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

Background Exposure to volatile organic compounds (VOCs) has been observed in both living and working environments. Volatile organic compounds metabolites (VOCMs) in urine can be used to assess the exposure to VOCs and potentially cause adverse effects on human body. Objective To quantitatively evaluate urinary VOCMs and their associations with renal function damage, and further trace the characteristics of potential environmental exposure to provide scientific evidence for effective prevention measures. Methods The study included a total of 6028 samples from four cross-sectional studies in the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018, with exposure and health outcomes matched. Generalized linear models were employed to assess the associations of urinary VOCMs (urinary creatinine adjusted) with urinary protein levels and estimated glomerular filtration rate (eGFR), with coviriables including gender, age, body mass index, education, smoking, alcohol consumption, exercise frequency, diabetes, and hypertension. Weighted quantile sum (WQS) approach was utilized to analyze the effects of mixed exposure and to rank the contribution of individual VOCMs. The associations between VOCMs and associated living environments and occupational exposure characteristics were further investigated. Results Among the enrolled study participants (n=6028), a total of 11 urinary VOCMs were measured, with 10 metabolites having a positive rate of over 80% (84.59%-99.99%). There were 604 individuals (10.0%) having urinary protein abnormalities and 2831 individuals (47.0%) with eGFR reduced. Through a single and a multiple generalized linear model, 5 VOCMs exhibited statistically significant associations with urinary protein abnormalities and/or reduced eGFR levels (P<0.05): N-acetyl-S-(N-methylaminocarbonyl)-L-cysteine (AMC), N-acetyl-S-(2-carboxyethyl)-L-cysteine (CEM), N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHB), 2-hydroxy-2-phenylacetic acid (MAD), and N-acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine (MB3). The WQS index indicated a significantly positive association between VOCMs and urinary protein abnormalities, and DHB contributed the most. The analysis on the potential sources of VOCs exposure showed that those who worked as a private entrepreneur or an employee (vs. government employees), rent houses (vs. owned real estate), had less number of rooms in the residence, fueled cars at self-service gas stations, and inhaled paint fumes in the past 48 h associated with higher VOCMs (P < 0.05) and DHB contributed the most. Conclusion Multiple VOCMs in urine are associated with significantly kidney function injuries. The mixture exposure to VOCMs is significantly associated with higher risks of urinary protein abnormalities. Occupational category, housing ownership, ways to fuel a car, and inhalation of paint odors are closely related with VOCMs levels.

Objective To observe the value of deep learning(DL)models for automatic classification of echocardiographic views.Methods Totally 100 patients after heart transplantation were retrospectively enrolled and divided into training set,validation set and test set at a ratio of 7∶2∶1.ResNet18,ResNet34,Swin Transformer and Swin Transformer V2 models were established based on 2D apical two chamber view,2D apical three chamber view,2D apical four chamber view,2D subcostal view,parasternal long-axis view of left ventricle,short-axis view of great arteries,short-axis view of apex of left ventricle,short-axis view of papillary muscle of left ventricle,short-axis view of mitral valve of left ventricle,also 3D and CDFI views of echocardiography.The accuracy,precision,recall,F1 score and confusion matrix were used to evaluate the performance of each model for automatically classifying echocardiographic views.The interactive interface was designed based on Qt Designer software and deployed on the desktop.Results The performance of models for automatically classifying echocardiographic views in test set were all good,with relatively poor performance for 2D short-axis view of left ventricle and superior performance for 3D and CDFI views.Swin Transformer V2 was the optimal model for automatically classifying echocardiographic views,with high accuracy,precision,recall and F1 score was 92.56％,89.01％,89.97％and 89.31％,respectively,which also had the highest diagonal value in confusion matrix and showed the best classification effect on various views in t-SNE figure.Conclusion DL model had good performance for automatically classifying echocardiographic views,especially Swin Transformer V2 model had the best performance.Using interactive classification interface could improve the interpretability of prediction results to some extent.

Objective To evaluate the short-term clinical efficacy of photodynamic therapy(PDT)assisted mechanical debridement(MD)in the treatment of peri-implantitis.Methods According to the new international classification of periodontal diseases and peri-implant diseases in 2018,single tooth implants diagnosed as peri-implantitis were included.Before treatment,the probing depth(PD),modified sulcus bleeding index(mSBI),and modified plaque index(mPLI)were recorded as the baseline,with mSBI≥1 sites as the treatment sites.The MD group was a control group,and only mechanical subgingival debridement was performed.The PDT group was treated with photodynamic therapy twice,immediately after subgingival debridement and one week after.Follow-up was ar-ranged at 6 and 12 weeks after the end of treatment to examine the changes in PD,mSBI,and mPLI at the included implant treatment sites.Results A total of 35 patients were included in this study,with 38 teeth affected by peri-implantitis and 154 treatment sites.The PDT group and MD group included 20 and 18 implants respectively,with a total of 78 treatment sites included in the PDT group,51 sites with PD≥6 mm,and 27 sites with PD＜6 mm.A total of 76 treatment sites were included in the MD group,including 53 sites with PD≥6 mm and 23 sites with PD＜6 mm.At baseline,there was no statistically significant difference in PD,mSBI,and mPLI between the two groups.At 6 and 12 weeks after treatment,there were statistically significant differences in clinical indicators between the two groups compared to baseline(P＜0.05).Among them,the mSBI in the PDT group was significantly lower than that in the MD group at 6 weeks after treatment(P＜0.05).At sites with PD≥6 mm,the mSBI of the PDT group was significantly lower than that of the MD group at 6 and 12 weeks after treatment(P＜0.05).The number of implants in the PDT group and MD group that reached the treatment endpoint at 12 weeks follow-up was 70.00%and 55.56%,respectively,and there was no difference between the two groups(P＞0.05).Conclusion Photodynamic therapy assisted with mechanical debridement can effectively treat peri-implantitis and is a safe and ef-fective auxiliary method,and has significant therapeutic effects on in-flammation control and improvement of mSBI in those sites with PD≥6 mm.

Alzheimer's disease(AD)is a severe threat to human health and one of the three major causes of human death.Double-stranded RNA-dependent protein kinase(PKR)is an interferon-induced protein kinase involved in innate immunity.In the occurrence and development of AD,PKR is upregulated and continu-ously activated.On the one hand,the activation of PKR triggers an integrated stress response in brain cells.On the other hand,it indirectly upregulates the expression of 3-site amyloid precursor protein cleaving enzyme 1 and facilitates the accumulation of amyloid-β protein(Aβ),which could activate PKR activator to further activate PKR,thus forming a sustained accumulation cycle of Aβ.In addition,PKR can promote Tau phosphorylation,thereby reducing microtubule stability in nerve cells.Inflammation in brain tissue,neurotoxicity resulted from Aβaccumulation,and disruption of microtubule stability led to the progression of AD and the declines of memory and cognitive function.Therefore,PKR is a key molecule in the development and progression of AD.Effective PKR detection can aid in the diagnosis and prediction of AD progression and provide opportunities for clinical treat-ment.The inhibitors targeting PKR are expected to control the activity of PKR,thereby controlling the progression of AD.Therefore,PKR could be a target for the development of therapeutic drugs for AD.

【Objective】 To investigate the relationship between ABO blood types and the risk of malignant tumors in Chaoshan area, Guangdong. 【Methods】 Chi-square test was used to analyze the distribution of ABO blood types between 45 890 patients with malignant tumors from the Cancer Hospital of Shantou University Medical College and 42 465 healthy blood donors from Shantou Central Blood Bank. 【Results】 Among the main types of malignant tumors, the distributions of ABO blood types in patients with esophageal cancer or head and neck cancer were significantly different from that in the normal population (χ²=11.16, P<0.05; χ²=74.36, P<0.05; respectively). People with type B were identified with high risk of esophageal cancer and head and neck cancer (OR=1.09, 95% CI=1.03-1.15, P<0.05; OR=1.46, 95% CI=1.34-1.60, P<0.05), whereas those with type A or O were identified with low risk of head and neck cancer (OR=0.87, 95% CI=0.79-0.96, P<0.05; OR=0.83, 95% CI=0.76-0.90, P<0.05). 【Conclusion】 ABO blood type distribution in patients with esophageal cancer or head and neck cancer in Chaoshan area may be different from that in normal population, suggesting that different ABO blood types may be associated with the risk of esophageal cancer and head and neck cancer.

Periodontology is one of the important disciplines in oral clinical medicine, which covers a wide range of subjects and intersects with many basic disciplines. Under the environment of the implementation of modular teaching in Shanghai Jiao Tong University School of Medicine, the assessment method with separate propositions for the teaching and research section is still adopted. There is a mismatch between the assessment mode and the curriculum setting; the basic subject propositions are difficult to be combined with clinical cases; the knowledge point assessment is single, and the students' ability to integrate the knowledge points cannot be assessed. The development and construction of the comprehensive examination database for periodontology was based on curriculum integration, gathering the teaching backbones of various disciplines, focusing on periodontology, radiating all related disciplines, unifying the proposition outline, proposition type, proposition principle, combining with relevant knowledge points of various disciplines based on clinical cases, and tried to apply to clinical students majoring in stomatology. The use of the examination database promotes students' ability to flexibly apply theoretical knowledge to clinical case analysis, further promotes the reform of modular teaching, lays a solid foundation for future clinical work, and meanwhile provides an important basis for directions of the teaching and research section.

Objective:To analyze the consistency and correlation between the Chinese Version of Swanson Nolan and Pelham, Version Ⅳ Scale (SNAP-Ⅳ) and the Integrated Visual and Auditory Continuous Performance Test (IVA-CPT) in the assessment of attention deficit hyperactivity disorder (ADHD), thus providing a reliable basis for the diagnosis of ADHD, and reducing the misdiagnosis rate and missed diagnosis rate.Methods:Clinical data of children to be diagnosed as ADHD in the Department of Children′s Rehabilitation, Yuying Children′s Hospital of the Second Affiliated Hospital of Wenzhou Medical University from October 2019 to July 2020 were collected.A total of 282 SNAP-Ⅳ and IVA-CPT profiles were collected, and the Kappa test and Pearson test were used to retrospectively analyzed for their consistency and correlation in the diagnosis of ADHD. Results:SNAP-Ⅳ and IVA-CPT were consistent in the diagnosis of ADHD (Kappa value=0.514, total coincidence rate=65.6%, P<0.000 1). Inattention subset scores of SNAP-Ⅳ were consistent with the assessment of ADHD by IVA-CPT (Kappa value=0.485, total coincidence rate=75.5%, P<0.000 1). Inattention subset scores of SNAP-Ⅳ were negatively correlated with the Full Scale Attention Quotient (FAQ) in IVA-CPT ( r=-0.71, P<0.000 1). Hyperactivity-impulsive subscale in the SNAP-Ⅳ and IVA-CPT were consistent in the assessment of hyperactivity-impulsive behavior (Kappa value=0.585, total coincidence rate=81.6%, P<0.000 1). Hyperactivity-impulse subset scores were negatively correlated with the Full Scale Response Control Quotient (FRCQ) in IVA-CPT ( r=-0.74, P<0.000 1). Conclusions:Both SNAP-Ⅳ and IVA-CPT have certain diagnostic potential of ADHD, showing good consistency and correlation.They can be both used to provide a more comprehensive diagnosis basis, thereby reducing the misdiagnosis rate and missed diagnosis rate of ADHD.

Objective:To explore the feasibility, accuracy and reproducibility of a novel, fully automated three-dimensional echocardiography right ventricular(RV) quantification software(3D Anto RV) to evaluate the RV volume and RV ejection fraction (RVEF) using artificial intelligence in patients after heart transplantation (HT) comparing with the gold reference-cardiac magnetic resonance (CMR).Methods:Forty-six patients after HT who were scheduled for echocardiogram at their routine follow-up examinations and also agreed to undergo CMR examination within the following 24 hours in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from October 2018 to June 2019 were prospectively included. The right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV), right ventricular stroke volume (RVSV) and RVEF of HT patients were measured by CMR 3D Auto RV and conventional semi-automated three-dimensional echocardiography RV quantification software (Tomtec 4D RV function 2.0). The results of the 3D Auto RV and conventional semi-automated Tomtec were respectively compared with CMR using paired two-tailed student′s t-tests, Pearson correlation coefficients and Bland-Altman analyses. Results:The feasibility of the 3D Auto RV was 87%.The fully automated analysis realized in 27 (59%) patients by 3D Auto RV and the analysis time required only (12±1)s. The results of the remaining 19 (41%) patients needed manual adjustment and the mean analysis time in manual adjustment was also <2 min that was shorter than the conventional semi-automated three-dimensional echocardiography RV quantification software[(108±15)s vs (160±34)s, P<0.001]. For the results of RV volumes: There were good correlations between the 3D Auto RV and CMR, conventional semi-automated Tomtec and CMR for the measurements of RVEDV, RVESV and RVSV ( r=0.77-0.84, all P<0.001). In addition, compared with CMR, although there were significantly underestimated RV volumes by the 3D Auto RV and conventional semi-automated Tomtec, the negative bias was smaller in the 3D Auto RV than the conventional semi-automated Tomtec. For the results of RVEF: the corresponding RVEF derived from 3D Auto RV and CMR showed an excellent correlation and consistency ( r=0.84, P<0.001; bias=-1.1%, Limit of agreement=-8.1%-6.0%). In addition, the correlations between the manual adjustment by 3D Auto RV and the CMR ( r=0.63-0.72, all P<0.001) was lower than the correlations between the 3D Auto RV and the CMR ( r=0.76-0.82, all P<0.001) for RV volumes and RVEF.Finally, 3D Auto RV had a good reproducibility. Conclusions:The new fully 3D Auto RV quantification software underestimate RV volumes that less than the conventional semi-automated Tomtec. And the 3D Auto RV quantification software can accurately evaluate the RVEF in patients after HT with rapid analysis and higher reproducibility, which may also support the routine adoption of this method during follow-ups of HT patients in the daily clinical workflow.