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*

BACKGROUND:Degenerative scoliosis is defined as a condition that occurs in adulthood with a coronal cobb angle of the spine>10° accompanied by sagittal deformity and rotational subluxation,which often produces symptoms of spinal cord and nerve compression,such as lumbar pain,lower limb pain,numbness,weakness,and neurogenic claudication.The finite element method is a mechanical analysis technique for computer modelling,which can be used for spinal mechanics research by building digital models that can realistically restore the human spine model and design modifications. OBJECTIVE:To review the application of finite element method in the etiology and treatment of degenerative scoliosis. METHODS:The literature databases CNKI,PubMed,and Web of Science were searched for articles on the application of finite element method in degenerative scoliosis published before October 2023.Search terms were"finite element analysis,biomechanics,stress analysis,degenerative scoliosis,adult spinal deformity"in Chinese and English.Fifty-four papers were finally included. RESULTS AND CONCLUSION:(1)The biomechanical findings from the degenerative scoliosis model constructed using the finite element method were identical to those from the in vivo experimental studies,which proves that the finite element method has a high practical value in degenerative scoliosis.(2)The study of the etiology and treatment of degenerative scoliosis by the finite element method is conducive to the prevention of the occurrence of the scoliosis,slowing down the progress of the scoliosis,the development of a more appropriate treatment plan,the reduction of complications,and the promotion of the patients'surgical operation.(3)The finite element method has gradually evolved from a single bony structure to the inclusion of soft tissues such as muscle ligaments,and the small sample content is increasingly unable to meet the research needs.(4)The finite element method has much room for exploration in degenerative scoliosis.

Objective To investigate the risk factors of latent blood loss after internal fixation of intertrochanteric fracture of femur.Methods The clinical data of 112 patients with intertrochanteric fracture of femur treated with internal fixation in our hospital from May 2019 to July 2022 were retrospectively analyzed,and the hidden blood loss after surgery was recorded.SPSS software was used to analyze the influencing factors of hidden blood loss after internal fixation of intertrochanteric fracture of femur.Results None of the 152 patients with intertrochanteric fracture of femur had serious complications or died during perioperative period,and the wound was not infected.The fixation alignment was good.The postoperative dominant blood loss was(236.37±71.52)ml,the recessive blood loss was(709.74±132.36)ml,and the total blood loss was(946.11±205.61)ml.The recessive blood loss was significantly higher than the dominant blood loss(P＜0.05).Multiple linear regression analysis showed that age,hypertension,diabetes,fracture type,preoperative anticoagulation,time from injury to operation,and operation time were all risk factors for latent blood loss after internal fixation of intertrochanteric fracture of femur(P＜0.05).Conclusion Age,hypertension,diabetes,fracture type,preoperative anticoagulation,time from injury to operation and operation time are all risk factors for latent blood loss after internal fixation of intertrochanteric fracture of femur.According to these factors,medical staff can formulate corresponding prevention and treatment programs to reduce the latent blood loss after internal fixation of intertrochanteric fracture of femur.

BACKGROUND:The highest incidence of spinal fracture is in the thoracolumbar segment,and its symptoms are back pain,posterior convexity deformity,activity limitation,or with spinal cord nerve injury causing lower limb pain,numbness,and even paraplegia and other complications.The finite element method is a digital computer modeling technique,which can simulate the physical model and carry out force analysis realistically.OBJECTIVE:To review the application of finite element method in thoracolumbar spine fractures.METHODS:We searched the Chinese and English literature databases PubMed,Web of Science,and CNKI for relevant literature on the application of the finite element analysis method in spinal thoracolumbar fracture published before March 2024.The search terms in Chinese and English were:finite element analysis methods,biomechanical phenomena,stress analysis,thoracolumbar fractures,spinal fractures.Finally,55 papers were included.RESULTS AND CONCLUSION:(1)The exploration of thoracolumbar fractures caused by different etiologies(osteoporotic,traumatic,and pathological)through the finite element method is conducive to a deeper understanding of the biomechanics of various types of thoracolumbar fractures,and to improve the individualized and fine-tuned treatment of thoracolumbar fractures.(2)The finite element analysis of a single sample or a small number of samples has the chance,and a larger number of samples are required for the future finite element analysis to reduce the chance caused by the sample.(3)The rigid structure of bones alone cannot meet the biomechanical working conditions of the integrity of the physical object,and future finite element models need to incorporate all the structures of the physical object(e.g.,soft tissues,such as muscles and ligaments)as far as possible.(4)The finite element method has been used in more studies on osteoporotic and traumatic thoracolumbar spine fractures,which will need to be more in-depth in the future,and less in the field of pathologic thoracolumbar fractures,which has a wider scope for future research.

BACKGROUND:The highest incidence of spinal fracture is in the thoracolumbar segment,and its symptoms are back pain,posterior convexity deformity,activity limitation,or with spinal cord nerve injury causing lower limb pain,numbness,and even paraplegia and other complications.The finite element method is a digital computer modeling technique,which can simulate the physical model and carry out force analysis realistically.OBJECTIVE:To review the application of finite element method in thoracolumbar spine fractures.METHODS:We searched the Chinese and English literature databases PubMed,Web of Science,and CNKI for relevant literature on the application of the finite element analysis method in spinal thoracolumbar fracture published before March 2024.The search terms in Chinese and English were:finite element analysis methods,biomechanical phenomena,stress analysis,thoracolumbar fractures,spinal fractures.Finally,55 papers were included.RESULTS AND CONCLUSION:(1)The exploration of thoracolumbar fractures caused by different etiologies(osteoporotic,traumatic,and pathological)through the finite element method is conducive to a deeper understanding of the biomechanics of various types of thoracolumbar fractures,and to improve the individualized and fine-tuned treatment of thoracolumbar fractures.(2)The finite element analysis of a single sample or a small number of samples has the chance,and a larger number of samples are required for the future finite element analysis to reduce the chance caused by the sample.(3)The rigid structure of bones alone cannot meet the biomechanical working conditions of the integrity of the physical object,and future finite element models need to incorporate all the structures of the physical object(e.g.,soft tissues,such as muscles and ligaments)as far as possible.(4)The finite element method has been used in more studies on osteoporotic and traumatic thoracolumbar spine fractures,which will need to be more in-depth in the future,and less in the field of pathologic thoracolumbar fractures,which has a wider scope for future research.

Objective To investigate the risk factors of latent blood loss after internal fixation of intertrochanteric fracture of femur.Methods The clinical data of 112 patients with intertrochanteric fracture of femur treated with internal fixation in our hospital from May 2019 to July 2022 were retrospectively analyzed,and the hidden blood loss after surgery was recorded.SPSS software was used to analyze the influencing factors of hidden blood loss after internal fixation of intertrochanteric fracture of femur.Results None of the 152 patients with intertrochanteric fracture of femur had serious complications or died during perioperative period,and the wound was not infected.The fixation alignment was good.The postoperative dominant blood loss was(236.37±71.52)ml,the recessive blood loss was(709.74±132.36)ml,and the total blood loss was(946.11±205.61)ml.The recessive blood loss was significantly higher than the dominant blood loss(P＜0.05).Multiple linear regression analysis showed that age,hypertension,diabetes,fracture type,preoperative anticoagulation,time from injury to operation,and operation time were all risk factors for latent blood loss after internal fixation of intertrochanteric fracture of femur(P＜0.05).Conclusion Age,hypertension,diabetes,fracture type,preoperative anticoagulation,time from injury to operation and operation time are all risk factors for latent blood loss after internal fixation of intertrochanteric fracture of femur.According to these factors,medical staff can formulate corresponding prevention and treatment programs to reduce the latent blood loss after internal fixation of intertrochanteric fracture of femur.

Background::Programmed death 1 (PD-1) blockade plus chemotherapy has become the new first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC). Yet not all NSCLC patients benefit from this regimen. This study aimed to investigate the predictors of PD-1 blockade plus chemotherapy in untreated advanced NSCLC.Methods::We integrated clinical, genomic, and survival data from 287 patients with untreated advanced NSCLC who were enrolled in one of five registered phase 3 trials and received PD-1 blockade plus chemotherapy or chemotherapy alone. We randomly assigned these patients into a discovery cohort ( n = 125), a validation cohort ( n = 82), and a control cohort ( n = 80). The candidate genes that could predict the response to PD-1 blockade plus chemotherapy were identified using data from the discovery cohort and their predictive values were then evaluated in the three cohorts. Immune deconvolution was conducted using transcriptome data of 1014 NSCLC patients from The Cancer Genome Atlas dataset. Results::A genomic variation signature, in which one or more of the 15 candidate genes were altered, was correlated with significantly inferior response rates and survival outcomes in patients treated with first-line PD-1 blockade plus chemotherapy in both discovery and validation cohorts. Its predictive value held in multivariate analyses when adjusted for baseline parameters, programmed cell death ligand 1 (PD-L1) expression level, and tumor mutation burden. Moreover, applying both the 15-gene panel and PD-L1 expression level produced better performance than either alone in predicting benefit from this treatment combination. Immune landscape analyses revealed that tumors with one or more variation in the 15-gene panel were associated with few immune infiltrates, indicating an immune-desert tumor microenvironment.Conclusion::These findings indicate that a 15-gene panel can serve as a negative prediction biomarker for first-line PD-1 blockade plus chemotherapy in patients with advanced NSCLC.

Objective To explore the predictive value of 3D quantitative shape features based on enhanced CT for disease-free survival(DFS)of primary gastric gastrointestinal stromal tumors(GIST)patients receiving curative resection.Methods From January 2010 to December 2016,a total of 154 patients with primary gastric GIST who received curative resection in Zhongshan Hospital,Fudan University were retrospectively collected.The conventional CT imaging features and 3D quantitative shape features of tumors were evaluated,and the influencing factors of DFS were analyzed by univariate and multivariate Cox regression.Cut-off values were extracted,and Kaplan-Meier curves were used for survival analysis.Results Maximum 3D diameter(HR=1.829,95% CI 1.389-2.408,P＜0.001)and spherical disproportion(HR=2.153,95% CI 1.474-3.146,P＜0.001)were independent risk factors for DFS in primary gastric GIST.Kaplan-Meier curves showed that patients with maximum 3D diameter＞90.5 mm and spherical disproportion＞1.5 showed shorter DFS after curative resection(P＜0.001).Conclusion Maximum 3D diameter and spherical disproportion based on preoperative enhanced CT are valuable in the diagnosis of postoperative DFS in primary gastric GIST.

Humans ; Aminoquinolines/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation/genetics* ; Standard of Care

Objective:To analyze the relationship between plasma uranium concentration and renal injury.Methods:A case-control study was conducted in Hunan province, involving 102 renal injury cases and 102 matched controls. The association between plasma uranium concentration and renal injury was analyzed using conditional logistic regression models, and the dose-response relationship was analyzed through restricted cubic spline regression. The linear regression model and Spearman correlation were used to analyze the association between plasma uranium concentration and renal injury indicators.Results:The median of plasma uranium concentration was 8.94 ng/L in all subjects and 10.19 ng/L in the case group. The plasma uranium may be a risk factor for renal injury, with a dose-response relationship between the both representing nonlinear association ( χ2=5.15, P<0.05). The risk of renal injury was 4.21 times higher in the group exposed to highest uranium concentration than that in the group exposed to lowest uranium concentration. Plasma uranium concentration was closely related to glomerular filtration rate, serum creatinine and β 2-microglobulin ( r=0.211, -0.142, 0.195, P<0.05). Conclusions:The plasma uranium concentration is significantly associated with the renal injury, which may provide epidemiology evidence for the prevention of renal injury.