OBJECTIVES: As early as the Apollo 11 mission, astronauts experienced ocular, skin, and upper airway irritation after lunar dust (LD) was brought into the return cabin, drawing attention to its potential biological toxicity. However, the biological effects of LD exposure through the digestive system remain poorly understood. This study aimed to evaluate the impact of digestive exposure to lunar dust simulant (LDS) on gut microbiota and on the intestine, liver, kidney, lung, and bone in mice. METHODS: Eight-week-old female C57BL/6J mice were used. LDS was used as a substitute for lunar dust, and Shaanxi loess was used as Earth dust (ED). Mice were randomly divided into a phosphate buffered saline (PBS) group, an ED group (500 mg/kg), and a LDS group (500 mg/kg), with assessments at days 7, 14, and 28. Mice were gavaged once every 3 days, with body weight recorded before each gavage. At sacrifice, fecal samples were analyzed by 16S ribosomal RNA (rRNA) sequencing; inflammatory cytokine expression [interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α)] in intestinal, liver, and lung tissues was measured by real-time reverse transcription PCR (real-time RT-PCR); hematoxylin and eosin (HE) staining was performed on lung, liver, and intestinal tissues; Periodic acid-Schiff (PAS) staining was used to assess the integrity of the intestinal mucus barrier, and immunohistochemical staining was performed to evaluate the expression of mucin-2 (MUC2). Serum biochemical tests assessed hepatic and renal function. Femoral bone mass was analyzed by micro-computed tomography (micro-CT); osteoblasts and osteoclasts were assessed by osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) staining. Bone marrow immune cell subsets were analyzed by flow cytometry. RESULTS: At day 10, weight gain was slowed in ED and LDS groups. At days 22 and 28, body weight in both ED and LDS groups was significantly lower than controls (both P<0.05). LDS exposure increased microbial species richness and diversity at day 7. Compared with the PBS and ED groups, mice in the LDS group showed increased relative abundance of Deferribacterota, Desulfobacterota, and Campylobacterota, and decreased Firmicutes, with increased Helicobacter typhlonius and reduced Lactobacillus johnsonii and Lactobacillusmurinus. HE and PAS staining of the colon showed that mucosal structural disruption and goblet cell loss were more severe in the LDS group. In addition, immunohistochemistry revealed a significant downregulation of MUC2 expression in this group (P<0.05). No obvious pathological alterations were observed in liver HE staining among the 3 groups, and none of the groups exhibited notable hepatic or renal dysfunction. HE staining of the lungs in the ED and LDS groups showed increased perivascular inflammatory cell infiltration (both P<0.05). CONCLUSIONS LDS exposure via the digestive route induces gut dysbiosis, intestinal barrier disruption, pulmonary inflammation, bone loss, and bone marrow immune imbalance. These findings indicate that LD exposure poses potential health risks during future lunar missions. Targeted restoration of beneficial gut microbiota may represent a promising strategy to mitigate LD-related health hazards.
Animals ; Dust ; Mice ; Mice, Inbred C57BL ; Dysbiosis/etiology* ; Female ; Gastrointestinal Microbiome/drug effects* ; Moon ; Liver/metabolism* ; Digestive System/microbiology* ; Lung/metabolism* ; Kidney

OBJECTIVES: Due to prolonged exposure to cosmic radiation and meteorite impacts, lunar surface dust forms nanoscale angular particles with strong electrostatic adsorption properties. These dust particles pose potential inhalation risks, yet their pulmonary toxicological mechanisms remain unclear. Given the need for dust exposure protection in future lunar base construction and resource development, this study established an acute exposure model using lunar soil simulant (LSS) and used Earth soil (ES; Loess from Shaanxi, China) as a comparison to investigate lung injury mechanisms. METHODS: C57BL/6 mice were randomly assigned to 3 groups: Phosphate buffered saline (PBS), LSS, and ES, with 5 to 7 mice per group. Mice in the LSS and ES groups received a single intratracheal instillation to induce acute inhalation exposure. Body weight was monitored for 28 days. Mice were euthanized at days 3, 7, 14, and 28 post-exposure, and peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected. Immune cell subsets in BALF were analyzed using flow cytometry. Hematoxylin-eosin (HE) staining assessed lung structure and inflammation; periodic acid-Schiff (PAS) staining evaluated airway mucus secretion; Masson staining examined collagen deposition. Real-time reverse transcription PCR (real-time RT-PCR) was used to measure the mRNA expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and epithelial barrier genes (Occludin, Cadherin-1, and Zo-1). Lung tissues at day 7 were subjected to transcriptomic sequencing, followed by immune infiltration and pathway enrichment analyses to determine immunoregulatory mechanisms. RESULTS: Body weight in the ES group progressively declined after day 18 (all P<0.05), while the LSS group showed no significant changes compared with the control group. HE staining showed both LSS and ES induced inflammatory cell infiltration around airways and vasculature, which persisted for 28 days but gradually lessened over time. PAS staining revealed marked mucus hypersecretion in the LSS group at day 3, followed by gradual recovery; no significant mucus changes were observed in the ES group. Masson staining indicated no obvious pulmonary fibrosis in either group within 28 days. Real-time RT-PCR demonstrated significant upregulation of IL-1β and TNF-α in both LSS and ES groups, peaking on day 7, accompanied by downregulation of epithelial barrier genes (Occludin, Cadherin-1, and Zo-1)(all P<0.05). Transcriptomic analysis showed that both LSS and ES activated chemokine-related pathways and enriched leukocyte migration and neutrophil recruitment pathways. Further validation revealed upregulation of CXCL2 and MMP12 in the LSS group, whereas CXCL3 and MMP12 were predominantly elevated in the ES group. CONCLUSIONS Both LSS and ES can induce sustained lung injury and neutrophil infiltration in mice, though the underlying molecular mechanisms differ. Compared with ES, exposure to LSS additionally triggers a transient eosinophilic response, suggesting that lunar dust particles possess stronger immunostimulatory potential and higher biological toxicity.
Animals ; Mice ; Mice, Inbred C57BL ; Soil ; Lung Injury/etiology* ; Dust ; Bronchoalveolar Lavage Fluid ; Moon ; Lung/pathology* ; Inhalation Exposure/adverse effects* ; Male

Objective:To explore the effect of arrhythmia in early and intermediate postoperative stages of the Fontan procedure.Methods:Patients undergoing Fontan procedure at Shanghai Children's Medical Center within 2015 to 2018 were included.Identified data obtained from retrospective，observational dataset including demographic information，patient diagnoses，baseline characteristics，operation details，ECG data，ultrasound cardiograph data，in-hospital medical intervention，in-hospital mortality，out-patient medical intervention，readmission，and complications.Results:Among the 277 children，early arrhythmia occurred in 173 cases（62.5%），medium- and long-term arrhythmia occurred in 35 cases（12.6%），and 69 cases（24.91%）had no arrhythmia，of which only 55 cases（19.9%）needed early intervention with drugs.Malignant arrhythmia was an independent predictor of poor prognosis（ OR 5.835 95% CI 1.738-19.596, P=0.004）.Among all arrhythmia，atrioventricular junction arrhythmia had the highest incidence.During the follow-up，we found that most of the arrhythmia that had occurred in the early postoperative period could return to normal in three months after the operation，while the rhythm gradually stabilized at four years after the operation，the persistent arrhythmia almost no longer returned to normal，and the normal rhythm basically did not recur.For patients who did not develop arrhythmia in the early postoperative period，the peak of new arrhythmia occurred within one year after surgery，and most of them were persistent arrhythmia. Conclusion:The development of an arrhythmia is associated with a heightened risk of subsequent failure of the Fontan circulation，especially malignant arrhythmia.However，the incidence of malignant arrhythmia is not high.In addition，most of the arrhythmias that had occurred in the early postoperative period could return to normal in three months after surgery，and the rhythm gradually stabilized in four years after surgery.While no arrhythmia in the early postoperative period，the peak of new arrhythmia occur within one year after surgery，and most of them are persistent arrhythmia.

Objective:To explore the effect of arrhythmia in early and intermediate postoperative stages of the Fontan procedure.Methods:Patients undergoing Fontan procedure at Shanghai Children's Medical Center within 2015 to 2018 were included.Identified data obtained from retrospective，observational dataset including demographic information，patient diagnoses，baseline characteristics，operation details，ECG data，ultrasound cardiograph data，in-hospital medical intervention，in-hospital mortality，out-patient medical intervention，readmission，and complications.Results:Among the 277 children，early arrhythmia occurred in 173 cases（62.5%），medium- and long-term arrhythmia occurred in 35 cases（12.6%），and 69 cases（24.91%）had no arrhythmia，of which only 55 cases（19.9%）needed early intervention with drugs.Malignant arrhythmia was an independent predictor of poor prognosis（ OR 5.835 95% CI 1.738-19.596, P=0.004）.Among all arrhythmia，atrioventricular junction arrhythmia had the highest incidence.During the follow-up，we found that most of the arrhythmia that had occurred in the early postoperative period could return to normal in three months after the operation，while the rhythm gradually stabilized at four years after the operation，the persistent arrhythmia almost no longer returned to normal，and the normal rhythm basically did not recur.For patients who did not develop arrhythmia in the early postoperative period，the peak of new arrhythmia occurred within one year after surgery，and most of them were persistent arrhythmia. Conclusion:The development of an arrhythmia is associated with a heightened risk of subsequent failure of the Fontan circulation，especially malignant arrhythmia.However，the incidence of malignant arrhythmia is not high.In addition，most of the arrhythmias that had occurred in the early postoperative period could return to normal in three months after surgery，and the rhythm gradually stabilized in four years after surgery.While no arrhythmia in the early postoperative period，the peak of new arrhythmia occur within one year after surgery，and most of them are persistent arrhythmia.

Objective:To prevent postoperative myocardial oedema or other causes of acute heart failure in congenital cardiac disease,anticipating delay sternal closure may reduce the number of children requiring cardiopulmonary resuscitation after surgery.The aim of this study was to describe the rate of delay sternal closure after surgery for congenital cardiac disease and to analyse the risk factors that may be associated with it.Methods:We retrospectively reviewed all surgeries with extracorporeal circulation in the cardiothoracic surgery intensive care unit of Shanghai Children's Medical Center in the past five years,from September 2014 to December 2018.The study cohort was divided into the delay sternal closure group (n=418) and the control group (routine chest closure,n=12 188) according to whether a delay sternal closure was applicated.Risk factors associated with delay sternal closure were identified by multivariate Logistic regression analysis.Results:A total of 12 606 cases were eligible,of which 418 (3.32%) were in the delayed sternal closure group.The most common cardiac diagnosis in the delayed sternal group was transposition of the great arteries (26.8%,112/418),whereas the most common cardiac diagnosis in the control group was ventricular septal defect (45.9%,5 599/12 188).All-cause mortality in children in the delayed sternal closure group was 3.3% (14/418) compared with 0.4% (46/12 188) in the control group,with a statistically significant difference ( P<0.05).Multivariate Logistic regression analysis showed that the need for delayed sternal closure were associated with age ( OR 0.164,95% CI 0.079-0.338, P<0.001),positive intropic support before surgery ( OR 0.42,95% CI 0.252-0.699, P=0.001),sex（ OR 0.742，95% CI 0.648-1.098， P<0.05），mean body weight（ OR 1.192，95% CI 1.078-1.318， P<0.001），positive intropic support before surgery（ OR 0.370，95% CI 0.252-0.699， P<0.001），complicated surgery ( OR 0.241,95% CI 0.159-0.367, P<0.001) and extracorporeal circulation diversion time ( OR 6.412,95% CI 4.339-9.475, P<0.001). Conclusion:Delayed sternal closure is an important management strategy for congenital cardiac surgery in infants and children.Delayed sternal closure is associated with age，sex,mean body weight at the time of surgery,positive intropic support before surgery，complicated surgery and extracorporeal circulation diversion time.

Regulated cell death (RCD) is a critical physiological process essential in maintaining skin homeostasis. Among the various forms of RCD, ferroptosis stands out due to its distinct features of iron accumulation, lipid peroxidation, and involvement of various inhibitory antioxidant systems. In recent years, an expanding body of research has solidly linked ferroptosis to the emergence of skin disorders. Therefore, understanding the mechanisms underlying ferroptosis in skin diseases is crucial for advancing therapy and prevention strategies. This review commences with a succinct elucidation of the mechanisms that underpin ferroptosis, embarks on a thorough exploration of ferroptosis’s role across a spectrum of skin conditions, encompassing melanoma, psoriasis, systemic lupus erythematosus (SLE), vitiligo, and dermatological ailments precipitated by ultraviolet (UV) exposure, and scrutinizes the potential therapeutic benefits of pharmacological interventions aimed at modulating ferroptosis for the amelioration of skin diseases.

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Background: ChatGPT is a large language model (LLM) based on artificial intelligence (AI) capable of responding in multiple languages and generating nuanced and highly complex responses. While ChatGPT holds promising applications in medical education, its limitations and potential risks cannot be ignored. Methods: A scoping review was conducted for English articles discussing ChatGPT in the context of medical education published after 2022. A literature search was performed using PubMed/MEDLINE, Embase, and Web of Science databases, and information was extracted from the relevant studies that were ultimately included. Results: ChatGPT exhibits various potential applications in medical education, such as providing personalized learning plans and materials, creating clinical practice simulation scenarios, and assisting in writing articles. However, challenges associated with academic integrity, data accuracy, and potential harm to learning were also highlighted in the literature. The paper emphasizes certain recommendations for using ChatGPT, including the establishment of guidelines. Based on the review, 3 key research areas were proposed: cultivating the ability of medical students to use ChatGPT correctly, integrating ChatGPT into teaching activities and processes, and proposing standards for the use of AI by medical students. Conclusion ChatGPT has the potential to transform medical education, but careful consideration is required for its full integration. To harness the full potential of ChatGPT in medical education, attention should not only be given to the capabilities of AI but also to its impact on students and teachers.

Objective:To investigate the epidemiological and clinical characteristics of human parainfluenza viruses (HPIVs) infection among hospitalized children with community-acquired pneumonia (CAP) in China, and provide basic data for diagnosis, treatment and prevention of HPIVs infection.Methods:From November 2014 to February 2020, 5 448 hospitalized children with CAP were enrolled in 14 hospitals in 11 provinces and municipalities directly under the Central Government in southern China and northern China. Nasopharyngeal aspirates or throat swabs were collected, and the nucleic acids of 18 types respiratory viruses including HPIV1-4 were screened by suspension array technology. Demographic data and clinical information were collected for statistical analysis.Results:The total detection rate of HPIVs in 5 448 children with CAP was 8.83% (481/5 448), and the detection rate in males was higher than that in females (62.79% vs. 37.21%; χ2=0.000, P=0.992). The detection rate of HPIVs in 1~< 3 years age group was higher than that in other age groups, and the difference was statistically significant ( χ2=61.893, P<0.001). The detection rate of HPIVs in the northern region was higher than that in the southern region (9.02% vs 8.65%), but the difference was not statistically significant ( χ2=0.239, P=0.625). The prevalence of HPIV1-4 in northern and southern China was not completely same. HPIV1 was mainly prevalent in autumn in both northern and southern regions. HPIV2 was prevalent in summer in northern China, and the detection rate was low in southern China. HPIV3 reached its peak in both spring and summer in both northern and southern China, but its duration was longer in southern China than in northern China. HPIV4 is mainly popular in autumn in both southern China and northern China. Among 481 children infected with HPIVs, 58.42% (281/481) were infected with HPIV alone, and the main clinical manifestations were cough (90.75%) and fever (68.68%). Out of the HPIV-positive cases, 42.62% (205/481) were co-infected with another type of HPIV or a different virus, while 11.43% (55/481) had co-infections with two or more different viruses. HPIV3 was the most common type of co-infection with other viruses. HPIV3 infection accounted for the largest proportion (76.80%) in 47 HPIVs-positive children with severe pneumonia. Conclusions:HPIVs is one of the most important pathogens causing CAP in children in China, and children under 3 years of age are the main populations of HPIVs infection. The prevalence characteristics of all types of HPIVs in children in the north and south are not completely same. HPIV3 is the dominant type of HPIV infections and causes more severe diseases.

Objective:To understand the present situation of the construction of standardized asthma clinic for children in China, to explore the problems existing in the process of construction, and to promote the healthy development of standardized clinic construction.Methods:The process and current situation of the construction of standar-dized asthma clinics for children in China were reviewed and investigated, and the practical significance of the China Children′s Asthma Action Plan (CCAAP) in the construction of standardized asthma clinics for children was explored.Results:(1)By December 2020, 1 289 standardized asthma clinics for children and 135 regional demonstration centers had been built; 56 training sessions had been held, with a total of 2 560 doctors and 650 nurses trained, covering 2 560 hospitals across the country; and 4 518 patient education sessions were held.Online publicity covers a total of 1 million person-times, with an annual average of 1.33 million patients.(2)CCAAP improved the quality control level of standardized asthma clinic and promoted the standardized management of children.Conclusions:Through process optimization, professional evaluation, individual health education and real-time disease monitoring, standardized asthma clinic for children with asthma can effectively enhance asthma management awareness of children and their parents, improve disease awareness, and promote better control of asthma.It is an effective management model of asthma in children at present, and it is worthy of clinical promotion.CCAAP plays a good role in the construction of standardized outpatient clinic for asthma in children.The construction of standardized asthma clinic for children in China has achieved remarkable results, and the development trend is good in the future.