The p53 family remains a captivating focus of an extensive number of current studies. Accumulating evidence indicates that p53 abnormalities rank among the most prevalent in cancer. Given the numerous existing studies, which mostly focus on the mutations, expression profiles, and functional perturbations exhibited by members of the p53 family across diverse malignancies, this review will concentrate more on less explored facets regarding p53 activation and stabilization by the nuclear pore complex (NPC) in cancer, drawing on several studies. p53 integrates a broad spectrum of signals and is subject to diverse regulatory mechanisms to enact the necessary cellular response. It is widely acknowledged that each stage of p53 regulation, from synthesis to degradation, significantly influences its functionality in executing specific tasks. Over recent decades, a large body of data has established that mechanisms of regulation, closely linked with protein activation and stabilization, involve intricate interactions with various cellular components. These often transcend canonical regulatory pathways. This new knowledge has expanded from the regulation of genes themselves to epigenomics and proteomics, whereby interaction partners increase in number and complexity compared with earlier paradigms. Specifically, studies have recently shown the involvement of the NPC protein in such complex interactions, underscoring the further complexity of p53 regulation. Furthermore, we also discuss therapeutic strategies based on recent developments in this field in combination with established targeted therapies.

UNASSIGNED: To compare conventional transarterial chemoembolization (cTACE) and drug-eluting bead TACE (DEB-TACE) in terms of efficacy, survival, and adverse effects in patients with hepatocellular carcinoma who are not candidates for curative therapy.
UNASSIGNED: This was a retrospective study of patients with hepatocellular carcinoma who underwent cTACE or DEB-TACE for palliative treatment between January 2009 and December 2021. The Kaplan-Meier method was used for survival analysis. Values of p < 0.05 were considered statistically significant.
UNASSIGNED: We evaluated 268 patients, of whom 70 underwent DEB-TACE and 198 underwent cTACE. There was no significant difference between the groups regarding sex, age, or etiology of cirrhosis. The proportion of patients achieving a complete response on imaging examinations was higher in the cTACE group (31.8% vs. 16.1%), whereas that of patients achieving a partial response was higher in the DEB-TACE group (33.9% vs.19.7%), and the differences were significant (p = 0.014). The mortality rate was similar between the groups. The survival rate in the DEB-TACE and cTACE groups, respectively, was 87.0% and 87.9% at one year, 35.1% and 32.9% at three years, and 20.5% and 18.1% at five years (p = 0.661). There was no significant difference between the DEB-TACE and cTACE groups in terms of the frequency of adverse events (7.1% vs. 17.8%; p = 0.052). The most common complication in both groups was post-embolization syndrome.
UNASSIGNED: Although a complete response was more common among the patients who underwent cTACE, there was no difference in survival between the groups and the frequency of adverse events was similar.
UNASSIGNED: Comparar a eficácia, sobrevida e efeitos adversos entre cTACE e DEB-TACE em pacientes com carcinoma hepatocelular não candidatos a terapia curativa.
UNASSIGNED: Estudo retrospectivo de pacientes com carcinoma hepatocelular submetidos a cTACE ou DEB-TACE para tratamento paliativo entre janeiro de 2009 e dezembro de 2021. Foi utilizado o método Kaplan-Meier para análise de sobrevida. Valor de p < 0,05 foi considerado estatisticamente significante.
UNASSIGNED: Foram avaliados 268 pacientes, dos quais 70 foram submetidos a DEB-TACE e 198 foram submetidos a cTACE. Não houve diferença em relação ao sexo, idade e etiologia da cirrose. O grupo cTACE apresentou maior porcentual de resposta completa em exames de imagem (31,8% vs. 16,1%) e o grupo DEB-TACE apresentou maior porcentual de resposta parcial (33,9% vs.19,7%), com valor de p = 0,014. A mortalidade foi semelhante. As taxas de sobrevivência para os grupos DEB-TACE e cTACE foram 87,0% e 87,9% em um ano, 35,1% e 32,9% em três anos e 20,5% e 18,1% em cinco anos, respectivamente (p = 0,661). Em relação à frequência de eventos adversos, não houve diferença significativa entre os grupos (7,1% na DEB-TACE vs. 17,8% na cTACE; p = 0,052). A complicação mais comum, em ambos os grupos, foi a síndrome pós-embolização.
UNASSIGNED: Embora tenha sido observada maior frequência de resposta completa em pacientes submetidos a cTACE, não houve diferença na sobrevida dos pacientes entre os grupos. A taxa de eventos adversos também foi semelhante.

BACKGROUND: Endovascular embolization procedures are typically the primary treatment modality for arteriovenous fistula (AVF). The objective of this subset analysis was to evaluate the prospective long-term clinical outcomes of AVF patients treated with the SMART COIL System.
METHODS: Patients who had arteriovenous fistulas (AVF) and underwent endovascular coiling using the Penumbra SMART COIL system were part of a subset analysis within the SMART registry. The SMART registry is a post-market registry that is prospective, multicenter, and single-arm in design. After the treatment, these patients were monitored for a period of 12 ± 6 months.
RESULTS: A total of 41 patients were included. No patients (0/41) had a procedural device-related serious adverse event (SAE). Re-access involving a guidewire due to catheter kickout was unnecessary for 85.4% (35/41) of the patients. Complete occlusion after the procedure was achieved in 87.8% (36/41) of patients. The periprocedural SAE rate was 2.4% (1/41), and no periprocedural deaths occurred (0/41). During the follow-up period, there were instances of re-treatment in 3.4% (1/29) of patients. At one year, the lesion occlusion was better or stable in 93.3% (28/30) of patients. The rate of serious adverse events (SAE) from 24 hours to 1 year (±6 months) following the procedure was 26.8% (11/41). The one-year all-cause mortality rate stood at 2.4% (1/ 41), and at the one-year follow-up, 90.9% (20/22) of patients had a modified Rankin Scale score within the range of 0 to 2.
CONCLUSIONS: The coiling procedure for arteriovenous fistulas using the SMART COIL System proved to be safe and effective at the one-year follow-up.

The development of human papillomavirus (HPV) vaccines has made substantive progress, as represented by the approval of five prophylactic vaccines since 2006. Generally, the deployment of prophylactic HPV vaccines is effective in preventing newly acquired infections and incidences of HPV-related malignancies. However, there is still a long way to go regarding the prevention of all HPV infections and the eradication of established HPV infections, as well as the subsequent progression to cancer. Optimizing prophylactic HPV vaccines by incorporating L1 proteins from more HPV subtypes, exploring adjuvants that reinforce cellular immune responses to eradicate HPV-infected cells, and developing therapeutic HPV vaccines used either alone or in combination with other cancer therapeutic modalities might bring about a new era getting closer to the vision to get rid of HPV infection and related diseases. Herein, we summarize strategies for the development of HPV vaccines, both prophylactic and therapeutic, with an emphasis on the selection of antigens and adjuvants, as well as implications for vaccine efficacy based on preclinical studies and clinical trials. Additionally, we outline current cutting-edge insights on formulation strategies, dosing schedules, and age expansion among HPV vaccine recipients, which might play important roles in addressing barriers to vaccine uptake, such as vaccine hesitancy and vaccine availability.

UNASSIGNED: Interleukin-18 (IL-18), a pro-inflammatory cytokine belonging to the IL-1 Family, is a key mediator ofautoinflammatory diseases associated with the development of macrophage activation syndrome (MAS).High levels of IL-18 correlate with MAS and COVID-19 severity and mortality, particularly in COVID-19patients with MAS. As an inflammation inducer, IL-18 binds its receptor IL-1 Receptor 5 (IL-1R5), leadingto the recruitment of the co-receptor, IL-1 Receptor 7 (IL-1R7). This heterotrimeric complex subsequentlyinitiates downstream signaling, resulting in local and systemic inflammation.
UNASSIGNED: We reported earlier the development of a novel humanized monoclonal anti-human IL-1R7 antibody whichspecifically blocks the activity of human IL-18 and its inflammatory signaling in human cell and wholeblood cultures. In the current study, we further explored the strategy of blocking IL-1R7 inhyperinflammation in vivo using animal models.
UNASSIGNED: We first identified an anti-mouse IL-1R7 antibody that significantly suppressed mouse IL-18 andlipopolysaccharide (LPS)-induced IFNg production in mouse splenocyte and peritoneal cell cultures. Whenapplied in vivo, the antibody reduced Propionibacterium acnes and LPS-induced liver injury and protectedmice from tissue and systemic hyperinflammation. Importantly, anti-IL-1R7 significantly inhibited plasma,liver cell and spleen cell IFNg production. Also, anti-IL-1R7 downregulated plasma TNFa, IL-6, IL-1b,MIP-2 production and the production of the liver enzyme ALT. In parallel, anti-IL-1R7 suppressed LPSinducedinflammatory cell infiltration in lungs and inhibited the subsequent IFNg production andinflammation in mice when assessed using an acute lung injury model.
UNASSIGNED: Altogether, our data suggest that blocking IL-1R7 represents a potential therapeutic strategy to specificallymodulate IL-18-mediated hyperinflammation, warranting further investigation of its clinical application intreating IL-18-mediated diseases, including MAS and COVID-19.

暂无摘要。

Objective: This study aims to compare the antiviral treatment similarities and differences in the population covered by the 2024 version of the World Health Organization\'s (WHO) hepatitis B prevention and treatment guidelines and the current Chinese hepatitis B prevention and treatment guidelines, so as to explore their impact on the indications for antiviral therapy in Chinese patients with chronic hepatitis B (CHB). Methods: The information of patients with chronic hepatitis B virus infection who did not receive antiviral treatment was collected through the registration database of the China Clinical Research Platform for Hepatitis B Elimination. Descriptive statistics were conducted on the demographic, blood, biochemical, and virological levels of patients according to the treatment recommendations of the two versions of the guidelines. The Mann-Whitney U test and χ2 test were used to compare the differences and proportional distribution of the treatment populations covered by the two guidelines. The χ2 test was used to analyze the coverage rate of different antiviral treatment indications. Results: A total of 21,134 CHB patients without antiviral treatment were enrolled. 69.4% of patients met the 2024 versions of the WHO guidelines\' recommendations. 85.0% of patients met the current Chinese hepatitis B prevention and treatment guidelines. The WHO guidelines for antiviral therapy indications were met in younger patients with higher levels of ALT, AST, and APRI scores, as well as greater proportion of patients with higher viral loads (P<0.001). The WHO guidelines recommended a cut-off value of APRI>0.5, which raised the proportion of patients on antiviral therapy from 6.6% to 30.9%. 45.7% of patients met the antiviral indications for HBV DNA >2000 IU/ml with abnormal transaminase (ALT>30 U/L for males and ALT>19 U/L for females). The reduced APRI diagnostic cut-off value and ALT treatment threshold had further increased the treatment coverage rate by 91.6% in patients with chronic HBV infection in line with the 2024 versions of WHO guidelines. Conclusion: The reduction of the APRI diagnostic cut-off value and the ALT treatment threshold, based on the current hepatitis B guidelines of China, will further improve the treatment coverage of CHB patients.
目的： 比较世界卫生组织（WHO）2024年版乙型肝炎防治指南与中国现行乙型肝炎防治指南的抗病毒治疗覆盖人群的异同，探讨其对中国慢性乙型肝炎（CHB）患者抗病毒治疗适应证的影响。 方法： 通过中国消除乙型肝炎临床研究平台注册登记数据库，收集未接受抗病毒治疗的慢性乙型肝炎病毒感染患者信息，根据两版指南推荐治疗建议，对患者人口学、血液、生物化学、病毒学水平进行描述性统计，利用Mann-Whitney U检验和χ(2)检验比较两部指南所覆盖治疗人群的差异及其分布比例，并通过χ(2)检验分析不同抗病毒治疗指征的覆盖率。 结果： 共纳入21 134例未经抗病毒治疗的CHB患者，69.4%的患者符合2024年版WHO指南推荐，85.0%的患者符合现有中国乙型肝炎防治指南。符合WHO指南抗病毒治疗指征患者年龄更小，丙氨酸转氨酶(ALT)、天冬氨酸氨基转移酶(AST)、AST和血小板比值(APRI)评分水平、高病毒载量患者比例更高（P < 0.001）。WHO指南推荐APRI > 0.5这一界值将抗病毒治疗从6.6%提高至30.9%；其中45.7%患者符合HBV DNA > 2 000 IU/ml伴转氨酶异常（男性ALT > 30 U/L及女性ALT > 19 U/L）这一抗病毒治疗指征。依据2024年版WHO指南意见，通过下调APRI诊断界值、下调ALT治疗阈值将进一步提高慢性HBV感染患者治疗覆盖率至91.6%。 结论： 基于我国现有乙型肝炎指南，通过降低APRI诊断界值和ALT治疗阈值将进一步提高CHB患者治疗覆盖率。.

UNASSIGNED: References to transformative and therapeutic benefits of digital storytelling are often made, yet this remains an under-explored area, which we foreground in this study.
UNASSIGNED: A phenomenological research design was adopted to explore through interview how a purposive sample of Patient Voices storytellers experienced participation in more than one digital storytelling workshop. Analysis was through thematic coding, linguistic analysis and use of van Manen\'s lifeworld existentials framework.
UNASSIGNED: We find that for this particular group, the therapeutic and transformative experiences that re-centre and re-frame personal meaning do so through inter-personal connections and can be understood as a process of social learning. The lifeworld existentials analysis demonstrates that a pluralist and relational conception of wellbeing holds and there is a close relationship between this and Yalom\'s 11 therapeutic factors.
UNASSIGNED: Drawing on group analytic literature, we suggest the concept of a social learning methodology as useful in grounding further research that seeks to understand the beneficial impacts of digital storytelling methodologies in healthcare and in contributing evidence in this field with fidelity to the lived experience as central.

Medicinal plants are rich sources of pharmaceutically important compounds and have been utilized for the treatment of various diseases since ancient times. Valeriana jatamansi Jones, also known as Indian valerian, holds a special place among temperate Himalayan medicinal plants and is renowned for its therapeutic properties in addressing a variety of ailments. The therapeutic potential of V. jatamansi is attributed to the presence of valuable compounds such as valepotriates, sesquiterpenoids, valeriananoids, jatamanins, lignans, cryptomeridiol, maaliol, xanthorrhizzol, and patchouli alcohol found in its rhizome and roots. This study employed various treatments, including the cultivation of V. jatamansi with the inoculation of Funneliformis mosseae, F. constrictus, and a consortium of arbuscular mycorrhizal fungi (AMF), to investigate their influence on biomass production, chlorophyll content, and the accumulation of bioactive compounds in V. jatamansi. The results revealed significant improvement in these parameters in the inoculated plants. The parameters of plants inoculated with F. mosseae were the highest, followed by those of plants inoculated with F. constrictus and a mixture of AMFs. This study not only underscores the potential of native AMF for promoting the growth of V. jatamansi but also elucidates their role in influencing the synthesis of bioactive compounds. The cultivation of V. jatamansi with native AMF has emerged as a sustainable and eco-friendly approach, providing the dual benefit of enhancing both the medicinal and economic value of this valuable plant. This research contributes valuable insights into the practical application of mycorrhizal associations for the cultivation of medicinal plants, bridging the realms of agriculture and pharmaceuticals.

Urine-derived stem cells (USCs) have gained the attention of researchers in the biomedical field in the past few years . Regarding the several varieties of cells that have been used for this purpose, USCs have demonstrated mesenchymal stem cell-like properties, such as differentiation and immunomodulation. Furthermore, they could be differentiated into several lineages. This is very interesting for regenerative techniques based on cell therapy. This review will embark on describing their separation, and profiling. We will specifically describe the USCs characteristics, in addition to their differentiation potential. Then, we will introduce and explore the primary uses of USCs. These involve thier utilization as a platform to produce stem cells, however, we shall concentrate on the utilization of USCs for therapeutic, and regenerative orofacial applications, providing an in-depth evaluation of this purpose. The final portion will address the limitations and challenges of their implementation in regenerative dentistry.