OBJECTIVES: Exposure to rare earth elements (REEs) has been linked to various systemic diseases, but their impact on the offspring blood-brain barrier (BBB) via the gut-brain axis remains unclear. This study aims to investigate the effects of maternal exposure to neodymium oxide (Nd₂O₃) on the BBB integrity of offspring rats, and to evaluate the potential protective role of bifidobacterium tetrad viable tablets (BTVT) against Nd₂O₃-induced intestinal and BBB damage. METHODS: Healthy adult SD rats were mated at a 1:1 male-to-female ratio, with the day of vaginal plug detection marked as gestational day 0. A total of 60 pregnant rats were randomly assigned to the following groups: Control, 50 mg/(kg·d) Nd₂O₃, 100 mg/(kg·d) Nd₂O₃, 200 mg/(kg·d) Nd₂O₃, and 200 mg/(kg·d) Nd₂O₃ + BTVT group. Treatments were administered by daily oral gavage throughout pregnancy and lactation. On postnatal day 21 (weaning), offspring feces, brain, and colon tissues were collected. Hematoxylin and eosin (HE) staining was used to assess structural changes in brain and intestinal tissues. Short-chain fatty acids (SCFAs) in feces were quantified by gas chromatography-mass spectrometry (GC-MS). Evans Blue (EB) dye extravasation assessed BBB permeability. Gene and protein expression levels of tight junction proteins occludin and zonula occludens-1 (ZO-1) were measured by reverse transcription PCR (RT-PCR) and Western blotting (WB), respectively. Neodymium levels in brain tissue were determined via inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: HE staining revealed that maternal Nd₂O₃ exposure caused mucosal edema, increased submucosal spacing, and lymphocyte infiltration in offspring colon, as well as neuronal degeneration and vacuolization in brain tissue. BTVT intervention alleviated these changes. GC-MS analysis showed that levels of acetic acid, propionic acid, butyric acid, and isobutyric acid significantly decreased, while valeric acid and isovaleric acid increased in offspring of Nd₂O₃-exposed mothers (P<0.05). BTVT significantly restored levels of acetic, propionic, and isobutyric acids and reduced valeric acid content (P<0.05). EB permeability was significantly elevated in Nd₂O₃-exposed offspring brains (P<0.05), but reduced with BTVT treatment (P<0.05). RT-PCR and WB showed downregulation of occludin and ZO-1 expression following Nd₂O₃ exposure (P<0.05), which was reversed by BTVT (P<0.05). ICP-MS results indicated significantly increased brain neodymium levels in offspring from all Nd₂O₃-exposed groups (P<0.05), while BTVT significantly reduced neodymium accumulation compared to the 200 mg/(kg·d) Nd₂O₃ group (P<0.05). CONCLUSIONS Maternal exposure to Nd₂O₃ during pregnancy and lactation disrupts intestinal health and BBB integrity in offspring, elevates brain neodymium accumulation, and induces neuronal degeneration. BTVT effectively mitigates Nd₂O₃-induced intestinal and BBB damage in offspring, potentially through modulation of the gut-brain axis.
Animals ; Female ; Blood-Brain Barrier/pathology* ; Pregnancy ; Rats, Sprague-Dawley ; Rats ; Male ; Neodymium/toxicity* ; Prenatal Exposure Delayed Effects/prevention & control* ; Lactation ; Maternal Exposure/adverse effects* ; Brain

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

In general, bioassay-guided fractionation and isolation of bioactive constituents from botanical materials frequently ended up with the reward of a single compound. However, botanical materials typically exert their therapeutic actions through multi-pathway effects due to the intrinsic complex nature of chemical constituents. In addition, the content of bioactive compounds in botanical materials is largely dependent on humidity, temperature, soil, especially geographical origins, from which rapid and accurate identification of plant materials is pressingly needed. These long-standing obstacles collectively impede the deep exploitation and application of these versatile natural sources. To address the challenges, a new paradigm integrating biogravimetric analyses and machine learning-driven origin classification (BAMLOC) was developed. The biogravimetric analyses are based on absolute qHNMR quantification and in vivo zebrafish model-assisted activity index calculation, by which bioactive substance groups jointly responsible for the bioactivities in all fractions are pinpointed before any isolation effort. To differentiate origin-different botanical materials varying in the content of bioactive substance groups, principal component analysis, linear discriminant analysis, and hierarchical cluster analysis in conjunction with supervised support vector machine are employed to classify and predict production areas based on the detection of volatile organic compounds by E-nose and GC-MS. Expanding BAMLOC to Codonopsis Radix enables the identification of polyacetylenes and pyrrolidine alkaloids as the bioactive substance group for immune restoration effect and accurately determines the origins of plants. This study advances the toolbox for the discovery of bioactive compounds from complex mixtures and lays a more definitive foundation for the in-depth utilization of botanical materials.

【Objective】 To explore the relationship of victimization, bullying tolerance and anxiety/depression in adolescents, and to examine the moderating effect of cognitive emotion regulation strategies on the relationship between bullying tolerance and anxiety/depression, in order to provide basis for intervention. 【Methods】 From January 2019 to July 2020, 1 768 adolescents were selected into this survey, and completed Bully/Victim Questionnaire, Primary and Secondary School Bullying Tolerance Questionnaire, Cognitive Emotion Regulation Questionnaire and the 28 General Health questionnaires. 【Results】 Adolescents′ victimization was relatively common and serious, the proportion of verbal bullying, relational bullying, and physical bullying was 57.64% (1 019/1 768), 36.60% (647/1 768), and 22.40% (396/1 768), respectirely. The scores of anxiety and depression of adolescents with different gender (t=2.00), school stage (F=101.38) and academic performance (F=27.91) were statistically significant (P<0.05).Victimization and bullying tolerance had predictive effect on adolescents′ anxiety/depression (β=0.14, 0.13, P<0.01).Positive strategies, negative strategies had significant moderating effects on the relationship between bullying tolerance and anxiety/depression(β=-0.10、0.08, P<0.01).The simple slope analysis showed that at high positive strategy level, bullying tolerance had no significant predictive effect on anxiety/depression (P>0.05), while at a low positive strategy level, bullying tolerance had significant predictive effect on anxiety/depression (β=0.28, P<0.01).At a high negative strategy level, bullying tolerance had a significant predictive effect on anxiety/depression (β=0.25, P<0.01), while at a low negative strategy level, bullying tolerance had no significant predictive effect on anxiety/depression (P>0.05). 【Conclusions】 Victimization and bullying tolerance positively predict adolescent anxiety/depression.High levels of positive and low levels of negative strategies effectively inhibit the risk of anxiety/depression, while low levels of positive and high levels of negative strategies amplify the risk of anxiety/depression.

Objective:To investigate the molecular mechanisms of chronic rhinosinusitis (CRS), to identify key cell subgroups and genes, to construct effective diagnostic models, and to screen for potential therapeutic drugs.Methods:Key cell subgroups in CRS were identified through single-cell transcriptomic sequencing data. Essential genes associated with CRS were selected and diagnostic models were constructed by hdWGCNA (high dimensional weighted gene co-expression network analysis) and various machine learning algorithms. Causal inference analysis was performed using Mendelian randomization and colocalization analysis. Potential therapeutic drugs were identified using molecular docking technology, and the results of bioinformatics analysis were validated by immunofluorescence staining. Graphpad Prism, R, Python, and Adobe Illustrator software were used for data and image processing.Results:An increased proportion of basal and suprabasal cells was observed in CRS, especially in eosinophilic CRS with nasal polyps (ECRSwNP), with P=0.001. hdWGCNA revealed that the "yellow module" was closely related to basal and suprabasal cells in CRS. Univariate logistic regression and LASSO algorithm selected 13 key genes ( CTSC, LAMB3, CYP2S1, TRPV4, ARHGAP21, PTHLH, CDH26, MRPS6, TENM4, FAM110C, NCKAP5, SAMD3, and PTCHD4). Based on these 13 genes, an effective CRS diagnostic model was developed using various machine learning algorithms (AUC=0.958). Mendelian randomization analysis indicated a causal relationship between CTSC and CRS (inverse variance weighted: OR=1.06, P=0.006), and colocalization analysis confirmed shared genetic variants between CTSC and CRS (PPH4/PPH3>2). Molecular docking results showed that acetaminophen binded well with CTSC (binding energy:-5.638 kcal/mol). Immunofluorescence staining experiments indicated an increase in CTSC +cells in CRS. Conclusion:This study integrates various bioinformatics methods to identify key cell types and genes in CRS, constructs an effective diagnostic model, underscores the critical role of the CTSC gene in CRS pathogenesis, and provides new targets for the treatment of CRS.

A retrospective study was conducted on data of 23 patients with pancreatic duct diseases who were underwent peroral pancreatoscopy (POPS) at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from August 2020 to October 2022. The intraoperative observation, postoperative complications, and the diagnosis and treatment of POPS for pancreatic duct diseases were analyzed. All patients underwent POPS and achieved technical success. Among them, 7 patients were diagnosed as having intraductal papillary mucinous neoplasm of pancreas and 3 pancreatic malignant tumor. Eight patients with pancreatolithiasis accepted laser or eletrohydraulic lithotripsy under POPS. Abdominal pain improved in 2 patients with chronic pancreatitis after treatment. Melena disappeared in 2 patients with pancreatic duct hemorrhage or pancreatic enterostomy inflammation after conservative treatment. The symptom of 1 patient with pancreatic enterostomy stenosis improved after balloon dilation. There was no complication in the 23 patients, and the operation time was 35-90 min. The results indicate POPS is safe, effective with distinctive advantages in the diagnosis and treatment for pancreatic duct diseases.

Objective:To evaluate the effect of verbascoside on cold ischemia-reperfusion injury following heterotopic heart transplantation in mice and the relationship with nuclear factor kappa B (NF-κB)/nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) signaling pathway.Methods:This experiment was performed in two parts. Part Ⅰ animal experiment Eighteen SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 24-28 g, were divided into 3 groups ( n=6 each) by the random number table method: control group (C group), cold ischemia-reperfusion (I/R) group (I/R group) and cold I/R + verbascoside group (I/R+ VB group). Cold I/R injury model of mouse heart transplantation was prepared by neck heterotopic heart transplantation using the modified non-suture cuff technique. The donor heart in group C was immediately transplanted to the recipient after removal, while the donor heart in group I/R was stored in the 4 ℃ University of Wisconsin solution for 8 h before transplantation to the recipient, and verbascoside 20 mg/kg was intraperitoneally injected at 3 days before surgery in donor and recipient mice in I/R+ VB group. At the end of reperfusion, the myocardial tissue of the transplanted heart was obtained after assessing the beating score for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity by enzyme-linked immunosorbent assay. Part of the donor myocardium was taken for examination of the pathological results. The expression of NF-κB, p-NF-κB, NOD-like receptor protein 3 (NLRP3), ACS and caspase-1 was detected by Western blot. The expression of IL-1β, TNF-α and IL-6 mRNA was detected by real-time polymerase chain reaction. Part Ⅱ cell experiment Rat cardiomyocyte H9c2 cold hypoxia-reoxygenation model was developed, and the cells were divided into 3 groups ( n=24 each) by the random number table method: control group (C group), cold hypoxia-reoxygenation group (H/R group), and cold hypoxia-reoxygenation+ verbascoside group (H/R+ VB group). The cells were exposed to hypoxia for 18 h at 10 ℃ followed by restoration of reoxygenation for 24 h at 37 ℃ to develop the cold hypoxia-reoxygenation model. The cell viability and LDH activity were determined. The expression of NF-κB and NLRP3 was detected by Western blot, and the expression of phosphorylated NF-κB (p-NF-κB) was detected by immunofluorescence staining. Results:Part Ⅰanimal experiment Compared with C group, the MDA content was significantly increased, the beating score of grafts and SOD activity were decreased, and the expression of p-NF-κB, NLRP3, ACS and caspase-1 and IL-1β, TNF-α and IL-6 mRNA was up-regulated ( P<0.05), and myocardial histopathological injury was aggravated in I/R group. Compared with I/R group, the content of MDA was significantly decreased, the beating score of grafts and SOD activity were increased, the expression of p-NF-κB, NLRP3, ACS and caspase-1 and IL-1β, TNF-α and IL-6 mRNA was down-regulated ( P<0.05), and the myocardial histopathological injury was alleviated in I/R+ VB group. Part Ⅱ cell experiment Compared with C group, the cell viability was significantly decreased, the activity of LDH was increased, and the expression of p-NF-κB, NLRP3, ACS, caspase-1 and p-NF-κB was up-regulated in H/R group ( P<0.05). Compared with H/R group, the cell viability was significantly increased, the activity of LDH was decreased, and the expression of p-NF-κB, NLRP3, ACS, caspase-1 and p-NF-κB was down-regulated in H/R+ VB group ( P<0.05). Conclusions:Verbascoside can alleviate cold I/R injury following heterotopic heart transplantation in mice, and the mechanism may be related to inhibition of activation of NF-κB/NLRP3 signaling pathway.

Objective:To evaluate the role of histone deacetylase 3 (HDAC3) in high glucose hypoxia/reoxygenation (H/R) injury to primary rat cardiomyocytes and the relationship with autophagy.Methods:The primary cardiomyocytes extracted from newborn Sprague-Dawley rats, aged about 1-3 days, were divided into 5 groups ( n=24 each) according to the random number table method: control group (C group, glucose concentration 5.5 mmol/L), H/R group, high glucose group (H group, glucose concentration 30 mmol/L), high glucose H/R group (HH/R group), and high glucose H/R + HDAC3 inhibitor RGFP966 group (HH/R+ RG group). Fifty percent glucose injection was used to prepare high-glucose medium (final concentration 30 mmol/L). Cells were cultured in a hypoxic environment (5% CO 2-0.9% O 2-94.1% N 2) for 6 h, followed by reoxygenation in a normoxic environment for 2 h to establish the cardiomyocyte H/R model in H/R group.RGFP966 at a final concentration of 10 μmol/L was added at 24 h before H/R in HH/R+ RG group.At 2 h of reoxygenation, the cell viability was measured using CCK-8 kit, the activity of lactic dehydrogenase (LDH) in the cell supernatant was determined using enzyme-linked immunosorbent assay, the level of autophagy was detected with a confocal microscope after cells were transfected with autophagy double-labeled adenovirus (mRFP-GFP-LC3), and the expression of HDAC3, p62, LC3 Ⅱ and LC3 Ⅰ was detected using Western blot.LC3Ⅱ/LC3Ⅰ ratio was calculated. Results:Compared with group C, the cell viability was significantly decreased, and the activity of LDH in supernatant was increased in H/R and H groups, the number of autophagosomes was significantly increased, the expression of HDAC3 in cardiomyocytes was up-regulated, the expression of p62 was down-regulated, and the LC3 Ⅱ/I ratio was increased in group H/R, and the number of autophagosomes was significantly decreased, the expression of HDAC3 and p62 in cardiomyocytes was up-regulated, and the LC3 Ⅱ/I ratio was decreased in group H ( P<0.05). Compared with group H/R, the cell viability was significantly decreased, the activity of LDH in supernatant was increased, the number of autophagosomes was decreased, the expression of HDAC3 and p62 in cardiomyocytes was up-regulated, and the LC3 Ⅱ/I ratio was decreased in group HH/R ( P<0.05). Compared with group H, the cell viability was significantly decreased, the activity of LDH in supernatant was increased, the number of autophagosomes was increased, the expression of HDAC3 and p62 in cardiomyocytes was up-regulated, and the LC3 Ⅱ/I ratio was increased in group HH/R ( P<0.05). Compared with group HH/R, the cell viability was significantly increased, the activity of LDH in supernatant was decreased, the number of autophagosomes was increased, the expression of HDAC3 and p62 in cardiomyocytes was down-regulated, and the LC3 Ⅱ/I ratio was increased in group HH/R+ RG ( P<0.05). Conclusion:Up-regulation of HDAC3 expression is involved in high glucose H/R injury to primary rat cardiomyocytes, which is related to decreasing the level of autophagy.

Objective:To explore overall survival(OS) and prognostic factors of brainstem gliomas (BSG) after intensity modulated radiotherapy (IMRT) by a retrospective single-center analysis.Methods:A total of twenty-one patients with BSG were collected in the Department of Radiation Oncology, Peking University Cancer Hospital from January 2012 to September 2019. All patients underwent IMRT. OS and potential prognostic factors were analyzed, including gender, age, operation type, imaging classification, tumor location, WHO grade, chemotherapy, radiotherapy pattern, time interval between morbidity and the first treatment, and radiation dose.Results:Eighteen of twenty-one patients were followed up more than 3 months. The median follow-up time was 15.5 (5.3-25.6) months. The median overall survival (mOS) was 20 (14.1-25.8) months. The 1 and 2-year OS rates were 86.2% and 34.5% respectively. Operation type, imaging classification, tumor location, WHO grade and radiotherapy pattern were the prognosis factors ( χ2=4.829-20.261, P<0.05). Conclusions:Patients with maximal safe surgical resection, focal endogenesis / exogenesis, tumor located in mesencephalon, low-grade gliomas and/or received postoperative radiotherapy have a better prognosis. It has certain reference value for guiding the clinical practice.

Objective To evaluate the effect of tyrosol on myocardial ischemia-reperfusion (I/R) injury in diabetic rats and the role of silent mating-type information regulation 1 (SIRT1)/adenosine monophosphate-activated protein kinase (AMPK)/endothelial nitric oxide synthase (eNOS) signaling pathway.Methods SPF healthy adult male Sprague-Dawley rats,weighing 200-220 g,were intraperitoneally injected with streptozotocin 60 mg/kg to establish the model of diabetes mellitus.Fifty-six diabetic rats were divided into 4 groups (n =14 each) using a random number table method:sham operation group (S group),myocardial I/R group (I/R group),myocardial I/R plus tyrosol group (I/R+T group),and myocardial I/R plus tyrosol plus SIRT1 inhibitor EX527 group (I/R+T+E group).In I/R+T and I/R+T+E groups,tyrosol 20 mg · kg-1 · d-1 was given by gavage for 45 consecutive days,and the equal volume of normal saline was given in the other two groups.In I/R+T+E group,EX527 5 mg · kg-1 · d-1 was intraperitoneally injected for 3 consecutive days before ischemia,and EX527 5 mg/kg was intraperitoneally injected at 20 min before repeffusion.Myocardial I/R was induced by ligation of the left anterior descending branch of coronary artery for 30 min followed by 2-h reperfusion.The myocardial infarct volume was measured by TTC staining.The levels of creatine kinase-MB (CK-MB),lactic dehydrogenase (LDH) and 5-F2t-isoprostane in serum and superoxide dismutase (SOD) in myocardial tissues were detected by enzyme-linked immunosorbent assay.The expression of SIRT1,AMPK,phosphorylated AMPK (p-AMPK),eNOS and p-eNOS was detected by Western blot.Results Compared with S group,the levels of serum CK-MB,LDH and 15-F2t-Isoprostane and myocardial infarction volume were significantly increased,the SOD activity was decreased,and the SIRT1 expression was down-regulated in I/R group,and the levels of serum CKMB,LDH and 15-F2t-Isoprostane and myocardial infarction volume were significantly increased,the SOD activity was decreased,the SIRT1 expression was down-regulated,and the expression of p-AMPK and peNOS was up-regulated in I/R+T and I/R+T+E groups (P＜0.05).Compared with I/R group,the levels of serum CK-MB,LDH and 15-F2t-Isoprostane and myocardial infarction volume were significantly decreased,the SOD activity was increased,and the expression of SIRT1,p-AMPK and p-eNOS was up-regulated in I/R+T group (P＜0.05),and no significant change was found in the parameters mentioned above in I/R+ T+E group (P＞0.05).Compared with I/R+T group,the levels of CK-MB,LDH and 15-F2t-isoprostane in serum and myocardial infarct volume were significantly increased,the SOD activity was increased,and the expression of SIRT1,p-AMPK and p-eNOS was down-regulated in I/R+T+E group (P＜0.05).Conclusion Tyrosol can mitigate myocardial I/R injury,and the mechanism may be related to activating SIRT1/AMPK/eNOS signaling pathway and inhibiting oxidative stress response in diabetic rats.