Circulating tumor cells (CTCs) are tumor cells that have sloughed off the primary tumor and extravasate into and circulate in the blood. Understanding of the metastatic cascade of CTCs has tremendous ...potential for the identification of targets against cancer metastasis. Detecting these very rare CTCs among the massive blood cells is challenging. However, emerging technologies for CTCs detection have profoundly contributed to deepening investigation into the biology of CTCs and have facilitated their clinical application. Current technologies for the detection of CTCs are summarized herein, together with their advantages and disadvantages. The detection of CTCs is usually dependent on molecular markers, with the epithelial cell adhesion molecule being the most widely used, although molecular markers vary between different types of cancer. Properties associated with epithelial-to-mesenchymal transition and stemness have been identified in CTCs, indicating their increased metastatic capacity. Only a small proportion of CTCs can survive and eventually initiate metastases, suggesting that an interaction and modulation between CTCs and the hostile blood microenvironment is essential for CTC metastasis. Single-cell sequencing of CTCs has been extensively investigated, and has enabled researchers to reveal the genome and transcriptome of CTCs. Herein, we also review the clinical applications of CTCs, especially for monitoring response to cancer treatment and in evaluating prognosis. Hence, CTCs have and will continue to contribute to providing significant insights into metastatic processes and will open new avenues for useful clinical applications.
Cryptococcal meningitis (CM) is the leading cause of mortality among patients infected with human immunodeficiency virus (HIV). Although treatment strategies for CM are continually being developed, ...the mortality rate is still high. Therefore, we need to explore more therapeutic strategies that are aimed at hindering its pathogenic mechanism. In the field of CM, several studies have observed rapid iron accumulation and lipid peroxidation within the brain, all of which are hallmarks of ferroptosis, which is a type of programmed cell death that is characterized by iron dependence and lipid peroxidation. In recent years, many studies have confirmed the involvement of ferroptosis in many diseases, including infectious diseases such as
infection and coronavirus disease-2019 (COVID-19). Furthermore, ferroptosis is considered as immunogenic and pro-inflammatory as the ferroptotic cells release damage-associated molecular pattern molecules (DAMPs) and alarmin, both of which regulate immunity and pro-inflammatory activity. Hence, we hypothesize that there might be a relationship between this unique cell death modality and CM. Herein, we review the evidence of ferroptosis in CM and consider the hypothesis that ferroptotic cell death may be involved in the cell death of CM.
Currently, mechanisms and therapeutic approaches have been thoroughly studied in various prevalent malignant tumors, such as breast and lung cancer. However, there is inevitable tumor progression and ...drug resistance. Uncovering novel treatment strategies to inhibit tumor development is important. Ferroptosis, a form of cell death associated with iron and lipid peroxidation, has drawn extensive attention. In this paper, we reviewed the underlying mechanisms of ferroptosis (i.e., iron, glutathione, and lipid metabolism) and its role in various tumors (i.e., lung cancer, liver carcinoma, breast cancer, and pancreatic cancer). Moreover, we summarized ferroptosis-related anti-tumor drugs and emphasized the potential of combined treatment of anti-tumor drugs and radiotherapy in an effort to provide novel anti-tumor treatments.
This study proposes a hybrid approach for accurately predicting water demand by integrating socio-economic variables, such as population and GDP (per capita), with climatic variables, including ...temperature and precipitation. The prediction model utilizes an Extreme Learning Machine (ELM), effectively capturing the dynamic relationships between the input variables and water demand. The Improved Ant Nesting Algorithm is employed to fine-tune the weights and biases to optimize the network's performance. To evaluate the predictive accuracy of the model, a comprehensive dataset consisting of socio-economic and climatic factors is utilized for training and testing purposes. Performance metrics, namely Root Mean Square Error (RMSE) and Correlation Coefficients (R2), are employed as evaluation criteria. The results demonstrate that the hybrid approach achieves accurate water supply predictions, showcasing its potential to contribute significantly to effective water resource management and decision-making processes. Based on the results, IANA-ELM is considered the best model due to its high R2 values. Specifically, in the training data, the R2 values are 0.693 for population, 0.624 for GDP per capita, 0.607 for temperature, and 0.708 for rainfall. Similarly, in the test data, the R2 values are 0.672 for population, 0.608 for GDP per capita, 0.592 for temperature, and 0.708 for rainfall. This integrated approach provides a robust tool for policymakers, water utility companies, and researchers in the field of water managements, enabling them to make informed decisions based on accurate predictions of water demand.
Acute central nervous system (CNS) injuries, such as stroke, traumatic brain injury (TBI), and spinal cord injury (SCI) present a grave health care challenge worldwide due to high morbidity and ...mortality, as well as limited clinical therapeutic strategies. Established literature has shown that oxidative stress (OS), inflammation, excitotoxicity, and apoptosis play important roles in the pathophysiological processes of acute CNS injuries. Recently, there have been many studies on the topic of ferroptosis, a form of regulated cell death characterized by the accumulation of iron-dependent lipid peroxidation. Some studies have revealed an emerging connection between acute CNS injuries and ferroptosis. Ferroptosis, induced by the abnormal metabolism of lipids, glutathione (GSH), and iron, can accelerate acute CNS injuries. However, pharmaceutical agents, such as iron chelators, ferrostatin-1 (Fer-1), and liproxstatin-1 (Lip-1), can inhibit ferroptosis and may have neuroprotective effects after acute CNS injuries. However, the specific mechanisms underlying this connection has not yet been clearly elucidated. In this paper, we discuss the general mechanisms of ferroptosis and its role in stroke, TBI, and SCI. We also summarize ferroptosis-related drugs and highlight the potential therapeutic strategies in treating various acute CNS injuries. Additionally, this paper suggests a testable hypothesis that ferroptosis may be a novel direction for further research of acute CNS injuries by providing corresponding evidence.
Aging is associated with multiple degenerative diseases, including atherosclerosis, osteoporosis, and Alzheimer's disease. As the most intuitive manifestation of aging, skin aging has received the ...most significant attention. Skin aging results from various intrinsic and extrinsic factors. Aged skin is characterized by wrinkles, laxity, elastosis, telangiectasia, and aberrant pigmentation. The underlying mechanism is complex and may involve cellular senescence, DNA damage, oxidative stress (OS), inflammation, and genetic mutations, among other factors. Among them, OS plays an important role in skin aging, and multiple antioxidants (e.g., vitamin C, glutathione, and melatonin) are considered to promote skin rejuvenation. In addition, stem cells that exhibit self-replication, multi-directional differentiation, and a strong paracrine function can exert anti-aging effects by inhibiting OS. With the further development of stem cell technology, treatments related to OS mitigation and involving stem cell use may have a promising future in anti-skin aging therapy.
Meningioma is the most common intracranial tumor, and recent studies have drawn attention to the importance of further research on malignant meningioma. According to the World Health Organization ...(WHO) grading, meningioma is classified into 15 subtypes with three grades of malignancy. However, due to a lack of descriptions of molecular subtypes, genetic mutations, or other features, there were deficiencies in the WHO classification. The DNA methylation-based meningioma classification published in 2017 used DNA copy number analysis, mutation profiling, and RNA sequencing to distinguish six clinically relevant methylation classes, which contributed to a better prediction of tumor recurrence and prognosis. Further studies indicated that gene variation and gene mutations, such as those in neurofibromin 2
(NF2)
and
BRCA1
, were related to the high WHO grade, malignant invasion, and recurrence. Among the mutant genes described above, some have been associated with differential DNA methylation. Herein, we searched for articles published in PubMed and Web of Science from January 2000 to May 2020 by entering the keywords “meningioma,” “methylation,” and “gene mutation,” and found a number of published studies that analyzed DNA methylation in meningiomas. In this review, we summarize the key findings of recent studies on methylation status and genetic mutations of meningioma and discuss the current deficits of the WHO grading. We also propose that a methylation-based meningioma classification could provide clues in the assessment of individual risk of meningioma recurrence, which is associated with clinical benefits for patients.
Medical education is a demanding lifelong learning process, which includes three tightly connected stages: college education, post-graduate education, and continuous education. Residency, the first ...several years after a college education, is a pivotal time in the development of a qualified doctor. Additionally, residents are the main force that undertakes much of the clinical work in hospitals. Therefore, guaranteeing and improving residents' clinical skills and abilities through the standardized training of resident physicians (STRP) is important. However, compared with other hospitals in the Zhejiang Province, the STRP assessment results of residents in our hospital were not satisfactory in recent years. Therefore, the objective of this study was to find the problems causing the unsatisfactory performance and identify the role of the "Plan-Do-Check-Action" (PDCA) plan in providing a valuable framework for future training.
Relevant studies of STRP in China and abroad were investigated by the literature review. According to published data by the Health Commision of Zhejiang Province, we collected the STRP assessment rsults of a total number of 12,036 residents. The inclusion cretria of these residents include: (1) 3rd-year residents. (2) taking STRP in the Zhejiang Province during 2016-2018 or 2017-2019. (3) the first time taking the clinical practice ability examination (CPAE) in 2018 or 2019. The results of 634 3rd-year residents from The Second Affiliated Hospital of Zhejiang University (SAHZU) were provided by the Department of Medical Education and were analyzed in depth. Three hundred and eight residents from SAHZU received normal training and took the CPAE in 2018, whereas 326 residets received PDCA and took the CPAE in 2019. PDCA is a program designed to improve the performance of residency in SAHZU. It includes the formulation and implementation of specific training plans, the check of effects, and continuous improvements. There was no change in the STRP assessment in these 2 years and the indicator of performance in the STRP assessment was the first pass rate (FPR). Statistical analyses were performed using Pearson's
test, Yates-corrected
test, or Fisher's exact test (SPSS Statistics, version 25). A
-value of < 0.05 was considered significant.
A total number of 6,180 and 5,856 examinees in the Zhejiang Province took the clinical practice ability examination in 2018 and 2019, respectively. In 2018, a total of 308 residents from 20 departments of the SAHZU took the STRP assessment. In 2019, a total of 326 residents from 22 departments of the SAHZU underwent the PDCA plan and took the STRP assessment. Compared with the results in 2018, the average FPR in the Zhejiang Province increased by 2.92% from 87.87 to 90.79% (
< 0.001). The FPR of the SAHZU increased by 7.88% from 85.06 to 92.94% (
= 0.001). In the SAHZU, the FPRs of the Department of Emergency and Department of Anesthesiology improved 34.51% (
= 0.024) and 20.36% (
= 0.004), respectively. There were no significant differences between the performances in the 2 years of the other 20 departments. There were improved results in the "Clinical Thinking and Decision-Making" and "Operation of Basic Skills" assessment stations with increases of 3.01% (
= 0.002) and 3.94% (
= 0.002), respectively. No statistically significant differences in the FPRs of the other six stations were found. The performances in all the stations in the final tests were better than in the stimulation tests (
< 0.001).
Although our sample size was relatively small, our results showed a small success of the PDCA plan in improving the quality of the STRP, especially for the residents in the Departments of Emergency and Anesthesiology. The PDCA plan also contributed to enhancing residents' abilities in the "Clinical Thinking and Decision-Making" and "Operation of Basic Skills" stations. Taken together, the PDCA plan may provide a practical framework for developing future training plans.
Regeneration of a part of the diseased liver after surgical resection is mainly achieved by the proliferation of the remaining healthy liver cells. However, in case of extreme loss of liver cells or ...in the final stages of chronic liver disease, most liver cells are depleted or lose their ability to proliferate. Therefore, to foster liver regeneration, it is of great clinical and scientific significance to improve the survival and proliferation ability of residual hepatocytes. In this study, we conducted experiments on a zebrafish model of targeted ablation of liver cells to clarify the role of fibroblast growth factor 21 (FGF21). We found that FGF21 increased the regeneration area of the damaged liver and improved the survival rate of damaged liver cells by inhibiting cell apoptosis and reducing oxidative stress. Our results also showed that administration of FGF21 upregulated autophagy, and the beneficial effects of FGF21 were reversed by the well-known autophagy inhibitor chloroquine (CQ), indicating that FGF21-activated autophagy played a central role in the treatment. We further showed that the enhancement of autophagy induced by FGF21 was due to the activation of the AMPK-mTOR signaling pathway. Taken together, these data provide new evidence that FGF21 is an effective autophagy regulator that can significantly improve the survival of damaged livers.
Billions of cells undergo turnover and die via apoptosis throughout our lifetime. A prompt clearance of these apoptotic cells and debris by phagocytic cells, a process known as efferocytosis, is ...important in maintaining tissue homeostasis. Accordingly, impaired efferocytosis due to the defective clearance and disrupted stages can lead to a growing number of inflammation- and immune-related diseases. Although numerous studies have shown the mechanisms of efferocytosis, its role in disorders, such as non-tumor and tumor diseases, remains poorly understood. This review summarizes the processes and signal molecules in efferocytosis, and efferocytosis-related functions in non-tumor (e.g., atherosclerosis, lung diseases) and tumor diseases (e.g., breast cancer, prostate cancer), as well as describes the role of involved cytokines. Of note, there is a dual role of efferocytosis in the abovementioned disorders, and a paradoxical effect among non-tumor and tumor diseases in terms of inflammation resolution, immune response, and disease progression. Briefly, intact efferocytosis and cytokines promote tissue repair, while they contribute to tumor progression via the tumor microenvironment and macrophage politzerization. Additionally, this review provides potential targets associated with TAM (TYRO3, AXL, MERTK) receptors and cytokines, such as tumor necrosis factor α and CXCL5, suggesting potential novel therapeutic ways in treating diseases.
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A clearance of apoptotic cells by phagocytic cells, a process known as efferocytosis, is important in maintaining tissue homeostasis. Impaired efferocytosis due to defective clearance leads to inflammation- and immune-related diseases. This review summarizes the processes and signal molecules in efferocytosis, and efferocytosis-related functions in non-tumor and tumor diseases, as well as describes the role of involved cytokines.
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