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

Objective:This study aimed to evaluate the efficacy and safety of lenalidomide combined with bortezomib and dexamethasone (VRD) in the treatment of newly diagnosed multiple myeloma (MM) .Methods:A total of 150 newly diagnosed patients with MM diagnosed in The First Affiliated Hospital of Soochow University from November 2018 to February 2021 and received VRD as the induction regimen were included to evaluate the safety and efficacy of VRD induction therapy for newly diagnosed MM.Results:The median follow-up was 22 months, two patients (1.3%) died early after treatment, and 148 patients (98.7%) completed induction therapy. 116 patients (77.3%) were mobilized to collect autologous hematopoietic stem cells, 101 cases (87.1%) were qualified in the collection, of which 48 cases (41.4%) were excellent in the collection. The 3-year progression-free survival (PFS) rate was 59%, and the 3-year overall survival (OS) rate was 83%. After induction, complete remission (CR) /stringent CR rate was 54.4%, ≥ very good partial remission rate was 77.3%, overall response rate was 86.0%, and minimal residual disease negative rate was 46.0%. There was no statistically significant difference in the efficacy of cytogenetic high-risk patients compared with standard risk patients ( P=0.456) . The median PFS time of cytogenetic high-risk patients was shorter than that of standard risk patients (not reached vs 33 months, P=0.014) . There was no statistically significant difference in the median OS time (not reached vs not reached, P=0.072) . The highest incidence of hematological adverse events was thrombocytopenia (72%) , followed by neutropenia (42%) and anemia (20%) . The highest incidence of non-hematological adverse events was peripheral neuritis (56.7%) . The main digestive tract symptoms include constipation (30.0%) and diarrhea (17.3%) . Upper respiratory tract infection (23.3%) and lung infection (7.3%) are the main infections. The incidence of adverse thrombocytopenia (90.0% vs 63.7%, P=0.001) , neutropenia (54.2% vs 36.3%, P=0.038) , anemia (33.3% vs 13.7%, P=0.005) , diarrhea (27.1% vs 12.7%, P=0.030) , limb edema (20.8% vs 3.9%, P=0.030) , fever (20.8% vs 4.9%, P=0.006) , thrombosis (8.3% vs 0, P=0.016) , and renal function deterioration (20.8% vs 3.9%, P=0.030) in patients with renal insufficiency was higher than that in patients with normal renal function. Conclusion:The VRD regimen has a significant effect on newly diagnosed MM, does not affect the hematopoietic stem cell collection, and has controllable adverse events; however, the incidence of adverse events was higher in patients with renal insufficiency.

Objective To observe the incidence and clinical feature of sleep-related breathing disorder in patients with idiopathic pulmonary fibrosis (IPF). Methods Thirty-four IPF patients who were measured by polysomnography (PSG) were collected in the Department of Respiration of Tianjin Medical University General Hospital. According to the results of apnea hypoventilation index (AHI), patients were divided into pure IPF group (AHI<5 events/h, n=7) and IPF combined with obstructive sleep apnea hypopnea syndrome (IPF+OSAHS) group (AHI≥5 events/h, n=27). The PSG reports of two groups were analyzed, and the correlation between AHI and pulmonary function and oxygen saturation in sleep and at wake were analyzed. Results (1)Thirty-four IPF patients were all demonstrated sleep disorders, low sleep efficiency, increased proportion of stageⅠand stageⅡand decreased proportion of stageⅢand rapid eye movement (REM). The arousal index and the proportion of stageⅠand stageⅡwere higher in IPF+OSAHS group than those of pure IPF group (P<0.01), while the proportion of stageⅢwas lower in IPF+OSAHS group than that of pure IPF group (P<0.01). There was no significant difference in stage REM between two groups. (2)Twenty-seven patients (79%) combined with OSAHS, among which five subjects (15%) were mild OSAHS with 5 events/h≤AHI<15 events/h, and 22 subjects (65%) were moderate-severe with AHI≥15 events/h. The main type of sleep-disorder breathing was hypoventilation, which mainly happened in stage REM. (3) Thirty-four IPF patients showed sleep hypoxemia, and the oxygen desaturation index (ODI) was higher in IPF-OSAHS group than those of pure IPF group (P<0.05). (4)The AHI was positively correlated with body mass index (r=0.791, P<0.05), and was negatively correlated with forced vital capacity (FVC%pred) (r=-0.574, P<0.05) and forced expiratory volume in 1 second (FEV1%pred) in IPF patients (r=-0.664, P<0.05). The lowest oxygen saturation (LSO2) and mean oxygen saturation (MSO2) in sleep were positively related with oxygen saturation at wake (r=0.421 and r=0.464, P<0.05 respectively). Conclusion The IPF patients show severe sleep disorder and hypoxemia, which can be worsen by OSAHS and produce negative effect on daily life. We should initiate active treatment in patients with sleep-related breathing disorders.