关键词： Organoids   Primary liver cancers   Induced pluripotent stem cell s (iPSCs)   Patienttissues   Derived liver organoids   In vitro  

摘要： Primary liver cancer (PLC) represents a significant proportion of all human cancers and constitutes a substantial health and economic burden to society. Traditional therapeutic approaches such as surgical resection and chemotherapy often fail due to tumour relapse or innate tumour chemoresistance. There is a dearth of efficient treatments for PLC in part due to the poor capacity of current laboratory models to reflect critical features of the native tumour in vivo. The increasing incorporation of organoid systems has led to a resurgence of interest in liver cancer research. Organoid systems show promise as the gold standard for recapitulating tumours in vitro. Further, developments in culturing techniques will improve the various shortcomings of the current systems. Induced pluripotent stem cell (iPSC)-derived liver organoids are a promising alternative to the conventional liver organoid model as it circumvents the need to rely on primary resections which are often scarce. In this concise review, we will discuss novel techniques for organoid culture with a focus on organoid cocultures and their advantages over traditional organoid systems. A detailed technical protocol for the generation of iPSC-derived liver organoids is provided as an appendix.

关键词： BPSD   complementary and alternative medicine   dementia   integrative medicine   overview  

摘要： Background: Dementia is causing a huge medical and socioeconomic burden. Along with strategies to delay cognitive decline in dementia, behavioral and psychological symptoms of dementia (BPSD) are major contributing factor to the burden of dementia, and have been an important clinical issue for successful management of dementia. However, pharmacological strategies such as antipsychotics raise concerns in terms of risk-to-benefit ratio in managing BPSD. Therefore, there is a need for an effective and safe alternative in BPSD management. From this point of view, various complementary and alternative medicines (CAMs) are attracting attention in BPSD management. Therefore, the overview will make it possible to evaluate the feasibility of using CAM as a potential treatment strategy for BPSD in terms of evidence-based medicine. Methods and analysis: Comprehensive searching will be performed in 13 bibliographic databases from their inception dates to November 2021. Systematic reviews and/or meta-analyses that examined the effectiveness and safety of CAM modalities including herbal medicine, acupuncture, acupressure, aromatherapy, meditation, and relaxation on BPSD, will be included. The methodological quality of included reviews will be assessed by using the A MeaSurement Tool to Assess systematic Reviews-2. Two independent researchers will conduct study search, study selection, data extraction, and quality assessment processes. Results: The results of overview will be disseminated by the publication of a manuscript in a peer-reviewed journal or presentation at a relevant conference. Conclusion: The findings of this overview will help to solve the major public health problem related to dementia, and will provide patients with dementia, their caregivers, clinicians, and health policy makers credible evidence in mitigating the burden of dementia. Ethics and dissemination: As this protocol is for an overview of systematic reviews and meta-analyses, ethical approval is not requ

关键词： Intellectual disability   respite   staff views   family experiences   qualitative research  

摘要： Background: Respite care has traditionally been conceptualised as a short residential break which allows families a break from caring responsibilities. In recent years, alternative respite services have been developed which promote greater social integration and normalisation for people with intellectual and other disabilities. Specific aim: The present study sought to explore the views of service managers and families on the definitions, aims, outcomes and general experiences of these programmes among a sample of adults with intellectual disabilities (ID) using a range of alternative respite services. Method: Participants were managers of respite services for people with ID (n = 6) and family members (predominantly parents, n = 32) of adults receiving respite services from these organisations. All participants were provided with appropriate information on the study and gave consent. Semi-structured interviews were used to explore participants' perspectives on alternative respite provision for adults with ID. Data were analysed using thematic analysis, with multiple analysts involved to allow for reflection on the interpretation of data. Findings: Managers and families showed diversity in the conceptualisations of respite services, with themes highlighting the importance of the break for both people with ID and families, as well as a clear focus on the needs of and developmental outcomes for the person with ID. As such respite was viewed as both a model of service and an outcome for families and individuals with ID. These differing views appeared to have implications for views on who was the target beneficiary of respite. Discussion: The present study reflects alternative respite as a diverse experience for people with ID, their family members and the service providers supporting them. Nevertheless, views were generally positive. Further consideration of the nature of respite services beyond the traditional conceptualisation is warranted.

摘要： Objective. To evaluate the safety and reliability of a novel technique of single-port laparoscopic-assisted percutaneous precise closure of the inguinal hernia sac in children. Methods. From September 2016 through September 2019, children with inguinal hernia(s) treated with single-port laparoscopic-assisted percutaneous extraperitoneal closure using a guide wire were enrolled in this study. Operative time, surgical complications, recurrence rate, and cosmetic results were collected. Results. A total of 917 cases with inguinal hernia(s) were collected. Among them, there were 886 (96.61%) boys and 31 girls. Their mean age was 5.2 +/- 3.7 years. There were 693 (75.57%) cases with unilateral hernia. There were 224 cases with bilateral hernias or patent processus vaginalis, including 135 (14.72%) cases with an open contralateral ring which was confirmed intraoperatively. Twenty-three (2.51%) needed another port to complete the hernia sac separation. The operation time was 24.7 +/- 5.2 min and 14.6 +/- 3.8 min in bilateral and unilateral ones. Three cases complained of numbness in the thigh region or groin pain which subsided without medication in the 2(nd) postoperative month. There was no recurrence, and the incision scars were nearly invisible. Conclusion. Single-port laparoscopic-assisted percutaneous extraperitoneal closure using a guide wire is a safe, less cost, and reliable technique in the treatment of inguinal hernia in children.

摘要： In a recent research paper Dr. Suxing Jin et al. reported two multispecific Pt-IV complexes DNP and NP with non-steroidal anti-inflammatory drug naproxen (NPX) as the axial ligand(s). Herein, we clarify the mechanism of action of DNP, its therapeutic target and intracellular redox-status.

摘要： Totipotency refers to single cells' developmental capacity to form an entire organism. Understanding how totipotent stem cells form has implications for chimera generation. In a recent Cell study, Shen et al. (2021) report that inhibition of spliceosomes resets conventional pluripotent stem cells to a cellular state with totipotency features.

关键词： Nephrotoxicity   Zebrafish   Alternative method   Gene expression   Histopathology  

摘要： Due to an increasing demand for testing of new and existing chemicals and legal restrictions for the use of animals, there is a strong need for alternative approaches to assess systemic toxicity. Embryonic and larval zebrafish (Danio rerio) are increasingly recognized as a promising alternative whole-animal model that may be able to overcome limitations of cell-based in vitro assays and bridge the gap between high-throughput in vitro screening and low-throughput in vivo tests in animals. Despite the relatively simple anatomical structure of the zebrafish larval kidney (pronephros) - composed of only two nephrons - the pronephros shares major functions and cell types with mammalian nephrons. Glomerular filtration begins at 48 h post fertilization. The aim of the present study was to investigate if early zebrafish larvae might be a suitable model for nephrotoxicity testing. On day 3 post fertilization, larval zebrafish were treated with selected nephrotoxins (aristolochic acid, cadmium chloride, potassium bromate, ochratoxin A, gentamicin) for 48 h. Histological evaluation of zebrafish larvae exposed to model nephrotoxins revealed tubule injury as evidenced by dilated tubules with loss of the brush border, tubule cell necrosis and disorganization of the tubular epithelium. These changes were most severe after treatment with gentamicin, which also impaired pronephros function as evidenced by reduced clearance of FITC-dextran. Whole-mount in situ hybridization showing loss of cdh17 expression revealed site-specific injury to the proximal tubule segment. Analysis of genes previously identified as novel biomarkers of kidney injury in mammals showed upregulation of the kidney injury marker genes heme oxygenase 1 (hmox1), clusterin (clu), secreted phosphoprotein/osteopontin (spp1), connective tissue growth factor (ctgf) and kim-1 (havcr-1) in response to nephrotoxin treatment, although the response of individual genes varied across compounds. Consistent with the severity of

关键词： multisystem inflammatory syndrome in children   CytoSorb   cytokine storm   hemoperfusion   children   pediatric intensive care  

摘要： Background: Multisystem inflammatory syndrome in children (MIS-C) has emerged during the COVID-19 pandemic as a new SARS-CoV-2-related entity, potentially responsible for a life-threatening clinical condition associated with myocardial dysfunction and refractory shock. Case: We describe for the first time in a 14-year-old girl with severe MIS-C the potential benefit of an adjuvant therapy based on CytoSorb hemoperfusion and continuous renal replacement therapy with immunomodulatory drugs. Conclusions: We show in our case that, from the start of extracorporeal blood purification, there was a rapid and progressive restoration in cardiac function and hemodynamic parameters in association with a reduction in the most important inflammatory biomarkers (interleukin 6, interleukin 10, C-reactive protein, ferritin, and D-dimers). Additionally, for the first time, we were able to show with analysis of the sublingual microcirculation a delayed improvement in most of the important microcirculation parameters in this clinical case of MIS-C.

关键词： Lattice QCD   Particle correlations & fluctuations   Quantum field theory   Quark-gluon plasma  

摘要： In this Letter, we introduce a novel scheme for extrapolating the equation of state of QCD to finite chemical potential that features considerably improved convergence properties and allows us to extend its reach to unprecedentedly high baryonic chemical potentials. We present continuum extrapolated lattice results for the new expansion coefficients and show the thermodynamic observables up to μB/T≤3.5. This novel expansion does not suffer from the shortcomings that characterize the traditional Taylor expansion method, such as difficulties inherent in performing such an expansion with a limited number of coefficients and the poor signal-to-noise ratio that affects Taylor coefficients determined from lattice calculations.

关键词： multisystem inflammatory syndrome in children   pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2   COVID-19 infection   COVID-19   SARS-CoV-2   Kawasaki-like  

摘要： MIS-C is a novel clinical syndrome in children and adolescents, was first encountered in the spring of 2020 as a post COVID-19 multisystem inflammatory syndrome. The highest number of SARS-CoV-2 infections in Austria were registered in November 2020. In December 2020, eight patients with MIS-C were hospitalized at the pediatric department of Klinik Donaustadt, a large municipal hospital in Vienna. Six of the patients needed pediatric intensive care. As we lack any international consensus on the diagnosis and treatment of this severe complication, we used a multidisciplinary approach. The purpose was to establish an internal standard for maximizing the efficacy and safety of treatment, and standardizing the clinical management of this disease.