Search

摘要： 本文总结了替奈普酶治疗急性缺血性卒中的临床研究结果并展望了替奈普酶更广泛的临床应用和需求前景。目前的研究已经证实了在缺血性卒中发病4.5 h内，替奈普酶替代阿替普酶进行静脉溶栓治疗的实力。虽然在急性缺血性卒中的特殊人群和超再灌注时间窗治疗中，替奈普酶的有效性和安全性尚缺乏足够的循证医学证据，但目前已经开展了较多的相关研究，部分正在进行的研究将为上述患者的治疗提供更多依据。 Abstract: This paper summarizes the clinical research results of tenecteplase in the treatment of acute ischemic stroke and looks forward to the broader clinical application and demand of tenecteplase. The current study has confirmed the strength of tenecteplase as a replacement for alteplase in intravenous thrombolysis within 4.5 hours of the onset of ischemic stroke. Although there is insufficient evidence-based medical evidence on the efficacy and safety of tenecteplase in the special population of acute ischemic stroke and treatment beyond the reperfusion time window, many related studies have been conducted to date. Some ongoing research will provide more evidence for the treatment of these patients.

Abstract Peripheral nerve injury (PNI)-induced neuropathic pain (NP) is a severe disease with high prevalence in clinics. Gene reprogramming and tissue remodeling in the dorsal root ganglia (DRG) and spinal cord (SC) drive the development and maintenance of neuropathic pain (NP). However, our understanding of the NP-associated spatial molecular processing landscape of SC and the non-synaptic interactions between DRG neurons and SC cells remains limited. We here integrate spatial transcriptomics (ST) with single-nucleus RNA-sequencing (snRNA-seq) and bulk RNA-sequencing (bulk RNA-seq) to characterize regional pathological heterogeneity of the SC under NP conditions. First, the SC of NP mice manifests unique spatial atlases of genes, cell populations, cell-cell cross-talks, signaling pathways, and transcriptional regulatory networks compared to sham mice. We further report that injured DRG sensory neurons and the corresponding ventral horn of the SC show similar expression patterns after PNI. In addition, for the first time, we systematically exhibit “cross-talk omics” between the DRG neurons and SC dorsal horn neurons and glial cells, indicating an altered communication profile under NP conditions. Together, our findings decode the spatial and cellular heterogeneity of molecular pathological mechanisms underlying NP, providing a foundation for designing therapeutic targets for this disorder.

Abstract Background The COVID-19 pandemic has taken a toll on frontline health care workers (HCWs), leading to poor mental and physical well-being. We conducted a large, cluster randomized controlled trial to implement an adapted Stress First Aid (SFA) intervention to support HCW well-being using a train-the-trainer (TTT) approach for rapid deployment in the United States and collected qualitative data through interviews to understand implementation. The goal of this study is to understand barriers and facilitators to deploying SFA using a TTT model, with particular emphasis on the acceptability, uptake, and barriers from the implementation. Methods We conducted seven individual and seven group semi-structured qualitative interviews with 28 trainers (i.e., site champions) who delivered SFA training to their local HCWs from Spring 2021 to Winter 2022 in hospitals and health care centers within the United States. We utilized both inductive and deductive approaches to coding transcripts. All transcripts were coded in Dedoose. We used the Consolidated Framework for Implementation Research (CFIR) to rigorously assess implementation experiences. Results Site champions highlighted leadership buy-in, protected time and incentives, and teams as implementation facilitators, while implementation barriers included unhelpful training materials and content, time constraints and scheduling difficulties, and pandemic-related factors, such as COVID-19 surges. SFA implementation processes varied: some champions had virtual SFA presentations, while others held informal discussions about SFA material in person. Champions also differed on their perceptions of SFA sustainability: some indicated it would be difficult to sustain SFA in their organization due to limited structure and time, while others stated they would continue to utilize it. Conclusion Limited research has examined the implementation of HCW well-being interventions using a TTT approach in a changing environment. Site champions were able to implement SFA during a period of rapid and frequent change and shared several implementation facilitators and barriers related to the SFA intervention. In the future, addressing the implementation barriers proactively and prioritizing the implementation facilitators may prove to be useful for large-scale interventions implemented during disease outbreaks and pandemics.

Abstract Background Eveningness chronotype—the tendency for later sleep and wake times—arises from a confluence of psychosocial, behavioral, and biological factors. With the onset and progression of puberty, many young people develop an eveningness chronotype, which remains prevalent through the transition into adulthood. Eveningness has been associated with increased risk for poorer health. While eveningness is modifiable, maintaining the necessary behavior changes can be challenging. The science on habits demonstrates that habit formation is a key mechanism for maintaining behavior change over time. Learning theory offers schedules of reinforcement that also hold promise for enhancing the maintenance of behavior change. The present study will evaluate the Habit-based Sleep Health Intervention (HABITs)—which combines the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) with the science of habits—and a text message intervention informed by learning theory to attempt to sustainably modify the contributors to eveningness among young adults (18–30 years of age). Methods Participants (N = 160) will be randomly allocated to HABITs and HABITs + Texts. Both interventions include HABITs which involves three 50-min sessions followed by six 30-min sessions. Alongside the latter six sessions, HABITs + Texts will concurrently receive the text message intervention. Aims 1–3 will compare HABITs + Texts to HABITs on improvements in the outcomes of (1) utilization of sleep health behaviors and habit formation, (2) sleep and circadian functioning, and (3) functioning in five health-relevant domains, in the short (post-treatment) and longer (6-month and 12-month follow-up) term. Exploratory analysis will (1) compare HABITs and HABITs + Texts on (a) if sleep health behavior habit formation mediates the effects of intervention on improvement in outcomes and (b) if intervention effects are moderated by select variables, and (2) to evaluate if HABITs (regardless of the text message intervention) is associated with an improvement in outcomes in the short and longer term. Discussion This study has the potential to advance knowledge on (1) the value of leveraging the science of habits and learning theory in behavior change interventions, (2) the use of a low-cost and efficient intervention for habit formation and maintenance, (3) interventions that address eveningness chronotype, and (4) processes related to behavior change during emerging adulthood. Trial registration Clinicaltrials.gov NCT05167695. Registered on December 22, 2021.

Abstract Background Poor memory for treatment is associated with poorer treatment adherence and poorer patient outcomes. The memory support intervention (MSI) was developed to improve patient memory for treatment with the goal of improving patient outcomes. The aim of this study protocol is to conduct a confirmatory efficacy trial to test whether a new, streamlined, and potent version of the MSI improves outcomes for midlife and older adults. This streamlined MSI is comprised of constructive memory supports that will be applied to a broader range of treatment content. The platform for this study is the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C). We will focus on midlife and older adults who are low income and experiencing mobility impairments. Methods Participants (N = 178) will be randomly allocated to TranS-C + MSI or TranS-C alone. Both intervention arms include eight 50-min weekly sessions. Assessments will be conducted at pre-treatment, post-treatment, 6-, and 12-month follow-up (6FU and 12FU). Aim 1 will compare the effects of TranS-C + MSI versus TranS-C alone on sleep and circadian functioning, daytime functioning, well-being, and patient memory. Aim 2 will test whether patient memory for treatment mediates the relationship between treatment condition and patient outcomes. Aim 3 will evaluate if previously reported poor treatment response subgroups will moderate the relationship between treatment condition and (a) patient memory for treatment and (b) treatment outcome. Exploratory analyses will compare treatment condition on (a) patient adherence, patient-rated treatment credibility, and patient utilization of treatment contents, and (b) provider-rated acceptability, appropriateness, and feasibility. Discussion This study has the potential to provide evidence for (a) the efficacy of a new simplified version of the MSI for maintaining health, well-being, and functioning, (b) the wider application of the MSI for midlife and older adults and to the treatment of sleep and circadian problems, and (c) the efficacy of the MSI for sub-groups who are likely to benefit from the intervention. Trial registration ClinicalTrials.gov NCT05986604. Registered on 2 August 2023.

Abstract Background Robot-Assisted Gait Training (RAGT) is a novel technology widely employed in the field of neurological rehabilitation for patients with subacute stroke. However, the effectiveness of RAGT compared to conventional gait training (CGT) in improving lower extremity function remains a topic of debate. This study aimed to investigate and compare the effects of RAGT and CGT on lower extremity movement in patients with subacute stroke. Methods Comprehensive search was conducted across multiple databases, including PubMed, Web of Science, Cochrane Library, EBSCO, Embase, Scopus, China National Knowledge Infrastructure, Wan Fang, SinoMed and Vip Journal Integration Platform. The database retrieval was performed up until July 9, 2024. Meta-analysis was conducted using RevMan 5.4 software. Results A total of 24 RCTs were included in the analysis. The results indicate that, compared with CGT, RAGT led to significant improvements in the Fugl-Meyer Assessment for Lower Extremity [MD = 2.10, 95%CI (0.62, 3.59), P = 0.005], Functional Ambulation Category[MD = 0.44, 95%CI (0.23, 0.65), P

Abstract Background Empathy is one of the fundamental factors enhancing the therapeutic effects of physician–patient relationships, but there has been no relevant research in China on the pediatric resident physicians’ capacity for empathy or the influencing factors. Methods A mixed-methods study was undertaken. The student version of the Jefferson Scale of Empathy was used to assess 181 postgraduate residents at Shanghai Children’s Medical Center and Shanghai Children’s Hospital. Differences in empathy ability among pediatric resident physicians of different genders and specialties were analyzed using independent sample t-tests and Mann–Whitney U tests. A one-way analysis of variance was used to analyze the differences in empathy ability at different educational levels and years of medical residency training. Seven third-year postgraduate pediatric residents from Shanghai Children’s Medical Center participated in semi-structured interviews exploring the influencing factors. We analyzed the interview transcripts using thematic analysis. Results The scale was completed by 154 pediatric residents. No statistically significant differences in empathy were found between educational level, postgraduate year, gender, or specialty. The factors influencing empathy in doctor–patient communication included the person who accompanied the child to see the doctor, how the children cooperated with doctors for medical treatment, the volume of pediatric outpatient and emergency visits, and the physician’s ability to withstand pressure. All interviewed resident physicians regarded learning empathy as important but rarely spent extra time learning it. Conclusions The evaluation results of resident physicians on changes in empathy after improving clinical abilities vary according to their understanding of empathy, and the work environment has an important impact on pediatricians’ empathy ability. Their empathy score is relatively low, and this requires exploration and intervention.

Most of the pyroptosis inhibitors targeted Gasdermin D (GSDMD) are functioning by restraining GSDMD-N (p30) oligomerization. For the first time, this work discovered a pyroptosis inhibitor taking effect by degrading p30 and GSDMD. As the principal bioactive constituent in Erigeron breviscapus, scutellarin (SCU) assumes a pivotal role in the realm of anti-inflammatory processes. In this study, SCU demonstrated efficacy in hindering pyroptosis mediated by the NOD-like receptor protein 3 (NLRP3) inflammasome, absent in melanoma 2 (AIM2) inflammasome, NLR-family CARD-containing protein 4 (NLRC4) inflammasome, and that activated through the non-canonical pathway. The inhibitory effect is achieved by thwarting apoptosis-associated speck-like protein containing CARD (ASC) oligomerization and inducing the ubiquitin-dependent selective autophagy of p30/GSDMD. Throughout the autophagic process, SCU facilitates selective autophagy of the pyroptosis executor p30/GSDMD through K33-linked polyubiquitination at Lys51 catalyzed by the E3 ligase tripartite motif-containing 21 (TRIM21). This process contributes to the recognition of p30/GSDMD by the cargo receptor sequestosome 1 (SQSTM1)/p62. The characteristic positions SCU as a prospective clinical intervention for a broader spectrum of inflammatory-related disorders.

ABSTRACT During the evolution of parasites, co‐speciation and host‐range expansion are thought to play roles in establishing associations with hosts, while sorting events can lead to dissolution of those associations. To address the roles of these processes, we focus on avian haemosporidian parasites infecting hosts of the intensively studied great tit species complex. We estimated the phylogeography of lineages detected in the species complex, and quantified their transition probabilities among hosts. Lineages detected in different host species presented a strong geographical signal but did not form monophyletic groups. Yet, distributions of lineages are not merely the result of their dispersal limitations, as many lineages that infect only one focal species can be found in birds sympatric with other focal species. Besides, closely related lineages that infect the same host species reach more similar rates of infection than expected by chance. Finally, Haemoproteus and Leucocytozoon lineages infecting P. major, the most recently dispersed species, were more generalized than others, consistent with a pattern of generalist parasites expanding their host ranges by infecting newly encountered host species. Our results suggest that host–parasite associations in this system are mainly the result of sorting events and host‐range expansion of parasites, rather than co‐speciation.

Abstract The double‐Intertropical Convergence Zone (ITCZ) bias is a common model bias, which has puzzled the climate model community for several decades. Here, by comparing a high‐ and low‐resolution state‐of‐the‐art model CESM1, it is found that the double‐ITCZ bias is largely reduced in the high‐resolution CESM1. The key reason is the realistic colder sea surface temperature (SST) over the southeast Pacific (SEP) in the high‐resolution model. This realistic SEP SST is mainly due to a spuriously deeper mixed layer with a more realistic wind, as the sensitivity of mixed layer depth to wind is overestimated in both versions of CESM1. The better representation of terrain, such as Andes Mountains, elevates warm advection from inland to the coastal region, which maintains the inversion structure favorable for low cloud. The resultant increased coastal cloud in the high‐resolution CESM1 causes the colder coastal SST, thus improving the wind and deepening the mixed layer.

ABSTRACT Aims and objective To investigate the impact of acupuncture on post‐stroke cognitive impairment (PSCI). Background PSCI is a major barrier to stroke patients’ rehabilitation, and acupuncture is one of the treatments. However, the benefit of acupuncture on PSCI is unclear. Design A meta‐analysis and systematic review of randomized controlled trials (RCTs). Methods Up to February 1, 2024, databases in PubMed, MEDLINE, Scopus, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, VIP, and Wanfang Data were searched. The risk of bias was investigated using the Cochrane Handbook for systematic reviews of treatments. Random‐effect and fix‐effect models were used to report the effects. Results There were 29 randomized clinical trials with 2477 participants included. The findings demonstrated that the Mini‐Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scores were higher in the acupuncture group than medicine group (mean difference [MD] = 1.74, 95% confidence interval (CI) CI [1.26, 2.23], I2 = 59%, p

Abstract Tumour cell senescence can be induced by various factors, including DNA damage, inflammatory signals, genetic toxins, ionising radiation and nutrient metabolism. The senescence‐associated secretory phenotype (SASP), secreted by senescent tumour cells, possesses the capacity to modulate various immune cells, including macrophages, T cells, natural killer cells and myeloid‐derived suppressor cells, as well as vascular endothelial cells and fibroblasts within the tumour microenvironment (TME), and this modulation can result in either the promotion or suppression of tumorigenesis and progression. Exploring the impact of SASP on the TME could identify potential therapeutic targets, yet limited studies have dissected its functions. In this review, we delve into the causes and mechanisms of tumour cell senescence. We then concentrate on the influence of SASP on the tumour immune microenvironment, angiogenesis, extracellular matrix and the reprogramming of cancer stem cells, along with their associated tumour outcomes. Last, we present a comprehensive overview of the diverse array of senotherapeutics, highlighting their prospective advantages and challenge for the treatment of cancer patients. Key points Senescence‐associated secretory phenotype (SASP) secretion from senescent tumour cells significantly impacts cancer progression and biology. SASP is involved in regulating the remodelling of the tumour microenvironment, including immune microenvironment, vascular, extracellular matrix and cancer stem cells. Senotherapeutics, such as senolytic, senomorphic, nanotherapy and senolytic vaccines, hold promise for enhancing cancer treatment efficacy.