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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.

Purpose: The study sought to compare the number of cycles (NOS) for the first and second thirty-seconds (FASTS) within 1 min of accommodative facility (AF) and vergence facility (VF) testing to explore possibilities of reducing testing time to 30 s. Methods: In this cross-sectional study, a multistage sample of school children (aged 8–17 years) was taken through ocular-visual screening. Eligible participants (586) underwent refraction, stereo-acuity measurement, AF testing using ± 2D lens flippers, and VF testing using 3Δ BI/12Δ BO flipper prisms. The NOS within the FASTS of AF and VF tests were compared, respectively. Results: A statistically insignificant mean difference of 0.01 cycles was found between the NOS for the FASTS of monocular AF in the right eye (Wilcoxon Signed Rank test, p = .715). Statistically significant differences of 0.06, 0.14, and 0.09 cycles (Wilcoxon Signed Rank test, p < .05) which are not clinically meaningful were found for monocular AF in the left eye, binocular AF, and VF with no level of agreement on Bland Altman analysis, respectively. There were no clinically meaningful differences between the first 30-s cycles multiplied by two (FTSMT) and the full 1-min test period cycles for monocular AF, binocular AF, and VF. Conclusion: The FTSMT approach may be applied during gross screening to shorten testing time as further study is recommended for its diagnostic validity. [ABSTRACT FROM AUTHOR]

Colon cancer poses a significant threat to human life with a high global mortality rate. Early and accurate detection is crucial for improving treatment quality and the survival rate. This paper presents a comprehensive approach to enhance colon cancer detection and classification. The histopathological images are gathered from the CRC‐VAL‐HE‐7K dataset. The images undergo preprocessing to improve quality, followed by augmentation to increase dataset size and enhance model generalization. A deep learning based transformer model is designed for efficient feature extraction and enhancing classification by incorporating a convolutional neural network (CNN). A cross‐transformation model captures long‐range dependencies between regions, and an attention mechanism assigns weights to highlight crucial features. To boost classification accuracy, a Siamese network distinguishes colon cancer tissue classes based on probabilities. Optimization algorithms fine‐tune model parameters, categorizing colon cancer tissues into different classes. The multi‐class classification performance is evaluated in the experimental evaluation, which demonstrates that the proposed model provided highest accuracy rate of 98.84%. In this research article, the proposed method achieved better performance in all analyses by comparing with other existing methods. Research Highlights: Deep learning‐based techniques are proposed.DL methods are used to enhance colon cancer detection and classification.CRC‐VAL‐HE‐7K dataset is utilized to enhance image quality.Hybrid particle swarm optimization (PSO) and dwarf mongoose optimization (DMO) are used.The deep learning models are tuned by implementing the PSO‐DMO algorithm. [ABSTRACT FROM AUTHOR]

Background/Objectives: Angiogenesis is involved in the pathogenesis of hereditary hemorrhagic telangiectasia (HHT). VEGF, ANG2, TGFβ1, and ENG are the most studied angiogenic factors, but their clinical significance in blood samples is still not completely defined. The genetic study of HHT mutations is the test of choice for diagnosing the disease, but this route is expensive, and the causative mutation is not found in up to 10% of cases. Therefore, the use of angiogenic biomarkers could facilitate a cheaper and easier approach to the diagnosis of HHT. To determine the diagnostic and prognostic value of the VEGFA, TGFβ1, ANG2, and ENG plasmatic concentrations in patients with HHT. Methods: All the participants were clinically evaluated and the concentrations of these angiogenic factors were measured using MILLIPLEX®MAP immunoassays in plasma samples collected from 44 patients with HHT and 19 controls. To evaluate the diagnostic validity of these parameters, we estimated the maximum Youden index of the ROC curve and evaluated their diagnostic value using multiple logistic regression. Results: Patients with HHT had increased blood levels of TGFβ1 and decreased ENG compared to the control group. We could not identify any angiogenic markers related to the clinical severity or epistaxis. TGFβ1 and ENG exhibited a higher discriminant capacity for HHT, especially patients with HHT1, and it was possible to develop signatures of these factors with diagnostic value. Conclusions: We identified several angiogenic factors that may be important diagnostic biomarkers for HHT and propose that the combination of TGFβ1 and ENG could represent a signature with diagnostic value for this disease. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionsEndoglin/CD105-microvessel density (CD105-MVD) is identified as one of the most potential methods for semi-quantification of angiogenesis in human cancer tissues. Present study aimed to examine the diagnosticand prognostic value of CD105-MVD in two clinically distinct subtypes of urothelial carcinoma of bladder (UCB) namely non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) patients.Message expression of endoglin was analysed by real-time quantitative polymerase chain reaction (RT-qPCR) and MVD measurement was done by immunohistochemical staining in 90 UCB [NMIBC: 60; MIBC: 30] patients. SEM studies were carried out to examine tumor vasculature and extent of neoangiogenesis in NMIBC and MIBC patients.Elevated message expression of CD105 showed statistical significance with tumor stage, grade, smoking/tobacco chewing history in NMIBC andage in MIBC cohort. Higher values of CD105-MVD showed statistical relevance with tumor stage, grade, size, smoking/tobacco chewing history in NMIBC cohort. Kaplan Meier test identified high CD105-MVD as strong predictor of poor RFS in NMIBC patients.Association of CD105 expression and MVD with the clinicohistopathological features as well as poor survival outcomes potentially identify it as a preferred marker of clinical significance in a given cohort of UCB patients.Clinical significanceStrong association of CD105 at message level with the demographics of UCB patients identifies it as a marker of diagnosis in a given cohort of patients.Survival analysis examined CD105-MVD as an independent strong predictor of poor recurrence free survival in NMIBC patients.Present study provides clear evidence of increased vascular density, vascular sprouts proliferation and new blood vessel formation with disease aggressiveness indicating CD105 as a preferred marker of neoangiogenesis in the given cohort of patients.The study describes CD105-MVD as a biomarker of diagnosis and prognosis with the sensitivity of 91.67% and 93.33% in a given cohort of NMIBC and MIBC patients.Strong association of CD105 at message level with the demographics of UCB patients identifies it as a marker of diagnosis in a given cohort of patients.Survival analysis examined CD105-MVD as an independent strong predictor of poor recurrence free survival in NMIBC patients.Present study provides clear evidence of increased vascular density, vascular sprouts proliferation and new blood vessel formation with disease aggressiveness indicating CD105 as a preferred marker of neoangiogenesis in the given cohort of patients.The study describes CD105-MVD as a biomarker of diagnosis and prognosis with the sensitivity of 91.67% and 93.33% in a given cohort of NMIBC and MIBC patients. [ABSTRACT FROM AUTHOR]

Objective: Claudin18.2 has been established as a putative therapeutic target in human solid malignancies. The aim of this study is to determine claudin18.2 expression as a clinicopathological and prognostic factor in human solid tumors through a systematic review and meta-analysis. Articles were systematically reviewed for studies that included the correlation between claudin18.2 expression and clinicopathological features and prognosis in solid tumors. Meta-analysis was conducted to estimate either odds ratio and 95% confidence intervals (CIs) of clinicopathological factors or hazard ratio and 95% CIs of survival outcomes for claudin18.2 expression in all available solid tumors. Results: 21 studies including 5,331 patients were identified. Overall proportion of claudin18.2 positivity was 29.7%. Analyses of clinicopathological features demonstrated that claudin18.2 positivity correlated with male predominance, lower T stage, more frequent MUC5AC positivity when all primary tumors included. In subgroup analysis, gastric cancer showed significant correlation between high claudin18.2 expression and frequent EBV infection, male predominance and lower T stage. In lung cancer, claudin18.2 expression was associated with favorable overall survival. However, analyses of survival outcomes in all solid tumors showed that claudin18.2 expression was not associated with overall survival and pooled disease-free survival, tumor-specific survival, progression-free survival and relapse-free survival. Conclusions: Our study emphasizes evaluation of claudin18.2 expression as a potential prognostic factor in lung adenocarcinoma and further exploration in other solid tumors as well. Systematic review registration: https://www.crd.york.ac.uk/prospero/ , identifier CRD42023468651. [ABSTRACT FROM AUTHOR]

We aimed to analyze the clinical profile and malignancy indicators in dermatomyositis (DM) with anti‐transcriptional intermediary factor 1 antibody (anti‐TIF1γ‐Ab). A comparison was made between clinical information of anti‐TIF1γ DM patients with and without malignancy. Additionally, a review of the literature on anti‐TIF1γ DM and malignancy was conducted by searching PubMed and EMBASE databases. In our cohort of 37 patients, 27.0% (10/37) developed malignancy. The timeframe during which these 10 patients developed malignancy ranged from 21 months prior to the diagnosis of DM to 36 months following the diagnosis of DM. Specifically, one patient was diagnosed with breast cancer at the age of 36. Comparing the groups with and without malignancy, we found that age over 65 years (40% vs 7.4%, P = 0.035), a shorter duration from the onset of symptoms to the diagnosis of DM (2.5 vs 10 months, P = 0.003), and higher erythrocyte sedimentation rate (ESR) levels (23 vs 10 mm/h, P = 0.048) were found to be associated with an increased risk of malignancy. Conversely, the presence of Gottron's papules (63% vs 20%, P = 0.029) may suggest a lower likelihood of malignancy. The literature review revealed that the prevalence of myositis‐associated malignancy was 40.7% (340/836), with variations ranging from 19% to 82.9% across different series. In summary, factors such as age over 65 years, a shorter duration between symptom onset and diagnosis of DM, and elevated ESR levels may indicate an increased risk of malignancy in anti‐TIF1γ DM patients. [ABSTRACT FROM AUTHOR]

Background Familial hypercholesterolemia (FH) is an autosomal dominant inherited disorder characterized by severe hypercholesterolemia and significantly elevated levels of serum low-density lipoprotein cholesterol (LDL-C). Patients with FH are at an increased risk of premature atherosclerotic cardiovascular disease, and early detection and treatment can improve their survival rates. Objective This study aims to explore the clinical value and significance of screening for FH among patients with hypercholesterolemia in community populations. Methods During the period from July to December 2023, a total of 164 patients diagnosed with hyperlipidemia and exhibiting LDL-C levels ≥4.90 mmol/L underwent gene sequencing at Department of Cardiology, the Affiliated Suzhou Hospital of Nanjing Medical University and its 5 community health centers within the medical alliance. Based on quartile intervals of LDL-C levels, the patients were stratified into four groups: Q1 group (LDL-C ≤5.10 mmol/L, n=43), Q2 group (5.10 mmol/L≤LDL-C≤5.32 mmol/L, n=40), Q3 group (5.32 mmol/L≤LDL-C≤5.67 mmol/L, n=41), and Q4 group (LDL-C≥5.67 mmol/L, n=40). Baseline data and laboratory test results of the patients were collected. Results A total of 164 patients with hypercholesterolemia were included, with a prevalence of awareness of dyslipidemia at 39.02% (64/164), and 21.95% (36/164) of the patients had previously taken lipid-lowering medications. The comparison of total cholesterol (TC) and LDL-C among Q1 to Q4 groups showed statistically significant differences (P0.05) . Conclusion In community populations with hypercholesterolemia and LDL-C ≥ 4.9 mmol/L, the rate of FH gene mutations is relatively high, and the rate of other primary (genetic) lipid metabolism gene mutations is also high. Screening for FH among patients with hypercholesterolemia in community populations has significant clinical importance and value.

Abstract Objective Mycoplasma pneumoniae is a major causative pathogen in community-acquired pneumonia. Respiratory viral coinfections in children with Mycoplasma pneumoniae pneumonia (MPP) are not uncommon and cause severe clinical manifestations. This study aims to investigate the impacts of viral coinfection in MPP patients and hopes to offer novel insights for discriminating between MPP and MPP coinfection. Methods This study recruited 748 children hospitalized for MP pneumonia between January 2021 and October 2023. Patients were classified into two groups: MPP coinfected with respiratory virus group and MPP group. All children underwent polymerase chain reaction testing for respiratory pathogens. Baseline clinical features and demographic data were obtained retrospectively through medical records. Results The retrospective study included 748 patients, with a viral coinfection rate of 38.75%. Patients in the MPP coinfected with respiratory virus group have a higher disease burden than those in the non-coinfection group. Our findings indicate that patients with Mycoplasma pneumonia co-infected with respiratory viruses had longer hospital stays and prolonged fever post-admission, as well as more severe conditions and a higher incidence of extrapulmonary complications. MPP coinfection was associated with the following factors: patients with extrapulmonary complications of gastroenteritis (OR = 4.474, 95%CI = 1.733–11.554, P = 0.002), longer hospital stay (OR = 1.109, 95%CI = 1.012–1.217, P = 0.027), longer days of fever after admission (OR = 1.215 95%CI = 1.006–1.469, P = 0.043), elevated white blood cell count (OR = 1.332 95%CI = 1.082–1.640, P = 0.007), decreased neutrophil count (OR = 0.768 95%CI = 0.602–0.981, P = 0.035), higher fibrinogen levels (OR = 1.652 95%CI = 1.138–2.398, P = 0.008), and raised lactate dehydrogenase levels (OR = 1.007 95%CI = 1.003–1.011, P = 0.001). Conclusions We determined the clinical significance of respiratory viral coinfection in children with MPP. Timely identification of MPP coinfection and provision of early and comprehensive therapeutic measures are vital in shortening the disease severity and improving prognosis.

Abstract Background The various systems of diagnosis and classification of mental disorders underline the need to evaluate the interference caused by the different disorders in a person’s daily life. The Maladjustment Inventory (MI) evaluates the impairment in the individual’s functioning in a brief and self-applied way, through six items. The objective of this research was to explore the psychometric properties of the MI scores through two studies, one with a Spanish clinical sample (Study 1) and another with a Spanish university students’ sample (Study 2). Methods The total sample was made up of 928 participants (81.1% women, n = 495 clinical sample). Descriptive analyses, exploration of internal structure and reliability, exploratory and confirmatory factor analyses, relationship with other variables (quality of life, anxiety, depression, neuroticism and extraversion), and percentiles and T-scores were performed. Results The results showed good psychometric properties of the MI, with a good fit model for one factor solution in both samples, Cronbach’s alpha coefficient of 0.84–88, and evidence of validity based on the relationship with other variables. Conclusion The good psychometric properties of the MI, together with its brevity, make it a recommended instrument for the evaluation of interference in both clinical and research contexts.

Signal transducer and activator of transcription 4 (STAT4) is a member of the STAT family, which is a group of transcription factors that regulate cytokine signaling. Genetic polymorphisms in STAT4 strongly influence immune responses and disease outcomes, especially in cancer and autoimmune diseases. Several studies have indicated that certain STAT4 gene variants are associated with alterations in STAT4 expression and/or activity and that there is a close relationship between STAT4 polymorphisms and drug efficacy. However, the underlying mechanisms are complex, and the roles of these polymorphisms in disease acquisition, progression, and severity are of widespread concern. Therefore, we provide an overview of the clinical significance of polymorphisms in STAT4 and the mechanisms by which these STAT4 variants are involved in various diseases. [ABSTRACT FROM AUTHOR]

Background: The various systems of diagnosis and classification of mental disorders underline the need to evaluate the interference caused by the different disorders in a person's daily life. The Maladjustment Inventory (MI) evaluates the impairment in the individual's functioning in a brief and self-applied way, through six items. The objective of this research was to explore the psychometric properties of the MI scores through two studies, one with a Spanish clinical sample (Study 1) and another with a Spanish university students' sample (Study 2). Methods: The total sample was made up of 928 participants (81.1% women, n = 495 clinical sample). Descriptive analyses, exploration of internal structure and reliability, exploratory and confirmatory factor analyses, relationship with other variables (quality of life, anxiety, depression, neuroticism and extraversion), and percentiles and T-scores were performed. Results: The results showed good psychometric properties of the MI, with a good fit model for one factor solution in both samples, Cronbach's alpha coefficient of 0.84–88, and evidence of validity based on the relationship with other variables. Conclusion: The good psychometric properties of the MI, together with its brevity, make it a recommended instrument for the evaluation of interference in both clinical and research contexts. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Methods Results Conclusion Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults and the 5‐year survival remains low.We analyzed the gene expression profiles of the complement and coagulation cascades pathway (CCCP) in 998 bone marrow (BM) and 122 peripheral blood (PB) samples of ALL patients and healthy individuals obtained from the TCGA database and evaluated their clinical significance in terms of being diagnostic and prognostic biomarkers.We identified 18 CCCP genes (SERPINA1, C5AR1, F5, CD55, PLAUR, C3AR1, THBD, CD59, PLAU, VWF, CFD, F13A1, C1QA, C1QB, C1QC, A2M, SERPINE1 and CR2) differentially expressed in the BM samples of ALL patients compared to healthy individuals. The expression levels of CD55, F13A1 and CR2 in BM were linked with the overall survival of ALL patients. While in PB only 11 CCCP genes (e.g., SERPINA1, C5AR1, F5, PLAUR, C3AR1, THBD, CFD, F13A1, C1QA, SERPINE1, and CR2) were differentially expressed and F13A1 was significantly associated with ALL patient survival. Machine learning enabled us to predict ALL using the CCCP genes and the accuracy can reach 0.9701 and 0.9167 using the BM and PB, respectively. Furthermore, using single‐cell RNA sequencing, we found that the differential expression of CCCP genes was found with diversity in the BM‐derived immune cells of ALL patients.Our findings suggest that the CCCP genes may play a key role in the progression of ALL and can be used as potential therapeutic targets and diagnostic markers. [ABSTRACT FROM AUTHOR]

Purpose: This comprehensive review thoroughly explores the clinical significance of the palmomental reflex (PMR) in neurological disorders. PMR is a primitive reflex that, when reemerging in adults, indicates underlying neurological dysfunction. Method: The article elaborates on the clinical assessment techniques, neurophysiological basis, and applications of PMR in various neurological disorders, including neurodegenerative diseases, cerebrovascular disorders, traumatic brain injury, and multiple sclerosis. Finding: By understanding the modulation and suppression mechanisms of PMR, valuable insights into the specific neurological impairments associated with these disorders can be gained. Conclusion: The potential of PMR as a diagnostic marker, prognostic indicator, and treatment monitoring tool is increasingly evident. [ABSTRACT FROM AUTHOR]

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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]

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]

Background: The paper aims to investigate the expression level of NLRP3 inflammasome and its related cell molecules in early diabetes kidney disease (EDKD) in the elderly and its clinical application value. Methods: From October 2021 to April 2023, 50 elderly patients with T2DM (T2DM group), 50 elderly patients with EDKD (EDKD group) and 50 elderly people who passed the health check-up (healthy group) were chosen as the study subjects. Plasma NLRP3 inflammasome and related cells (blood leukocyte count, monocyte count, lymphocyte count) molecular (NT-proBNP and others) levels are tested, and Pearson correlation analysis is utilized to explore the correlation among plasma NLRP3 inflammasome and related cells, molecules, and renal function indicators (UACR, BUN, Ucr) in elderly patients with EDKD. Results: (1) The three groups' comparison in HbA1c, FIns, HOMA-IR, UACR, BUN, Ucr, SOD, MCP-1, and TNF-α levels were with P<0.05. The levels of TG and LDL-C in the EDKD group were higher than those in the T2DM and the healthy groups; the levels of FPG, HbA1c, FINs, HOMA-IR, UACR, SOD, MCP-1, TNF-α in the EDKD and T2DM groups were higher than those in the healthy group, while SOD was smaller than that in the healthy group; the levels of BUN, Ucr, hs-CRP, FPG, HbA1c, FINs, HOMA-IR, UACR, SOD, MCP-1, TNF-α in the EDKD group were higher than those in the T2DM group, while SOD was smaller than that in the T2DM group. The above results were with P<0.05. (2) It has P<0.05 in Monocyte count, NLRP3, NT-proBNP, caspase-1, ASC and others in the three groups. Those in the EDKD and T2DM groups were higher than those in the healthy group. The levels of these indicators in the EDKD group were higher than those in the T2DM group, with P<0.05. NLRP3, Caspase-1, ASC, IL-1β, and IL-18 were positively correlated with UACR, BUN, and Ucr in the EDKD group. All the above differences were P<0.05. Conclusions: NLRP3 inflammasome and its related molecules caspase-1, ASC, IL-1β, IL-18 and other levels increase in early elderly EDKD and are closely related to the severity of EDKD. [ABSTRACT FROM AUTHOR]

To investigate the expression levels and clinical significance of serum copeptin (Copeptin), hypoxia inducible factor-1α (HIF-1α) and Beclin1 (Beclin1) in patients with decompensated hepatitis B cirrhosis (HBV-DC) and liver failure. 141 patients with HBV-DC and liver failure were selected as case group, and 73 healthy subjects who underwent physical examination during the same period were included in control group. Case group was divided into survival group and death group according to the survival status of the patients within 12 months of follow-up. The levels of serum Copeptin, HIF-1α and Beclin1 were detected. The related influencing factors of death in patients with HBV-DC and liver failure were analyzed by multivariate Logistic regression. The levels of serum Copeptin, HIF-1α and Beclin1 in case group were higher than those in control group (P<0.05). The serum levels of Copeptin, HIF-1α and Beclin1 in death group were higher than those in survival group (P<0.05). The elevated of model for end-stage liver disease (MELD) score, Copeptin, HIF-1α, and Beclin1 were risk factors for death in patients with HBV-DC and liver failure (P<0.05). The levels of serum Copeptin, HIF-1α and Beclin1 in patients with HBV-DC and liver failure are increase, which are independent risk factors for death. [ABSTRACT FROM AUTHOR]

Objective: To analyze the expression and clinical significance of E-box binding zinc finger protein 2 (ZEB2) and signal peptide-CUB-EGF-like domain protein 3 (SCUBE3) in non-specific invasive breast cancer (IBC-NST) tissues. Methods: The cinoma and adjacent tissues were collected from 168 IBC-NST patients in our hospital from March 2018 to December 2020, The relationship between ZEB 2 and SCUBE3 protein expression and clinicopathological features and prognosis was analyzed. Results: The positive expression rate of ZEB 2 and SCUBE3 protein in cancer tissues was significantly higher than that in adjacent tissues (P<0.05). The proportion of positive ZEB 2 and SCUBE3 protein expression in IBC-NST tumor ≥2, TNM staging stage, lymph node metastasis were higher than those with IBC-NST tumor <2, TNM stage I-stage, lymph node metastasis, and other types, respectively (P<0.05). The 3-year progression-free survival time (PFS) rate of patients with positive ZEB 2 and SCUBE3 expression was lower than those with ZEB 2 and SCUBE3 negative expression, respectively (P<0.05). Conclusion: The positive expression rates of ZEB2 and SCUBE3 protein in IBC-NST tissues are significantly increased, and the positive expression of ZEB2 and SCUBE3 protein is closely related to the tumor maximum diameter, TNM stage, lymph node metastasis and poor prognosis of IBC-NST patients. [ABSTRACT FROM AUTHOR]

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]

As widely noted in the literature and by international bodies such as the American Statistical Association, severe misinterpretations of P-values, confidence intervals, and statistical significance are sadly common in public health. This scenario poses serious risks concerning terminal decisions such as the approval or rejection of therapies. Cognitive distortions about statistics likely stem from poor teaching in schools and universities, overly simplified interpretations, and – as we suggest – the reckless use of calculation software with predefined standardized procedures. In light of this, we present a framework to recalibrate the role of frequentist-inferential statistics within clinical and epidemiological research. In particular, we stress that statistics is only a set of rules and numbers that make sense only when properly placed within a well-defined scientific context beforehand. Practical examples are discussed for educational purposes. Alongside this, we propose some tools to better evaluate statistical outcomes, such as multiple compatibility or surprisal intervals or tuples of various point hypotheses. Lastly, we emphasize that every conclusion must be informed by different kinds of scientific evidence (e.g., biochemical, clinical, statistical, etc.) and must be based on a careful examination of costs, risks, and benefits.

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.

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]

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]

Background Probiotics, which are live microorganisms beneficial to human health, have garnered significant attention in recent years due to their potential therapeutic and preventive effects on various health conditions. The human gut microbiota, comprising trillions of microorganisms, plays a crucial role in digestion, metabolism, immune function, and overall health. Disruptions in the gut microbiota have been associated with various diseases, including gastrointestinal disorders, metabolic syndrome, immune-related conditions, and even mental health disorders. Objective The objective of conducting an evidence-based review on the potential of probiotics is to assess their efficacy, safety, and mechanisms of action in various health conditions. Methods A literature search was conducted in PubMed, Scopus, along EBSCO databases. The topics include " Probiotics", " History", " Composition", " Clinical significance, Prevention ", or " Recent advancements,". Results This involves gathering and analyzing scientific research, clinical trials, and meta- analyses to evaluate the effects of probiotics on specific health outcomes. The review aims to provide an unbiased synthesis of available evidence to inform healthcare professionals, researchers, and policymakers about the role of probiotics in disease prevention, treatment, and maintenance of overall health. Key objectives may include: Conclusion In conclusion, an evidence-based review on probiotics aims to assess their efficacy, safety, and mechanisms of action across various health conditions. By synthesizing scientific research and clinical trials, such reviews provide valuable insights into the role of probiotics in disease management, overall health promotion, and potential adverse effects. Through rigorous analysis, these reviews inform healthcare professionals, researchers, and policymakers about the appropriate use of probiotics to optimize health outcomes. [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]

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]

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]

ABSTRACT The present case report investigates the influence of SYNTHESIT dietary supplements on serum cholesterol levels in a 69-year-old male patient with dyslipidemia from Sevastopol, Russia. During the observation period, the patient’s cholesterol levels initially decreased after he began taking SYNTHESIT. However, this was followed by a slight increase in cholesterol levels as the supplement regimen continued. The results indicate that SYNTHESIT has an inconsistent effect on cholesterol; it lowers it at first and then causes a small increase over time. This case underlines the need for further studies to explore the long-term effects of SYNTHESIT on cholesterol management and its possible implications for dyslipidemia treatment strategies.

ObjectiveClaudin18.2 has been established as a putative therapeutic target in human solid malignancies. The aim of this study is to determine claudin18.2 expression as a clinicopathological and prognostic factor in human solid tumors through a systematic review and meta-analysis. Articles were systematically reviewed for studies that included the correlation between claudin18.2 expression and clinicopathological features and prognosis in solid tumors. Meta-analysis was conducted to estimate either odds ratio and 95% confidence intervals (CIs) of clinicopathological factors or hazard ratio and 95% CIs of survival outcomes for claudin18.2 expression in all available solid tumors.Results21 studies including 5,331 patients were identified. Overall proportion of claudin18.2 positivity was 29.7%. Analyses of clinicopathological features demonstrated that claudin18.2 positivity correlated with male predominance, lower T stage, more frequent MUC5AC positivity when all primary tumors included. In subgroup analysis, gastric cancer showed significant correlation between high claudin18.2 expression and frequent EBV infection, male predominance and lower T stage. In lung cancer, claudin18.2 expression was associated with favorable overall survival. However, analyses of survival outcomes in all solid tumors showed that claudin18.2 expression was not associated with overall survival and pooled disease-free survival, tumor-specific survival, progression-free survival and relapse-free survival.ConclusionsOur study emphasizes evaluation of claudin18.2 expression as a potential prognostic factor in lung adenocarcinoma and further exploration in other solid tumors as well.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023468651.

Signal transducer and activator of transcription 4 (STAT4) is a member of the STAT family, which is a group of transcription factors that regulate cytokine signaling. Genetic polymorphisms in STAT4 strongly influence immune responses and disease outcomes, especially in cancer and autoimmune diseases. Several studies have indicated that certain STAT4 gene variants are associated with alterations in STAT4 expression and/or activity and that there is a close relationship between STAT4 polymorphisms and drug efficacy. However, the underlying mechanisms are complex, and the roles of these polymorphisms in disease acquisition, progression, and severity are of widespread concern. Therefore, we provide an overview of the clinical significance of polymorphisms in STAT4 and the mechanisms by which these STAT4 variants are involved in various diseases.

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.

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.

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.