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 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.

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 A clinical comprehensive evaluation of five biologic targeted drugs for the treatment of severe eosinophilic asthma （SEA） was conducted to provide objective evidence for the rational selection of these medications in medical institutions. METHODS Using the evaluation methods from the Chinese Medical Institution Drug Evaluation and Selection Rapid Guide （ Third Edition ）， the effectiveness， safety， pharmaceutical characteristics， cost-effectiveness， and other attributes of five biologics targeting SEA （omalizumab， mepolizumab， benralizumab， dupilumab， and tezepelumab） already marketed in China were quantitatively scored across five dimensions， and their recommendation levels were categorized based on the scores. RESULTS The comprehensive scoring results showed that mepolizumab scored 81.29， making it a highly recommended variety； benralizumab scored 78.05， dupilumab scored 77.84 and omalizumab scored 70.14，all of which are recommended varieties； tezepelumab scored 67.77， considered weakly recommended variety. CONCLUSIONS Mepolizumab shows excellent performance in eosinophil clearance， good accessibility， and is more cost-effective than the others， making it more selective in SEA treatment； omalizumab has more advantages in the treatment of SEA patients with elevated immunoglobulin E levels； dupilumab can be used as the preferred treatment for SEA patients with chronic obstructive pulmonary disease.

OBJECTIVE A clinical comprehensive evaluation of five biologic targeted drugs for the treatment of severe eosinophilic asthma （SEA） was conducted to provide objective evidence for the rational selection of these medications in medical institutions. METHODS Using the evaluation methods from the Chinese Medical Institution Drug Evaluation and Selection Rapid Guide （ Third Edition ）， the effectiveness， safety， pharmaceutical characteristics， cost-effectiveness， and other attributes of five biologics targeting SEA （omalizumab， mepolizumab， benralizumab， dupilumab， and tezepelumab） already marketed in China were quantitatively scored across five dimensions， and their recommendation levels were categorized based on the scores. RESULTS The comprehensive scoring results showed that mepolizumab scored 81.29， making it a highly recommended variety； benralizumab scored 78.05， dupilumab scored 77.84 and omalizumab scored 70.14，all of which are recommended varieties； tezepelumab scored 67.77， considered weakly recommended variety. CONCLUSIONS Mepolizumab shows excellent performance in eosinophil clearance， good accessibility， and is more cost-effective than the others， making it more selective in SEA treatment； omalizumab has more advantages in the treatment of SEA patients with elevated immunoglobulin E levels； dupilumab can be used as the preferred treatment for SEA patients with chronic obstructive pulmonary disease.

ObjectiveTo quantitatively analyze and evaluate the content of China's assistive technology industry policies. MethodsBased on the three-dimensional framework of policy "objectives-instruments-intensity", this study examined 101 national-level assistive technology industry policies issued between 2011 and 2024. Policy text analysis was conducted to assess the matching and coordination among policy objectives, policy instruments and policy intensity. Furthermore, the policy modeling consistency (PMC) index model was applied to establish an evaluation system consisting of nine primary indicators and 35 secondary indicators, and six key policies were quantitatively evaluated. ResultsThe policy objectives mainly focused on optimizing the industrial development structure, also emphasized supportive environments for industrial development and the enhancement of innovation capacity. Policy instruments were dominated by supply-oriented and environment-oriented instruments, supplemented by demand-oriented instruments, aiming to strengthen technological foundations and competitiveness, promote standardized development, and facilitate industrial development and upgrading. Regarding the matching between policy objectives and instruments, multiple instruments were adopted to support different objectives, with different priorities. In terms of the matching between policy objectives and policy intensity, policies mainly emphasized improving the accessibility of assistive technology products and meeting the rehabilitation needs of different populations. Regarding the matching between policy instruments and policy intensity, supply-oriented instruments were more frequently adopted and showed higher policy intensity, indicating strong governmental efforts to optimize production factor allocation and enhance the capacity of market entities. The average PMC index score was 6.45, indicating relatively high policy quality, strong internal consistency, stable policy orientation, and clear objectives. The PMC scores for policy evaluation and policy instrument dimensions were relatively high, while some policies showed relatively narrow objectives. ConclusionChina's assistive technology industry policies demonstrate relatively high quality. Future policy development should further strengthen industrial innovation capacity, optimize the structure of policy instruments, and improve the alignment between policy objectives and instruments.

Objective To investigate the efficacy and safety of EGFR-TKIs monotherapy and its combination therapy in the first-line treatment of advanced non-small cell lung cancer （NSCLC） patients with EGFR mutations. Methods Databases such as PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were systematically searched to collect eligible phase Ⅱ/Ⅲ randomized controlled trials （RCTs）, with the time range from the establishment of the databases to June 2023. Two researchers independently screened the literature, extracted data, and assessed the risk of bias in the studies. Outcome data, including overall survival （OS）, progression-free survival （PFS）, objective response rate （ORR）, grade 3 or higher adverse events （≥3 AEs）, and serious adverse events （SAEs）, were collected. A network meta-analysis was performed using R software （version 4.2.1） under the Bayesian theoretical framework. Subgroup analyses of survival outcomes （OS, PFS） were conducted based on different clinical and pathophysiological characteristics of the patients. Results A total of twenty-eight phase Ⅱ/Ⅲ RCTs were included in the study, involving a total of 7 460 patients and 18 first-line treatment regimens. The results showed that in terms of efficacy, gefitinib + pemetrexed-containing chemotherapy performed best in OS and ORR, while osimertinib + bevacizumab performed best in PFS. In terms of safety, furmonertinib had the lowest incidence of ≥3 grade AEs, and osimertinib had the lowest incidence of SAEs. Subgroup analysis results indicated that the efficacy and safety of various treatment regimens differed among patients with different clinical and pathological characteristics. Conclusion Monotherapy with third-generation EGFR-TKIs, represented by osimertinib, serves as the preferred therapeutic option considering both efficacy and safety profiles. While some combination therapies could enhance survival benefits, need to be vigilant about increased toxicity. Clinical decision-making should be tailored based on patients’ mutation subtypes, comorbidities, and tolerance.

Objective To explore the efficacy and safety of Yuxiao Prescription in the treatment of patients with stage III-IV diabetic kidney disease(DKD)characterized by qi and yin deficiency and phlegm-stasis obstruction in the real world.Methods A total of 112 patients with stage Ⅲ-Ⅳ DKD with qi-yin deficiency and phlegm-stasis obstruction who visited the outpatient department of Beijing Changping Hospital of Traditional Chinese Medicine from April 2022 to June 2024 were selected as the research subjects.They were divided into the control group and the Chinese materia medica group based on whether they were treated with Yuxiao Prescription through prospective cohort research methods.Propensity score matching(PSM)was used to balance the confounding factors between the groups.The control group received standardized Western medicine treatment,while the Chinese materia medica group was treated with Yuxiao Prescription in addition to the treatment of the control group,one dosage per day,twice a day,orally.The treatment for both groups lasted for three months.The clinical efficacy of two groups was observed,and their urinary protein,renal function,blood glucose,blood lipids,body mass index(BMI)and TCM syndrome scores before and after treatment were compared.Adverse reactions of both groups were monitored.Results After PSM,a total of 84 balanced samples were obtained between the two groups,with 42 samples in each group.The total effective rate of Chinese materia medica group was 90.48%(38/42),while the control group was 73.81%(31/42),with statistical significance(P<0.05).Compared with before treatment,the urinary albumin/creatinine ratio,urinary microalbumin,and 24-hour urinary protein quantitative levels decreased in both groups after treatment(P<0.05).Chinese materia medica group showed a decrease in blood creatinine and a significant increase in estimated glomerular filtration rate after treatment(P<0.05);after treatment,the improvement of the above indicators in the Chinese materia medica group was better than that in the control group(P<0.05).Compared with before treatment,both groups showed a decrease in fasting blood glucose,2-hour postprandial blood glucose,glycated hemoglobin(HbA1c),total cholesterol and low-density lipoprotein cholesterol levels after treatment(P<0.05).The BMI of Chinese materia medica group significantly decreased after treatment(P<0.05);after treatment,the HbA1c level and BMI in the Chinese materia medica group were lower than those in the control group(P<0.05).Compared with before treatment,the TCM syndrome scores in both groups decreased after treatment(P<0.05);after treatment,the TCM syndrome score in the Chinese materia medica group was lower than that in the control group(P<0.05).The adverse reaction rate of the Chinese materia medica group was 4.76%(2/42),while that of the control group was 7.14%(3/42),without statistical significance between the two groups(P>0.05).Conclusion The combination of Yuxiao Prescription and conventional therapy can effectively reduce proteinuria,improve renal function,and help improve glucose and lipid metabolism in patients with stage Ⅲ-Ⅳ DKD characterized by qi and yin deficiency and phlegm-stasis obstruction,thereby delaying the progression of the disease.