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er, colorectal cancer, prostate cancer, liver cancer, and stomach cancer were the most common cancers in Zhejiang Province. Effective prevention and control measures should be established after considering the different characteristics of cancers in urban and rural areas.

Long non-coding RNA (lncRNA) actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) functions as a competing endogenous RNA to regulate target genes expression by sponging microRNAs (miRs) to play cancer-promoting roles in cancer stem cells. However, the regulatory mechanism of AFAP1-AS1 in cervical cancer (CC) stem cells is unknown. The present study aimed to provide a new therapeutic target for the clinical treatment of CC.

Hyaluronic acid receptor cluster of differentiation 44 variant exon 6 (CD44v6)(+) CC cells were isolated by flow cytometry (FCM). Small interfering RNAs of AFAP1-AS1 (siAFAP1-AS1) were transfected into the (CD44v6)(+) cells. The levels of AFAP1-AS1 were measured by quantitative real-time PCR (qRT-PCR). Sphere formation assay, cell cycle analysis, and Western blotting were used to detect the effect of siAFAP1-AS1. RNA Pull-down and Luciferase reporter assay were used to verify the relationship between miR-27b-3p and AFAP1-AS1 or vascular endothelial growth factor (VEGF)-C.

CD44v6(+) CC cells had remarkable stemness and a high level of AFAP1-AS1. However, AFAP1-AS1 knockdown with siAFAP1-AS1 suppressed the cell cycle transition of G(1)/S phase and inhibited self-renewal of CD44v6(+) CC cells, the levels of the stemness markers octamer-binding transcription factor 4 (OCT4), osteopontin (OPN), and cluster of differentiation 133 (CD133), and the epithelial-mesenchymal transition (EMT)-related proteins Twist1, matrix metalloprotease (MMP)-9, and VEGF-C. In the mechanism study, miR-27b-3p/VEGF-C signaling was demonstrated to be a key downstream of AFAP1-AS1 in the CD44v6(+) CC cells.

LncRNA AFAP1-AS1 knockdown inhibits the CC cell stemness by upregulating miR-27b-3p to suppress VEGF-C.

LncRNA AFAP1-AS1 knockdown inhibits the CC cell stemness by upregulating miR-27b-3p to suppress VEGF-C.

Macrophage accumulation within atherosclerotic plaque is a primary driver of disease progression. However, recent advances in both phenotypic and functional heterogeneity of these cells have allowed for improved insight into potential regulation of macrophage function within lesions. In this review, we will discuss recent insights on macrophage heterogeneity, lipid processing, metabolism, and proliferation in atherosclerosis. Furthermore, we will identify outstanding questions in the field that are pertinent to future studies.

With the recent development of single-cell RNA sequencing, several studies have highlighted the diverse macrophage populations within plaques, including pro-inflammatory, anti-inflammatory, lipid loaded and tissue resident macrophages. Furthermore, new data has suggested that differential activation of metabolic pathways, including glycolysis and fatty acid oxidation, may play a key role in determining function. Recent works have highlighted that different populations retain varying capacity to undergo proliferation; regulating the proliferation pathway may be highly effective in reducing plaque in advanced lesions.

Macrophage populations within atherosclerosis are highly heterogeneous; differences in cytokine production, lipid handling, metabolism, and proliferation are seen between subpopulations. Understanding the basic cellular mechanisms that drive this heterogeneity will allow for the development of highly specific disease modulating agents to combat atherosclerosis.

Macrophage populations within atherosclerosis are highly heterogeneous; differences in cytokine production, lipid handling, metabolism, and proliferation are seen between subpopulations. Understanding the basic cellular mechanisms that drive this heterogeneity will allow for the development of highly specific disease modulating agents to combat atherosclerosis.

Although the so-called cytokine storm has been early described and related to a dramatic evolution in severe COVID-19 patients, it soon became clear that those patients display clinical and biological evidence of an immunosuppressive state characterized, among other, by a profound lymphopenia. The negative role of this immune suppression on the outcome raises the question on immune therapies that might improve patient's condition.

Important positive effects of active immune therapies, such as IL-7 or thymosin-α are already described and warrant confirmation in larger prospective trials. For other therapies, such as interferons, firm conclusions for critically ill COVID-19 patients are lacking as those patients were often excluded from the published trials. A-1331852 Treatment with immunoglobulins or convalescent plasma is a passive strategy to provide specific immunity. Unfortunately, results from large RCTs do not support their use presently.

In this article, we provide a review on active and passive immune boosting strategies that might help treating the most severe COVID-19 patients. We mainly focus on active strategies that include IL-7, thymosin-α, interferons, and vitamin D. Although some positive effects are described, they certainly warrant confirmation in large randomized controlled trials.

In this article, we provide a review on active and passive immune boosting strategies that might help treating the most severe COVID-19 patients. We mainly focus on active strategies that include IL-7, thymosin-α, interferons, and vitamin D. Although some positive effects are described, they certainly warrant confirmation in large randomized controlled trials.

Randomized clinical trials (RCTs) have come to be accepted as the gold standard for assessing the efficacy and effectiveness of therapeutics and interventions in medicine. In this paper, we aim to describe some evolving concepts associated with the design and conduct of RCTs and outline new approaches aiming to increase efficiency and reduce costs.

A well-powered and performed RCT is usually a study involving several different centers from different geographical areas that enrolls a large number of patients in diverse clinical settings. Altogether, these features increase the generalizability of the study and make the rapid implementation of the findings more likely. However, this does not come without cost. Among several possible alternatives to conventional RCTs, the most important ones are related to the unit of randomization (individual vs. cluster), study design (conventional vs. adaptive), randomization scheme (fixed vs. response-adaptive), data collection (conventional case report forms vs. registry-embedded) and statistical approach (frequentist vs. Bayesian).

While conventional RCTs remain the gold standard for generating evidence, new trial designs may be considered to reduce sample size and costs while improving trial efficiency and power. However, they raise new challenges for testing feasibility, conduct, ethical oversight and statistical analysis.

While conventional RCTs remain the gold standard for generating evidence, new trial designs may be considered to reduce sample size and costs while improving trial efficiency and power. However, they raise new challenges for testing feasibility, conduct, ethical oversight and statistical analysis.

Hoarding disorder was recently recognized as an independent diagnosis; it is characterized by the accumulation of objects causing a functional impairment and is commonly associated with increased risk of injury or death. Limited data exist about deaths of persons found in hoarding environments. This study investigated the characteristics and circumstances surrounding deaths found in "hoarding" environments. Using the electronic record management system, a search for the term "hoard" from 2017 to 2018 identified 138 cases. The mean age was 67 years, 56% were male, 76% were White, and 86% of decedents lived alone. Decomposition was noted in 61% of cases. A full autopsy was performed in 36 cases (26%); natural was the most common manner of death (80%), followed by accident (14%). Cases in which hoarding was thought to be contributory to the cause of death occurred in 5 cases. A qualitative hoard evaluation was done on 29 cases (21%) with available photographs. A hoarding level was assigned using the Clutter Hollowed by accident (14%). Cases in which hoarding was thought to be contributory to the cause of death occurred in 5 cases. A qualitative hoard evaluation was done on 29 cases (21%) with available photographs. A hoarding level was assigned using the Clutter Hoarding Scale with an average of 3.39/5. Overall, the analysis showed deaths in pathological hoarding environments appeared to impact all socioeconomic groups and was associated with increased risk of accidental death and being found in a state of decomposition.

It is well known that elder neglect entails a number of physical and psychological consequences, as well as being an independent risk factor for death. In the present study, we describe 5 forensic cases of death of older adults where the diagnosis of neglect only emerged postmortem through the combination of the scene investigation, the often-scarce circumstantial data, and the autopsy findings. The gathering of this information allowed the presence of risk factors-not previously assessed or reported-to be identified. Nevertheless, complete medical information was lacking both for the isolation of the victims with their caregivers and for the absence of every social and health support in self-neglect. More research is needed also in the forensic pathology field with standardized methods to contribute to prevention strategies and to avoid that victims of elder neglect remain hidden also after death.

It is well known that elder neglect entails a number of physical and psychological consequences, as well as being an independent risk factor for death. In the present study, we describe 5 forensic cases of death of older adults where the diagnosis of neglect only emerged postmortem through the combination of the scene investigation, the often-scarce circumstantial data, and the autopsy findings. The gathering of this information allowed the presence of risk factors-not previously assessed or reported-to be identified. Nevertheless, complete medical information was lacking both for the isolation of the victims with their caregivers and for the absence of every social and health support in self-neglect. More research is needed also in the forensic pathology field with standardized methods to contribute to prevention strategies and to avoid that victims of elder neglect remain hidden also after death.

Fatal paraquat ingestion presents many interesting pathological findings for the forensic pathologist. The majority of prior research regarding paraquat poisoning has focused on the lung and liver, this article is further directed to and presents some of the histopathological findings present in the brain. Typical macroscopic and histopathological findings of paraquat poisoning were identified in the liver and lungs. The brain was found to be edematous with widening of the centrum semiovale, whereas histologically, it was found that there was extravasation of erythrocytes into the surrounding Virchow-Robin spaces, a finding normally associated with blunt force head injury and, therefore, commonly interpreted by forensic pathologists as a cortical contusion hemorrhage.

Fatal paraquat ingestion presents many interesting pathological findings for the forensic pathologist. The majority of prior research regarding paraquat poisoning has focused on the lung and liver, this article is further directed to and presents some of the histopathological findings present in the brain.