Non-alcoholic fatty liver disease and sleep disorders.

Studies have shown that non-alcoholic fatty liver disease (NAFLD) may be associated with sleep disorders. In order to explore the explicit relationship between the two, we systematically reviewed the effects of sleep disorders, especially obstructive sleep apnea (OSA), on the incidence of NAFLD, and analyzed the possible mechanisms after adjusting for confounding factors. NAFLD is independently associated with sleep disorders. Different sleep disorders may be the cause of the onset and aggravation of NAFLD. An excessive or insufficient sleep duration, poor sleep quality, insomnia, sleep-wake disorders, and OSA may increase the incidence of NAFLD. Despite that some research suggests a unidirectional causal link between the two, specifically, the onset of NAFLD is identified as a result of changes in sleep characteristics, and the reverse relationship does not hold true. Nevertheless, there is still a lack of specific research elucidating the reasons behind the higher risk of developing sleep disorders in individuals with NAFLD. Further research is needed to establish a clear relationship between NAFLD and sleep disorders. This will lay the groundwork for earlier identification of potential patients, which is crucial for earlier monitoring, diagnosis, effective prevention, and treatment of NAFLD.

Identification of ZIC2 as a Potential Biomarker Linked with the Clinical Progression and Immune Infiltration of Oral Cancer: A Multicenter Study.

Aim: To investigate the specific expression profile, clinicopathological significance and mechanism of Zic family member 2 (ZIC2) in oral cancer were unclear. Patients and Methods. We explored the expression pattern and clinicopathological significance of ZIC2 in oral cancer through performing in-house tissue microarray and integrated analysis global RNA-seq and microarrays containing large samples. The molecular basis of ZIC2 in oral cancer was further investigated in the aspects of transcription network and immune correlations. We also performed in vitro experiments and calculated drug sensitivity of oral cancer with different ZIC2 expression levels in response to hundreds of compounds. Results: All data unanimously proved the significant overexpression of ZIC2 in oral cancer. The upregulation of ZIC2 was remarkably associated with the malignant clinical progression of oral cancer. ZIC2 was predicted to be targeted by miRNAs such as miR-3140, miR-4999, and miR-1322. The infiltration level of CD8+ T and central memory cells was positively related to the overexpression of ZIC2. Oral cancer patients with higher ZIC2 expression showed higher drug sensitivity to two compounds including AZD8186 and ERK_2240. Conclusions: We demonstrated the upregulation of ZIC2 in oral cancer and its promoting effect on the clinical advancement of oral cancer. The potential clinical value of ZIC2 in oral cancer deserves attention.

Excessive iron deposition in root apoplast is involved in growth arrest of roots in response to low pH.

The rhizotoxicity of protons (H+) in acidic soils is a fundamental constraint that results in serious yield losses. However, the mechanisms underlying H+-mediated inhibition of root growth are poorly understood. In this study, we revealed that H+-induced root growth inhibition in Arabidopsis depends considerably on excessive iron deposition in the root apoplast. Reducing such aberrant iron deposition by decreasing the iron supply or disrupting the ferroxidases LOW PHOSPHATE ROOT 1 (LPR) and LPR2 attenuates the inhibitory effect of H+ on primary root growth efficiently. Further analysis showed that excessive iron deposition triggers a burst of highly reactive oxygen species, consequently impairing normal root development. Our study uncovered a valuable strategy for improving the ability of plants to tolerate H+ toxicity by manipulating iron availability.

Clinical significance and prospective mechanism of increased CDKN2A expression in small cell lung cancer.

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.

[Gene Mutation Types of Thalassemia in Chongzuo Childbearing-age Population of Guangxi Zhuang Autonomous Region of China].

OBJECTIVE: To investigate the gene mutation and genotype distribution of thalassemia in the population of childbearing age in Chongzuo area of Guangxi. METHODS: Six α-thalassemia and 17 ß-thalassemia gene mutations common in Chinese were detected by gap-polymerase chain reaction (gap-PCR) combined with agarose gel eletrophoresis and reserve dot bolt hybridization in 29 266 cases of child-bearing age suspected of thalassemia. RESULTS: A total of 19 128 (65.36%) cases were identified with thalassemia. The detection rate of α-thalassemia, ß-thalassemia and α-combining ß-thalassemia was 45.25% (13 242/29 266), 15.47% (4 526/29 266) and 4.65% (1 360/29 266), respectively. A total carrying rate of 8 kinds of α-thalassemia gene mutations was 26.74% (15 649/58 532), including 12.51% for --SEA, followed by 5.70% for -α3.7, and 0.24% for --Thai. Among 32 α-thalassemia genotypes, the most common five were --SEA/αα, -α3.7/αα, αCSα/αα, -α4.2/αα and αWSα/αα, accounting for 47.27%, 18.31%, 8.56%, 8.52% and 7.91%, respectively, as well as 0.97% for --Thai/αα. A total carrying rate of 13 kinds of ß-thalassemia gene mutations was 10.07% (5 897/58 532), including 3.63% for CD41-42, followed by 2.55% for CD17, and 0.003% for -50 (G>A). Among 17 ß-thalassemia genotypes, the most common six were CD41-42/N, CD17/N, CD71-72/N, CD26/N, 28/N and IVSI-1/N, accounting for 36.15%, 25.81%, 9.43%, 8.18%, 8.09% and 7.75%. The homozygous genotype CD26/CD26 [hemoglobin (Hb): 121 g/L] and -28/-28 (Hb: 56 g/L) were respectively detected in one case, and double heterozygous genotype were detected in 5 cases, including 3 cases of CD41-42/CD26 (Hb: 41 g/L, 51 g/L, 63 g/L, respectively), 1 case of -28/IVSI-1 (Hb: 53 g/L), and 1 case of CD71-72/CD26 (Hb: 89 g/L), in which patients with moderate or severe anemia had a history of blood transfusion. Among 104 α-combining ß-thalassemia genotypes, the most common were --SEA/αα, -α3.7/αα combining CD41-42/N and --SEA/αα combining CD17/N, accounting for 12.13%, 9.63% and 9.26%, respectively. In addition, 1 case of --SEA/-α3.7 combining -28/IVSI-1 (Hb: 83 g/L) and 1 case of -α3.7/αα combining CD41-42/ CD41-42 (Hb: 110 g/L) were detected without history of blood transfusion, while 1 case of αWSα/αα combining CD41-42/CD17 (Hb: 79 g/L) and 1 case of --SEA/αα combining CD17/-28 (Hb: 46 g/L) were detected with history. CONCLUSIONS: The detection rate of thalassemia genes is high and the mutations are diverse in the population of childbearing age in Chongzuo area of Guangxi. The common deletion genotype is --SEA/αα in α-thalassemia and CD41-42/N in ß-thalassemia, and deletion genotype --Thai is not rare. There is a certain incidence of intermediate and severe ß-thalassemia, and most patients require transfusion therapy. The results are beneficial for genetic consultation and intervention of thalassemia.

[Analysis of HKαα Genotype and Hematological Characteristics in South Guangxi].

OBJECTIVE: To investigate the detection rate and hematologic phenotype of HKαα thalassemia in south Guangxi, in order to provide reference for the prevention and control of thalassemia and prenatal and postnatal care consultation in this region. METHODS: Gene testing was performed on pre-marital medical examinations, pre-pregnancy eugenic health examinations, prenatal examinations and hospitalized thalassemia-positive persons in south of Guangxi, and the results were analyzed. RESULTS: A total of 183 190 thalassemia patients were included in this study, the age was mainly concentrated in 26-35 years old (101 709 cases, accounting for 55.521%), and 40 HKαα mutations were detected, detection rate was 0.022%, including 5 cases in Nanning, 22 cases in Qinzhou, 2 cases in Fangchenggang, 11 cases in Beihai. A total of 29 ethnic groups were included in the survey, but HKαα gene was observed only in Han nationality (0.0380%) and Zhuang nationality (0.0068%). A total of 8 genotypes carrying HKαα mutations were detected in this study ( HKαα/--SEA, ßN/ ßN, HKαα/αα, ß-28/ ßN, HKαα/αα, ß-50/ ßN, HKαα/αα, ßCD17/ ßN, HKαα/αα, ßCD27/28/ß N, HKαα/αα, ßCD41-42/ ßN, HKαα/αα, ßCD71-72/ ßN, and HKαα/αα, ßN/ ßN). Except for most cases with HKαα/αα, ßN/ ßN genotypes with no significant changes in the hematological indexes, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) of other genotypes were decreased, showing microcytic hypochromic performance, mild anemia or no anemia. CONCLUSION: HKαα carrier is often misdiagnosed as -α3.7 carrier, which easily leads to missed diagnosis or misdiagnosis. Therefore, it is necessary to continuously improve the diagnostic level of laboratory testing personnels and genetic counselors to avoid unnecessary interventional puncture operations and birth of children with moderate and severe thalassemia.

What should be the future direction of development in the field of prostate cancer with lung metastasis?

BACKGROUND: Since the start of the 21st century, prostate cancer with lung metastasis (PCLM) has accumulated significant scientific research output. However, a systematic knowledge framework for PCLM is still lacking. AIM: To reconstruct the global knowledge system in the field of PCLM, sort out hot research directions, and provide reference for the clinical and mechanism research of PCLM. METHODS: We retrieved 280 high-quality papers from the Web of Science Core Collection and conducted a bibliometric analysis of keywords, publication volume, and citation frequency. Additionally, we selected differentially expressed genes from global high-throughput datasets and performed enrichment analysis and protein-protein interaction analysis to further summarize and explore the mechanisms of PCLM. RESULTS: PCLM has received extensive attention over the past 22 years, but there is an uneven spatial distribution in PCLM research. In the clinical aspect, the treatment of PCLM is mainly based on chemotherapy and immunotherapy, while diagnosis relies on methods such as prostate-specific membrane antigen positron emission tomography/computed tomography. In the basic research aspect, the focus is on cell adhesion molecules and signal transducer and activator of transcription 3, among others. Traditional treatments, such as chemotherapy, remain the mainstay of PCLM treatment, while novel approaches such as immunotherapy have limited effectiveness in PCLM. This study reveals for the first time that pathways related to coronavirus disease 2019, cytokine-cytokine receptor interaction, and ribosome are closely associated with PCLM. CONCLUSION: Future research should focus on exploring and enhancing mechanisms such as cytokine-cytokine receptor interaction and ribosome and improve existing mechanisms like cadherin binding and cell adhesion molecules.

CDK6 is a novel predictive and prognosis biomarker correlated with immune infiltrates in multiple human neoplasms, including small cell lung carcinoma.

The roles of cyclin-dependent kinase 6 (CDK6) in various cancers, including small cell lung carcinoma (SCLC), remain unclear. Here, 111,54 multi-center samples were investigated to determine the expression, clinical significance, and underlying mechanisms of CDK6 in 34 cancers. The area under the curve (AUC), Cox regression analysis, and the Kaplan-Meier curves were used to explore the clinical value of CDK6 in cancers. Gene set enrichment analysis and correlation analysis were performed to detect potential CDK6 mechanisms. CDK6 expression was essential in 24 cancer cell types. Abnormal CDK6 expression was observed in 14 cancer types (e.g., downregulated in breast invasive carcinoma; p < 0.05). CDK6 allowed six cancers to be distinguished from their controls (AUC > 0.750). CDK6 expression was a prognosis marker for 13 cancers (e.g., adrenocortical carcinoma; p < 0.05). CDK6 was correlated with several immune-related signaling pathways and the infiltration levels of certain immune cells (e.g., CD8+ T cells; p < 0.05). Downregulated CDK6 mRNA and protein levels were observed in SCLC (p < 0.05, SMD = - 0.90). CDK6 allowed the identification of SCLC status (AUC = 0.91) and predicted a favorable prognosis for SCLC patients (p < 0.05). CDK6 may be a novel biomarker for the prediction and prognosis of several cancers, including SCLC.

ITGB4 Serves as an Identification and Prognosis Marker Associated with Immune Infiltration in Small Cell Lung Carcinoma.

Integrin beta 4 (ITGB4) is a vital factor for numerous cancers. However, no reports regarding ITGB4 in small cell lung carcinoma (SCLC) have been found in the existing literature. This study systematically investigated the expression and clinical value of ITGB4 in SCLC using multi-center and large-sample (n = 963) data. The ITGB4 expression levels between SCLC and control tissues were compared using standardized mean difference and Wilcoxon rank-sum test. The clinical significance of the gene in SCLC was observed using Cox regression and Kaplan-Meier curves. ITGB4 is overexpressed in multiple cancers and represents significant value in distinguishing among cancer samples (AUC = 0.91) and predicting the prognoses (p < 0.05) of patients with different cancers. In contrast, decreased ITGB4 mRNA expression was determined in SCLC (SMD < 0), and this finding was further confirmed at protein levels using in-house specimens (p < 0.05). This decrease in expression may be attributed to the regulatory role of estrogen receptor 1. ITGB4 may participate in the progression of SCLC by affecting several signaling pathways (e.g., tumor necrosis factor signaling pathway) and a series of immune cells (e.g., dendritic cells) (p < 0.05). The gene may serve as a potential marker for predicting the disease status (AUC = 0.97) and prognoses (p < 0.05) of patients with SCLC. Collectively, ITGB4 was identified as an identification and prognosis marker associated with immune infiltration in SCLC.

MMP12 serves as an immune cell-related marker of disease status and prognosis in lung squamous cell carcinoma.

Background: Worldwide, lung squamous cell carcinoma (LUSC) has wreaked havoc on humanity. Matrix metallopeptidase 12 (MMP12) plays an essential role in a variety of cancers. This study aimed to reveal the expression, clinical significance, and potential molecular mechanisms of MMP12 in LUSC. Methods: There were 2,738 messenger RNA (mRNA) samples from several multicenter databases used to detect MMP12 expression in LUSC, and 125 tissue samples were validated by immunohistochemistry (IHC) experiments. Receiver operator characteristic (ROC) curves, Kaplan-Meier curves, and univariate and multivariate Cox regression analyses were used to assess the clinical value of MMP12 in LUSC. The potential molecular mechanisms of MMP12 were explored by gene enrichment analysis and immune correlation analysis. Furthermore, single-cell sequencing was used to determine the distribution of MMP12 in multiple tumor microenvironment cells. Results: MMP12 was significantly overexpressed at the mRNA level (p < 0.05, SMD = 3.13, 95% CI [2.51-3.75]), which was verified at the protein level (p < 0.001) by internal IHC experiments. MMP12 expression could be used to differentiate LUSC samples from normal samples, and overexpression of MMP12 itself implied a worse clinical prognosis and higher levels of immune cell infiltration in LUSC patients. MMP12 was involved in cancer development and progression through two immune-related signaling pathways. The high expression of MMP12 in LUSC might act as an antigen-presenting cell-associated tumor neoantigen and activate the body's immune response. Conclusions: MMP12 expression is upregulated in LUSC and high expression of MMP12 serves as a risk factor for LUSC patients. MMP12 may be involved in cancer development by participating in immune-related signaling pathways and elevating the level of immune cell infiltration.

Identification through machine learning of potential immune- related gene biomarkers associated with immune cell infiltration in myocardial infarction.

BACKGROUND: To investigate the potential role of immune-related genes (IRGs) and immune cells in myocardial infarction (MI) and establish a nomogram model for diagnosing myocardial infarction. METHODS: Raw and processed gene expression profiling datasets were archived from the Gene Expression Omnibus (GEO) database. Differentially expressed immune-related genes (DIRGs), which were screened out by four machine learning algorithms-partial least squares (PLS), random forest model (RF), k-nearest neighbor (KNN), and support vector machine model (SVM) were used in the diagnosis of MI. RESULTS: The six key DIRGs (PTGER2, LGR6, IL17B, IL13RA1, CCL4, and ADM) were identified by the intersection of the minimal root mean square error (RMSE) of four machine learning algorithms, which were screened out to establish the nomogram model to predict the incidence of MI by using the rms package. The nomogram model exhibited the highest predictive accuracy and better potential clinical utility. The relative distribution of 22 types of immune cells was evaluated using cell type identification, which was done by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. The distribution of four types of immune cells, such as plasma cells, T cells follicular helper, Mast cells resting, and neutrophils, was significantly upregulated in MI, while five types of immune cell dispersion, T cells CD4 naive, macrophages M1, macrophages M2, dendritic cells resting, and mast cells activated in MI patients, were significantly downregulated in MI. CONCLUSION: This study demonstrated that IRGs were correlated with MI, suggesting that immune cells may be potential therapeutic targets of immunotherapy in MI.

Downregulation of zinc finger protein 71 in laryngeal squamous cell carcinoma tissues and its potential molecular mechanism and clinical significance: a study based on immunohistochemistry staining and data mining.

BACKGROUND: The molecular mechanism of laryngeal squamous cell carcinoma (LSCC) is not completely clear, which leads to poor prognosis and treatment difficulties for LSCC patients. To date, no study has reported the exact expression level of zinc finger protein 71 (ZNF71) and its molecular mechanism in LSCC. METHODS: In-house immunohistochemistry (IHC) staining (33 LSCC samples and 29 non-LSCC samples) was utilized in analyzing the protein expression level of ZNF71 in LSCC. Gene chips and high-throughput sequencing data collected from multiple public resources (313 LSCC samples and 192 non-LSCC samples) were utilized in analyzing the exact mRNA expression level of ZNF71 in LSCC. Single-cell RNA sequencing (scRNA-seq) data was used to explore the expression status of ZNF71 in different LSCC subpopulations. Enrichment analysis of ZNF71, its positively and differentially co-expressed genes (PDCEGs), and its downstream target genes was employed to detect the potential molecular mechanism of ZNF71 in LSCC. Moreover, we conducted correlation analysis between ZNF71 expression and immune infiltration. RESULTS: ZNF71 was downregulated at the protein level (area under the curve [AUC] = 0.93, p < 0.0001) and the mRNA level (AUC = 0.71, p = 0.023) in LSCC tissues. Patients with nodal metastasis had lower protein expression level of ZNF71 than patients without nodal metastasis (p < 0.05), and male LSCC patients had lower mRNA expression level of ZNF71 than female LSCC patients (p < 0.01). ZNF71 was absent in different LSCC subpopulations, including cancer cells, plasma cells, and tumor-infiltrated immune cells, based on scRNA-seq analysis. Enrichment analysis showed that ZNF71 and its PDCEGs may influence the progression of LSCC by regulating downstream target genes of ZNF71. These downstream target genes of ZNF71 were mainly enriched in tight junctions. Moreover, downregulation of ZNF71 may influence the development and even therapy of LSCC by reducing immune infiltration. CONCLUSION: Downregulation of ZNF71 may promote the progression of LSCC by reducing tight junctions and immune infiltration; this requires further study.

The clinical significance of integrin subunit alpha V in cancers: from small cell lung carcinoma to pan-cancer.

BACKGROUND: Little is known about the relationship between integrin subunit alpha V (ITGAV) and cancers, including small cell lung cancer (SCLC). METHODS: Using large sample size from multiple sources, the clinical roles of ITGAV expression in SCLC were explored using differential expression analysis, receiver operating characteristic curves, Kaplan-Meier curves, etc. RESULTS: Decreased mRNA (SMD = - 1.05) and increased protein levels of ITGAV were detected in SCLC (n = 865). Transcription factors-ZEB2, IK2F1, and EGR2-may regulate ITGAV expression in SCLC, as they had ChIP-Seq (chromatin immunoprecipitation followed by sequencing) peaks upstream of the transcription start site of ITGAV. ITGAV expression made it feasible to distinguish SCLC from non-SCLC (AUC = 0.88, sensitivity = 0.78, specificity = 0.84), and represented a risk role in the prognosis of SCLC (p < 0.05). ITGAV may play a role in cancers by influencing several immunity-related signaling pathways and immune cells. Further, the extensive pan-cancer analysis verified the differential expression of ITGAV and its clinical significance in multiple cancers. CONCLUSION: ITGAV served as a potential marker for prognosis and identification of cancers including SCLC.

Rhino-Orbital-Cerebral Mycosis and Extranodal Natural Killer or/and T-Cell Lymphoma, Nasal Type.

Background: Extranodal natural killer/T-cell lymphoma, nasal type is a syndrome of middle face destruction with an association to Epstein-Barr virus. Fungi have been recovered from the diseased tissue now and then but were often seen as a lymphoma-associated secondary infection. However, there are ENKTL-NT cases with the recoveries of fungi and complete recovery with antifungal therapy, which are quite similar to rhino-orbital-cerebral mycosis (ROCM) that often confuses the physicians. Methods: We searched Medline for English-language manuscripts limited to "human" and "case reports," "letters," "reviews," and "clinical conferences" from 1966 to 2022. We used MeSH terms "lymphoma, extranodal nk-t-cell" [MeSH Terms] or "lethal midline granuloma" [MeSH Terms], in combination with MeSH terms "microbiology" [subheading] or "microbiology" [all fields] or "fungi" [all fields] or "fungi" [MeSH Terms] for ENKTL-NT with infections. We used MeSH terms "Mycoses" in combination with "Nose" [Mesh] OR "Orbital Diseases" [Mesh] for rhino-orbital-cerebral fungal infections. Results: We appraised 149 included articles and extracted references related to ENKTL-NT and/or ROCM. Themes and subcategories were subsequently derived. Our findings revealed that ROCM and ENKTL-NT are characterized by progressive and destructive ulcers in the midline face or rhino-orbital structures. ROCM is mainly caused by fungi in the order of Mucorales, and ENKTL-NT is usually associated with Epstein-Barr virus and sometimes fungi. Radiologically, both are characterized by non-specific features of sinusitis, soft tissue infection, and necrosis. Pathologically, ROCM and ENKTL-NT share the same characteristics of inflammation, necrosis, and granuloma. ROCM is characterized by the detection of fungi in tissue, while ENKTL-NT is typically positive for NK/T-cell markers and cytotoxic granule-associated proteins, proliferation, and vascular damage of angioinvasion, which could be incited by Mucor irregularis and Rhizopus arrhizus in patients and mice. Conclusion: ENKTL-NT and ROCM share many similarities in clinical presentations, radiology, and histopathology, and might have the same etiology. This may explain why the two diseases are tangled together in the reported cases, and suggests the role that the fungi may play in the development of these ENKTL-NT/ROCM diseases. The reason why ENKTL-NT and ROCM are sometimes confused is that the main pathogens of ROCM, Mucor irregularis and Rhizopus arrhizus, are the fungal causative agents of ENKTL-NT.

Clinical assessment and molecular mechanism of the upregulation of Toll-like receptor 2 (TLR2) in myocardial infarction.

OBJECTIVE: The prevalence and mortality of cardiovascular diseases remain ranked first worldwide. Myocardial infarction (MI) is the central cause of death from cardiovascular diseases, seriously endangering human health. The clinical implication of toll-like receptor 2 (TLR2) remains contradictory, and its mechanism is still unknown. Hence, the objective of this study was to elucidate the clinical value and molecular mechanism of TLR2 in MI. METHODS: All high-throughput datasets and eligible literature were screened, and the expression levels of TLR2 were collected from the MI. The integrated expression level of TLR2 was displayed by calculating the standardized mean difference (SMD) and the area under the curve (AUC) of the summary receiver operating characteristic curve (sROC). The related TLR2 genes were sent for pathway analyses by gene ontology (GO), Kyoto encyclopedia of genes and genome (KEGG), and disease ontology (DO). Single-cell RNA-seq was applied to ascertain the molecular mechanism of TLR2 in MI. RESULTS: Nine microarrays and four reported data were available to calculate the comprehensive expression level of TLR2 in MI, including 325 cases of MI and 306 cases of controls. The SMD was 2.55 (95% CI = 1.35-3.75), and the AUC was 0.76 (95% CI = 0.72-0.79), indicating the upregulation of TLR2 in MI. The related TLR2 genes were primarily enriched in the pathways of atherosclerosis, arteriosclerotic cardiovascular disease, and arteriosclerosis, suggesting the clinical role of TLR2 in the progression of MI. Afterward, TLR2 was upregulated in myeloid cells in MI. CONCLUSIONS: TLR2 may have a crucial role in progressing from coronary atherosclerosis to MI. The upregulation of TLR2 may have a favorable screening value for MI.

Expression Profile and Molecular Basis of Cyclin-Dependent Kinases Regulatory Subunit 2 in Endometrial Carcinoma Detected by Diversified Methods.

Purpose: Our purpose was to systematically appraise the clinicopathological significance and explore the molecular bases of CKS2 in endometrial carcinoma. Patients and Methods: We measured the clinicopathological significance of CKS2 using diverse methods of public RNA-seq, microarrays, and in-house tissue microarrays to investigate the molecular basis of CKS2 in endometrial carcinoma through upstream transcriptional analysis, immune infiltration correlation analysis, and co-expression analysis. Results: Both the analysis for public RNA-seq plus the microarray data and in-house tissue microarray confirmed the significant overexpression of CKS2 in a total of 1,021 endometrial carcinoma samples compared with 279 non-cancer endometrium samples (SMD = 2.10, 95% CI = 0.72-3.48). The upregulated CKS2 was significantly related to the lymph node metastasis and advanced clinical grade of endometrial carcinoma patients (p < 0.001). Mutation types such as amplification and mRNA occurred with high frequency in the CKS2 gene in endometrial carcinoma patients. A series of miRNAs and transcription factors, such as hsa-miR-26a, hsa-miR-130a, hsa-miR-30, E2F4, MAX, and GABPA, were predicted to regulate the transcription and expression of CKS2. Significant links were found between CKS2 expression and the infiltration level of B cells, CD4+ T cells, and neutrophils in endometrial carcinoma. CKS2-coexpressed genes were actively involved in pathways such as the mitotic cell cycle process, PID aurora B pathway, and prolactin signaling pathway. Conclusion: The overexpressed CKS2 showed positive correlations with the clinical progression of endometrial carcinoma and was associated with various cancer-related biological processes and pathways, showing potential as a promising clinical biomarker for endometrial carcinoma.

Expression of IER3 in hepatocellular carcinoma: clinicopathology, prognosis, and potential regulatory pathways.

Background: Immediate early response 3 (IER3) is correlated to the prognosis of several cancers, but the precise mechanisms underlying the regulation by IER3 of the occurrence and development of hepatocellular carcinoma (HCC) remain unknown. Methods: The expression level of IER3 was examined by using in-house immunohistochemistry (IHC), public gene chip, and public RNA-sequencing (RNA-seq). The standardized mean difference (SMD) was calculated to compare the expression levels of IER3 between HCC patients and controls. The summary receiver operating characteristics (sROC) was plotted to comprehensively understand the discriminatory capability of IER3 between HCC and non-HCC group. The Kaplan-Meier curves and the combined hazard ratios (HRs) were used to determine the prognostic value of IER3 in HCC. Moreover, differentially expressed genes (DEGs) and co-expression genes (CEGs) were used to explored the molecular mechanisms of IER3 underlying HCC. hTFtarget was used to predict the transcription factors (TFs) of IER3. The binding site of TFs and the IER3 promoter region was forecasted using the JASPAR website. The relevant ChIP-seq data were used to determine whether TF peaks were present in the IER3 transcription initiation. Results: A significantly increased expression of IER3 protein was found in HCC tissue relative to non-HCC tissue as detected by IHC (p < 0.001). Compared to 1,263 cases of non-HCC tissues, IER3 in 1483 cases of HCC tissues was upregulated (SMD = 0.42, 95% confidence interval [CI] [0.09-0.76]). The sROC showed that IER3 had a certain ability at differentiating HCC tissues (area under the curve (AUC) = 0.65, 95% CI [0.61-0.69]). Comprehensive analysis of the effect of IER3 on the prognosis of patients with HCC demonstrated that higher IER3 expression was associated with poor prognosis in HCC (HRs = 1.30, 95% CI [1.03-1.64]). Pathway enrichment analysis revealed that IER3-related genes were mostly enriched in the PI3K-Akt signaling pathway, cancer-related signaling pathways, the p53 signaling pathway, and other signaling pathways. Regulatory factor X5 (RFX5) was identified as a possible regulator of IER3-related TF. Conclusion: IER3 may be a potential prognostic marker for HCC. The molecular mechanisms of IER3 in HCC warrant further study.

Genotypes of thalassemia in children: an analysis of 30 417 cases. / 30 417ä¾‹å„¿ç«¥åœ°ä¸­æµ·è´«è¡€åŸºå› ç±»åž‹åˆ†æž.

OBJECTIVES: To investigate the distribution of genotypes of thalassemia in children in Guangxi, China. METHODS: A total of 30 417 children with positive results of thalassemia screening in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2011 to December 2019 were enrolled. Single-tube multiplex PCR, agarose gel electrophoresis, and reverse dot blot hybridization technique were used for the detection of common α- and ß-thalassemia genes. Gap-PCR or gene sequence analysis was performed for 2 703 children suspected of rare thalassemia. RESULTS: Among the 30 417 children with positive results of thalassemia screening, 23 214 (76.32%) were diagnosed with thalassemia, and the detection rates of α-thalassemia, ß-thalassemia, and α-thalassemia with ß-thalassemia were 47.77%, 23.75%, and 4.80% respectively. A total of 13 types of α-thalassemia alleles (18 480 alleles in total) were detected, mainly --SEA (54.98%), including seven rare alleles, i.e., --THAI (0.43%), HKαα (0.02%), -α30 (0.01%), -α1.0 (0.01%), -α2.4 (0.01%), -α21.9 (0.01%), and HBA2:C272-279 del (0.01%). A total of 17 types of ß-thalassemia alleles (9 168 alleles in total) were detected, mainly CD41-42 (47.79%), followed by CD17 (25.53%), including three rare alleles, i.e., IVS-II-5 (0.02%), IVS-I-2 (0.01%), and Gγ(Aγδß)0 (0.01%). A total of 37 genotypes were detected in 14 531 children with α-thalassemia, among which the most common 6 genotypes were --SEA/αα (52.20%), -α3.7/αα (13.24%), αCSα/αα (7.52%), -α4.2 (6.06%), --SEA/-α3.7 (5.91%), and αWSα/αα (3.41%), accounting for 88.34%. A total of 49 genotypes were detected in 7 223 children with ß-thalassemia, among which the most common 6 genotypes were CD41-42/ßN (45.81%), CD17/ßN (24.30%), IVS-II-654/ßN (7.49%), -28/ßN (5.62%), CD71-72/ßN (4.42%), and CD26/ßN (3.94%), accounting for 91.13%. A total of 137 genotypes were detected in 1 460 children with both α- and ß-thalassemia, mainly --SEA/αα combined with CD41-42/ßN (14.17%) and CD17/ßN (8.35%). A total of 2 050 children were diagnosed with hemoglobin H disease (α0/α+), among whom 134 had ß-thalassemia heterozygote and 12 had Bart hydrops fetalis syndrome (--SEA/--SEA); 355 children were diagnosed with ß-thalassemia double heterozygote, and 128 were diagnosed with ß-thalassemia homozygote, including 93 children with α-thalassemia. CONCLUSIONS: There are diverse gene mutations and rich genotypes of thalassemia among children in Guangxi, and α-thalassemia is more common, with --SEA/αα as the major genotype. There is a high proportion of children with both α- and ß-thalassemia, and there are relatively high incidence rates of ß-thalassemia double heterozygote and homozygote (intermedia and major).