Systemic inflammatory response index is a predictor of prognosis in gastric cancer patients: Retrospective cohort and meta-analysis

Jing-Yao Ren, Meng Xu, Xiang-Dong Niu, Shi-Xun Ma, Ya-Jun Jiao, Da Wang, Miao Yu, Hui Cai

Abstract BACKGROUND The systemic inflammatory response index (SIRI) has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms. However, research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer surgery.AIM To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients, who received robotic radical gastric cancer surgery.METHODS Initially, an exhaustive retrieval was performed in the PubMed, the Cochrane Library, EMBASE, Web of Science, and Scopus databases to identify relevant studies. Subsequently, a meta-analysis was executed on 6 cohort studies identifying the value of the SIRI in assessing the survival of gastric cancer patients. Additionally, the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators. The association between preoperative SIRI levels and 5-year overall survival (OS) and disease-free survival (DFS) was assessed.RESULTS The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer. Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer. SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities, T-stage, carcinoembryonic antigen levels, the development of early serious postoperative complications, and the rate of lymph node metastasis.CONCLUSION SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.

Key Words: Systemic inflammatory response index; Prognosis; Gastric cancer; Complications; Meta-analysis

INTRODUCTION

Gastric cancer, driven by high disease burden and lethality, pose an urgent issue for the community[1]. It is considered the third major cause of mortality and the fifth most prevalent malignancy among oncology patients[2]. Tremendous surgical advancements in the management of gastric cancer have been made across the last few decades, with the emergence of robotic gastric surgery as an undeniably powerful advantage[3]. Findings indicate that robotic gastrectomy may be of additional worth in lymph node dissection and early postoperative course[4]. Although the effectiveness of enhanced chemotherapy and surgical alternatives has been demonstrated in these patients, the prognosis is still unsatisfactory[1]. The Correa sequence, a classical model of gastric cancer progression, states that the inflammatory response is a crucial contributor to the tumor advancement process. Chronic inflammation of the gastric mucosa can contribute to the development of gastric cancer[5], by releasing systemic biochemical cytokines in response to inflammation, and the resulting carcinoma cell development drives postoperative recurrence and metastasis[6]. A growing body of recent research revealed that tumor-associated inflammatory fluences were strongly relevant to the survival and probability in cancer patients[7]. The systemic inflammatory response index (SIRI) is emerging as a comprehensive parameter which is calculated by neutrophil count × monocyte count/Lymphocyte count, and it is capable of recognizing inflammatory conditions in individuals. The SIRI has also shown considerable value in the prognostic assessment of patients with many solid tumors, such as lung cancer[8], liver cancer[9], tongue cancer[10], and bladder cancer[11]. Therefore, to more accurately understand the prognostic relevance of peripheral blood SIRI values in gastric cancer patients, we collected all the available data in a meta-analysis and then retrospectively collected baseline data from patients who underwent robotic radical gastric surgery to further explore the relationship between SIRI values, clinicopathological characteristics, and patient prognosis.

MATERIALS AND METHODS

Meta-analysis

Inclusion and exclusion criteria:The inclusive criteria were: (1) A connection between serum SIRI values and the overall survival (OS) or disease-free survival (DFS) of patients with gastric cancer was reported; (2) an assessment of the hazard ratios (HR) and the corresponding 95% confidence intervals (CI) was available; and (3) the full text was accessible. The exclusion criteria were: (1) Unoriginal articles (reviews, commentaries, editorials, conference abstracts, and case reports; (2) articles without sufficient HR survival data; and (3) duplicate studies.

Search procedure and study selection:The process of searching and selecting the studies for this meta-analysis adhered to the guidelines of the Preferred Reporting Items for Systematic Evaluation and Meta-Analyses. The main search terms used were "gastric cancer", "stomach neoplasm" and "systemic inflammatory response index". Detailed search strategies can be found in the Supplementary material.

Data extraction:Two investigators independently collected two aspects of data from the included studies: (1) Fundamental data, including the initial author's name, publication year, country, study type, population, number of patients enrolled, inclusion period, cut-off values and methods for identifying cutoff values, and treatment method; and (2) prognostic data, including the type of survival and duration of follow-up, and since all included studies reported HRs for OS/DFS in univariate and/or multivariate analyses, HR and 95%CI were used directly to combine individual outcomes, with HRs from multivariate analyses preferred. The quality of the included studies was strictly assessed, according to the Newcastle-Ottawa Scale.

Data analysis:A meta-analysis was conducted using Stata statistical software to examine the included studies. The I2andPcoefficient were utilized to evaluate the heterogeneity among the studies. An the I2value equal to or below 50% and aPvalue equal to or above 0.1, was deemed acceptable for implementing the fixed effect model (FEM). Conversely, if the heterogeneity was determined to be substantial, the random effect model was employed. Numerical data are described by relative risk, odds ratio, and 95%CI. APvalue of < 0.05 was designated as statistical significance.

Single-center retrospective study

Data collection:We conducted an investigation of patients with histologically verified gastric cancer from January 2018 to December 2019 in Gansu Provincial People's Hospital. The investigation followed the principles of the Declaration of Helsinki and obtained approval was obtained from the Ethics Committee The study was conducted according to the approved protocol (ethical consent: 21/10/2022-410, Medical Ethics Committee of Gansu Provincial Hospital). Data on gender, age, tumor diameter, tumor location, lymph node metastasis rate, degree of differentiation, immunohistochemical results (ki67, P53, and Her2), tumor-node-metastasis (TNM) staging (with reference to the American Joint Committee on Cancer (AJCC) criteria for TNM gastric cancer staging (8thed.)], American society of anesthesiology scores, surgical approach, extent of the resection, duration of surgery, blood loss, and perioperative blood transfusion, length of hospital stay, duration of postoperative enteral nutrition and early postoperative complications were gathered from the electronic medical database. The longest diameter measured in routine postoperative pathological specimens was used as the tumor size. The primary tumor location was classified as upper, middle and hypogastric. The degree of differentiation was classified as low/moderate differentiation and high differentiation. Comorbidities were defined in patients with one or more conditions that included of hypertension, diabetes mellitus, and coronary heart disease. Early postoperative complications were defined as those that developed while hospitalized or within 30 d of having surgery, and all complications were graded in terms of severity based on the Clavien-Dindo classification. Grade I or II complications were classified as mild and grade III and higher complications considered severe. Blood specimens were collected from patients within a week prior to surgery to obtain laboratory parameters values.

The criteria for inclusion were:(1) Between 18 and 80 years of age with a clear preoperative clinical diagnosis and postoperative pathological results confirming gastric malignancy; and (2) patients undergoing a first robot-assisted radical R0 resection. The criteria for exclusion were: (1) Patients with distant tumor metastasis; (2) patients with comorbid hematological diseases, autoimmune diseases, infectious diseases, or liver function abnormalities that may affect leukocytes; (3) patients receiving neoadjuvant therapy (radiotherapy or chemotherapy) before surgery; (4) patients with comorbid other malignant tumors; and (5) patients undergoing emergency surgery or with incomplete information. The participants included in the study were followed up by telephone contact, outpatient review, and inpatient treatment. Included patients were carefully monitored every 3 to 6 months after surgery. Annual follow-up was performed after 2 years. Follow-up outcomes were OS and DFS at 5 years postoperatively. The definition of DFS was the period from the start of diagnosis to and any locally recurring disease, distant metastasis, or the last follow-up. OS was defined as the duration between the start of diagnosis and disease-related mortality or the end of the study. The last follow-up was completed in June 2023.

Statistical analyses

All statistical calculations were performed using IBM SPSS Statistics for Windows version 26.0 (IBM Corporation, Armonk, NY, United States). Categorical information is presented as the number of cases (n) and percentages (%). For quantitative data, non-normally distributed continuous-type information is expressed by the medians and interquartile ranges, and normally distributed measures are described as the mean ± SD. Either the Student'st-test or Mann-WhitneyUtest was used to compare groups, depending on the normality of the statistic distribution. Theχ2test was utilized to detect disparities among the classification groups. The optimal threshold for each outcome was determined using the receiver operating characteristic (ROC) curve with the Youden index. Cox proportional hazards models were utilized to estimate the risk ratio for OS and DFS, with HR and 95%CIs reported. A statistically significant level was defined asP< 0.05.

RESULTS

Meta-analysis

Literature search results:A total of 174 articles were identified by the search strategy, including 14 articles in PubMed, 18 articles in the Cochrane Library, 3 articles in EMBASE, 103 articles in the Web of Science and 36 articles in Scopus. Fortythree duplicate articles were deleted, 111 were excluded by evaluating the title and abstract, and 14 were excluded by reading the full text, of which only 6 articles contained risk ratio information and were eligible for the survival outcome analysis. There were 2114 cases overall. The process of literature screening is illustrated in Figure 1. Table 1 presents fundamental descriptions of the included studies.

Figure 1 Literature screening flowchart.

Table 1 The fundamental description of the inclusion studies

SIRI and prognosis of gastric cancer patients:Two studies involving 347 cases described the relationship between SIRI values and OS and DFS. They were combined for meta-analysis. No discernible variability was found between the studies existed (I2< 0.001%,P= 0.271), and the FEM was applied to merge the HR and 95%CI. The findings of the meta-analysis demonstrated that a higher SIRI value was consistently correlated with a poor survival in cancer patients (DFS: HR = 2.36, 95%CI: 1.91-2.92;P< 0.001; OS: HR = 2.02, 95%CI: 1.70-2.41;P< 0.001, Figure 2).

Figure 2 Meta-analysis prognostic forest plot. OS: Overall survival; DFS: Disease-free survival.

Retrospective studies

Baseline materials:A total of 161 participants were included in the retrospective analysis. Table 2 displays the baseline data and clinicopathological traits of the included patients. The study involved 128 males and 33 females. The average age of the subjects was 61.80 ± 9.26 years (30-84 years). The mean preoperative body mass index of all patients was 22.30 ± 3.35 kg/m2. In accordance with the AJCC staging criteria 8thedition, stages I, II, and III were assigned to 26 (16.1%), 49 (30.4%), and 86 (53.4%) patients, respectively. The average follow-up interval for all patients was 42 months (6-60 months). The ideal SIRI cut-off value in ROC analysis was 1.38. By applying the cutoff, 106 (65.8%) individuals had high SIRI values, and 55 (34.2%) with low SIRI values. Preoperative SIRI levels in gastric cancer patients were linked to the presence of comorbidities (P= 0.006), T-stage (P= 0.015), carcinoembryonic antigen (CEA) level (P= 0.003), the presence of early serious postoperative complications (P= 0.001), and the lymph node invasion rate (P= 0.023) (Table 2).

Table 2 Patient baseline characteristics and their correlations with systemic inflammatory response index level after robotic gastrectomy

Cox regression survival analysis:Among the included gastric cancer patients, univariate analysis revealed that older age (P< 0.001), large tumor volume (P= 0.025), late clinical stage (P= 0.005), positive CEA (P< 0.001), intrasurgical blood loss > 200 mL (P= 0.016), lymph node metastasis greater than 4.6% (P< 0.001), serious complications after surgery (P< 0.001), and no complementary chemotherapy (P= 0.001) were associated with shorter 5-year postoperative survival time. The multifactorial model demonstrated that age (HR: 1.067, 95%CI: 1.035-1.099;P< 0.001), TNM stage (P= 0.025), the occurrence of serious complications after surgery (HR: 7.244, 95%CI: 3.780-13.781;P< 0.001), P53 mutation (HR: 0.392, 95%CI: 0.231-0.663;P< 0.001), and Ki67 levels (P= 0.003) were influential prognostic variables for 5-year OS (Table 3). Similarly, COX survival analysis indicated that age (P= 0.003), the presence of comorbidities (P= 0.045), TNM stage (P= 0.003), and the presence of serious postoperative complications (P< 0.001), were individual prognostic factors for DFS (Supplementary Table 1). In univariate analysis, lower SIRI values were associated with longer OS and DFS (HR: 3.787, 95%CI: 2.376-6.034,P< 0.001; HR: 8.884, 95%CI: 4.735-15.070,P< 0.001). According to the multivariable analysis, patients in the low SIRI group had improved survival results. (HR: 2.696, 95%CI: 1.579-4.404,P< 0.001; HR: 6.406, 95%CI: 3.370-12.178,P< 0.001). Further, The OS and DFS Kaplan-Meier survival curves for the SIRI values of all patients are illustrated in Figure 3.

Figure 3 Effect of systemic inflammation response index score on prognosis in patients with robotic gastrectomy. A: Effect of systemic inflammatory response index (SIRI) on overall survival in patients; B: Effect of SIRI on disease-free survival in patients. P value was calculated by the log-rank test.SIRI: Systemic inflammatory response index.

Table 3 Univariate and multivariate Cox regression analyses for overall survival in patients with robotic gastrectomy

According to the Cox regression model analysis, age, TNM stage, and severe postoperative complications were important factors affecting prognosis. Therefore, we performed further subgroup analyses. The participants were categorized into senior and junior age cohorts using 60 years as the cut-off age. The findings demonstrated that, in the junior and senior age categories, OS and DFS, respectively, were longer in the low SIRI value group (Figure 4A-D). In contrast, the individuals with SIRI value less than 1.38 exhibited longer OS and DFS in the TNM stage I and stage II subgroups (Figure 4E and F). In the TNM stage III group, patients with low levels of SIRI levels also had a relatively better prognosis (Figure 4G and H). Not surprisingly, OS and DFS were longer in the low SIRI group than in the high SIRI group compared to the subgroups with no or minor postoperative complications, respectively (Figure 4I and J), and with the exception of the OS rate (Figure 4K), the serious complications group experienced the same DFS rate (Figure 4L).

Figure 4 Effect of systemic inflammatory response index score on overall survival and disease-free survival in different subgroups of patients with robotic gastrectomy. A: Overall survival (OS) of patients in the low age group; B: Disease-free survival (DFS) of patients in the low age group; C:OS of patients in the high age group; D: DFS of patients in the high age group; E: OS of patients in the tumor-node-metastasis (TNM) I-II group; F: DFS of patients in the TNMI-II group; G: OS of patients in the TNMIII group; H: DFS of patients in the TNMIII group; I: OS of patients in the postoperative group with no or minor complications; J: DFS of patients in the postoperative group with no or minor complications; K: OS of patients in the postoperative group with severe complications; L:DFS of patients in the postoperative group with severe complications (P value was calculated by the log-rank test). SIRI: Systemic inflammatory response index.

DISCUSSION

Gastric cancer is a prevalent type of tumor with consistently high morbidity and mortality rates worldwide[12]. Robotic gastric cancer surgery has progressed rapidly in recent years, and its future prospects continue to attract attention. Robotic surgery has obvious technical advantages and superior efficacy compared with conventional laparoscopy[13]. The progression and prognosis of patients with stomach cancer are influenced by various contributing conditions, with inflammation being an important contributor[14]. The prolonged presence of inflammation may harm the gastric mucosa and cause aberrant cellular proliferation[14]. The activation of the inflammatory response creates favorable for the proliferation and colonization of remnant tumor cells, which promotes the local recurrence and distant metastasis of cancer and reduces patient survival[15]. SIRI, an indicator used for assessing a patient's inflammatory status by integrating multiple inflammatory cells values, has certain advantages and prospects for application. However, the accuracy and reliability of utilizing the SIRI require further research and validation. Therefore, we conducted a meta-analysis to examine the significance of SIRI values in predicting the prognoses of gastric cancer patients and investigated its predictive potential for oncological survival benefits in patients undergoing robotic gastric cancer surgery with the aim of providing clinicians with more comprehensive information that can assist in making more accurate diagnostic and therapeutic decisions.

Tumorigenesis involves the establishment of a preneoplastic inflammatory environment[16]. Neutrophils, as an important immune component of the inflammatory response, have an essential function in tumorigenesis and development. Neutrophils can exert a direct oncogenic effect by releasing reactive oxygen species, which induce oxidative DNA damage and increase the mutational load in intestinal models of inflammation-driven cancers[17]. Neutrophils also directly support tumor cell proliferation by releasing factors such as prostaglandin E2, and interleukin (IL)-1 receptor antagonist (IL-1RA) through various paracrine signaling pathways[18]. A recent study also found that neutrophils in the circulation supported metastatic cancer cells by forming clusters of cells[19] involved in distant metastasis and disease recurrence.

Monocytes are an integral part of the tumor microenvironment and act on the tumor population through multifarious mechanisms, including the induction of immunological tolerance, angiogenesis and increased tumor cell dissemination[20]. Monocytes are capable of excreting immune suppressants, such as transforming growth factor β and IL-10, which inhibit the sensitivity of immune cells and attenuate the immunological processes helping tumor cells to evade attack by the immune system[21]. Monocytes can differentiate into endothelial cell-like cells that are involved in the tumor angiogenesis process. These cells can produce antiangiogenic agents (vascular endothelial growth factor), which facilitate neovascularization and provide sufficient nutrients and oxygen to the tumor[22]. Monocytes can secrete matrix metalloproteinases, which are enzymes that can degrade the stroma and encourage the invasion and metastasis of the tumor cells[23].

T-cell infiltration that develops in human cancers is a regulator of natural disease progression[24]. Cytotoxic T lymphocytes can directly kill tumor cells. Lymphocytes can influence tumor development by modulating the immune response. Certain lymphocyte subsets, such as regulatory T cells, can downregulate the immunological response which reduces attacks on tumor cells[25]. Alternatively, other lymphocyte subsets, such as helper T cells, can augment the immune response and promote the killing of tumor cells[26]. Lymphocytes can develop memory immunity, which includes a long-term antibody and cellular immune responses to tumor cells[27].

The SIRI is unique in reflecting the sophisticated interactions and complementary activities of the primary immune cells in the cancer microenvironment. This novel metric is intended for evaluating the survival of patients with malignancies and reflects the state of equilibrium between the immune and inflammatory systems of the host. Increasing clinical studies have reported that SIRI values are strongly associated with the survival time of a wide range of tumor types. Chenet al[28] reported that nasopharyngeal cancer patients with higher SIRI values experienced considerably shorter OS. A separate study reported that postmenopausal women with breast cancer with low SIRI values exhibited notably longer OS[29]. SIRI values demonstrated favorable prognostic ability in a number of solid tumors, including pancreatic, gastric and oesophageal carcinomas[30,31]. The SIRI is suitable for frequent testing during follow-up because it can be conveniently calculated from a hematological count. Both the value and the dynamics of SIRI have the potential to assessing the efficacy of adjuvant radiotherapy, the selection of suitable patients for specific targeted therapies and immunotherapies, and monitoring for possible recurrences. Similarly, SIRI values were associated with OS and DFS in gastric cancer patients in our meta-analysis, providing valid evidence for its potential to predict prognosis. In the population of patients undergoing robotic gastric cancer surgery, SIRI values were also a stable independent prognostic factor for long-term oncological outcomes, with the low SIRI group showing improved survival compared to the high SIRI group. SIRI has the advantages of being easily accessible, with low cost and good reproducibility. SIRI values, using a combination of multiple metrics, can more accurately assess a patient's inflammatory status and tumor load. The continuous improvement and optimization of robotic gastric cancer surgery will enable it to become the mainstream of minimally invasive gastric cancer surgery, and our findings make SIRI an encouraging tool to add credibility to decisionmaking regarding cancer treatment strategies.

Our study had the following limitations: (1) This study was conducted retrospectively. Thus, a prospective investigation with a large sample size is needed to validate the potential implication of SIRI values in patients undergoing robotic gastric cancer surgery and clarify the optimal SIRI cutoff value; (2) the study did not dynamically assess changes in SIRI values; and (3) the mechanisms associated with SIRI values and cancer prognosis prediction remain unclear and require in-depth studies and confirmation.

CONCLUSION

Overall, the conclusion of our meta-analysis supports an intrinsic link between SIRI levels and the prognosis of patients with gastric cancer. The findings of our cohort study showed that preoperative SIRI values independently contributed to the OS and DFS in patients who underwent robotic surgery for stomach cancer. The evaluation of SIRI levels can help surgeons and oncologists to more effectively manage preoperative treatment more effectively and develop postoperative management strategies for gastric cancer patients.

ARTICLE HIGHLIGHTS

Research background

Gastric cancer is a prevalent type of tumor with consistently high morbidity and mortality rates worldwide. Robotic gastric cancer surgery has progressed rapidly in recent years, and its future prospects continue to attract attention. Robotic surgery has obvious technical advantages and superior efficacy compared with conventional laparoscopy. The progression and prognosis of patients with stomach cancer are influenced by various contributing conditions, with inflammation being an important contributor. The prolonged presence of inflammation may harm the gastric cancer and cause aberrant cellular proliferation. The activation of the inflammatory response creates favorable for the proliferation and colonization of remnant tumor cells, which promotes the local recurrence and distant metastasis of cancer and reduces patient survival. Systemic inflammatory response index (SIRI), an indicator used for assessing a patient's inflammatory status by integrating multiple inflammatory cells values, has certain advantages and prospects for application.

Research motivation

The accuracy and reliability of using the SIRI need further research and validation. Therefore, we performed a metaanalysis to examine the relevance of SIRI values to the prognoses of gastric cancer patients and investigated its predictive value for oncological survival benefits in patients undergoing robotic gastric cancer surgery with the aim of providing clinicians with more comprehensive information that can assist in making more accurate diagnostic and therapeutic decisions.

Research objectives

The main objective of this study was to examine the relevance of SIRI values to the prognoses of gastric cancer patients and investigate its predictive value for oncological survival benefits in patients undergoing robotic gastric cancer surgery. Our findings make SIRI an encouraging tool to add credibility to decision-making regarding cancer treatment strategies.

Research methods

We performed a meta-analysis to examine the correlation between SIRI values and the prognosis of patients with gastric cancer and investigated its predictive value for oncological survival benefit in patients who underwent robotic gastric cancer surgery by analyzing data from a retrospective cohort.

Research results

Overall, the conclusion of our meta-analysis supports an intrinsic link between SIRI levels and the prognosis of patients with gastric cancer. The findings of our cohort study showed that preoperative SIRI values independently contributed to the overall survival and disease-free survival in patients who underwent robotic surgery for stomach cancer.

Research conclusions

The SIRI is unique in reflecting the sophisticated interactions and complementary activities of the major immune cells in the cancer microenvironment. This new metric is designed to assess survival in patients with malignancy and reflects the state of equilibrium between the immune and inflammatory systems of the host. Our findings make SIRI an encouraging tool to add credibility to decision-making regarding cancer treatment strategies.

Research perspectives

A prospective investigation with a large sample size is needed to validate the potential implication of SIRI values in patients undergoing robotic gastric cancer surgery and clarify the optimal SIRI cutoff value. The mechanisms associated with SIRI values and cancer prognosis prediction remain unclear and require in-depth studies and confirmation.

FOOTNOTES

Co-first authors:Jing-Yao Ren and Meng Xu.

Author contributions:Ren JY conceived and designed the study; Xu M revised the manuscript and provided important guidance on data analysis; Ren JY, Xu M, Niu XD, Ma SX, Jiao YJ, Wang D and Yu M conducted all data collection and analysis and compiled charts; all authors were involved in the critical review of the results and have contributed to, read, and approved the final manuscript. Ren JY and Xu M contributed equally to this work as co-first authors. Substantial contribution: Ren JY and Xu M have made substantial contributions to the research project. This included involvement in the data collection and analysis, and the revision of the research content. Responsibility for research results: Ren JY and Xu M bear some responsibility for the research results and have been involved in the critical review and approval of the final submitted version. Adherence to guidelines: We adhere to the guidelines provided by academic journals and publishing organizations to ensure that all listed authors meet the relevant standards and requirements. In summary, we believe that designating Ren JY and Xu M as co-first authors is fitting for our manuscript as it accurately reflects our team's collaborative spirit, equal contributions, and diversity.

Supported byNational Natural Science Foundation of China, No. 8236110677; Natural Science Foundation of Gansu Province, No. 18JR2RA033; Gansu Da Vinci Robot High-End Diagnosis and Treatment Team Construction Project, National Key Research and Development Program, No. 2020RCXM076.

Institutional review board statement:This study was reviewed and approved by the Ethics Committee of Gansu Provincial Hospital (ethical consent: 21/10/2022-410).

Informed consent statement:This study has been granted exemption from informed consent. All procedures and protocols were reviewed and approved by the Institutional Review Board (IRB) prior to the commencement of the study. The IRB determined that the study met the criteria for exemption under the federal regulations governing human subject’s research. We have followed all necessary ethical guidelines and regulations throughout the study.

Conflict-of-interest statement:All the Authors have no conflict of interest related to the manuscript.

Data sharing statement:The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

STROBE statement:The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Open-Access:This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Country/Territory of origin:China

ORCID number:Ya-Jun Jiao 0000-0003-3980-2492; Hui Cai 0000-0001-5857-1744.

S-Editor:Qu XL

L-Editor:A

P-Editor:Zhang YL