ObjectiveTo explore the mechanism by which Buyang Huanwutang regulates the glutathione peroxidase 4 （GPX4）-acyl-CoA synthetase long-chain family member 4 （ACSL4） axis to inhibit ferroptosis and promote neurological functional recovery after spinal cord injury （SCI）. MethodsNinety rats were randomly divided into five groups： sham operation group， model group， low-dose Buyang Huanwutang group （12.5 g·kg^-1）， high-dose Buyang Huanwutang group （25 g·kg^-1）， and Buyang Huanwutang + inhibitor group （25 g·kg^-1 + 5 g·kg^-1 RSL3）. The SCI model was established by using the allen method. Tissue was collected on the 7th and 28th days after operation. Motor function was assessed by using the Basso-Beattie-Bresnahan （BBB） scale. Hematoxylin-eosin （HE）， Nissl， and Luxol fast blue （LFB） staining were performed to observe spinal cord histopathology. Transmission electron microscopy was used to examine mitochondrial ultrastructure. Immunofluorescence staining was used to detect the number of NeuN-positive cells and the fluorescence intensity of myelin basic protein （MBP）， GPX4， and ACSL4. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） was used to analyze the mRNA expression of GPX4 and ACSL4. Enzyme linked immunosorbent assay （ELISA） was performed to measure the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD）. Colorimetric assays were used to determine the iron content in spinal cord tissue. ResultsCompared to the sham operation group， the model group exhibited significantly reduced BBB scores （P<0.01）， severe pathological damage in spinal cord tissue， and marked mitochondrial ultrastructural disruption. In addition， the model group showed a decrease in the number of NeuN-positive cells （P<0.01）， reduced fluorescence intensity of MBP and GPX4 （P<0.01）， lower levels of GSH and SOD （P<0.01）， and downregulated mRNA expression of GPX4 （P<0.01）. Moreover， compared to the sham operation group， the model group had elevated levels of ROS， MDA， and tissue iron content （P<0.01）， along with increased fluorescence intensity and mRNA expression of ACSL4 （P<0.01）. Compared with the model group and Buyang Huanwutang + inhibitor group， the Buyang Huanwutang group showed significantly improved BBB scores （P<0.05， P<0.01） and exhibited less severe spinal cord tissue damage， reduced edema and inflammatory cell infiltration， increased neuronal survival， and more intact myelin structures. Additionally， mitochondrial ultrastructure was significantly improved in the Buyang Huanwutang group. Compared to the model group and Buyang Huanwutang + inhibitor group， the Buyang Huanwutang group significantly increased the number of NeuN-positive cells and the fluorescence intensity of MBP （P<0.05， P<0.01）. Furthermore， Buyang Huanwutang significantly increased the fluorescence intensity and mRNA expression of GPX4 （P<0.01） and decreased the fluorescence intensity and mRNA expression of ACSL4 （P<0.01） compared to the model group and Buyang Huanwutang + inhibitor group. Finally， the Buyang Huanwutang group significantly decreased ROS， MDA， and tissue iron content （P<0.01） and significantly increased GSH and SOD levels （P<0.01） compared to the model group and Buyang Huanwutang + inhibitor group. ConclusionBuyang Huanwutang inhibits ferroptosis through the GPX4/ACSL4 axis， reduces secondary neuronal and myelin injury and oxidative stress， and ultimately promotes the recovery of neurological function.

Palliative care is a way to help end-of-life populations improve their quality of life， and its development in practice cannot be separated from the level of education in palliative care. At present， some medical schools in palliative care education compared with western developed countries have problems such as imperfect construction of hospice curriculum system， lack of medical students’ hospice knowledge； insufficient interdisciplinary teaching faculty， weak palliative care awareness of medical students； single teaching evaluation mode； weak palliative care practice teaching links. To this end， it is necessary to improve the palliative care curriculum system， explore rich and diverse teaching methods； strengthen interdisciplinary teaching and faculty development， enhancing the awareness of palliative care among medical students；establish a scientific and effective evaluation method， carry out multi-dimensional dynamic assessment； expand the palliative care practice teaching base， and accurately improve the practical skills of medical students in palliative care， and other countermeasures to improve the level of palliative care education， and to help the strategy of Healthy China.

Volatile organic compounds (VOCs) and semi-volatile organic compounds (SVOCs) are common organic compounds in indoor and outdoor air, and enter the human body primarily through the respiratory tract and directly damage the respiratory system. Previous studies have suggested that exposure to VOCs/SVOCs may associate with the prevalence, incidence, and progression of asthma, but the extent of the associations is still vague. Furthermore, biomarkers for efficient and simple asthma diagnosis, typing, and attack prediction remain unclear at this stage. From the perspective of the collection and detection methods of VOCs/SVOCs, this paper summarized the epidemiological associations and underlying biological mechanisms between VOCs/SVOCs exposure and the prevalence, incidence, and progression of asthma in children/adults. It also demonstrated the application of VOCs/SVOCs in recent years in assisting asthma diagnosis, such as distinguishing asthma patients from the healthy population, differentiating different asthma phenotypes, and predicting asthma acute exacerbations, aiming to provide a scientific basis for improving current asthma management.

To analyze the clinical characteristics of acute diquat poisoning complicated by central nervous system injury (CNSI) and identify early risk factors, aiming to provide a theoretical basis for reducing mortality in diquat poisoning with CNSI.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

The persistent high prevalence and poor survival outcomes of lung cancer underscore the urgent need for innovative therapeutic modalities. Here, we present a novel multifunctional delivery platform for the synergistic treatment of lung malignancies, combining in situ-triggerable photodynamic therapy (PDT) with radiotherapy. The new platform CLL was developed by loading a new reactive oxygen species (ROS)-triggerable photosensitizer, luminol-conjugated chlorin e6 (Ce6), into liposomes. CLL can be activated through the bioluminescence resonance energy transfer effect under oxidative stress, thereby producing singlet oxygen for targeted tumor treatment without external irradiation. In vitro studies showed significant cytotoxic effects of CLL in both 4T1 and A549 tumor cells. Furthermore, a PDT-radiopharmaceutical combination nanotherapy CLL-¹⁷⁷Lu was engineered by incorporating the radionuclide ¹⁷⁷Lu into CLL. CLL-¹⁷⁷Lu demonstrated synergistic antitumor effects in 4T1 and A549 tumor cells, as well as in mouse models of 4T1 breast cancer lung metastasis or A549 tumor xenografts. Mechanistically, CLL-¹⁷⁷Lu can induce singlet oxygen/ROS generation, enhance tumor cell apoptosis, and promote M1 macrophage-mediated immunotherapy. Preliminary assessments showed a favorable profile for CLL-¹⁷⁷Lu, highlighting its potential as a promising nanotherapy for cancer treatment. Additionally, CLL can serve as a versatile platform for delivering a range of therapies to achieve synergistic antitumor effects.

Allergic conjunctivitis is a common ocular surface condition. Although corticosteroids are potent anti-inflammatory agents for its management, their use is often restricted by potential side effects. Conventional eye drops face challenges such as short retention time and poor corneal permeability, resulting in low drug bioavailability. To overcome these limitations, we developed a preservative-free synthetic high-density lipoprotein (sHDL) nanodisc eye drop containing dexamethasone palmitate. This novel formulation enhances drug stability and extends retention time on the ocular surface. In a mouse model of ovalbumin (OVA)-induced allergic conjunctivitis, the nanodisc eye drop significantly alleviated symptoms while reducing corticosteroid concentration, demonstrating excellent safety and biocompatibility. This innovative approach shows great promise for the treatment of allergic conjunctivitis and may lay the groundwork for new therapeutic strategies in anterior ocular disease management.

The gradual acceleration of the aging population in China has led to an increased demand for mobility aids,and the reliability of domestic wheeled walking-aid is one of their important attributes,but there is little research on the reliability of mobility aids.This paper conducts the failure mode,effects and criticality analysis on domestic wheeled walking-aid.By collecting,collating and analyzing the 26 failure modes,the key modules are the chassis and the lifting system.The key modules are obtained,and the failure data is analyzed to find out that the lifetime distribution model is log-normal and the 0.95 lower confidence limit for reliability life of product t0.9 is 2489.4 hours.The study aims to provide ideas for the reliability analysis of other active medical devices and calls for the formation of a reliability study review point for the industry that meets the requirements of Chinese medical device regulations.

Objective To identify the pathogenic bacteria such as Staphylococcus aureus and Enterococcus faecalis in bloodstream infec-tions with high confidence based on three deep learning models such as GoogleNet,ResNet101,and Vgg19,compare the performance and classification ability of these models,and explore the feasibility of applying the deep learning models for the rapid identification of pathogenic bacteria in bloodstream infections.Methods The preprocessed Gram-stained bacterial images,including 1 682 images for Staphylococcus aureus and 1 723 for Enterococcus faecalis,and 688 blank control microscopic images were input into three models for training and validation,respectively.Among them,1 344 images for Staphylococcus aureus,1 376 for Enterococcus faecalis,and 544 blank control images were used for training,and the remaining images were used for validation.The model with the best performance was identified according to the classification parameters between the models.Results The ResNet101 model had the lowest cross-en-tropy loss value(0.008 710 3),the largest Epoch value(93),and the highest accuracy rate(99％)for identifying the three types of validation set images.The cross-entropy loss value,Epoch value,and accuracy rate of the GoogleNet model were 0.063 89,86 and 98.6％,respectively,for identifying the three types of validation set images.Those of the Vgg19 model were 0.035 682,86 and 97.7％,respectively.Conclusion The ResNet101 model has the best performance in the classification of three kinds of images.The deep learning model may accurately,reliably and rapidly identify the Gram-stained images of pathogenic bacteria such as Staphylococcus aureus and Enterococcus faecalis in bloodstream infections.