This study aims to investigate the potential of oncolytic nanoparticles encapsulating Coxsackievirus A21 (CVA21) full-genome mRNA (CVA21@ONP) to resurrect CVA21 and induce apoptosis in host cells, as well as the antitumor immune effects of CVA21@ONP in immunocompetent tumor-bearing BALB/c mice. We used lipid nanoparticles (LNPs) to encapsulate CVA21 full-genome mRNA, thus preparing CVA21@ONP. The killing efficacy of CVA21@ONP was determined by the plaque assay and cell counting kit-8 (CCK-8), and the apoptosis in HT29 and CT26-iRFP cells was evaluated by flow cytometry. Mice were administrated with CVA21@ONP at high and low doses intratumorally, and the growth of tumors expressing infra-red fluorescent protein (iRFP) was monitored. Additionally, the types and changes of immune cells in the spleen were analyzed by flow cytometry. The results demonstrated that CVA21@ONP successfully resurrected CVA21 in both HT29 and U87MG cells. The plaque assay revealed robust killing effects of CVA21@ONP against both human and murine cell lines, and flow cytometry results showed increased early and late apoptotic cells. Notably, intratumoral detection revealed significantly down-regulated expression of iRFP in both high- and low-dose CVA21@ONP groups. Flow cytometry results further indicated that CVA21@ONP treatment effectively reduced the levels of immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), in the spleen, while enhancing T cell-dependent antitumor immune responses. These findings suggest that CVA21@ONP can replicate and survive extensively both in vitro and in vivo, activating the immune system of mice administrated with CVA21@ONP to target cells at the tumor site, thereby remodeling the tumor immune microenvironment and accelerating the suppression or even complete regression of tumors. The oncolytic performance of CVA21@ONP has been verified through intratumoral injection administration in this study, aimed at further exploring its therapeutic potential and promoting the development of the field of tumor treatment.
Animals ; Nanoparticles/chemistry* ; Mice ; Mice, Inbred BALB C ; Humans ; Apoptosis ; Oncolytic Viruses/genetics* ; Oncolytic Virotherapy/methods* ; Cell Line, Tumor ; RNA, Messenger/genetics* ; HT29 Cells

Objective:To investigate the current status and challenges of pediatric life support training in China and provide references for improving training quality.Methods:A cross-sectional study was conducted to collect data from pediatric life support training centers across the country，covering basic institutional information，training capacity and training faculty，training program funding，as well as existing challenges and issues.The domestic registry of training centers in 2023 was obtained through the American Heart Association's online platform.After contacting and verifying each center，an online questionnaire was distributed，and the aggregated data were statistically analyzed.Results:A total of 42 institutions participated in the survey，including 19 children's hospitals，14 general hospitals，6 maternal and child health hospitals，2 women and children’s hospitals，and 1 training institution.The distribution of training centers showed a concentration in coastal areas，with the top three provinces/municipalities being Guangdong（7/42，16.7%），Zhejiang（6/42，14.3%），and Shanghai（4/42，9.5%）.As of December 31 2023，the 42 institutions had an annual basic life support（BLS）training volume of 8 587 individuals，the median was 120 (100,200)，and an annual pediatric advanced life support（PALS）training volume of 2 448 individuals，the median was 30 (20,50).Among the 42 institutions，there were 598 BLS instructors and 306 PALS instructors.Among the surveyed institutions，24（24/42，57.1%）reported BLS instructor teams comprising fewer than 10 members，and 33（33/42，78.6%）reported PALS instructor teams comprising fewer than 10.Only 7 centers(7/42,16.7%）reported having dedicated funding support.The top three challenges were：training sessions occupying instructors’personal time（27/42，64.3%），low instructor compensation（16/42，38.1%），and issues with the data submission system（16/42，38.1%）.Conclusion:Pediatric life support training centers in China are primarily children’s hospitals，with a geographical concentration in coastal areas，which is also reflected in the distribution of training scale and instructor resources.Most centers have relatively small training scales and limited instructor capacity，with many instructors conducting training during their personal time.These issues may hinder the implementation and effectiveness of training programs.

Objective:To investigate the current status and challenges of pediatric life support training in China and provide references for improving training quality.Methods:A cross-sectional study was conducted to collect data from pediatric life support training centers across the country，covering basic institutional information，training capacity and training faculty，training program funding，as well as existing challenges and issues.The domestic registry of training centers in 2023 was obtained through the American Heart Association's online platform.After contacting and verifying each center，an online questionnaire was distributed，and the aggregated data were statistically analyzed.Results:A total of 42 institutions participated in the survey，including 19 children's hospitals，14 general hospitals，6 maternal and child health hospitals，2 women and children’s hospitals，and 1 training institution.The distribution of training centers showed a concentration in coastal areas，with the top three provinces/municipalities being Guangdong（7/42，16.7%），Zhejiang（6/42，14.3%），and Shanghai（4/42，9.5%）.As of December 31 2023，the 42 institutions had an annual basic life support（BLS）training volume of 8 587 individuals，the median was 120 (100,200)，and an annual pediatric advanced life support（PALS）training volume of 2 448 individuals，the median was 30 (20,50).Among the 42 institutions，there were 598 BLS instructors and 306 PALS instructors.Among the surveyed institutions，24（24/42，57.1%）reported BLS instructor teams comprising fewer than 10 members，and 33（33/42，78.6%）reported PALS instructor teams comprising fewer than 10.Only 7 centers(7/42,16.7%）reported having dedicated funding support.The top three challenges were：training sessions occupying instructors’personal time（27/42，64.3%），low instructor compensation（16/42，38.1%），and issues with the data submission system（16/42，38.1%）.Conclusion:Pediatric life support training centers in China are primarily children’s hospitals，with a geographical concentration in coastal areas，which is also reflected in the distribution of training scale and instructor resources.Most centers have relatively small training scales and limited instructor capacity，with many instructors conducting training during their personal time.These issues may hinder the implementation and effectiveness of training programs.

Esophageal cancer is a common malignant tumor of digestive tract.Remarkable regional difference is a prominent feature of the clinical epidemiology of esophageal cancer.They are mainly manifested in incidence rate,incidence type,onset age,and gene mutation.These differences may be related to dietary habits,lifestyle,and environmental factors.In recent years,research on the regional differences in esophageal cancer has gradually deepened.This article summarizes the differences in incidence rate,incidence type,gene mutations,epigenetics,risk factors,and prognosis of esophageal cancer in different regions,including Asia(China,India,Japan,and other countries),Europe,America(the United States),Africa,and other regions.Understanding these differences can help doctors and public health experts understand the risk factors and causes of esophageal cancer and further develop highly effective prevention and treatment strategies to reduce the occurrence and mortality rate of this malignancy.

Simulation-based medical education（SBME）is an important model in international medical education.With the development of SBME domestically,various forms such as in-situ simulation,team simulation,interdisciplinary simulation,and hybrid simulation are gradually emerging.While post-graduate education and competency receive more attention,SBME has shown its value in areas including education and training,clinical thinking,assessment,and evaluation,as well as improving medical quality and patients safety,especially in the management of emergency and critical care crisis resources.However,the progress of pediatric SBME has been slow despite attracting significant attention within the field of pediatric critical care.The establishment of pediatric critical care skills simulation,scenario simulation,in-situ simulation and other training methods can not only enable clinicians to achieve“standardized operation” and “team collaboration”,but also promote“system transformation”,greatly improving the medical quality of pediatric critical care while ensuring patients safety.

The awake prone position plays an important role in the treatment of hypoxemia and the improvement of respiratory distress symptoms in non-intubated patients. It is widely used in clinical practice because of its simple operation, safety, and economy. To enable clinical medical staff to scientifically and normatively implement prone position for awake patients without intubation, the committees of consensus formulation, guided by evidence-based methodology and Delphi method, conducted literature search, literature quality evaluation and evidence synthesis around seven topics, including indications and contraindications, evaluation, implementation, monitoring and safety management, termination time, complication prevention and health education of awake prone position. After two rounds of expert letter consultation, Expert consensus on implementation strategy of awake prone positioning for non-intubated patients in China (2023) was formulated, and provide guidance for clinical medical staff.
Humans ; Consensus ; Prone Position ; Wakefulness ; China ; Dyspnea

T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.

Virtual reality (VR) is a technology, which can simulate human vision, touch, hearing and other sensory functions, and it synthesizes a computer-generated 3D world to provide immersive experiences.VR technology has the characteristics of interactivity, immersion and imagination, and its application in medical education and simulation training improves the quality and efficiency of learning.At the same time, VR technology also plays a certain role in clinical treatment such as surgery, rehabilitation, psychology, sedation and analgesia.With the development of VR technology, its application in pediatric medicine field is expected to solve some difficulties of pediatric practitioners.For example, the application of virtual standard patient in pediatric training, and VR technology relieving pain and anxiety.

Objective:To analyze the effects of microvascular invasion (MVI) and anatomical hepatectomy on early recurrence and survival of patients with hepatocellular carcinoma (HCC).Methods:The data of 246 patients with HCC admitted to 215 Hospital of Shaanxi Nuclear Industry, Chinese PLA General Hospital and Beijing Tsinghua Chang Gung Hospital from July 2008 to June 2019 were retrospectively analyzed, including 208 males and 38 females, aged (53.8±9.6) years. According to the occurrence of MVI, 246 patients were divided into the MVI group ( n=83) and control group ( n=163, without MVI). Hepatitis B virus (HBV) infection, preoperative alpha-fetoprotein (AFP), maximum tumor diameter, intraoperative blood loss were compared between the two groups. The recurrence-free survival and cumulative survival were compared between the two groups before and after the inverse probability weighted correction for propensity score. Results:The propensity score was calculated by logistic regression model. After inverse probability weighted correction, the virtual sample size was 247 cases (82 cases in MVI group and 165 cases in control group). The proportion of HBV infection, with a serum level of AFP > 200 μg/L, the maximum diameter of tumor and the intraoperative blood loss were higher in MVI group (all P<0.05). The risk of early recurrence in patients undergoing anatomical hepatectomy ( n=107) was lower than that in patients undergoing non-anatomical hepatectomy ( n=139) (univariate Cox regression analysis of HR=1.60, 95% CI: 1.06 to 2.42, P=0.020), but the overall survival was comparable (univariate Cox regression analysis of HR=1.66, 95% CI: 0.80 to 3.42, P=0.200). The recurrence-free survival (RFS) of MVI group was lower than that of the control group, and the postoperative cumulative survival rate was also lower before the inverse probability weighted correction of the tendency score. The RFS in MVI group was lower than that in control group after the tendency score was adjusted by inverse probability weighting ( HR=2.62, 95% CI: 1.61 to 4.27, P<0.001). There was no significant difference in the cumulative survival between the MVI and control group ( HR=2.09, 95% CI: 0.89 to 4.93, P=0.050). Conclusion:MVI is associated with early postoperative recurrence in patients with HCC, and the early recurrence rate after anatomical hepatectomy is lower than that after non-anatomical hepatectomy.

Objective:To summarize the experience of the precise prevention and control strategy of novel coronavirus infection in the pediatric intensive care unit(PICU)during the epidemic of the Omicron variant.Methods:A retrospective analysis was performed on the strategies and management experience of precise prevention and control of novel coronavirus infection in PICU at Pediatric Hospital of Fudan University from March 1 to May 10, 2022.Results:According to the national and Shanghai novel coronavirus infection prevention and control standards, the PICU in our hospital, in accordance with the specialty characteristics of PICU, cooperated with the hospital′s department of infection and medical department to jointly construct a precise ward management strategy for the outbreak of the omicron mutants infection.Precise prevention and control management strategies were formulated from four aspects: the admission process of critically ill children, the division of PICU ward areas and nosocomial infection protection, the reception management system for children′s family members, and the " bubble management" system for PICU staff, and run them for 3 months.During the epidemic, there was no nosocomial infection of novel coronavirus infection in children or medical staff.During the period, a total of 140 critically ill children were admitted, including 87 cases transferred from the general ward in the hospital, 48 cases from the emergency department(non-febrile, 3 cases transferred by the transfer team), four cases from fever clinic, and one case from control ward.Four of the critically ill children had no emergency nucleic acid test report when they were admitted to the PICU.Among the 140 critically ill children, 54 patients received mechanical ventilation, 18 patients received blood purification, and two patients were monitored after liver transplantation.Seventy-eight (55.7%) children had underlying diseases.Conclusion:During the current round of novel coronavirus epidemic in Shanghai, PICU in our hospital formulated the admission and ward management procedures for critically ill children, which ensured the prevention and control of nosocomial infection of novel coronavirus, and at the same time ensured the treatment of critically ill children to the greatest extent.