Sepsis-induced B-cell dysfunction is a pivotal driver of adaptive immunosuppression, although the underlying molecular mechanisms remain incompletely elucidated. CD74, a multifunctional immunoregulatory protein, is known to mediate tumor immune evasion and immunosuppression during infection via modulation of inflammatory pathways; however, its specific role in B-cell dysfunction during sepsis has not been defined. Through integrated clinical and experimental analyses, we observed significant downregulation of CD74 in the peripheral blood of septic patients (based on GSE datasets), which correlated with adverse clinical outcomes. Validation in a cecal ligation and puncture-induced sepsis model in C57BL/6J mice demonstrated that CD74 deficiency markedly increased mortality, elevated pro‑inflammatory cytokine levels (tumor necrosis factor‑α, interleukin [IL]‑6, IL‑1β, monocyte chemoattractant protein-1; measured by enzyme-linked immunosorbent assay), and impaired bacterial clearance. Mechanistically, CD74 is a member of the regulated intramembrane proteolysis protein family. Following intramembrane cleavage, its intracellular domain (CD74‑ICD) is released and translocates to the nucleus, where it interacts with the key transcription factor Pax5 (as confirmed by co‑immunoprecipitation and immunofluorescence). This interaction leads to activation of the PI3K‑AKT signalling pathway, thereby preserving B-cell functional competence. Single‑cell transcriptomic analysis further supported the functional relevance of the CD74‑Pax5 axis in septic B cells. In summary, this study identifies CD74 as a critical regulator of sepsis-associated B-cell immunosuppression and highlights its therapeutic potential for immune reconstitution in sepsis.

Breast cancer persists as the second leading cause of cancer-related mortality in women globally. Identifying key molecular drivers governing tumor growth and invasion could substantially improve diagnostic precision and therapeutic outcomes. This study employed 4T1 triple-negative breast cancer cells (TNBC) to establish a clinically relevant sequential metastasis model. Using this model, we identified a progressive upregulation of myelin and lymphocyte protein (MAL) expression, which demonstrated a strong positive correlation with breast cancer growth and progression. Integrated methodologies—combining transcriptomic sequencing, functional cellular assays, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-mediated gene knockout, and in vivo intervention studies—revealed MAL's dual oncogenic function in promoting both primary tumor growth and metastatic spread. Mechanistically, MAL drives tumorigenesis by upregulating secreted phosphoprotein 1 (SPP1), thereby activating the Janus Kinase 2-Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) signaling axis to stimulate angiogenesis and accelerate proliferation. Simultaneously, it subverts anti-tumor immunity by exploiting major histocompatibility complex (MHC) class Ib molecules, suppressing T-cell infiltration and impairing CD8+ T-cell tumor-lytic activity within the tumor microenvironment. Critically, targeted inhibition of MAL effectively curtailed breast cancer progression, underscoring its promise as a novel therapeutic target for metastatic breast cancer intervention.

Preventing venous thromboembolism (VTE) in obstetrics remains challenging, with cases still occurring despite preventive measures. The aim of this study is to investigate the underlying causes by analyzing potential issues in current postpartum VTE prevention strategies in China. This retrospective study was conducted in our hospital from May 2021 to August 2024. VTE risk was assessed using the Chinese Expert Consensus on VTE Prevention and Treatment during Pregnancy and Puerperium (Chinese Consensus), and preventive measures were implemented accordingly. Clinical variables, timing of prophylaxis, and the predictive accuracy of the Chinese Consensus were analyzed. The VTE group had higher D-dimer levels and longer hospital stays and shorter gestational ages (P < 0.05). Significant differences were observed in postpartum hemorrhage (PPH), premature birth, autoimmune diseases, and cesarean delivery (P < 0.05). Despite 65.4% receiving thromboprophylaxis, 25.2% developed VTE, with higher incidences in those without prophylaxis. Pneumatic therapy and LMWH were effective in high-risk patients (P < 0.05). Early VTE occurred 6 h postpartum, with 41.8% within 48 h. Most preventive measures were initiated at 24–48 h postpartum, potentially delaying optimal protection. The ROC analysis showed an AUC of 0.497 (P = 0.937), indicating limited predictive efficacy of the Chinese Consensus. Current postpartum VTE prevention is inadequate, as some at-risk patients still miss the opportunity for pneumatic therapy and LMWH anticoagulation after delivery. Initiating LMWH prophylaxis 24 h postpartum appears to be delayed. The predictive ability of the Chinese Consensus for assessing VTE risk is limited. Future research is essential to optimize prevention strategies and reduce the incidence of postpartum VTE.

Background: Venous thromboembolism (VTE) remains a leading cause of sudden death in obstetric patients. Despite advancements in diagnostic and therapeutic approaches, the incidence of VTE continues to rise. This study aimed to validate the accuracy of currently used risk assessment models (RAMs) for predicting postpartum VTE. Methods: This retrospective study was conducted from February 2019 to February 2024. The Chinese Expert Consensus on the Prevention and Treatment of VTE during Pregnancy and Puerperium (Chinese Consensus), and the Queensland Clinical Guideline (QLD guideline) were used to evaluate VTE risk. Risk factors were compared between the VTE group and the control groups. The predictive performance of the two RAMs was assessed by analyzing the area under the curve (AUC) of the receiver operating characteristic (ROC). Results: A total of 560 postpartum women were included, comprising 140 cases with VTE and 420 cases without VTE (controls). Significant differences between the two groups were observed for D-dimer levels, platelet (PLT) count, length of hospital stay, gestational age, body mass index (BMI) ≥25 kg/m2, postpartum hemorrhage (PPH), premature birth, and delivery mode (all p < 0.05). A higher proportion of anti-phospholipid antibody positivity was found in the VTE group (p = 0.054), while assisted reproductive technology (ART), emergency cesarean delivery, and elevated total cholesterol levels were more frequent in the control group (p < 0.05). Cesarean delivery was the most frequent risk factor triggering VTE, followed by age ≥35 years, and ART. However, stillbirth (n = 2, 66.7%), anti-phospholipid antibody positivity (n = 9, 52.9%), and PPH (n = 13, 52%) demonstrated the highest proportions of VTE. Notably, VTE occurred in the low-risk group, with an incidence of 20.6% according to the QLD guideline and 24.6% according to the Chinese Consensus. 2 VTE cases were observed in patients with a score of 0. The QLD guideline exhibited higher sensitivity than the Chinese Consensus (0.81 vs. 0.69), but lower specificity (0.64 vs. 0.83). The AUCs for predicting postpartum VTE were 0.624 (p < 0.001) for the QLD guideline and 0.538 (p > 0.05) for the Chinese Consensus. Conclusions: PPH, anti-phospholipid antibody positivity, and D-dimer levels were closely associated with thrombosis. Both the QLD guideline and the Chinese Consensus showed suboptimal performance in estimating VTE risk. Further research is urgently needed to develop more effective RAMs to aid in the prevention of postpartum VTE.

BACKGROUND:Immunosuppression is closely related to the pathogenesis of sepsis, but the underlying mechanisms have not yet been fully elucidated. In this study, we aimed to examine the role of the Sterile Alpha Motif, Src Homology 3 domain and nuclear localization signal 1 (SAMSN1) in sepsis and elucidate its potential molecular mechanism in sepsis induced immunosuppression. METHODS:RNA sequencing databases were used to validate SAMSN1 expression in sepsis. The impact of SAMSN1 on sepsis was verified using gene knockout mice. Flow cytometry was employed to delineate how SAMSN1 affects immunity in sepsis, focusing on immune cell types and T cell functions. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated gene editing in RAW264.7 macrophages enabled interrogation of SAMSN1 's regulatory effects on essential macrophage functions, including cell proliferation and phagocytic capacity. The mechanism of SAMSN1 in the interaction between macrophages and T cells was investigated using the RAW264.7 cell line and primary cell lines. RESULTS:SAMSN1 expression was significantly increased in patients with sepsis and was positively correlated with sepsis mortality. Genetic deletion of Samsn1 in murine sepsis model improved T cell survival, elevated T cell cytolytic activity, and activated T cell signaling transduction. Concurrently, Samsn1 knockout augmented macrophage proliferation capacity and phagocytic efficiency. In macrophage, SAMSN1 binds to Kelch-like epichlorohydrin-associated protein 1 (KEAP1), causing nuclear factor erythroid 2-related factor 2 (NRF2) to dissociate from the KEAP1-NRF2 complex and translocate into the nucleus. This promotes the transcription of the coinhibitory molecules CD48/CD86/carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1), which bind to their corresponding receptors natural killer cell receptor 2B4/CD152/T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) on the surface of T cells, inducing T-cell exhaustion. CONCLUSIONS:SAMSN1 deletion augmented adaptive T cell immunity and macrophage phagocytic-proliferative dual function. Furthermore, it mediates the KEAP1-NRF2 axis, which affects the expression of coinhibitory molecules on macrophages, leading to T-cell exhaustion. This novel immunosuppression mechanism potentially provides a candidate molecular target for sepsis immunotherapy.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. However, how this dysregulation occurs remains to be elucidated. In this study, we use single-cell RNA sequencing (scRNA-seq) and conventional RNA-seq to analyze the immune landscape of sepsis and observe that adaptive immunity is acutely and strongly suppressed. This systemic immunosuppression occurs not only in the peripheral blood but also in all other immune compartments, including the spleen, lymph nodes, and bone marrow. Clinical data show that these adaptive immunity-related genes may have the potential to be used to distinguish patients with sepsis from those with common infections. CD47 is found to play a pivotal role in this immunosuppression by inducing the production of amyloid-β (Aβ), which interacts with CD74 on B cells, leading to B-cell suppression and subsequent adaptive immunosuppression. Blocking CD47-Aβ signaling significantly reduces organ injury and improves the survival rate of septic mice by restoring phagocytic cell functions and alleviating B-cell suppression and adaptive immunosuppression.

BACKGROUND:Sepsis, a life-threatening condition driven by dysregulated host responses to infection, is associated with long-term cognitive impairments resembling Alzheimer's disease (AD). However, the molecular mechanisms linking sepsis-induced cognitive dysfunction and AD remain unclear. We hypothesized that shared genetic pathways underlie cognitive deficits in both conditions. METHODS:Cecal ligation and puncture (CLP) in C57BL/6 J mice modeled sepsis-induced cognitive decline and amyloid pathology. Brain tissue datasets (GSE33000 for AD; GSE135838 for sepsis) were analyzed via Weighted Gene Co-expression Network Analysis (WGCNA), machine learning, and functional enrichment. Key genes were validated through ROC analysis, immune infiltration profiling, and in vivo/in vitro experiments. RESULTS:Sepsis accelerated cognitive decline and AD-like pathology in mice. Bioinformatics identified CLIC1 and IFITM2 as co-diagnostic genes linked to immune dysregulation in both sepsis and AD. Immune infiltration revealed reduced neutrophils/NK cells, M1 macrophage polarization, and naïve-to-memory B cell shifts in sepsis versus AD. CLIC1 and IFITM2 were upregulated in CLP mice and cytokine-stimulated human cerebral endothelial cells, aligning with bioinformatics predictions. CONCLUSION:CLIC1 and IFITM2, pivotal in immune cell activation, emerged as shared biomarkers of sepsis-related cognitive impairment and AD. These findings highlight immune-driven molecular intersections in cognitive deficits, offering novel targets for mechanistic research and therapeutic development.

Background Sepsis is defined as multi-organ dysfunction caused by dysregulated host response to infection. This dysregulated host response includes enhanced inflammatory responses and suppressed adaptive immunity, but the molecular mechanisms behind it have not yet been elucidated. CD72, a type II transmembrane protein that is primarily expressed in B cells, was found to play an immunomodulatory role in the immune system and was associated with mortality in patients with sepsis. However, whether CD72 affects the pathogenesis of sepsis by influencing the immune response remains unclear. Methods We first collected peripheral blood from 40 healthy volunteers and 57 septic patients and analyzed the mRNA levels of CD72 and the expression of its soluble form sCD72 using Realtime-PCR and ELISA. We then employed the CRISPR/Cas9 system to generate CD72 knockout mice (CD72-KO) and established a cecal ligation and puncture (CLP) model to analyze the effects of CD72 gene deletion on the survival, organ injury and immune response of septic mice by Kaplan-Meier survival analysis, pathological sections and flow cytometry. We also observe the effects of excess sCD72 on survival and immune response in sepsis by injecting recombinant CD72 protein into mice. Finally, the mechanism of sCD72 affecting sepsis immunity was analyzed by fluorescence staining, confocal microscopy and flow cytometry. Results We found that when sepsis occurs, the levels of CD72 mRNA and cell surface CD72 in immune cells decrease, while the level of soluble sCD72 in the blood increases significantly. Excessive sCD72 increased sepsis mortality in a dose-dependent manner, which can bind to CD100 on the surface of T cells and enter the cytoplasm, leading to impaired T cell functions, including a decrease in CD4+IFN-γ+, CD8+Perforin+, CD8+GZMB+, and CD8+FASL+ population and an increase in inflammatory CD4+TNF-α+ population, thereby suppressing adaptive immunity while enhancing inflammatory response. Conclusion The immunosuppression of sepsis has been recognized, but the underlying mechanism has not been fully elucidated. Our study identified for the first time that sCD72 is an important mediator that cause adaptive immunosuppression during sepsis, which leads to T cell suppression by competitively binding to CD100 on the surface of T cells. Our study provides novel insights in our understanding of sepsis-related immunosuppression and may provide translational opportunities for the design of new diagnostic biomarkers and therapeutic targets for sepsis.

The mortality rate of sepsis is approximately 22.5%, accounting for 19.7% of the total global mortality. Since Lewis Thomas proposed in 1972 that "it is our response that makes the disease (sepsis)" rather than the invading microorganisms, numerous drugs have been developed to suppress the "overwhelming" inflammatory response, but none of them has achieved the desired effect. Continued failure has led investigators to question whether deaths in septic patients are indeed caused by uncontrolled inflammation. Here, we review the history of clinical trials based on evolving concepts of sepsis pathogenesis over the past half century, summarize the factors that led to the failure of these historical drugs and the prerequisites for the success of future drugs, and propose the basic principles of preclinical research to ensure successful clinical translation. The strategy of targeting inflammatory factors are like attempting to eliminate invaders by suppressing the host's armed forces, which is logically untenable. Sepsis may not be that complex; rather, sepsis may be the result of a failure to fight microbes when the force of an invading pathogen overwhelms our defenses. Thus, strengthening the body's defense forces instead of suppressing them may be the correct strategy to overcome sepsis.

Immunosuppression has been found to be closely related to the pathogenesis of sepsis, but the underlying mechanisms have not yet been fully elucidated. In this study, we identified that SH3 domain and nuclear localization signals 1 (SAMSN1), a gene encoding a putative adaptor protein, plays an important role in immunosuppression in sepsis. The expression of SAMSN1 was significantly increased in patients with sepsis and was positively correlated with sepsis mortality. When sepsis occurs, the number of monocyte-macrophages increases significantly, among which SAMSN1 is highly expressed. SAMSN1 binds to KEAP1, causing NRF2 to dissociate from the KEAP1- NRF2 complex and translocate into the nucleus, promoting the transcription of co inhibitory molecules CD48/CD86/CEACAM1, which bind to their corresponding receptors 2B4/CTLA4/TIM3 on the surface of T cells, inducing T cell exhaustion. SAMSN1 blockade alleviated organ injuries and improved survival of septic mice. Our study reveals a novel mechanism that triggers immunosuppression in sepsis and may provide a candidate molecular target for sepsis immunotherapy. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by National Key R&D Program of China (2022YFC2504500 to Yan Kang) andby National Natural Science Foundation of China (82172142 to Fei Xiao, 82272199 to Xuelian Liao). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The observational study using human blood samples for RNA-Seq was approved by Ethics Committee on Biomedical Research, West China Hospital of Sichuan University (registered observational trial: ChiCTR2100047060). The informed consent was obtained from all subjects. This trial was examined and cleared by the Medical Ethics Committee under the ethical approval No.2020641. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The RNA-Seq data used to validate the SAMSN1 mRNA levels in Fig. 1c, d have been deposited in the Genome Sequence Archive (Genomics, Proteomics & Bioinformatics 2021) in National Genomics Data Center (Nucleic Acids Res 2022), China National Center for Bioinformation/ Beijing Institute of Genomics, Chinese Academy of Sciences (GSA-Human: HRA002988) that are publicly accessible at https:// ngdc.cncb.ac.cn/gsa-human. The RNA-Seq data of RAW264.7-WT and RAW264.7-KO cells in Fig. 6 have been deposited in the NCBI/SRA repository, accession number GSE262688 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE262688). All experimental data and detailed information about this study should be directed to Prof. Wei Zhang (zhangwei197610@wchscu.edu.cn).

Background Observational studies have suggested an association between multiple sclerosis (MS) and cortical structure, but the results have been inconsistent. Objective We used two-sample Mendelian randomization (MR) to assess the causal relationship between MS and cortical structure. Methods MS data as the exposure trait, including 14,498 cases and 24,091 controls, were obtained from the International Multiple Sclerosis Genetics Consortium. Genome-wide association study (GWAS) data for cortical surface area (SAw/nw) and thickness (THw/nw) in 51,665 individuals of European ancestry were obtained from the ENIGMA Consortium. The inverse-variance weighted (IVW) method was used as the primary analysis for MR. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Enrichment analysis was performed on MR analyses filtered by sensitivity analysis. Results After IVW and sensitivity analysis filtering, only six surviving MR results provided suggestive evidence supporting a causal relationship between MS and cortical structure, including lingual SAw ( p = .0342, beta (se) = 5.7127 (2.6969)), parahippocampal SAw ( p = .0224, beta (se) = 1.5577 (0.6822)), rostral middle frontal SAw ( p = .0154, beta (se) = − 9.0301 (3.7281)), cuneus THw ( p = .0418, beta (se) = − 0.0020 (0.0010)), lateral orbitofrontal THw ( p = .0281, beta (se) = 0.0025 (0.0010)), and lateral orbitofrontal THnw ( p = .0417, beta (se) = 0.0029 (0.0014)). Enrichment analysis suggested that leukocyte cell-related pathways, JAK-STAT signaling pathway, NF-kappa B signaling pathway, cytokine-cytokine receptor interaction, and prolactin signaling pathway may be involved in the effect of MS on cortical morphology. Conclusion Our results provide evidence supporting a causal relationship between MS and cortical structure. Enrichment analysis suggests that the pathways mediating brain morphology abnormalities in MS patients are mainly related to immune and inflammation-driven pathways.

Objective: To validate the accuracy of four early warning scores for early identification of women at risk. Methods: This was a retrospective study of pregnant women admitted in obstetrics Critical Care Unit (ICU). Capacity of the Modified Obstetric Early Warning Score (MOEWS), ICNARC Obstetric Early Warning Score (OEWS), Maternal Early Obstetric Warning System (MEOWS chart), and Maternal Early Warning Trigger (MEWT) were compared in predicting severe maternal morbidity. Area under receiver operator characteristic (AUROC) curve was used to evaluate the predictive performance of scoring system. Results: A total of 352 pregnant women were enrolled and 290 were identified with severe maternal morbidity. MOEWS was more sensitive than MEOWS chart, ICNARC OEWS and MEWT (96.9 % vs. 83.4 %, 66.6 % and 44.8 %). MEWT had the highest specificity (98.4 %), followed by MOEWS (83.9 %), ICNARC OEWS (75.8 %) and MEOWS chart (48.4 %). AUROC of MOEWS, ICNARC OEWS, MEOWS chart, and MEWT for prediction of maternal mortality were 0.91 (95 % CI: 0.874-0.945), 0.765(95 % CI: 0.71-0.82), 0.657(95 % CI: 0.577-0.738), and 0.716 (95 % CI, 0.659-0.773) respectively. MOEWS had the highest AUCs in the discrimination of serious complications in hypertensive disorders, cardiovascular disease, obstetric hemorrhage and infection. For individual vital signs, maximum diastolic blood pressure (DBP), maximum systolic blood pressure (SBP), maximum respiratory rate (RR) and peripheral oxygen saturation (SPO2) demonstrated greater predictive ability. Conclusion: MOEWS is more accurate than ICNARC OEWS, MEOWS chart, and MEWT in predicting the deterioration of women. The prediction ability of DBP, SBP, RR and SPO2 are more reliable.

Background: Immune system dysfunction and blood-brain barrier (BBB) impairment are implicated in multiple sclerosis (MS) risk and severity. However, the causal relationships and potential therapeutic targets remain unclear. Methods: Leveraging the MRC IEU OpenGWAS data infrastructure, we extracted 1254 peripheral immune systems and 792 BBB biomarkers as genetic instruments for exposure. MS risk data from the International Multiple Sclerosis Genetics Consortium (IMSGC) (47,429 MS cases, 68,374 controls) served as one outcome, replicated in FinnGen (1048 cases, 217,141 controls) and the UK Biobank (1679 cases, 461,254 controls). Genetic associations with MS severity derived from IMSGC and MultipleMS Consortium GWAS data (12,584 cases). Two-sample, bidirectional, and protein drug-target MR analyses were conducted, along with interaction analysis of identified proteins and druggability assessment. Results: Causal relationships between 45 immunological markers, 15 BBB markers, and MS risk were strongly supported. In peripheral immunity, the causal associations with MS are predominantly concentrated in CD4+ T cells and CD8+ T cells. Notably, anti-Epstein-Barr virus nuclear antigen (EBNA) IgG levels exhibited the most significant causal effect on MS risk (OR = 225.62, P = 5.63E-208), replicated in the MS severity (OR = 1.11, P = 0.04). Weak causal evidence was found between 62 immunological markers, 35 BBB markers, and MS severity. Reverse MR analysis suggested potential causal effects of MS risk on 8 markers. Drug-targeted MR analysis indicated potential therapeutic benefits in reducing MS risk for CD40 (OR = 0.71, P = 7.24E-13, PPH4 = 97.6 %), AHSG (OR = 0.88, P = 2.91E-05, PPH4 = 94.4 %), and FCRL3 (Sun BB et al.: OR = 0.83, P = 8.93E-09, PPH4 = 94.2 %, Suhre K et al.: OR = 0.88, P = 5.20E-08, PPH4 = 99.2 %). Conclusions: This study provides evidence supporting the causal effects of immune system and BBB dysfunction on MS risk and severity. It emphasizes the significant role of anti-EBNA IgG levels, CD4+ T cells, and CD8+ T cells in MS, and delineates the potential therapeutic benefits of targeting three proteins associated with MS risk: CD40, AHSG, and FCRL3.

BACKGROUND Peripherally inserted central catheters (PICCs) are commonly used in hospitalized patients with liver cancer for the administration of chemotherapy, nutrition, and other medications. However, PICC-related thrombosis is a serious complication that can lead to morbidity and mortality in this patient population. Several risk factors have been identified for the development of PICC-related thrombosis, including cancer type, stage, comorbidities, and catheter characteristics. Understanding these risk factors and developing a predictive model can help healthcare providers identify high-risk patients and implement preventive measures to reduce the incidence of thrombosis. AIM To analyze the influencing factors of PICC-related thrombosis in hospitalized patients with liver cancer, construct a predictive model, and validate it. METHODS Clinical data of hospitalized patients with liver cancer admitted from January 2020 to December 2023 were collected. Thirty-five cases of PICC-related thrombosis in hospitalized patients with liver cancer were collected, and 220 patients who underwent PICC placement during the same period but did not develop PICC-related thrombosis were randomly selected as controls. A total of 255 samples were collected and used as the training set, and 77 cases were collected as the validation set in a 7:3 ratio. General patient information, case data, catheterization data, coagulation indicators, and Autar Thrombosis Risk Assessment Scale scores were analyzed. Univariate and multivariate unconditional logistic regression analyses were performed on relevant factors, and the value of combined indicators in predicting PICC-related thrombosis in hospitalized patients with liver cancer was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS Univariate analysis showed statistically significant differences (P < 0.05) in age, sex, Karnofsky performance status score (KPS), bedridden time, activities of daily living impairment, parenteral nutrition, catheter duration, distant metastasis, and bone marrow suppression between the thrombosis group and the non-thrombosis group. Other aspects had no statistically significant differences (P > 0.05). Multivariate regression analysis showed that age ≥ 60 years, KPS score ≤ 50 points, parenteral nutrition, stage III to IV, distant metastasis, bone marrow suppression, and activities of daily living impairment were independent risk factors for PICC-related thrombosis in hospitalized patients with liver cancer (P < 0.05). Catheter duration of 1-6 months and catheter duration > 6 months were protective factors for PICC-related thrombosis (P < 0.05). The predictive model for PICC-related thrombosis was obtained as follows: P predictive probability = [exp (Logit P )]/[1 + exp (Logit P )], where Logit P = age × 1.907 + KPS score × 2.045 + parenteral nutrition × 9.467 + catheter duration × 0.506 + tumor-node-metastasis (TNM) staging × 2.844 + distant metastasis × 2.065 + bone marrow suppression × 2.082 + activities of daily living impairment × 13.926. ROC curve analysis showed an area under the curve (AUC) of 0.827 (95%CI: 0.724-0.929, P < 0.001), with a corresponding optimal cut-off value of 0.612, sensitivity of 0.755, and specificity of 0.857. Calibration curve analysis showed good consistency between the predicted occurrence of PICC-related thrombosis and actual occurrence (P > 0.05). ROC analysis showed AUCs of 0.888 and 0.729 for the training and validation sets, respectively. CONCLUSION Age, KPS score, parenteral nutrition, TNM staging, distant metastasis, bone marrow suppression, and activities of daily living impairment are independent risk factors for PICC-related thrombosis in hospitalized patients with liver cancer, while catheter duration is a protective factor for the disease. The predictive model has an AUC of 0.827, indicating high predictive accuracy and clinical value.

Aquaporin 4-immunoglobulin G (AQP4-IgG) specifically targets aquaporin 4 in approximately 80

Abstract Background Peripheral glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are sensitive markers of neuroinflammation and neuronal damage. Previous studies with highly selected participants have shown that peripheral GFAP and NfL levels are elevated in the pre-clinical phase of Alzheimer’s disease (AD) and dementia. However, the predictive value of GFAP and NfL for dementia requires more evidence from population-based cohorts. Methods This was a prospective cohort study to evaluate UK Biobank participants enrolled from 2006 to 2010 using plasma GFAP and NfL measurements measured by Olink Target Platform and prospectively followed up for dementia diagnosis. Primary outcome was the risk of clinical diagnosed dementia. Secondary outcomes were cognition. Linear regression was used to assess the associations between peripheral GFAP and NfL with cognition. Cox proportional hazard models with cross-validations were used to estimate associations between elevated GFAP and NfL with risk of dementia. All models were adjusted for covariates. Results A subsample of 48,542 participants in the UK Biobank with peripheral GFAP and NfL measurements were evaluated. With an average follow-up of 13.18 ± 2.42 years, 1312 new all-cause dementia cases were identified. Peripheral GFAP and NfL increased up to 15 years before dementia diagnosis was made. After strictly adjusting for confounders, increment in NfL was found to be associated with decreased numeric memory and prolonged reaction time. A greater annualized rate of change in GFAP was significantly associated with faster global cognitive decline. Elevation of GFAP (hazard ratio (HR) ranges from 2.25 to 3.15) and NfL (HR ranges from 1.98 to 4.23) increased the risk for several types of dementia. GFAP and NfL significantly improved the predictive values for dementia using previous models (area under the curve (AUC) ranges from 0.80 to 0.89, C-index ranges from 0.86 to 0.91). The AD genetic risk score and number of APOE*E4 alleles strongly correlated with GFAP and NfL levels. Conclusions These results suggest that peripheral GFAP and NfL are potential biomarkers for the early diagnosis of dementia. In addition, anti-inflammatory therapies in the initial stages of dementia may have potential benefits.

AbstractBackgroundGut microbiota alterations in multiple sclerosis (MS) patients have been reported in observational studies, but whether these associations are causal is unclear.ObjectiveWe performed a Mendelian randomization study (MR) to assess the causal effects of gut microbiota on MS.MethodsIndependent genetic variants associated with 211 gut microbiota phenotypes were selected as instrumental variables from the largest genome‐wide association studies (GWAS) previously published by the MiBioGen study. GWAS data for MS were obtained from the International Multiple Sclerosis Genetics Consortium (IMSGC) for primary analysis and the FinnGen consortium for replication and collaborative analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy.ResultsAfter inverse‐variance‐weighted and sensitivity analysis filtering, seven gut microbiota with potential causal effects on MS were identified from the IMSGC. Only five metabolites remained significant associations with MS when combined with the FinnGen consortium, including genus Anaerofilum id.2053 (odds ratio [OR] = 1.141, 95% confidence interval [CI]: 1.021–1.276, p = .021), Ruminococcus2 id.11374 (OR = 1.190, 95% CI: 1.007–1.406, p = .042), Ruminococcaceae UCG003 id.11361 (OR = 0.822, 95% CI: 0.688–0.982, p = .031), Ruminiclostridium5 id.11355 (OR = 0.724, 95% CI: 0.585–0.895, p = .003), Anaerotruncus id.2054 (OR = 0.772, 95% CI: 0.634–0.940, p = .010).ConclusionOur MR analysis reveals a potential causal relationship between gut microbiota and MS, offering promising avenues for advancing mechanistic understanding and clinical investigation of microbiota‐mediated MS.