Single-cell immune profiling of mouse liver aging reveals Cxcl2+ macrophages recruit neutrophils to aggravate liver injury.

BACKGROUND AND AIMS: Immune cells play a crucial role in liver aging. However, the impact of dynamic changes in the local immune microenvironment on age-related liver injury remains poorly understood. We aimed to characterize intrahepatic immune cells at different ages to investigate key mechanisms associated with liver aging. APPROACH AND RESULTS: We carried out single-cell RNA sequencing on mouse liver tissues at 4 different ages, namely, the newborn, suckling, young, and aged stages. The transcriptomic landscape, cellular classification, and intercellular communication were analyzed. We confirmed the findings by multiplex immunofluorescence staining, flow cytometry, in vitro functional experiments, and chimeric animal models. Nine subsets of 89,542 immune cells with unique properties were identified, of which Cxcl2+ macrophages within the monocyte/macrophage subset were preferentially enriched in the aged liver. Cxcl2+ macrophages presented a senescence-associated secretory phenotype and recruited neutrophils to the aged liver through the CXCL2-CXCR2 axis. Through the secretion of IL-1ß and TNF-α, Cxcl2+ macrophages stimulated neutrophil extracellular traps formation. Targeting the CXCL2-CXCR2 axis limited the neutrophils migration toward the liver and attenuated age-related liver injury. Moreover, the relationship between Cxcl2+ macrophages and neutrophils in age-related liver injury was further validated by human liver transplantation samples. CONCLUSIONS: This in-depth study illustrates that the mechanism of Cxcl2+ macrophage-driven neutrophil activation involves the CXCL2-CXCR2 axis and provides a potential therapeutic strategy for age-related liver injury.

Phylogenetic Comparative Analysis of Single-Cell Transcriptomes Reveals Constrained Accumulation of Gene Expression Heterogeneity during Clonal Expansion.

In the same way that a phylogeny summarizes the evolutionary history of species, a cell lineage tree describes the process of clonal expansion, in which gene expression differences between cells naturally accrue as a result of stochastic partitioning and imperfect expression control. How is functional homeostasis, a key factor in the biological function of any population of cells, maintained in the face of such continuous accumulation of transcriptomic heterogeneity remains largely unresolved. To answer this question, we experimentally determined the single-cell transcriptomes and lineage relationships of up to 50% cells in single-HEK293-seeded colonies. Phylogenetic comparative analyses of the single-cell transcriptomes on the cell lineage tree revealed three lines of evidence for the constrained accumulation of transcriptome heterogeneity among cells, including rapid saturation of transcriptomic heterogeneity upon four cell divisions, reduced expression differences within subtrees closer to expression boundaries, and cofluctuations among genes. Our analyses showcased the applicability of phylogenetic comparative methods in cell lineage trees, demonstrated the constrained accumulation of transcriptomic heterogeneity, and provided novel insight into the functional homeostasis of cell populations.

Abnormal prefrontal functional network in adult obstructive sleep apnea: A resting-state fNIRS study.

To assess prefrontal brain network abnormality in adults with obstructive sleep apnea (OSA), resting-state functional near infrared spectroscopy (rs-fNIRS) was used to evaluate 52 subjects, including 27 with OSA and 25 healthy controls (HC). The study found that patients with OSA had a decreased connection edge number, particularly in the connection between the right medial frontal cortex (MFG-R) and other right-hemisphere regions. Graph-based analysis also revealed that patients with OSA had a lower global efficiency, local efficiency, and clustering coefficient than the HC group. Additionally, the study found a significant positive correlation between the Montreal Cognitive Assessment (MoCA) score and both the connection edge number and the graph-based indicators in patients with OSA. These preliminary results suggest that prefrontal rs-fNIRS could be a useful tool for objectively and quantitatively assessing cognitive function impairment in patients with OSA.

A Prediction Model for Clinical Outcomes of COVID-19 Hospitalized Patients: Construction and Accuracy Assessment.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic spread rapidly with considerable morbidity nationwide since China's liberalization in December 2022. Our work has focused on identifying different predictive factors from the laboratory examination of critically ill patients, and forecasting the unfavorable outcome of critically ill patients with COVID-19 through a combined diagnosis of biological markers. METHODS: We conducted a retrospective study at the Department of First Affiliated Hospital of Wenzhou Medical University, China, from December 24, 2022, to January 10, 2023, where 434 critically ill patients who met the inclusion criteria were involved. Machine analysis was employed to search for the parameters with the highest predictive value to calculate COVID-19 mortality by exploiting 66 typical laboratory results. RESULTS: Combined diagnosis of serum albumin (ALB), lactate dehydrogenase (LDH), direct bilirubin (Dbil), ferritin, pulse oxygen saturation (SpO2), and neutrophil count (NEUT#) was evaluated, and the result with the highest predictive value (NEUT#) was selected as the predictor for COVID-19 mortality with a sensitivity of 89.2% and a specificity of 77.4%. CONCLUSIONS: The increased levels of LDH, Dbil, ferritin, and NEUT#, along with lowered ALB and SpO2 levels are the most decisive variables for forecasting the mortality for COVID-19 according to our machine-learning-based model. The combined diagnosis could be used to improve further diagnostic performance.

Association between postoperative pathological results and non-sentinel nodal metastasis in breast cancer patients with sentinel lymph node-positive breast cancer.

OBJECTIVE: For patients with 1-2 positive sentinel lymph nodes (SLN) identified by biopsy, the necessity of axillary lymph node dissection (ALND) remains a matter of debate. The primary aim of this study was to investigate the association between postoperative pathological factors and non-sentinel lymph node (NSLN) metastases in Chinese patients diagnosed with sentinel node-positive breast cancer. METHODS: This research involved a total of 280 individuals with SLN-positive breast cancer. The relationship between postoperative pathological variables and non-sentinel lymph node metastases was scrutinized using univariate, multivariate, and stratified analysis. RESULTS: Among the 280 patients with a complete count of SLN positives, 126 (45.0%) exhibited NSLN metastasis. Within this group, 45 cases (35.71%) had 1 SLN positive, while 81 cases (64.29%) demonstrated more than 1 SLN positive. Multivariate logistic regression analysis revealed that HER2 expression status (OR 2.25, 95% CI 1.10-4.60, P = 0.0269), LVI (OR 6.08, 95% CI 3.31-11.14, P < 0.0001), and the number of positive SLNs (OR 4.17, 95% CI 2.35-7.42, P < 0.0001) were positively correlated with NSLNM. CONCLUSION: In our investigation, the risk variables for NSLN metastasis included LVI, HER2 expression, and the quantity of positive sentinel lymph nodes. However, further validation is imperative, including this institution, distinct institutions, and diverse patient populations.

Effect of nonpharmacological interventions on nutrition status, complications and quality of life in head and neck cancer patients undergoing radiotherapy: A systematic review and meta-analysis.

PURPOSE: To evaluate the effect of nonpharmacological therapies on nutrition status, complications and quality of life in head and neck cancer patients and to provide a basis for clinical practice. METHODS: This systematic review was reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Ten databases were systematically searched for all available articles from construction to November 2023. Two researchers independently conducted literature screening, data extraction and quality evaluation. Cochrane Review Manager 5.3 was used for meta-analysis. RESULTS: Finally, 27 RCT studies including 2814 patients with head and neck cancer were included. Five categories of interventions were used: nutritional support, exercise, swallowing function training, psychological intervention and low-level laser therapy. Nonpharmacological interventions can improve body weight loss in patients with HNC at the end of treatment (MD: 1.66 kg; 95% CI: 0.80 to 2.51), and subgroup analysis showed that nutritional support, psychological intervention and low-level laser therapy were effective. Nonpharmacological interventions can also ameliorate decreases in BMI (MD: 0.71; 95% CI: 0.16 to 1.26) and reduce the incidence of malnutrition (RR: 0.76; 95% CI: 0.67 to 0.86), oral mucositis (RR: 0.54; 95% CI: 0.37 to 0.80) and gastrointestinal complications (RR: 0.61; 95% CI: 0.38 to 0.96) during radiotherapy; however, no significant differences were found in other complications and quality of life. CONCLUSION: Nonpharmacological interventions can improve the nutrition status of patients with head and neck cancer and reduce the incidence of severe oral mucositis and gastrointestinal complications during radiotherapy but have no significant impact on quality of life.

Cuproptosis correlates with immunosuppressive tumor microenvironment based on pan-cancer multiomics and single-cell sequencing analysis.

Recent studies suggest that cuproptosis, a novel mode of cell death, may be associated with the development of cancer. However, no studies are showing its role in tumorigenesis, progression, and prognosis. In the present study, we comprehensively analyzed the expression difference, gene variation and methylation modification of cuproptosis-related genes (CRGs) in pan-cancer. Then, Single sample gene set enrichment analysis (ssGSEA) was used to calculate individual cuproptosis scores (CS). The association of CS with copy number variation, clinical features, immune-related genes, TMB, MSI, and tumor immune dysfunction and exclusion (TIDE) was comprehensively assessed. Single-cell transcriptome sequencing (scRNA-seq) to analyze the activation of cuproptosis in the tumor microenvironment. Immunohistochemistry (IHC) were used to validate the expression of cuproptosis hub-gene. Our study shows that CRGs were significantly expressed in a variety of tumors, and CDKN2A had the highest mutation frequency (49%) in all tumors. A significant increase in the CS was observed in most cancers and were associated with poor prognosis in the majority of tumors. CS was significantly negatively correlated with tumor microenvironment scores in more than 10 tumors and positively correlated with PD-L1 in 11 tumors, suggesting involvement in tumor immune escape. scRNA-seq suggests that CRG scores significantly increased in the cancer cells. This study opens avenues for further research on the role of cuproptosis in the occurrence and development of cancer and the development of targeted therapies based on cuproptosis.

Prediction of Antibiotic Resistance Evolution by Growth Measurement of All Proximal Mutants of Beta-Lactamase.

The antibiotic resistance crisis continues to threaten human health. Better predictions of the evolution of antibiotic resistance genes could contribute to the design of more sustainable treatment strategies. However, comprehensive prediction of antibiotic resistance gene evolution via laboratory approaches remains challenging. By combining site-specific integration and high-throughput sequencing, we quantified relative growth under the respective selection of cefotaxime or ceftazidime selection in ∼23,000 Escherichia coli MG1655 strains that each carried a unique, single-copy variant of the extended-spectrum ß-lactamase gene blaCTX-M-14 at the chromosomal att HK022 site. Significant synergistic pleiotropy was observed within four subgenic regions, suggesting key regions for the evolution of resistance to both antibiotics. Moreover, we propose PEARP and PEARR, two deep-learning models with strong clinical correlations, for the prospective and retrospective prediction of blaCTX-M-14 evolution, respectively. Single to quintuple mutations of blaCTX-M-14 predicted to confer resistance by PEARP were significantly enriched among the clinical isolates harboring blaCTX-M-14 variants, and the PEARR scores matched the minimal inhibitory concentrations obtained for the 31 intermediates in all hypothetical trajectories. Altogether, we conclude that the measurement of local fitness landscape enables prediction of the evolutionary trajectories of antibiotic resistance genes, which could be useful for a broad range of clinical applications, from resistance prediction to designing novel treatment strategies.

Triangular bright solitons in nonlinear optics and Bose-Einstein condensates.

We demonstrate what we believe to be novel triangular bright solitons that can be supported by the nonlinear Schrödinger equation with inhomogeneous Kerr-like nonlinearity and external harmonic potential, which can be realized in nonlinear optics and Bose-Einstein condensates. The profiles of these solitons are quite different from the common Gaussian or sech envelope beams, as their tops and bottoms are similar to the triangle and inverted triangle functions, respectively. The self-defocusing nonlinearity gives rise to the triangle-up solitons, while the self-focusing nonlinearity supports the triangle-down solitons. Here, we restrict our attention only to the lowest-order fundamental triangular solitons. All such solitons are stable, which is demonstrated by the linear stability analysis and also clarified by direct numerical simulations. In addition, the modulated propagation of both types of triangular solitons, with the modulated parameter being the strength of nonlinearity, is also presented. We find that such propagation is strongly affected by the form of the modulation of the nonlinearity. For example, the sudden change of the modulated parameter causes instabilities in the solitons, whereas the gradual variation generates stable solitons. Also, a periodic variation of the parameter causes the regular oscillation of solitons, with the same period. Interestingly, the triangle-up and triangle-down solitons can change into each other, when the parameter changes the sign.

Effects of NAD+ precursors on blood pressure, C-reactive protein concentration and carotid intima-media thickness: A meta-analysis of randomized controlled trials.

BACKGROUND: There are contradictory effects regarding the effect of NAD+ precursor on blood pressure and inflammation. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of NAD+ precursor supplementation on blood pressure, C-reactive protein (CRP) and carotid intima-media thickness (CIMT). METHODS: PubMed/MEDLINE, Web of Science, SCOPUS and Embase databases were searched using standard keywords to identify all controlled trials investigating the effects of NAD+ precursor on blood pressure, CRP and CIMT. Pooled weighted mean difference (WMD) and 95% confidence intervals (95% CI) were achieved by random-effects model analysis for the best estimation of outcomes. RESULTS: Twenty-nine articles (with 8664 participants) were included in this article. Results from meta-analyses of RCTs from random-effects models indicated a significant reduction in systolic (SBP) (weighted mean difference (WMD): -2.54 mmHg, p < .001) and diastolic blood pressure (DBP) (WMD: -2.15 mmHg, p < .001), as well as in CRP (WMD: -.93 mg/L, 95% CI -1.47 to -.40, p < .001) concentrations and CIMT (WMD: -.01 mm, 95% CI -.02 to -.00, p = .005) with the NAD+ precursors supplementation compared with the control group. In addition, a greater effect of supplementation with NAD+ precursors in reducing blood pressure (BP) were observed with the highest dose (≥2 g) and duration of the intervention (>12 weeks), as well as with NA supplementation when compared to NE. CONCLUSIONS: Overall, these findings suggest that NAD+ precursor supplementation might have a beneficial effect on cardiovascular risk factors such as BP, CRP concentration and CIMT.

Effect of preoperative peripheral blood platelet volume index on prognosis in patients with invasive breast cancer.

Aim: This study was designed to investigate the prognostic value of the platelet volume index in patients with invasive breast cancer (IBC). Methods: A total of 524 patients with IBC were enrolled in this study, with a median follow-up time of 6.76 years. The relationship between platelet volume indices and breast cancer prognosis was analyzed. Results: There is a strong correlation between a higher platelet distribution width-to-platelet count ratio (PDW/P) and poorer disease-free survival (DFS) in patients with IBC. The DFS rate was significantly lower among individuals with elevated PDW/P ratios compared with those with lower ratios. Conclusion: The PDW/P ratio is an independent risk factor for predicting DFS in patients with IBC.

HMGA2-Snai2 axis regulates tumorigenicity and stemness of head and neck squamous cell carcinoma.

Cancer stem cells (CSCs) are a tumorigenic cell subpopulation, which contributes to treatment resistance, tumor recurrence, and metastasis. This study aimed to investigate the role and underlying molecular targets of high mobility group AT-hook 2 (HMGA2) in the progression and CSCs regulation of head and neck squamous cell carcinoma (HNSCC). HMGA2 mRNA and protein expression levels were examined in HNSCC specimens and cells by qRT-PCR, Western blot, and immunohistochemistry. The roles of HMGA2 were validated via loss-of-function and exogenous overexpression experiments in vitro and in vivo, and CSCs properties were assessed by tumorsphere formation assay. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays provided further insight into the molecular mechanisms by which HMGA2 regulates stemness. HMGA2 was abnormally overexpressed in HNSCC, and it promoted the expression of the CSCs markers including SOX2, CD133, CD44, ALDH1A1, and Bmi1. HMGA2 was correlated with stemness, malignant progression, and reduced survival in HNSCC. Luciferase reporter assay indicated that Snai2 was a direct downstream target gene of HMGA2. Mechanistically, ChIP-qPCR assay showed that HMGA2 was recruited to three binding sites on the Snai2 promoter, directly facilitating the transcription of Snai2 in HNSCC. Snai2 overexpression reversed the inhibitory effect of HMGA2 interference on the proliferation, invasion, and metastasis of HNSCC and CSC marker expression in vitro and in vivo. HMGA2 promoted the malignant progression of HNSCC and acquired CSCs properties through direct regulation of Snai2, thereby suggesting that targeting the HMGA2-Snai2 axis might be a promising therapeutic strategy for HNSCC.

Lymphovascular invasion is a significant risk factor for non-sentinel nodal metastasis in breast cancer patients with sentinel lymph node (SLN)-positive breast cancer: a cross-sectional study.

BACKGROUND: A connection between lymphovascular invasion and axillary lymph node metastases in breast cancer has been observed, but the findings are inconsistent and primarily based on research in Western populations. We investigated the association between lymphovascular invasion and non-sentinel lymph node (non-SLN) metastasis in breast cancer patients with sentinel lymph node (SLN) metastasis in western China. METHODS: This study comprised 280 breast cancer patients who tested positive for SLN through biopsy and subsequently underwent axillary lymph node dissection (ALND) at The People's Hospital of Guangxi Zhuang Autonomous Region between March 2013 and July 2022. We used multivariate logistic regression analyses to assess the association between clinicopathological characteristics and non-SLN metastasis. Additionally, we conducted further stratified analysis. RESULTS: Among the 280 patients with positive SLN, only 126 (45%) exhibited non-SLN metastasis. Multivariate logistic regression demonstrated that lymphovascular invasion was an independent risk factor for non-SLN in breast cancer patients with SLN metastasis (OR = 6.11; 95% CI, 3.62-10.32, p < 0.05). The stratified analysis yielded similar results. CONCLUSIONS: In individuals with invasive breast cancer and 1-2 positive sentinel lymph nodes, lymphovascular invasion is the sole risk factor for non-SLN metastases. This finding aids surgeons and oncologists in devising a plan for local axillary treatment, preventing both over- and undertreatment.

Risk factors of non-sentinel lymph node metastasis in breast cancer with 1-2 sentinel lymph node macrometastases underwent total mastectomy: a case-control study.

BACKGROUND: The randomized trials which include ACOSOG Z0011 and IBCSG 23-01 had found that the survival rates were not different in patients with cT1/2N0 and 1-2 sentinel lymph node (SLN)-positive, macro/micrometastases who underwent breast-conserving therapy, and micrometastases who underwent total mastectomy (TM), when axillary lymph node dissection (ALND) was omitted. However, for patients with cT1/2N0 and 1-2 SLN macrometastases who underwent TM; there was still insufficient evidence from clinical studies to support whether ALND can be exempted. This study aimed to investigate the risk factors of non-sentinel lymph node (nSLN) metastasis in breast cancer patients with 1-2 SLN macrometastases undergoing TM. METHODS: The clinicopathological data of 1491 breast cancer patients who underwent TM and SLNB from January 2017 to February 2022 were retrospectively analyzed. Univariate and multivariate analyses were performed to analyze the risk factors for nSLN metastasis. RESULTS: A total of 273 patients with 1-2 SLN macrometastases who underwent TM were enrolled. Postoperative pathological data showed that 35.2% patients had nSLN metastasis. The results of multivariate analysis indicated that tumor size (TS) (P = 0.002; OR: 1.051; 95% CI: 1.019-1.084) and ratio of SLN macrometastases (P = 0.0001; OR: 12.597: 95% CI: 4.302-36.890) were the independent risk factors for nSLN metastasis in breast cancer patients with 1-2 SLN macrometastases that underwent TM. The ROC curve analysis suggested that when TS ≤22 mm and ratio of SLN macrometastases ≤0.33, the incidence of nSLN metastasis could be reduced to 17.1%. CONCLUSIONS: The breast cancer patients with cT1/2N0 stage, undergoing TM and 1-2 SLN macrometastases, when the TS ≤22 mm and macrometastatic SLN does not exceed 1/3 of the total number of detected SLN, the incidence of nSLN metastasis is significantly reduced, but whether ALND can be exempted needs further exploration.

Bidirectional Genetic Control of Phenotypic Heterogeneity and Its Implication for Cancer Drug Resistance.

Negative genetic regulators of phenotypic heterogeneity, or phenotypic capacitors/stabilizers, elevate population average fitness by limiting deviation from the optimal phenotype and increase the efficacy of natural selection by enhancing the phenotypic differences among genotypes. Stabilizers can presumably be switched off to release phenotypic heterogeneity in the face of extreme or fluctuating environments to ensure population survival. This task could, however, also be achieved by positive genetic regulators of phenotypic heterogeneity, or "phenotypic diversifiers," as shown by recently reported evidence that a bacterial divisome factor enhances antibiotic resistance. We hypothesized that such active creation of phenotypic heterogeneity by diversifiers, which is functionally independent of stabilizers, is more common than previously recognized. Using morphological phenotypic data from 4,718 single-gene knockout strains of Saccharomyces cerevisiae, we systematically identified 324 stabilizers and 160 diversifiers and constructed a bipartite network between these genes and the morphological traits they control. Further analyses showed that, compared with stabilizers, diversifiers tended to be weaker and more promiscuous (regulating more traits) regulators targeting traits unrelated to fitness. Moreover, there is a general division of labor between stabilizers and diversifiers. Finally, by incorporating NCI-60 human cancer cell line anticancer drug screening data, we found that human one-to-one orthologs of yeast diversifiers/stabilizers likely regulate the anticancer drug resistance of human cancer cell lines, suggesting that these orthologs are potential targets for auxiliary treatments. Our study therefore highlights stabilizers and diversifiers as the genetic regulators for the bidirectional control of phenotypic heterogeneity as well as their distinct evolutionary roles and functional independence.

Analysis of Risk Factors of Early Mortality After Pericardiectomy For Constrictive Pericarditis.

BACKGROUND: We aimed to investigate risk factors of early mortality following pericardiectomy. METHODS: This was a retrospective study of patients undergoing pericardiectomy between January 1994 and May 2021 at The People's Hospital of Guangxi Zhuang Autonomous Region, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, and The People's Hospital of Liuzhou City. RESULTS: This study included 826 patients, who were divided into two groups: group with operative deaths (N = 66) and group without operative deaths (N = 760). There were 66 operative deaths (66/826, 8.0%). The causes of operative deaths were multiorgan failure (86/826, 10.4%). Preoperative CVP (P < 0.001), chest drainage (P < 0.001), surgical duration (P < 0.001), fluid balance postoperative day D2 (P < 0.001), and tuberculosis pericarditis (P = 0.001) in group with operative deaths were significantly higher than those in group without operative deaths. Univariate and multivariate analyses showed that factors associated with operative deaths include male (P < 0.001), age (P < 0.001), ICU retention time (P < 0.001), postoperative hospitalization time (P < 0.001), preoperative central venous pressure (P = 0.018), postoperative central venous pressure (P < 0.001), D0 fluid balance (P < 0.001), D2 fluid balance (P < 0.001), postoperative chest drainage (P = 0.029), surgical duration (P = 0.003), serum creatinine baseline (P = 0.002), serum creatinine 24h after surgery (P < 0.001), serum creatinine 48h after surgery (P < 0.001), blood lactate (P < 0.001), and tuberculosis pericarditis (P = 0.033). CONCLUSION: In our study, incomplete pericardial dissection, fluid overload, and tuberculosis pericarditis are associated with operative deaths following pericardiectomy.

Incomplete Pericardial Dissection, Fluid Overload, Delayed Diagnosis And Treatment, And Tuberculosis Pericarditis Are Associated With Low Cardiac Output Syndrome Following Pericardiectomy.

BACKGROUND: We aimed to investigate risk factors of LCOS following pericardiectomy. METHODS: This was a retrospective study of patients undergoing pericardiectomy at three hospitals between January 1994 and May 2021. RESULTS: A total of 826 patients were divided into two groups: group with LCOS (N = 126) and group without LCOS (N = 700). The incidence of postoperative LCOS was 15.3%. There were 66 operative deaths (8.0%). Univariable and multivariable analyses showed that factors are associated with LCOS, including postoperative LVEDD (P < 0.001), preoperative LVEDD (P < 0.001), time between symptoms and surgery (P < 0.001), thickness of pericardium (P < 0.001), intubation time (P = 0.002), hospitalized time postoperative (P < 0.001), preoperative central venous pressure (P = 0.016), postoperative central venous pressure (P = 0.034), D0 fluid balance (P = 0.019), D2 fluid balance (P = 0.017), postoperative chest drainage (P < 0.001), surgical duration (P < 0.001), bleeding during operation (P = 0.001), serum creatinine 24h after surgery (P < 0.001), serum creatinine 48h after surgery (P = 0.017), fresh-frozen plasma (P = 0.005), packed red cells (P = 0.006), and tuberculosis pericarditis (P = 0.026). CONCLUSION: In our study, incomplete pericardial dissection, fluid overload, delayed diagnosis and treatment, and tuberculosis pericarditis are associated with LCOS following pericardiectomy.

HOXB7 acts as an oncogenic biomarker in head and neck squamous cell carcinoma.

BACKGROUND: The homeobox gene Homeobox B7 (HOXB7) is overexpressed across a range of cancers and promotes tumorigenesis through varying effects on proliferation, survival, migration and invasion. However, its expression pattern and oncogenic role of HOXB7 in head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. Here, we aimed to explore the expression pattern of HOXB7, its clinical significance as well as functional roles in HNSCC. METHODS: HOXB7 mRNA expression in HNSCC was determined by data mining and analyses from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) datasets. The protein abundance of HOXB7 was measured by immunohistochemistry in 119 primary HNSCC samples and associations between its expression and clinicopathological parameters and patient survival were evaluated. The pro-tumorigenic roles of HOXB7 in HNSCC were further delineated in vitro by loss-of-function assay. And a xenograft tumor model was established in nude mice to assess the role of HOXB7 in tumor growth. Connectivity Map (CMap) analysis was performed to identify bioactive small molecules which might be potential inhibitors for HOXB7. RESULTS: Bioinformatics analyses showed that HOXB7 mRNA was significantly overexpressed in 8 independent HNSCC datasets from TCGA and GEO databases. HOXB7 protein was markedly upregulated in HNSCC samples as compared to normal counterparts and its overexpression significantly associated with high pathological grade, advanced clinical stage, cervical node metastasis (P = 0.0195, 0.0152, 0.0300) and reduced overall and disease-free survival (P = 0.0014, 0.0007). Univariate and multivariate Cox regression analyses further revealed HOXB7 as an independent prognostic factor for patients' overall survival. Moreover, HOXB7 knockdown significantly inhibited cell proliferation, migration and invasion and induced cell apoptosis in HNSCC cells, and resulted in compromised tumour growth in vivo. Furthermore, CMap (Connectivity map) analysis has identified three potential bioactive small molecule inhibitors (NU-1025, thiamine, vinburnine) for HOXB7 targeted therapy in HNSCC. CONCLUSIONS: Our findings revealed that overexpression of HOXB7 was associates with tumour aggressiveness and unfavourable prognosis by serving a novel prognostic biomarker in HNSCC. Moreover, HOXB7 might be involved in the development and progression of HNSCC as an oncogene, and thereby might be a potential therapeutic target for HNSCC.

Aberrant overexpression of transcription factor Forkhead box D1 predicts poor prognosis and promotes cancer progression in HNSCC.

OBJECTIVES: Forkhead box D1, the core transcription factor member of FOX family, has gradually seen as a key cancerous regulatory. However, its expression and carcinogenicity in head and neck squamous cell carcinoma (HNSCC) have not been reported yet. This study was to investigate its expression pattern, clinicopathological significance and biological roles in HNSCC. METHODS: HNSCC data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was used to indicate the detailed expression pattern and outcome association of FOXD1, while Western Blot assay to detect FOXD1 level in a panel of HNSCC cell lines as well as immunocytochemistry to explore FOXD1 protein abundance and sublocation. Series of siRNA-mediated FOXD1 knock-down experiments to assess the proliferation, migration, invasion and anti- apoptosis ability after FOXD1 down-regulation. Bioinformatic analysis to find out which biological function and cancer-related pathways of FOXD1 associated genes involved in. RESULTS: FOXD1 mRNA was significantly overexpressed in TCGA-HNSCC, GSE6631, GSE12452, GSE25099 and GSE30784. Besides, IHC results shown that nuclear location FOXD1 protein was significantly higher in primary HNSCC specimens from cohort involved in this study. Also, FOXD1 abundance was significantly correlated with cervical node metastasis and poor over-all/disease-free survival after combination analysis with patient pathological information. siRNA-mediated FOXD1 knock-down significantly inhibited cell proliferation, migration and invasion and induced apoptosis in HNSCC cells. Further analysis of GSEA, GO and KEGG showed that FOXD1 expression was significantly associated with oncological function and cancer-related pathways. CONCLUSIONS: Taken together, our study implies that the potential oncogene, FOXD1, facilitates oncological behavior who can be identified as a brand-new HNSCC biomarker with diagnostic and prognostic significance.

Does Serum Vitamin D Level Affect COVID-19 Infection and Its Severity?-A Case-Control Study.

BACKGROUND: As effective medication to treat COVID-19 is currently unavailable, preventive remedies may be particularly important. OBJECTIVE: To examine the relationship between serum 25-hydroxy vitamin D (25(OH)D) level and COVID-19 infection, its severity, and its clinical case characteristics. METHODS: This case-control study compared serum 25(OH)D levels and rates of vitamin D deficiency (VDD) between 80 healthy controls and 62 patients diagnosed with COVID-19 and admitted to Guangxi People's Hospital, China, 2/16/2020-3/16/2020. Cases were categorized into asymptomatic, mild/moderate, and severe/critical disease. Logistic regression analysis was conducted to examine the associations between 25(OH)D level, or VDD, and case status/severity of COVID-19 while controlling for demographics and comorbidities. A threshold level of vitamin D for conveying COVID-19 risk was estimated. RESULTS: Severe/critical COVID-19 cases were significantly older and had higher percentages of comorbidity (renal failure) compared to mild cases. The serum 25(OH)D concentration in COVID-19 patient was much lower than that in healthy control. And 25(OH)D level was the lowest in severe/critical cases, compared with mild cases. In further, significantly higher rates of VDD were found in COVID-19 cases (41.9%) compared to healthy controls (11.1%). And VDD was the greatest in severe/critical cases (80%), compared with mild cases (36%). These statistically significant associations remained even after controlling for demographics and comorbidities. A potential threshold of 25(OH)D (41.19 nmol/L) to protect against COVID-19 was identified. CONCLUSION: Elderly and people with comorbidities were susceptible to severe COVID-19 infection. VDD was a risk factor for COVID-19, especially for severe/critical cases. While further confirmation is needed, vitamin D supplementation may have prevention or treatment potential for COVID-19 disease.