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BACKGROUND: Esophageal squamous cell carcinoma (ESCC) patients carries a poor prognosis, with limited effective therapeutic targets. This study aimed to clarify the clinical significance of guanine nucleotide-binding protein like 3-like (GNL3L) protein expression in ESCC and its role in malignant progression. METHODS: GNL3L expression and associated cancer-promoting pathways in ESCC were interrogated via bioinformatics analysis through use of The Cancer Genome Atlas (TCGA) database. Subsequent verification of GNL3L protein expression in ESCC, coupled with clinical data, was conducted through immunohistochemistry and followed by a comprehensive prognostic analysis. We further investigated potential signaling pathways facilitating ESCC progression, employing a combination of bioinformatics analysis and immunohistochemical (IHC) experiments. RESULTS: Bioinformatics analysis unveiled a significant elevation in GNL3L expression, particularly in gastrointestinal tumors and ESCC. Immunohistochemistry confirmed elevated GNL3L expression in ESCC tissues. Regression analysis established a correlation between elevated GNL3L expression and advanced tumor node metastasis (TNM) stage, with high expression associated with poor prognosis in patients with ESCC. Our integrated approach of bioinformatics and IHC analysis indicated a potential role of the signal transducers and activators of transcription 3 (STAT3) signaling pathway in ESCC progression. CONCLUSIONS: High GNL3L expression significantly contributes to the malignant progression of ESCC. This study further elucidates the mechanisms driving ESCC progression and offers possible insights for more effective diagnosis and treatment strategies.

The study by Dang and colleagues in this issue is a timely reminder of the need for careful consideration when it comes to the inclusion of putative new diagnoses in the diagnostic and statistical manual of mental disorders (DSM). The authors conclude that findings from their systematic review and meta‐analysis of recent literature bearing on the DSM‐5 other specified feeding and eating disorders (OSFED) category "support the conceptualization of atypical AN, PD and NES as clinically significant EDs with similar severity to full‐threshold EDs." This commentary attempts to provide some additional context, historical context in particular, that the author believes may be helpful when considering the potential implications of Dang and colleagues' findings. This is achieved through reference to the construct, well‐known in the sociology and feminist literature, of medicalization and by highlighting certain issues relevant to the determination of "clinical significance." I hope that readers approaching Dang and colleagues' research from the currently dominant, medical‐model perspective might be persuaded of the importance of considering alternative perspectives when interpreting findings from research of this kind. [ABSTRACT FROM AUTHOR]

Background: This study investigated the role of cyclin-dependent kinase 9 (CDK9) expression levels and prognosis in acute myeloid leukemia (AML) by examining its expression at the time of initial diagnosis. Methods: Bone marrow samples from 60 AML patients were collected for the observation group, with 20 normal human bone marrow samples serving as controls. Clinical and pathological data were gathered from the AML patients. Real-time quantitative PCR (RT-qPCR) was employed to measure CDK9 expression levels in both groups, and the association between CDK9 expression, clinical characteristics, and prognosis in AML patients was analyzed. Kaplan-Meier curves were used to assess the impact of CDK9 on overall survival (OS) in AML, while Cox regression analysis was performed to identify prognostic factors in AML patients. Results: The expression of CDK9 was significantly elevated in AML patients, compared to the control group (p < 0.05). High CDK9 expression was associated with increased white blood cell (WBC) count, poor treatment response, and worse prognosis compared to low expression (p < 0.05). Additionally, patients with high CDK9 expression exhibited significantly shortened OS compared to those with low expression (p < 0.05). High CDK9 expression emerged as an independent risk factor influencing prognosis in AML. Conclusions: CDK9 is markedly upregulated in AML patients, suggesting its potential utility as both a prognostic indicator and a therapeutic target, particularly for patients with unfavorable clinical and pathological characteristics and poor prognosis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression and clinical significance of serum nucleotide-binding oligomerization do- main-like receptor protein 3 (NLRP3) inflammasome and its downstream inflammatory factors in patients with allergic rhinitis (AR). Methods: 206 AR patients (AR group) admitted to our hospital from April 2021 to September 2023 were selected, and patients were di- vided into mild group (107 cases) and moderate to severe group (99 cases) according to the severity of the disease, another 168 healthy volunteers (control group) who underwent physical examination in our hospital during the same period were selected. The levels of serum NLRP3 inflammasome, interleukin (IL)-1ẞ and IL-18 were detected in two groups. The symptoms of AR patients were evaluated by al- lergic rhinitis rating scale (SFAR). The correlation between serum NLRP3 inflammasome, IL-1B, IL-18 and SFAR score in AR patients was analyzed by Pearson method. The value of NLRP3 inflammasome, IL-1ẞ and IL-18 in the diagnosis of AR and the prediction of moderate to severe AR were analyzed by receiver operating characteristic (ROC) curve. Results: The levels of serum NLRP3 inflamma- some, IL-1ẞ and IL-18 in AR group were higher than those in control group(P<0.05). The levels of serum NLRP3 inflammasome, IL-1B, IL-18 and SFAR score in moderate and severe group were higher than those in mild group (P<0.05). The levels of serum NLRP3 inflam- masome, IL-1ẞ and IL-18 in AR patients were positively correlated with SFAR score(P<0.05). The area under the curve (AUC) of NLRP3 inflammasome, IL-1B, and IL-18 in the diagnosis of AR was 0.796, 0.821, and 0.800 respectively, the AUC of the combined diagnosis of the three indicators was 0.930, which was higher than that of each indicator alone. The AUC of NLRP3 inflammasome, IL-1ẞ and IL-18 in predicting moderate to severe AR was 0.793, 0.770 and 0.736 respectively, the AUC of the combined prediction of the three indicators was 0.893, which was higher than that of each indicator alone. Conclusion: The serum levels of NLRP3 inflammasome, IL-1ẞ and IL-18 in AR patients are significantly increase, which are relate to the aggravation of AR. The combine detection of NLRP3 inflammasome and its downstream inflammatory factors has a high value in the diagnosis of AR and the prediction of moderate to severe AR. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression and clinical significance of serum Klotho, fibroblast growth factor 23 (FGF23) and insulin-like growth factor-1 (IGF-1) in patients with chronic periodontitis (CP). Methods: 108 patients with CP (CP group) who admitted to our hospital from January 2022 to June 2023 were selected, and 92 patients with oral health who underwent ultrasonic tooth cleaning in our hospital during the same period were selected (control group), CP patients were divided into mild group (55 cases) and moderate to severe group (53 cases) according to the severity of CP. The levels of serum Klotho, FGF23, IGF-1, inflammatory factors interleukin (IL) -6, IL-1ẞ and tumor necrosis factor-a (TNF-a) in CP group and control group were detected, and the periodontal clinical indicators of probing depth (PD), attachment loss (CAL) and bleeding index (BI) in CP group were examined. The correlation between serum Klotho, FGF23, IGF-1 and periodontal clinical indicators and inflammatory factors were analyzed by Pearson method. The value of serum Klotho, FGF23 and IGF-1 in the diagnosis of CP were analyzed by receiver operating characteristic (ROC) curve. Results: The levels of serum FGF23, IL-6, IL-1ẞ and TNF-a in CP group were higher than those in control group (P < 0.05) and the levels of serum Klotho and IGF-1 were lower than those in control group (P < 0.05) The levels of serum FGF23, IL-6, IL-1B, TNF-α, PD, CAL and BI in moderate to severe group were higher than those in mild group (P < 0.05) and the levels of serum Klotho and IGF-1 were lower than those in mild group (P < 0.05) The level of serum FGF23 of CP patients was positively correlated with IL-6, IL-1B, TNF-α, PD, CAL and BI (P < 0.05) and the serum Klotho and IGF-1 levels were negatively correlated with IL-6, IL-1B, TNF-α, PD, CAL and BI (P < 0.05) The area under the curve of serum Klotho, FGF23 and IGF-1 in the diagnosis of CP was 0.819, 0.816 and 0.861, respectively, the area under the curve of the combined diagnosis of the three indexes was 0.978, which was higher than that of the single diagnosis of each index. Conclusion: The increase of serum FGF23 level, and the decrease of Klotho and IGF-1 levels in CP patients are related to the occurrence of periodontal inflammation and tissue destruction, the combined detection of serum Klotho, FGF23 and IGF-1 has high value in the diagnosis of CP. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease, which is characterized by the selective loss of the upper and lower motor neurons. The pathogenesis of ALS remains to be elucidated and has been connected to genetic, environmental and immune conditions. Evidence from clinical and experimental studies has suggested that the immune system played an important role in ALS pathophysiology. Autoantibodies are essential components of the immune system. Several autoantibodies directed at antigens associated with ALS pathogenesis have been identified in the serum and/or cerebrospinal fluid of ALS patients. The aim of this review is to summarize the presence and clinical significance of autoantibodies in ALS. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the expression level of upstream stimulator 1 (USF1) in the bone marrow of newly diagnosed acute myeloid leukemia (AML) patients and investigate its clinical and prognostic significance. Methods: Bone marrow samples from 60 newly diagnosed AML patients constituted the observation group, while 20 samples from healthy individuals formed the control group. Real-time quantitative PCR (qRT-PCR) was used to measure the USF1 expression in both groups and to analyze its correlation with clinicopathological features and prognosis in AML patients. Kaplan-Meier curves were utilized to assess the impact of USF1 on the overall survival (OS) in AML patients. The prognostic factors of AML were examined by using Cox regression analysis. Results: A univariate analysis revealed a significantly higher USF1 expression in the AML patients compared to the control group (p < 0.001), with no difference in the clinicopathological features between the low-expression group and the control group. However, there was a significant difference between the high-expression group and the control group (p < 0.01). Moreover, the OS of the high USF1 expression group was notably shorter than of the low USF1 expression group (p < 0.0001). A multivariate analysis identified high USF1 expression and age ≥ 60 years as independent risk factors for a poor AML prognosis. Conclusions: High expression of USF1 is linked to a worse prognosis and shorter survival time in AML patients. USF1 may serve as an indicator of prognosis and survival in AML patients and could be a potential target for AML treatment. [ABSTRACT FROM AUTHOR]

Background Acute myocardial infarction (AMI) is one of the common cardiovascular diseases, and despite the widespread use of biomarkers for myocardial necrosis, morbidity and mortality of AMI remain high. Objective To investigate the expression levels and clinical significance of miR-126, mitochondrial components and adhesion molecules in endothelial microparticles (EMPs) . Methods A total of 50 patients with AMI (AMI group), 50 patients with stable coronary artery disease (SCAD) (SCAD group) and 50 healthy subjects (control group) were enrolled in the People's Hospital of Xinjiang Uygur Autonomous Region from September 2021 to September 2022. AMI patients and SCAD patients were hospitalized in our hospital and received percutaneous coronary intervention (PCI), and all healthy subjects were evaluated by the physical examination center of our hospital. Peripheral blood samples and general data of three groups were collected. The morphology of the microparticles (MPs) was observed by transmission electron microscopy (TEM), the level of EMPs was identified by flow cytometry, and the expression of miR-126 in EMPs was detected by fluorescence quantitative PCR. ELISA was used to detect the levels of mitochondrial reactive oxygen species (ROS) and intracellular adhesion molecules [vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, and P-selectin] in EMPs. Results As observed by TEM, the membrane structure of the isolated MPs was intact and its diameter ranged from 100 to 400 nm. Compared with the control group, the expression of miR-126 in plasma EMPs in the AMI group was significantly decreased (P

The statistical significance of a clinical trial analysis result is determined by a mathematical calculation and probability based on null hypothesis significance testing. However, statistical significance does not always align with meaningful clinical effects; thus, assigning clinical relevance to statistical significance is unreasonable. A statistical result incorporating a clinically meaningful difference is a better approach to present statistical significance. Thus, the minimal clinically important difference (MCID), which requires integrating minimum clinically relevant changes from the early stages of research design, has been introduced. As a follow-up to the previous statistical round article on P values, confidence intervals, and effect sizes, in this article, we present hands-on examples of MCID and various effect sizes and discuss the terms statistical significance and clinical relevance, including cautions regarding their use.

Summary Aberrant alternative splicing (AS) contributes to leukemogenesis, but reports on the clinical and biological implications of aberrant AS in acute myeloid leukaemia (AML) remain limited. Here, we used RNA‐seq to analyse AS in AML cells from 341 patients, comparing them to healthy CD34+ haematopoietic stem cells (HSCs). Our findings highlight distinct AS patterns in the nuclear transcription factor Y subunit alpha (NFYA) gene, with two main isoforms: NFYA‐L (Long) and NFYA‐S (Short), differing in exon 3 inclusion. Patients with lower NFYA‐L but higher NFYA‐S expression, termed NFYA‐S predominance, displayed more favourable characteristics and better outcomes following intensive chemotherapy, regardless of age and European LeukemiaNet risk classification, compared to those with higher NFYA‐L but lower NFYA‐S expression, termed NFYA‐L predominance. The prognostic effects were validated using The Cancer Genome Atlas cohort. Transcriptome analysis revealed upregulated cell cycle genes in NFYA‐S predominant cases, resembling those of active HSCs, demonstrating relative chemosensitivity. Conversely, NFYA‐L predominant cases, as observed in KMT2A‐rearranged leukaemia, were associated with relative chemoresistance. NFYA‐S overexpression in OCI‐AML3 cells promoted cell proliferation, S‐phase entry and increased cytarabine sensitivity, suggesting its clinical and therapeutic relevance in AML. Our study underscores NFYA AS as a potential prognostic biomarker in AML. [ABSTRACT FROM AUTHOR]

Objective: The present umbrella review aims to collate and summarize the findings from previous meta-analyses on the Triglyceride and Glucose (TyG) Index, providing insights to clinicians, researchers, and policymakers regarding the usefulness of this biomarker in various clinical settings. Methods: A comprehensive search was conducted in PubMed, Scopus, and Web of Science up to April 14, 2024, without language restrictions. The AMSTAR2 checklist assessed the methodological quality of the included meta-analyses. Statistical analyses were performed using Comprehensive Meta-Analysis (CMA) software. Results: A total of 32 studies were finally included. The results revealed significant associations between the TyG index and various health outcomes. For kidney outcomes, a high TyG index was significantly associated with an increased risk of contrast-induced nephropathy (CIN) (OR = 2.24, 95% CI: 1.82–2.77) and chronic kidney disease (CKD) (RR = 1.46, 95% CI: 1.32–1.63). High TyG index was significantly associated with an increased risk of type 2 diabetes mellitus (T2DM) (RR = 3.53, 95% CI: 2.74–4.54), gestational diabetes mellitus (GDM) (OR = 2.41, 95% CI: 1.48–3.91), and diabetic retinopathy (DR) (OR = 2.34, 95% CI: 1.31–4.19). Regarding metabolic diseases, the TyG index was significantly higher in patients with obstructive sleep apnea (OSA) (SMD = 0.86, 95% CI: 0.57–1.15), metabolic syndrome (MD = 0.83, 95% CI: 0.74–0.93), and non-alcoholic fatty liver disease (NAFLD) (OR = 2.36, 95% CI: 1.88–2.97) compared to those without these conditions. In cerebrovascular diseases, a higher TyG index was significantly associated with an increased risk of dementia (OR = 1.14, 95% CI: 1.12–1.16), cognitive impairment (OR = 2.31, 95% CI: 1.38–3.86), and ischemic stroke (OR = 1.37, 95% CI: 1.22–1.54). For cardiovascular outcomes, the TyG index showed significant associations with an increased risk of heart failure (HF) (HR = 1.21, 95% CI: 1.12–1.30), atrial fibrillation (AF) (SMD = 1.22, 95% CI: 0.57–1.87), and hypertension (HTN) (RR = 1.52, 95% CI: 1.25–1.85). Conclusion: The TyG index is a promising biomarker for screening and predicting various medical conditions, particularly those related to insulin resistance and metabolic disorders. However, the heterogeneity and methodological quality of the included studies suggest the need for further high-quality research to confirm these findings and refine the clinical utility of the TyG index. [ABSTRACT FROM AUTHOR]

Objective To observe the expression changes of micro RNA-23a(miR-23a) and apoptotic protease-activating factor-1 (APAF-1) in endometrial carcinoma tissues and analyze its clinical significance. Methods 123 specimens of endometrial carcinoma in our hospital from May 2018 to May 2020 were selected as endometrial carcinoma group, and the para cancerous tissue was selected as the normal group. Expression of miR-23a and APAF-1 were examined in endometrial tissues; the relationship between miR-23a and APAF-1 and the clinicopathology of patients and the correlation between the two were analyzed; Kaplan-Meier method was used to analyze the survival of patients with endometrial cancer. Results Compared with the normal group, the expression level of miR-23a in endometrial carcinoma group was significantly increased, the expressions of APAF-1 mRNA and protein decreased significantly (P < 0.05); miR-23a and APAF-1 were significantly correlated with clinical stage, histological differentiation and myometrial invasion (P < 0.05); Pearson analysis showed that miR-23a was negatively correlated with APAF-1 (P < 0.05); Kaplan-Meier curves showed that PFS and OS were significantly higher in the miR-23a low-expression group as well as the APAF-1-positive expression group than in the miR-23a high-expression group and the APAF-1-negative expression group(P < 0.05). Conclusion The expression level of miR-23a is increased and APAF-1 expression is decreased in endometrial carcinoma, both of which correlate with endometrial cancer progression and patient prognosis, are expected to be biomarkers for clinical assessment of disease progression and prognosis in early-stage patients. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to assess the expression levels of NAP1L5 in individuals diagnosed with acute myeloid leukemia (AML) and to investigate its clinical and prognostic significance in those with primary AML. Methods: Between June 2021 and June 2023, the Department of Hematology at the First Affiliated Hospital of Bengbu Medical University collected 100 bone marrow specimens from primary AML patients and 30 from individuals with idiopathic thrombocytopenic purpura (ITP) for this medical research study. The researchers gathered comprehensive clinical data from patients diagnosed with acute myeloid leukemia (AML). Quantitative realtime polymerase chain reaction (qRT-PCR) was utilized to measure the mRNA levels of NAP1L5 in both the experimental and the control group. The investigation involved analyzing the association between NAP1L5 expression related to AML, clinical features, and overall prognosis. The study employed the Kaplan-Meier method to evaluate the impact of NAP1L5 expression on the overall survival time (OS) in AML patients, while the Cox hazard regression model was used to identify significant prognostic factors. Results: NAP1L5 was found to be significantly more expressed in individuals with AML compared to those with ITP. Patients diagnosed with AML and exhibiting elevated NAP1L5 expression levels correlated with older age, ineffective response to chemotherapy, and a more unfavorable prognosis compared to those with lower NAP1L5 expression. Additionally, the group with high expression demonstrated a noticeably decreased overall survival (OS), compared to the group with low expression. Furthermore, a significant association was observed between the elevated NAP1L5 expression levels and an unfavorable clinical outcome in patients diagnosed with AML. Conclusions: The initial exploration of the elevated expression of NAP1L5 in AML and its clinical significance offers potential targets for AML treatment and prognostic evaluation. [ABSTRACT FROM AUTHOR]

Allergic Rhinitis (AR), a prevalent condition in otorhinolaryngology, is mediated by Type 1 hypersensitivity through IgE, characterized by Type 2 inflammatory response and eosinophil infiltration in the nasal mucosa. Since AR disease exhibits significant heterogeneity in symptom severity, an objective assessment of AR severity may facilitate better individualized treatment. To explore the changes in peripheral blood IL-9, Th9, and BAFF levels of allergic rhinitis (AR) in patients and the clinical significance associated with it. A retrospective study selected 80 AR patients admitted from January 2022 to October 2022 as the case group, dividing them into mild and moderate-to-severe groups based on symptom scores. Concurrently, 50 patients without AR, who were treated for nasal bone fractures or underwent septoplasty, were selected as the group for comparison. Alterations in the expression levels of peripheral blood IL-9, Th9, and BAFF were analyzed and compared among the different groups. The diagnostic value of serum BAFF for the severity of AR was analyzed using the receiver operating characteristic (ROC) curve. Noticeable variations were observed in clinical variables among the three groups such as, total IgE levels, peripheral blood eosinophil count and proportion, TNSS, and VAS (P< 0.05), while no statistically significant differences were observed in other variables (P> 0.05). The comparison of IL-9, Th9, and BAFF among the three groups revealed statistically significant differences (P< 0.05). Analysis using multivariate logistic regression revealed that IL-9 (OR = 2.365), Th9 (OR = 2.186), BAFF (OR = 2.307) were influencing factors of moderate-to-severe AR (P< 0.05). The ROC curve indicated that the AUC for the diagnosis of moderate-to-severe AR by IL-9, Th9, BAFF were 0.770, 0.734, 0.761, respectively, and the combined detection AUC was 0.888, an area under the curve higher than individual testing. Changes in peripheral blood IL-9, Th9, and BAFF levels in AR patients may function as indicators to assess the level of severity in diagnostic procedures. [ABSTRACT FROM AUTHOR]

BACKGROUND: It was found that the ligands and receptors of Notch are both cell membrane surface proteins, which are important proteins to mediate intercellular communication, and the Notch signaling pathway plays a crucial regulatory role in the proliferation and differentiation of mesenchymal stem cells. OBJECTIVE: To review the regulatory mechanism of the Notch signaling pathway on the proliferation and differentiation of mesenchymal stem cells, summarize and clarify the research advance in how the Notch signaling pathway regulates the proliferation and differentiation of mesenchymal stem cells, and provide theoretical support for the future use of stem cells to treat various related diseases. METHODS: By using the computer, the first author searched the relevant studies involving Notch signaling pathway regulation of mesenchymal stem cell proliferation and differentiation on CNKI, Wanfang, VIP, PubMed, Web of Science, and Nature databases with Chinese search terms “mesenchymal stem cells, Notch, Notch signaling pathway, proliferation, differentiation” and the English search terms “mesenchymal stem cells, MSC, Notch, Notch signaling pathway, proliferation, differentiation”. Part of the literature was searched in combination with the literature tracing method. Finally, 87 articles were included in the review analysis. RESULTS AND CONCLUSION: (1) Notch signaling pathway is a conserved signaling pathway in multicellular organisms, which plays an important role in regulating cell differentiation, proliferation, apoptosis, and the cell cycle by mediating communication between neighboring cells through receptor-ligand binding. (2) Mesenchymal stem cells are a class of adult stem cells with self-proliferative and multi-directional differentiation potential, which can be regulated by external signaling pathways to affect their proliferation and differentiation. Notch signaling pathway, as one of them, when Notch ligands are activated, the Notch proteins will undergo two protein hydrolysis cleavages to release Notch intracellular structural domain NICD, which then enters the nucleus and thus promotes the transcription of target genes to regulate the proliferation and differentiation of mesenchymal stem cells from different sources, such as bone marrow, adipose, and umbilical cord. However, the specific mechanisms that regulate the proliferation and differentiation of mesenchymal stem cells from different tissue sources of the same species are different. (3) The Notch signaling pathway can regulate the differentiation of mesenchymal stem cells into different target cells, but due to different target cells, the expression levels of receptors or ligands in the Notch signaling pathway vary. (4) Clinical targeting of the Notch signaling pathway to promote mesenchymal stem cells for the treatment of various refractory diseases, such as aplastic anemia, severe joint injuries, ischemic strokes, and myocardial infarctions, has a promising application. (5) By exploring the Notch signaling pathway via regulating the expression levels of its receptors and ligands in bone marrow mesenchymal stem cells from rat, mouse, and human, it can be found that the Notch signaling pathway expression levels in the proliferation and differentiation of mesenchymal stem cells from different species origins are also different. (6) The role of mesenchymal stem cells in tissue engineering has been gradually highlighted due to their advantages of safety, low immune rejection, and wide therapeutic prospects. The Notch signaling pathway regulates the proliferation and differentiation of mesenchymal stem cells with a wide range of influencing factors, and subsequent studies should further optimize the influencing factor variables and explore the standardized studies of regulating the proliferation and differentiation of mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

Introduction: Glioma, a prevalent and deadly brain tumor, is marked by significant cellular heterogeneity and metabolic alterations. However, the comprehensive cell-of-origin and metabolic landscape in high-grade (Glioblastoma Multiforme, WHO grade IV) and low-grade (Oligoastrocytoma, WHO grade II) gliomas remains elusive. Methods: In this study, we undertook single-cell transcriptome sequencing of these glioma grades to elucidate their cellular and metabolic distinctions. Following the identification of cell types, we compared metabolic pathway activities and gene expressions between high-grade and low-grade gliomas. Results: Notably, astrocytes and oligodendrocyte progenitor cells (OPCs) exhibited the most substantial differences in both metabolic pathways and gene expression, indicative of their distinct origins. The comprehensive analysis identified the most altered metabolic pathways (MCPs) and genes across all cell types, which were further validated against TCGA and CGGA datasets for clinical relevance. Discussion: Crucially, the metabolic enzyme phosphodiesterase 8B (PDE8B) was found to be exclusively expressed and progressively downregulated in astrocytes and OPCs in higher-grade gliomas. This decreased expression identifies PDE8B as a metabolism-related oncogene in IDH-mutant glioma, marking its dual role as both a protective marker for glioma grading and prognosis and as a facilitator in glioma progression. [ABSTRACT FROM AUTHOR]

In the dynamic landscape of modern healthcare, the ability to anticipate and diagnose diseases, particularly in cases where early treatment significantly impacts outcomes, is paramount. Cancer, a complex and heterogeneous disease, underscores the critical importance of early diagnosis for patient survival. The integration of metabolomics information has emerged as a crucial tool, complementing the genotype-phenotype landscape and providing insights into active metabolic mechanisms and disease-induced dysregulated pathways. This review explores a decade of developments in the search for biomarkers validated within the realm of cancer studies. By critically assessing a diverse array of research articles, clinical trials, and studies, this review aims to present an overview of the methodologies employed and the progress achieved in identifying and validating biomarkers in metabolomics results for various cancer types. Through an exploration of more than 800 studies, this review has allowed to establish a general idea about state-of-art in the search of biomarkers in metabolomics studies involving cancer which include certain level of results validation. The potential for metabolites as diagnostic markers to reach the clinic and make a real difference in patient health is substantial, but challenges remain to be explored. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of clinical significance reporting in contemporary comparative effectiveness research (CER). Background: In CER, a statistically significant difference between study groups may or may not be clinically significant. Misinterpreting statistically significant results could lead to inappropriate recommendations that increase health care costs and treatment toxicity. Methods: CER studies from 2022 issues of the Annals of Surgery, Journal of the American Medical Association, Journal of Clinical Oncology, Journal of Surgical Research, and Journal of the American College of Surgeons were systematically reviewed by 2 different investigators. The primary outcome of interest was whether the authors specified what they considered to be a clinically significant difference in the “Methods.” Results: Of 307 reviewed studies, 162 were clinical trials and 145 were observational studies. Authors specified what they considered to be a clinically significant difference in 26 studies (8.5%). Clinical significance was defined using clinically validated standards in 25 studies and subjectively in 1 study. Seven studies (2.3%) recommended a change in clinical decision-making, all with primary outcomes achieving statistical significance. Five (71.4%) of these studies did not have clinical significance defined in their methods. In randomized controlled trials with statistically significant results, sample size was inversely correlated with effect size (r = −0.30, P = 0.038). Conclusions: In contemporary CER, most authors do not specify what they consider to be a clinically significant difference in study outcome. Most studies recommending a change in clinical decision-making did so based on statistical significance alone, and clinical significance was usually defined with clinically validated standards. [ABSTRACT FROM AUTHOR]

Low back pain (LBP) and neck pain predominate as the primary causes of disability. Cell‐ and platelet‐rich plasma (PRP) products are potential therapies with clinical trials and reviews promoting their efficacy. Nonetheless, they frequently disregard the clinical significance of reported improvements. In this systematic review, the effectuated improvements in pain, disability, quality of life (QoL), and radiographic images are comprehensively described and scored on their clinical significance. An electronic database literature search was conducted on July 2023 for in‐human assessment of cell or PRP products to alleviate discogenic pain. Papers were screened on quantitative pain, disability, QoL, radiographic improvements, and safety outcomes. Risk of bias was assessed through MINORS and Cochrane Source of Bias tools. Reported outcomes were obtained, calculated, and assessed to meet minimal clinically important difference (MCID) standards. From 7623 screened papers, a total of 80 articles met the eligibility criteria, presenting 68 specific studies. These presented at least 1974 treated patients. Overall, cell/PRP injections could alleviate pain and disability, resulting in MCID for pain and disability in up to a 2‐year follow‐up, similar to those observed in patients undergoing spinal fusion. Included trials predominantly presented high levels of bias, involved heterogeneous study designs, and only a minimal number of randomized controlled trials. Nonetheless, a clear clinically significant impact was observed for cell‐ and PRP‐treated cohorts with overall good safety profiles. These results highlight a strong therapeutic potential but also underline the need for future cost‐effectiveness assessments to determine the benefits of cell/PRP treatments. [ABSTRACT FROM AUTHOR]

Background: Although it has been shown that cyclin dependent kinase inhibitor 2A (CDKN2A) plays a significant role in a number of malignancies, its clinicopathological value and function in small cell lung cancer (SCLC) is unclear and warrants additional research. Methods: The clinical significance of CDKN2A expression in SCLC was examined by multiple methods, including comprehensive integration of mRNA level by high throughput data, Kaplan–Meier survival analysis for prognostic value, and validation of its protein expression using in-house immunohistochemistry. Results: The expression of CDKN2A mRNA in 357 cases of SCLC was evidently higher than that in the control group (n = 525) combing the data from 20 research centers worldwide. The standardized mean difference (SMD) was 3.07, and the area under the curve (AUC) of summary receiver operating characteristic curve (sROC) was 0.97 for the overexpression of CDKN2A. ACC, COAD, KICH, KIRC, PCPG, PRAD, UCEC, UVM patients with higher CDKN2A expression had considerably worse overall survival rates than those with lower CDKN2A expression with the hazard ratio (HR) > 1. Conclusion: CDKN2A upregulation extensively enhances the carcinogenesis and progression of SCLC. [ABSTRACT FROM AUTHOR]

Far upstream element-binding protein 1 (FUBP1) is a single-stranded nucleic acid-binding protein that binds to the Far Upstream Element (FUSE) sequence and is involved in important biological processes, including DNA transcription, RNA biogenesis, and translation. Recent studies have highlighted the significance of aberrant expression or mutations in FUBP1 in the development of various tumors, with FUBP1 overexpression often indicating oncogenic roles in different tumor types. However, it is worth noting that recent research has discovered its tumor-suppressive role in cancer, which is not yet fully understood and appears to be tissue- or context-dependent. This review summarizes the association between FUBP1 and diverse cancers and discusses the functions of FUBP1 in cancer. In addition, this review proposes potential clinical implications and outlines future research directions to pave the way for the development of targeted therapeutic strategies focusing on FUBP1.

ObjectiveThe objective of this study is to assess the prognostic value of Ki67 and p16 proteins in laryngeal cancer.Materials and methodsThis retrospective cohort analysis comprised 260 patients diagnosed with laryngeal cancer. Immunohistochemistry (IHC) was employed to assess the expression levels of p16 and Ki67, and their correlation with the survival time of laryngeal cancer patients was analyzed.ResultsThe Ki67 index level exhibited a significant association with the prognosis of laryngeal cancer. Patients with higher Ki67 index levels demonstrated shorter survival times, more severe pathological classification, and higher tumor stages (P < 0.05). Conversely, no significant differences in prognostic characteristics of laryngeal cancer were observed in the p16 (-/+) population (P > 0.05). The median survival times for patients with Ki67 index levels of 0-35%, 36-70%, and 70-100% were 3.54 years, 2.10 years, and 1.92 years, respectively. After adjusting for age, smoking, alcohol consumption, pathological classification, surgical intervention, recurrence, and metastasis, the risk of death for patients with Ki67 index levels of 70-100% was 2.0504 times higher than that of patients with Ki67 index levels of 0-35% (95% CI: 1.2997-3.2345, P = 0.0020).ConclusionThe Ki67 index level is strongly associated with survival time and the risk of death in laryngeal cancer, making it a valuable prognostic indicator. However, the prognostic value of p16 levels in laryngeal cancer is limited. These findings provide important insights for prognosis evaluation and treatment decision-making in patients with laryngeal cancer.

ObjectiveThis study strives to the variation and significance of microRNA-21 (miR-21) in children with congenital heart disease (CHD)-related pulmonary artery hypertension (PAH).MethodsChildren with CHD (n = 179) were selected as subjects, including 101 children without PAH and 78 children with PAH. All children underwent general data collection, laboratory examination, echocardiography and cardiac catheterization. After detection of serum miR-21 expression, the predictive value and the impacts of serum miR-21 for PAH and postoperative critical illness were analyzed.ResultsSerum creatine kinase isoenzyme (CK-MB), B-type natriuretic peptide (BNP) and miR-21 were elevated, but ejection fraction (EF) and cardiac index (CI) were decreased in the CHD-PAH group. Serum miR-21 assisted in predicting PAH in CHD children, with the area under curve (AUC) of 0.801 (95% CI of 0.735∼0.857), a cut-off value of 2.56, sensitivity of 73.08, and specificity of 72.28%. Serum miR-21 in children with CHD-PAH was correlated with clinicopathological indicators such as systolic pulmonary artery pressure, mean pulmonary arterial pressure, BNP and CI. Serum miR-21 helped predict the development of postoperative critical illness in children with CHD-PAH, with an AUC of 0.859 (95% CI: 0.762–0.927, cut-off value: 4.55, sensitivity: 69.57%, specificity: 92.73%). Increased serum miR-21 was an independent risk factor of postoperative critical illness in children with CHD-PAH.ConclusionSerum miR-21 was upregulated in children with CHD-PAH, which may serve as a predictive biomarker for the onset of PAH and postoperative critical illness in CHD children.

Recently, topics related to targeted gene therapy and diagnosis have become increasingly important in disease research. The progression of many diseases is associated with specific gene signaling pathways. Therefore, the identification of precise gene targets in various diseases is crucial for the development of effective treatments. Laminin subunit beta 3 (LAMB3), a component of laminin 5, functions as an adhesive protein in the extracellular matrix and plays a vital role in regulating cell proliferation, migration, and cell cycle in certain diseases. Previous studies have indicated that LAMB3 is highly expressed in numerous tumorous and non-tumorous conditions, including renal fibrosis; squamous cell carcinoma of the skin, thyroid, lung, pancreatic, ovarian, colorectalr, gastric, breast, cervical, nasopharyngeal, bladder, prostate cancers; and cholangiocarcinoma. Conversely, it is underexpressed in other conditions, such as hepatocellular carcinoma, epidermolysis bullosa, and amelogenesis imperfecta. Consequently, LAMB3 may serve as a molecular diagnostic and therapeutic target for various diseases through its involvement in critical gene signaling pathways. This paper reviews the research status of LAMB3 and its role in related diseases.

Abstract Background Neurospecific Enolase (NSE), a multifunctional protein, is present in various tissues of the body and plays an important role in many disease processes, such as infection, inflammation, tumours, injury, and immunity. In recent years, the application of NSE in respiratory diseases has become increasingly widespread and a research hotspot. Objective This study aims to explore the relationship between NSE and childhood pneumonia, providing assistance for the diagnosis and assessment of pneumonia. Methods Using prospective research and case-control methods, We selected 129 children with pneumonia hospitalised in Weifang People’s Hospital from September 2020 to April 2022 as the case group. Among them were 67 cases of Mycoplasma pneumoniae pneumonia (MP+), 62 cases of non-Mycoplasma pneumoniae pneumonia (MP -), and 21 cases of severe pneumonia. At the same time, 136 children who underwent outpatient health examinations were selected as the control group. The levels of NSE, ESR, CRP in cases group and NSE in control group were measured separately. Result The NSE levels in the MP + group were 17.86 (14.29–22.54) ng/mL, while those in the MP- group were 17.89 (14.10–21.66) ng/mL, both of which were higher than the control group’s NSE levels of 13.26(12.18,14.44) ng/mL (H = 46.92, P = 0.000). There was no statistically significant difference in NSE levels between the MP + and MP - groups (P > 0.05). The NSE level in the severe pneumonia group was 27.38 (13.95–34.06) ng/mL, higher than that in the mild pneumonia group, which was 17.68 (14.27–21.04) ng/mL, (P = 0.024). The AUC values for diagnosing pneumonia are NSE0.714, CRP0.539, and ESR0.535, with NSE having the highest diagnostic value. Conclusion Serum NSE can serve as an inflammatory indicator for paediatric pneumonia, which has important clinical guidance significance for the diagnosis, condition evaluation, and prognosis of paediatric pneumonia.

Objective·To investigate the expression and clinical significance of geranylgeranyl diphosphate synthase1 (GGPS1) in lung squamous cell carcinoma (LUSC) by bioinformatics and immunohistochemistry.Methods·Firstly, the transcriptome data of LUSC tissues and paired normal tissues were downloaded from UCSC Xena platform. The data were standardized and differentially expressed by R language, and verified by UALCAN database. UALCAN and LinkedOmics databases were used to analyze the relationship between GGPS1 expression and clinicopathological features in LUSC patients. The Kaplan-Meier Plotter database was used to explore the effect of GGPS1 expression on prognosis in LUSC patients. The least absolute shrinkage and selection operator (LASSO) regression analyses were applied to screen gene correlation coefficients and risk scores. The diagnostic value of GGPS1 for LUSC was evaluated by nomogram and calibration curve. The protein-protein interaction (PPI) network of GGPS1 was constructed by using STRING and GeneMANIA databases. R language was used to select the differential genes related to GGPS1, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed. The expression of GGPS1 in LUSC patients was detected by immunohistochemistry, and its correlation with clinicopathological features and prognosis was analyzed.Results·Through the TIMER2.0 database, it was found that GGPS1 expression was increased in most tumors and was highly expressed in LUSC. The expression of GGPS1 in LUSC was higher than that in adjacent tissues in UCSC Xena and UALCAN databases (both P

Abstract Background The minimal important difference is a valuable metric in ascertaining the clinical relevance of a treatment, offering valuable guidance in patient management. There is a lack of available evidence concerning this metric in the context of outcomes related to female urinary incontinence, which might negatively impact clinical decision-making. Objectives To summarize the minimal important difference of patient-reported outcome measures associated with urinary incontinence, calculated according to both distribution- and anchor-based methods. Methods This is a systematic review conducted according to the PRISMA guidelines. The search strategy including the main terms for urinary incontinence and minimal important difference were used in five different databases (Medline, Embase, CINAHL, Web of Science, and Scopus) in 09 June 2021 and were updated in January 09, 2024 with no limits for date, language or publication status. Studies that provided minimal important difference (distribution- or anchor-based methods) for patient-reported outcome measures related to female urinary incontinence outcomes were included. The study selection and data extraction were performed independently by two different researchers. Only studies that reported the minimal important difference according to anchor-based methods were assessed by credibility and certainty of the evidence. When possible, absolute minimal important differences were calculated for each study separately according to the mean change of the group of participants that slightly improved. Results Twelve studies were included. Thirteen questionnaires with their respective minimal important differences reported according to distribution (effect size, standard error of measurement, standardized response mean) and anchor-based methods were found. Most of the measures for anchor methods did not consider the smallest difference identified by the participants to calculate the minimal important difference. All reports related to anchor-based methods presented low credibility and very low certainty of the evidence. We pooled 20 different estimates of minimal important differences using data from primary studies, considering different anchors and questionnaires. Conclusions There is a high variability around the minimal important difference related to patient-reported outcome measures for urinary incontinence outcomes according to the method of analysis, questionnaires, and anchors used, however, the credibility and certainty of the evidence to support these is still limited.

Background: Neurospecific Enolase (NSE), a multifunctional protein, is present in various tissues of the body and plays an important role in many disease processes, such as infection, inflammation, tumours, injury, and immunity. In recent years, the application of NSE in respiratory diseases has become increasingly widespread and a research hotspot. Objective: This study aims to explore the relationship between NSE and childhood pneumonia, providing assistance for the diagnosis and assessment of pneumonia. Methods: Using prospective research and case-control methods, We selected 129 children with pneumonia hospitalised in Weifang People's Hospital from September 2020 to April 2022 as the case group. Among them were 67 cases of Mycoplasma pneumoniae pneumonia (MP+), 62 cases of non-Mycoplasma pneumoniae pneumonia (MP -), and 21 cases of severe pneumonia. At the same time, 136 children who underwent outpatient health examinations were selected as the control group. The levels of NSE, ESR, CRP in cases group and NSE in control group were measured separately. Result: The NSE levels in the MP + group were 17.86 (14.29–22.54) ng/mL, while those in the MP- group were 17.89 (14.10–21.66) ng/mL, both of which were higher than the control group's NSE levels of 13.26(12.18,14.44) ng/mL (H = 46.92, P = 0.000). There was no statistically significant difference in NSE levels between the MP + and MP - groups (P > 0.05). The NSE level in the severe pneumonia group was 27.38 (13.95–34.06) ng/mL, higher than that in the mild pneumonia group, which was 17.68 (14.27–21.04) ng/mL, (P = 0.024). The AUC values for diagnosing pneumonia are NSE0.714, CRP0.539, and ESR0.535, with NSE having the highest diagnostic value. Conclusion: Serum NSE can serve as an inflammatory indicator for paediatric pneumonia, which has important clinical guidance significance for the diagnosis, condition evaluation, and prognosis of paediatric pneumonia. [ABSTRACT FROM AUTHOR]

ObjectiveMethodsResultsConclusionIn light of the increasing importance of immunotherapy in bladder cancer treatment, this study is aim to investigate the expression and clinical significance of programmed cell surface death-1 (PD-1) in bladder cancer patients without lymph node metastasis, and to compare and analyze the difference of PD-1 in draining lymph nodes and tumor tissues.The expression of PD-1 on T cells and the proportion of positive PD-1 + T cells of IFN-γ and CD105a were detected by flow cytometry, and the correlation between PD-1 expression and clinical parameters was analyzed.The percentage of PD-1 positive cells in drainage lymph nodes was higher than that in tumor tissues (P < 0.001). PD-1 positive cells accounted for the highest proportion in CD3 + T cells. The proportion of IFN-γ-positive PD-1 + T cells in draining lymph nodes was significantly higher than that in tumor tissues (P < 0.001), while there was no significant difference in CD105a positive PD-1 + T cells between tumor tissues and draining lymph nodes. Pathological grade, tumor size and stage were positively correlated with PD-1 expression level in the lymph nodes.The high expression of PD-1 in patients with bladder cancer without lymph node metastasis, especially in draining lymph nodes, suggests that PD-1 may play a key role in the regulation of tumor immune microenvironment. The correlation between PD-1 and clinical parameters indicates its potential prognostic value. These findings provide important clinical implications for PD-1 targeted therapy, but further prospective studies are needed to determine the application value of PD-1 in therapeutic strategies. [ABSTRACT FROM AUTHOR]

Genetic testing, including whole genome, whole exome, and other next‐generation sequencing technologies, has evolved vastly in the past decade. With this, the number of identified genes and genetic variants is constantly increasing. Although a variety of databases and online tools exist that summarize, categorize, and classify genes, a clear guideline of which information is needed when reporting a gene and what to do when identifying a new gene is lacking. This includes the correct nomenclature, descriptive information about genetic loci and genetic variation, aliases, and correlated phenotypes. This tutorial is meant to serve as an introduction to reporting genes in a paper and provides an overview of available databases and tools to obtain all necessary information on the genes of interest. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression and clinical significance of tear interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9) and transforming growth factor-ẞ1 (TGF-β1) of patients with type 2 diabetes mellitus (T2DM) complicated with dry eye(DE). Methods: A total of 97 patients with T2DM admitted to our hospital from May 2021 to October 2023 were selected and divided into T2DM group and T2DM combined with DE group according to whether DE was combined. In addition, 45 healthy subjects who underwent physical examination during the same period were selected as the control group. The expression levels of tear IL-6, MMP-9 and TGF-B1 of the three groups were detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of tear IL-6, MMP-9 and TGF-β1 of DE patients with different disease severity were compared. The influencing factors of T2DM complicated with DE were analyzed by univariate and multivariate Logistics regression analysis. The receiver operating characteristic curve (ROC) was used to analyze the predictive value of tear IL-6, MMP-9 and TGF-β1 for T2DM complicated with DE. Results: The expression levels of IL-6, MMP-9 and TGF-B1 in tears of T2DM combined with DE group were higher than those of T2DM group, and those of T2DM group were higher than those of control group(P<0.05). The expression levels of tear IL-6, MMP-9, TGF-β1 and ocular surface disease index (OSDI) score in the severe group were higher than those in the moderate group, and those in the moderate group were higher than those in the mild group (P<0.05). The tear film rupture time (BUT) and tear secretion test (SIT) in the severe group were lower than those in the moderate group, and those in the moderate group were lower than those in the mild group (P<0.05). The results of univariate analysis showed that age, fasting blood glucose (FBG), fasting insulin (FINS), high-sensitivity C-reactive protein (hs-CRP), BUT, SIT and OSDI scores were all influencing factors of T2DM complicated with DE (P<0.05), the results of multivariate analysis showed that OSDI score and the increase of tear IL-6, MMP-9 and TGF-β1 were independent risk factors for T2DM complicated with DE (P<0.05), and the in- crease of BUT and SIT were protective factors(P<0.05). Conclusion: The expression of tear IL-6, MMP-9 and TGF-B1 of T2DM patients with DE is increased, which can aggravate the condition of DE. The combined detection of the three indicators has a high predictive value for the risk of T2DM complicated with DE. [ABSTRACT FROM AUTHOR]

Background and Objectives: Facial vascular anatomy plays a pivotal role in both physiological context and in surgical intervention. While data exist on the individual course of the facial artery and vein, to date, the spatial relationship of the vasculature has been ill studied. The aim of this study was to assess the course of facial arteries, veins and branches one relative to another. Materials and Methods: In a total of 90 halved viscerocrania, the facial vessels were injected with colored latex. Dissection was carried out, the relation of the facial vessels was studied, and the distance at the lower margin of the mandible was measured. Furthermore, branches including the labial and angular vessels were assessed. Results: At the base of the mandible, the facial artery was located anterior to the facial vein in all cases at a mean distance of 6.2 mm (range 0–15 mm), with three cases of both vessels adjacent. An angular vein was present in all cases, while an angular artery was only present in 34.4% of cases. Conclusions: The main trunk of the facial artery and vein yields a rather independent course, with the facial artery always located anterior to the vein, while their branches, especially the labial vessels, demonstrate a closer relationship. [ABSTRACT FROM AUTHOR]

Obejective: To investigate the expression and clinical significance of long non-coding RNA lung adenocarcinoma metastasis-associated lung adenocarcinoma transcript 1 (LncRNA MALAT1) and microRNA-769-5p (miR-769-5p) in serum and gingival crevicular fluid of patients with chronic periodontitis. Methods: 117 patients with chronic periodontitis who were admitted to our hospital from June 2020 to July 2023 were selected as observation group, patients were divided into 39 cases in mild group, 42 cases in moderate group and 36 cases in severe group according to the severity of chronic periodontitis, another 117 healthy volunteers were selected as control group. The expression levels of LncRNA MALAT1 and miR-769-5p in serum and gingival crevicular fluid were compared between control group and observation group. The expression levels of LncRNA MALAT1 and miR-769-5p in serum and gingival crevicular fluid, the levels of inflammatory indexes [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interferon-γ (IFN-γ)] in serum and gingival crevicular fluid, periodontal indexes [periodontal pocket depth (PD), attachment loss (AL), gingival crevicular bleeding index (SBI), plaque index (PLI)] were compared among different disease severity. The correlation between inflammatory indicators, periodontal indicators and the expression levels of miR-769-5p and LncRNA MALAT1 in serum and gingival crevicular fluid in patients with chronic periodontitis were analyzed by Pearson correlation analysis. The diagnostic value of LncRNA MALAT1 and miR-769-5p in serum and gingival crevicular fluid for chronic periodontitis were analyzed by receiver operating characteristic (ROC) curve. Results: The expression levels of LncRNA MALAT1 in serum and gingival crevicular fluid in observation group were higher than those in control group (P<0.05), and the expression levels of miR-769-5p in serum and gingival crevicular fluid were lower than those in control group (P<0.05). The expression levels of LncRNA MALAT1 in serum and gingival crevicular fluid and IL-6, TNF-α, IFN-γ, PD, AL, SBI and PLI in mild group were lower than those in moderate group (P<0.05), and moderate group were lower than those of severe group (P<0.05). The expression levels of miR-769-5p in serum and gingival crevicular fluid were higher in mild group than in moderate group (P<0.05), and moderate group were higher than those of severe group (P<0.05). The expression level of LncRNA MALAT1 in serum and gingival crevicular fluid of patients with chronic periodontitis was positively correlated with IL-6, TNF-α, IFN-γ, PD, AL, SBI and PLI (P<0.05). The expression level of miR-769-5p in serum and gingival crevicular fluid was negatively correlated with IL-6, TNF-α, IFN-γ, PD, AL, SBI and PLI (P<0.05). The expression level of LncRNA MALAT1 in serum and gingival crevicular fluid was negatively correlated with the expression level of miR-769-5p (P<0.05). The area under the curve (AUC) of serum LncRNA MALAT1, miR-769-5p and combined detection in the diagnosis of chronic periodontitis were 0.800, 0.743 and 0.877 respectively. The AUC of gingival crevicular fluid LncRNA MALAT1, miR-769-5p and combined detection in the diagnosis of chronic periodontitis were 0.786, 0.849 and 0.891 respectively. Conclusion: The expression level of LncRNA MALAT1 in serum and gingival crevicular fluid of patients with chronic periodontitis is increase, and the expression level of miR-769-5p is decrease, which can aggravate the inflammatory reaction and periodontitis symptoms, the combine detection of LncRNA MALAT1 and miR-769-5p in serum and gingival crevicular fluid has high diagnostic value for chronic periodontitis. [ABSTRACT FROM AUTHOR]

Accessory bones around the elbow are scarce, with a reported mean incidence rate of 0.77%. The rarest one is the os supratrochleare anterius, with only a handful of documented cases in the literature. Despite their scarcity, various types of ossicles have been documented, posing diagnostic challenges and potential misinterpretation on X-rays. Herein, we report a case of an accidentally found os supratrochleare anterius in a 43-year-old pig farmer presenting with symptoms of tennis elbow. After conservative treatment with nonsteroidal anti-inflammatory drugs and physiotherapy, he made a full recovery within 2 weeks. This report emphasizes the rarity of the ossupra trochleare anterius, the importance of accurate diagnosis, and the need for continued research and awareness of this anatomical variation. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression of circRNA_0001445 in plasma in senile osteoporosis (SOP) and its clinical significance. Methods Patients hospitalized in the Department of Geriatric, the First People's Hospital of Changzhou from November 2020 to May 2022 were collected. All subjects were measured bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) and divided into SOP group, osteopenia group and normal bone mass group according to BMD level. The clinical data and circRNA_0001445 expression levels were compared in each group. The correlation between circRNA_0001445 and BMD was analyzed by Pearson correlation analysis. The risk factors of SOP were analyzed by binary logistic regression. The diagnostic value of circRNA_0001445 in SOP was analyzed by receiver operating characteristic (ROC) curve. The changes of circRNA_0001445 expression levels before and after treatment was compared by paired-samples t test or paired-samples rank sum test. Results A total of 150 patients were included in this study, each group had 50 samples. The expression of circRNA_ 0001445 in SOP group (0.58±0.30) was significantly lower than that in osteopenia group (0.88±0.35) and normal bone mass group (1.15±0.62), P<0.001; Pearson correlation analysis showed that circRNA_0001445 expression was positively correlated with lumbar spine BMD (r = 0.427, P< 0.001), femoral neck BMD (r = 0.363, P < 0.001) and hip BMD ( r = 0.435, P < 0.001). Binary logistic regression showed high TC ( OR = 2.74,95\%CI : 1.473-5.099), low BMI ( OR = 0 0.674,95% CI: 0.543-0.837) and circRNA_0001445 (OR=0.019, 95% CI: 0.002-0.144) were risk factors for SOP, P< 0.05. ROC curve analysis showed that circRNA_0001445 could distinguish SOP patients from normal bone mass patients (AUC = 0. 810, 95% CI: 0.728- 0.892), osteopenia patients (AUC=0.756, 95% CI: 0. 662-0.849) and non-SOP patients (AUC=0.783, 95% CI:0. 706-0. 860). After 1 year of SOP treatment, the expression of circRNA_0001445 was higher than before (1.13±0.61 vs 2. 14±0.61), P<0.001. Conclusion The circRNA_0001445 showed low expression in SOP, which has certain clinical value for diagnosis and treatment monitoring of SOP. [ABSTRACT FROM AUTHOR]

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Background: The minimal important difference is a valuable metric in ascertaining the clinical relevance of a treatment, offering valuable guidance in patient management. There is a lack of available evidence concerning this metric in the context of outcomes related to female urinary incontinence, which might negatively impact clinical decision-making. Objectives: To summarize the minimal important difference of patient-reported outcome measures associated with urinary incontinence, calculated according to both distribution- and anchor-based methods. Methods: This is a systematic review conducted according to the PRISMA guidelines. The search strategy including the main terms for urinary incontinence and minimal important difference were used in five different databases (Medline, Embase, CINAHL, Web of Science, and Scopus) in 09 June 2021 and were updated in January 09, 2024 with no limits for date, language or publication status. Studies that provided minimal important difference (distribution- or anchor-based methods) for patient-reported outcome measures related to female urinary incontinence outcomes were included. The study selection and data extraction were performed independently by two different researchers. Only studies that reported the minimal important difference according to anchor-based methods were assessed by credibility and certainty of the evidence. When possible, absolute minimal important differences were calculated for each study separately according to the mean change of the group of participants that slightly improved. Results: Twelve studies were included. Thirteen questionnaires with their respective minimal important differences reported according to distribution (effect size, standard error of measurement, standardized response mean) and anchor-based methods were found. Most of the measures for anchor methods did not consider the smallest difference identified by the participants to calculate the minimal important difference. All reports related to anchor-based methods presented low credibility and very low certainty of the evidence. We pooled 20 different estimates of minimal important differences using data from primary studies, considering different anchors and questionnaires. Conclusions: There is a high variability around the minimal important difference related to patient-reported outcome measures for urinary incontinence outcomes according to the method of analysis, questionnaires, and anchors used, however, the credibility and certainty of the evidence to support these is still limited. [ABSTRACT FROM AUTHOR]

Background: A vast number of researchers have discovered high levels of human epidermal growth factor receptor-2 (HER2) expression in urothelial carcinoma (UC), but they do not use a uniform scoring system. Based on the 2021 edition of clinical pathological expert consensus on HER-2 testing in UC in China, we investigated the expression level and clinical significance of HER2 in high-grade UC. Furthermore, we looked at the prognosis of patients with locally advanced/metastatic UC after combining HER2 targeting antibody-drug conjugates (ADC) medication disitamab vedotin (DV) with programmed cell death protein 1 (PD-1) inhibitor tislelizumab. Patients and methods: From 2019 to 2022, we collected paraffin specimens of UC from the Department of Urology at the Provincial Hospital Affiliated to Shandong First Medical University. HER2 expression-related factors were investigated. Patients with advanced UC who have failed systemic chemotherapy at least once and had received immune checkpoint inhibitor (ICI) medication during second-line treatment were selected and treated with DV in combination with tislelizumab. We assessed the therapy's efficacy and safety. Results: 185 patients with high-grade UC were included in this investigation. 127 patients (68.7%) were HER2 positive (IHC 2+/3+) according to the 2021 Clinical pathological expert consensus on HER2 testing in UC in China. The clinical stage of UC differed statistically significantly between the HER2-and HER2+ groups (p = 0.019). Sixteen advanced UC patients were treated with DV and tislelizumab for a median of 14 months. The disease control rate was 87.5%, while the objective response rate (ORR) was 62.5%. The ORR of HER2+ individuals was higher than that of HER2-individuals (70.0% vs. 50.0%). The median progression-free survival or overall survival was not reached. In this study, the incidence of treatment-related adverse events was 68.8% (11/16), with all of them being grade 1 or 2 adverse reactions. Conclusion: HER2 protein expressed at a high percentage in UC, and 68.7% patients expressed HER2 positive (IHC 2+/3+). HER2+ expression is positively correlated with higher clinical stage of UC. HER2 targeted ADC drug disitamab vedotin combining with PD-1 inhibitor tislelizumab has shown efficacy, safety and controllable adverse reactions in the treatment of advanced UC. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is a common malignant tumor in female. In recent years, with the change of fertility pattern and lifestyle, the incidence of breast cancer is increasing year by year, seriously endangering the health and life of women. MRI is suitable for follow-up evaluation of the course of neoadjuvant chemotherapy in LABC, but there are few related studies and reports. Based on the above background, it is necessary to further evaluate the value of functional magnetic resonance imaging in neoadjuvant chemotherapy in patients with triple negative breast cancer, so as to lay a theoretical foundation for the popularization and application of this detection method. Based on this, this study was to explore the value, diagnostic efficacy and clinical importance of functional magnetic resonance imaging in evaluating the efficacy of neoadjuvant chemotherapy in patients with triple negative breast cancer. Methods: A total of 62 patients with triple-negative breast cancer who received neoadjuvant chemotherapy in our hospital from September 2017 to September 2022 were selected. To compare the differences of functional magnetic resonance imaging (fMRI) between effective and ineffective patients with neoadjuvant chemotherapy, the related data were statistically analyzed. Results: There was no significant difference between the mode of tumor withdrawal and the pathological complete remission of tumor tissue (P>0.05). There was no significant difference in anti-Trop-2 antibody-drug conjugates (ADC) data before and after chemotherapy between over-expressed patients with human epidermal growth factor receptor-2 (HER-2) and non-over-expressed patients with HER-2 (P>0.05). The levels of ADC and D ADC in pathological complete remission patients after chemotherapy were significantly higher than those in non-pathological complete remission patients (P<0.05). Using the DADC value as the evaluation parameter, the pathological response of tumor tissue was classified as the "gold standard" to draw the ROC curve, the area under curve (AUC) was 0.673, the cut-off of DADC to evaluate the significant response of tumor tissue after chemotherapy was 1.418, the sensitivity of evaluating the efficacy was 71.9%, and the specificity was 55.0%. Conclusion: Functional magnetic resonance imaging (fMRI) has diagnostic value for neoadjuvant chemotherapy in patients with triple negative breast cancer. According to the change of ADC value, the curative effect can be predicted early and the treatment strategy can be adjusted in time. [ABSTRACT FROM AUTHOR]

Introduction: Quantitative research and quality improvement (QI) both seek to improve care provided to patients. However, clinicians often blur the lines between how to appropriately analyze data from these methodologies. Clinicians may inappropriately use statistical analyses for QI initiatives, rather than using run and statistical process control (SPC) charts to analyze improvements in outcomes. Objective: The purpose of this article was to address the analytic methods used for QI initiatives in the clinical setting in an effort to show clinicians how to identify meaningful improvements in clinical practice. Methods: In this article, we provide an example comparing the same evidence-based practice/QI initiative (chlorhexidine gluconate bathing in a medical intensive care unit) using a quasi-experimental pretest/posttest research design with statistical analyses completed with t tests with analyses using run and SPC charts to show the data trended over time. Using a pretest/posttest design, chlorhexidine gluconate bathing compliance improved from 63%to 65%, a nonsignificant change, P = .075. These same data plotted on run and SPC charts, however, show a shift and a trend, indicating clinically significant improvements per QI methodologies. Conclusion: The example in this article highlights the pitfall of relying only on statistical analyses and P values to determine the importance of a clinical project, and provides a practical example for how run or SPC charts can be used to identify improvements over time. [ABSTRACT FROM AUTHOR]

Objective·To investigate the expression and clinical significance of geranylgeranyl diphosphate synthase1 (GGPS1) in lung squamous cell carcinoma (LUSC) by bioinformatics and immunohistochemistry. Methods·Firstly, the transcriptome data of LUSC tissues and paired normal tissues were downloaded from UCSC Xena platform. The data were standardized and differentially expressed by R language, and verified by UALCAN database. UALCAN and LinkedOmics databases were used to analyze the relationship between GGPS1 expression and clinicopathological features in LUSC patients. The Kaplan-Meier Plotter database was used to explore the effect of GGPS1 expression on prognosis in LUSC patients. The least absolute shrinkage and selection operator (LASSO) regression analyses were applied to screen gene correlation coefficients and risk scores. The diagnostic value of GGPS1 for LUSC was evaluated by nomogram and calibration curve. The protein-protein interaction (PPI) network of GGPS1 was constructed by using STRING and GeneMANIA databases. R language was used to select the differential genes related to GGPS1, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed. The expression of GGPS1 in LUSC patients was detected by immunohistochemistry, and its correlation with clinicopathological features and prognosis was analyzed. Results·Through the TIMER2.0 database, it was found that GGPS1 expression was increased in most tumors and was highly expressed in LUSC. The expression of GGPS1 in LUSC was higher than that in adjacent tissues in UCSC Xena and UALCAN databases (both P<0.05). It was found that the expression level of GGPS1 was higher in patients with late stage in UALCAN and LinkedOmics databases, and the overall survival (OS) of LUSC patients with high expression of GGPS1 was shorter (P<0.05) in the Kaplan-Meier Plotter database. Assessment of LUSC patients based on LASSO regression had good risk prediction efficacy. Constructing an individualised prediction model for LUSC patients has the best prediction accuracy. The results of GO and KEGG showed that GGPS1-related genes were mainly related to protein metabolism, regulation of lipid and cholesterol metabolism, nicotine addiction, phosphatidylinositol3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), peroxisome proliferator-activated receptors (PPAR) signaling pathway and so on. The metabolic function of GGPS1 may promote tumorigenesis. The results of immunohistochemistry showed that GGPS1 was mainly located in the cytoplasm, and the expression of GGPS1 in LUSC tissues was higher than that in adjacent tissues (P<0.05). The high expression of GGPS1 was related to tumor size, lymph node metastasis and TNM stage of LUSC patients (all P<0.05), and the OS of patients with high expression of GGPS1 was significantly shorter than that of patients with low expression (P=0.000). Multivariate Cox regression analysis suggested that GGPS 1 could be used as an independent prognostic factor for LUSC. Conclusion·Compared with normal lung tissue, the expression of GGPS1 in LUSC is significantly increased, especially in patients with large tumor volume, positive lymph node metastasis and advanced stage. GGPS1 overexpression is an independent predictor of poor prognosis in LUSC patients. GGPS1 is expected to become a new molecular target for the diagnosis, treatment and prevention of LUSC. [ABSTRACT FROM AUTHOR]

Shiga toxin-producing Escherichia coli (STEC) infection can cause a broad spectrum of symptoms spanning from asymptomatic shedding to mild and bloody diarrhea (BD) and even life-threatening hemolytic-uremic syndrome (HUS). As a member of the serine protease autotransporters of Enterobacteriaceae (SPATE) family, EspP has the ability to degrade human coagulation factor V, leading to mucosal bleeding, and also plays a role in bacteria adhesion to the surface of host cells. Here, we investigated the prevalence and genetic diversity of espP among clinical STEC isolates from patients with mild diarrhea, BD, and HUS, as well as from asymptomatic individuals, and assessed the presence of espP and its subtypes in correlation to disease severity. We found that 130 out of 239 (54.4%) clinical STEC strains were espP positive, and the presence of espP was significantly associated with BD, HUS, and O157:H7 serotype. Eighteen unique espP genotypes (GTs) were identified and categorized into four espP subtypes, i.e., espPα (119, 91.5%), espPγ (5, 3.8%), espPδ (4, 3.1%), and espPε (2, 1.5%). espPα was widely distributed, especially in strains from patients with BD and HUS, and correlated with serotype O157:H7. Serogroup O26, O145, O121, and O103 strains carried espPα only. Ten GTs were identified in espPα, and espPα/GT2 was significantly associated with severe disease, i.e., BD and HUS. Additionally, espP was strongly linked to the presence of eae gene, and the coexistence of espPα and stx2/stx2a + stx2c was closely related to HUS status. To sum up, our data demonstrated a high prevalence and genetic diversity of the espP gene in clinical STEC strains in Sweden and revealed an association between the presence of espP, espP subtypes, and disease severity. espP, particularly the espPα subtype, was prone to be present in more virulent STEC strains, e.g., "top-six" serotypes strains. [ABSTRACT FROM AUTHOR]

With the global spread of human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS), the pursuit of potent treatments has ascended as a paramount concern in global healthcare. Traditional Chinese medicine (TCM) has been used for thousands of years in China and other East Asian countries and it offers remedies for an extensive array of ailments, including HIV and AIDS. This review focuses on the clinical significance of single herbs and composite tonics in TCM with antiviral activity against HIV. Initially, the anti-HIV activity of single herbs was analyzed in detail. Many herbs have been shown to have significant anti-HIV activity. The active ingredients of these herbs exhibit their anti-HIV effects through various mechanisms, such as inhibiting viral replication, preventing viral binding to host cells, and interfering with the viral lifecycle. Furthermore, we delved into the clinical significance of HIV-associated formulations provided as a result of Chinese compound prescription. These combinations of herbal ingredients are designed to amplify therapeutic efficacy and minimize adverse effects. Clinical trials have demonstrated the therapeutic benefits of these prescriptions for individuals infected with HIV. The intricate composition of these prescriptions potentially augments their anti-HIV activity through synergistic effects. Additionally, this review underscores the clinical importance of TCM in the context of HIV treatment. While numerous herbs and prescriptions exhibit anti-HIV activity, their safety and efficacy in clinical applications warrant further investigation. When combined with contemporary antiretroviral drugs, TCM may serve as an adjunctive therapy, assisting in reducing side effects, and enhancing patients' quality of life. To optimally harness these natural resources, further exploration is imperative to ascertain their efficacy, safety, and optimal utilization, thereby offering a broader spectrum of therapeutic options for HIV-afflicted individuals.

ABSTRACT Redundant carbapenemase-producing (RCP) bacteria, which carry double or multiple carbapenemases, represent a new and concerning phenomenon. The objective of this study is to conduct a comprehensive analysis of the epidemiology and genetic mechanisms of RCP strains to support targeted surveillance and control measures. A retrospective analysis was conducted using surveillance data from 277 articles. Statistical analysis was performed to determine and evaluate species prevalence, proportions of carbapenemases, antibiotic susceptibility profiles, sample information, and patient outcomes. Complete plasmid sequencing data were utilized to investigate potential antimicrobial resistance or virulence advantages that strains may gain from acquiring redundant carbapenemases. RCP bacteria are widely distributed globally, and their prevalence is increasing over time. Several countries, including China, India, Iran, Turkey, and South Korea, have reported more than 100 RCP strains. The most commonly reported RCP species are Klebsiella pneumoniae and Acinetobacter baumannii, which exhibit varying proportions of carbapenemase combinations. Certain species-carbapenemase combinations, such as K. pneumoniae carrying New Delhi metallo-β-lactamase (NDM) + oxacillinase (OXA) (56.76%) and K. pneumoniae carbapenemase (KPC) + Verona integron-encoded metallo-β-lactamase (VIM) (50.00%) carbapenemases, are associated with high mortality rates. In patients with RCP strains isolated from the bloodstream and respiratory system, the mortality rates are 58.70% and 69.23%, respectively. Analysis of plasmids from RCP strains suggests that they may acquire additional antibiotic resistance phenotypes and virulence factors. Carbapenem-resistant bacteria carrying redundant carbapenemases pose a significant global health threat. This study provides valuable insights into the epidemiology and genetic mechanisms of these bacteria, supporting the development of effective control and prevention strategies to mitigate their transmission.IMPORTANCEThis study examined the global distribution patterns of 1,780 bacteria with double or multiple carbapenemases from 277 articles and assessed their clinical impact. The presence of multiple carbapenemases increases the chances of co-resistance to other classes of antibiotics and more virulence factors, further complicating the clinical management of infections.

Abstract Low back pain (LBP) and neck pain predominate as the primary causes of disability. Cell‐ and platelet‐rich plasma (PRP) products are potential therapies with clinical trials and reviews promoting their efficacy. Nonetheless, they frequently disregard the clinical significance of reported improvements. In this systematic review, the effectuated improvements in pain, disability, quality of life (QoL), and radiographic images are comprehensively described and scored on their clinical significance. An electronic database literature search was conducted on July 2023 for in‐human assessment of cell or PRP products to alleviate discogenic pain. Papers were screened on quantitative pain, disability, QoL, radiographic improvements, and safety outcomes. Risk of bias was assessed through MINORS and Cochrane Source of Bias tools. Reported outcomes were obtained, calculated, and assessed to meet minimal clinically important difference (MCID) standards. From 7623 screened papers, a total of 80 articles met the eligibility criteria, presenting 68 specific studies. These presented at least 1974 treated patients. Overall, cell/PRP injections could alleviate pain and disability, resulting in MCID for pain and disability in up to a 2‐year follow‐up, similar to those observed in patients undergoing spinal fusion. Included trials predominantly presented high levels of bias, involved heterogeneous study designs, and only a minimal number of randomized controlled trials. Nonetheless, a clear clinically significant impact was observed for cell‐ and PRP‐treated cohorts with overall good safety profiles. These results highlight a strong therapeutic potential but also underline the need for future cost‐effectiveness assessments to determine the benefits of cell/PRP treatments.

The purpose of the research was to identify ultrasound criteria of extranodal extension (ENE) in metastases of papillary thyroid cancer and to evaluate the clinical significance of ENE.Material and Methods. Ultrasound signs of ENE in 283 cervical lymph node metastases from papillary thyroid cancer were analyzed. Extranodal extension in 137 metastases was diagnosed by ultrasound and verified by histological examination. Micrometastases invisible on ultrasound were detected in 144 patients; metastases located inside the organ were detected in 147 patients; metastases located outside the organ were revealed in 136 patients; the size of 98 metastases was less than 1 cm; the size of 185 metastases was more than 1 cm; the age of 51 patients was under 55 years; 132 patients were older than 55 years. Diagnostic significance of ENE and its clinical significance were estimated according to χ2 Pirson criteria.Results: Two ultrasound criteria: shape change and blurred margins of metastases indicated the presence of ENE. The small number of ultrasound false-negative findings indicated the need for further research. The number of micrometastases not detected by ultrasound was 2-fold higher in patients who had metastases with ENE than in patients who had metastases without ENE. The number of patients with ENE in metastases inside the organ (T1a, T1b, T2 and T3b) was 2.7 times lower compared to patients with metastases developed outside the organ (T3a, T4a, T4b); ENE was observed in metastases of different size and did not depend on age groups.Conclusion. The ultrasound method allows intravital detection of ENE in metastases of papillary thyroid cancer. The extension is accompanied by a significantly high number of micrometastases in the neck tissue. It is detected more often in metastases located outside the organ, regardless of the size and age of the patients. The extra-nodal extension should be considered as a criterion for an unfavorable prognosis.

Abstract Background Reliable species identification of cultured isolates is essential in clinical bacteriology. We established a new study algorithm named NOVA – Novel Organism Verification and Analysis to systematically analyze bacterial isolates that cannot be characterized by conventional identification procedures MALDI-TOF MS and partial 16 S rRNA gene sequencing using Whole Genome Sequencing (WGS). Results We identified a total of 35 bacterial strains that represent potentially novel species. Corynebacterium sp. (n = 6) and Schaalia sp. (n = 5) were the predominant genera. Two strains each were identified within the genera Anaerococcus, Clostridium, Desulfovibrio, and Peptoniphilus, and one new species was detected within Citrobacter, Dermabacter, Helcococcus, Lancefieldella, Neisseria, Ochrobactrum (Brucella), Paenibacillus, Pantoea, Porphyromonas, Pseudoclavibacter, Pseudomonas, Psychrobacter, Pusillimonas, Rothia, Sneathia, and Tessaracoccus. Twenty-seven of 35 strains were isolated from deep tissue specimens or blood cultures. Seven out of 35 isolated strains identified were clinically relevant. In addition, 26 bacterial strains that could only be identified at the species level using WGS analysis, were mainly organisms that have been identified/classified very recently. Conclusion Our new algorithm proved to be a powerful tool for detection and identification of novel bacterial organisms. Publicly available clinical and genomic data may help to better understand their clinical and ecological role. Our identification of 35 novel strains, 7 of which appear to be clinically relevant, shows the wide range of undescribed pathogens yet to define.

So far, the monoclonal hypothesis of tumor occurrence and development cannot be justified. The genetic diversity selection hypothesis for the occurrence and development of lung cancer links Mendelian genetics with Darwin's theory of evolution, suggesting that the genetic diversity of tumor cell populations with polyclonal origins-monoclonal selection-subclonal expansion is the result of selection pressure. Normal cells acquire mutations in oncogenic driver genes and have a selective advantage over other cells, becoming tumor initiating cells; In the interaction with the tumor microenvironment (TME), the vast majority of initiating cells are recognized and killed by the human immune system. If immune escape occurs, the incidence of malignant tumors will greatly increase, and subclonal expansion, intratumour heterogeneity, etc. will occur. This article proposed the hypothesis of genetic diversity selection and analyzed its clinical significance.