Analysis of Associated Factors, Construction, and Application of a Predictive Model for Lymph Node Metastasis in Colorectal Cancer.

Background: In colorectal cancer (CRC) , understanding lymph node metastasis (LNM) is critical for effective treatment. Better approaches are required for identifying and assessing the risk contributions of factors influencing lymph node metastasis in colorectal cancer. Objective: This study aims to analyze factors associated with LNM in CRC and develop a risk prediction model. Methods: A retrospective cohort study was conducted and a total of 181 CRC patients admitted between March 2020 and April 2023 were selected as research participants. Among them, 47 patients developed LNM, while the remaining 134 did not. Clinical data, including age, sex, pathological stages, were collected. Logistic regression was employed to identify factors influencing LNM in CRC, forming the basis for constructing a risk model. The diagnostic efficiency of this model was assessed through receiver operating characteristic (ROC) curves. Results: Tumor nodules and histological types showed no correlation with LNM in CRC (P > .05). However, pathological staging, vascular and neural invasion, use of VEGF inhibitors, and preoperative CEA were identified as independent risk factors for LNM in CRC (P < .05). The established model demonstrated a good fit with the observations. ROC curve analysis indicated an area under the curve (AUC) of 0.884 for predicting LNM in CRC, signifying excellent predictive performance. Conclusions: The risk model, formulated on factors associated with LNM in CRC, serves as a efficient tool in assessing the probability of LNM. It provides invaluable insights that can significantly enhance clinical approaches to the diagnosis and treatment of CRC in the future.

Prognostic modeling for nasopharyngeal carcinoma (NC) undergoing concurrent chemoradiotherapy using clinical and enhanced MRI-Delta radiomics data: A preliminary study.

BACKGROUND: Nasopharyngeal carcinoma (NC) is one of the prevalent malignancies of the head and neck region with poor prognosis. OBJECTIVE: The aim of this study is to establish a predictive model for assessing NC prognosis based on clinical and MR radiomics data, subsequently to develop a nomogram for practical application. METHODS: Retrospective analysis was conducted on clinical and imaging data collected between May 2010 and August 2018, involving 211 patients diagnosed with histologically confirmed NC who received concurrent chemoradiotherapy or radical surgery in Xiangyang No. 1 People's Hospital. According to 5-10 years of follow-up results, the patients were divided into two groups: the study group (n= 76), which experienced recurrence, metastasis, or death, and the control group (n= 135), characterized by normal survival. Training and testing subsets were established at a 7:3 ratio, with a predefined time cutoff. In the training set, three prediction models were established: a clinical data model, an imaging model, and a combined model using the integrated variation in clinical characteristics along with MR radiomics parameters (Delta-Radscore) observed before and after concurrent chemoradiotherapy. Model performance was compared using Delong's test, and net clinical benefit was assessed via decision curve analysis (DCA). Then, external validation was conducted on the test set, and finally a nomogram predicting NC prognosis was created. RESULTS: Univariate analysis identified that the risk factors impacting the prognosis of NC included gender, pathological type, neutrophil to lymphocyte ratio (NLR), degree of tumor differentiation, MR enhancement pattern, and Delta-Radscore (P< 0.05). The combined model established based on the abovementioned factors exhibited significantly higher predictive performance [AUC: 0.874, 95% CI (0.810-0.923)] than that of the clinical data model [AUC: 0.650, 95% CI (0.568-0.727)] and imaging model [AUC: 0.824, 95% CI (0.753-0.882)]. DCA also demonstrated superior clinical net benefit in the combined model, a finding further verified by results from the test set. The developed nomogram, based on the combined model, exhibited promising performance in clinical applications. CONCLUSION: The Delta-Radscore derived from MR radiomics data before and after concurrent chemoradiotherapy helps enhance the performance of the NC prognostic model. The combined model and resultant nomogram provide valuable support for clinical decision-making in NC treatment, ultimately contributing to an improved survival rate.

CXCR5+TIM-3-PD-1+ stem-like cytotoxic CD8+ T cells: elevated in chronic rhinosinusitis and associated with disease severity.

Background: Chronic rhinosinusitis (CRS) is a chronic inflammatory disease with an autoimmune background. Altered expression levels of T cell immunoglobulin and mucin-domain containing-3 (TIM-3), C-X-C chemokine receptor type 5 (CXCR5), and programmed cell death protein 1 (PD-1) are implicated in the progression of inflammatory and autoimmune diseases. Moreover, CXCR5+TIM-3-PD-1+ stem-like cytotoxic T cells function as memory stem cells during chronic disease processes and retain cytotoxicity-related gene networks. Objectives: To explore the expressions of CXCR5, TIM-3, and PD-1 on T cells and their correlation with clinical parameters in CRS. Methods: Flow cytometry was used to assess the expressions and co-expressions of CXCR5, TIM-3, and PD-1 on T cells in the tissues of the paranasal sinus and peripheral blood of patients with CRS as well as healthy controls. Immunofluorescence was used to assess the co-localization of TIM-3, CXCR5, and PD-1 with T cells. The disease severity of our patients with CRS was evaluated using the Lund-Mackay score. A complete blood count was also performed for the patients with CRS. Results: Expression levels of CXCR5 and PD-1 on T cells were significantly increased in the nasal tissues of patients with CRS. Compared with those in healthy controls, patients with CRS had high percentages of CXCR5+TIM-3-PD-1+ CD8+ and CD4+ T cells in nasal tissues, while no significant difference was observed in peripheral blood levels. Patients with CRS had a higher density of nasal CXCR5+TIM-3-PD-1+ T cells than that in healthy controls. CXCR5+TIM-3-PD-1+ CD8+ T cell levels in the nasal polyps of patients with CRS were negatively correlated with the patients' Lund-Mackay scores. The levels of CXCR5+TIM-3-PD-1+ T cells in nasal tissues were also negatively associated with disease duration and positively associated with the chronic inflammatory state of CRS. Conclusions: The level of CXCR5+TIM-3-PD-1+ stem cell-like T cells, especially CXCR5+TIM-3-PD-1+ CD8+ T cells, is increased in CRS. Therefore, inducing CXCR5+TIM-3-PD-1+ T cell exhaustion may be an effective immunotherapy for CRS.

Downregulation of lncRNA CDKN2B-AS1 attenuates inflammatory response in mice with allergic rhinitis by regulating miR-98-5p/SOCS1 axis.

Long non-coding RNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) in various diseases has been verified. However, the underlying mechanism of CDKN2B-AS1 contributes to the development of allergic rhinitis (AR) remains unknown. To evaluate the impact of CDKN2B-AS1 on AR, BALB/c mice were sensitized by intraperitoneal injection of normal saline containing ovalbumin (OVA) and calmogastrin to establish an AR model. Nasal rubbing and sneezing were documented after the final OVA treatment. The concentrations of IgE, IgG1, and inflammatory elements were quantified using ELISA. Hematoxylin and eosin (H&E) staining and immunofluorescence were used to assess histopathological variations and tryptase expression, respectively. StarBase, TargetScan and luciferase reporter assays were applied to predict and confirm the interactions among CDKN2B-AS1, miR-98-5p, and SOCS1. CDKN2B-AS1, miR-98-5p, and SOCS1 levels were assessed by quantitative real-time PCR (qRT-PCR) or western blotting. Our results revealed that CDKN2B-AS1 was obviously over-expressed in the nasal mucosa of AR patients and AR mice. Down-regulation of CDKN2B-AS1 significantly decreased nasal rubbing and sneezing frequencies, IgE and IgG1 concentrations, and cytokine levels. Furthermore, down-regulation of CDKN2B-AS1 also relieved the pathological changes in the nasal mucosa, and the infiltration of eosinophils and mast cells. Importantly, these results were reversed by the miR-98-5p inhibitor, whereas miR-98-5p directly targeted CDKN2B-AS1, and miR-98-5p negatively regulated SOCS1 level. Our findings demonstrate that down-regulation of CDKN2B-AS1 improves allergic inflammation and symptoms in a murine model of AR through the miR-98-5p/SOCS1 axis, which provides new insights into the latent functions of CDKN2B-AS1 in AR treatment.

BmPGPR-L4 is a negative regulator of the humoral immune response in the silkworm Bombyx mori.

Toll, immune deficiency and prophenoloxidase cascade represent vital immune signaling pathways in insects. Peptidoglycan recognition proteins (PGRPs) are innate immune receptors that activate and regulate the immune signaling pathways. Previously, we reported that BmPGPR-L4 was induced in the silkworm Bombyx mori larvae by bacteria and peptidoglycan challenges. Here, we focused on the function of BmPGRP-L4 in regulating the expression of antimicrobial peptides (AMPs). The hemolymph from BmPGRP-L4-silenced larvae exhibited an enhanced inhibitory effect on the growth of Escherichia coli, either by growth curve or inhibitory zone experiments. Coincidentally, most of the AMP genes were upregulated after RNAi of BmPGRP-L4. Oral administration of heat-inactivated E. coli and Staphylococcus aureus after RNAi of BmPGRP-L4 resulted in the increased expression of BmPGRP-L4 in different tissues of the silkworm larvae, revealing an auto-regulatory mechanism. By contrast, the expression of most AMP genes was downregulated by oral bacterial administration after RNAi of BmPGRP-L4. The above results demonstrate that BmPGRP-L4 recognizes bacterial pathogen-associated molecular patterns and negatively regulates AMP expression to achieve immunological homeostasis. As a negative regulator, BmPGPR-L4 is proposed to be involved in the feedback regulation of the immune signaling pathways of the silkworm to prevent excessive activation of the immune response.

Visual and bibliometric analysis of chronic rhinosinusitis and nasal polyps.

Background: Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by persistent sinonasal inflammation and sinus microbiome dysbiosis. Nasal polyps (NPs) are one of the main manifestations that cause diverse clinical symptoms of CRS. Objective: We sought to conduct a bibliometric and visual analysis of articles on CRS and NPs published between 2003 and 2022 to provide researchers with the current state of research and potential directions. Methods: We searched relevant articles from 2003 to 2022 in the Web of Science database. VOSviewer and the Bibliometrix R package were used to perform the bibliometric analysis. Results: A total of 3907 publications were retrieved. The United States made the highest contributions to global research, followed by China. Northwestern University had the most publications. The most published author was C. Bachert, followed by R. P. Schleimer and R. J. Schlosser. The authors with the most co-citations were C. Bachert, W. J. Fokkens, and P. Gevaert. Moreover, the journal with the most publications was the International Forum of Allergy & Rhinology, and the Journal of Allergy and Clinical Immunology was the most cited. "Covid-19," "biologics," and "type 2 inflammation" were the top current research hotspots. Conclusions: The United States and Northwestern University were the leading country and institution in researching CRS and NPs. C. Bachert was the most influential expert. The International Forum of Allergy & Rhinology and the Journal of Allergy and Clinical Immunology were leading journals. "Covid-19," "biologics," and "type 2 inflammation" were the trending topics.

Assessment of serum soluble CD40 ligand levels in patients with chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a disease highly associated with abnormal regulation of T and B cells. The underlying pathophysiology of inflammatory pathways has critical implications for the diagnosis and management of CRS. Soluble CD40-ligand (sCD40L) is a cleaved form of CD40L present in plasma which functions the same way as CD40L, which has been observed as an inflammatory biomarker in many diseases. CD40L-positive cells control B-cell maturation, proliferation, apoptosis, and antibody production by binding to its receptor CD40 on B-cells. And our results show for the first time that patients with CRS have lower serum sCD40L levels compared to healthy subjects and that decreased sCD40L levels in patients correlate with increased CD40L-positive cell counts in the sinonasal mucosa. In addition, eosinophilic chronic rhinosinusitis (eCRS) patients tend to exhibit more CD40L-positive cells in the sinonasal mucosa compared to non-eCRS patients. This supports the notion that local blockade of CD40/CD40L may suppress pathogenic T/B cell responses and reduce tissue inflammation. Significantly, sCD40L and CD40L may be involved in the development and progression of CRS by impairing peripheral blood B-cell function and enhancing the local inflammatory response in the sinonasal mucosa.

[Advances in next-generation sequencing technology to analyze the microbiome of patients with chronic sinusitis].

Chronic rhinosinusitis （CRS） is a chronic inflammatory disease of the sinus mucosa, and the pathogenesis of CRS has not been fully elucidated, and the impact of dysbiosis of the microbiome in the nasal cavity and even in the gut on the pathogenesis of CRS remains controversial. Next-generation sequencing technology, a culture-independent high-throughput sequencing method, contributes to a comprehensive understanding of the CRS microbiome. This article reviews the progress of research on the relevance of bacteria and other microorganisms to CRS and the microbial characteristics of the sinus and intestinal tract of patients with CRS, introduces next-generation sequencing technologies for the study of the CRS microbiome, and discusses the therapeutic prospects of CRS and the possibility of probiotic therapy.

LDLa containing C-type lectin mediates phagocytosis of V.anguillarum and regulates immune effector genes in shrimp.

C-type lectins (CTLs) function as pattern recognition receptors (PRRs) by recognizing invading microorganisms, thereby triggering downstream immune events against infected pathogens. In this study, a novel CTL containing a low-density lipoprotein receptor class A (LDLa) domain was obtained from Litopenaeus vannamei, designed as LvLDLalec. Stimulation by the bacterial pathogen Vibrio anguillarum (V. anguillarum) resulted in remarkable up-regulation of LvLDLalec, as well as release of LvLDLalec into hemolymph. The rLvLDLalec protein possessed broad-spectrum bacterial binding and agglutinating activities, as well as hemocyte attachment ability. Importantly, LvLDLalec facilitated the bacterial clearance in shrimp hemolymph and protected shrimp from bacterial infection. Further studies revealed that LvLDLalec promoted hemocytes phagocytosis against V. anguillarum and lysosomes were involved in the process. Meanwhile, LvLDLalec participated in humoral immunity through activating and inducing nuclear translocation of Dorsal to regulate phagocytosis-related genes and antimicrobial peptides (AMPs) genes, thereby accelerated the removal of invading pathogens in vivo and improved the survival rate of L. vannamei. These results unveil that LvLDLalec serves as a PRR participate in cellular and humoral immunity exerting opsonin activity to play vital roles in the immune regulatory system of L. vannamei.

A clinical predictive model for pre-transplantation Klebsiella pneumoniae colonization and relevance for clinical outcomes in patients receiving allogeneic hematopoietic stem cell transplantation.

The purpose of this study is to establish a clinical prediction model to discriminate patients at high risk of Klebsiella pneumoniae (KP) colonization before allogeneic hematopoietic stem cell transplantation (allo-HSCT) and evaluate the impact of KP colonization on clinical outcomes after allo-HSCT. We retrospectively collected data from 2,157 consecutive patients receiving allo-HSCT between January 2018 and March 2022. KP colonization was defined as a positive test for KP from a pharyngeal or anal swab before allo-HSCT. Logistic regression was used to build a clinical prediction model. Cox regression analyses were performed to explore the effect of KP colonization on clinical outcomes. Among all the inpatients, 166 patients had KP colonization and 581 with no positive pathogenic finding before transplantation. Seven candidate predictors were entered into the final prediction model. The prediction model had an area under the curve of 0.775 (95% CI 0.723-0.828) in the derivation cohort and 0.846 (95% CI: 0.790-0.902) in the validation cohort. Statistically significantly different incidence rates were observed among patient groups with clinically predicted low, medium, and high risk for KP infection (P < 0.001). The presence of KP colonization delayed platelet engraftment (P < 0.001) and patients with KP colonization were more likely to develop KP bloodstream infections within 100 days after allo-HSCT (P < 0.0001). Patients with KP colonization had higher non-relapse mortality (P = 0.032), worse progression-free survival (P = 0.0027), and worse overall survival within 100 days after allo-HSCT (P = 0.013). Our findings suggest that increased awareness of risks associated with pre-transplantation bacterial colonization is warranted.IMPORTANCESeveral studies have identified that Klebsiella pneumoniae (KP) is among the most common and deadly pathogens for patients in hospital intensive care units and those receiving transplantation. However, there are currently no studies that evaluate the impact of KP colonization to patients undergoing allogeneic hematopoietic stem cell transplantation. Our results confirm that pre-existing KP colonization is relatively common in a hematology transplant ward setting and negatively affects post-transplantation prognosis. Our clinical prediction model for KP colonization can support early intervention in patients at high risk to avoid subsequent bloodstream infections and improve survival outcomes. Altogether, our data suggest that increased awareness of risks associated with pre-transplantation bacterial colonization is warranted. Future studies are needed to confirm these findings and to test early intervention strategies for patients at risk of complications from KP infection.

The protein kinase A signaling pathway mediates the effect of electroacupuncture on excessive contraction of the bladder detrusor in a rat model of neurogenic bladder.

BACKGROUND: Neurogenic bladder (NB) is a form of neurological bladder dysfunction characterized by excessive contraction of the bladder detrusor. Protein kinase A (PKA) signaling is involved in the contraction of the detrusor muscle. AIMS: To investigate whether PKA signaling mediates the effect of electroacupuncture (EA) on the excessive contraction of the bladder detrusor in NB. METHODS: Sixty rats were randomly divided into control, sham, NB, NB + EA, and NB + EA + H89 (a PKA receptor antagonist) groups. The modified Hassan Shaker spinal cord transection method was used to generate a NB model. After EA intervention for one week, urodynamic tests were used to evaluate bladder function, hematoxylin and eosin staining was conducted to assess morphological changes, enzyme-linked immunosorbent assay (ELISA) was performed to measure the concentration of PKA, and Western blotting was conducted to measure the protein levels of phosphorylated myosin light chain kinase (p-MLCK)/p-MLC. RESULTS: The results showed that NB resulted in morphological disruption, impairment of urodynamics, and decreases in the concentration of PKA and the protein levels of p-MLCK/p-MLC. EA reversed the changes induced by NB dysfunction. However, the improvement in urodynamics and the increases in the concentration of PKA and the protein levels of p-MLCK/p-MLC were inhibited by H89. CONCLUSION: Our findings indicate that the PKA signaling pathway mediates the beneficial effect of EA on excessive contraction of the bladder detrusor in a rat model of NB.

Overexpressed Gαi1 exerts pro-tumorigenic activity in nasopharyngeal carcinoma.

The current study tested the expression and potential functions of Gαi1 in nasopharyngeal carcinoma (NPC). The Cancer Genome Atlas (TCGA) database results demonstrate that Gαi1 transcripts' number in NPC tissues is significantly higher than that in the normal nasal epithelial tissues. Its overexpression correlates with poor survival in certain NPC patients. Moreover, Gαi1 is significantly upregulated in NPC tissues of local primary patients and in different primary human NPC cells. Whereas its expression is relatively low in cancer-surrounding normal tissues and in primary nasal epithelial cells. Genetic silencing (via shRNA strategy) or knockout (via CRISPR-sgRNA method) of Gαi1 substantially suppressed viability, proliferation, cell cycle progression, and migration in primary NPC cells, causing significant caspase-apoptosis activation. Contrarily, ectopic Gαi1 expression exerted pro-tumorigenic activity and strengthened cell proliferation and migration in primary NPC cells. Gαi1 is important for Akt-mTOR activation in NPC cells. Akt-S6K phosphorylation was downregulated after Gαi1 shRNA or KO in primary NPC cells, but strengthened following Gαi1 overexpression. In Gαi1-silenced primary NPC cells, a S473D constitutively-active mutant Akt1 (caAkt1) restored Akt-S6K phosphorylation and ameliorated Gαi1 shRNA-induced proliferation inhibition, migration reduction and apoptosis. Bioinformatics analyses proposed zinc finger protein 384 (ZNF384) as a potential transcription factor of Gαi1. In primary NPC cells, ZNF384 shRNA or knockout (via CRISPR-sgRNA method) decreased Gαi1 mRNA and protein expression, whereas ZNF384 overexpression upregulated it. Importantly, there was an increased binding between ZNF384 protein and the Gαi1 promoter in human NPC tissues and different NPC cells. In vivo studies showed that intratumoral injection of Gαi1-shRNA-expressing adeno-associated virus (AAV) impeded subcutaneous NPC xenograft growth in nude mice. Gαi1 downregulation, Akt-mTOR inactivation, and apoptosis induction were detected in Gαi1-silenced NPC xenograft tissues. Gαi1 KO also effectively inhibited the growth of NPC xenografts in nude mice. Together, overexpressed Gαi1 exerts pro-tumorigenic activity in NPC possibly by promoting Akt-mTOR activation.

The maize ATP-binding cassette (ABC) transporter ZmMRPA6 confers cold and salt stress tolerance in plants.

KEY MESSAGE: ZmMRPA6 was cloned and characterized as the first ATP-binding cassette (ABC) transporter in maize to be proven to participate in cold and salt tolerance. Homologous genes AtABCC4 and AtABCC14 of ZmMRPA6 also responded to salt stress. ATP-binding cassette (ABC) proteins are major transmembrane transporters that play significant roles in plant development against various abiotic stresses. However, available information regarding stress-related ABC genes in maize is minimal. In this study, a maize ABC transporter gene, ZmMRPA6, was identified through genome-wide association analysis (GWAS) for cold tolerance in maize seeds germination and functionally characterized. During germination and seedling stages, the zmmrpa6 mutant exhibited enhanced resistance to cold or salt stress. Mutated of ZmMRPA6 did not affect the expression of downstream response genes related cold or salt response at the transcriptional level. Mass spectrometry analysis revealed that most of the differential proteins between zmmrpa6 and wild-type plants were involved in response to stress process including oxidative reduction, hydrolase activity, small molecule metabolism, and photosynthesis process. Meanwhile, the plants which lack the ZmMRPA6 homologous genes AtABCC4 or AtABCC14 were sensitive to salt stress in Arabidopsis. These results indicated that ZmMRPA6 and its homologous genes play a conserved role in cold and salt stress, and functional differentiation occurs in monocotyledonous and dicotyledonous plants. In summary, these findings dramatically improved our understanding of the function of ABC transporters resistance to abiotic stresses in plants.

Oil candidate genes in seeds of cotton (Gossypium hirsutum L.) and functional validation of GhPXN1.

BACKGROUND: Cottonseed oil is a promising edible plant oil with abundant unsaturated fatty acids. However, few studies have been conducted to explore the characteristics of cottonseed oil. The molecular mechanism of cottonseed oil accumulation remains unclear. RESULTS: In the present study, we conducted comparative transcriptome and weighted gene co-expression network (WGCNA) analysis for two G. hirsutum materials with significant difference in cottonseed oil content. Results showed that, between the high oil genotype 6053 (H6053) and the low oil genotype 2052 (L2052), a total of 412, 507, 1,121, 1,953, and 2,019 differentially expressed genes (DEGs) were detected at 10, 15, 20, 25, and 30 DPA, respectively. Remarkably, a large number of the down-regulated DEGs were enriched in the phenylalanine metabolic processes. Investigation into the dynamic changes of expression profiling of genes associated with both phenylalanine metabolism and oil biosynthesis has shed light on a significant competitive relationship in substrate allocation during cottonseed development. Additionally, the WGCNA analysis of all DEGs identified eight distinct modules, one of which includes GhPXN1, a gene closely associated with oil accumulation. Through phylogenetic analysis, we hypothesized that GhPXN1 in G. hirsutum might have been introgressed from G. arboreum. Overexpression of the GhPXN1 gene in tobacco leaf suggested a significant reduction in oil content compared to the empty-vector transformants. Furthermore, ten other crucial oil candidate genes identified in this study were also validated using quantitative real-time PCR (qRT-PCR). CONCLUSIONS: Overall, this study enhances our comprehension of the molecular mechanisms underlying cottonseed oil accumulation.

Interpreting High-Dimensional Projections With Capacity.

Dimensionality reduction (DR) algorithms are diverse and widely used for analyzing high-dimensional data. Various metrics and tools have been proposed to evaluate and interpret the DR results. However, most metrics and methods fail to be well generalized to measure any DR results from the perspective of original distribution fidelity or lack interactive exploration of DR results. There is still a need for more intuitive and quantitative analysis to interactively explore high-dimensional data and improve interpretability. We propose a metric and a generalized algorithm-agnostic approach based on the concept of capacity to evaluate and analyze the DR results. Based on our approach, we develop a visual analytic system HiLow for exploring high-dimensional data and projections. We also propose a mixed-initiative recommendation algorithm that assists users in interactively DR results manipulation. Users can compare the differences in data distribution after the interaction through HiLow. Furthermore, we propose a novel visualization design focusing on quantitative analysis of differences between high and low-dimensional data distributions. Finally, through user study and case studies, we validate the effectiveness of our approach and system in enhancing the interpretability of projections and analyzing the distribution of high and low-dimensional data.

Risk Factors for Carbapenem-Resistant Enterobacteriaceae Colonization and the Effect on Clinical Outcomes and Prognosis in Allogeneic Hematopoietic Stem Cell Transplanted Patients.

Purpose: The current study assesses which are the main risk factors, clinical outcome and prognosis following the colonization of CRE in patients that underwent allo-HSCT. Patients and Methods: A total of 343 patients subjected to allo-HSCT in the period comprised between June 2021 and June 2022 were enrolled in this retrospective study. The CRE colonization was diagnosed by clinical history and routine microbial culture of perirectal swab. In this regard, a clinical prediction model was designed based on independent risk factors underlying the pre-transplantation CRE colonization using a backward stepwise logistic regression, followed by the evaluation of its discrimination and calibration efficacies, along with clinical usefulness. Furthermore, univariate and multivariate Cox regression analyses were then conducted to assess the risk factors for post-transplantation clinical outcomes. Results: Out of 343 patients enrolled in this study, 135 (39.3%) reported CRE colonization. The independent risk factor variables for CRE colonization were incorporated into the nomogram to build a prediction model, which showed an area under the curve of 0.767 (95% CI: 0.716-0.818), and well-fitted calibration curves (χ2 = 1.737, P = 0.9788). The patients with CRE colonization reported a significantly lower platelet engraftment rate with a higher risk of post-transplantation BSI when compared with the non-CRE colonization group (P = 0.02 and P < 0.001; respectively). The non-relapse mortality (NRM) value was higher in the CRE patients (P < 0.05), consistently with a survival probability that was thus significantly lower for the same timeframe (P < 0.05). Conclusion: A reliable clinical prediction model for pre-transplantation CRE colonization was developed that demonstrated that the CRE colonization negatively affects platelet engraftment and survival outcomes following allo-HSCT.

FAM134B-induced endoplasmic reticulum (ER)-phagy exacerbates cisplatin-insulted hair cell apoptosis ：Possible relation to excessive ER stress.

AIMS: FAM134B, the initial endoplasmic reticulum (ER)-phagy receptor identified, facilitates ER-phagy during ER stress. The malfunction of FAM134B has been demonstrated to have a crucial role in the pathological mechanisms of diverse human ailments. However, the role of FAM134B-mediated ER-phagy in ototoxicity, particularly in cisplatin-induced ototoxicity, remains unclear. The present study endeavors to investigate whether FAM134B is expressed in House Ear Institute-Organ of Corti 1 (HEI-OC1) and C57BL/6 murine cochlear hair cells (HCs), and to explore its potential function in cisplatin-mediated ototoxicity, with the aim of discovering new insights that can mitigate or forestall the irreversible adverse effect of cisplatin. METHODS: Immunofluorescence (IF) staining was used to test the expression pattern of FAM134B, levels of C/EBP-homologous protein (CHOP), autophagy, and co-localization ratio of lysosomes and ER. Western blotting was employed to measure changes in expression levels of FAM134B, LC3B, ER stress-related proteins, LAMP1 and apoptotic mediators. Cell apoptosis was examined using transferase dUTP nick end labeling (TUNEL) assay and flow cytometry. RESULTS: In the present investigation, it was observed that FAM134B exhibited a diffuse expression pattern in the cytoplasm and nuclei of control HEI-OC1 cells. Following cisplatin administration, FAM134B was found to accumulate and form distinct dots around the nuclei, concomitant with increased levels of ER-phagy, ER stress, unfolded protein response (UPR), and cell apoptosis. Additionally, knockdown of FAM134B resulted in reduced ER-phagy, mitigated ER stress and UPR, and decreased apoptotic activity in HEI-OC1 cells following cisplatin exposure. CONCLUSIONS: Collectively, the findings of this study demonstrate that FAM134B-mediated ER-phagy enhances the susceptibility of HCs to ER stress and apoptosis in response to cisplatin-induced stress. This suggests a sequential progression of ER-phagy, ER stress and apoptosis following cisplatin stimulus, and implies the potential therapeutic benefit of inhibiting of FAM134B-mediated ER-phagy in the prevention of cisplatin-related ototoxicity.

Role of stem cell-like memory T cells in autoimmune diseases. / å¹²ç»†èƒžæ ·è®°å¿†Tç»†èƒžåœ¨è‡ªèº«å ç–«æ€§ç–¾ç— ä¸­çš„ä½œç”¨.

Stem cell-like memory T (TSCM) cell is a memory T cell subset with characteristics of long life span, consistent self-renewing, and the multipotent capacity to reconstitute the memory and effector T cell subsets. TSCM cell is the least differentiated cell in the memory T lymphocyte system, endowed with the stem cell-like ability, and it is essential for maintaining functional immunity. In addition, owing to its robust potential for immune reconstitution, it is central player in many physiological and pathological human processes. TSCM cell plays an important role in the occurrence and development of various autoimmune diseases. The specific role of TSCM cell in autoimmune diseases may make it a potential target for the treatment of multiple autoimmune diseases, driving effective immune reconstitution in therapy.

Frequency detection, frequency discrimination, and spectro-temporal pattern perception in older and younger typically hearing adults.

Elderly adults often experience difficulties in speech understanding, possibly due to age-related deficits in frequency perception. It is unclear whether age-related deficits in frequency perception differ between the apical or basal regions of the cochlea. It is also unclear how aging might differently affect frequency discrimination or detection of a change in frequency within a stimulus. In the present study, pure-tone frequency thresholds were measured in 19 older (61-74 years) and 20 younger (22-28 years) typically hearing adults. Participants were asked to discriminate between reference and probe frequencies or to detect changes in frequency within a probe stimulus. Broadband spectro-temporal pattern perception was also measured using the spectro-temporal modulated ripple test (SMRT). Frequency thresholds were significantly poorer in the basal than in the apical region of the cochlea; the deficit in the basal region was 2 times larger for the older than for the younger group. Frequency thresholds were significantly poorer in the older group, especially in the basal region where frequency detection thresholds were 3.9 times poorer for the older than for the younger group. SMRT thresholds were 1.5 times better for the younger than for the older group. Significant age effects were observed for SMRT thresholds and for frequency thresholds only in the basal region. SMRT thresholds were significantly correlated with frequency thresholds only in the older group. The poorer frequency and spectro-temporal pattern perception may contribute to age-related deficits in speech perception, even when audiometric thresholds are nearly normal.