Single-cell sequencing of head and neck carcinoma: Transcriptional landscape and prognostic model based on malignant epithelial cell features.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the development of novel therapeutic strategies for HNSCC requires a profound understanding of tumor cells and the tumor microenvironment (TME). Additionally, HNSCC has a poor prognosis, necessitating the use of genetic markers for predicting clinical outcomes in HNSCC. In this study, we performed single-cell sequencing analysis on tumor tissues from seven HNSCC patients, along with one adjacent normal tissue. Firstly, the analysis of epithelial cell clusters revealed two clusters of malignant epithelial cells, characterized by unique gene expression patterns and dysregulated signaling pathways compared to normal epithelial cells. Secondly, the examination of the TME unveiled extensive crosstalk between fibroblasts and malignant epithelial cells, potentially mediated through ligand-receptor interactions such as COL1A1-SDC1, COL1A1-CD44, and COL1A2-SDC1. Furthermore, transcriptional heterogeneity was observed in immune cells present in the TME, including macrophages and dendritic cells. Finally, leveraging the gene expression profiles of malignant epithelial cells, we developed a prognostic model comprising six genes, which we validated using two independent datasets. These findings shed light on the heterogeneity within HNSCC tumors and the intricate interplay between malignant cells and the TME. Importantly, the developed prognostic model demonstrates high efficacy in predicting the survival outcomes of HNSCC patients.

Randomized, placebo-controlled trial of orally administered vitamin K1 for warfarin-associated coagulopathy in Chinese patients with mechanical heart valves.

PURPOSE: Warfarin-associated coagulopathy commonly occurs in patients undergoing treatment with this anticoagulant. This trial aimed to determine the efficacy of using low-dose orally administered vitamin K1 to lower international normalized ratio (INR) values into the target range in a cohort of Chinese patients with mechanical heart valves. METHODS: This was a double-blind, placebo-controlled, randomized trial. Chinese patients with mechanical heart valves who were undergoing warfarin treatment and who had INR values from 4.0 to 10.0 without bleeding were the subjects of this study. These patients were randomized into two treatment groups and were orally administered either vitamin K1 (2.5 mg) or placebo. Warfarin was discontinued in both groups until INR values were ≤ 2.5. INR values on the day following treatment were the primary study outcome, with INR values on the following days and adverse clinical events over a 3-month follow-up serving as secondary study outcomes. RESULTS: In total, 80 patients were enrolled in the present study, and 40 patients each were assigned to the placebo and vitamin K1 treatment groups. Patients administered vitamin K1 exhibited a quick reduction in INR values relative to patients administered placebo (29 of 40 [72.5%] vs. 0 of 44 [0%] patients exhibiting INR values from 1.5-2.5 on the day following treatment, respectively, p = 0.000). Lower bleeding incidence was observed among patients administered vitamin K1 relative to those administered placebo during follow-up (4 [10%] vs. 12 [30%] patients, respectively, p = 0.045). There were no instances of thromboembolic complications or warfarin resistance in either group. CONCLUSION: Low-dose oral vitamin K1 can be effectively administered to Chinese patients with mechanical heart valves taking warfarin to rapidly reduce elevated INR values.

Laryngeal paraganglioma: The analysis of misdiagnosed cases and literature review.

Laryngeal paraganglioma (LP) is an exceptionally rare neuroendocrine tumor, underscoring importance of accurate identification to preclude misdiagnoses. In this review, we presented two typical misdiagnosed LPs, and offered reviews of LP cases reported over the preceding decade and all documented misdiagnosed LP cases. Furthermore, we systematically investigated the underlying causes of misdiagnosis and elucidated key points for effective differentiation. A retrospective analysis of 28 LP cases revealed a predominant occurrence in middle-aged women, with an average history of 25.1 months. Through an analysis of all misdiagnosed cases (n = 37), supraglottic LPs were frequently misidentified as laryngeal carcinomas and vascular tumors, while subglottic LPs were often misdiagnosed as thyroid cancers. And the occurrence of misdiagnosis resulted in delayed and inappropriate treatments, contributing to the deterioration of LP patients (14 cases, 37.8%). In conclusion, this review endeavored to heighten awareness of LPs, with the ultimate goal of advancing diagnostic precision and enhancing patient outcomes.

Extracellular Vesicles from Urine-Derived Stem Cell for Tissue Engineering and Regenerative Medicine.

The potential of urine-derived stem cells (USCs) for tissue engineering and regenerative medicine has attracted much attention during the last few decades. However, it has been suggested that the effects of the USCs may be endowed by their paracrine extracellular vesicles (EVs) rather than their differentiation. Compared with the USCs, the USC-EVs can cross the barriers more easily and safely, and their inclusions may mediate intercellular communication and promote the tissue repair. This article has summarized the current knowledge and applications about the USC-EVs in tissue engineering and regenerative medicine, and discussed the prospects and challenges for using them as an alternative to cell therapy. Impact statement Urine-derived stem cells (USCs) represent a newly discovered type of stem cells, and studies have proved that the beneficial effects of the USCs may be manifested through their paracrine extracellular vesicles (EVs) rather than through their own differentiation, which opens up new avenues for tissue engineering and regenerative medicine strategies. Therefore, this review aims to summarize the latest research progress and potential clinical applications of the USC-EVs, highlighting the promising potential of the USC-EVs as a therapeutic option in kidney regeneration, genital regeneration, nerve regeneration, bone and cartilage regeneration, and wound healing.

Security and cost comparison of INR self-testing and conventional hospital INR testing in patients with mechanical heart valve replacement.

BACKGROUND: International normalized ratio (INR) self-testing can improve the management of anticoagulation therapy with warfarin for the patients following mechanical heart valve replacement. Several reviews and studies have demonstrated self-management as an option to improve patient's outcome considerably after mechanical heart valve replacement. We sought to analyze the security, economy and discuss the prospect of self-testing of anticoagulation therapy in patients following mechanical heart valve replacement in China, and evaluate the accuracy and stability of CoaguChek XS portable INR-testing device. METHODS: This was a prospective self-controlled clinical study conducted with 526 patients receiving oral warfarin anticoagulation therapy after mechanical heart valve replacement in the period of Mar.1, 2012 - Nov.1, 2012 in Cardiovascular Surgery Department of West China Hospital of Sichuan University. The same patient performed INR testing with CoaguChek XS portable coagulometer (group1) and central lab (group 2) in parallel. The follow-up time was 6 months. Meanwhile, a questionnaire was handed out to survey the expenses required for the re-examination visits to the hospital, time, and anticoagulation complications. RESULTS: No severe anticoagulation complications occurred in all the patients. No significant difference of the INR results were observed between group 1 and group 2, they showed significant relevance, r = 0.953(p < 0.05). Compared with the conventional method of INR testing in hospital, the portable coagulometer is convenient, quick and less traumatic. Self-testing of anticoagulation therapy reduced the cost and the time required for re-examination. CONCLUSIONS: Results of CoaguChek XS monitor are precise and have a good consistency and stability as compared with traditional laboratory testing. For the patients receiving anticoagulation therapy after mechanical heart valve replacement, the self-testing of anticoagulation therapy with portable coagulometer is a safe choice, and it has a promising future application in China.

Renal protective effect of sirtuin 1.

Silent information regulator 2 (Sir2) is a nicotinamide adenine dinucleotide- (NAD(+)-) dependent deacetylase. The homology of SIRT1 and Sir2 has been extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD(+) and is therefore linked to cellular energy metabolism and the redox state through multiple signalling and survival pathways. During the past decade, investigators have reported that SIRT1 activity is essential in cancer, neurodegenerative diseases, diabetes, cardiovascular disease, and other age-related diseases. In the kidneys, SIRT1 may inhibit renal cell apoptosis, inflammation, and fibrosis. Therefore its activation may also become a new therapeutic target in the patients with chronic kidney disease including diabetic nephropathy. In this paper, we would like to review the protective functions of sirtuins and the role of SIRT1 in the onset of kidney disease based on previous studies, including diabetic nephropathy, acute renal injury, chronic kidney disease as well as lupus nephritis.