Peroxisome proliferator activated receptor-α (PPAR-α) is significantly expressed in various tissues such as the liver, kidney, myocardium, and skeletal muscle, which plays a central role in the development of various diseases by regulating key physiological processes such as energy homeostasis, redox balance, inflammatory response, and ferroptosis. As an important metabolic and excretory organ of the body, renal dysfunction can lead to water and electrolyte imbalance, toxin accumulation, and multiple system complications. The causes of kidney injury are complex and diverse, including acute injury factors (such as ischemia/reperfusion, nephrotoxic drugs, septic shock, and immune glomerulopathy), as well as chronic progressive causes [such as metabolic disease-related nephropathy, hypertensive nephropathy (HN)], and risk factors such as alcohol abuse, obesity, and aging. This review briefly describes the structure, function, and activity regulation mechanism of PPAR-α, systematically elucidates the molecular regulatory network of PPAR-α in the pathological process of kidney injury including acute kidney injury (AKI) such as renal ischemia/reperfusion injury (IRI), drug-induced AKI, sepsis-associated acute kidney injury (SA-AKI), glomerulonephritis, chronic kidney disease (CKD) such as diabetic nephropathy (DN), HN, and other kidney injury, and summarizes the mechanisms related to PPAR-α regulation of kidney injury, including regulation of metabolism, antioxidation, anti-inflammation, anti-fibrosis, and anti-ferroptosis. This review also evaluates PPAR-α's medical value as a novel therapeutic target, and aims to provide theoretical basis for the development of kidney protection strategies based on PPAR-α targeted intervention.
Humans ; PPAR alpha/metabolism* ; Acute Kidney Injury/therapy* ; Animals ; Kidney/metabolism*

Objective:To explore baseline clinical and imaging characteristics of children with neonatal arterial ischaemic stroke based on their long-term motor function prognoses.Methods:A retrospective cohort study was conducted. Clinical data, including magnetic resonance imaging (MRI) and electroencephalogram (EEG) findings, were collected from 31 neonates diagnosed with ischemic stroke admitted to the Department of Neonataology, Maternal and Child Health Hospital of Hubei Province between January 2015 and December 2019. Unified follow-up was conducted between May and July 2024. Long-term motor function outcomes were assessed using the modified Rankin scale(mRS) and categorized into two groups: the good motor function group (mRS score 0-1) and the motor impairment group (mRS score≥2).Baseline clinical and imaging data were summarized for all children, and differences between the two groups were analyzed using the Mann-Whitney U test and Fisher′s exact test. Results:A total of 31 neonates (21 males, 10 females) with an admission age of 1-19 days, all diagnosed within 28 days of birth, were included. At follow-up, 4-8 years after disease onset, 26 neonates (84%) showed good motor function, while 5 (16%) had motor impairments. Compared to the good motor function group, the motor impairment group had higher proportions of females (4/5 vs. 23% (6/26)), main middle cerebral artery (MCA) infarction (4/5 vs. 19% (5/26)), basal ganglia involvement (4/5 vs. 27% (7/26)), corticospinal tract involvement (posterior limb of internal capsule (PLIC) 5/5 vs. 38% (10/26) and cerebral peduncles 5/5 vs. 31% (8/26)) shown by MRI images, and meconium-stained amniotic fluid (4/5 vs. 15% (4/26))(all P<0.05).No significant differences were observed in gestational age, birth weight, abnormalities in muscle tone or primitive reflexes at admission or discharge, or abnormal EEG findings (all P>0.05). Conclusions:Neonatal arterial ischemic stroke commonly manifests as seizures, which are generally controllable, with a relatively stable clinical course and a low incidence of long-term motor impairment. Children with long-term motor impairments are more likely to have main MCA infarction, basal ganglia and corticospinal tract involvement (PLIC and cerebral peduncles), as well as meconium-stained amniotic fluid. This condition is also more commonly observed in females.

In recent years,the Ross procedure has been increasingly applied in the treatment of aortic valve disease in children and young patients.However,right ventricular outflow tract(RVOT)reconstruction in this procedure often relies on allogeneic or artificial materials,which may lead to complications such as calcification and valve dysfunction.This article reports a case of protective Ross procedure using completely autologous tissue to construct a right ventricular-pulmonary artery(RV-PA)conduit.The patient was an 11-year-old male who presented with severe aortic stenosis combined with regurgitation.During the operation,his dilated ascending aortic wall and fresh pericardium were used to construct an autologous valved conduit for RV-PA reconstruction.This innovative technique achieves RV-PA reconstruction without allogeneic tissue,provides a new technical approach for the Ross procedure.Short-term results are satisfactory and the medium-and long-term outcomes require further follow-up verification.

In recent years,the Ross procedure has been increasingly applied in the treatment of aortic valve disease in children and young patients.However,right ventricular outflow tract(RVOT)reconstruction in this procedure often relies on allogeneic or artificial materials,which may lead to complications such as calcification and valve dysfunction.This article reports a case of protective Ross procedure using completely autologous tissue to construct a right ventricular-pulmonary artery(RV-PA)conduit.The patient was an 11-year-old male who presented with severe aortic stenosis combined with regurgitation.During the operation,his dilated ascending aortic wall and fresh pericardium were used to construct an autologous valved conduit for RV-PA reconstruction.This innovative technique achieves RV-PA reconstruction without allogeneic tissue,provides a new technical approach for the Ross procedure.Short-term results are satisfactory and the medium-and long-term outcomes require further follow-up verification.

Objective:To explore baseline clinical and imaging characteristics of children with neonatal arterial ischaemic stroke based on their long-term motor function prognoses.Methods:A retrospective cohort study was conducted. Clinical data, including magnetic resonance imaging (MRI) and electroencephalogram (EEG) findings, were collected from 31 neonates diagnosed with ischemic stroke admitted to the Department of Neonataology, Maternal and Child Health Hospital of Hubei Province between January 2015 and December 2019. Unified follow-up was conducted between May and July 2024. Long-term motor function outcomes were assessed using the modified Rankin scale(mRS) and categorized into two groups: the good motor function group (mRS score 0-1) and the motor impairment group (mRS score≥2).Baseline clinical and imaging data were summarized for all children, and differences between the two groups were analyzed using the Mann-Whitney U test and Fisher′s exact test. Results:A total of 31 neonates (21 males, 10 females) with an admission age of 1-19 days, all diagnosed within 28 days of birth, were included. At follow-up, 4-8 years after disease onset, 26 neonates (84%) showed good motor function, while 5 (16%) had motor impairments. Compared to the good motor function group, the motor impairment group had higher proportions of females (4/5 vs. 23% (6/26)), main middle cerebral artery (MCA) infarction (4/5 vs. 19% (5/26)), basal ganglia involvement (4/5 vs. 27% (7/26)), corticospinal tract involvement (posterior limb of internal capsule (PLIC) 5/5 vs. 38% (10/26) and cerebral peduncles 5/5 vs. 31% (8/26)) shown by MRI images, and meconium-stained amniotic fluid (4/5 vs. 15% (4/26))(all P<0.05).No significant differences were observed in gestational age, birth weight, abnormalities in muscle tone or primitive reflexes at admission or discharge, or abnormal EEG findings (all P>0.05). Conclusions:Neonatal arterial ischemic stroke commonly manifests as seizures, which are generally controllable, with a relatively stable clinical course and a low incidence of long-term motor impairment. Children with long-term motor impairments are more likely to have main MCA infarction, basal ganglia and corticospinal tract involvement (PLIC and cerebral peduncles), as well as meconium-stained amniotic fluid. This condition is also more commonly observed in females.

Objective To explore the risk factors of aspiration during hospitalization in patients with ischemic stroke (IS) and establish a predictive model. Methods Based on the case-control design, clinical materials of 316 IS patients treated in the Department of Neurology of Suzhou Ninth Hospital Affiliated to Soochow University from March 2022 to October 2023 were retrospectively collected. According to incidence of aspiration during hospitalization, the patients were divided into case group with 89 cases (aspiration occurred during hospitalization) and control group with 227 cases (no aspiration occurred during hospitalization). Univariate and multivariate Logistic regression analyses were performed in both groups to screen out the risk factors of aspiration during hospitalization in IS patients. R software was used to extract 70 % of the data from the two groups as the training set (establishing a Nomogram model), and the remaining 30 % data was used as test set. Value of predictive model was evaluated by area under the curve (AUC) of the receiver operating characteristic (ROC) curve, calibration curve, and decision curve. Results There were significant differences in the terms of age, the National Institutes of Health Stroke Scale (NIHSS) score, number of lesions, homocysteine (Hcy) level, spontaneous cough, and grading of Wada drinking water test between the case group and the control group (P < 0.05). Multivariate Logistic analysis showed that large age (OR=2.201, 95 %CI, 1.254 to 3.865), high NIHSS score (OR=4.816, 95 %CI, 1.652 to 14.041), multiple lesions (OR=2.649, 95 %CI, 1.249 to 5.613), high level of Hcy (OR=1.501, 95 %CI, 1.044 to 2.158), weakened or absent spontaneous cough (OR=3.384, 95 %CI, 1.639 to 6.987), and high grading of Wada drinking water test (OR=2.878, 95 %CI, 1.422 to 5.783) were the risk factors of aspiration during hospitalization in IS patients (P < 0.05). In the training set, the AUC of the Nomogram model for predicting aspiration during hospitalization in IS patients was 0.872 (95 %CI, 0.827 to 0.919), and was 0.859 (95 %CI, 0.807 to 0.904) in the test set. The calibration curve analysis showed that P value was 0.869 in the training set and 0.898 in the test set. The decision curve analysis for both the training set and test set showed that the Nomogram model was of good clinical applicability. Conclusion The risk of aspiration during hospitalization in IS patients is related to large age, high NIHSS score, multiple lesions, high level of Hcy, weakened or absent spontaneous cough, and high grading of Wada drinking water test. The Nomogram predictive model established on these factors can effectively evaluate the risk of aspiration during hospitalization in IS patients.

Objective:To explore the effects of neutrophilic granule protein (NGP) on the expression of lipocalin 2 (LCN2) in inflammatory macrophages and its mechanism.Methods:NGP-high-expressed RAW264.7 cells (NGP/RAW cells) and negative control RAW264.7 cells (NC/RAW cells) were cultured in vitro. Primary peritoneal macrophages of NGP-high-expressed mice and wild-type C57BL/6 mice were extracted, then cultured in vitro. The cell inflammatory model was established by stimulating with 10 mg/L lipopolysaccharide (LPS, LPS group), and the phosphate buffer solution (PBS) control group was set up. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of LCN2 in different types of cells. The protein expression of phosphorylated signal transduction and activator of transcription 1 (p-STAT1) was detected with Western blotting. Other NGP/RAW cells and NC/RAW cells were treated with 10 mg/L LPS, 5 mg/L STAT1 pathway inhibitor (fludarabine)+10 mg/L LPS, respectively. The PBS control group was set up. ELISA was used to detect the level of LCN2. Results:In different types of cells, the levels of LCN2 were increased significantly after LPS stimulation in the LPS group as compared with those in the PBS control group, and peaked at 24 hours (μmol/L: 25.61±1.02 vs. 0.46±0.02 in NC/RAW cells, 74.51±2.14 vs. 0.25±0.04 in NGP/RAW cells, 10.13±0.22 vs. 0.01±0.01 in primary macrophages of wild-type C57BL/6 mice, 28.35±0.61 vs. 0.08±0.01 in primary macrophages of NGP-high-expressed mice, all P < 0.05), indicating that the expression of LCN2 in macrophages altered during inflammation reaction. The level of LCN2 in NGP/RAW cells was found significantly increased at different time points after LPS stimulation comparing with that in NC/RAW cells (μmol/L: 8.32±0.22 vs. 3.12±0.11 at 6 hours, 23.12±0.86 vs. 8.12±0.32 at 12 hours, 74.51±2.14 vs. 25.61±1.02 at 24 hours, all P < 0.05), along with the expression of p-STAT1 was significantly up-regulated. The level of LCN2 in the primary macrophages of NGP-high-expressed mice was also significantly increased at 24 hours after LPS stimulation comparing with that in the primary macrophages of wild-type C57BL/6 mice (μmol/L: 28.35±0.61 vs. 10.13±0.22, P < 0.05). However, after pretreated with STAT1 pathway inhibitors, the production of LCN2 in NGP/RAW cells was decreased significantly comparing with that in the LPS group (μmol/L: 6.81±0.19 vs. 22.54±0.58, P < 0.05). But the inhibitors had no significant effect on LCN2 production in NC/RAW cells showing no significant difference as compared with LPS group (μmol/L: 8.04±0.20 vs. 7.86±0.15, P > 0.05), indicating that NGP could up-regulate the expression of LCN2 in macrophages stimulated by LPS by promoting STAT1 activation. Conclusion:NGP could positively regulate LCN2 expression in inflammatory macrophages by activating STAT1 pathway.

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.