Objective:To investigate the genetic etiology of 15 patients with suspected Marfan syndrome(MFS).Methods:Fifteen patients clinically suspected of having MFS who attended the Women and Children′s Hospital Affiliated to Qingdao University between January 2020 and August 2024 were enrolled. Amniotic fluid samples from fetuses and EDTA-anticoagulated peripheral blood samples from the patients and their family members were collected. Genomic DNA was extracted and subjected to whole exome sequencing(WES). Variants identified in positive cases were further validated by Sanger sequencing. The pathogenicity of the detected variants was assessed according to the guidelines and supplemental criteria of the American College of Medical Genetics and Genomics(ACMG).Results:All 15 patients were found to carry variants in the FBN1 gene, including 9 pathogenic variants, 5 likely pathogenic variants, and 1 variant of uncertain significance(VUS). Notably, eight novel pathogenic or likely pathogenic variants not previously reported in the literature were identified: c. 213G>C, c. 469G>T, c. 3337+ 2dup, c. 4087+ 1G>T, c. 7331_7334dup, c. 8146del, c. 8227dup, and c. 8425_8426insG. According to the revised Ghent criteria(2010), only 2 patients could be clinically diagnosed with MFS prior to WES. However, after incorporating WES-derived molecular evidence, 8 patients fulfilled the diagnostic criteria for MFS.Conclusion:The combination of WES and clinical phenotype assessment can substantially improve the diagnostic yield for MFS. Furthermore, the identification of these novel FBN1 variants expands the mutational spectrum of the gene and provides valuable evidence for future genetic counselling, prenatal diagnosis, and pathogenicity interpretation of neighboring variants.

Objective: : Baculovirus inhibitory of apoptosis repeat-containing 5 (BIRC5) is critically implicated in various types of tumors. However, the specific mechanisms by which it operates in glioma are yet to be fully understood. Methods: : The data sourced from The Cancer Genome Atlas and Gene Expression Omnibus were merged and analyzed using the R software to investigate the relationship between BIRC5 expression and prognosis and diagnosis outcomes. This exploration was conducted utilizing various biological information repositories. The correlation between BIRC5 and immunity was obtained based on TIMER and TISIDB databases. Results: : Gliomas displayed a markedly elevated level of BIRC5 expression compared to adjacent tissues. Patients with glioma who exhibit elevated levels of BIRC5 experience poorer prognoses and shorter survival times. Subgroup classification further revealed that heightened expression of BIRC5 led to diminished overall survival. Analysis of logistic regression and COX indicated that expression of BIRC5 serves as a risk factor in glioma development. Functional enrichment pathways showed that the 72 hub genes related to BIRC5 were mainly closely related to nuclear division, spindle, tubulin binding, and cell cycle in glioma patients. BBIRC5 methylation suggested that BIRC5 might influence the immune response regulation and the tumor microenvironment within gliomas. BIRC5 is associated with many chemicals. Additionally, studies conducted using cell experiments and pathological sections have consistently shown that BIRC5 expression is higher in tumor cells compared to normal cells and tissues. Conclusion : BIRC5 holds promise as a valuable tool in the diagnosis, prognosis, and management of gliomas.

Objective To investigate the potential mechanism of Erchen Pingwei formula in treating obesity with insulin resistance(IR)by using network pharmacology and molecular docking technology.Methods The main active ingredients and their potential target proteins were obtained from Traditional Chinese Medicine System Pharmacology database and analysis platform and Swiss Target Prediction databases,therapeutic target database,online Mendelian inheritance in man database and genecards databases were used to screen the disease targets related to IR and obesity,and Venny mapping tool was used to screen the intersection of herbal formula and disease targets,and Cytoscape 3.10.0 software was used to construct protein-protein interaction(PPI)network diagrams.Gene Ontology(GO)enrichment,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis on the intersection targets were conducted by using DAVID database,molecular docking and visualization analysis were carried out by Autodock and Pymol.Results 136 active ingredients and 236 active targets of Erchen Pingwei formula were retrieved,with 2527 IR active targets,1598 obesity active targets,and 91 drug-disease intersecting targets.GO and KEGG enrichment analyses showed that quercetin,kaempferol,and naringenin were the main active ingredients of Erchen Pingwei formula,through the regulation of protein kinase B,interleukin-6,tumor protein p53,peroxisome proliferator activated receptor,estrogen receptor α and other core targets,affecting lipid and atherosclerosis,insulin resistance,advanced glycation end product-receptor signaling pathway,and playing a therapeutic role in obesity.Conclusion Erchen Pingwei formula treats obesity with IR via a multi-component,multi-target,and multi-pathway mechanism.

BACKGROUND:Bone microenvironment is also rich in various immune cells and cytokines,which are closely related to bone cells and form an interactive network.Therefore,bone aging is not only caused by the senescence of osteocytes,but also accelerated by age-related changes in the immune system.OBJECTIVE:To review the age-related changes of bone marrow mesenchymal stem cells,osteoblasts,osteoclasts,and immune cells in the bone microenvironment,emphasize the key role of the immune microenvironment in bone aging,and the potential of immunotherapy in the treatment of bone aging.METHODS:We searched PubMed and China National Knowledge Infrastructure for articles on the interaction between bone cell senescence and immune cell senescence using"osteocytes,bone aging,immune microenvironment,immune cells,cytokines,immunosenescence,immunotherapy"as Chinese and English search terms.According to the inclusion and exclusion criteria,128 articles were finally included in the review.RESULTS AND CONCLUSION:Bone aging is a common pathological condition in the elderly,characterized by the interaction of multiple biological processes,among which immune factors play a key role.The cells,molecules,and signaling pathways in the immune microenvironment together constitute a complex network,and the imbalance of this network will accelerate the process of bone aging.The combination of anti-cellular aging and immunotherapy may bring new methods for the treatment of bone aging diseases,including the removal of senescent cells,targeted drugs for senescence-related secretory phenotypes,targeted therapy of inflammatory cytokines,immune cell regulation therapy,stem cell therapy,and molecular therapy.To more effectively and reasonably remove senescent cells,a deeper understanding of the mechanism of senescent cells is needed,which will help to identify senescent cells more accurately.Immunotherapy shows great potential and prospects in the treatment of bone aging,but there are some potential risks.It is believed that with the advancement of science and technology,people can more accurately understand the genetic information and immune status of the human body and develop more personalized immunotherapy plans.

Objective:To explore the experiences and needs of discharged patients with ischemic stroke during the implementation of home-based digital-intelligent blood pressure management.Methods:Using purposive sampling method, 13 acute ischemic stroke patients admitted to the Department of Neurology of Xuanwu Hospital of Capital Medical University and discharged to receive home-based digital-intelligent blood pressure management were selected for face-to-face semi-structured interviews between March and May 2024. Colaizzi 7-step analysis was used for the analysis.Results:A total of three themes and six sub-themes were extracted, namely, the double-edged effect under digital-intelligent empowerment (current situation of collision between technological novelty and cognitive generation gap, and contradiction between precision priority and lagging user experience), inertial resistance and behavioral reshaping in the process of digital-intelligent intervention (behavioral intervention exclusion under life inertia and self-efficacy enhancement driven by digital intelligence), and the "support disconnection" and the need for system reconstruction in home-based rehabilitation (professional guidance "vacuum" identity anxiety, and imbalance in the tension of family support networks) .Conclusions:Home-based blood pressure digital-intelligent management devices and programs for ischemic stroke patients need to be improved and developed. The role of multidisciplinary teams should be actively utilized, the digital divide should be emphasized, and post-disease family relationships should be reconstructed to further enhance patients' awareness of long-term blood pressure management.

Objective To explore the impact of irregular shape of head CT hematomas on postoperative re-bleeding and prognosis of patients with spontaneous intracerebral hemorrhage(ICH)who undergo craniotomy for hematoma evacuation.Methods We retrospectively enrolled consecutive patients with ICH who underwent craniotomy for hematoma evacuation in the Department of Neurosurgery of the Second People's Hospital of Guiyang Affiliated to Guizhou Medical University from January 2019 to June 2024.Baseline and clinical data were collected form the patients,including age,gender,smoking history,drinking history,hypertension,diabetes,history of anticoagulant use,admission systolic and diastolic blood pressure,admission National Institutes of Health stroke scale(NIHSS)score,Glasgow coma scale(GCS)score,time from onset to the first head CT,neutrophil-to-lymphocyte ratio(NLR),and platelet-to-lymphocyte ratio(PLR).Admission head CT scans were used to assess hematoma shape(regular or irregular),hematoma location(basal ganglia,lobar,multifocal),hematoma volume,perihematomal edema volume,the presence of midline shift,and intraventricular extension.Volume of the hematoma was assessed 2 days after surgery.Postoperative re-bleeding is defined as an increase in the volume of the hematoma by 12.5 ml compared to the previous postoperative CT scan within 2 weeks after surgery,or the reappearance of high-density areas in the focal area of the head CT scan during follow-up after complete hematoma clearance.Conduct patients follow-ups via telephone at 6 months postoperatively to assess their modified Rankin scale(mRS)scores.The sliding dichotomy method was applied to define prognosis based on the patients' baseline characteristics and disease severity.The prognostic score was calculated using formula:10 × admission GCS score-age-0.64 × admission hematoma volume.A prognostic score＞27.672 was considered potentially favorable,while a score ≤ 27.672 was considered potentially unfavorable.For patients with a potentially favorable prognosis,an mRS score of 0-2 was defined as a good outcome,and a score of 3-6 as a poor outcome.For those with a potentially unfavorable prognosis,an mRS score of 0-3 was defined as a good outcome,and a score of 4-6 as a poor outcome.In the comparison of baseline and clinical data between patients with regular and irregular hematoma shapes,factors with P＜0.05 were included in propensity score matching(PSM)to adjust for confounding variables.A 1∶1 matching was performed using the nearest neighbor method with a caliper value set to 0.25.Variables with statistically significant differences between groups after PSM matching were included in the multivariate Logistic regression analysis to identify influencing factors for postoperative re-bleeding and poor prognosis in ICH patients undergoing craniotomy hematoma evacuation.The predictive value of irregular hematoma shape for postoperative rebleeding and poor prognosis in ICH patients was analyzed using receiver operating characteristic(ROC)curve analysis.Results(1)A total of 440 ICH patients were enrolled,including 342 males and 98 females,aged from 20 to 84 years with a mean age of(56±12)years.Statistically significant differences were observed in baseline and clinical data between patients with regular and irregular hematoma shapes before PSM,including age,admission GCS score,NIHSS score,NLR,proportion of patients with hematoma rupture into ventricles,preoperative hematoma volume,proportion of patients with midline shift,preoperative volume of hematoma surrounding edema,proportion of patients with hematoma located in multiple sites,and postoperative 2-day hematoma volume(all P＜0.05).After propensity score matching of these factors,298 ICH patients were included in the statistical analysis,comprising 228 males and 70 females,with an age range of 20 to 84 years and a mean age of(57±12)years.Following PSM,no statistically significant differences were observed in the baseline and clinical characteristics between patients with irregular and regular hematoma shapes(all P＞0.05).(2)After propensity score matching,28 patients experienced postoperative re-bleeding while 270 did not.Significant differences were observed between the two groups in the following factors:proportion of patients with a history of anticoagulant use,admission PLR,NLR,irregular hematoma shape,and hematoma volume at 2 days after operation(all P＜0.05).No statistically significant differences were found in the remaining baseline and clinical characteristics(all P＞0.05).Using postoperative re-bleeding as the dependent variable and incorporating factors with P＜0.05 from the univariate analysis as independent variables,multivariate Logistic regression analysis identified irregular hematoma shape(OR,2.821,95％CI 1.142-6.968,P=0.025)and larger hematoma volume at 2 days post-operation(OR,1.062,95％CI 1.026-1.099,P＜0.01)as independent risk factors for re-bleeding following intracranial hematoma evacuation in ICH patients.ROC curve analysis demonstrated that irregular hematoma shape predicted postoperative re-bleeding with an area under the curve(AUC)of 0.62,showing a sensitivity of 71.4％and a specificity of 52.2％.(3)After propensity score matching,174 patients had poor prognosis while 124 had good prognosis.Significant intergroup differences were observed in age,admission GCS score,NIHSS score,irregular hematoma shape,proportion of patients with hematomas located in the basal ganglia and cerebral lobes,and hematoma volume at 2 days post-operation(all P＜0.05).No statistically significant differences were found in the remaining baseline and clinical characteristics(all P＞0.05).Using poor prognosis as the dependent variable and incorporating factors with P＜0.05 from univariate analysis as independent variables,multivariate Logistic regression analysis revealed that advanced age(OR,1.039,95％CI 1.015-1.064,P=0.002),high admission NIHSS score(OR,1.068,95％CI 1.025-1.113,P=0.002),irregular hematoma shape(OR,2.675,95％CI 1.582-4.524,P＜0.01),and larger hematoma volume at 2 days post-operation(OR,1.033,95％CI 1.002-1.064,P=0.038)were independent risk factors for poor prognosis.Conversely,lobar hematoma location(OR,0.192,95％CI 0.073-0.504,P＜0.01)was identified as a protective factor.ROC curve analysis showed that irregular hematoma shape predicted poor prognosis after intracranial hematoma evacuation with an AUC of 0.61,demonstrating a sensitivity of 59.2％and specificity of 62.9％.Conclusion Irregular hematoma shape on head CT is an independent risk factor for both postoperative re-bleeding and poor prognosis in ICH patients undergoing craniotomy for hematoma evacuation.

Objective:To investigate the genetic etiology of 15 patients with suspected Marfan syndrome(MFS).Methods:Fifteen patients clinically suspected of having MFS who attended the Women and Children′s Hospital Affiliated to Qingdao University between January 2020 and August 2024 were enrolled. Amniotic fluid samples from fetuses and EDTA-anticoagulated peripheral blood samples from the patients and their family members were collected. Genomic DNA was extracted and subjected to whole exome sequencing(WES). Variants identified in positive cases were further validated by Sanger sequencing. The pathogenicity of the detected variants was assessed according to the guidelines and supplemental criteria of the American College of Medical Genetics and Genomics(ACMG).Results:All 15 patients were found to carry variants in the FBN1 gene, including 9 pathogenic variants, 5 likely pathogenic variants, and 1 variant of uncertain significance(VUS). Notably, eight novel pathogenic or likely pathogenic variants not previously reported in the literature were identified: c. 213G>C, c. 469G>T, c. 3337+ 2dup, c. 4087+ 1G>T, c. 7331_7334dup, c. 8146del, c. 8227dup, and c. 8425_8426insG. According to the revised Ghent criteria(2010), only 2 patients could be clinically diagnosed with MFS prior to WES. However, after incorporating WES-derived molecular evidence, 8 patients fulfilled the diagnostic criteria for MFS.Conclusion:The combination of WES and clinical phenotype assessment can substantially improve the diagnostic yield for MFS. Furthermore, the identification of these novel FBN1 variants expands the mutational spectrum of the gene and provides valuable evidence for future genetic counselling, prenatal diagnosis, and pathogenicity interpretation of neighboring variants.

Objective:To evaluate the efficacy and safety of the Chi-BEAM regimen (chidamide combined with carmustine, etoposide, cytarabine, and melphalan) followed by autologous hematopoietic stem cell transplantation (ASCT) in patients with high-risk or relapsed/refractory lymphoma.Methods:This retrospective case series included 78 patients with newly treated high-risk or relapsed/refractory lymphoma who underwent ASCT with the Chi-BEAM conditioning regimen in the Department of Hematology, the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), from June 2021 to May 2024. Descriptive statistics were employed to evaluate clinical characteristics, efficacy, and adverse events. The Kaplan-Meier method was applied to calculate cumulative progression-free survival (PFS) and overall survival (OS) rates.Results:The median age of the 78 evaluable patients was 47 years (range 16-68), with 8 patients (10.3%) aged ≥60 years. At the first post-transplant assessment (3 months), the objective response rate was 94.9% (74/78). The median follow-up was 20.1 months (range 2.9-44.9). The median PFS time was 20.1 months (range 1.6-45.1), with a 2-year cumulative PFS rate of 81.8%. The median OS time was 20.6 months (range 3.1-45.1), with a cumulative 2-year OS rate of 93.2%. The regimen was well-tolerated; mild-to-moderate hypocalcemia within 1 week post-infusion and transient mild erythrocyturia on the infusion day were the primary adverse reactions.Conclusion:The Chi-BEAM regimen combined with ASCT demonstrates both safety and clinical benefit in patients with high-risk or relapsed/refractory lymphoma.

Objective To investigate the potential mechanism of Erchen Pingwei formula in treating obesity with insulin resistance(IR)by using network pharmacology and molecular docking technology.Methods The main active ingredients and their potential target proteins were obtained from Traditional Chinese Medicine System Pharmacology database and analysis platform and Swiss Target Prediction databases,therapeutic target database,online Mendelian inheritance in man database and genecards databases were used to screen the disease targets related to IR and obesity,and Venny mapping tool was used to screen the intersection of herbal formula and disease targets,and Cytoscape 3.10.0 software was used to construct protein-protein interaction(PPI)network diagrams.Gene Ontology(GO)enrichment,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis on the intersection targets were conducted by using DAVID database,molecular docking and visualization analysis were carried out by Autodock and Pymol.Results 136 active ingredients and 236 active targets of Erchen Pingwei formula were retrieved,with 2527 IR active targets,1598 obesity active targets,and 91 drug-disease intersecting targets.GO and KEGG enrichment analyses showed that quercetin,kaempferol,and naringenin were the main active ingredients of Erchen Pingwei formula,through the regulation of protein kinase B,interleukin-6,tumor protein p53,peroxisome proliferator activated receptor,estrogen receptor α and other core targets,affecting lipid and atherosclerosis,insulin resistance,advanced glycation end product-receptor signaling pathway,and playing a therapeutic role in obesity.Conclusion Erchen Pingwei formula treats obesity with IR via a multi-component,multi-target,and multi-pathway mechanism.

Objective: : Baculovirus inhibitory of apoptosis repeat-containing 5 (BIRC5) is critically implicated in various types of tumors. However, the specific mechanisms by which it operates in glioma are yet to be fully understood. Methods: : The data sourced from The Cancer Genome Atlas and Gene Expression Omnibus were merged and analyzed using the R software to investigate the relationship between BIRC5 expression and prognosis and diagnosis outcomes. This exploration was conducted utilizing various biological information repositories. The correlation between BIRC5 and immunity was obtained based on TIMER and TISIDB databases. Results: : Gliomas displayed a markedly elevated level of BIRC5 expression compared to adjacent tissues. Patients with glioma who exhibit elevated levels of BIRC5 experience poorer prognoses and shorter survival times. Subgroup classification further revealed that heightened expression of BIRC5 led to diminished overall survival. Analysis of logistic regression and COX indicated that expression of BIRC5 serves as a risk factor in glioma development. Functional enrichment pathways showed that the 72 hub genes related to BIRC5 were mainly closely related to nuclear division, spindle, tubulin binding, and cell cycle in glioma patients. BBIRC5 methylation suggested that BIRC5 might influence the immune response regulation and the tumor microenvironment within gliomas. BIRC5 is associated with many chemicals. Additionally, studies conducted using cell experiments and pathological sections have consistently shown that BIRC5 expression is higher in tumor cells compared to normal cells and tissues. Conclusion : BIRC5 holds promise as a valuable tool in the diagnosis, prognosis, and management of gliomas.