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.

Objective:To analyze the clinical and prognostic characteristics of patients with immune checkpoint inhibitor (ICI) -related colitis.Methods:A retrospective observational research method was conducted. Clinical data from patients diagnosed with ICI-related colitis at Beijing Friendship Hospital between January 2016 and May 2024 were collected. Clinical severity was assessed using the common terminology criteria for adverse event (CTCAE) grading, Mayo Score, Truelove & Witts Score, and endoscopic severity was assessed using Mayo endoscopic score (MES), ulcerative colitis endoscopic index of severity (UCEIS), and MD Anderson Cancer Center endoscopic inflammation grading (MD grading). Spearman rank correlation analysis was performed to evaluate the correlation between different scoring systems.Results:A total of 15 patients were included, with 10 males and 5 females, and the median age was 64.0 (55.5, 71.0) years. Thirteen patients were treated with programmed cell death protein 1 (PD-1) monoclonal antibodies, and 2 patients were treated with programmed cell death-ligand 1 (PD-L1) monoclonal antibodies. The median onset time of the 15 patients was 66.5 (41.0, 168.0) days after ICI treatment. All patients had diarrhea, only 25% patients presented with abdominal pain, and 20%-33% patients had fever, abdominal distension, nausea, and vomiting. Most of the inflammatory indicators were non-specific. Among the 14 patients who underwent CT examinations, 2 patients had no abnormal manifestations, 10 patients had left colon involvement, mainly manifested as thickening of the colon wall, and 6 of these patients had full-thickness involvement. Among the 12 patients who underwent colonoscopy examination, except for one patient with no abnormalities, 11 patients had rectal and sigmoid colon involvement, the proportions of the descending colon, ascending colon, and terminal ileum involvement decreased successively, and the involved mucosa was mainly manifested as disappearance of vascular texture, mucosal congestion and edema, erosion to shallow ulcers, and lumen stenosis. The lesions in 5 patients were distributed continuously similar to ulcerative colitis, and the lesions in 6 patients were distributed segmentally, 1 of them had an isolated deep ulcer in the rectum under endoscopy. Correlation analysis revealed significant correlations between endoscopic scores (MES, UCEIS, and MD grading; all P < 0.001). Truelove & Witts score strongly correlated with the Mayo score ( ρ = 0.88, P < 0.001). Among clinical-endoscopic comparisons, the Mayo score exhibited the strong positive correlation with endoscopic scores (all P < 0.05), followed by the Truelove & Witts score (all P < 0.05), and CTCAE diarrhea grading only had positive correlation with MD grading ( P = 0.034). However, CTCAE colitis grading showed no significant correlation with endoscopic scores (all P > 0.05). During a mean follow-up of 13.5 months, 10 patients received corticosteroid therapy, and 5 received alternative treatments. Corticosteroid-treated patients showed favorable clinical responses, and rapid tapering feasible occurred in parts of mild-to-moderate patients without relapse. However, perforation occurred in 2 patients with small bowel involvement. Conclusions:The main clinical manifestations of patients with ICI-related colitis are diarrhea. Imaging studies suggest thickening of the colonic wall. Endoscopic findings show the highest involvement in the left colon. Truelove&Witts score and Mayo score is strongly correlated. Corticosteroid therapy exhibits a rapid response, and the prognosis of patients with small intestine involvement is poor.

Shewanella oneidensis MR-1, a Gram-negative bacterium with a significant role in the adsorption and reduction of uranium in wastewater and a quorum-sensing effect, can be used to remove uranium from wastewater. Exogenous signaling molecules (acyl-homoserine lactones, AHLs) can be added to induce the quorum sensing behavior for rapid biofilm formation, thereby improving the removal efficiency of this bacterium for uranium. Extracellular polymeric substances (EPS), as the significant components of biofilm, play a key role in biofilm formation. To investigate the quorum sensing behavior induced by AHLs, we systematically investigated the effects of AHLs on the EPS secretion and biofilm properties of S. oneidensis MR-1 by regulating parameters such as AHL species, concentration, addition time point, and contact time. The results showed that the addition of 10 μmol/L N-butyryl-l-homoserine lactone (C4-HSL) after 6 h of culture and continued incubation to reach the time point of 72 h significantly promoted the secretion of EPSs, in which the content of extracellular proteins and extracellular polysaccharides was increased by 15.2% and 28.2%, respectively, compared with that of the control group. The biofilm electrodes induced by signaling molecules showed superior properties, which were evidenced by an increase of exceeding 20 μm in biofilm thickness, an increase of 33.9% in the proportion of living cells, enhanced electroactivity, and an increase of 10.7% in the uranium removal rate. The biofilm electrode was confirmed to immobilize uranium in wastewater mainly by electrosorption, physicochemical adsorption, and electro-reduction through characterization means such as X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). This study provides a new technical idea for the efficient recovery of uranium in wastewater and enriches the theoretical system of quorum sensing regulation of electroactive biofilms.
Biofilms/drug effects* ; Acyl-Butyrolactones/pharmacology* ; Quorum Sensing/drug effects* ; Uranium/metabolism* ; Shewanella/metabolism* ; Adsorption ; Uranium Compounds/metabolism* ; Wastewater/chemistry* ; Biodegradation, Environmental ; Extracellular Polymeric Substance Matrix/metabolism*

Objective To clarify the demographic characteristics,disease spectrum,and related mortali-ty risks of intensive care unit(ICU)patients,in order to better manage ICU patients.Methods A total of 35 294 ICU patients admitted to West China Hospital from July 1,2010 to July 31,2020 were selected as the research subjects,and their demographic characteristics,disease spectrum,and mortality risk were analyzed.Results The median age of the patients was 55.5(42.5,67.5)years old,of which 62.5%were male.The top five disease groups are tumors(C00-D48,13 524 cases,accounting for 38.3%),digestive system diseases(K00-K93,6 469 cases,accounting for 18.3%),injuries,poisoning,and consequences caused by certain exter-nal reasons(S00-T98,3 810 cases,accounting for 10.8%),circulatory system diseases(I00-I99,3 745 cases,accounting for 10.6%),and respiratory system diseases(J00-J99,3 443 cases,accounting for 9.8%).These five types of diseases account for a total of 87.8%of ICU admissions.The mortality rate of patients was 7.5%(2 663/35 294),and the risk of death for male patients was about 21.0%higher than that for female patients.Patients with respiratory diseases had a higher risk of death than those with other diseases.Conclusion The increasing number of cancer patients and high mortality rate in ICU pose challenges to personalized manage-ment of critically ill cancer patients.

Zebrafish larvae are useful for identifying chemicals against lateral line (LL) hair cell (HC) damage and this type of chemical screen mainly focuses on searching for protectors against cell death. To expand the candidate pool of HC protectors, a self-built acoustic escape response (AER)-detecting system was developed to apply both low-frequency near-field sound transmission and AER image acquisition/processing modules. The device quickly confirmed the changed LL HC functions caused by most known ototoxins, protectors, and neural transmission modifiers, or knockdown of LL HC-expressing genes. With ten devices wired in tandem, five 'hit' chemicals were identified from 124 cyclin-dependent kinase inhibitors to partially restore cisplatin-damaged AER in less than a day. AS2863619, ribociclib, and SU9516 among the hits, protected the HCs in the mouse cochlea. Therefore, using free-swimming larval zebrafish, the self-made AER-detecting device can efficiently identify compounds that are protective against HC damage, including cell death and loss-of-function.
Animals ; Zebrafish ; Hair Cells, Auditory/physiology* ; Lateral Line System/cytology* ; Escape Reaction/physiology* ; Larva ; Mice ; Cisplatin/toxicity* ; Drug Evaluation, Preclinical/methods*

Objective To explore the role of ocular vestibular evoked myogenic potential (oVEMP) and unilateral centrifugation subjective visual vertical (UC-SVV) tests in evaluating the utricular function of patients with Meniere’s disease (MD) at different clinical stages. Methods A total of 97 unilateral MD patients at Shandong Provincial ENT Hospital from July 2019 to September 2021 were selected. All patients underwent oVEMP, UC-SVV, and pure tone audiometry tests. MD patients were classified into clinical stages 1, 2, 3, and 4, with stages 1 and 2 defined as early stage and stages 3 and 4 as late stage. The results of utricular function tests (abnormal rates of oVEMP, UC-SVV, and oVEMP＋UC-SVV) were compared among patients at different stages. Spearman correlation analysis was used to evaluate the correlation between utricular function and clinical staging. Results Among the 97 MD patients, the abnormal rate of oVEMP was 66.0% (64/97), and the abnormal rate of UC-SVV was 55.7% (54/97). The abnormal rates of oVEMP and oVEMP＋UC-SVV in early-stage patients were significantly lower than those in late-stage patients (P＜0.05), while the difference in UC-SVV abnormal rates between the two groups was not statistically significant. Intra-group comparisons showed that the abnormal rate of oVEMP＋UC-SVV in stage 1 patients was significantly lower than that in stage 2 patients (P＜0.05), without significant difference in the other indices. There were no significant differences among the three indices in stages 3 and 4 patients. Spearman correlation test results indicated that the abnormal rate of oVEMP (r＝0.336, P＝0.001) and the abnormal rate of oVEMP＋UC-SVV (r＝0.301, P＝0.003) were weakly positively correlated with clinical staging, while there was no correlation between the abnormal rate of UC-SVV and clinical staging (r＝0.022, P＝0.832). Conclusions Both oVEMP and UC-SVV tests can assess utricular function in MD patients at different clinical stages. Their combination is helpful of early-stage (stages 1 and 2) MD diagnosis.

Objective To examine the causes of incision infections following lower extremity open fractures and develop a predictive model for assessing the risk.Methods A total of 104 patients with open fractures of the lower extremity,who received internal fixation from January 2022 to August 2023.According to whether there was incision infection after the operation,the patients were divided into infection group and non-infection group.The aim of the study was to analyze the distribution of pathogenic bacteria causing postoperative incision infections.Single-factor and multifactor Logistic regression analyses were employed to examine the factors influencing postoperative incisional infections.Subsequently,a risk prediction model for these infections was developed.The predictive capacity of this model was assessed using ROC curves.Results In the cohort of 104 patients with open fractures of the lower limb,the occurrence rate of postoperative incision infections was 19.23％.A total of 45 non-repeated pathogenic bacteria were isolated,among which gram-positive bacteria accounted for 53.33％,gram-negative bacteria 42.22％,fungi 4.44％.Gram-positive bacteria showed 100％resistance to ampicillin/sulbactam and penicillin,while resistance rates for erythromycin and clindamycin exceeded 90％.Among gram-negative bacteria,resistance rates to cefazolin,sulfamethoxazole/trimethoprim,levofloxacin,ampicillin/sulbactam,ciprofloxacin,and gentamicin were all above 67％.Notably,resistance rates for cefazolin,sulfamethoxazole,and trimethoprim surpassed 90％.Univariate and multifactorial logistic stepwise regression analysis highlighted that time elapsed from injury to surgery,duration of surgery,length of hospital stay,perioperative prophylactic medication,and Gustilo classification were significant risk factors for postoperative incisional infections in patients with the condition(P＜0.05).The ROC curves illustrated that the risk prediction model accurately forecasted the incidence of postoperative incisional infections in patients with open fractures of the lower extremity,with an area under the curve of 0.861(95％ CI:0.811 to 0.911),boasting a sensitivity of 90.50％and a specificity of 72.92％.Conclusion The main pathogen of wound infection after open fracture of lower extremity is Gram-negative,the time from injury to operation,operation time,hospitalization time,prophylactic medication during perioperative period and GUSTILO classification were the influencing factors of postoperative wound infection.In addition,the establishment of risk prediction model has a good prediction effect on the incidence of postoperative wound infection in patients with this disease.

Objective:To study the feasibility of detecting vertical semicircular canal function and to analyze the three-dimensional(3D)characteristics and normal reference value in healthy young people.Methods:This was a cross-sectional study conducted from January to June 2024. A three-axis rotating chair was used to perform vertical sinusoidal rotation on 52 healthy young adults (26 males and 26 females, aged 18-40 years) in the left anterior-right posterior (LARP) and right anterior-left posterior (RALP) semicircular canal planes. For each plane, nystagmus was induced with six combinations of different angles and velocity front and back rotation angles of ±30°,±60°,±90°, and velocities of 40°/s and 80°/s, the slow phase velocity (SPV) and their symmetry of 3D nystagmus were analyzed. SPSS 20.0 was used to compare the statistical differences in these two parameters across different stimulation protocols.Results:There were no spontaneous nystagmus in the 52 subjects, and all tests were finished. Except the combinations of (±30°-40°/s), three components of nystagmus were induced stably in the rest of the stimulations. The SPVs of vertical components were no statistically insignificant ( P>0.05), and some horizontal or torsion components were statistically significant ( P<0.05). The 95% reference range of the symmetry was≤25% in the vertical and≤30% in the torsional component of the nystagmus except for (±30°-80°/s), the symmetry was 32.2% and 49.2% respectively. The trend changes of the three components were consistent, among which the vertical and torsional components induced by (±60°-80°/s) and (±90°-80°/s) were the best, the SPV value of the vertical components was higher in the latter group than the former apart from the front RALP, while no significant difference was found in the torsional components ( P>0.05). Conclusion:The (±90°-80°/s) combination is the optimal method to detect the function of vertical semicircular canal in 3D chair test. When observing torsional component, the combining scheme of (±60°-80°/s) and (±90°-80°/s) is better. Considering tolerance, the (±60°-80°/s) combination is recommended.

BACKGROUND:Recent studies have shown that Du Meridian electroacupuncture has a unique effect on alleviating spinal cord injury,but the underlying mechanisms require further clarification.OBJECTIVE:To investigate the regulatory effects and the associated action mechanisms of Du Meridian electroacupuncture on ferroptosis after cervical spinal cord injury in rats.METHODS:One hundred SD rats were randomly divided into sham,model,Du Meridian electroacupuncture,RSL3,and Du Meridian electroacupuncture+RSL3 groups.The sham group underwent only laminectomy.The other four groups were subjected to cervical spinal cord injury by the Allen method.The Du Meridian electroacupuncture group received electroacupuncture after cervical spinal cord injury.The RSL3 group received intraperitoneal injections of glutathione peroxidase 4 inhibitor RSL3 after cervical spinal cord injury.The Du Meridian electroacupuncture+RSL3 group received both electroacupuncture and RSL3 intervention after cervical spinal cord injury.Samples were collected on postoperative days 7 and 28 to assess motor function,histological morphology,neuronal survival,glial scar formation,oxidative stress levels,Fe2+content,glutathione peroxidase 4,and long-chain acyl-CoA synthetase 4 expression.RESULTS AND CONCLUSION:(1)Finally,90 rats completed the follow-up experiment,with 18 rats in each group.(2)FLS and BBB scores were significantly higher in the Du Meridian electroacupuncture group compared with the model and Du Meridian electroacupuncture+RSL3 groups(P＜0.05).(3)Compared with the model group,Du Meridian electroacupuncture improved cervical spinal cord tissue morphology and mitochondrial ultrastructure,while these effects were inhibited by RSL3.(4)Du Meridian electroacupuncture increased the expression of microtubule-associated protein 2,glutathione peroxidase 4,glutathione,and superoxide dismutase(P＜0.05)and reduced the expression of glial fibrillary acidic protein,long-chain acyl-CoA synthetase 4,reactive oxygen species,malondialdehyde,and Fe2+compared with the model group(P＜0.05).However,RSL3 reversed the inhibitory effects of Du Meridian electroacupuncture on ferroptosis,lipid peroxidation and oxidative stress.(5)The results suggest that Du Meridian electroacupuncture inhibits ferroptosis by regulating the glutathione peroxidase 4/long-chain acyl-CoA synthetase 4 axis,thereby reducing secondary neuronal damage and glial scar formation after cervical spinal cord injury and improving neurological function.

Connective tissue disease in children is a systemic multi-system damage caused by chronic inflammation of systemic connective tissue and blood vessels.Lung is often the first organ invaded by the disease, and interstitial lesions are an important manifestation of lung damage, with an increasing incidence.Initial clinical manifestations of this disease are often insidious and lack specificity.When its clinical symptoms are detectable, lung lesions often have progressed and the lung tissue structure remodeling has occurred.Therefore, early diagnosis and treatment are crucial to improve its prognosis.In this article, the clinical characteristics, diagnosis and treatment of connective tissue disease-associated interstitial lung disease in children were reviewed, in order to help improve its diagnosis and treatment.