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.

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:At present,there are few reports on the postoperative efficacy of arthroscopic coracoid tunnel-free suspension fixation and coracoid single tunnel fixation in the treatment of acromioclavicular joint dislocation at home and abroad.The specific clinical efficacy of the two procedures and whether there are other risks need to be explored. OBJECTIVE:To compare the short-term postoperative clinical efficacy of arthroscopic TightRope band plate fixation with single tunnel fixation of the coracoid process and tunnel-free suspension fixation of the coracoid process in the treatment of acute type Ⅲ-Ⅴ acromioclavicular joint dislocation. METHODS:A retrospective analysis was performed in 45 patients with acromioclavicular joint dislocation who met the inclusion criteria admitted to the Sixth Affiliated Hospital of Xinjiang Medical University from June 2019 to September 2022,and were divided into coracoid single tunnel fixation group(20 cases)and coracoid tunnel-free suspension fixation group(25 cases)according to the surgical treatment plan.Operation time,incision length,blood loss,Constant-Murley score,visual analogue scale score,the American Shoulder and Elbow Surgeons(ASES)score and intraoperative and postoperative complications of the shoulder joint before operation,3 months after surgery and the last follow-up were compared between the two groups. RESULTS AND CONCLUSION:All patients successfully completed the operation,and there was no important nerve or blood vessel damage during the operation.The operation time of the coracoid tunnel-free suspension fixation group was significantly shorter than that of the coracoid tunnel-free suspension fixation group(P<0.05).There was no significant difference in intraoperative blood loss and incision length between the two groups(P>0.05).All patients were followed up for 12 to 24 months,with an average of(15.29±2.73)months.In the coracoid single tunnel fixation group,at 3 months after operation and the final follow-up,the visual analogue scale score was significantly lower than the preoperative score(P<0.05);Constant-Murley score and ASES score were significantly increased compared with the preoperative values(P<0.05).In the coracoid tunnel-free suspension fixation group,at 3 months after operation and the final follow-up,the visual analogue scale score was significantly lower than the preoperative score(P<0.05);the Constant-Murley score and the ASES score were both significantly higher than the preoperative scores(P<0.05).At 3 months after operation,the Constant-Murley score of the coracoid tunnel-free suspension fixation group was higher than that of the coracoid single tunnel fixation group(P<0.05),while there was no significant difference in visual analogue scale and ASES scores between the two groups(P>0.05).There was also no significant difference in the visual analogue scale,Constant-Murley,and ASES scores between the two groups at the corresponding time points before surgery and at the final follow-up(P>0.05).Intraoperative and postoperative complications:In the coracoid single tunnel fixation group,there was one case of coracoid cortical rupture and fracture during the tunnel drilling during the operation,and one case of a loss of reduction at 3 months after operation,which was repositioned and fixed with hook plate transposition of the coracoacromial ligament.All patients had good acromioclavicular joint function recovery and no re-dislocation at the final follow-up.All patients in the coracoid tunnel-free suspension fixation group did not suffer from coracoid fractures,loss of reduction and other complications during surgery,postoperatively and at the last follow-up.To conclude,these two arthroscopic treatments for acute type Ⅲ-Ⅴ acromioclavicular joint dislocation have the advantages of less trauma,reliable reduction and fixation,and good recovery of shoulder joint function after operation.However,compared with the coracoid single tunnel technique,the coracoid tunnel-free suspension fixation requires shorter time,faster recovery of shoulder joint function in the short term,and avoids the establishment of bone tunnels on the coracoid process,which reduces the probability of iatrogenic fracture of the coracoid process during operation and provides a higher degree of safety.

Objective To explore the influence of nicorandil and tirofiban on coronary microcircula-tion and myocardial remodeling in patients with acute myocardial infarction(AMI)after percuta-neous coronary intervention(PCI).Methods A total of 118 AMI patients undergoing PCI in our hospital from January 2020 to January 2024 were enrolled,and divided into nicorandil group(n=39,nicorandil on the basis of routine treatment),tirofiban group(n=37,tirofiban on the basis of routine treatment)and combined group(n=42,nicorandil and tirofiban on the basis of routine treatment)according to their treatment regimens.The levels of the coagulation-related factors,coronary microcirculation indicators,microvascular function,myocardial remodeling indicators,oxidative stress indicators and major adverse cardiovascular events were compared among the three groups.Results In 7 d after PCI,prothrombin time(PT)value,activated partial prothrom-bin time(APTT),left ventricular ejection fraction(LVEF)value and serum levels of von Wille-brand factor(vWF),tissue factor(TF)and superoxide dismutase(SOD)were increased,while in-dex of microcirculatory resistance(IMR),left ventricular end-systolic volume(LVESV)value,left ventricular end-diastolic volume(LVEDV)value and serum endothelin(ET)level were de-creased in the three groups when compared with the corresponding levels before surgery(P＜0.05).At the time point,the combined group had higher LVEF value and serum levels of vWF,TF and SOD,while lower IMR,LVESV and LVEDV values and serum ET level when compared to the nicorandil group and tirofiban group(P＜0.05).The incidence of reperfusion arrhythmia(2.38％vs 16.22％and 15.38％,P＜0.05),incidence of angina pectoris within 6 months after surger-y(2.38％vs 18.92％and 15.38％,P＜0.05),and readmission rate of heart failure(2.38％vs 16.22％and 17.95％,P＜0.05)were notably lower in the combined group than the other two groups(P＜0.05).Conclusion For AMI patients after PCI,combination of nicorandil and tirofi-ban can effectively improve the postoperative coronary microcirculation,promote myocardial re-modeling,improve body's oxidative stress status and vascular endothelial function,and reduce the occurrence of cardiovascular adverse events.

Guidelines for Digital Ancient Books of TCM Indexing(T/CIATCM 119-2024)is based on the theoretical knowledge,disciplinary methods,and practical applications of TCM classical cataloging.Taking digital ancient books of TCM as the object,it systematically reveals the content of TCM knowledge,which is an essential indexing processing standard for building an intelligent retrieval system for TCM ancient books,and can provide support for the deep development and innovative utilization of TCM knowledge.It can not only promote the co-construction and sharing of ancient book resources in the TCM industry,but also promote the standardization construction and application of TCM information.This standard specifies the principles,methods,and examples of free indexing of digital ancient books of TCM based on their original content.It is applicable to the indexing and processing of digital ancient books of TCM for TCM professional libraries and related institutions,and to the data processing and construction of various types of TCM ancient book databases.

Objective To investigate the angiographic manifestations and interventional treatment outcomes of inferior vena cava occlusion associated with dangerous collateral vessels in Budd-Chiari syndrome(BCS).Methods The data of 43 BCS patients with inferior vena cava occlusion and dangerous collateral vessels were retrospectively analyzed.All 43 patients underwent digital subtraction angiography(DSA)of the inferior vena cava and recanalization treatment of the occluded segment of the inferior vena cava.Results DSA in 43 patients showed that the inferior vena cava was occluded,and a total of 70 dangerous collateral vessels originated from the occluded end.All patients were successfully treated.DSA showed that the blood flow in the inferior vena cava was unobstructed and the dangerous collateral vessels disappeared.No complications,such as rupture or bleeding of the inferior vena cava,occurred during the interventional treatment.The 43 patients were followed up for 6-75 months after interventional treatment,and re-occlusion occurred in 6 cases.All patients made it through.Conclusion DSA can clearly show the dangerous collateral vessels originating from the occluded end of the inferior vena cava in BCS,and interventional treatment is safe and effective.

Objective To investigate the relation between obstructive sleep apnea(OSA)and tinnitus.Meth-ods The data of subjects aged 20 years or above who participated in tinnitus and sleep questionnaire survey from the 2005-2008 and 2015-2018 National Health and Nutrition Surveys(NHANES)had been used,the people at risk of OSA were selected via the STOP-Bang questionnaire,and the association between the people at risk of OSA and tinnitus was determined by a Logistic regression model.Results Among the 5 183 participants,83.3％(4 320/5 183)and 16.7％(863/5 183)were classified into the non-tinnitus and tinnitus group,respectively.The tinnitus group had higher STOP-Bang scores(3.71±1.51)than those of the group without tinnitus(2.81±1.62)(P＜0.001).The observed prevalence rates of tinnitus in the low-risk,middle-risk and high-risk group were 8.1％(175/1 973),20.5％(435/1 689),27.8％(253/658),respectively.The multivariate Logistic regression model showed that patients with middle-risk and high-risk of OSA had an increased risk of tinnitus compared with low-risk group,with the OR values and confidence intervals of 2.348(1.920～2.871)and 3.136(2.488～3.953),respec-tively(P＜0.001).Conclusion People at risk of OSA are independently risk factors of tinnitus.Higher risk of OSA is associated with higher prevalence and higher risk of tinnitus.