Objective To investigate the heterogeneity and key molecular features of epithelial cells in triple-negative breast cancer (TNBC), identify prognostic biomarkers, and develop a robust survival prediction model. Methods Using TNBC single-cell transcriptomic data, epithelial cells were extracted, normalized, and subclustered to characterize their molecular signatures and functional differences. High-dimensional weighted gene co-expression network analysis (hdWGCNA) was applied to establish co-expression modules in epithelial cells. Multiple machine learning algorithms were integrated to select key prognostic genes and develop a risk-score model, whose performance was evaluated using receiver operating characteristic (ROC) curves and Kaplan-Meier (K-M) survival analysis. In addition, the immune microenvironment features and potential drug-response differences between the high- and low-risk groups were systematically assessed. Finally, PCR was performed to validate the expression differences of the key genes between tumor and normal tissues. Results We characterized the composition and molecular features of TNBC epithelial subpopulations and identified a TNBC-associated epithelial subset. By integrating hdWGCNA with machine learning approaches, 10 key genes were selected to construct a prognostic model, which effectively stratified patients into distinct survival-risk groups and demonstrated favorable predictive performance in ROC and K-M analyses. Immune profiling revealed the differences in the infiltration levels of seven immune cell types and immune function-related features between the high- and low-risk groups. Drug-sensitivity analysis suggested potential differential responses to eight agents across the risk groups. PCR validation further confirmed the differential expression of the ten signature genes between tumor and normal tissues. Conclusion This study reveals epithelial heterogeneity in TNBC at single-cell resolution and establishes a 10-gene prognostic model, which may facilitate the stratification of TNBC risk and the evaluation of immune characteristics and potential therapeutic strategies.

BACKGROUND:Age-related macular degeneration and deep vein thrombosis may share common pathophysiological mechanisms,but there is a lack of direct evidence regarding their relationship.Traditional studies are confounded by confounding factors and reverse causation.OBJECTIVE:To investigate the causal relationship between age-related macular degeneration and deep vein thrombosis based on Mendelian randomization design.METHODS:Through a two-way Mendelian randomization analysis,single nucleotide polymorphisms of exposure and outcomes were obtained from publicly available genome-wide association studies,with deep vein thrombosis data from the FinnGen database in a European population with a sample size of 363 612 and 1 048 575 single nucleotide polymorphisms.In addition,we obtained data on age-related macular degeneration from the IEUOpenGWAS project,also from a European population sample of 105 248 cases covering 11 304 110 single nucleotide polymorphisms.In R4.4.1,we used the TwoSampleMR package(version 0.6.8)to explore the causal effects of exposure factors on outcomes.At the same time,we also conducted a sensitivity analysis via MR-Egger regression,weighted median,weighted model and simple model methods to ensure that the assessment results were robust and reliable.In addition,we used the"heterogeneity"function to test for heterogeneity,and the"horizontal pleiotropy"function and the MR-PRESSO test to further assess horizontal pleotropy.The Cochran's Q test was used to determine whether there was statistical heterogeneity between single nucleotide polymorphisms,and the leave-one-out method was used to assess whether single nucleotide polymorphisms would significantly interfere with Mendelian randomization analysis.Funnel plots were drawn to assess the potential bias of single nucleotide polymorphisms.Forest plots were plotted to show the effect estimates of single nucleotide polymorphisms on exposure and outcomes,and their confidence intervals were plotted.Scatter plots were plotted to evaluate the relationship between the potency of single nucleotide polymorphisms and their causal effect size on outcome estimates.RESULTS AND CONCLUSION:Both forward and reverse studies showed that there was no causal association between age-related macular degeneration and the occurrence of deep vein thrombosis(P＞0.05).Sensitivity analysis showed that the main analysis results were reliable and robust,with no outliers,heterogeneity,and horizontal pleiotropy,and no single nucleotide polymorphism significantly affected the overall effect estimate.Although it is based on European population data,it has methodological reference value for Chinese biomedical research on complex disease associations.In this field,China can carry out multi-center large-sample studies,accurately analyze the internal links between Chinese population-related diseases,and provide a basis for prevention and treatment strategies and clinical practice.

Objective To summarize and analyze the efficacy and influencing factors of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia relapsing after the first allo-HSCT. Methods Clinical data of 17 patients with acute leukemia who underwent second allo-HSCT at Peking University First Hospital from January 2005 to December 2024 were retrospectively analyzed. Results Among the 17 patients, 7 achieved long-term disease-free survival after second transplantation. The median progression-free survival after successful second transplantation was 7 months (range 8 days to 69 months). The relapse fatality was 24%, and the transplant-related fatality was 35%. Conclusions Second transplantation is an effective treatment for relapsed and refractory acute leukemia, but the relapse fatality and transplant-related fatality remain high. Patient age, time of relapse after the first transplantation and disease status before second transplantation are all factors that affect the efficacy of second transplantation. Younger age, late relapse and complete remission of disease before second transplantation are all beneficial for long-term disease-free survival after second transplantation.

OBJECTIVE To conduct a clinical comprehensive evaluation of five marketed thrombopoietin receptor agonists （TPO-RA） approved in China， providing quantitative evidence for drug selection and therapeutic decision-making in medical institutions. METHODS Relevant data on Romiplostim for injection， Eltrombopag olamine tablets， Herombopag olamine tablets， Avatrombopag maleate tablets， and Lusutrombopag tablets were collected. Based on the Chinese Rapid Guide for Drug Evaluation and Selection in Medical Institutions （Second Edition）， 12 formulations of these five TPO-RA were scored quantitatively and comparatively across five dimensions： pharmacological characteristics， efficacy， safety， cost-effectiveness， and other attributes. RESULTS The comprehensive scores of the 12 formulations ranged from 62.56 to 75.50 points， with most scoring ≥70 points. Using the highest-scoring formulation for each generic name as a representative， the overall rankings of the five TPO-RA were as follows： Lusutrombopag tablets （75.50 points）， Eltrombopag olamine tablets （75.10 points）， Avatrombopag maleate tablets （70.40 points）， Romiplostim for injection （63.93 points）， and Herombopag olamine tablets （63.52 points）. Lusutrombopag tablets scored relatively high in pharmacological characteristics， safety， and cost-effectiveness， while Eltrombopag olamine tablets performed well in efficacy and cost-effectiveness. The other formulations showed varying scores across evaluation dimensions. CONCLUSIONS The five TPO-RA demonstrate favorable overall clinical value， with Lusutrombopag tablets and Eltrombopag olamine tablets ranking higher in comprehensive scores， these two drugs should be prioritized in drug selection and formula optimization by medical institutions.

BACKGROUND:Age-related macular degeneration and deep vein thrombosis may share common pathophysiological mechanisms,but there is a lack of direct evidence regarding their relationship.Traditional studies are confounded by confounding factors and reverse causation.OBJECTIVE:To investigate the causal relationship between age-related macular degeneration and deep vein thrombosis based on Mendelian randomization design.METHODS:Through a two-way Mendelian randomization analysis,single nucleotide polymorphisms of exposure and outcomes were obtained from publicly available genome-wide association studies,with deep vein thrombosis data from the FinnGen database in a European population with a sample size of 363 612 and 1 048 575 single nucleotide polymorphisms.In addition,we obtained data on age-related macular degeneration from the IEUOpenGWAS project,also from a European population sample of 105 248 cases covering 11 304 110 single nucleotide polymorphisms.In R4.4.1,we used the TwoSampleMR package(version 0.6.8)to explore the causal effects of exposure factors on outcomes.At the same time,we also conducted a sensitivity analysis via MR-Egger regression,weighted median,weighted model and simple model methods to ensure that the assessment results were robust and reliable.In addition,we used the"heterogeneity"function to test for heterogeneity,and the"horizontal pleiotropy"function and the MR-PRESSO test to further assess horizontal pleotropy.The Cochran's Q test was used to determine whether there was statistical heterogeneity between single nucleotide polymorphisms,and the leave-one-out method was used to assess whether single nucleotide polymorphisms would significantly interfere with Mendelian randomization analysis.Funnel plots were drawn to assess the potential bias of single nucleotide polymorphisms.Forest plots were plotted to show the effect estimates of single nucleotide polymorphisms on exposure and outcomes,and their confidence intervals were plotted.Scatter plots were plotted to evaluate the relationship between the potency of single nucleotide polymorphisms and their causal effect size on outcome estimates.RESULTS AND CONCLUSION:Both forward and reverse studies showed that there was no causal association between age-related macular degeneration and the occurrence of deep vein thrombosis(P＞0.05).Sensitivity analysis showed that the main analysis results were reliable and robust,with no outliers,heterogeneity,and horizontal pleiotropy,and no single nucleotide polymorphism significantly affected the overall effect estimate.Although it is based on European population data,it has methodological reference value for Chinese biomedical research on complex disease associations.In this field,China can carry out multi-center large-sample studies,accurately analyze the internal links between Chinese population-related diseases,and provide a basis for prevention and treatment strategies and clinical practice.

Objective:To identify the risk factors for acute graft-versus-host disease (aGVHD) in patients with acute myeloid leukemia (AML) undergoing haploidentical hematopoietic stem cell transplantation (HID-HSCT) .Methods:A total of 141 AML patients who underwent HID-HSCT at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, from January 2020 to July 2021 were included. The cumulative incidence of aGVHD was analyzed using the Fine-Gray competing risk model, with relapse and death as competing events, to compare differences between groups. Potential risk factors were evaluated by univariable and multivariable Cox proportional hazards regression analyses to determine their independent effects on aGVHD.Results:Among the 141 patients, 86 (61.0%) were male and 55 (39.0%) were female, with a median age at transplantation of 34 years. Within 100 days post-transplant, 59 patients developed grade Ⅱ-Ⅳ aGVHD, whereas 86 patients experienced no or grade Ⅰ aGVHD (the grade 0-Ⅰ aGVHD group) . Survival analysis showed that the 3-year overall survival was 68.7% (95% CI: 57.7%-81.9%) in the grade Ⅱ-Ⅳ aGVHD group, compared with 78.8% (95% CI: 70.4%-88.3%) in the grade 0 - Ⅰ aGVHD group, with the difference not being statistically significant ( P=0.190) . Univariable analysis identified donor age ( P=0.020, HR=1.020, 95% CI: 1.000-1.040) and the female donor-male recipient sex combination ( P=0.033, HR=1.980, 95% CI: 1.160-3.380) as risk factors for grade Ⅱ-Ⅳ aGVHD. Multivariable analysis confirmed that donor age ( P=0.005, HR=1.026, 95% CI: 1.008-1.047) and the female donor-male recipient sex combination ( P=0.002, HR=2.339, 95% CI: 1.354-4.037) were independent risk factors for aGVHD. Patients receiving grafts from donors aged >45 years had a significantly higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD compared with those receiving grafts from donors ≤45 years [54.7% (95% CI: 42.3%-67.0%) vs 31.6% (95% CI: 21.0%-42.1%) , P=0.006]. Similarly, patients with the female donor-male recipient sex combination had a higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD than those with other sex combinations [56.8% (95% CI: 40.4%-73.1%) vs 36.9% (95% CI: 27.5%-46.3%) , P=0.015]. Conclusion:Older donor age and the female donor-male recipient sex combination remain independent risk factors for aGVHD in patients with AML undergoing HID-HSCT.

Objective:To investigate the efficacy and influencing factors of iodine-125 seed implantation in the treatment of recurrent radioiodine refractory differentiated thyroid carcinoma (RAIR-DTC) .Methods:Retrospective analysis of 18 patients with recurrent RAIR-DTC treated with iodine-125 particle implantation at Ward One, Department of Oncology, Hebei General Hospital from Sept. 2015 to Mar. 2022 was performed. A total of 35 lesions were involved, all permanently implanted with iodine-125 particles under image guidance, with particle activity ranging from 0.3mCi to 0.8mCi, and prescription doses ranging from 80 to 140 Gy. The study observed the objective response rate, local control rate, survival rate, adverse reactions, and factors influencing treatment efficacy.Results:After a follow-up period of 8 to 115 months,according to the objective efficacy evaluation criteria of solid tumors 1.1,the objective response rates were 51.4% (18/35) ,80.0% (28/35) ,68.6% (24/35) ,60.0% (21/35) ,42.9% (15/35) at 3,6,12,24,36 months postoperatively,respectively.The local control rates were 100% (35/35) ,100% (35/35) ,80.0% (28/35) ,62.9% (22/35) ,51.4% (18/35) at 3,6,12,24,36 months postoperatively,respectively.The 1-,2-, and 3-year postoperative survival rates were 83.3% (15/18) ,72.2% (13/18) ,61.1% (11/18) ,respectively.During the follow-up period,4 patients developed progressive lesions in the target area.One grade I radioactive skin injury,one grade Ⅱ radioactive skin injury,and no residual particle-related adverse reactions.The results of multivariate analysis showed that D90,tumor involvement of the esophagus were the factors influencing the recent efficacy.The area under the ROC curve for D90 was 0.804 with the best bound of 106.5Gy.Conclusion:Iodine-125 particle implantation is safe and effective for recurrent RAIR-DTC.D90,tumor involvement of the esophagus are the influencing factors of the recent efficacy,and the D90≥106.5Gy treatment effect is better.

Objective Advances in synthetic DNA technology have made it much easier to fake human DNA samples.There are literature reports that fake human DNA can be synthesized by different methods and implanted in the field to confuse the investigation or mislead the trial.Therefore,distinguishing authentic human DNA from synthetic DNA and performing individual identification has become a critical scientific challenge.Methods We define a novel composite genetic marker(methylation-microhaplotype)by combining CpG sites stably hypermethylated or hypomethylated in natural human DNA and nearby immediately adjacent microhaplotype sites.A total of 19 locis were obtained according to the screening criteria,and a composite detection system for methylation-microhaplotypes was established using MPS technology.Random volunteer DNA samples were extracted and synthetic DNA samples were prepared based on whole genome amplification techniques.Population DNA samples were analyzed to evaluate forensic parameters and methylation variability of the methylation-microhaplotype markers.Comparative analyses of human and synthetic DNA were conducted to assess the markers'ability to discriminate between the two and to detect/type both components in mixed mixed samples.Results The composite detection system composed of 19 locis demonstrated high individual identification ability,achieving a cumulative individual identification probability of 0.999 999 999 996 86.12 hypermethylated locis and 7 hypomethylated locis had relatively stable methylation levels in 57 human DNA samples.According to the allele methylation rate(Ram)value,the system can effectively identify natural and synthetic DNA samples.Meanwhile,for mixed DNA samples,the presence of human and synthetic DNA samples can be found and genotyped.Conclusion Methylation-microhaplotype genetic markers,which can discover human DNA and synthetic DNA and can detect the presence and genotyping of them from mixed samples,is a potential useful tool for forensic DNA analysis.

Objective To investigate the real experience and needs of home enteral nutrition(HEN)support for patients with cancer pain so as to provide references for formulating effective clinical nursing intervention programs.Methods Purposive sampling was used to select the patients with cancer pain under HEN in the Department of Pain of our hospital between January and December 2022.Semi-structured interviews were conducted in the study.Data were analysed and summarised,then the themes were extracted using Colaizzi's 7-step method.Results Three themes were extracted,including positive experiences(pain relief,improved nutritional status,sense of family belonging and increased confidence in self-management)and negative experiences(sleep disturbance,limited activities,worry about adversary reactions and complications,and fear of intubation).Patients also expressed the need for more nutritional knowledge and social support(hope for professional guidance and supports from medical resource and policy).Conclusion Medical providers should enhance the management efficiency of the patients with cancer pain and their family members,pay attention to the psychological assessment and intervention during HEN,and strengthen the diversified supports and nursing follow-up of the patients.Effective interventions should be implemented to solve issues that arise during HEN to ensure a smooth and safe implementation.

Objective To investigate the effect of different strand lengths of 125I seeds with the same activity on the dose of different reference points around the seeds.Methods The scanned images were transferred to the three-dimensional treatment planning system(3D-TPS)according to DICOM format.The target volume was delineated at 5 mm and 10 mm above and below the center of the phantom,and a 0.8 mCi seeds strand was simulated.The 1-20 seeds were arranged with an equal spacing of 5 mm(5 mm-100 mm).The 5 mm points above and below the center of the seeds strand were defined as point A and point A',and the 10 mm points above and below the center were defined as point B and point B'.5 mm above and below the edge of the seeds strand on the left side were defined as AL points and AL'points,and 5 mm above and below the edge of the seeds strand on the right side were defined as AR points and AR'points.Similarly,points 10 mm above the above mentioned positions were defined as BL points,BL'points,BR points,BR'points.The average dose symmetry points were measured at AL,AL',AR,and 5 mm,10 mm,15 mm and 20 mm inside AR' of the 45 mm-100 mm seeds strand.The dose at the center was compared with the dose at the end points.The dose at the center point A was compared with the average dose at the symmetry points of 5 mm,10 mm,15 mm and 20 mm inside of the end points AL,AL',AR and AR',and the dose at each point was curve fitting.The correlation between each point and seeds strands of different lengths was analyzed.Results There was a positive correlation between the dose and the length of each point.There was no statistically significant difference between the center point and the end point.There was a statistically significant difference in dosage at points 5 mm and 10 mm inside from point A,while there was no statistically significant difference in dosage at points 15 mm and 20 mm inside from point A.The dose of A,A',B and B' point increased steadily with the increase of seed chain length,and the fitting curves were obtained respectively:y=e(-0.620/x+5.28)(R2=0.992),y=e(-0.640/x+5.34)(R2=0.987),y=e(-0.82/x+4.80)(R2=0.984),y=e(-0.82/x+4.83)(R2=0.9g1).Conclusion The doses at points A,A',B,and B'are positively correlated with seeds strand length and have a high degree of stability.Point A can be used as a reference point for the target area dose of the seeds strand,and point B can be used as a reference point for the dose to critical organs.The dose at other positions is more variable and thus has a certain degree of uncertainty as a reference point for the seeds strand dose.