Pediatric bronchopneumonia (BP) has afflicted more than 43.6% of infants and young children worldwide, as it is the most prevalent infectious disease among this patient population, with a rising incidence in recent years. 1,2 Dominantly triggered by pathogenic bacterial infection, pediatric BP has the most significant impact on pulmonary function, 3 which can cause severe respiratory dysfunction in children or even a series of neurological, digestive, circulatory, and other systemic diseases, directly threatening the life safety of children. 4,5 Clinical guidelines on pediatric BP point out that early diagnosis and treatment are the keys to ensuring the healthy growth of children. 6 However, at present, the diagnostic conditions for the disease in the clinic are still minimal, with imaging technology as the main evaluation index, which makes it impossible to realize large-scale clinical screening. 7 Therefore, finding an effective scheme that can quickly identify pediatric BP has been a hot and challenging issue in clinical research for a long time.

Golgi glycoprotein 73 (GP73), which exists in the transmembrane protein of Golgi, is an ideal serum marker for the early diagnosis and recurrence assessment of liver diseases, with high specificity and sensitivity. 8,9 It also has a very significant evaluation effect on pancreatic cancer, viral hepatitis B, and other inflammatory diseases. 10,11 Granulocyte colony-stimulating factor (G-CSF) is the main effector cell mediating the hepatitis response, which regulates the inflammatory response and immune response of the body by recruiting and aggregating hepatic stellate cells. 12,13 Research has proposed that G-CSF is of great reference significance as a marker for the early diagnosis of tuberculosis. Based on previous research on the mechanism of action of GP73 and G-CSF, the authors speculate that they also have a certain connection with the occurrence and development of pediatric BP. Nevertheless, no research has been conducted to confirm this hypothesis.

Accordingly, in the face of the increasing incidence of pediatric BP, the authors preliminarily confirmed the clinical implications of GP73 and G-CSF in the disease through experiments, aiming to provide new directions for future research regarding pediatric BP diagnosis and treatment.

Pediatric BP is a common disease that affects children's life safety. Clinically, its etiology is closely related to the living environment, genetic factors, and nutrition intake. 14 The onset of pediatric BP is usually extremely rapid and may develop into severe pneumonia if not treated in a timely and effective manner, further increasing the risk of the disease. 15 At present, efforts are being made to explore sensitive markers of BP at home and abroad, aiming to improve the early detection rate of pediatric BP, but no significant breakthrough has been made yet. 16 This research, by analyzing the clinical implications of GP73 and G-CSF in children with BP, can lay a reliable foundation for the two as keys to the future diagnosis and treatment of pediatric BP.

First, the authors detected peripheral blood GP73 and G-CSF in cases and controls and determined their elevated levels in cases, which was consistent with the results of previous studies on the expression profiles of the two, 17,18 suggesting that both of them may interfere with BP onset and progression in children. GP73, as a Golgi transmembrane protein, has been found to be expressed in various organs, such as the liver, stomach, and peripheral blood, to varying degrees, but its mechanism of action has not yet been fully defined. 19 Mao and Wang demonstrated that GP73 inhibited epithelial cell proliferation and differentiation; additionally, it can act as a negative regulator of host innate immunity, inhibiting the host immune response and increasing the risk of pathogen infection. 20,21 Therefore, GP73 may be crucial in pediatric BP, a disease largely caused by decreased immunocompetence and pathogen infection. While G-CSF is primarily produced by T lymphocytes and macrophages, it can induce granulocyte aggregation by binding to target cell receptors. 22 Hoshina et al. indicated that G-CSF can prolong the life cycle of eosinophils by enhancing their adsorption and aggregation on vascular endothelium at inflammatory sites. In addition, it is able to release chemical toxicity by activating eosinophils in the human body, causing tissue damage and increasing lung susceptibility. 23,24 In renal ischemia-reperfusion injury, the continuous increase in G-CSF constantly stimulates aggravation of the inflammatory response and tissue damage, resulting in long-term incurable disease. 25 The authors speculate that in children with BP, the lung tissue is damaged by the invasion of foreign pathogens, which leads to a continuous increase in G-CSF and acceleration of BP. Then, the authors analyzed their diagnostic value for pediatric BP, which is the key to all BP research. 26 Compared with the current pediatric BP diagnosis scheme, the advantages of blood markers lie in the convenience of access, rapid detection, convenient preservation, and wide range of sample screening at any time. Thus, the early detection rate of BP is improved, and the treatment time for children is shortened. The present study's findings showed that both GP73 and G-CSF were effective in predicting the occurrence of BP, and the specificity of their combined detection reached 86.42%, demonstrating that GP73 and G-CSF have the potential to become diagnostic markers of pediatric BP in the future.

To further understand the clinical implications of GP73 and G-CSF in pediatric BP, the authors analyzed the correlation of the two with patient pathology. The results identified that GP73 and G-CSF, which are closely related to X-ray classification and complications in OG, decreased after treatment and were positively correlated with hs-CRP, especially in children with respiratory failure. hs-CRP, as one of the most sensitive indicators of inflammatory conditions in the human body, is also a common observation indicator for pediatric BP. 27 In a previous study, hs-CRP was found to have a trend of positive correlation with G-CSF and G-CSF mobilization stimulated an overactivation of inflammation in ischemic cardiomyopathy. 28 Both GP73 and G-CSF levels correlated well with hs-CRP levels, implying that hs-CRP could also reflect the progression of BP and be easily detected. To the best of our knowledge, the correlation between GP73 and hs-CRP levels has not been investigated. In future studies, the correlation of GP73 and G-CSF levels with hs-CRP levels could be useful for detecting BP. All the above results fully demonstrate that GP73 and G-CSF are closely related to pediatric BP progression, which further confirms their great potential value in the disease.

Apart from that, as a kind of lung injury disease with rapid onset, the effect of the pathogen on lung function is the most direct pathological manifestation of pediatric BP. 29 Respiratory failure, a critical complication that directly threatens the life safety of children, is also one of the most common complications of pediatric BP. 30 Therefore, if the significance of GP73 and G-CSF in children with BP complicated by respiratory failure can be further proven, it will provide an important guarantee for the safety of children in the future. In subsequent studies, the authors found that GP73 and G-CSF were higher in children with BP complicated with respiratory failure than in those without respiratory failure, and their predictive value for respiratory failure was extremely significant, which preliminarily confirmed the above stated viewpoint. However, in this experiment, GP73 combined with G-CSF was not as effective as single detection in predicting BP respiratory failure. The reason, the authors speculate, might be that the effect of GP73 and G-CSF on predicting respiratory failure in BP is already very significant, so the effect will not be further enhanced by the combination of the two. On the other hand, it may be that ROC analysis usually requires large case data to be more accurate, while the number of cases included in this study is small, resulting in contingency calculations. Finally, through logistic regression analysis, the authors found that independent of the course of the disease, hs-CRP, X-ray classification, GP73, and G-CSF were factors contributing to respiratory failure in children with BP, which reverified the significance of GP73 and G-CSF in the disease.

As previously stated, due to the small number of participants included, statistical calculations may contain errors. Additionally, because this study did not include a more detailed grouping design for children with BP, the authors will investigate the significance of GP73 and G-CSF in pediatric BP with different pathogens and disease courses in the future. Additionally, due to a dearth of in vitro experiments, the authors are unable to confirm the precise mechanism by which GP73 and G-CSF act in pediatric BP. The preceding are critical points that merit further discussion in the future.

GP73 and G-CSF, with elevated levels in children with BP, are strongly linked to disease progression and are the factors contributing to respiratory failure, which may be the key to diagnosing and treating pediatric BP in the future.

None.