as well as the inhibition of caspase-3 activation by caspase-8,reducing apoptosis in renal tubular epithelial cells.

Objective This study aims to investigate the influence of multimedia technology and micro-lesson combined with case-based teaching on the nursing ability of radiation therapy intern nurses.Methods Sixty-four nursing interns from the radiation therapy department of our hospital between January 2022 and September 2024 were selected.They were randomly divid-ed into two groups,with 32 in each group.The control group received traditional mentoring,while the observation group received multimedia technology and micro-lesson combined with case-based teaching in addition to traditional mentoring.The teaching effects were compared between the two groups.Results The nursing competency level of the interns after performing tasks in the control group was significantly lower than that in the observation group,with statistical significance(P＜0.05).There was no statistically significant difference in the nursing competency level before task implementation between the two groups(P＞0.05).In terms of nursing quality,the control group had a significantly lower level than the observation group,with statistical signifi-cance(P＜0.05).There was no statistically significant difference in nursing quality before task implementation between the two groups(P＞0.05).When comparing the satisfaction level of the two groups of interns with the course teaching effect,the control group had a significantly lower satisfaction level than the observation group,with statistical significance(P＜0.05).Conclusion The use of multimedia technology and micro-lesson combined with case-based teaching can effectively improve the clinical nurs-ing ability of intern nurses.Therefore,this method is worth promoting and applying in clinical settings.

Objective:To study the spatial distribution and characteristics of iodine content in residential drinking water in Shaanxi Province, and provide a basis for scientific prevention and control of iodine deficiency disorders.Methods:From March to October 2022, an investigation was conducted in all counties (districts, referred to as counties) of Shaanxi Province, with administrative villages as survey units. For centralized water supply systems, two terminal water samples were collected, and iodine content was measured separately, with the average value representing the drinking water iodine content at that location. For decentralized water supply systems, a 10% sampling method was used to divide each administrative village into five areas (east, south, west, north, and center), with 10% of water wells sampled from each area (if fewer than 10 water wells, the well with the largest drinking population was selected; if fewer than 5 wells, all wells were sampled). One water sample was collected from each water well, and iodine content was determined using the arsenic-cerium catalytic spectrophotometry method. Spatial autocorrelation and spatial scan analysis were used to analyze the spatial distribution and characteristics of drinking water iodine content.Results:A total of 53 990 drinking water samples were collected, with a median water iodine content of 6.66 μg/L, ranging from 0.10 to 779.40 μg/L. Drinking water iodine content was detected in 112 counties, showing a significant spatial positive correlation (global autocorrelation, Moran's I = 0.74, Z = 43.83, P < 0.001). Local autocorrelation analysis showed that the difference in the distribution of iodine content in drinking water among 36 counties was statistically significant ( P < 0.05), with 22 counties showing low-low clustering and 12 counties showing high-high clustering. Spatial scanning identified three water iodine clustering areas, including two high-water iodine cluster areas and one low-water iodine cluster area. Conclusions:The distribution of iodine content in residential drinking water in Shaanxi Province shows significant spatial clustering and heterogeneity, requiring targeted interventions to achieve precise prevention and control of iodine deficiency disorders.

Objective To evaluate the cost-effectiveness of low-dose steroid combined with tacrolimus or cyclophosphamide in treating adult idiopathic membranous nephropathy(IMN).Methods A prospective cohort design was used to collect clinical data on IMN patients admitted to the Affiliated Hospital of Hebei University from December 2018 to April 2022.The patients were divided into the exposure group(low-dose steroid combined with tacrolimus)and control group(low-dose steroid combined with cyclophosphamide)according to the treatment regimen.Propensity score matching was employed to balance the baseline characteristics between the two groups.The total response rate was taken as the effect index,cost-effectiveness analysis was conducted by using the decision tree model,and single factor sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the cost-effectiveness analysis results.Results A total of 112 patients with IMN were included.After propensity score matching,46 patients were included in the exposed and control groups,respectively.The total remission rate of the exposure group was 84.78％,with the cost of 13,352.64 yuan and the cost-effectiveness ratio of 157.50.In the control group,the total remission rate was 80.43％,the cost was 8,154.18 yuan,and the cost-effectiveness ratio was 101.38.The incremental cost-effectiveness ratio of the two groups was 1 195.05,and the sensitivity analysis results were consistent with those of the cost-effectiveness analysis.Conclusion The two treatment schemes have their own advantages in the treatment of IMN.The cost-effectiveness ratio of low-dose hormone combined with tacrolimus is relatively higher,and the combination of low-dose hormone with cyclophosphamide is more economical.Both schemes have certain clinical promotion value..

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.