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Objective To find the prevalence of sarcopenia in patients with multiple system atrophy(MSA)and to explore the muscle related risk factors that affect the ability if living and exercise of patients. Methods Through a cross-sectional study, patients with Parkinson's disease(PD) and movement disorders who visited the multidisciplinary outpatient clinic of Peking Union Medical College Hospital from October 2022 to December 2023 were included. Their demographic data and disease duration were collected. The modified Barthel Index (simplified Chinese version) was applied to evaluate the participants' living ability. The severity of movement disorders and non-motor symptoms were evaluated by the Unified PD rating scale. The body composition, grip strength, SARC-F score were used to evaluate the muscle condition of patients and the diagnosis of sarcopenia and pre sarcopenia were made according to EWGSOP2. Results Among 44 patients included in this study, 8(18.8%) were diagnosed with sarcopenia, 17(38.6%) were pre-sarcopenia and 19(43.2) had normal muscle condition. There were significant differences in disease-related clinical characteristics among the three groups. MSA patients were characterized by older age(P＜0.01).They had lower BMI (P＜0.01), and worse disease symptom score (P＜0.01), SARC-F score(P＜0.05), and activity score (P＜0.01), significantly reduced fat removal weight (P＜0.01) and phase angle (P＜0.05). Regression analysis showed that SARC-F score, grip strength, limb skeletal muscle index and fat free weight were all independent risk factors affecting the ability of living and exercise of MSA patients. Conclusions The preval-ence of MSA sarcopenia is higher and sarcopenia is closely associated with more severe clinical illness and lower living ability. It is an independent risk factor for increased living ability score and motor function score.

Purpose: Postinduction hypotension (PIH), occurring between anaesthesia induction and surgical incision, is particularly concerning in older adults undergoing transcatheter aortic valve replacement (TAVR) due to their multiple comorbidities and age-related cardiovascular changes. This study aimed to assess the relationship between PIH and postoperative adverse events in TAVR patients. Patients and Methods: A total of 777 patients underwent TAVR at The Second Affiliated Hospital of Zhejiang University School of Medicine from January 1, 2020 to February 28, 2023. Four thresholds of MAP were defined, including two absolute thresholds (< 65, < 60 mmHg) and two relative thresholds (20% and 30% lower than baseline). The relationships between PIH and the composite outcome, which included all-cause in-hospital mortality, stroke, acute kidney injury (AKI), and myocardial infarction (MI), were examined using unadjusted analysis, 1:1 propensity score matching(PSM), and inverse probability of treatment weighting (IPTW). Results: A total of 643 older adults were included in the study ultimately. The composite outcome incidence was significantly greater in patients with PIH than in those without PIH (relative risk [RR]: 2.47, 95% CI: 1.66– 3.73 for MAP < 60 mmHg; RR: 1.66, 95% CI: 1.14– 2.46 for a > 30% decrease from baseline). PIH was significantly associated with stroke (RR: 5.22, 95% CI: 1.98– 17.75) and AKI (RR: 2.82, 95% CI: 1.73– 4.79) with a MAP < 60 mmHg. Conclusion: PIH significantly increases the risk of composite outcomes, especially stroke and AKI, in TAVR patients. [ABSTRACT FROM AUTHOR]

mTOR activation leads to enhanced survival signaling in acute myeloid leukemia (AML) cells. The active-site mTOR inhibitors (asTORi) represent a promising new approach to targeting mTOR in AKT/mTOR signaling. MLN0128 is an orally-administered, second-generation asTORi, currently in clinical development. We examined the anti-leukemic effects and the mechanisms of action of MLN0128 in AML cell lines and primary samples, with a particular focus on its effect in AML stem/progenitor cells. MLN0128 inhibited cell proliferation and induced apoptosis in AML by attenuating the activity of mTOR complex 1 and 2. Using time-of-flight mass cytometry, we demonstrated that MLN0128 selectively targeted and functionally inhibited AML stem/progenitor cells with high AKT/mTOR signaling activity. Using the reverse-phase protein array technique, we measured expression and phosphorylation changes in response to MLN0128 in 151 proteins from 24 primary AML samples and identified several pro-survival pathways that antagonize MLN0128-induced cellular stress. A combined blockade of AKT/mTOR signaling and these pro-survival pathways facilitated AML cell killing. Our findings provide a rationale for the clinical use of MLN0128 to target AML and AML stem/progenitor cells, and support the use of combinatorial multi-targeted approaches in AML therapy.

We aimed to study the regulatory roles and mechanism of circular nuclear factor IX (circNFIX) in cancer growth and stemness properties of ovarian cancer (OC). CircNFIX and SH3RF3 levels in OC tissues and cells were tested by quantitative real‐time PCR. RNase R treatment quantified circNFIX RNA stability. Molecular interaction among circNFIX, LIN28B, and SH3RF3 was predicted by bioinformatics software and validated through RNA immunoprecipitation (RIP) assay. The gain‐ or loss‐experiments of circNFIX on capabilities of metastasis and stemness in vitro were assessed using Cell Counting Kit‐8, Transwell, western blot, and sphere‐formation assays. CircNFIX and SH3RF3 were markedly elevated in OC tissues and OC cells. Knocking down circNFIX repressed the proliferation, migration, invasion, and stemness properties of A2780 and SKOV3 cells. The RIP assay verified the direct binding relationship between LIN28B, circNFIX, and SH3RF3. Additionally, overexpression of circNFIX elevated the SH3RF3 expression, while this effect was reversed by LIN28B silence. Rescue experiments demonstrated that the overexpression of SH3RF3 reversed the knockdown of circNFIX on OC cells' proliferation, metastasis, and stemness properties. CircNFIX improved the mRNA stability and translation of SH3RF3 via recruiting LIN28B, thus promoting the proliferation, invasion, and stemness properties of OC cells in vitro. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is a gynecological cancer with high mortality. OC‐derived exosomal circRNAs can regulate angiogenesis. This study aims to explore the role and mechanism of exosomal circRNA nuclear factor I X (CircNFIX) derived from OC cells in angiogenesis. Quantitative real‐time polymerase chain reaction was employed to evaluate the levels of circNFIX, miR‐518a‐3p, and tripartite motif protein 44 (TRIM44) in OC and adjacent tissues. Exosomes from the ovarian surface epithelial cell (HOSEpiC) and OC cells (SKOV3 or OVCAR3) were isolated by differential centrifugation. Exosomes were cocultured with the human umbilical vein endothelial cells (HUVECs). The angiogenesis capacity was analyzed by Tube formation assay. 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) and Transwell assays were used to determine the cell viability and migration ability. The dual‐luciferase report, RNA immunoprecipitation (RIP), and RNA pull‐down assays were applied to validate the gene's interaction. CircNFIX and TRIM44 expression were higher and miR‐518a‐3p was lower in OC tissues than in the adjacent tissues. Upregulated circNFIX and TRIM44 were significantly correlated with the tumor size and International Federation of Gynecology and Obstetrics (FIGO) stage of OC patients. HUVECs treated OC‐derived exosomes had higher proliferation, migration, and angiogenesis capacities than the control group. While OC‐derived exosomal circNFIX silencing restrained HUVECs' proliferation, migration, and angiogenesis, compared with the OC‐derived exosomes group. OC‐derived exosomal circNFIX positively regulated TRIM44 expression by targeting miR‐518a‐3p in HUVECs. OC‐derived exosomal circNFIX promoted angiogenesis by regulating the Janus‐activated kinase/signal transducer and activator of transcription 1 (JAK/STAT1) pathway via miR‐518a‐3p/TRIM44 axis in HUVECs. [ABSTRACT FROM AUTHOR]

Introduction In several types of cancer, a distinct subpopulation of cancer cells has a greater capacity to initiate new tumors compared with the bulk of the tumor cells upon transplantation [...], Cancer stem cells (CSCs) are a small subpopulation of cancer cells that have increased resistance to conventional therapies and are capable of establishing metastasis. However, only a few biomarkers of CSCs have been identified. Here, we report that ganglioside GD2 (a glycosphingolipid) identifies a small fraction of cells in human breast cancer cell lines and patient samples that are capable of forming mammospheres and initiating tumors with as few as 10 GD2+ cells. In addition, the majority of GD2+ cells are also CD44hiCD24lo, the previously established CSC-associated cell surface phenotype. Gene expression analysis revealed that GD3 synthase (GD3S) is highly expressed in GD2+ as well as in CD44hiCD24lo cells and that interference with GD3S expression, either by shRNA or using a pharmacological inhibitor, reduced the CSC population and CSC-associated properties. GD3S knockdown completely abrogated tumor formation in vivo. Also, induction of epithelial-mesenchymal transition (EMT) in transformed human mammary epithelial cells (HMLER cells) dramatically increased GD2 as well as GD3S expression in these cells, suggesting a role of EMT in the origin of GD2+ breast CSCs. In summary, we identified GD2 as a new CSC-specific cell surface marker and GD3S as a potential therapeutic target for CSCs, with the possibility of improving survival and cure rates in patients with breast cancer.