Prognostic nutritional index (PNI) has been widely investigated as a predictor of outcomes in patients with cancer; however, a comprehensive synthesis evaluating the breadth, methodological quality, and certainty of this evidence is lacking. We aimed to systematically review and critically appraise existing meta-analyses on the association between PNI and cancer prognostic outcomes. We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews from database inception through 28 February, 2025. Methodological quality of included systematic reviews and meta-analyses was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and the certainty of evidence was graded according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. The protocol was registered prospectively on the International Platform of Registered Systematic Review and Meta-analysis Protocols platform (INPLASY2025110096). A total of 64 systematic reviews and meta-analyses, comprising 265 quantitative syntheses, were included. Of these, 224 (84.5%) reported statistically significant quantitative syntheses (P < 0.05) under random-effects models. AMSTAR assessment classified 44 (68.8%) systematic reviews and meta-analyses as high quality. GRADE evaluation indicated that 121 (45.7%) quantitative syntheses were supported by high-certainty evidence. Elevated PNI was consistently associated with improved overall survival (OS) across both pan-cancer and cancer-specific analyses. In pan-cancer populations, higher PNI was significantly associated with longer OS, prolonged progression-free survival, and higher objective response rates. Significant prognostic benefits of elevated PNI for OS were also observed in specific malignancies, including pancreatic cancer, gastric cancer, advanced-stage lung cancer, and glioma. Although a higher PNI is robustly associated with favorable prognostic outcomes in diverse cancers, marked heterogeneity in PNI cutoff values across studies underscores the urgent need for standardized, population-specific thresholds validated through prospective diagnostic accuracy studies.

The study aims were to present in vitro susceptibilities of clinical isolates from Gram-negative bacteria bloodstream infections (GNBSI) collected in China. GNBSI isolates were collected from 18 tertiary hospitals in 7 regions of China from 2018 to 2020. Minimum inhibitory concentrations were assessed using a Trek Diagnostic System. Susceptibility was determined using CLSI broth microdilution, and breakpoints were interpreted using CLSI M100 (2021). A total of 1,815 GNBSI strains were collected, with E. coli (42.4%) and Klebsiella pneumoniae (28.6%) being the most prevalent species, followed by P. aeruginosa (6.7%). Susceptibility analyses revealed low susceptibilities (<40%) of ESBL-producing E. coli and K. pneumonia to third-/fourth-generation cephalosporins, monobactamases, and fluoroquinolones. High susceptibilities to colistin (95.0%) and amikacin (81.3%) were found for K. pneumoniae , while Acinetobacter baumannii exhibited a high susceptibility (99.2%) to colistin but a low susceptibility to other antimicrobials (<27.5%). Isolates from ICUs displayed lower drug susceptibility rates of K. pneumoniae and A. baumannii than isolates from non-ICUs (all P < 0.05). Carbapenem-resistant and ESBL-producing K. pneumoniae detection was different across regions (both P < 0.05). E. coli and K. pneumoniae were major contributors to GNBSI, while A. baumannii exhibited severe drug resistance in isolates obtained from ICU departments.

Asthma comprises one of the most common chronic inflammatory conditions, yet still lacks effective diagnostic markers and treatment targets. To gain deeper insights, we comprehensively analyzed microarray datasets of airway epithelial samples from asthmatic patients and healthy subjects in the Gene Expression Omnibus database using three machine learning algorithms. Our investigation identified a pivotal gene, STEAP4. The expression of STEAP4 in patients with allergic asthma was found to be reduced. Furthermore, it was found to negatively correlate with the severity of the disease and was subsequently validated in asthmatic mice in this study. A ROC analysis of STEAP4 showed the AUC value was greater than 0.75. Functional enrichment analysis of STEAP4 indicated a strong correlation with IL-17, steroid hormone biosynthesis, and ferroptosis signaling pathways. Subsequently, intercellular communication analysis was performed using single-cell RNA sequencing data obtained from airway epithelial cells. The results revealed that samples exhibiting low levels of STEAP4 expression had a richer MIF signaling pathway in comparison to samples with high STEAP4 expression. Through both in vitro and in vivo experiments, we further confirmed the overexpression of STEAP4 in airway epithelial cells resulted in decreased expression of MIF, which in turn caused a decrease in the levels of the cytokines IL-33, IL-25, and IL-4; In contrast, when the STEAP4 was suppressed in airway epithelial cells, there was an upregulation of MIF expression, resulting in elevated levels of the cytokines IL-33, IL-25, and IL-4. These findings suggest that STEAP4 in the airway epithelium reduces allergic asthma Th2-type inflammatory reactions by inhibiting the MIF signaling pathway.

BackgroundN6-methyladenosine (m6A) RNA methylation modifications have been widely implicated in the metabolic reprogramming of various cell types within the tumor microenvironment (TME) and are essential for meeting the demands of cellular growth and maintaining tissue homeostasis, enabling cells to adapt to the specific conditions of the TME. An increasing number of research studies have focused on the role of m6A modifications in glucose, amino acid and lipid metabolism, revealing their capacity to induce aberrant changes in metabolite levels. These changes may in turn trigger oncogenic signaling pathways, leading to substantial alterations within the TME. Notably, certain metabolites, including lactate, succinate, fumarate, 2-hydroxyglutarate (2-HG), glutamate, glutamine, methionine, S-adenosylmethionine, fatty acids and cholesterol, exhibit pronounced deviations from normal levels. These deviations not only foster tumorigenesis, proliferation and angiogenesis but also give rise to an immunosuppressive TME, thereby facilitating immune evasion by the tumor.Aim of reviewThe primary objective of this review is to comprehensively discuss the regulatory role of m6A modifications in the aforementioned metabolites and their potential impact on the development of an immunosuppressive TME through metabolic alterations.Key scientific concepts of reviewThis review aims to elaborate on the intricate networks governed by the m6A-metabolite-TME axis and underscores its pivotal role in tumor progression. Furthermore, we delve into the potential implications of the m6A-metabolite-TME axis for the development of novel and targeted therapeutic strategies in cancer research.

It has been reported that airway epithelial cells and ferroptosis have certain effect on asthma. However, the action mechanism of ferroptosis-related genes in airway epithelial cells of asthmatic patients is still unclear. Firstly, the study downloaded the GSE43696 training set, GSE63142 validation set and GSE164119 (miRNA) dataset from the gene expression omnibus database. 342 ferroptosis-related genes were downloaded from the ferroptosis database. Moreover, differentially expressed genes (DEGs) between asthma and control samples in the GSE43696 dataset were screened by differential analysis. Consensus clustering analysis was performed on asthma patients to classify clusters, and differential analysis was performed on clusters to obtain inter-cluster DEGs. Asthma-related module was screened by weighted gene co-expression network analysis. Then, DEGs between asthma and control samples, inter-cluster DEGs and asthma-related module were subjected to venn analysis for obtaining candidate genes. The last absolute shrinkage and selection operator and support vector machines were respectively applied to the candidate genes to screen for feature genes, and functional enrichment analysis was performed. Finally, a competition endogenetic RNA network was constructed and drug sensitivity analysis was conducted. There were 438 DEGs (183 up-regulated and 255 down-regulated) between asthma and control samples. 359 inter-cluster DEGs (158 up-regulated and 201 down-regulated) were obtained by screening. Then, the black module was significantly and strongly correlated with asthma. The venn analysis yielded 88 candidate genes. 9 feature genes (NAV3, ITGA10, SYT4, NOX1, SNTG2, RNF182, UPK1B, POSTN, SHISA2) were screened and they were involved in proteasome, dopaminergic synapse etc. Besides, 4 mRNAs, 5 miRNAs, and 2 lncRNAs collectively formed competition endogenetic RNA regulatory network, which included RNF182-hsa-miR-455-3p-LINC00319 and so on. The predicted therapeutic drug network map contained NAV3-bisphenol A and other relationship pairs. The study investigated the potential molecular mechanisms of NAV3, ITGA10, SYT4, NOX1, SNTG2, RNF182, UPK1B, POSTN, SHISA2 in airway epithelial cells of asthmatic patients through bioinformatics analysis, providing a reference for the research of asthma and ferroptosis.

Table S1: MS/MS analyses of APE2 pull-down proteins in 293T cells

Normal morphology in other organs.

Slight increase of APE2 expression in mouse PTCs after carboplatin and oxaliplatin treatment.

As an important component of the immunosuppressive tumor microenvironment (TME), it has been established that mesenchymal stem cells (MSCs) promote the progression of tumor cells. MSCs can directly promote the proliferation, migration, and invasion of tumor cells via cytokines and chemokines, as well as promote tumor progression by regulating the functions of anti-tumor immune and immunosuppressive cells. MSCs-derived extracellular vesicles (MSCs-EVs) contain part of the plasma membrane and signaling factors from MSCs; therefore, they display similar effects on tumors in the immunosuppressive TME. The tumor-promoting role of macrophage migration inhibitory factor (MIF) in the immunosuppressive TME has also been revealed. Interestingly, MIF exerts similar effects to those of MSCs in the immunosuppressive TME. In this review, we summarized the main effects and related mechanisms of tumor-associated MSCs (TA-MSCs), TA-MSCs-EVs, and MIF on tumors, and described their relationships. On this basis, we hypothesized that TA-MSCs-EVs, the MIF axis, and TA-MSCs form a positive feedback loop with tumor cells, influencing the occurrence and development of tumors. The functions of these three factors in the TME may undergo dynamic changes with tumor growth and continuously affect tumor development. This provides a new idea for the targeted treatment of tumors with EVs carrying MIF inhibitors.

Mesenchymal stem cells (MSCs) are multipotent stromal cells that have the ability to differentiate into multiple cell types. Several studies have shown that exosomes secreted by MSCs (MSCs-Exo) play an important role in tumor growth, angiogenesis, invasion, and drug resistance. However, contradictory results have suggested that MSCs-Exo can also suppress tumors through specific mechanisms, such as regulating immune responses and intercellular signaling. Consequently, the relationship between MSCs-Exo and tumors remains controversial. However, it is undeniable that exosomes, as natural vesicles, can be excellent drug carriers and show promise for application in targeted tumor therapy. Here, we review the current knowledge regarding the involvement of MSCs-Exo in tumor progression and their potential as drug delivery systems in targeted therapy. We argue that MSCs-Exo can be used as safe carriers of antitumor drugs.

All cells, including prokaryotes and eukaryotes, could release extracellular vesicles (EVs). EVs contain many cellular components, including RNA, and surface proteins, and are essential for maintaining normal intercellular communication and homeostasis of the internal environment. EVs released from different tissues and cells exhibit excellent properties and functions (e.g., targeting specificity, regulatory ability, physical durability, and immunogenicity), rendering them a potential new option for drug delivery and precision therapy. EVs have been demonstrated to transport antitumor drugs for tumor therapy; additionally, EVs' contents and surface substance can be altered to improve their therapeutic efficacy in the clinic by boosting targeting potential and drug delivery effectiveness. EVs can regulate immune system function by affecting the tumor microenvironment, thereby inhibiting tumor progression. Co-delivery systems for EVs can be utilized to further improve the drug delivery efficiency of EVs, including hydrogels and liposomes. In this review, we discuss the isolation technologies of EVs, as well as engineering approaches to their modification. Moreover, we evaluate the therapeutic potential of EVs in tumors, including engineered extracellular vesicles and EVs' co-delivery systems.

Purpose The objective of this study was to investigate the molecular characteristics and potential resistance mechanisms of linezolid-resistant (LZR) Staphylococcus capitis isolates from a tertiary hospital in China. Methods S. capitis isolates were obtained from clinical patient specimens; three of the isolates came from blood cultures and one from the hydrothorax. The agar dilution and E-test methods were used to identify antibiotic resistance. The chloramphenicol-florfenicol resistance (cfr) gene carrier status of the strains was determined by PCR. Whole-genome sequencing (WGS) was used to identify point mutations and L3, L4, and L22 mutations and to study the genetic environment of the cfr gene and the relationships between strains. Results The 4 isolates obtained in this study were all linezolid-resistant Staphylococcus strains. A similar of susceptibility profile pattern was observed in all four S. capitis strains, each of which exhibited a multidrug-resistant phenotype. A potentially novel mutation, C2128T, was identified, and the cfr genes of S. capitis strains were all positive. Additionally, the same mutations (C2128T and G2600T) were identified in all 23S rRNA sequences of the isolates, whereas mutations were lacking in the L3, L4, and L22 ribosomal proteins. The genetic environments surrounding cfr were identical in all four isolates. A schematic diagram of the phylogenetic tree showed that they were closely related to AYP1020, CR01, and TW2795, and a total of seven drug resistance genes were identified in these strains. Conclusions The study indicated that the resistance of the Staphylococcus capitis strains to linezolid was caused by multiple mechanisms, and a potential novel mutation, C2128T, that may have an impact on bacterial resistance was identified.

准确测定先天性肾上腺皮质增生症(CA H)患者体内的各激素水平一直是困扰检验工作人员的难题.液相色谱-串联质谱法(LC-MS/MS)是目前公认的具有较大应用潜力的检测方法.本文从CA H患者的类固醇激素代谢情况,LC-MS/MS检测类固醇激素的方法学建立要点及LC-MS/MS用于CA H诊治的研究现状进行综述,明确了LC-MS/MS有避免非特异性物质干扰,解决免疫分析法的高假阳性,检测标本多样化及能够快速进行类固醇代谢谱分析的优点,是一种能够为临床内分泌疾病的诊断与疗效监测提供精准、高效的检测手段.同时本文也对此检测技术的不足进行了阐述.

We investigated the allele and genotype frequencies of two common CRTH2 single nucleotide polymorphisms (SNPs) [G1544C and A1651G (rs 545659)] in the 3'-untranslated region and the relationship between these SNPs and serum IL-13 levels in Chinese children patients with asthma. For G1544C and A1651G SNPs, there were significant differences in allele and genotype frequencies between asthma patients and controls. Haplotype analysis yielded additional evidence of linkage disequilibrium for the 1544G-1651G haplotype (P < 0.01). Moreover, serum IL-13 levels were significantly different among genotypes in G1544C, A1651G SNPs. These results suggest that SNPs of G1544C and A1651G might be act as susceptibility genetic factors of asthma.

The balance between T helper type 1 (Th1) and T helper type 2 (Th2) cells is critical for both innate and acquired immune reactions. However, the precise mechanisms of T helper-cell differentiation remain unclear. As an important T-cell activation molecule, CD44 participates in the differentiation of Th1 and Th2 cells. We demonstrated that CD44 variant exon v5 (CD44 v5) is highly expressed by induced human Th2 cells. To investigate the role of the CD44 v5 domain in Th2 cell differentiation, we treated human CD4+ T cells with anti-CD44v5 antibody and observed that the levels of phosphorylated STAT6 and GATA3 and the secretion of interleukin-4 (IL-4) were significantly decreased after the treatment. We also further found that the inhibition of Th2 differentiation was caused by the degradation of the alpha chain of IL-4 receptor (IL-4Rα), the CD44 v5 domain colocalized with IL-4Rα on cell surface and the degradation of IL-4Rα increased after CD44 v5 domain blocking or ablating. Our results indicated that CD44v5 antibody treatment interrupted the interaction between CD44 v5 domain and IL-4Rα, but the CD44 v5 domain blockage would not spoil the colocalization between IL-4R expression and T-cell receptor and the immunological synapse formation; similar results were also found in CD44v5-deficient CD4+ T cells. In conclusion, we revealed the function of the CD44 v5 domain in Th2 cell differentiation; blocking or ablating the CD44 v5 domain could accelerate IL-4Rα degradation and then induce the Th2 cell inhibition.

Dear Editor, Klebsiella pneumoniae (K. pneumoniae, Kpn) bloodstream infection (BSI) has a considerable prevalence and high mortality worldwide.1–3 The emergence of carbapenemresistant BSI-Kpns, especially those with hypervirulence, poses a challenge for BSI-Kpn control worldwide.4–6 We conducted a large-scale multicenter epidemiological study and in-depth genomic analysis of BSI-Kpns in China, describing a complete molecular epidemiological picture (clinical features, sequence types (STs)/serotypes, antimicrobial resistance/hypervirulence, phenotype/genotype) of BSI-Kpns. We also revealed the correlations between clinical characteristics and the genotypes of BSI-Kpns. A total of 239 Kpns were identified by screening 1219 Gram-negative bacteria causing BSI from 24 representative hospitals in different regions of China in 2018 (Table 1 and Figure 1; Table S1 and Figure S1). A total of 67.36% (161/239) infections were hospital-onset (HO), and the others were community-onset (CO). A total of 66.11% (158/239) patients weremales, andmiddle-aged (41–65 years, 118/239, 49.37%) and aged (>65 years, 81/239, 33.89%) patients accounted for a significantly higher percentage (p-value < 0.0001) (Table 1; Table S2). We further sequenced the whole genomes of 239 BSI-Kpns using Illumina Technology (Tables S3 and S4). ST analysis indicated that these strains covered 78 different STs, including seven new STs (Table S5). The most common STs were ST11, ST23 and ST65, together accounting for 41% (98/239) of BSI-Kpns (Table 1). Sixty-six (84.6%) STs were found in≤ three BSI-Kpns each. Serotypes of capsular (K) and lipopolysaccharide (O) antigens were also predicted (Table 1). We detected 50 different K-loci, with K64 (53/239, 22.18%) predominating, followed byK1 (27/239, 11.30%), K2 (27/239, 11.30%), andK47 (11/239, 4.60%). Twelve O-loci were detected, O1 and O2 were the most common, together accounting for 79.5% (190/239) of BSI-Kpns (Table 1). The distribution of strains in different regions showed different characteristics: the majority of strains in East China are ST11/K64/O2v1, while the

人工智能正在影响着检验医学实验室的日常,从检验标本的采集、传输、检测到检验结果自动审核及综合评估,人工智能技术已经开始渗入到检验医学过程的多个环节,基于智能接口技术的人工智能将加速医学实验室的自动化和标准化建设,以检验大数据和深度学习算法相结合的人工智能技术也将有助于在已有的检验大数据中发现新知识、开发新模型、优化新标准,最终辅助在医患之间建立最佳的诊疗决策.该文对人工智能技术在检验医学领域的最新应用进行阐述,并对人工智能在未来检验医学领域的部分应用场景进行初步探讨.

Rationale: Severe asthma is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of asthmatic bronchial epithelial cells have provided biological insights and underscored possible pathological mechanisms; however, the molecular basis in severe asthma is still poorly understood.Objective: The objective of this study was to identify the features of asthma and uncover the molecular basis of severe asthma in distinct molecular phenotype.Methods: The k-means clustering and differentially expressed genes (DEGs) were performed in 129 asthma individuals in the Severe Asthma Research Program. The DEG profiles were analyzed by weighted gene co-expression network analysis (WGCNA), and the expression value of each gene module in each individual was annotated by gene set variation analysis (GSVA).Results: Expression analysis defined five stable asthma subtype (AS): 1) Phagocytosis-Th2, 2) Normal-like, 3) Neutrophils, 4) Mucin-Th2, and 5) Interferon-Th1 and 15 co-expressed gene modules. “Phagocytosis-Th2” enriched for receptor-mediated endocytosis, upregulation of Toll-like receptor signal, and myeloid leukocyte activation. “Normal-like” is most similar to normal samples. “Mucin-Th2” preferentially expressed genes involved in O-glycan biosynthesis and unfolded protein response. “Interferon-Th1” displayed upregulation of genes that regulate networks involved in cell cycle, IFN gamma response, and CD8 TCR. The dysregulation of neural signal, REDOX, apoptosis, and O-glycan process were related to the severity of asthma. In non-TH2 subtype (Neutrophils and Interferon-Th1) with severe asthma individuals, the neural signals and IL26-related co-expression module were dysregulated more significantly compared to that in non-severe asthma. These data infer differences in the molecular evolution of asthma subtypes and identify opportunities for therapeutic development.Conclusions: Asthma is a heterogeneous disease. The co-expression analysis provides new insights into the biological mechanisms related to its phenotypes and the severity.

Multiple myeloma is an incurable refractory hematologic malignancy arising from plasma cells in the bone marrow. Here we investigated miR-26a function in multiple myeloma and tested single-wall carbon nanotube delivery of miR-26a in vitro and in vivo. miR-26a was downregulated in patients with multiple myeloma cells compared with plasma cells from healthy donors. miR-26a overexpression inhibited proliferation and migration and induced apoptosis in multiple myeloma cell lines. To identify the targets of miR-26a, RPMI8226-V-miR-26-GFP and RPMI8226-V-GFP cells were cultured using stable isotope labeling by amino acids in cell culture (SILAC) medium, followed by mass spectrometry analysis. In multiple myeloma cells overexpressing miR-26a, CD38 protein was downregulated and subsequently confirmed to be a direct target of miR-26a. Depletion of CD38 in multiple myeloma cells duplicated the multiple myeloma inhibition observed with exogenous expression of miR-26a, whereas restoration of CD38 overcame the inhibition of miR-26a in multiple myeloma cells. In a human multiple myeloma xenograft mouse model, overexpression of miR-26a inhibited CD38 expression, provoked cell apoptosis, and inhibited cell proliferation. Daratumumab is the first CD38 antibody drug for monotherapy and combination therapy for patients with multiple myeloma, but eventually resistance develops. In multiple myeloma cells, CD38 remained at low level during daratumumab treatment, but a high-quality response is sustained. In daratumumab-resistant multiple myeloma cells, CD38 expression was completely restored but failed to correlate with daratumumab-induced cell death. Therefore, a therapeutic strategy to confer selection pressure to maintain low CD38 expression in multiple myeloma cells may have clinical benefit. SIGNIFICANCE: These results highlight the tumor suppressor function of miR-26a via its targeting of CD38 and suggest the therapeutic potential of miR-26a in patients with multiple myeloma.

目的 评估抗凝血酶(antithrombin,AT)在脓毒血症患者不同阶段的诊断价值.方法 采用单一中心的多因素病理对照研究,收集脓毒血症患者入院后各时间段血清检测AT-Ⅲ活性及其他凝血项目、炎症因子检测结果,多因素配合分析检验特异性和敏感度.结果 在脓毒症组中,PT-T、DD、FDP水平显著升高,PLT、Fbg、AT-Ⅲ水平显著降低(P＜0.05).AT-Ⅲ、PT-T、FDP和PLT为脓毒症早期诊断较好的生物学指标;AT-Ⅲ、FDP和PLT可以更准确地预测脓毒症不良预后.结论 AT-Ⅲ水平作为单一生物学指标对于脓毒症诊断和判断不良预后具有重要价值.