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1.
J Adv Res ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38960276

ABSTRACT

INTRODUCTION: Growing interest toward RNA modification in cancer has inspired the exploration of gene sets related to multiple RNA modifications. However, a comprehensive elucidation of the clinical value of various RNA modifications in breast cancer is still lacking. OBJECTIVES: This study aimed to provide a strategy based on RNA modification-related genes for predicting therapy response and survival outcomes in breast cancer patients. METHODS: Genes related to thirteen RNA modification patterns were integrated for establishing a nine-gene-containing signature-RMscore. Alterations of tumor immune microenvironment and therapy response featured by different RMscore levels were assessed by bulk transcriptome, single-cell transcriptome and genomics analyses. The biological function of key RMscore-related molecules was investigated by cellular experiments in vitro and in vivo, using flow cytometry, immunohistochemistry and immunofluorescence staining. RESULTS: This study has raised an effective therapy strategy for breast cancer patients after a well-rounded investigation of RNA modification-related genes. With a great performance of predicting patient prognosis, high levels of the RMscore proposed in this study represented suppressive immune microenvironment and therapy resistance, including adjuvant chemotherapy and PD-L1 blockade treatment. As the key contributor of the RMscore, inhibition of WDR4 impaired breast cancer progression significantly in vitro and in vivo, as well as participated in regulating cell cycle and mTORC1 signaling pathway via m7G modification. CONCLUSION: Briefly, this study has developed promising and effective tactics to achieve the prediction of survival probabilities and treatment response in breast cancer patients.

2.
Ann Clin Microbiol Antimicrob ; 23(1): 62, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38978096

ABSTRACT

BACKGROUND: This study analyzed the genetic traits and fitness costs of vancomycin-resistant Enterococcus faecium (VREfm) blood isolates carrying Tn1546-type transposons harboring the vanA operon. METHODS: All E. faecium blood isolates were collected from eight general hospitals in South Korea during one-year study period. Antimicrobial susceptibility testing and vanA and vanB PCR were performed. Growth rates of E. faecium isolates were determined. The vanA-positive isolates were subjected to whole genome sequencing and conjugation experiments. RESULTS: Among 308 E. faecium isolates, 132 (42.9%) were positive for vanA. All Tn1546-type transposons harboring the vanA operon located on the plasmids, but on the chromosome in seven isolates. The plasmids harboring the vanA operon were grouped into four types; two types of circular, nonconjugative plasmids (Type A, n = 50; Type B, n = 46), and two types of putative linear, conjugative plasmids (Type C, n = 16; Type D, n = 5). Growth rates of vanA-positive E. faecium isolates were significantly lower than those of vanA-negative isolates (P < 0.001), and reduction in growth rate under vancomycin pressure was significantly larger in isolates harboring putative linear plasmids than in those harboring circular plasmids (P = 0.020). CONCLUSIONS: The possession of vanA operon was costly to bacterial hosts in antimicrobial-free environment, which provide evidence for the importance of reducing vancomycin pressure for prevention of VREfm dissemination. Fitness burden to bacterial hosts was varied by type and size of the vanA operon-harboring plasmid.


Subject(s)
Anti-Bacterial Agents , Bacterial Proteins , Carbon-Oxygen Ligases , DNA Transposable Elements , Enterococcus faecium , Microbial Sensitivity Tests , Operon , Plasmids , Plasmids/genetics , Enterococcus faecium/genetics , Humans , Bacterial Proteins/genetics , Republic of Korea , Carbon-Oxygen Ligases/genetics , Anti-Bacterial Agents/pharmacology , Whole Genome Sequencing , Gram-Positive Bacterial Infections/microbiology , Vancomycin-Resistant Enterococci/genetics , Vancomycin Resistance/genetics , Genetic Fitness , Vancomycin/pharmacology , Conjugation, Genetic
3.
J Pers Med ; 14(6)2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38929878

ABSTRACT

An older age is associated with severe progression and poor prognosis in coronavirus disease 2019 (COVID-19), and mechanical ventilation is often required. The specific characteristics of older patients undergoing mechanical ventilation and their prognostic factors are largely unknown. We aimed to identify potential prognostic factors in this group to inform treatment decisions. This retrospective cohort study collected data from patients with COVID-19 at 22 medical centers. Univariate and multivariate Cox regression analyses were performed to assess factors that influence mortality. We allocated 434 patients in geriatric (≥80 years) and elderly (65-79 years) groups. The former group scored significantly higher than the elderly group in the clinical frailty scale and sequential organ failure assessment, indicating more severe organ dysfunction. Significantly lower administration rates of tocilizumab and extracorporeal membrane oxygenation and higher intensive care unit (ICU) and in-hospital mortality were noted in the geriatric group. The factors associated with ICU and in-hospital mortality included high creatinine levels, the use of continuous renal replacement therapy, prone positioning, and the administration of life-sustaining treatments. These results highlight significant age-related differences in the management and prognosis of critically ill older patients with COVID-19. Increased mortality rates and organ dysfunction in geriatric patients undergoing mechanical ventilation necessitate age-appropriate treatment strategies to improve their prognoses.

4.
Cell Death Discov ; 10(1): 222, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719807

ABSTRACT

Neutrophil heterogeneity is involved in autoimmune diseases, sepsis, and several cancers. However, the link between neutrophil heterogeneity and T-cell immunity in thyroid cancer is incompletely understood. We investigated the circulating neutrophil heterogeneity in 3 undifferentiated thyroid cancer (UTC), 14 differentiated thyroid cancer (DTC) (4 Stage IV, 10 Stage I-II), and healthy controls (n = 10) by transcriptomic data and cytometry. Participants with UTC had a significantly higher proportion of immature high-density neutrophils (HDN) and lower proportion of mature HDN in peripheral blood compared to DTC. The proportion of circulating PD-L1+ immature neutrophils were significantly increased in advanced cancer patients. Unsupervised analysis of transcriptomics data from circulating HDN revealed downregulation of innate immune response and T-cell receptor signaling pathway in cancer patients. Moreover, UTC patients revealed the upregulation of glycolytic process and glutamate receptor signaling pathway. Comparative analysis across tumor types and stages revealed the downregulation of various T-cell-related pathways, such as T-cell receptor signaling pathway and T-cell proliferation in advanced cancer patients. Moreover, the proportions of CD8+ and CD4+ T effector memory CD45RA+ (TEMRA) cells from peripheral blood were significantly decreased in UTC patients compared to DTC patients. Finally, we demonstrated that proportions of tumor-infiltrated neutrophils were increased and related with poor prognosis in advanced thyroid cancer using data from our RNA-seq and TCGA (The Cancer Genome Atlas) data. In conclusion, observed prevalence of circulating immature high-density neutrophils and their immunosuppressive features in undifferentiated thyroid cancers underscore the importance of understanding neutrophil dynamics in the context of tumor progression in thyroid cancer.

5.
Front Immunol ; 15: 1382520, 2024.
Article in English | MEDLINE | ID: mdl-38698857

ABSTRACT

Background: The Y-box-binding proteins (YBX) act as a multifunctional role in tumor progression, metastasis, drug resistance by regulating the transcription and translation process. Nevertheless, their functions in a pan-cancer setting remain unclear. Methods: This study examined the clinical features expression, prognostic value, mutations, along with methylation patterns of three genes from the YBX family (YBX1, YBX2, and YBX3) in 28 different types of cancer. Data used for analysis were obtained from Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. A novel YBXs score was created using the ssGSEA algorithm for the single sample gene set enrichment analysis. Additionally, we explored the YBXs score's association with the tumor microenvironment (TME), response to various treatments, and drug resistance. Results: Our analysis revealed that YBX family genes contribute to tumor progression and are indicative of prognosis in diverse cancer types. We determined that the YBXs score correlates significantly with numerous malignant pathways in pan-cancer. Moreover, this score is also linked with multiple immune-related characteristics. The YBXs score proved to be an effective predictor for the efficacy of a range of treatments in various cancers, particularly immunotherapy. To summarize, the involvement of YBX family genes is vital in pan-cancer and exhibits a significant association with TME. An elevated YBXs score indicates an immune-activated TME and responsiveness to diverse therapies, highlighting its potential as a biomarker in individuals with tumors. Finally, experimental validations were conducted to explore that YBX2 might be a potential biomarker in liver cancer. Conclusion: The creation of YBXs score in our study offered new insights into further studies. Besides, YBX2 was found as a potential therapeutic target, significantly contributing to the improvement of HCC diagnosis and treatment strategies.


Subject(s)
Biomarkers, Tumor , Gene Expression Regulation, Neoplastic , Liver Neoplasms , Tumor Microenvironment , Humans , Biomarkers, Tumor/genetics , Liver Neoplasms/genetics , Liver Neoplasms/diagnosis , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Prognosis , Y-Box-Binding Protein 1/genetics , Y-Box-Binding Protein 1/metabolism , Mutation , Drug Resistance, Neoplasm/genetics , Gene Expression Profiling , Cell Line, Tumor , DNA Methylation
6.
Article in English | MEDLINE | ID: mdl-38749491

ABSTRACT

Background: The use of immune checkpoint inhibitors (ICIs) in patients with advanced lung cancer is increasing. Despite ongoing studies to predict the efficacy of ICIs, its use in clinical practice remains difficult. Thus, we aimed to discover a predictive marker by analyzing blood cell characteristics and developing a scoring system for patients treated with ICIs. Methods: This was a prospective multicenter study in patients with advanced non-small cell lung cancer (NSCLC) who received ICIs as second-line treatment from June 2021 to November 2022. Blood cell parameters in routine blood samples were evaluated using an automated hematology analyzer. Immune checkpoint inhibitor score (IChIS) was calculated as the sum of neutrophil count score and immature granulocyte score. Results: A total of 143 patients from 4 institutions were included. The treatment response was as follows: partial response, 8.4%; stable disease, 37.1%; and progressive disease, 44.8%. Median progression-free survival and overall survival after ICI treatment was 3.0 and 8.3 months, respectively. Median progression-free survival in patients with an IChIS of 0 was 4.0 months, which was significantly longer than 1.9 months in patients with an IChIS of 1 and 1.0 month in those with an IChIS of 2 (p = 0.001). The median overall survival in patients with an IChIS of 0 was 10.2 months, which was significantly longer than 6.8 and 1.8 months in patients with an IChIS of 1 and 2, respectively (p < 0.001). Conclusions: Baseline IChIS could be a potential biomarker for predicting survival benefit of immunotherapy in NSCLC.

7.
Environ Res ; 252(Pt 1): 118881, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38582430

ABSTRACT

Nitrate reduction in bio-electrochemical systems (BESs) has attracted wide attention due to its low sludge yields and cost-efficiency advantages. However, the high resistance of traditional electrodes is considered to limit the denitrification performance of BESs. Herein, a new graphene/polypyrrole (rGO/PPy) modified electrode is fabricated via one-step electrodeposition and used as cathode in BES for improving nitrate removal from wastewater. The formation and morphological results support the successful formation of rGO/PPy nanohybrids and confirm the part covalent bonding of Py into GO honeycomb lattices to form a three-dimensional cross-linked spatial structure. The electrochemical tests indicate that the rGO/PPy electrode outperforms the unmodified electrode due to the 3.9-fold increase in electrochemical active surface area and 6.9-fold decrease in the charge transfer resistance (Rct). Batch denitrification activity tests demonstrate that the BES equipped with modified rGO/PPy biocathode could not only achieve the full denitrification efficiency of 100% with energy recovery (15.9 × 10-2 ± 0.14 A/m2), but also favor microbial attach and growth with improved biocompatible surface. This work provides a feasible electrochemical route to fabricate and design a high-performance bioelectrode to enhance denitrification in BESs.


Subject(s)
Denitrification , Electrodes , Graphite , Polymers , Pyrroles , Graphite/chemistry , Polymers/chemistry , Pyrroles/chemistry , Electrochemical Techniques/methods , Bioelectric Energy Sources , Nitrates/chemistry , Carbon/chemistry , Carbon Fiber/chemistry
8.
J Microbiol ; 62(2): 101-112, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38589765

ABSTRACT

Candida albicans (C. albicans) is one of the most common opportunistic fungi worldwide, which is associated with a high mortality rate. Despite treatment, C. albicans remains the leading cause of life-threatening invasive infections. Consequently, antimicrobial peptides (AMPs) are potential alternatives as antifungal agents with excellent antifungal activity. We previously reported that Css54, found in the venom of Centrurodies suffusus suffusus (C. s. suffusus) showed antibacterial activity against zoonotic bacteria. However, the antifungal activity of Css54 has not yet been elucidated. The objective of this study was to identify the antifungal activity of Css54 against C. albicans and analyze its mechanism. Css54 showed high antifungal activity against C. albicans. Css54 also inhibited biofilm formation in fluconazole-resistant fungi. The antifungal mechanism of action of Css54 was investigated using membrane-related assays, including the membrane depolarization assay and analysis of the membrane integrity of C. albicans after treatment with Css54. Css54 induced reactive oxygen species (ROS) production in C. albicans, which affected its antifungal activity. Our results indicate that Css54 causes membrane damage in C. albicans, highlighting its value as a potential therapeutic agent against C. albicans infection.


Subject(s)
Antifungal Agents , Candida albicans , Animals , Antifungal Agents/pharmacology , Scorpions , Peptides/pharmacology , Fluconazole/pharmacology , Microbial Sensitivity Tests , Biofilms
9.
Animals (Basel) ; 14(8)2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38672388

ABSTRACT

Understanding the spatial variation and formation mechanism of biological diversity is a hot topic in ecological studies. Comparing with α diversity, ß diversity is more accurate in reflecting community dynamics. During the past decades, ß diversity studies usually focused on plants, mammals, and birds. Studies of amphibian ß diversity in montane ecosystems, in particular, tadpoles, are still rare. In this study, Mount Emei, located in southwestern China, was selected as the study area. We explored the tadpole ß diversity in 18 streams, based on a two-year survey (2018-2019). Our results indicated a high total ß diversity in tadpole assemblages, which was determined by both turnover and nestedness processes, and the dominant component was turnover. Both the total ß diversity and turnover component were significantly and positively correlated with geographical, elevational, and environmental distances, but no significant relationship was detected between these and the nestedness component. Moreover, the independent contributions of river width, current velocity, and chlorophyll α were larger than that of geographical and elevational distance. Overall, tadpole ß diversity was determined by both spatial and environmental factors, while the contribution of environmental factors was larger. Future studies can focus on functional and phylogenetic structures, to better understand the tadpole assembly process.

10.
Tuberc Respir Dis (Seoul) ; 87(3): 292-301, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38547860

ABSTRACT

Stage 3 non-small cell lung cancer (NSCLC) exhibits significant diversity, making it challenging to define an optimal treatment. A collaborative multidisciplinary approach is essential in crafting individualized treatments. Previously, targeted therapies and immunotherapies were commonly used to treat patients with advanced and metastatic lung cancer. Such treatments are now being extended to individuals considered surgery, as well as patients once considered unsuitable for surgery. These changes have increased surgical success and substantially reduced postoperative recurrence. However, the possibility of severe adverse effects from immunotherapy can deter some patients from performing surgery. It is essential to carefully explore the clinical traits and biomarkers of patients who may benefit the most from immunotherapy, and patients for whom immunotherapy should not be prescribed. In summary, it's crucial to effectively integrate the latest immunotherapy in treating stage 3 NSCLC patients, thereby increasing their opportunities for surgical intervention, and ensuring they receive the best possible care.

11.
Microorganisms ; 12(3)2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38543567

ABSTRACT

Gram-negative bacterial endotoxins can cause pathophysiological effects such as high fever when introduced into the bloodstream. Therefore, endotoxin testing is necessary when producing injectable pharmaceuticals. The pharmaceutical industry has widely used Limulus amebocyte lysate (LAL) to certify product quality. However, ethical concerns have been raised and the increasing scarcity of Limulus polyphemus necessitates the development of novel testing techniques. Recombinant factor C (rFC) was developed using genetic engineering techniques. The aim of this study was to investigate the validity of rFC testing and compare it with the LAL method. The specificity, linearity, accuracy, precision, and robustness of the rFC assay were evaluated. After validation, the rFC assay was found to be suitable for endotoxin detection. We compared the accuracy of the rFC and LAL assays using reference standard endotoxin. The rFC assay was as accurate as the LAL assay. We also compared the two assays using biopharmaceuticals. Greater interference occurred in some samples when the rFC assay was used than when the LAL assay was used. However, the rFC assay overcame the interference when the samples were diluted. Overall, we suggest that rFC can be applied to test biopharmaceuticals.

13.
Tuberc Respir Dis (Seoul) ; 87(2): 145-154, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38368903

ABSTRACT

The consequences of coronavirus disease 2019 (COVID-19) are particularly severe in older adults with a disproportionate number of severe and fatal outcomes. Therefore, this integrative review aimed to provide a comprehensive overview of the clinical characteristics, management approaches, and prognosis of older patients diagnosed with COVID-19. Common clinical presentations in older patients include fever, cough, and dyspnea. Additionally, preexisting comorbidities, especially diabetes and pulmonary and cardiovascular diseases, were frequently observed and associated with adverse outcomes. Management strategies varied, however, early diagnosis, vigilant monitoring, and multidisciplinary care were identified as key factors for enhancing patient outcomes. Nonetheless, the prognosis remains guarded for older patients, with increased rates of hospitalization, mechanical ventilation, and mortality. However, timely therapeutic interventions, especially antiviral and supportive treatments, have demonstrated some efficacy in mitigating the severe consequences in this age group. In conclusion, while older adults remain highly susceptible to severe outcomes from COVID-19, early intervention, rigorous monitoring, and comprehensive care can play a pivotal role in improving their clinical outcomes.

14.
Water Res ; 253: 121220, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38341969

ABSTRACT

A novel integrated pilot-scale A-stage high rate activated sludge, B-stage short-cut biological nitrogen removal and side-stream enhanced biological phosphorus removal (A/B-shortcut N-S2EBPR) process for treating municipal wastewater was demonstrated with the aim to achieve simultaneous and carbon- and energy-efficient N and P removal. In this studied period, an average of 7.62 ± 2.17 mg-N/L nitrite accumulation was achieved through atypical partial nitrification without canonical known NOB out-selection. Network analysis confirms the central hub of microbial community as Nitrospira, which was one to two orders of magnitude higher than canonical aerobic oxidizing bacteria (AOB) in a B-stage nitrification tank. The contribution of comammox Nitrospira as AOB was evidenced by the increased amoB/nxr ratio and higher ammonia oxidation activity. Furthermore, oligotyping analysis of Nitrospira revealed two dominant sub-clusters (microdiveristy) within the Nitrospira. The relative abundance of oligotype II, which is phylogenetically close to Nitrospira_midas_s_31566, exhibited a positive correlation with nitrite accumulation in the same operational period, suggesting its role as comammox Nitrospira. Additionally, the phylogenetic investigation suggested that heterotrophic organisms from the family Comamonadacea and the order Rhodocyclaceae embedding ammonia monooxygenase and hydroxylamine oxidase may function as heterotrophic nitrifiers. This is the first study that elucidated the impact of integrating the S2EBPR on nitrifying populations with implications on short-cut N removal. The unique conditions in the side-stream reactor, such as low ORP, favorable VFA concentrations and composition, seemed to exert different selective forces on nitrifying populations from those in conventional biological nutrient removal processes. The results provide new insights for integrating EBPR with short-cut N removal process for mainstream wastewater treatment.


Subject(s)
Ammonia , Nitrites , Phylogeny , Oxidation-Reduction , Bacteria/genetics , Nitrification
15.
Am J Cancer Res ; 14(1): 97-113, 2024.
Article in English | MEDLINE | ID: mdl-38323275

ABSTRACT

Cathepsin C (CTSC), also known as dipeptidyl peptidase I, is a cathepsin with lysosomal exocysteine protease activity and a central coordinator for the activation of neutrophil-derived serine proteases in the lysosomes of neutrophils. Although the role of CTSC in various cancers, including liver and breast cancers, has recently been reported, its role in non-small cell lung cancer (NSCLC) is largely unknown. This study aimed to investigate the functional role of CTSC in NSCLC and the molecular mechanisms underlying CTSC involvement in disease progression. CTSC overexpression markedly enhanced the growth, motility, and invasiveness of NSCLC cells in vitro and in vivo. CTSC knockdown using shRNA in NSCLC cells reversed the migratory and invasive behavior of NSCLC cells. CTSC also induced epithelial-mesenchymal transition through the Yes-associated protein signaling pathway. In addition, our analyses of clinical samples confirmed that high CTSC expression was associated with lymph node metastasis and recurrence in lung adenocarcinoma. In conclusion, CTSC plays an important role in the progression of NSCLC. Thus, targeting CTSC may be a promising treatment option for patients with NSCLC.

16.
Cancers (Basel) ; 16(3)2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38339350

ABSTRACT

The extracellular matrix (ECM) exerts physiological activity, facilitates cell-to-cell communication, promotes cell proliferation and metastasis, and provides mechanical support for tumor cells. The development of solid tumors is often associated with increased stiffness. A stiff ECM promotes mechanotransduction, and the predominant transcription factors implicated in this phenomenon are YAP/TAZ, ß-catenin, and NF-κB. In this study, we aimed to investigate whether YAP is a critical mediator linking matrix stiffness and PD-L1 in lung adenocarcinoma. We confirmed that YAP, PD-L1, and Ki-67, a marker of cell proliferation, increase as the matrix stiffness increases in vitro using the lung adenocarcinoma cell lines PC9 and HCC827 cells. The knockdown of YAP decreased the expression of PD-L1 and Ki-67, and conversely, the overexpression of YAP increased the expression of PD-L1 and K-67 in a stiff-matrix environment (20.0 kPa). Additionally, lung cancer cells were cultured in a 3D environment, which provides a more physiologically relevant setting, and compared to the results obtained from 2D culture. Similar to the findings in 2D culture, it was confirmed that YAP influenced the expression of PD-L1 and K-67 in the 3D culture experiment. Our results suggest that matrix stiffness controls PD-L1 expression via YAP activation, ultimately contributing to cell proliferation.

17.
Ecol Evol ; 14(2): e10902, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38371862

ABSTRACT

Exploring the microhabitat determinants of organisms distribution and functional traits differences can help us better understand the importance of intraspecific variations in ecological niches. Investigations on animals functional niche primarily focused on differences among species and tended to neglect the potential variability within species, despite the fact that the ecological and evolutionary importance of intraspecific variations was widely recognized. In this study, we examined the influence of microhabitat features on the intraspecific variability of the distribution and functional traits of a highest elevational distributed lizard species Phrynocephalus erythrurus. To do so, field work was conducted between July and August, 2020 and August and September, 2021 in Namtso watershed in central Xizang, China. Specifically, 11 transects were sampled for P. erythrurus individuals, which were measured for a set of 10 morphological traits. Moreover, 11 microhabitat variables that potentially affect the distribution of lizards were also measured for each transect. Our results indicated that juveniles, males, and females exhibited different functional traits, allowing them to occupy distinct functional space. The distribution of juveniles, males, and females was determined by different microhabitat variables such as illuminance and air temperature. More importantly, these variables also determined the intraspecific functional traits variability in this lizard species. All of these results supported previous claims that intraspecific traits variation should be incorporated into functional ecological studies, and diverse microhabitat features should be conserved to maintain high intraspecific diversity. Future studies can focus on the food analysis to explore the linkage between functional traits and resources utilization within animal populations.

18.
BMC Palliat Care ; 23(1): 42, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38355511

ABSTRACT

BACKGROUND: In the intensive care unit (ICU), we may encounter patients who have completed a Do-Not-Resuscitate (DNR) or a Physician Orders to Stop Life-Sustaining Treatment (POLST) document. However, the characteristics of ICU patients who choose DNR/POLST are not well understood. METHODS: We retrospectively analyzed the electronic medical records of 577 patients admitted to a medical ICU from October 2019 to November 2020, focusing on the characteristics of patients according to whether they completed DNR/POLST documents. Patients were categorized into DNR/POLST group and no DNR/POLST group according to whether they completed DNR/POLST documents, and logistic regression analysis was used to evaluate factors influencing DNR/POLST document completion. RESULTS: A total of 577 patients were admitted to the ICU. Of these, 211 patients (36.6%) had DNR or POLST records. DNR and/or POLST were completed prior to ICU admission in 48 (22.7%) patients. The DNR/POLST group was older (72.9 ± 13.5 vs. 67.6 ± 13.8 years, p < 0.001) and had higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (26.1 ± 9.2 vs. 20.3 ± 7.7, p < 0.001) and clinical frailty scale (5.1 ± 1.4 vs. 4.4 ± 1.4, p < 0.001) than the other groups. Solid tumors, hematologic malignancies, and chronic lung disease were the most common comorbidities in the DNR/POLST groups. The DNR/POLST group had higher ICU and in-hospital mortality and more invasive treatments (arterial line, central line, renal replacement therapy, invasive mechanical ventilation) than the other groups. Body mass index, APAHCE II score, hematologic malignancy, DNR/POLST were factors associated with in-hospital mortality. CONCLUSIONS: Among ICU patients, 36.6% had DNR or POLST orders and received more invasive treatments. This is contrary to the common belief that DNR/POLST patients would receive less invasive treatment and underscores the need to better understand and include end-of-life care as an important ongoing aspect of patient care, along with communication with patients and families.


Subject(s)
Physicians , Terminal Care , Humans , Resuscitation Orders , Retrospective Studies , Intensive Care Units
19.
Sci China Life Sci ; 67(4): 653-662, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38198029

ABSTRACT

PIWI-interacting RNAs (piRNAs) are a class of small noncoding RNA molecules that specifically bind to piwi protein family members to exert regulatory functions in germ cells. Recent studies have found that piRNAs, as tissue-specific molecules, both play oncogenic and tumor suppressive roles in cancer progression, including cancer cell proliferation, metastasis, chemoresistance and stemness. Additionally, the atypical manifestation of piRNAs and PIWI proteins in various malignancies presents a promising strategy for the identification of novel biomarkers and therapeutic targets in the diagnosis and management of tumors. Nonetheless, the precise functions of piRNAs in cancer progression and their underlying mechanisms have yet to be fully comprehended. This review aims to examine current research on the biogenesis and functions of piRNA and its burgeoning importance in cancer progression, thereby offering novel perspectives on the potential utilization of piRNAs and piwi proteins in the management and treatment of advanced cancer.


Subject(s)
Neoplasms , RNA, Small Untranslated , Humans , Argonaute Proteins/genetics , Argonaute Proteins/metabolism , Neoplasms/metabolism , Piwi-Interacting RNA , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism
20.
Biomedicines ; 12(1)2024 Jan 06.
Article in English | MEDLINE | ID: mdl-38255225

ABSTRACT

Coronavirus disease 2019 (COVID-19), is an ongoing issue in certain populations, presenting rapidly worsening pneumonia and persistent symptoms. This study aimed to test the predictability of rapid progression using radiographic scores and laboratory markers and present longitudinal changes. This retrospective study included 218 COVID-19 pneumonia patients admitted at the Chungnam National University Hospital. Rapid progression was defined as respiratory failure requiring mechanical ventilation within one week of hospitalization. Quantitative COVID (QCOVID) scores were derived from high-resolution computed tomography (CT) analyses: (1) ground glass opacity (QGGO), (2) mixed diseases (QMD), and (3) consolidation (QCON), and the sum, quantitative total lung diseases (QTLD). Laboratory data, including inflammatory markers, were obtained from electronic medical records. Rapid progression was observed in 9.6% of patients. All QCOVID scores predicted rapid progression, with QMD showing the best predictability (AUC = 0.813). In multivariate analyses, the QMD score and interleukin(IL)-6 level were important predictors for rapid progression (AUC = 0.864). With >2 months follow-up CT, remained lung lesions were observed in 21 subjects, even after several weeks of negative reverse transcription polymerase chain reaction test. AI-driven quantitative CT scores in conjugation with laboratory markers can be useful in predicting the rapid progression and monitoring of COVID-19.

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