Objective:To apply bioinformatics methods to screen and analyze differentially expressed genes and biological processes specific to peripheral blood mononuclear cells in postmenopausal women with osteoporosis.Methods:From the Gene Expression Omnibus database, GSE56814, GSE56815, and GSE2208 datasets were screened as the research objects. The limma package in R language was used to screen differentially expressed genes, and the multigene Meta-analysis function in Metascape platform was utilized to perform enrichment analysis of gene ontology and pathway. Protein-protein interaction network construction, module analysis, core gene, and enrichment analysis will be carried out.Results:In the GSE56814 dataset, there were 84 significantly up-regulated genes and 73 significantly down-regulated genes. In the GSE56815 dataset, there were 8 significantly up-regulated genes and 33 significantly down-regulated genes. In the GSE2208 dataset, there were 21 significantly up-regulated genes and 10 significantly down-regulated genes. The multigene Meta-analysis identified 3 modules and 19 core genes in the Metascape platform. The core genes of MCODE1 included STXBP2, EIF2S2, EIF3J, PTPN6, FLNA, HLA- DQA1, CTSD, HSPA6, HLA- DPB1, EIF3E, PLEC. They mainly enriched formation of cytoplasmic translation initiation complex, antigen processing and presentation of exogenous peptide antigen via major histocompatibility complex Ⅱ, cytoplasmic translational initiation, nsp1 from SARS-CoV-2 inhibits translation initiation in the host cell, programmed cell death 1 signaling pathway, allograft rejection reaction. The core genes of MCODE2 included FOS, FOSB, EGR1, EGR2, JUNB. They mainly enriched RNA polymerase Ⅱ-specific, DNA-binding transcription activator activity, cellular response to salt, nerve growth factor-stimulated transcriptional pathways, nuclear kinase and transcription factor activation activation pathways, neurotrophic receptor tyrosine kinase 1 signaling pathway. The core genes of MCODE3 included CEBPA, H2AC6, SPI1. They mainly enriched transcriptional regulation of granulopoiesis. Conclusion:This study obtained a total of 3 modules, 19 core genes, and enriched them in the biological processes related to postmenopausal osteoporosis, providing new ideas and biological targets for exploring its occurrence pathogenesis and drug treatment.

Objective To identify potential subtypes of demoralization syndrome among stroke patients undergoing neuroendovascular procedures using latent profile analysis,and to examine differences in death anxiety among these subtypes.Method This cross-sectional study used convenience sampling to recruit 202 stroke patients undergoing neuroendovascular procedures at a hospital from November 2024 to March 2025.Participants completed the General Information Questionnaire,Despair Scale(DS),and the Chinese version of the Templer's Death Anxiety Scale(CT-DAS).Using R software,we estimated a series of latent profile models(ranging from 2 to 6 profiles)based on four manifestations of demoralization syndrome:loss of meaning and purpose,dysphoria,helplessness and hopelessness,and sense of failure.Starting from the 2-profile model,we incrementally increased the number of profiles and compared model fit indices to identify the optimal solution.Subsequently,logistic regression analysis was conducted to identify the factors influencing DS scores according to the latent profile classifications.We compared DS scores across subgroups and performed bivariate correlation analysis between DS and CT-DAS subdimensions(Affective,Stress&Pain,Time Awareness,and Cognitive).Results The DS scores classified stroke patients into two distinct subtypes of demoralization syndrome:A Meaninglessness-Dysphoria Group(51.00%,103/202)and a Helplessness-Hopelessness Group(49.00%,99/202).The HHG demonstrated significantly higher proportions(P<0.05)of female patients,those hospitalized for 6～10 days,recipients of arterial stenosis/occlusion surgery,individuals with junior high school or higher education,employed subjects,and rural residents compared to the MDG.Binary logistic regression analysis revealed:Lower probability of HHG membership for urban(OR=0.159,P<0.001)and city(OR=0.224,P=0.007)residents versus rural counterparts;Higher HHG probability in patients hospitalized 6-10 days versus 1～5 days(OR=2.311,P=0.017);Elevated HHG risk among junior high school(OR=4.956,P<0.001)and high school or above graduates(OR=5.102,P=0.001)relative to those with primary education or less;Increased HHG probability in aneurysm embolization(OR=2.419,P=0.040)and arterial stenosis/occlusion surgery(OR=2.733,P=0.014)recipients compared to cerebrovascular angiography patients.The HHG scored significantly lower on the cognitive dimension of death anxiety than the MDG(t=2.421,P=0.016),while showing no differences in affective,stress&pain,or time awareness dimensions(P>0.05).Bivariate Pearson correlations indicated dysphoria(DS)positively correlated with Affective(r=0.192,P=0.006),Time Awareness(r=0.172,P=0.015),and Cognitive(r=0.139,P=0.049)of death anxiety.Conclusions Stroke patients undergoing neuroendovascular procedures exhibit elevated levels of death anxiety,with significant varia-tions observed across different subtypes of demoralization syndrome.Residential location,hospitalization duration,anxiety severity,and surgical type constitute significant determinants of demoralization syndrome.Targeted clinical interventions should be implemented to alleviate demoralization severity and mitigate death anxiety.

Objective To identify potential subtypes of demoralization syndrome among stroke patients undergoing neuroendovascular procedures using latent profile analysis,and to examine differences in death anxiety among these subtypes.Method This cross-sectional study used convenience sampling to recruit 202 stroke patients undergoing neuroendovascular procedures at a hospital from November 2024 to March 2025.Participants completed the General Information Questionnaire,Despair Scale(DS),and the Chinese version of the Templer's Death Anxiety Scale(CT-DAS).Using R software,we estimated a series of latent profile models(ranging from 2 to 6 profiles)based on four manifestations of demoralization syndrome:loss of meaning and purpose,dysphoria,helplessness and hopelessness,and sense of failure.Starting from the 2-profile model,we incrementally increased the number of profiles and compared model fit indices to identify the optimal solution.Subsequently,logistic regression analysis was conducted to identify the factors influencing DS scores according to the latent profile classifications.We compared DS scores across subgroups and performed bivariate correlation analysis between DS and CT-DAS subdimensions(Affective,Stress&Pain,Time Awareness,and Cognitive).Results The DS scores classified stroke patients into two distinct subtypes of demoralization syndrome:A Meaninglessness-Dysphoria Group(51.00%,103/202)and a Helplessness-Hopelessness Group(49.00%,99/202).The HHG demonstrated significantly higher proportions(P<0.05)of female patients,those hospitalized for 6～10 days,recipients of arterial stenosis/occlusion surgery,individuals with junior high school or higher education,employed subjects,and rural residents compared to the MDG.Binary logistic regression analysis revealed:Lower probability of HHG membership for urban(OR=0.159,P<0.001)and city(OR=0.224,P=0.007)residents versus rural counterparts;Higher HHG probability in patients hospitalized 6-10 days versus 1～5 days(OR=2.311,P=0.017);Elevated HHG risk among junior high school(OR=4.956,P<0.001)and high school or above graduates(OR=5.102,P=0.001)relative to those with primary education or less;Increased HHG probability in aneurysm embolization(OR=2.419,P=0.040)and arterial stenosis/occlusion surgery(OR=2.733,P=0.014)recipients compared to cerebrovascular angiography patients.The HHG scored significantly lower on the cognitive dimension of death anxiety than the MDG(t=2.421,P=0.016),while showing no differences in affective,stress&pain,or time awareness dimensions(P>0.05).Bivariate Pearson correlations indicated dysphoria(DS)positively correlated with Affective(r=0.192,P=0.006),Time Awareness(r=0.172,P=0.015),and Cognitive(r=0.139,P=0.049)of death anxiety.Conclusions Stroke patients undergoing neuroendovascular procedures exhibit elevated levels of death anxiety,with significant varia-tions observed across different subtypes of demoralization syndrome.Residential location,hospitalization duration,anxiety severity,and surgical type constitute significant determinants of demoralization syndrome.Targeted clinical interventions should be implemented to alleviate demoralization severity and mitigate death anxiety.

Immune checkpoint inhibitor-related pneumonitis(CIP)is a relatively common immune-related adverse event.The current treatment for CIP mainly relies on glucocorticoids,with 70％～80％of patients being controlled by conventional glucocorticoid therapy.However,steroid-unresponsive CIP is often se-vere and can be life-threatening.There is no standard treatment protocol for steroid-unresponsive CIP,highlighting a significant unmet clinical need.This paper reviews the diagnosis,treatment progress,and exploratory research of steroid-unresponsive CIP to provide evidence-based guidelines and directions for clinical and translational research.

Immune checkpoint inhibitor-related pneumonitis(CIP)is a relatively common immune-related adverse event.The current treatment for CIP mainly relies on glucocorticoids,with 70％～80％of patients being controlled by conventional glucocorticoid therapy.However,steroid-unresponsive CIP is often se-vere and can be life-threatening.There is no standard treatment protocol for steroid-unresponsive CIP,highlighting a significant unmet clinical need.This paper reviews the diagnosis,treatment progress,and exploratory research of steroid-unresponsive CIP to provide evidence-based guidelines and directions for clinical and translational research.

Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

Extracellular vesicles(EVs)are nano-sized bilayer vesicles that are shed or secreted by virtually every cell type.A variety of biomolecules,including proteins,lipids,coding and non-coding RNAs,and mitochondrial DNA,can be selectively encapsulated into EVs and delivered to nearby and distant recipient cells,leading to alterations in the recipient cells,suggesting that EVs play an important role in intercellular communication.EVs play effective roles in physiology and pathology and could be used as diagnostic and therapeutic tools.At present,although the mechanisms of exosome biogenesis and secretion in donor cells are well understood,the molecular mechanism of EV recognition and uptake by recipient cells is still unclear.This review summarizes the current understanding of the molecular mechanisms of EVs'biological journey in recipient cells,from recognition to uptake and cargo release.Furthermore,we highlight how EVs escape endolysosomal degradation after uptake and thus release cargo,which is crucial for studies applying EVs as drug-targeted delivery vehicles.Knowledge of the cellular processes that govern EV uptake is important to shed light on the functions of EVs as well as on related clinical applications.

Objective:This study analyzed the expression of CD24 antigen on bone marrow plasma cells (BMPC) of patients with multiple myeloma (MM) and the predictive value of induction therapy.Methods:This clinical observational study utilized 258 MM patients samples treated at the Hematology Department of Beijing Jishuitan Hospital who met the inclusion criteria in the Department of Hematology, Capital Medical University, from August 12th, 2022 to February 1st, 2024. According to the different stages of the disease, patients were divided into three groups: 78 cases of Newly Diagnosed Multiple Myeloma(NDMM) (42 males and 36 females, aged 62±11), 56 cases of the relapse refractory group (34 males and 22 females, aged 64±9), and 124 cases of the disease remission group (68 males and 56 females, aged 62±10). Multiparameter flow cytometry (MFC) was used to detect the expression level of CD24 antigen on BMPC and the relationship between CD24 and MM disease status. The clinical data and test results of 78 NDMM patients at initial diagnosis were retrospectively analyzed, including gender, age, MFC detection of the positive expression rate of antigens (CD19, CD20, CD24, CD27, CD56), the results of efficacy evaluation after induction therapy, ISS staging, R-ISS staging, blood hemoglobin, β2-microglobulin, human serum albumin, serum creatinine, lactate dehydrogenas, correction of calcium, BMPC ratio, and the results of FISH. The patients were divided into a deep remission group [including complete remission (CR) and very good partial remission (VGPR)] with 43 cases and a non-deep remission group (non CR and VGPR) with 17 cases according to the difference of antigen positive expression rate after induction therapy. The differences of antigen expression on BMPC between the two groups were compared. Binary logistic regression was used to analyze the relationship between the expression of each antigen and the efficacy after induction therapy in patients, and the results showed that CD24 was more correlated with the achievement of deep remission after induction therapy than other antigens. Therefore, taking the positive expression rate of CD24 in NDMM patients at the initial diagnosis and deep remission after induction therapy as the research objects, the predictive value of CD24 for NDMM patients reaching deep remission after induction therapy was analyzed by using receiver operating characteristic curve (ROC), and the optimal cutoff value was obtained. NDMM was divided into two groups according to the cut-off value, and the differences between the two groups in clinical baseline data and prognostic indicators were compared.Results:The positive rates of plasma cell CD24 expression in the NDMM group, the relapse refractory group and the disease remission group were 2.18 (95% CI 0.08-81.85)%, 3.81 (95% CI 0.10-64.56)%, 8.74 (95% CI 0.79-95.55)% respectively. Compared with the disease remission group, the NDMM and relapse refractory group was lower ( Z=-7.889, -5.282, respectively, P<0.001). Univariate analysis showed that there was a significant difference in the positive expression rate of CD24 at initial diagnosis between the deep remission group and the non-deep remission group ( Z=-3.265, P<0.001), while there was no significant difference in CD19 ( Z=-0.271, P=0.787), CD20 ( Z=-0.205, P=0.837), CD27 ( Z=-0.582, P=0.560), and CD56 ( Z=-0.328, P=0.743) between the two groups. Binary logistic regression analysis showed that compared with other antigens [CD19 ( OR=1.045, 95% CI 0.975-1.120, P=0.217), CD20 ( OR=1.000, 95% CI 0.971-1.030, P=0.976), CD27 ( OR=0.997, 95% CI 0.977-1.016, P=0.734), CD56 ( OR=1.006, 95% CI 0.990-1.006, P=0.449)], the expression of CD24 ( OR=0.423, 95% CI 0.990-1.006, P=0.449) on BMPC in NDMM patients was most closely related to the achievement of deep remission was achieved after induction therapy. The lower the proportion of CD24 at the initial diagnosis was, the lower the probability of achieving deep remission after induction therapy was. The area under the curve (AUC) of CD24 in predicting deep remission after induction therapy was 0.772 (95% CI 0.655-0.889, P=0.001), with a sensitivity of 60.50%, a specificity of 85.00%, and the optimal critical value was 2.21%. Compared with the group with plasma CD24 positive rate>2.21%, the group with plasma CD24 positive rate<2.21% had a higher proportion of male (39.47%vs 65.00%, χ2=5.092, P=0.024), ISS stagingⅢ (41.67% vs 58.33%, χ2=6.175, P=0.046), β2 microglobulin (3.19 mg/L vs 4.14 mg/L, Z=-2.257, P=0.024), and BMPC [(8.672±1.827)% vs (19.530±3.188)%, t=-2.963, P=0.004] detected by MFC, and the differences were statistically significant. Conclusions:The low positive rate of plasma cell CD24 is closely related to the higher tumor burden and the worse disease status of MM patients. In addition, the positive expression rate of CD24 is at initial diagnosis can predict the efficacy achieved after induction therapy, and the lower positive rate of CD24 is, the worse the efficacy achieved after induction therapy. At the same time, MFC detection of CD24 is convenient and efficient in the evaluation and prediction of MM.

Objective:Multidrug-resistant tuberculosis(MDR-TB)has a high mortality and is always one of the major challenges in global TB prevention and control.Analyzing the factors that may impact the adverse outcomes of MDR-TB patients is helpful for improving the systematic management and optimizing the treatment strategies for MDR-TB patients.For follow-up data,the Cox proportional hazards regression model is an important multifactor analysis method.However,the method has significant limitations in its application,such as the fact that it is difficult to deal with the impacts of small sample sizes and other practical issues on the model.Therefore,Bayesian and conventional Cox regression models were both used in this study to analyze the influencing factors of death in MDR-TB patients during the anti-TB therapy,and compare the differences between these 2 methods in their application. Methods:Data were obtained from 388 MDR-TB patients treated at Lanzhou Pulmonary Hospital from November 1,2017 to March 31,2021.Survival analysis was employed to analyze the death of MDR-TB patients during the therapy and its influencing factors.Conventional and Bayesian Cox regression models were established to estimate the hazard ratios(HR)and their 95% confidence interval(95% CI)for the factors affecting the death of MDR-TB patients.The reliability of parameter estimation in these 2 models was assessed by comparing the parameter standard deviation and 95% CI of each variable.The smaller parameter standard deviation and narrower 95% CI range indicated the more reliable parameter estimation. Results:The median survival time(1st quartile,3rd quartile)of the 388 MDR-TB patients included in the study was 10.18(4.26,18.13)months,with the longest survival time of 31.90 months.Among these patients,a total of 12 individuals died of MDR-TB and the mortality was 3.1%.The median survival time(1st quartile,3rd quartile)for the deceased patients was 4.78(2.63,6.93)months.The majority of deceased patients,accounting for 50%,experienced death within the first 5 months of anti-TB therapy,with the last mortality case occurring within the 13th month of therapy.The results of the conventional Cox regression model showed that the risk of death in MDR-TB patients with comorbidities was approximately 6.96 times higher than that of patients without complications(HR=6.96,95% CI 2.00 to 24.24,P=0.002)and patients who received regular follow-up had a decrease in the risk of death by approximately 81% compared to those who did not receive regular follow-up(HR=0.19,95% CI 0.05 to 0.77,P=0.020).In the results of Bayesian Cox regression model,the iterative history plot and Blue/Green/Red(BGR)plot for each parameter showed the good model convergence,and parameter estimation indicated that the risk of death in patients with a positive first sputum culture was lower than that of patients with a negative first sputum culture(HR=0.33,95% CI 0.08 to 0.87).Additionally,compared to patients without complications,those with comorbidities had an approximately 6.80-fold increase in the risk of death(HR=7.80,95% CI 1.90 to 21.91).Patients who received regular follow-up had a 90% reduction in the risk of death compared to those who did not receive regular follow-up(HR=0.10,95% CI 0.01 to 0.30).The comparison between these 2 models showed that the parameter standard deviations and corresponding 95% CI ranges of other variables in the Bayesian Cox model were significantly smaller than those in the conventional model,except for parameter standard deviations of receiving regular follow-up(Bayesian model was 0.77;conventional model was 0.72)and pulmonary cavities(Bayesian model was 0.73;conventional model was 0.73). Conclusion:The first year of anti-TB therapy is a high-risk period for mortality in MDR-TB patients.Complications are the main risk factors of death in MDR-TB patients,while patients who received regular follow-up and had positive first sputum culture presented a lower risk of death.For data with a small sample size and low incidence of outcome,the Bayesian Cox regression model provides more reliable parameter estimation than the conventional Cox model.

Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.
Humans ; Venous Thromboembolism/etiology* ; Multiple Myeloma/diagnosis* ; Risk Assessment ; Risk Factors ; ROC Curve ; Retrospective Studies