Cellular senescence is a kind of cellular state triggered by endogenous or exogenous stimuli, which is mainly characterized by stable cell cycle arrest and complex senescence-associated secretory phenotype (SASP). Once senescent cells accumulate in tissues, they may eventually accelerate the progression of age-related diseases, such as atherosclerosis, osteoarthritis, chronic lung diseases, cancers, etc. Recent studies have shown that the disorders of lipid metabolism are not only related to age-related diseases, but also regulate the cellular senescence process. Based on existing research evidences, the changes in lipid metabolism in senescent cells are mainly concentrated in the metabolic processes of phospholipids, fatty acids and cholesterol. Obviously, the changes in lipid-metabolizing enzymes and proteins involved in these pathways play a critical role in senescence. However, the link between cellular senescence, changes in lipid metabolism and age-related disease remains to be elucidated. Herein, we summarize the lipid metabolism changes in senescent cells, especially the senescent cells that promote age-related diseases, as well as focusing on the role of lipid-related enzymes or proteins in senescence. Finally, we explore the prospect of lipids in cellular senescence and their potential as drug targets for preventing and delaying age-related diseases.

暂无摘要。

BACKGROUND: Volumetric Modulated Arc Therapy (VMAT) has recently become a pivotal treatment of oncological diseases due to the high-precise delineation of target volume contours with sparing organs at risk. This procedure requires a high level of experience and precision and is achievable only with advanced diagnostic support. Magnetic Resonance (MRI) and multimodality imaging, such as 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), are fundamental in implementing radiotherapy guidance.
METHODS: A 54-year-old patient underwent surgery twice to remove primitive and recurrent cardiac sarcomas of the left atrium. The appearance of a further relapse required radiotherapy as the only possible treatment. Cardiac MRI was then performed to define the degree of atrial mass invasiveness, and 18F-FDG PET/CT was performed to assess the activity and staging of the cardiac lesion. It revealed high 18F-FDG uptake not only in the left atrium lesion but also in a pancreatic lesion with elevated 18F-FDG uptake (SUV max 5.5). The pancreatic biopsy performed a few days later confirmed the myxoid sarcoma metastasis, and surgeons defined it as not operable due to the patient\'s clinical condition. Radiotherapy was then urgently performed with the VMAT technique. After 40 days, a cardiac MRI showed a reduction in the cardiac mass with improvement in the respiratory and cardiac symptoms; then, the patient started chemotherapy. One year after diagnosis, the patient is still alive and is receiving chemotherapy with gemcitabine and docetaxel with good compliance.
CONCLUSIONS: The correct and timely management of a patient suffering from a rare oncological disease has allowed a better and longer survival, especially due to VMAT, a sophisticated procedure that requires high expertise. This case also demonstrates that cardiac MRI and whole-body imaging procedures, such as 18FDG PET/CT, can be useful in staging patients with oncological diseases.

Inflammatory disease (ID) is a general term that covers all diseases in which chronic inflammation performs as the major manifestation of pathogenesis. Traditional therapies based on the anti-inflammatory and immunosuppressive drugs are palliative with the short-term remission. The emergence of nanodrugs has been reported to solve the potential causes and prevent recurrences, thus holding great potential for the treatment of IDs. Among various nanomaterial systems, transition metal-based smart nanosystems (TMSNs) with unique electronic structures possess therapeutic advantages owing to their large surface area to volume ratio, high photothermal conversion efficiency, X-ray absorption capacity, and multiple catalytic enzyme activities. In this review, the rationale, design principle, and therapeutic mechanisms of TMSNs for treatments of various IDs are summarized. Specifically, TMSNs can not only be designed to scavenge danger signals, such as reactive oxygen and nitrogen species and cell-free DNA, but also can be engineered to block the mechanism of initiating inflammatory responses. In addition, TMSNs can be further applied as nanocarriers to deliver anti-inflammatory drugs. Finally, the opportunities and challenges of TMSNs are discussed, and the future directions of TMSN-based ID treatment for clinical applications are emphasized.

Limb girdle muscular dystrophy type R1 disease is a progressive disease that is caused by mutations in the CAPN3 gene and involves the extremity muscles of the hip and shoulder girdle. The CAPN3 protein has proteolytic and non-proteolytic properties. The functions of the CAPN3 protein that have been determined so far can be listed as remodeling and combining contractile proteins in the sarcomere with the substrates with which it interacts, controlling the Ca2+ flow in and out through the sarcoplasmic reticulum, and regulation of membrane repair and muscle regeneration. Even though there are several gene therapies, cellular therapies, and drug therapies, such as glucocorticoid treatment, AAV- mediated therapy, CRISPR-Cas9, induced pluripotent stem cells, MYO-029, and AMBMP, which are either in preclinical or clinical phases, or have been completed, there is no final cure. Inhibitors and small molecules (tauroursodeoxycholic acid, salubrinal, rapamycin, CDN1163, dwarf open reading frame) targeting ER stress factors that are thought to be effective in muscle loss can be considered potential therapy strategies. At present, little can be done to treat the progressive muscle wasting, loss of function, and premature mortality of patients with LGMDR1, and there is a pressing need for more research to develop potential therapies.

UNASSIGNED: The neutrophil-to-lymphocyte ratio (NLR) is a useful marker of inflammation. However, the prognostic function of the NLR in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) blood stream infection (BSI) remains largely unknown. The aim of this study was to explore the potential relationship between the NLR and mortality in these patients.
UNASSIGNED: We performed a retrospective cohort study based on data retrieved from the computerized patient record system in a tertiary hospital from 1 January 2017 to 31 October, 2020. A total of 134 inpatients with CRKP BSI were enrolled in this study, including 54 fatal cases and 80 survival cases, 28 days after the onset of CRKP BSI. A logistic analysis was performed to assess the association between the NLR on the 4th day and 28-day mortality. Multivariate analyses were used to control for the confounders.
UNASSIGNED: The overall 28-day mortality rate of patients with a CRKP BSI episode was 40.3% (54/134). We conducted a multivariate analysis of the data of 134 patients and found that the NLR on the 4th day [odds ratio (OR) 1.148, 95% confidence interval (CI) 1.076-1.225, p < 0.001] and antibiotic exposure before BSI onset (OR 3.847, 95% CI 1.322-11.196, p = 0.013) were independent risk factors for 28-day mortality of patients with CRKP BSI, while appropriate initial therapy (AIT, OR 0.073, 95% CI 0.017-0.307, p < 0.001) was an independent protective factor. Among patients treated with AITs, the Cox proportional hazards regression analysis revealed a significant difference in prognosis (p = 0.006) between the ceftazidime/avibactam contained (CAZ) group and non CAZ-AVI groups. After dividing the non CAZ-AVI group into the tigecycline (TGC), colistin (COL), and TGC + COL groups, there were no differences between the CAZ-AVI group and the TGC group (p = 0.093), but CAZ-AVI group showed lower 28-day mortality than COL (p = 0.002) and TGC + COL (p = 0.002) groups. Meanwhile, there was no difference in NLR on the 1st day (p = 0.958) of patients in different groups but significant difference in NLR on the 4th day (p = 0.047).
UNASSIGNED: The NLR on the 4th day is a readily available and independent prognostic biomarker for patients with CRKP BSI. This marker may have the potential for use in evaluating the efficacy of different anti-infection therapy strategies at an early stage.

Breast cancer (BC), the second leading cause of cancer-related deaths after lung cancer, is the most common cancer type among women worldwide. BC comprises multiple subtypes based on molecular properties. Depending on the type of BC, hormone therapy, targeted therapy, and immunotherapy are the current systemic treatment options along with conventional chemotherapy. Several new molecular targets, miRNAs, and long non-coding RNAs (lncRNAs), have been discovered over the past few decades and are powerful potential therapeutic targets. Here, we review advanced therapeutics as new players in BC management.

The invertebrate model, Galleria mellonella, has been widely used to study host-pathogen interactions due to its cheapness, ease of handling, and similar mammalian innate immune system. G. mellonella larvae have been proven to be useful and a reliable model for analyzing pathogenesis mechanisms of multidrug resistant Acinetobacter baumannii, an opportunistic pathogen difficult to kill. This review describes the detailed experimental design of G. mellonella/A. baumannii models, and provides a comprehensive comparison of various virulence factors and therapy strategies using the G. mellonella host. These investigations highlight the importance of this host-pathogen model for in vivo pathogen virulence studies. On the long term, further development of the G. mellonella/A. baumannii model will offer promising insights for clinical treatments of A. baumannii infection.

UNASSIGNED: To explore engagement principles and contextual conditions in high-engagement therapy sessions involving youth with disabilities and service providers.
UNASSIGNED: From a larger project on therapy engagement, a dyadic case analysis was conducted involving three youth ages 8-15 with disabilities and their service providers. Participants were interviewed about their engagement experiences after high-engagement sessions focusing on speech articulation, transition goals, and physical mobility. Data were analyzed thematically, with an emphasis on engagement principles illustrated by the cases.
UNASSIGNED: There were four service provider engagement principles: (a) clients differ in what engages them and in how they display engagement (Individual Variation Principle), (b) there are multiple ways to engage clients (Personalizing Principle), (c) engagement is cultivated through relationship (Relationship Principle), and (d) it is important to monitor and be attuned to the client\'s level of engagement over a session (Monitoring Principle). Service providers\' use of engagement strategies varied due to contextual conditions, including therapy type and youths\' interests and preferences.
UNASSIGNED: The findings indicate the value of providers\' awareness of the dynamics of engagement, their use of personalized strategies to engage clients, and the fundamental importance of cultivating a good relationship and monitoring client engagement during therapy.IMPLICATIONS FOR REHABILITATIONService providers may benefit from being aware of common principles underlying the co-construction of engagement between service providers and clients.Service providers can use a variety of personalized strategies to heighten client engagement, and can work to cultivate a positive relationship.It is important to monitor clients\' non-verbal and verbal signs of engagement and respond to signs of disengagement during therapy.Contextual conditions affecting service providers\' use of engagement strategies include the nature of the therapy being provided and youths\' interests and preferences.

The stumbling-block in voice therapy is the patient\'s generalization of the new voice behavior in everyday life. Traditionally voice therapy is based on demonstration, i.e. during the therapy session the speech therapist uses her own voice and body to demonstrate for the patient how to produce voice in different training tasks. During the last decade a new voice therapy strategy, the Verbal Instruction Model (VIM), has been developed by the author. In VIM the speech therapist uses verbal instructions instead of demonstration when conveying the training tasks to the patient. Our clinical experience has shown that VIM seems to help getting over the stumbling-block of generalization. However, evidence for VIM voice therapy outcome remains to be scientifically studied and confirmed. The purpose of this paper is to describe VIM voice therapy and to discuss therapy strategies in the light of motor learning principles.