Cholecystokinin (CCK) has been confirmed to be essential in NMDA-dependent long-term potentiation (LTP) at mouse cortical synapses. This paper has proven that CCK is necessary for LTP induced by ...high-frequency stimulation of mouse hippocampal synapses projected from the entorhinal cortex. We show that the subunit of the axonal NMDA receptor dominant modulates the activity-induced LTP by triggering pre-synaptic CCK release. A functional pre-synaptic NMDA receptor is required to induce LTP mediated by the axonal Ca
elevation and CCK exocytosis at CCK-specific neurons. Genetic depletion of the GluN1 subunit of NMDA receptors on CCK neurons, which projected from the entorhinal cortex largely abolished the axonal Ca
elevation and disturbed the secretion of CCK in hippocampus. These results demonstrate that activity-induced LTP at the hippocampal synapse is CCK-dependent, and CCK secretion from the axonal terminal is modulated by pre-synaptic NMDA receptors.
Copper (II) is one of the most of important cofactors for numerous enzymes and has captured broad attention due to its role as a neurotransmitters for physiological and pathological functions. In ...this article, we present a reaction-based fluorescent sensor for Cu2+ detection (NIR-Cu) with near-infrared excitation and emission, including probe design, structure characterization, optical property test and biological imaging application. NIR-Cu is equipped with a functional group, 2-picolinic ester, which hydrolyzes in the presence of Cu2+ with high selectivity over completed cations. With the experimental conditions optimized, NIR-Cu (5μM) exhibits linear response for Cu2+ range from 0.1 to 5μM, with a detection limit of 29nM. NIR-Cu also shows excellent water solubility and are highly responsive, both desirable properties for Cu2+ detection in water samples. In addition, due to its near-infrared excitation and emission properties, NIR-Cu demonstrates outstanding fluorescent imaging in living cells and tissues.
•A reaction-based sensor for Cu2+ detection with NIR excitation and emission.•The detection limit for Cu2+ is as low as 29nM in aqueous buffer.•The probe shows special selectivity for Cu2+ over other metal ions.
Background Anxiety, nausea and vomiting are common side effects suffered by paediatric patients receiving chemotherapy. Emerging evidence supports the efficacy of immersive virtual reality (IVR) on ...improving anxiety and distress symptoms including nausea and vomiting among this vulnerable group. This trial aims to assess the feasibility and acceptability of IVR for preventing and managing anxiety, nausea and vomiting among paediatric cancer patients receiving their first chemotherapy. Method and analysis An exploratory trial supplemented by qualitative methods will be conducted. We will recruit 20 paediatric patients who are aged between 6 and 12 years, chemotherapy naïve, scheduled to receive their first intravenous chemotherapy and able to understand Chinese. Participants will be randomly allocated to intervention or control groups. The intervention group will receive the IVR intervention for three sessions as follows: 4 hours before chemotherapy, 5 minutes before and during their first course chemotherapy and 5 minutes before and during their second course chemotherapy. The control group will receive standard care only. Main outcome measures included (1) key parameters for the design of a definitive trial (i.e. screening, eligibility, consent and withdrawal rates); (2) anxiety, anticipatory and acute chemotherapy-induced nausea and vomiting for collection of preliminary data; (3) feasibility and acceptability of the intervention. Semi-structured interviews will be conducted with patients, parents and oncology nurses. Generalized estimating equations model will be used to compare each of the outcome measures across the time points between the two groups. Qualitative data will be analysed by conventional content analysis. Expected results The results of this exploratory trial will inform the design and conduct of future definitive trial. Trial registration number ChiCTR1900021694; Pre-results.
Abstract
The crucial role of interferon (IFN) signaling is well known in the restriction or eradication of pathogen invasion. Viruses take a variety of ways to antagonize host defense through ...eliminating IFN-signaling intracellularly for decades. However, the way by viruses target IFN-signaling extracellularly has not been discovered. Infection by both coronavirus SARS-CoV-2 and enterovirus 71 (EV71 or EV-A71) can cause severe diseases such as neurological disorders and even death in children.
1–3
Here, we show evidence that the protease of SARS-CoV-2 (3CL
pro
) and EV71 (2A
pro
) upregulates the expression and secretion of LDL
-
receptor-related protein-associated protein 1 (LRPAP1). As a ligand, the N-terminus of secreted LRPAP1 binds with the extracellular domain of IFNAR1 that triggers the receptor ubiquitination and degradation and promotes virus infection both in vitro, ex vivo in the mouse brain, and in vivo in newborn mice. A small peptide from the N-terminus of LRPAP1 effectively binds and causes IFNAR1 degradation that enhances both DNA and RNA viral infections, including herpesvirus HSV-1, hepatitis B virus (HBV), EV71, and beta-coronavirus HCoV-OC43; whereas α2M, a LRPAP1 inhibitor, arrests virus infections by stabilizing IFNAR1. Our study demonstrates a new mechanism used by viruses for evading host cell immunity, supporting a strategy for developing pan-antiviral drugs.
The effect of lifestyle on neurocognitive impairment among cancer survivors remain an understudied area. This study explored the association between lifestyle factors and neurocognitive outcomes ...(specifically, attention, memory, processing speed and cognitive flexibility) in AYA survivors (aged 15-39 years) of sarcoma.
This study recruited 116 AYA survivors (age 28.2 (SD = 8.2) years), who were diagnosed with osteosarcoma (49%) or soft-tissue sarcoma (51%) at age 13.3 (SD = 7.2) years. The neurocognitive battery included measures of attention, memory, motor-processing speed, and cognitive flexibility. Survivors reported health-damaging practices, which included: physical inactivity, smoking, alcohol intake, inadequate sleep (<7 h of actual sleep/day), sleep-related fatigue (Multidimensional Fatigue Scale) and long working hours (>9 h/day). General linear modeling was conducted to examine the association between lifestyle factors and neurocognitive outcomes, adjusting for age at diagnosis, sex, education attainment and clinical/treatment variables.
At 14.9 (SD = 7.6) years post-diagnosis, survivors demonstrated impairment in attentiveness (4.3-13.0%), processing speed (34.5%) and cognitive flexibility (18.1%). Nearly half (45.7%) had developed a chronic health condition (CHC). Low physical activity (estimate = -0.97,
= 0.003) and sleep-related fatigue (estimate = -0.08,
= 0.005) were associated with inattention. Survivors who worked >9 h/day (n = 15) demonstrated worse attention (estimate = 5.42,
= 0.023) and cognitive flexibility (estimate = 5.22,
= 0.005) than survivors who worked ≤9 h/day (n = 66). Interaction analysis (CHCs*
) showed that survivors who developed CHCs and reported low physical activity had worse attention (
= 0.032) and cognitive-flexibility (
= 0.019) scores than other subgroups.
Treatment-related CHCs, coupled with continued physical inactivity, may exacerbate inattention and executive dysfunction among survivors. Long working hours and sleep-related fatigue are associated with worse functioning; this finding should be validated with prospective assessment of work-related stressors and objective sleep measures.
Natural killer (NK)/T-cell lymphoma (NKTCL) is an aggressive malignancy with unique epidemiological, histological, molecular, and clinical characteristics. It occurs in two pathological forms, ...namely, extranodal NKTCL (ENKTCL) and aggressive NK leukemia, according to the latest World Health Organization (WHO) classification. Epstein-Barr virus (EBV) infection has long been proposed as the major etiology of lymphomagenesis. The adoption of high-throughput sequencing has allowed us to gain more insight into the molecular mechanisms of ENKTCL, which largely involve chromosome deletion and aberrations in Janus kinase (JAK)-signal transducer and activator of transcription (STAT), programmed cell death protein-1 (PD-1)/PD-ligand 1 (PD-L1) pathways, as well as mutations in tumor suppressor genes. The molecular findings could potentially influence the traditional chemoradiotherapy approach, which is known to be associated with significant toxicity. This article will review the latest molecular findings in NKTCL and recent advances in the field of molecular diagnosis in NKTCL. Issues of quality control and technical difficulties will also be discussed, along with future prospects in the molecular diagnosis and treatment of NKTCL.
IntroductionAnxiety, nausea and vomiting are common side effects suffered by paediatric patients receiving chemotherapy. Emerging evidence supports the efficacy of immersive virtual reality (IVR) on ...improving anxiety and distress symptoms including nausea and vomiting in this vulnerable group. This trial aims to evaluate the effects of IVR intervention on anxiety, chemotherapy-induced nausea and vomiting and anticipatory nausea and vomiting in patients with paediatric cancer receiving first chemotherapy.Method and analysisAn assessor-blinded, randomised controlled trial with a mixed methods evaluation approach. On the basis of our pilot results, 128 chemotherapy-naive patients with paediatric cancer scheduled to receive their first intravenous chemotherapy will be recruited from a public hospital and randomly allocated to intervention (n=64) or control groups (n=64). The intervention group will receive the IVR intervention for three sessions: 2 hours before the first chemotherapy, 5 min before and during their first chemotherapy and 5 min before and during their second chemotherapy, respectively. The control group will receive standard care only. A subsample of 30 participants in the intervention group will be invited for a qualitative interview. Study instruments are: (1) short form of the Chinese version of the State Anxiety Scale for Children, (2) visual analogue scale for anticipatory nausea and vomiting, (3) Chinese version of the Multinational Association of Supportive Care in Cancer Antiemesis Tool and (4) individual face-to-face semistructured interviews to explore intervention participants’ perceptions of the IVR intervention.Ethics and disseminationThis study has been approved by the Hong Kong Children’s Hospital Research Ethics Committee (HKCH-REC-2021-009). The findings will be disseminated in peer-reviewed journals and through local or interventional conference presentations.Trial registration numberChiCTR2100048732.
This study aims to examine how “One Country, Two Systems” has shaped and influenced the collaboration on cross-boundary air pollution control between the governments of the Hong Kong Special ...Administrative Region and the Guangdong province. The presence of the Chinese central government significantly fostered the start of this collaboration, but the implementation and collaborative relationship were relatively weak and unsustainable due to the two local governments’ largely different interests, goals and political demands. We found that the emphasis on “One Country” especially after 2003 led to the signature of more joint agreements in comparison with what the emphasis on “Two Systems” did between 1997 and 2003. Joint agreements appear to be necessary conditions for effective collaboration, but too many of them without satisfying implementation could have resulted in less concrete benefits. A balanced stress on “One Country” and “Two Systems” might bring an appropriate number of joint agreements with good implementation for more effective collaboration.
Evaluation of chemotherapy-induced nausea and vomiting (CINV) in the pediatric population is subject to diverse approaches. This scoping review summarizes the methods used in clinical studies that ...assessed nausea, vomiting or retching in children with cancer. We conducted a literature search of studies indexed in EMBASE and Ovid MEDLINE after 2000. Studies were included if they involved patients ≤18 years of age diagnosed with cancer, and had nausea, vomiting or retching as a primary study outcome. We excluded studies that reported only parent- or clinician-proxy measures without including the child's self-reported NVR, and those without specifying the NVR data collection process. The literature search identified twenty-four studies evaluating pediatric nausea, vomiting or retching. In the assessment of NVR, structured surveys were the most commonly used instrument for NVR assessment (75%) and the use of patient diaries (50%). Nine studies (38%) relied solely on self-reports from children as the outcome measure, while fifteen studies (62%) solicited input from parents/ caregivers and healthcare providers in addition to children's self-reports. Almost all the studies reported the frequency (n = 24) and/or severity (n = 23) of NVR symptoms and the use of antiemetic therapy (n = 19). Fewer studies evaluated distress caused by the symptoms (n = 2) and the effects of symptoms on activities of daily living (n = 4). Incorporating NVR measurement tools as part of standard of care for pediatric patients undergoing chemotherapy is strongly advocated. Based on the age group, we recommend the use of such tools comprising Likert scale, pictorial scales and structured scripts to assess various dimensions of a child's NVR experience.
As survivors of childhood cancer age, development of cancer treatment-related chronic health conditions often occur. This study aimed to describe the pattern of chronic prescription medication use ...and identify factors associated with polypharmacy among survivors of childhood cancer.
This was a retrospective study conducted at the pediatric oncology long-term follow-up clinic in Hong Kong. Eligible subjects included survivors who were (1) diagnosed with cancer before 18 years old, (2) were at least 3 years post-cancer diagnosis and had completed treatment for at least 30 days, and (3) receiving long-term follow-up care at the study site between 2015 and 2018. Dispensing records of eligible survivors were reviewed to identify medications taken daily for ≥30 days or used on an "as needed" basis for ≥6 months cumulatively within the past 12-month period. Polypharmacy was defined as the concurrent use of ≥5 chronic medications. Multivariable log-binomial modeling was conducted to identify treatment and clinical factors associated with medication use pattern and polypharmacy.
This study included 625 survivors (mean current age = 17.9 years, standard deviation SD = 7.2 years) who were 9.2 5.2 years post-treatment. Approximately one-third (n = 219, 35.0%) of survivors were prescribed at least one chronic medication. Frequently prescribed medication classes include systemic antihistamines (26.5%), sex hormones (19.2%), and thyroid replacement therapy (16.0%). Overall prevalence of polypharmacy was 5.3% (n = 33). A higher rate of polypharmacy was found in survivors of CNS tumors (13.6%) than in survivors of hematological malignancies (4.3%) and other solid tumors (5.3%) (
= .0051). Higher medication burden was also observed in survivors who had undergone cranial radiation (RR = 6.31; 95% CI = 2.75-14.49) or hematopoietic stem-cell transplantation (HSCT) (RR = 3.53; 95% CI = 1.59-7.83).
Although polypharmacy was observed in a minority of included survivors of childhood cancer, chronic medication use was common. Special attention should be paid to survivors of CNS tumors and survivors who have undergone HSCT or cranial radiation. These individuals should be monitored closely for drug-drug interactions and adverse health outcomes that may result from multiple chronic medications, particularly during hospitalization in an acute care setting.
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