Personalized prediction of diabetic foot ulcer recurrence in elderly individuals using machine learning paradigms.

BACKGROUND: This study utilizes machine learning to analyze the recurrence risk of diabetic foot ulcers (DFUs) in elderly diabetic patients, aiming to enhance prevention and intervention efforts. OBJECTIVE: The goal is to construct accurate predictive models for assessing the recurrence risk of DFUs based on high-risk factors, such as age, blood sugar control, alcohol consumption, and smoking, in elderly diabetic patients. METHODS: Data from 138 elderly diabetic patients were collected, and after data cleaning, outlier screening, and feature integration, machine learning models were constructed. Support Vector Machine (SVM) was employed, achieving an accuracy rate of 93%. RESULTS: Experimental results demonstrate the effectiveness of SVM in predicting the recurrence risk of DFUs in elderly diabetic patients, providing clinicians with a more accurate tool for assessment. CONCLUSIONS: The study highlights the significance of machine learning in managing foot ulcers in elderly diabetic patients, particularly in predicting recurrence risk. This approach facilitates timely intervention, reducing the likelihood of patient recurrence, and introduces computer-assisted medical strategies in elderly diabetes management.

The Syvn1 inhibits neuronal cell ferroptosis by activating Stat3/Gpx4 axis in rat with spinal cord injury.

Spinal cord injury (SCI) leads to secondary neuronal death, which severely impedes recovery of motor function. Therefore, prevention of neuronal cell death after SCI is an important strategy. Ferroptosis, a new form of cell death discovered in recent years, has been shown to be involved in the regulation of SCI. However, the role and potential mechanisms of ferroptosis in secondary SCI are not fully understood. In this study, we report that the E3 ubiquitin ligase Syvn1 suppresses ferroptosis and promotes functional recovery from SCI in vitro and in vivo. Mechanistically, screened with bioinformatics, immunoprecipitation, and mass spectrometry, we identified Stat3, a transcription factor that induces the expression of the ferroptosis inhibitor Gpx4, as a substrate of Syvn1. Furthermore, we identified neurons as the primary cellular source of Syvn1 signalling. Moreover, we determined the binding domains of Syvn1 and Stat3 in HEK 293 T cells using full-length proteins and a series of truncated Flag-tagged and Myc-tagged fragments. Furthermore, we created the cell and animal models with silencing or overexpression of Syvn1 and Stat3 and found that Syvn1 inhibits neuronal ferroptosis by stabilizing Stat3, which subsequently activates the ferroptosis regulator Gpx4 in SCI. In summary, the Syvn1-mediated Stat3/Gpx4 signalling axis attenuates neuronal ferroptosis, reduces neuronal death, and promotes SCI repair. Therefore, our findings provide potential new targets and intervention strategies for the treatment of SCI.

Long-term outcomes of endovascular therapy for right subclavian artery occlusive lesions: A multi-center experience.

OBJECTIVE: To review our multi-institutional experience with endovascular therapy for right subclavian artery occlusive disease and to evaluate the long-term outcomes. METHODS: We retrospectively evaluated all patients with right subclavian artery stenosis and occlusive disease who underwent endovascular therapy between March 2014 and September 2022 at two institutions. Patient baseline demographics, lesion characteristics, treatment strategies, and in-hospital and follow-up outcomes were prospectively collected and retrospectively analyzed. RESULTS: Between March 2014 and September 2022, 73 patients underwent endovascular treatment at the two institutions. The dominant cause of lesions in this cohort was atherosclerosis. Three different types of lesions were summarized, and the corresponding endovascular strategies were performed. 66 patients (90.4%) underwent successful endovascular treatment, and 62 patients (84.9%) underwent balloon-expandable stent deployment. The mean perioperative in-hospital stay was 4.0 days (range, 3-6 days). Two patients died due to myocardial infarction, and one died of cerebral hemorrhage resulting from a traffic accident within 30 days of the intervention. The median follow-up time was 31.6 months (range, 12-96 months). No complications, including death, stroke, stent fractures, or migration, were noted in any patient during the follow-up period. The overall complication rate was 7/73 (9.6%), and 5/7 (6.9%) of the complications required reintervention. CONCLUSIONS: Endovascular treatment of right subclavian artery lesions is safe, effective, and technically achievable. The reasonable use of balloon-expandable stents can achieve satisfactory outcomes with accurate orientation and promising patency.

Venetoclax combined chemotherapy versus chemotherapy alone for acute myeloid leukemia: a systematic review and meta-analysis.

Objective: To compare the efficacy and safety of venetoclax (VEN) in combination with chemotherapy (chemo) versus chemo alone in the treatment of acute myeloid leukemia (AML). Method: To compare the efficacy and/or safety of VEN+chemo versus chemotherapy alone for AML, PubMed, Embase, Web of Science, and the Cochrane Library were used to searching up to June 2023. Comparisons included complete remission (CR), CR with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), overall response rate (ORR), and adverse events (AEs). Result: A total of 9 articles were included, including 3124 patients. The baseline characteristics between two patient groups were similar. The combined analysis showed that compared with the group receiving chemo alone, the VEN+chemo group exhibited higher rates of CR, CRi, MLFS and ORR. Additionally, the VEN+chemo group had longer event-free survival (EFS) and overall survival (OS) durations. The incidence rates of AEs and serious AEs (SAEs) were similar between the two groups, but the early 30-day mortality rate was lower in the VEN+chemo group than in the chemo alone group. Conclusion: The VEN+chemo therapy demonstrates significant efficacy and safety profile in AML patients. However, more prospective studies are needed in the future to provide more accurate and robust evidence for treatment selection in patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023439288, identifier CRD42023439288.

USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway.

Ubiquitin-specific protease 3 (USP3) plays an important role in the progression of various tumors. However, the role of USP3 in osteosarcoma (OS) remains poorly understood. The aim of this study was to explore the biological function of USP3 in OS and the underlying molecular mechanism. We found that OS had higher USP3 expression compared with that of normal bone tissue, and high expression of USP3 was associated with poor prognosis in patients with OS. Overexpression of USP3 significantly increased OS cell proliferation, migration, and invasion. Mechanistically, USP3 led to the activation of the PI3K/AKT signaling pathway in OS by binding to EPHA2 and then reducing its protein degradation. Notably, the truncation mutant USP3-F2 (159-520) interacted with EPHA2, and amino acid 203 was found to play an important role in this process. And knockdown of EPHA2 expression reversed the pro-tumour effects of USP3-upregulating. Thus, our study indicates the USP3/EPHA2 axis may be a novel potential target for OS treatment.

Effects of COL1A1 and SYTL2 on inflammatory cell infiltration and poor extracellular matrix remodeling of the vascular wall in thoracic aortic aneurysm.

BACKGROUND: Thoracic aortic aneurysm (TAA) is a fatal cardiovascular disease, the pathogenesis of which has not yet been clarified. This study aimed to identify and validate the diagnostic markers of TAA to provide a strong theoretical basis for developing new methods to prevent and treat this disease. METHODS: Gene expression profiles of the GSE9106, GSE26155, and GSE155468 datasets were acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the "limma" package in R. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), random forest, and binary logistic regression analyses were used to screen the diagnostic marker genes. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate immune cell infiltration in TAA. RESULTS: A total of 16 DEGs were identified. The enrichment and functional correlation analyses showed that DEGs were mainly associated with inflammatory response pathways and collagen-related diseases. COL1A1 and SYTL2 were identified as diagnostic marker genes with a high diagnostic value for TAA. The expression of COL1A1 and SYTL2 was considerably higher in TAA vascular wall tissues than in the corresponding normal tissues, and there were significant differences in the infiltration of immune cells between TAA and normal vascular wall tissues. Additionally, COL1A1 and SYTL2 expression were associated with the infiltration of immune cells in the vascular wall tissue. Single-cell analysis showed that COL1A1 in TAA was mainly derived from fibroblasts and SYTL2 mainly from CD8+ T cells. In addition, single-cell analysis indicated that fibroblasts and CD8+ T cells in TAA were significantly higher than those in normal arterial wall tissue. CONCLUSIONS: COL1A1 and SYTL2 may serve as diagnostic marker genes for TAA. The upregulation of SYTL2 and COL1A1 may be involved in the inflammatory infiltration of the vessel wall and poor extracellular matrix remodeling, promoting the progression of TAA.

Analysis of Mean Corpuscular Volume and Red Cell Distribution Width in Patients with Aplastic Anemia.

To explore the characteristics of hemogram in patients with aplastic anemia (AA), especially mean corpuscular volume (MCV) and red cell distribution width (RDW). We examined the blood routine of 180 new-onset AA patients and used 166 patients with myelodysplastic syndrome (MDS) as controls. Among the 180 AA patients, 105 (58.3%) were diagnosed with severe AA (SAA), while 75 (41.7%) were diagnosed with non-severe AA (NSAA). Compared to MDS, patients with SAA generally had unfavorable hemogram, including significantly lower white blood cell (WBC), absolute neutrophil count (ANC), hemoglobin (Hb), platelet (PLT) and reticulocyte counts (RET). However, WBC, ANC and lymphocyte counts were higher in the NSAA group than in the MDS group; Hb and Ret were comparable between the two groups. 8.5% of SAA patients and 58.1% of NSAA patients presented with macrocytic anemia, whereas 25.7% of SAA and 64.0% of NSAA had a high RDW. In the MDS group, 54.7% of patients presented with macrocytic anemia, and 84.7% had increased RDW. WBC, ANC, PLT, and Ret in a high-RDW group (25.7% of SAA) were significantly higher than in a normal-RDW group (74.3% of SAA). Overall, most SAA patients exhibited normocytic-normochromic anemia, and their hemograms decreased more significantly; more than half of NSAA patients showed macrocytic-heterogeneous anemia, and their hemograms were similar to those of MDS. Patients with elevated RDW may have better residual bone marrow hematopoietic function than those with normal RDW but with more severe anemia.

Clinical implications of myeloid malignancy­related somatic mutations in aplastic anemia.

Aplastic anemia (AA) is a potentially fatal bone marrow failure syndrome characterized by a paucity of hematopoietic stem cells and progenitor cells with varying degrees of cytopenia and fatty infiltration of the bone marrow space. Recent advances in genomics have uncovered a link between somatic mutations and myeloid cancer in AA patients. At present, the impact of these mutations on AA patients remains uncertain. We retrospectively investigated 279 AA patients and 174 patients with myelodysplastic syndromes (MDS) and performed targeted sequencing of 22 genes on their bone marrow cells using next-generation sequencing (NGS). Associations of somatic mutations with prognostic relevance and response to treatment were analyzed. Of 279 AA patients, 25 (9.0%) patients had somatic mutations, and 20 (7.2%) patients had one mutation. The most frequently mutated genes were ASXL1(3.2% of the patients), DNMT3A (1.8%) and TET2 (1.8%). In the MDS group, somatic mutations were detected in 120 of 174 (69.0%) patients, and 81 patients (46.6%) had more than one mutation. The most frequently mutated genes were U2AF1 (24.7% of the patients), ASXL1 (18.4%) and TP53 (13.2%). Compared with MDS patients, AA patients had a significantly lower frequency of somatic mutations and mostly one mutation. Similarly, the median variant allele frequency was lower in AA patients than in MDS patients (6.9% vs. 28.4%). The overall response of 3 and 6 months in the somatic mutation (SM) group was 37.5% and 66.7%, respectively. Moreover, there was no significant difference compared with the no somatic mutation (N-SM) group. During the 2-years follow-up period, four (20%) deaths occurred in the SM group and 40 (18.1%) in the N-SM group, with no significant difference in overall survival and event-free survival between the two groups. Our data indicated that myeloid tumor-associated somatic mutations in AA patients were detected in only a minority of patients by NGS. AA and MDS patients had different gene mutation patterns. The somatic mutations in patients with AA were characterized by lower mutation frequency, mostly one mutation, and lower median allelic burden of mutations than MDS. Somatic mutations were a common finding in the elderly, and the frequency of mutations increases with age. The platelet count affected the treatment response at 3 months, and ferritin level affected the outcome at 6 months, while somatic mutations were not associated with treatment response or long-term survival. However, our cohort of patients with the mutation was small; this result needs to be further confirmed with large patient sample.

Effects of post-transplant maintenance therapy with decitabine prophylaxis on the relapse for acute lymphoblastic leukemia.

In adults with acute lymphoblastic leukemia (ALL), post-transplant relapse is a major risk factor for mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our study investigated the efficacy and safety of decitabine (dec) with ALL patients post-transplantation. We performed a retrospective cohort study to assess the efficacy of decitabine (dec) with post-transplant ALL at the First Affiliated Hospital of Zhengzhou University from February 2016 to September 2021. A total of 141 consecutive ALL patients were analyzed and divided into decitabine (dec, n = 65) and control (ctrl, n = 76) groups based on whether they were treated with decitabine after allo-HSCT. The 3-year cumulative incidence of relapse (CIR) rate in the dec group was lower than that in the ctrl group (19.6 vs. 36.1%, p = 0.031), with a hazard ratio of 0.491 (95% confidence interval [CI], 0.257-0.936). Additionally, subgroup analyses revealed that the 3-year CIR rate of T-ALL and Ph-negative B-ALL patients in the dec and ctrl groups was 11.7 vs. 35.9% and 19.5 vs. 42.2% (p = 0.035, p = 0.068) respectively. In summary, ALL patients, especially those with T-ALL and Ph-negative B-ALL, may benefit from decitabine as maintenance therapy following allo-HSCT.

Progression of Thoracic Aortic Dissection Is Aggravated by the hsa_circ_0007386/miR-1271-5P/IGF1R/AKT Axis via Induction of Arterial Smooth Muscle Cell Apoptosis.

BACKGROUND: The molecular mechanisms associated with thoracic aortic dissection (TAD) remain poorly understood. A comprehensive high-throughput sequencing-based analysis of the circRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) regulatory network in TAD has not been conducted. The purpose of this study is to identify and verify the key ceRNA networks which may have crucial biological functions in the pathogenesis of TAD. METHODS: Gene expression profiles of the GSE97745, GSE98770, and GSE52093 datasets were acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the GEO2R tools. Protein-protein interaction (PPI) networks of the hub genes were constructed using STRING; the hub genes and modules were identified by MCODE and CytoHubba plugins of the Cytoscape. We analyzed the hub genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. The functions of these hub genes were assessed using Cytoscape software. Our data-along with data from GSE97745, GSE98770, and GSE52093-were used to verify the findings. RESULTS: Upon combined biological prediction, a total of 11 ce-circRNAs, 11 ce-miRNAs, and 26 ce-mRNAs were screened to construct a circRNA-miRNA-mRNA ceRNA network. PPI network and module analysis identified four hub nodes, including IGF1R, JAK2, CSF1, and GAB1. Genes associated with the Ras and PI3K-Akt signaling pathways were clustered in the four hub node modules in TAD. The node degrees were most significant for IGF1R, which were also the most significant in the two modules (up module and hub module). IGF1R was selected as a key gene, and the hsa_circ_0007386/miR-1271-5P/IGF1R/AKT regulatory axis was established. The relative expression levels of the regulatory axis members were confirmed by RT-PCR in 12 samples, including TAD tissues and normal tissues. Downregulation of IGF1R expression in smooth muscle cells (SMCs) was found to induce apoptosis by regulating the AKT levels. In addition, IGF1R showed high diagnostic efficacy in both AD tissue and blood samples. CONCLUSIONS: The hsa_circ_0007386/miR-1271-5P/IGF1R/AKT axis may aggravate the progression of TAD by inducing VSMCs apoptosis. CeRNA networks could provide new insights into the underlying molecular mechanisms of TAD. In addition, IGF1R showed high diagnostic efficacy in both tissue and plasma samples in TAD, which can be considered as a diagnostic marker for TAD.

ARL13B promotes angiogenesis and glioma growth by activating VEGFA-VEGFR2 signaling.

BACKGROUND: Tumor angiogenesis is essential for solid tumor progression, invasion and metastasis. The aim of this study was to identify potential signaling pathways involved in tumor angiogenesis. METHODS: Genetically engineered mouse models were used to investigate the effects of endothelial ARL13B(ADP-ribosylation factor-like GTPase 13B) over-expression and deficiency on retinal and cerebral vasculature. An intracranially transplanted glioma model and a subcutaneously implanted melanoma model were employed to examine the effects of ARL13B on tumor growth and angiogenesis. Immunohistochemistry was used to measure ARL13B in glioma tissues, and scRNA-seq was used to analyze glioma and endothelial ARL13B expression. GST-fusion protein-protein interaction and co-immunoprecipitation assays were used to determine the ARL13B-VEGFR2 interaction. Immunobloting, qPCR, dual-luciferase reporter assay and functional experiments were performed to evaluate the effects of ARL13B on VEGFR2 activation. RESULTS: Endothelial ARL13B regulated vascular development of both the retina and brain in mice. Also, ARL13B in endothelial cells regulated the growth of intracranially transplanted glioma cells and subcutaneously implanted melanoma cells by controlling tumor angiogenesis. Interestingly, this effect was attributed to ARL13B interaction with VEGFR2, through which ARL13B regulated the membrane and ciliary localization of VEGFR2 and consequently activated its downstream signaling in endothelial cells. Consistent with its oncogenic role, ARL13B was highly expressed in human gliomas, which was well correlated with the poor prognosis of glioma patients. Remarkably, ARL13B, transcriptionally regulated by ZEB1, enhanced the expression of VEGFA by activating Hedgehog signaling in glioma cells. CONCLUSIONS: ARL13B promotes angiogenesis and tumor growth by activating VEGFA-VEGFR2 signaling. Thus, targeting ARL13B might serve as a potential approach for developing an anti-glioma or anti-melanoma therapy.

Impact of treatments before allogeneic hematopoietic stem cell transplantation in patients with higher-risk myelodysplastic syndrome.

OBJECTIVE: The study aimed to evaluate pre-allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment, compare the endpoints related to disease management between pre-HSCT cytoreduction patients and upfront transplantation patients with higher-risk myelodysplastic syndrome (MDS). METHODS: A total of 90 higher-risk MDS patients administered allo-HSCT in the Hematology Department of the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed, which included 28 patients with upfront transplantation and 62 patients with pre-transplant cytoreduction, including 30 patients received hypomethylating agents (HMA) and 32 patients received hypomethylating agents and induction chemotherapy (HMA+IC). Difference between the two groups regarding hematopoietic reconstruction, graft-versus-host disease (GVHD), relapse rate, non-relapse death (NRM), overall survival (OS) and relapse-free survival (RFS) was compared. RESULTS: No significant differences in OS, DFS and NRM were found between the upfront transplantation and pre-transplant cytoreduction groups, and cumulative cGVHD occurrence and relapse rates were 35.7 % and 14.5 % (P = 0.029), and 10.7 % and 12.9 % (p = 0.535), respectively. Survival rates were significantly higher in the upfront transplantation and HMA+IC groups compared with the HMA group (3-year OS: 67.9 %, 68.8 %, 43.3 %, P = 0.039; 3-year RFS: 64.3 %, 62.5 %, 43.3 %, P = 0.107; 3-year NRM: 25.0 %, 21.9 %, 50.0 %, P = 0.025). Compared with the upfront transplantation group, overall response to cytoreductive therapy (OR) and non-response to cytoreductive therapy (NR), 3-year OS were 67.9 %, 73.0 % and 32.0 % (P < 0.001), 3-year RFS were 64.3 %, 73.0 % and 24.0 % (P < 0.001) and 3-year NRM were 25.0 %, 21.6 %, and 56.0 %, respectively (P < 0.001). Upfront transplantation (n = 11) had better OS and RFS compared with the cytoreductive group (n = 10) in patients with ≥ 10 % bone marrow blast cells before transplantation (3-year OS: 63.64 %, 22.22 %, p = 0.010; 3-year DFS: 63.64 %, 20.00 %, p = 0.012, respectively). CONCLUSION: The pre-transplant treatment regimen was an independent prognostic factor of OS and NRM. If the donor is suitable, upfront transplantation may provide longer survival in higher-risk MDS patients, which, however, may also increase the incidence of cGVHD. Even in patients with bone marrow blast cells ≥ 10 % before transplantation, upfront transplantation was not worse than transplantation after cytoreductive therapy. While waiting for a transplant, HMA+IC therapy may be a good pre-transplant treatment option.

Prognostic prediction of novel risk scores (AML-DRG and AML-HCT-CR) in acute myeloid leukemia patients with allogeneic hematopoietic stem cell transplantation.

We aimed to validate and prove the novel risk score models of acute myeloid leukemia (AML)-specific disease risk group (AML-DRG) and AML-Hematopoietic Cell Transplant-composite risk (AML-HCT-CR) in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (AHCT). Among the 172 AML patients analysed, 48.3% (n = 83) were females. Median age was 31.5 years (range 14 to 62 years), two patients was more than 60 years old (1.2%). Median follow-up was 44 months (range 1 to 94 months). According to the AML-DRG model, 109, 49 and 14 patients were in low-, intermediate- and high-risk group, respectively. According to the AML-HCT-CR model, 108, 30, 20 and 14 patients were in low-, intermediate-, high- and very high-risk group, respectively. Our results showed that the AML-DRG and AML-HCT-CR models significantly predicted cumulative incidence of relapse (p < 0.001; p < 0.001). But AML-DRG model was not associated with NRM (p = 0.072). Univariate analysis showed that the AML-DRG model could better stratify AML patients into different risk groups compared to the AML-HCT-CR model. Multivariate analysis confirmed that prognostic impact of AML-DRG and AML-HCT-CR models on post-transplant OS was independent to age, sex, conditioning type, transplant modality, and stem cell source (p < 0.001; p < 0.001). AML-DRG and AML-HCT-CR models can be used to effectively predict post-transplant survival in patients with AML receiving AHCT. Compared to AML-HCT-CR score, the AML-DRG score allows better stratification and improved survival prediction of AML patients post-transplant.

Preoperative systemic inflammatory response index predicts long-term outcomes in type B aortic dissection after endovascular repair.

Objectives: Inflammation is a hallmark of the initial development and progression of aortic dissection. This study aimed to investigate the value of preoperative inflammatory biomarkers in predicting aorta-related adverse events (AAEs) after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection. Methods: We included all patients who underwent TEVAR for type B aortic dissection between November 2016 and November 2020 in this single-center, retrospective cohort study. Patients were divided into two groups: the AAEs group (n = 75) and the non-AAEs group (n = 126). Preoperative inflammatory biomarkers were recorded, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and systemic inflammatory response index (SIRI). Patients were followed-up for the development of AAEs. Prediction accuracy of inflammatory biomarkers for AAEs were evaluated using the area under the receiver operating characteristic curves. Results: This study included 201 patients, of whom 80.0% were men, with a mean age of 59.1 ± 12.5 years. A total of 75 patients developed AAEs after TEVAR. The AUCs of NLR, MLR, PLR, SII, and SIRI for AAEs were.746,.782,.534,.625 and.807, respectively. Age and SIRI were independent risk factors for the AAEs after TEVAR (HR 3.264, p <.001; HR 4.281, p <.001, respectively). Survival analysis revealed significantly lower AAE-free status in patients with preoperative SIRI > = 4 (p <.001). Conclusion: Increased preoperative SIRI and age are independent risk factors for AAEs after TEVAR in type B aortic dissection.

Comparison of techniques for left subclavian artery preservation during thoracic endovascular aortic repair: A systematic review and single-arm meta-analysis of both endovascular and surgical revascularization.

Background: Currently, the optimal technique to revascularize the left subclavian artery (LSA) during thoracic endovascular aortic repair (TEVAR) remains controversial. Our study seeks to characterize early and late clinical results and to assess the advantages and disadvantages of endovascular vs. surgical strategies for the preservation of LSA. Methods: PubMed, Embase and Cochrane Library searches were conducted under the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analyses) standards. Only literature published after January 1994 was included. Studies reporting on endovascular revascularization (ER), surgical revascularization (SR) for LSA preservation were included. 30-day mortality and morbidity rates, restenosis rates, and rates of early and late reintervention are measured as outcomes. Results: A total of 28 studies involving 2,759 patients were reviewed. All articles were retrospective in design. Single-arm analysis found no significant statistical differences in ER vs. SR in terms of 30-day mortality and perioperative complication rates. The mean follow-up time for the ER cohort was 12.9 months and for the SR cohort was 26.6 months, respectively. Subgroup analysis revealed a higher risk of perioperative stroke (4.2%) and endoleaks (14.2%) with the chimney technique compared to the fenestrated and single-branched stent approaches. Analysis of the double-arm studies did not yield statistically significant results. Conclusion: Both ER and SR are safe and feasible in the preservation of LSA while achieving an adequate proximal landing zone. Among ER strategies, the chimney technique may presents a greater risk of neurological complications and endoleaks, while the single-branched stent grafts demonstrate the lowest complication rate, and the fenestration method for revascularization lies in an intermediate position. Given that the data quality of the included studies were relatively not satisfactory, more randomized controlled trials (RCTs) are needed to provide convincing evidence for optimal approaches to LSA revascularization in the future.

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level.

BACKGROUND: Approximately 8-9% of the world's population is affected by autoimmune diseases, and yet the mechanism of autoimmunity trigger is largely understudied. Two unique cell death modalities, ferroptosis and pyroptosis, provide a new perspective on the mechanisms leading to autoimmune diseases, and development of new treatment strategies. METHODS: Using scRNA-seq datasets, the aberrant trend of ferroptosis and pyroptosis-related genes were analyzed in several representative autoimmune diseases (psoriasis, atopic dermatitis, vitiligo, multiple sclerosis, systemic sclerosis-associated interstitial lung disease, Crohn's disease, and experimental autoimmune orchitis). Cell line models were also assessed using bulk RNA-seq and qPCR. RESULTS: A substantial difference was observed between normal and autoimmune disease samples involving ferroptosis and pyroptosis. In the present study, ferroptosis and pyroptosis showed an imbalance in different keratinocyte lineages of psoriatic skinin addition to a unique pyroptosis-sensitive keratinocyte subset in atopic dermatitis (AD) skin. The results also revealed that pyroptosis and ferroptosis are involved in epidermal melanocyte destruction in vitiligo. Aberrant ferroptosis has been detected in multiple sclerosis, systemic sclerosis-associated interstitial lung disease, Crohn's disease, and autoimmune orchitis. Cell line models adopted in the study also identified pro-inflammatory factors that can drive changes in ferroptosis and pyroptosis. CONCLUSION: These results provide a unique perspective on the involvement of ferroptosis and pyroptosis in the pathological process of autoimmune diseases at the scRNA-seq level. IFN-γ is a critical inducer of pyroptosis sensitivity, and has been identified in two cell line models.

Patients With Symptomatic AAAs Are More Likely to Develop Lumen Partial-Thrombus After Endovascular Aortic Repair Than Asymptomatic Patients.

Background: According to their symptoms, abdominal aortic aneurysms (AAAs) can be divided into symptomatic and asymptomatic types. This study aimed to explore the differences and correlations between postoperative lumen thrombosis in these two groups after endovascular aortic repair (EVAR). Methods: A retrospective study using clinical data of 169 patients with AAA treated with EVAR collected in our hospital between January 2018 and January 2021 was conducted based on the inclusion and exclusion criteria for patient selection. Based on whether the patient had clinical symptoms at admission and the presence of a complete lumen thrombus during follow-up, the patients were divided into two sets of groups: a complete-thrombus group (n = 44) and a partial-thrombus group (n = 125), and a group with clinical symptoms (n = 32) and a group without clinical symptoms (n = 137). The clinical data of these groups were compared, and a further stratified analysis was performed. Results: A total of 169 patients were included in the analysis. An abdominal aorta stent graft was successfully implanted in all patients. The complete-thrombus rate of the patients in this study was 73.96%. Univariate analysis showed that the maximal aortic diameter and preoperative peripheral blood neutrophil levels affected the clinical symptoms of patients with AAA (p < 0.05). The complete thrombus rate of the lumen of the AAA was lower in patients with clinical symptoms than in those without symptoms during the follow-up period (p < 0.05). Female sex, preoperative hyperuricemia, and symptoms at admission were independent risk factors for a partial thrombus in the lumen during follow-up. Based on these independent risk factors, we constructed a scoring system to differentiate patients into low- (0 points), middle- (1 point), and high-risk (2 points) groups. The scoring system could distinguish the complete lumen thrombosis rate after EVAR to a certain extent. Conclusions: Patients with symptomatic AAAs were more likely to develop incomplete lumen thrombosis than asymptomatic patients during follow-up after EVAR.

Clinical characteristics, treatment, and prognosis of 118 cases of myeloid sarcoma.

Myeloid sarcoma is a rare manifestation of acute myeloid leukemia (AML) and is associated with poor overall survival (OS). The optimal treatment remains unclear. The study retrospectively evaluated 118 patients with myeloid sarcoma who were treated at the First Affiliated Hospital of Zhengzhou University from January 2010 to July 2021. All cases were diagnosed by tissue biopsy. 41 patients underwent genetic mutation analysis. The most frequent genetic mutations were KIT (16.6%), followed by TET2 (14.6%), and NRAS (14.6%). The median survival time of 118 patients was 4 months (range, 1-51 months), while the median survival time of 11 patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) was 19 months (range, 8-51 months). 4 (36.4%) of the 11 patients experienced relapse within 1 year after transplantation. 1 patient died from a severe infection. Of the 6 surviving patients, 5 patients have received maintenance treatment with decitabine after transplantation, and all remained in a state of recurrence-free survival. Patients with myeloid sarcoma have a very unfavorable outcome. Allo-HSCT is an effective treatment option. Recurrence remains the main cause of transplant failure. Maintenance treatment with decitabine after transplantation can prolong the recurrence-free survival time, although these results must be verified in a study with expanded sample size.

[Gene Mutation and Overexpression of Newly Diagnosed Multiple Myeloma Patients].

OBJECTIVE: To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients. METHODS: Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH). RESULTS: Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression. CONCLUSION: There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.