ABSTRACT Interleukin 6 (IL‐6), a type of cytokine, plays a role in the onset, progression, and prognosis of various diseases. IL‐6's single nucleotide polymorphisms (SNPs) markedly affect clinical conditions by influencing gene expression, including that of other cytokines. This review synthesizes existing literature to explore the relationship between IL‐6 SNPs and diseases. Current evidence indicates that these SNPs are associated with the clinicopathological features of different diseases, with these associations partly influenced by population ethnicity. Although IL‐6 SNPs could potentially serve as biomarkers for disease susceptibility and progression, larger‐scale studies across diverse regions and populations are required to confirm their clinical significance.
ABSTRACT The Clinical and Laboratory Standards Institute M100 document serves as a cornerstone standard for clinical microbiology laboratories in China. Maintaining the scientific rigor of its predecessors, the 36th edition incorporates updated epidemiological cutoff values, pharmacokinetic/pharmacodynamic data, and clinical efficacy evidence to revise several key components. Aimed at improving the clinical predictive value of antimicrobial susceptibility testing results and guiding precise anti‐infective therapy, this article provides a summary review of key updates in the 36th edition of Clinical and Laboratory Standards Institute M100. Key revisions include comprehensive species‐specific susceptibility breakpoints for major clinical pathogens, removal of outdated epidemiological cutoff values, optimization of laboratory testing procedures, updated antimicrobial susceptibility profiles for anaerobes, and adjustments to routine quality control criteria. Collectively, these changes further standardize and refine guidelines for diverse bacterial species.
ABSTRACT Background Hyperammonemia is a central feature of hepatic encephalopathy (HE) and contributes to astrocytic dysfunction; however, the mechanisms underlying ammonia‐induced cytoskeletal remodeling remain unclear. This study aimed to identify key molecular mediators of ammonia‐induced astrocyte injury and to elucidate the role of ACTA2 in this process. Methods We established an in vitro HE model using the human astrocyte line SVG p12 treated with either ammonium chloride (NH 4 Cl) (5–20 mM) or serum from patients with HE. Cellular responses were evaluated by Cell Counting Kit‐8 assay and flow cytometry. RNA sequencing was performed to identify key regulatory genes, followed by molecular and functional validation of the lead candidate, ACTA2 , which encodes alpha‐smooth muscle actin ( α ‐SMA), using knockdown and overexpression strategies. Filamentous actin organization was assessed by phalloidin staining and fluorescence microscopy. The expressions of water channel (aquaporin‐4) and junction‐associated proteins (zonula occludens‐1, occludin, claudin‐5) were measured to characterize astrocytic junctional protein alterations. Results NH 4 Cl exposure effectively recapitulated the cytotoxic effects of serum from patients with HE, revealing a distinct biphasic response: low‐dose ammonia (5 mM) transiently boosted metabolic activity, whereas higher doses (10–20 mM) reduced viability, promoted apoptosis, and caused G2/M phase arrest. RNA‐seq, cytoskeletal analysis, and biochemical validation identified ACTA2 downregulation as a sentinel event in ammonia‐induced injury. Functional assays demonstrated that ACTA2 deficiency phenocopied NH 4 Cl‐induced cytotoxicity, while its restoration significantly mitigated apoptosis and cell cycle arrest. Ammonia treatment led to upregulation of aquaporin‐4 alongside altered expression of junctional proteins, marked by diminished zonula occludens‐1 and claudin‐5 expression and elevated occludin levels. Mechanistically, NH 4 Cl reduced the phosphorylation of FAK (Tyr397) and proto‐oncogene tyrosine‐protein kinase Src (c‐Src) (Tyr416), whereas ACTA2 overexpression in NH 4 Cl‐treated cells restored their activation, implicating suppression of the α ‐SMA‐FAK/c‐Src signaling axis in ammonia‐induced astrocytic injury. Conclusion This study demonstrates that NH 4 Cl disrupts cell cytoskeletal stability by dose‐dependently downregulating ACTA2 and suppressing the downstream FAK/c‐Src pathway, thereby affecting the viability and fate of SVG p12 cells and inducing molecular alterations associated with HE. This provides new mechanistic insights into understanding ammonia‐induced astrocytic dysfunction.
ABSTRACT Anti‐P1 alloantibody is predominantly an immunoglobulin M class, cold reactive antibody that is non‐reactive at 37°C in routine pre‐transfusion serology and thus generally regarded as clinically insignificant. However, rare clinically significant anti‐P1 antibodies can cause an acute hemolytic transfusion reaction (AHTR), and routine pre‐transfusion testing at 37°C may miss such antibodies. We report a case of AHTR caused by an anti‐P1 antibody detectable only at 4°C, which evaded detection by unexpected antibody screening performed at 37°C. A 65‐year‐old woman with blood group B, RhD positive developed AHTR within 24 h following red blood cell transfusion. She presented with coffee‐colored urine, markedly elevated bilirubin and lactate dehydrogenase concentrations, and a progressive decline in hemoglobin concentrations. Pre‐transfusion antibody screening at 37°C was negative. A retrospective serological analysis identified anti‐P1 exclusively at 4°C, which was confirmed by pigeon egg white inhibition. The patient was P1 negative; incompatibility occurred only with the P1‐positive donor unit. After transfusion of P1 antigen‐negative red blood cells, the hemolysis resolved and hemoglobin concentrations recovered. In patients with a repeated transfusion history, serological testing at 37°C and 4°C, in conjunction with antigen‐matched selection, is essential to prevent AHTR caused by clinically significant cold reactive antibodies.
ABSTRACT Background Robust longitudinal studies evaluating the association between the C‐reactive protein–triglyceride–glucose index (CTI) and cardiometabolic multimorbidity (CMM) are scarce. To better understand the clinical value of the CTI, this study was conducted to explore the association of the CTI with CMM risk and progression, and to compare its predictive performance with indices incorporating central obesity. Methods This cohort study analyzed data from the China Health and Retirement Longitudinal Study spanning 2011–2020, including 9477 participants. The associations of the CTI, triglyceride–glucose (TyG), TyG–waist circumference (TyG–WC), and TyG‐waist‐to‐height ratio with CMM incidence were assessed using multivariable Cox regression. Predictive performance was compared using the area under the receiver operating characteristic curve (AUC), net reclassification index (NRI), and integrated discrimination improvement (IDI). Multi‐state models were used to analyze disease‐stage transitions. Results During follow‐up, 462 participants developed CMM. After full adjustment, a 1‐standard deviation increase in the CTI was associated with a 41% higher CMM risk (hazard ratio [HR]: 1.41, 95% confidence interval [CI]: 1.17–1.69). In direct comparison, TyG–WC showed the highest predictive AUC (0.704, 95% CI: 0.678–0.730). Adding the CTI to a conventional risk model significantly improved the NRI and IDI. Multistate modeling demonstrated that the CTI was associated with the progression from baseline health to diabetes mellitus, stroke, and heart disease, with a stronger association observed for diabetes mellitus (HR: 1.47, 95% CI: 1.36–1.60). Conclusions The CTI independently predicted CMM risk and progression. Although the TyG–WC index demonstrated superior predictive performance, the CTI remains a clinically convenient, blood‐based composite marker that captures the insulin resistance–inflammation pathway, offering a valuable tool for risk stratification.
ABSTRACT Crohn's disease and intestinal tuberculosis share similar clinical manifestations and pose significant diagnostic challenges. Inappropriate early treatment may lead to adverse outcomes. In developing countries with high intestinal tuberculosis prevalence and increasing Crohn's disease incidence, accurate diagnostic methods are urgently needed. This article reviews recent advances in diagnostic approaches for both diseases. Simple, non‐invasive and highly accurate laboratory tests are available that show promise for early diagnosis. While high‐resolution diagnostic models (including artificial intelligence‐based models) require more testing, they provide valuable references for difficult cases. Widely used pathological and imaging techniques have incorporated meaningful new indicators while maintaining broad clinical utility. Future research should focus on developing and validating promising clinical laboratory markers, as well as refining diagnostic models for improving real‐world practice.
ABSTRACT Post‐translational modifications (PTMs) of proteins have emerged as critical regulators in the pathogenesis of hematologic malignancies. This review synthesizes the latest research advances in the regulatory mechanisms, clinical relevance, and translational application of diverse PTMs, including phosphorylation, acetylation, succinylation, and lactylation, in blood cancers. We summarize how these modifications dynamically regulate the stability and interaction of key oncogenic proteins, thereby orchestrating tumor proliferation, apoptosis evasion, and chemotherapy resistance. Crucially, this article emphasizes the clinical potential of PTMs beyond therapeutic targeting, highlighting their emerging role as sensitive biomarkers for early diagnosis. By identifying the specific PTM landscapes across leukemias, lymphomas, and myeloma, we provide a framework for developing next‐generation diagnostic tools and precision therapies for hematologic malignancies.
Addison's disease, or primary adrenal insufficiency, is a rare endocrine disorder characterized by impaired adrenal hormone production. We report a case of a 10u2010yearu2010old boy with congenital adrenal hyperplasia and secondary Addison's disease on longu2010term corticosteroid therapy who presented with recurrent nonu2010bilious vomiting, lowu2010grade fever, headache, and epigastric pain. Physical examination revealed short stature (below the third percentile) and overweight status (90th percentile), likely related to prolonged steroid use. He was managed with intravenous fluids, adjustment of antibiotics, and optimized steroid therapy, leading to significant clinical improvement. This case highlights the complexity of managing pediatric adrenal insufficiency, particularly in patients receiving chronic corticosteroids. Lifelong individualized hormone replacement, careful dose adjustment, and regular monitoring are essential to prevent adrenal crises and longu2010term metabolic complications. A multidisciplinary approach involving endocrinologists, pediatricians, and supportive care teams is crucial for optimal outcomes in children with Addison's disease.
Background Lymph node metastasis is a significant indicator of recurrence and mortality in thyroid carcinoma and often guides treatment decisions. However, the characteristics and specific mechanisms of various cancer cells that metastasize to lymph nodes are not clear. This study aims to characterize the cellular heterogeneity and transcriptomic dynamics of thyroid cancer. We further seek to elucidate the role of the key transcription factor FOXA2 in orchestrating a prou2010metastatic and immunosuppressive program, specifically its regulation of Tu2010cell activity and apoptosis. Our ultimate goal is to identify potential therapeutic strategies for thyroid cancer with lymph node metastasis. Methods Using singleu2010cell RNAu2010seq analyses, we investigated the dynamic of cellular heterogeneity transcriptome regulation and microenvironmental factors in 15,591 single cells from paired samples of primary and lymph nodeu2010metastasized tumors. The function of key factor was further investigated using data from public database and in vitro experiments. Results We found that among all the six subclusters identified, the cancer cells (cluster 3) with higher tumor different ability (tumor different score) evolved into metastatic clusters infiltrating into lymph nodes. We also showed that the immune responseu2010activating cell surface receptor signaling pathway is enriched in malignant cells of the metastatic lymph node. The interactions between T cells and other cells were weakened, and CCLsu2010mediated signals out/income Tu2010cells are more likely to affect the interactions. Tumoru2010intrinsic forkhead box A2 (FOXA2) orchestrated the thyroid cancer cell immunologic/metastatic signature and its expression is related to prognosis. FOXA2 knockdown promoted thyroid cancer cell migration, proliferation, and Tu2010cell apoptosis. Moreover, its expression significantly influenced Tu2010cell activity by the CCL2/LCN2u2010mediated signal pathway. Conclusions These findings reveal that FOXA2 regulates cancer cell immunity by influencing Tu2010cell apoptosis in thyroid cancer. Our results provide a potential pharmacological strategy for immune therapy in thyroid cancer with lymph node metastasis.
ABSTRACT Background In clinical laboratories, reagent depletion can significantly compromise the accuracy of K+, Na+, and Cl− measurements, posing risks to patient safety. Patient‐based real‐time quality control (PBRTQC) has emerged as a valuable tool for early detection of analytical errors. However, the effectiveness of PBRTQC may be influenced using data processing methods. Among these, truncation, tail‐retention, and tail‐shrinkage are three commonly used data truncation techniques. Despite their potential, the clinical early‐warning performance of PBRTQC with these methods under reagent depletion conditions remains unclear. Therefore, this study aims to evaluate the clinical early‐warning efficacy of PBRTQC when integrated with these three data truncation methods (truncation, tail‐retention, and tail‐shrinkage) for K+, Na+, and Cl− measurements during reagent depletion scenarios. Methods A controlled experimental design was used with routine patient test results as the control group and simulated reagent depletion scenarios as experimental groups. PBRTQC was applied to integrated datasets processed by the three truncation methods. Alarm timeliness rates for detecting abnormal results were evaluated for K+, Na+, and Cl−. Results Under internal standard solution depletion, the number of samples required for error detection (NPed) for K+ using the truncation, tail‐retention, and tail‐shrinkage methods was 38, 10, and 10, respectively. For Na+, the NPed was 55, 5, and 10, respectively, while for Cl−, it was 0, 11 and 16, respectively. During diluent depletion, K+ and Na+ showed 0 with the truncation method but 10 for both the tail‐retention and tail‐shrinkage methods; Cl− showed 0 with the truncation method but 11 with the tail‐retention method and 16 with the tail‐shrinkage method. With reference solution depletion, the NPed for K+ using the truncation, tail‐retention, tail‐shrinkage methods was 42, 35, and 39, respectively; the NPed for Na+ was 135, 25, and 25, respectively; and the NPed for Cl− was 140, 31, and 36, respectively. Conclusion During a shortage of reagents, the effectiveness of early warning of the PBRTQC program was the highest with the tail‐retention method, followed by the tail‐shrinkage method. The truncation method showed the lowest effectiveness with the risk of missed error detection. Considering data variability, the tail‐shrinkage method is recommended as the optimal data processing method.
Background Blood donor deferral is a critical safeguard to protect both donor health and transfusion safety. However, deferral practices can adversely affect blood availability and donor retention. The aim of this study is to evaluate deferral patterns among voluntary blood donors and to identify opportunities to optimize deferral strategies. Methods Deferral data were retrospectively collected from the blood transfusion management system of a single center between January 2019 and December 2023. Statistical analyses were performed using SPSS version 25, with p u0026lt; 0.001 considered statistically significant. Results A total of 148,282 blood donors were included, of whom 18,343 (12.37%) were deferred. Temporary deferrals accounted for 10.95% (16,240/148,282) and permanent deferrals for 1.42% (2103/148,282). The leading causes of temporary deferral were abnormal alanine aminotransferase (ALT) levels, representing 51.33% (9415/18,343) of all deferrals, followed by low hemoglobin levels at 12.20% (2237/18,343), lipemic blood at 7.12% (1306/18,343), nonu2010medical reasons including time constraints, procedural complexity, and psychological concerns at 6.90% (1265/18,343), hypertension at 4.08% (749/18,343), and medication use at 2.26% (414/18,343). Permanent deferrals were most frequently attributed to hepatitis B surface antigen (HBsAg) positivity at 4.12% (755/18,343) and syphilis antibody positivity at 2.89% (530/18,343), while nucleic acid reactivity accounted for 0.26% (48/18,343). Conclusion Targeted donor education, optimization of preu2010donation screening, and refinement of deferral criteria may improve donor recruitment and retention while maintaining transfusion safety.
Background With high colorectal cancer (CRC) incidence, accurate early differentiation of precancerous polyps is critical for prognosis; while the goldu2010standard colonoscopyu2010biopsy is limited by invasiveness, cost and poor scalability, and routine blood tests lack efficiency with simple indicator combinations, machine learning's featureu2010mining capacity offers a solution. This study aimed to develop and evaluate a machine learning system for differentiating patients with CRC and colorectal polyps using routine blood indices. Methods A retrospective analysis was conducted on the clinical data of 284 patients with CRC and 79 patients with colorectal polyps who were diagnosed at the Chinese PLA General Hospital from October 2021 to February 2024. The extreme gradient boosting (XGBoost) algorithm was used to establish a machine learning model using demographic characteristics and routine blood indices. The Shapley additive explanation method was used to evaluate feature importance. Results The constructed XGBoost model achieved high levels in differentiating CRC and colorectal polyps, with a precision of 0.906, a recall of 0.817, an accuracy of 0.791, and an area under the receiver operating characteristic curve of 0.869. The Shapley additive explanation showed that the top five important features were fibrinogen, carcinoembryonic antigen, plasma thrombin time, ferritin, and Du2010dimer. Conclusion The XGBoost machine learning model based on blood indices has certain application value in the differential diagnosis of CRC and colorectal polyps, providing a new efficient tool for auxiliary diagnosis to assist clinical decisionu2010making.
