ObjectiveTo compare the clinical features of patients with hepatitis B virus （HBV）-related early-onset liver cancer and those with late-onset liver cancer， to assess the severity of the disease， and to provide a theoretical basis for the early diagnosis and treatment of liver cancer. MethodsA retrospective analysis was performed for 695 patients who were diagnosed with HBV-related liver cancer for the first time in Guangzhou Eighth People’s Hospital， Guangzhou Medical University， from January 2019 to August 2023， among whom 93 had early-onset liver cancer （defined as an age of50 years for female patients and40 years for male patients） and 602 had late-onset liver cancer （defined as an age of ≥50 years for female patients and ≥40 years for male patients）. Related clinical data were collected， including demographic data， clinical symptoms at initial diagnosis， comorbidities， smoking history， drinking history， family history， routine blood test results， biochemical parameters of liver function， serum alpha-fetoprotein（AFP）， virological indicators， coagulation function， and imaging findings. The pan-inflammatory indices neutrophil-to-lymphocyte ratio （NLR）， platelet-to-lymphocyte ratio （PLR）， and lymphocyte-to-monocyte ratio （LMR） were calculated， as well as FIB-4 index， aspartate aminotransferase-to-platelet ratio index （APRI）， S index， Model for End-Stage Liver Disease （MELD） score， Child-Turcotte-Pugh （CTP） score， albumin-bilirubin （AIBL） grade， and Barcelona Clinic Liver Cancer （BCLC） stage. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or Fisher’s exact test were used for comparison of categorical data between two groups. ResultsThere were significant differences between the two groups in the proportion of male patients and the incidence rates of diabetes， hypertension， and fatty liver disease （χ²=6.357， 15.230， 11.467， and 14.204， all P0.05）， and compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly higher proportion of patients progressing to liver cancer without underlying cirrhosis （χ²=24.657， P0.001） and a significantly higher proportion of patients with advanced BCLC stage （χ²=6.172， P=0.046）. For the overall population， the most common clinical symptoms included abdominal distension， abdominal pain， poor appetite， weakness， a reduction in body weight， edema of both lower limbs， jaundice， yellow urine， and nausea， and 55 patients （7.9%） had no obvious symptoms at the time of diagnosis and were found to have liver cancer by routine reexamination， physical examination suggesting an increase in AFP， or radiological examination indicating hepatic space-occupying lesion； compared with the late-onset liver cancer group， the patients in the early-onset liver cancer group were more likely to have the symptoms of abdominal distension， abdominal pain， and jaundice （all P0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly larger tumor diameter （Z=2.845， P=0.034）， with higher prevalence rates of multiple tumors and intrahepatic， perihepatic， or distant metastasis （χ²=5.889 and 4.079， both P0.05）， and there were significant differences between the two groups in tumor location and size （χ²=3.948 and 11.317， both P0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had significantly lower FIB-4 index， proportion of patients with HBsAg ≤1 500 IU/mL， and levels of LMR and Cr （all P0.05）， as well as significantly higher positive rate of HBeAg and levels of log₁₀ HBV DNA， AFP， WBC， Hb， PLT， NLR， PLR， TBil， ALT， Alb， and TC （all P0.05）. ConclusionCompared with late-onset liver cancer， patients with early-onset liver cancer tend to develop liver cancer without liver cirrhosis and have multiple tumors， obvious clinical symptoms， and advanced BCLC stage， which indicates a poor prognosis.

Objective To explore the application value of the simple foot immobilization device in radiotherapy for rectal cancer based on the inter-fractional setup error acquired by image-guided technology of cone beam computed tomography (CBCT). Methods A total of 49 rectal cancer patients received volumetric modulated arc therapy (VMAT) in Zhongshan Hospital, Fudan University from February 2021 to February 2023 were included. Inter-fractional setup errors of each patient were analyzed. Any situation where the inter-fractional setup error exceeded 7 mm in any three-dimensional direction during the inter-fractional treatment course (the first treatment was excluded) was defined as a failed positioning reproducibility. Binary logistic regression was used for independent factor analysis of the failed positioning reproducibility. Results In the X-axis, Y-axis, and Z-axis directions, the patients’ inter-fractional setup errors were (2.50±1.97) mm, (2.18±1.73) mm, and (1.17±1.06) mm, respectively. Age (OR＝0.880, 95%CI 0.801-0.967, P＝0.008) and radiotherapy mode (OR＝0.178, 95% CI 0.034-0.936, P＝0.042) were independent factors affecting failed positioning reproducibility. The area under the curve (AUC) of age predicting failed positioning reproducibility was 0.780, with an optimal cut-off value of 53.5 years old. Conclusions The simple foot immobilization device has good inter-fractional setup reproducibility for patients with rectal cancer who received radiotherapy, but it is not recommended for patients younger than 53.5 years with rectal cancer undergoing preoperative radiotherapy.

Objective:The aim was to analyze key indicators for the diagnosis and treatment of chronic hepatitis B（CHB），including virus detection rate，standardized treatment rate，and loss to follow-up rate，in order to provide a basis for optimizing diagnosis and treatment plans，improve the diagnosis and treatment level of CHB，and improve patient prognosis.Methods:Patients with CHB admitted to the Guangzhou Eighth People′s Hospital Affiliated to Guangzhou Medical University from January 2024 to January 2025 were enrolled. The datas were collected and organized using Excel. Statistical analysis was conducted using SPSS 26.0 software，with a focus on evaluating core indicators such as virus detection rate，standardized treatment rate，and loss to follow-up rate.Results:The positive rate of hepatitis B surface antigen（HBsAg）in non-specific patients was 28.95%，the antiviral treatment rate in specialized patients was 90.78%，and the standardized antiviral drug conversion treatment rate in low-level viremia（LLV）patients was 61.45%. The standardized antiviral drug conversion treatment rates for high-risk patients with combined kidney/bone injuries were 72.75% and 74.40%，respectively. The overall dropout rate was 10.47%，with a dropout rate of 13.80% for LLV patients.Conclusions:The antiviral treatment coverage rates in CHB patients were over 90%，but in certain groups（such as LLV patients and those with kidney or bone injuries），the standardized treatment rates were still low and loss to follow-up rates were high，suggesting the need to improve HBV screening，treatment for special populations，and patient adherence.

Objective:A novel grass-root community screening and management model of hepatitis B was developed in order to improve the diagnosis and treatment rate of hepatitis B in Guangzhou city.Methods:A three-tier collaborative framework［tertiary hospitals-center for disease control and prevention（CDC）-primary care clinics］implemented dual-track screening（fixed-site+mobile units）using rapid hepatitis B surface antigen（HBsAg）testing and structured surveys. Digital closed-loop management integrated screening，referral，and follow-up. Data were analyzed via SPSS 26.0.Results:Among 30 012 community-dwelling adults screened（Male∶Female=1∶1.68），overall HBsAg positive rate was 5.21%（1 565/30 012），peaking in the 50-59-year cohort（ χ2=271.80， P<0.001）. Hepatitis B knowledge awareness was critically low（39.24%）. Of 140 referred HBsAg-positive individuals，15 chronic carriers required no immediate antiviral therapy per guidelines. Treatment linkage surged from 32.8%（41/125）to 86.4%（108/125）post-intervention. aMAP hepatocellular carcinoma（HCC）risk stratification（n=82）revealed low（36.6%），intermediate（32.9%），and high-risk（30.5%）profiles. Conclusions:This coordinated，digitally-enhanced strategy significantly improved hepatitis B detection and treatment access. However，persistent knowledge gaps underscore the imperative for targeted community education and adherence support.

Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

Objective To investigate the impact of high mobility group box 1(HMGB1)on hydrogen peroxide(H2O2)-induced DNA damage and senescence in lens epithelial cells(LECs)under oxidative stress conditions.Methods Fluorescent quantitative real-time polymerase chain reaction(RT-PCR)technology was used to detect the mRNA expres-sion of HMGB1 in the anterior capsule tissue of patients with age-related cataract(ARC group)and epiretinal membrane(control group).Western blot analysis was employed to examine the changes in the protein expression of HMGB1 in the LEC line SRA01/04 after treatment with varying concentrations of H2O2(0,100,200,and 400 μmol·L-1).The optimal concentration was selected for subsequent establishment of a cellular oxidative damage model.The cultured SRA01/04 cells were divided into three groups:Control(untreated),HA(transfected with the control plasmid HA),and OE-HMGB1 groups(transfected with the HMGB1 plasmid).The mRNA and protein expression levels of HMGB1 were detected by RT-PCR and Western blot.The cultured SRA01/04 cells were divided into three groups:H2O2(treated with 400 μmol·L-1 H2O2),H2O2+HA(transfected with the control plasmid HA and simultaneously treated with 400 μmol·L-1 H2O2),and H2O2+OE-HMGB1 groups(transfected with the HMGB1 plasmid and simultaneously treated with 400 μmol·L-1 H2O2).Immunofluorescence was used to detect DNA oxidative damage in cells from each group.Western blot analysis was per-formed to assess the protein expression levels of phosphorylated histone H2A(γH2A),tumor protein p53(P53),cyclin-dependent kinase inhibitor 1A(P21),and cyclin-dependent kinase inhibitor 2A(P16)in cells from each group.Additional-ly,senescence-associated-β-galactosidase(SA-β-gal)staining was conducted to detect senescent changes in cells from each group.Results RT-PCR results indicated that the relative mRNA expression level of HMGB1 in the anterior capsule tissue of the ARC group was significantly decreased,compared with that in the control group(P＜0.001).Furthermore,in the H2O2-induced oxidative damage model,the relative protein expression level of HMGB1 decreased with the increase of the concentration of H2O2.Both RT-PCR and Western blot analyses revealed that the mRNA and protein expression levels of HMGB1 were both significantly elevated in the OE-HMGB1 group,compared with those in the HA group(both P＜0.001).The immunofluorescence staining results demonstrated that the protein expression of γH2A and the fluorescence intensity in the H2O2+OE-HMGB1 group were significantly decreases,compared with those in H2O2 and H2O2+HA groups(all P＜0.001).SA-β-gal staining results showed that the H2O2+OE-HMGB1 group had significantly less cells stained by SA-β-gal than H2O2 and H2O2+HA(both P＜0.001).Additionally,Western blot analysis revealed that,compared with those in H2O2 and H2O2+HA groups,the relative expression levels of senescence-associated proteins P53,P21,and P16 were significantly decreased in the H2O2+OE-HMGB1 group(all P＜0.01).Conclusion HMGB1 inhibits the accumula-tion of damaging DNA and senescence in LECs by enhancing DNA damage repair capabilities.

Objective:To evaluate the long-term outcomes and predictors of coronary atherosclerotic lesions deemed functionally non-ischemic (quantitative flow ratio(QFR)>0.80) and deferred from intervention.Methods:This study is a post-hoc analysis of the FAVOR Ⅲ China trial, which enrolled 3 825 patients with stable or unstable angina pectoris or with myocardial infarction occurring at least 72 hours prior to screening, between December 5, 2018 and January 9, 2020 from 26 research centers in China. Coronary vessels with QFR>0.80 and without interventional treatment were analyzed in this study. The primary endpoint was 3-year target vessel revascularization. Vessels with revascularization (revascularized group) during follow-up were matched 1∶1 using propensity score matching to comparable vessels without revascularization (non-revascularized group). Multivariate Cox regression analysis was used to identify the risk factors for target vessel revascularization (TVR).Results:A total of 6 212 functionally negative vessels with deferred intervention were included in the final analysis, among which 153 vessels (2.5%) underwent TVR during a 3-year follow-up. Prior to propensity score matching, 6 059 vessels comprised the non-revascularized group. At the vessel level, compared to the non-revascularized group, the revascularized group exhibited a significantly higher proportion of males (79.1% (121/153) vs. 70.2% (4 253/6 059), P=0.018), higher body mass index ((25.6±4.0) kg/m2 vs. (24.3±5.2) kg/m2, P=0.003), and a higher prevalence of hypertension (73.9% (113/153) vs. 65.1% (3 944/6 059), P=0.025). And 152 pairs of vessels were successfully matched. Multivariate Cox regression analysis identified in-stent restenosis lesions ( HR=2.59, 95% CI 1.28-5.23, P=0.008) as an independent risk factor for target vessel revascularization. Conclusions:Coronary lesions classified as functionally non-ischemic at baseline are not entirely stable and may progress to lesions that requiring revascularization over time. In-stent restenosis emerges as a critical independent predictor of revascularization.

Objective:Investigate the impact of calcification on the long-term outcomes of patients with coronary chronic total occlusion (CTO) after percutaneous coronary intervention (PCI).Methods:A retrospective cohort study was conducted. Patients who underwent PCI and had at least one CTO lesion at Fuwai Hospital between January 2010 and December 2013 were consecutively enrolled. Calcification was evaluated by coronary angiography, and patients were divided into two groups: moderate/severe calcification group and non/mild calcification group. Clinical follow-up was completed up to 5 years. Incidence of PCI-related complications and immediate procedural outcomes were compared between two groups, and the primary endpoint was the target lesion failure (TLF) at 5 years after PCI. Clinical follow-up endpoint events were analyzed using Kaplan-Meier survival analysis with log-rank test, and Cox multivariate regression model was used to evaluate the relationship between calcification and TLF.Results:The study included 2 659 CTO patients with an age of (57.2±10.5) years, of whom 442 (16.6%) were female, and among whom 13.5% (360/2 659) had moderate/severe calcification. Compared with the non/mild calcification group, the moderate/severe calcification group had a higher incidence of PCI-related complications (43.2% (156/361) vs. 32.5% (772/2 374), P<0.001) and procedural failure (34.3% (124/361) vs. 24.3% (577/2 374), P<0.001). Additionally, the moderate/severe calcification group showed a higher risk of the primary endpoint event (TLF) during the 5-year follow-up (19.8% vs. 15.3%, log-rank P=0.028). Higher incidence of cardiac death was observed in moderate/severe calcification group (5.7% vs. 2.7%, log-rank P=0.003). Cox multivariate regression analysis revealed that moderate/severe calcified plaques remained an independent risk factor for 5-year TLF after CTO-PCI ( HR=1.34, 95% CI: 1.01-1.79, P=0.043). Conclusion:Compared with CTO patients with non/mild calcification, those with moderate/severe calcification have higher procedural failure and complication rates, as well as poorer long-term prognosis, mainly due to an increase in cardiac death.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objective To investigate the relationship between serum glucagon-like peptide-1(GLP-1),monocyte chemoattractant protein-1(MCP-1),insulin-like growth factor binding protein-3(IGFBP-3)and glycolipid metabolism,bone metabolism and microvascular complications(MC)in children with type 1 diabe-tes mellitus(T1DM).Methods A total of 211 children with T1DM(T1DM group)admitted to Handan Cen-tral Hospital,Xingtai Traditional Chinese Medicine Hospital,Baoding First Central Hospital and Handan Ma-ternal and Child Health Hospital from January 2021 to February 2023 were selected,patients were divided into MC group(63 cases)and non-MC group(148 cases)according to whether MC was complicated within 1 year,and 108 healthy children who underwent physical examination during the same period were selected as control group.The levels of serum GLP-1,MCP-1,IGFBP-3 and glucose and lipid metabolism indexes[fasting plasma glucose(FPG),fasting insulin(FINS),glycosylated hemoglobin(HbA1c),homeostasis model assessment of insulin resistance(HOMA-IR),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)]and bone metabolism indexes[bone specific alkaline phosphatase(BALP),osteocalcin(OST),type I collagen cross-linked C-terminal peptide(CTX)]were detec-ted.The correlation between serum GLP-1,MCP-1,IGFBP-3 and glucose and lipid metabolism,bone metabo-lism in children with T1DM were analyzed by Pearson and Spearman correlation coefficient.Taking MC in children with T1DM as the dependent variable,the influencing factors were determined by multivariate uncon-ditional Logistic regression model,and the predictive value of serum GLP-1,MCP-1 and IGFBP-3 for MC were analyzed by receiver operating characteristic curve.Results The levels of serum GLP-1,FINS,HDL-C,BALP,OST and CTX in the T1DM group were lower than those in the control group,while the levels of MCP-1,IGFBP-3,FPG,HbA1c,HOMA-IR,TG and LDL-C in the T1DM group were higher than those in the control group,the differences were statistically significant(P<0.05).Serum GLP-1 in children with T1DM was negatively correlated with FPG,HbA1c,HOMA-IR,TG and LDL-C,and positively correlated with FINS,HDL-C,BALP,OST and CTX(P<0.05).MCP-1 and IGFBP-3 were positively correlated with FPG,HbA1c,HOMA-IR,TG and LDL-C,and negatively correlated with FINS,HDL-C,BALP,OST and CTX(P<0.05).Follow-up for 1 year,the incidence of MC in 211 children with T1DM was 29.86%(63/211).Elevated HbA1c,HOMA-IR,LDL-C,MCP-1 and IGFBP-3 were independent risk factors for MC in children with T1DM,and elevated GLP-1 was an independent protective factor(P<0.05).The area under the curve of ser-um GLP-1,MCP-1 and IGFBP-3 combined to predict MC in children with T1DM was 0.919,which was grea-ter than 0.781,0.788 and 0.794 predicted by serum GLP-1,MCP-1 and IGFBP-3 alone(P<0.05).Conclu-sion The decrease of serum GLP-1 level and the increase of MCP-1 and IGFBP-3 levels are related to glyco-lipid metabolism,bone metabolism disorder and MC in children with T1DM,the combined application of ser-um GLP-1,MCP-1 and IGFBP-3 has a good predictive value for MC in children with T1DM.