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.

This paper systematically reviewed the concept of authentication studies on traditional Chinese medicine （TCM） classics and the research achievements of scholars across historical and contemporary periods. We categorized the authentication studies on TCM classics into four types， including work-oriented authentication research， metho-dological studies on authentication， extended authentication research， and single-book authentication. Multiple methods were applied comprehensively， including investigating bibliographic documents of successive dynasties， analyzing the academic contents of medical books， studying the textual characteristics of medical books， examining the cited references in medical books， verifying the biographies of authors， and analyzing the interpolations and accretions in medical books， to distinguish the authenticity of TCM classics. The academic value of authenticity identification of TCM classics is concluded in three aspects，i.e. it serves as an important means to distinguish authenticity from falsehood in TCM classics， an important guarantee for inheriting the essence of TCM literature， and a key to unlocking the academic treasure trove of TCM classics and achieving inheritance-based innovation， which will lay a solid documentary foundation for constructing identification methodologies and standardized systems.

Existentialist philosophy focuses on human existence， explores subjectivity and uniqueness， and highlights the value of human existence. Advanced cancer patients generally suffer immense existential distress， each with their own modes of appearance and numerous possibilities. From the perspective of existentialist philosophy， targeting the group of advanced cancer patients， this paper clarified the analysis of “Dasein” （holistic phenomenon and modes of appearance）. Through recognition （achieving to deepen the inner scope of the subject and object） and comprehension （seeking appropriate “self-knowledge”）， it introduced the planning of variable possibilities. Subsequently， based on the patients’ pre-possessing， pre-seeing， and pre-grasping， explanatory activities were carried out to complete the “self-formation” in the planning. Ultimately， it facilitated the realization of existential meaning in the presupposition and proposed actionable clinical practices （meaning therapy and emotional touch therapy） to alleviate the existential distress of advanced cancer patients.

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.

As a pivotal strategy to alleviate the shortage of organ donors, xenotransplantation has achieved remarkable advances in both pre-clinical and clinical studies in recent years, driven by continuous optimization of gene modification techniques and immunosuppressive regimens. Nevertheless, clinical translation still confronts formidable challenges, including rejection and heightened infection risks, which severely compromise long-term graft survival. Consequently, the role of immunosuppressive regimens in xenotransplantation has become increasingly prominent. This article summarizes the mechanisms underlying xenogeneic immune rejection, the latest developments in immunosuppressive regimens, cutting-edge strategies for inducing immune tolerance and the major hurdles facing clinical xenotransplantation. It delves into potential optimization strategies and directions for future clinical research, aiming to offer theoretical insights and practical guidance for the safe and effective application of clinical xenotransplantation.

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 design a novel model for experiments on in vitro irradiation with radioactive seeds using a treatment planning system (TPS) and 3D printing technology and to preliminarily validate the design scientific rigor of the model via experiments on isodose brachytherapy (BT) and external beam radiotherapy (EBRT) on glioma cells in mice. Methods:The TPS was employed to design the model′s shape and calculate the number and positions of radioactive seeds, and 3D printing technology was utilized to fabricate the experimental model. The GL261 cell line was selected for in vitro irradiation experiments, with the mice divided into the control, EBRT, and BT groups. Mice in the EBRT and BT groups were treated with EBRT and BT, respectively, at doses of 2, 4, and 6 Gy. Then, changes in their cell viability, proliferation, and the level of intracellular reactive oxygen species (ROS) were assessed. Results:The model for in vitro irradiation with radioactive seeds was successfully designed and fabricated. The single photon emission computed tomography (SPECT) verified a uniform radioactive distribution within the model, with no significant cold spots. The BT and EBRT groups displayed decreased cell viability with an increase in the radiation dose. Compared to the EBRT group, the BT group exhibited significantly reduced cell viability (51.33% vs. 22.00%, t = 10.94, P < 0.05) and clone counts (172.67 ± 13.11 vs. 53.67 ± 10.22, t = 8.73, P < 0.05), but a significantly increased level of ROS (102.52 ± 6.87 vs. 144.81 ± 6.01, t = -5.26, P < 0.05) at a dose of 6 Gy. Conclusions:An effective model of in vitro irradiation with radioactive seeds is designed based on TPS and 3D printing technology. This provides an experimental model tool and target for research on the BT and EBRT mechanisms.

Objective:To employ single-photon emission computed tomography (SPECT)/CT for isodose assignment in 125I brachytherapy, assess the correlation between photon counts and dose values, and develop a clinical γ-ray visualization model for 125I brachytherapy. Methods:125I radioactive seeds were filled into a self-made 3D printed stereotactic template to build a stereotactic model. The model was scanned by SPECT/CT for photon counts at 0.5, 1.0, 1.5, 2.0 cm from the outermost peripheral seeds, and the corresponding dose values were measured using the Treatment Planning System (TPS). The fitting curve for the photon counts and the dose values was plotted using SPSS 27.0 software. Results:The photon counts of γ rays at distances of 0.5, 1.0, 1.5, and 2.0 cm from the peripheral particles were 7 603.57±1 806.35, 4 018.26±1 315.72, 2 074.04±791.53, and 1 080.34±424.79, respectively, showing a significant difference ( F=743.72, P<0.01). The dose values (in Gy) in the TPS at distances of 0.5, 1.0, 1.5, and 2.0 cm from the peripheral particles were 208.05±37.57, 125.43±17.74, 86.76±17.67, and 61.55±14.39, respectively, which were significantly different ( F=930.46, P<0.01). The photon counts were linearly correlated with the dose values ( y=0.02 x+ 46.45, R2=81.2%, P<0.01). Conclusions:SPECT/CT-based γ-ray photon count detection can be used to assign doses for 125I brachytherapy, enabling the visualization of γ rays in 125I brachytherapy. This approach has a distinct advantage over TPS, laying the foundation for the establishment of an alternative system to TPS.

Objective To investigate the relationship between the expression of nuclear factor ⅠB(NFⅠB)in myeloid cells and intestinal inflammation by constructing NFⅠB conditional gene knockout(cKO)mice.Methods Human Protein Atlas database,Genotype-Tissue Expression database,and FANTOM5 database were used to investigate the expression of NFⅠB in inflammatory cells.NFⅠB-floxed mice were constructed using CRISPR/Cas9 technology and hybridized with LyZ2-Cre transgenic mice.Myeloid specific NFⅠB cKO mice(NFⅠBfl/flLyz2-Cre)were obtained by self-crossing the progeny.After the genotype identification of mice by agarose gel electrophoresis,4 NFⅠB cKO mice of C57BL/6N strain were selected as experimental group,and 4 non-cKO mice were selected as control group.Both groups were induced with 2.5％dextran sulfate sodium salt(DSS)under the same condition to establish a chronic colitis model,and the severity of colitis was evaluated by clinical manifestations and histopathology.Results Analysis showed that NFⅠB was expressed in both myeloid granulocytes and monocytes,and the highest expression was found in neutrophils.NFⅠB cKO mice were successfully constructed using CRISPR/Cas9 technology and Cre-loxP system.DSS-induced enteritis NFⅠB cKO mice developed diarrhea,gross blood stools,reduced activity,and weight loss in a short time.The gross examination of the intestines showed that the colon of the NFⅠB cKO mice was significantly shorter than that of the non-cKO mice([8.23±0.35]cm vs[10.30±0.36]cm,P＜0.01).Intestinal H-E staining showed changes in mucosal glandular structure and connective tissue hyperplasia with extensive inflammatory cell infiltration in NFⅠB cKO mice.The histological score of NFⅠB cKO mice was significantly higher than that of non-cKO mice(4.25±0.50 vs 0.50±0.58,P＜0.01).Intestinal immunohistochemical staining showed that more CD11b positive cells were recruited in NFⅠB cKO mice than non-cKO mice.Conclusion Myeloid specific NFⅠB cKO mice have been successfully constructed,and NFⅠB in myeloid cells can reduce infiltration of immune cells(granulocytes or/and monocytes)to inhibit intestinal inflammation.

Tuberculosis is still the second leading cause of death from a single source of infection in the world.There is a two-way relationship between tuberculosis and the nutritional status of the body,which affects and causes each other.Vitamin D is an essential micronutrient,most research results show that vitamin D deficiency is common in tuberculosis patients,which is related to lack of sunlight,decreased dietary intake of vitamin D and anti-tuberculosis drug treatment.Low level vitamin D can increase tuberculosis susceptibility to some extent,but the research results are not completely consistent.This paper reviews the nutritional status of vitamin D in tuberculosis patients in recent years,the causes of vitamin D deficiency in tuberculosis patients and the relationship between vitamin D deficiency and susceptibility of tuberculosis,so as to provide references for further study on the role of vitamin D in tuberculosis prevention and treatment.