OBJECTIVES: Acute lung injury (ALI) is an acute respiratory failure syndrome characterized by impaired gas exchange. Due to the lack of effective targeted drugs, it is associated with high mortality and poor prognosis. Tripterygium wilfordii (TW) has demonstrated anti-inflammatory activity in the treatment of various diseases. This study aims to investigate the effects and underlying mechanisms of TW on myeloid-derived suppressor cells (MDSCs) in ALI, providing experimental evidence for TW as a potential adjuvant therapy for ALI. METHODS: Eighteen specific pathogen-free (SPF) C57BL/6 mice were randomly divided into normal control (NC; intranasal saline), lipopolysaccharide (LPS; 5 mg/kg intranasally to induce ALI), and LPS+TW (50 mg/kg TW by gavage on the first day of modeling, followed by 5 mg/kg LPS intranasally to induce ALI) groups (n=6 each). Lung injury and edema were assessed by histopathological scoring and wet-to-dry weight ratio. Cytokine levels [interleukin (IL)-1β, IL-6, IL-18, tumor necrosis factor-α (TNF-α)] in lung tissue lavage fluid were measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to assess the proportions of MDSCs, polymorphonuclear MDSCs (PMN-MDSCs), and monocytic MDSCs (M-MDSCs) in bone marrow, spleen, peripheral blood, and lung tissue, as well as reactive oxygen species (ROS) levels in lung tissues. Messenger RNA (mRNA) expression levels of inducible nitric oxide synthase (iNOS) and arginase-1 (ARG-1) in lung tissues were determined by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). PMN-MDSCs sorted from the lungs of LPS-treated mice were co-cultured with splenic CD3⁺ T cells and divided into NC, triptolide (TPL)-L, and TPL-H groups, with bovine serum albumin, 25 nmol/L TPL, and 50 nmol/L TPL, respectively. Flow cytometry was used to detect the effect of PMN-MDSCs on T-cell proliferation, and RT-qPCR was used to measure iNOS and ARG-1 mRNA expression. RESULTS: Compared with the NC group, the LPS group showed marked lung pathology with significantly increased histopathological scores and wet-to-dry ratios (both P<0.001). TW treatment significantly alleviated lung injury and reduced both indices compared with the LPS group (both P<0.05). Cytokine levels were significantly decreased in the LPS+TW group compared with the LPS group (all P<0.001). The proportions of MDSCs in CD45⁺ cells from spleen, bone marrow, peripheral blood, and lung, as well as PMN-MDSCs from spleen, peripheral blood, and lung, were significantly reduced in the LPS+TW group compared with the LPS group (all P<0.05), accompanied by reduced ROS levels in lung tissues (P<0.001). iNOS and ARG-1 mRNA expression in lung tissues was significantly lower in the LPS+TW group than in the LPS group (both P<0.001). In vitro, compared with the TPL-L group, the TPL-H group showed significantly increased CD3⁺ T-cell proliferation (P<0.001), and decreased iNOS and ARG-1 mRNA expression (all P<0.05). CONCLUSIONS TW alleviates the progression of LPS-induced ALI in mice, potentially by reducing the proportion of MDSCs in lung tissues and attenuating the immunosuppressive function of PMN-MDSCs.
Animals ; Acute Lung Injury/chemically induced* ; Myeloid-Derived Suppressor Cells/cytology* ; Tripterygium/chemistry* ; Mice, Inbred C57BL ; Mice ; Cell Differentiation/drug effects* ; Male ; Lipopolysaccharides ; Nitric Oxide Synthase Type II/genetics* ; Cytokines/metabolism* ; Reactive Oxygen Species/metabolism* ; Diterpenes/pharmacology* ; Epoxy Compounds ; Phenanthrenes

OBJECTIVES: To investigate the effect of Haematococcus pluvialis (HP) on bleomycin (BLM)-induced pulmonary fibrosis in mice and on TGF-β1-induced human fetal lung fibroblasts (HFL1). METHODS: Thirty male C57BL/6 mice were randomly divided into control group, BLM-induced pulmonary fibrosis model group, low- and high-dose HP treatment groups (3 and 21 mg/kg, respectively), and 300 mg/kg pirfenidone (positive control) group. The effects of drug treatment for 21 days were assessed by examining respiratory function, lung histopathology, and expression of fibrosis markers in the lung tissues of the mouse models. In TGF-β1-induced HFL1 cell cultures, the effects of treatment with 120, 180 and 240 μg/mL HP or 1.85 μg/mL pirfenidone for 48 h on expression levels of fibrosis markers were evaluated. Transcriptome analysis was carried out using the control cells and cells treated with TGF-β1 and 240 μg/mL HP. RESULTS: HP obviously alleviated BLM-induced lung function damage and fibrotic changes in mice, evidenced by improved respiratory function, lung tissue morphology and structure, inflammatory infiltration, and collagen deposition and reduced expressions of fibrotic proteins. HP at the high dose produced similar effect to PFD. In TGF-β1-induced HFL1 cells, treatment with 240 μg/mL HP significantly reduced the mRNA and protein expression levels of α-SMA and FN. Transcriptome analysis revealed that multiple key genes and pathways mediated the protective effect of HP against pulmonary fibrosis. CONCLUSIONS HP alleviates pulmonary fibrosis in both the mouse model and cell model, possibly as the result of the synergistic effects of its multiple active components.
Animals ; Pulmonary Fibrosis/chemically induced* ; Bleomycin/adverse effects* ; Mice, Inbred C57BL ; Male ; Mice ; Fibroblasts/drug effects* ; Lung/pathology* ; Transforming Growth Factor beta1/pharmacology* ; Myofibroblasts/drug effects* ; Humans ; Pyridones

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective:To explore the factors influencing the recovery of swallowing function after a brainstem hemorrhage and to construct a prediction model.Methods:Clinical data on 134 persons with dysphagia after a brainstem hemorrhage were collected retrospectively. According to their swallowing ability at discharge, the patients were divided into a swallowing recovery group and a non-recovery group. Univariate correlation analysis and multivariate logistic regression analysis were used to explore the independent factors influencing the recovery of swallowing function and to construct a prediction nomogram. The receiver operating characteristics (ROC) curves were evaluated to analyze the nomogram′s predictive value and those of the relevant influencing factors.Results:Sixty-two of the patients (46%) had recovered their swallowing function at discharge, while 72 (54%) had not. Univariate correlation analysis showed that there had been significant differences in tracheal intubation, NIHSS score, FOIS score, Barthel index and Glasgow coma scale (GCS )score between the two groups, on average. The multivariate logistic regressions showed that a low NIHSS score, a high FOIS score and a high GCS score were independent predictors of swallowing function recovery, so they were used in the prediction model. ROC curve analysis showed that the area under the curve (AUC) of the prediction model was 0.953 (95% CI: 0.902~0.982) with a sensitivity of 87% and a specificity of 93%. The model′s predictions were thus better than using an NIHSS score, GCS score or FOIS score alone. Conclusions:NIHSS score, GCS score and FOIS score can independently predict the recovery of swallowing function after a brainstem hemorrhage. A prediction model constructed using all three has good predictive power.

Objective:To observe any therapeutic effect of transcranial direct current stimulation (tDCS) combined with intermittent oroesophageal tube feeding (IOE) on dysphagia among ischemic stroke survivors.Methods:Eighty-four ischemic stroke survivors with dysphagia were randomized into an observation group and a control group, each of 42. In addition to conventional rehabilitation, swallowing training and IOE, the observation group received tDCS while the control group received sham stimulation. Before and after 14 days of this treatment, both groups′ swallowing, life quality and depression were evaluated using the Penetration Aspiration Scale (PAS), the Functional Oral Intake Scale (FOIS), the Dysphagia Handicap Index (DHI), and a 9-item patient health questionnaire (PHQ-9).Results:There were no significant differences between the two groups before the experiment in terms of their general data, their average PAS, FOIS, DHI or PHQ-9 scores, or the incidence of depression. After the treatment, significant improvement was observed in the above indicators among both groups, but with significantly better average PAS, FOIS, DHI [(51.25±6.78) vs. (44.78±5.75)] and PHQ-9 [(4.17±1.15) vs. (6.01±1.93)] scores and less depression (14.29% vs. 42.86%) in the observation group compared with the control group.Conclusions:Combining tDCS with IOE better improves swallowing function, depression, and life quality after an ischemic stroke.

Objective:To explore the risk factors for malnutrition after a traumatic brain injury and to construct a model which usefully predicts that risk.Methods:This was a retrospective study of 374 patients with a craniocerebral injury for whom the relevant clinical data were available. Based on their nutritional status, they were stratified into a malnutrition group ( n=220) and a control group ( n=154). Univariate and multivariate logistic regressions were evaluated seeking to identify the independent risk factors associated with malnutrition, and a prediction model was constructed based on the results. The model′s discrimination ability and accuracy were assessed using a receiver operating characteristics (ROC) curve. Results:A total of 220 patients (58.8%) developed malnutrition. Multifactorial logistic regression analysis showed that the independent risk factors for malnutrition were: age ≥60 years, pulmonary infection, dysphagia, cognitive impairment, a GCS score ≤8, or a Barthel index ≤40. In the ROC curve analysis, the area under the curve quantifying the model′s ability to predict malnutrition was 0.924 (95% CI: 0.896, 0.951), with a sensitivity of 0.868 and a specificity of 0.857, indicating its good prediction performance. Conclusions:Age ≥60 years, pulmonary infection, dysphagia, cognitive impairment, a GCS score ≤8 or a Barthel index ≤40 are independent predictors of malnutrition after a traumatic brain injury. The prediction model constructed based on those risk factors has demonstrated useful predictive power for malnutrition.

Objectives:To investigate the mid-term outcomes of percutaneous cement discoplasty(PCD)in the treatment of lumbar axial instability,and analyze its technical keypoints and indications.Methods:A retrospective analysis was conducted on 9 patients with axial lumbar instability treated with PCD from January 2018 to December 2019.There were 5 males and 4 females,aged 62-87 years(75.7±8.2 years),with a follow-up period of 0.5-3 years,averaged 2.3±1.0 years.Three cases had three-disc operation at the same time,three had double-space operation and three had single-space operation,involving L2/3 disc in 3 cases,L3/4 disc in 3 cases,L4/5 disc in 4 cases,and L5/S1 disc in 3 cases.Lumbar anteroposterior and lateral ra-diographs in supine and standing positions were performed before operation,at postoperative 1d,3,6,12 months and final follow-up to measure the height of intervertebral space of responsible level,as well as the sagittal area of intervertebral foramen at responsible level.Visual analogue scale(VAS)and Oswestry disability index(ODI)were used to evaluate the pain and function before surgery,at 1d,3 months,6 months,12 months and final follow-up after operation to assess the clinical efficacy.The amount of bone cement injected in each intervertebral disc,the time of operation and the amount of blood loss were recorded respectively.Results:All the patients successfully completed the operation,no bone cement leakage occurred.The VAS score and ODI after operation were significantly improved compared with those before operation(P＜0.05).The injection volume of bone cement per intervertebral disc was 3.50±0.73mL.The operative time of each disc was 16.33±1.28min,and the blood loss of each disc was 3.83±0.71mL.The height of intervertebral space of responsible level at various time points after operation was different from that before operation(P＜0.05),and there was no difference in any two time points after operation.The sagittal area of intervertebral foramen at each time point after operation was different from that before operation(P＜0.05),and there was difference be-tween postoperative 1d and the final follow-up values(P＜0.05).Conclusions:PCD can increase the height of the intervertebral space after surgery,relieve lumbar pain,and have a lasting effect in the treatment of lum-bar instability,which is safe with satisfactory mid-term effect,and not prone to bone cement leakage,but long-term large-sample follow-up is still needed.

Objective:To analyze the factors influencing the prognoses of stroke survivors with pseudobulbar palsy (PBP) dysphagia and construct a prediction model.Methods:Data on two hundred and fifty-one stroke survivors with PBP dysphagia were collected and analyzed retrospectively. The subjects were divided into a good prognosis group ( n=164) and a poor prognosis group ( n=87) according to the results of Kubota water swallowing tests administered at discharge. Their clinical data were analyzed using univariate correlation analysis, and the statistically significant independent variables found were further analyzed using multivariate logistic regression to obtain the important predictors of prognosis. R software was then used to assemble the useful factors into a nomogram prediction model. The area under the receiver operating characteristics (ROC) curve was employed to verify the model′s predictive power. Results:According to the univariate correlation analysis, significant differences were found between the two groups′ average National Institutes of Health Stroke Scale (NIHSS) scores, mouth opening grades and ages. The multivariate logistic regression analysis showed that NIHSS score, mouth opening grade and age could be useful and independent predictors of poor prognosis. The ROC curve analysis showed that the area under the curve for the nomogram model was 0.727, with a sensitivity of 59.8% and a specificity of 81.6%, suggesting that the model had good predictive power and was properly calibrated.Conclusions:NIHSS score, mouth opening grade and age are independent predictors of prognosis for stroke patients with PBP dysphagia. The nomogram model constructed in this study is of great value in developing a prognosis for such patients, which is helpful in the prevention and treatment of post-stroke dysphagia.