Gao SS, Guan XX, Miu XX, Yu SL, Zhu XP. Risk factors analysis and management strategy optimization for postoperative complications in neonatal necrotizing enterocolitis: A single-center retrospective study. World J Gastrointest Surg 2026; 18(10): 121417 [DOI: 10.4240/wjgs.121417]
Corresponding Author of This Article
Sheng-Lin Yu, MD, Chief Physician, Department of Neonatology, Children’s Hospital of Soochow University, No. 92 Zhongnan Street, Industrial Park, Suzhou 215000, Jiangsu Province, China. wm19711011@sina.com
Research Domain of This Article
Gastroenterology & Hepatology
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research-article
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World J Gastrointest Surg. Oct 27, 2026; 18(10): 121417 Published online Oct 27, 2026. doi: 10.4240/wjgs.121417
Risk factors analysis and management strategy optimization for postoperative complications in neonatal necrotizing enterocolitis: A single-center retrospective study
Co-corresponding authors: Sheng-Lin Yu and Xue-Ping Zhu.
Author contributions: Gao SS and Guan XX contributed equally to this study as co-first authors, including study design, data collection, statistical analysis, and manuscript drafting and revision; Yu SL and Zhu XP jointly provided project guidance, conducted quality control, critically revised the manuscript, and took overall responsibility for the study as co-corresponding authors; Miu XX participated in data collation, literature review, and manuscript proofreading. All the authors have read and approved the final version of the manuscript.
AI contribution statement: The authors declare that no AI tools were used in the development or writing of this manuscript and take full responsibility for its integrity, accuracy, and originality.
Institutional review board statement: This study has been reviewed and approved by the Medical Ethics Committee of Children’s Hospital of Soochow University, No. 2026CS028.
Informed consent statement: All the individuals who participated in this study provided their written informed consent prior to study enrolment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Corresponding author: Sheng-Lin Yu, MD, Chief Physician, Department of Neonatology, Children’s Hospital of Soochow University, No. 92 Zhongnan Street, Industrial Park, Suzhou 215000, Jiangsu Province, China. wm19711011@sina.com
Received: April 28, 2026 Revised: June 11, 2026 Accepted: July 3, 2026 Published online: October 27, 2026 Processing time: 173 Days and 21.7 Hours
Abstract
BACKGROUND
Neonatal necrotizing enterocolitis (NEC) is severe with high morbidity and mortality, and postoperative complications seriously affect prognosis.
AIM
To investigate the risk factors for postoperative complications in neonates with necrotizing enterocolitis (NEC) and provide evidence for optimizing perioperative management.
METHODS
Clinical data of 62 NEC infants undergoing exploratory laparotomy at the Children’s Hospital of Soochow University from August 2022 to September 2025 were retrospectively analyzed. The patients were divided into complication and non-complication groups based on the occurrence of major postoperative complications. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for postoperative complications.
RESULTS
Among the 62 infants, 28 (45.16%) developed major postoperative complications, with septic shock being the most common (25.81%). Combined univariate and multivariate logistic regression analysis showed that preoperative hemodynamic instability [odds ratio (OR) = 5.32, 95% confidence interval (CI): 1.84-15.39], intestinal resection length > 30 cm (OR = 4.18, 95%CI: 1.51-11.56), albumin < 30 g/L on postoperative day 3 (OR = 3.77, 95%CI: 1.42-10.00), and postoperative mechanical ventilation duration > 7 days (OR = 3.25, 95%CI: 1.21-8.74) were independent risk factors for postoperative complications of NEC (P < 0.05).
CONCLUSION
The occurrence of postoperative complications in neonates with NEC is closely related to the preoperative hemodynamic status, surgical extent, and early postoperative recovery. Perioperative circulatory support, refined surgical planning, early nutritional support, and respiratory management should be strengthened to reduce the risk of complications and to improve the prognosis of affected infants.
Core Tip: This retrospective study analyzed 62 neonates with necrotizing enterocolitis who underwent laparotomy. Four factors were associated with an increased risk of postoperative complications. These include problems with preoperative blood pressure, long intestinal resection, low postoperative albumin levels, and long-term mechanical ventilation. These findings provide evidence for improving patient management before and after surgery.
Citation: Gao SS, Guan XX, Miu XX, Yu SL, Zhu XP. Risk factors analysis and management strategy optimization for postoperative complications in neonatal necrotizing enterocolitis: A single-center retrospective study. World J Gastrointest Surg 2026; 18(10): 121417
Neonatal necrotizing enterocolitis (NEC) is one of the most common acute gastrointestinal emergencies. This condition is characterized by intestinal inflammation, ischemia, necrosis, and perforation, and is associated with high morbidity, mortality, and disability rates[1,2]. Surgery is a very important procedure that can save the lives of infants with severe NEC. The main objectives of the procedure are to remove the necrotic bowel segments, control the intra-abdominal infection, restore intestinal continuity or diversion of intestinal contents, restore bowel function, and reduce the intra-abdominal pressure[3,4]. However, due to immature intestinal development and poor immune function, especially in preterm neonates, combined with multiple insults such as surgical trauma and infection, NEC infants still face a high risk of postoperative complications[5,6]. These complications not only significantly prolong hospital stay and increase medical costs, but also directly affect long-term prognosis and quality of life and may even lead to death, imposing a heavy burden on families and society[7,8]. Therefore, an in-depth exploration of the risk factors for postoperative complications in NEC and the development of targeted optimized management strategies are of great theoretical significance and practical value for improving clinical outcomes in affected infants. This study retrospectively analyzed the clinical data of NEC infants undergoing surgery at a single center to identify independent risk factors for postoperative complications, with the aim of providing a reference for the clinical optimization of perioperative management strategies.
MATERIALS AND METHODS
Study subjects
This retrospective study was approved by the Ethics Committee of the Children’s Hospital of Soochow University, No. 2026CS028. The clinical data of 62 neonates diagnosed with NEC who underwent exploratory laparotomy at the Neonatal Department of the Children’s Hospital of Soochow University between August 2022 and September 2025 were retrospectively analyzed.
Inclusion criteria: (1) Diagnosed with NEC at modified Bell stage II (definite stage) or stage III (advanced stage); (2) Neonates with gestational age ≥ 28 weeks and ≤ 42 weeks; (3) Undergoing first exploratory laparotomy for NEC; (4) Informed consent for surgical treatment obtained from the legal guardians of the infants; and (5) Complete clinical data available. Exclusion criteria: (1) Secondary NEC caused by congenital gastrointestinal malformations, such as malrotation of the intestine and intestinal atresia; (2) Spontaneous intestinal perforation; (3) Treated with abdominal paracentesis and drainage without laparotomy; and (4) Severe loss of clinical data.
Study methods
Data were collected from the hospital electronic medical record system, including: (1) Baseline characteristics: Gender, gestational age, birth weight, mode of delivery, multiple pregnancy, use of prenatal corticosteroids; (2) Clinical data at NEC diagnosis: Postnatal age at diagnosis, Bell stage at diagnosis, preoperative ventilatory support, preoperative hemodynamic status; (3) Worst preoperative laboratory values: White blood cell count, platelet count, C-reactive protein (CRP), blood lactate; (4) Time from meeting surgical indications to initiation of surgery; (5) Surgical parameters: Surgical approach, site of intestinal resection, length of intestinal resection, operation duration, intraoperative blood loss, performance of abdominal irrigation; and (6) Postoperative outcomes: Duration of mechanical ventilation, duration of vasoactive drug use, albumin level on postoperative day 3, time to initiation of enteral nutrition, time to full enteral nutrition, total postoperative hospital stay, incidence and type of major postoperative complications, reoperation, and in-hospital survival.
Grouping: Infants were divided into complication and non-complication groups according to the occurrence of one or more of the following major postoperative complications during hospitalization: (1) Anastomotic leakage or intestinal fistula confirmed by imaging or reoperation; (2) Short bowel syndrome (SBS): Residual small bowel length < 25% of the expected total length or dependence on parenteral nutrition for more than 42 days; (3) Mechanical or adhesive intestinal obstruction requiring reoperation; (4) Deep surgical site infection or full-thickness wound dehiscence; (5) Postoperative septic shock; and (6) In-hospital death.
The length of the bowel resection was measured intraoperatively by the attending pediatric surgeon using a sterile ruler along the antimesenteric border of the resected bowel specimen. All measurements were recorded immediately after resection according to the departmental surgical protocol. The cutoff value of 30 cm for bowel resection length was selected based on the distribution characteristics of our cohort and clinical experience at our institution, and was used to distinguish extensive from limited bowel resection. Preoperative hemodynamic instability was defined as the presence of at least one of the following conditions within 24 hours before surgery: (1) Requirement for vasoactive drug support to maintain age-appropriate blood pressure; (2) Persistent hypotension despite adequate fluid resuscitation; and (3) Evidence of poor tissue perfusion, including prolonged capillary refill time (> 3 seconds), elevated lactate (> 4 mmol/L), or oliguria.
Statistical analysis
Statistical analysis was performed using SPSS 26.0 software. Normality tests were conducted for continuous variables. Normally distributed data were presented as mean ± SD, and compared between groups using independent-samples t-test. Non-normally distributed data are presented as median (interquartile range) and compared using the Mann-Whitney U test. Categorical variables were presented as n (%), and compared using χ2 test or Fisher’s exact test. Variables with statistical significance in univariate analysis were entered into a multivariate logistic regression model to identify independent risk factors for major postoperative complications of NEC. Odds ratios (OR) and 95% confidence intervals (CI) were determined. Statistical significance was set at P < 0.05.
RESULTS
Univariate analysis of factors associated with postoperative complications of NEC
A total of 62 NEC patients who underwent surgery were included in this study. Among them, 28 (45.16%) developed at least one major postoperative complication. The most common complication was postoperative septic shock (16 patients, 25.81%), followed by wound complications (9 patients, 14.52%), SBS (8 patients, 12.90%), bowel obstruction requiring reoperation (6 patients, 9.68%), and anastomotic leak/fistula (5 patients, 8.06%).
Univariate analysis showed that patients in the complication group differed significantly from those in the non-complication group in gestational age, birth weight, preoperative mechanical ventilation, preoperative hemodynamic status, preoperative platelet count, preoperative blood lactate, timing of surgery, surgical procedure, length of bowel resection (> 30 cm), duration of postoperative mechanical ventilation, duration of postoperative vasoactive drug use, serum albumin on postoperative day 3, time to initiation of enteral nutrition, time to full enteral nutrition, and postoperative length of hospital stay (all P < 0.05).
No significant differences were observed between the two groups in sex, mode of delivery, multiple gestations, antenatal steroid use, age at diagnosis, Bell stage, preoperative white blood cell count, preoperative CRP level, operation time, intraoperative blood loss, peritoneal lavage, or resection of the terminal ileum (all P > 0.05; Table 1).
Table 1 Univariate analysis of factors associated with postoperative complications of neonatal necrotizing enterocolitis, n (%)/median (interquartile range)/mean ± SD.
Variable
Complication group (n = 28)
No-complication group (n = 34)
χ2/t/Z
P value
Sex
χ2 = 0.125
0.724
Male
16 (57.14)
21 (61.76)
Female
12 (42.86)
13 (38.24)
Gestational age (weeks)
30.82 ± 2.51
34.15 ± 2.95
t = 4.782
< 0.001
Birth weight (g)
1350 (980, 1680)
2100 (1580, 2780)
Z = 4.256
< 0.001
Mode of delivery
χ2 = 0.706
0.401
Vaginal delivery
11 (39.29)
17 (50.00)
Cesarean section
17 (60.71)
17 (50.00)
Multiple gestation
7 (25.00)
5 (14.71)
χ2 = 1.051
0.305
Antenatal steroid use
20 (71.43)
18 (52.94)
χ2 = 2.143
0.143
Age at diagnosis (days)
13.46 ± 5.25
11.82 ± 4.76
t = 1.310
0.195
Bell stage
χ2 = 1.237
0.266
Stage II
6 (21.43)
12 (35.29)
Stage III
22 (78.57)
22 (64.71)
Preoperative mechanical ventilation
25 (89.29)
23 (67.65)
χ2 = 4.085
0.043
Preoperative hemodynamic instability
20 (71.43)
8 (23.53)
χ2 = 14.385
< 0.001
Preoperative laboratory parameters
Lowest preoperative white blood cell count (× 109/L)
7.52 ± 3.85
9.01 ± 4.12
t = -1.488
0.142
Lowest preoperative platelet count (× 109/L)
78.21 ± 45.36
135.88 ± 65.74
t = -4.025
< 0.001
Peak preoperative C-reactive protein (mg/L)
92.35 ± 48.21
85.67 ± 51.43
t = 0.528
0.599
Peak preoperative blood lactate (mmol/L)
4.51 ± 1.80
3.20 ± 1.20
t = 3.412
0.001
Timing of surgery
χ2 = 5.822
0.016
≤ 48 hours
9 (32.14)
22 (64.71)
> 48 hours
19 (67.86)
12 (35.29)
Surgical procedure
χ2 = 6.504
0.039
Primary anastomosis
5 (17.86)
14 (41.18)
Bowel resection with stoma
21 (75.00)
18 (52.94)
Others
2 (7.14)
2 (5.88)
Resection involving terminal ileum
23 (82.14)
20 (58.82)
χ2 = 3.853
0.050
Length of bowel resection
χ2 = 9.259
0.002
≤ 30 cm
11 (39.29)
27 (79.41)
> 30 cm
17 (60.71)
7 (20.59)
Operation time (minutes)
135.41 ± 35.22
120.26 ± 30.15
t = 1.825
0.073
Intraoperative blood loss (mL)
28.21 ± 15.34
21.76 ± 12.87
t = 1.805
0.076
Peritoneal lavage
26 (92.86)
30 (88.24)
χ2 = 0.416
0.519
Duration of postoperative mechanical ventilation (days)
8.68 ± 4.52
5.12 ± 3.21
t = 3.650
0.001
Duration of postoperative vasoactive drug use (days)
Multivariate logistic regression analysis of factors associated with postoperative complications of NEC
Variables that were statistically significant in the univariate analysis were converted into binary variables and coded as follows: Gestational age < 32 weeks, birth weight < 1500 g, requirement for preoperative mechanical ventilation, preoperative hemodynamic instability, preoperative platelet count < 100 × 109/L, elevated preoperative blood lactate level, timing of surgery > 48 hours, stoma formation, length of bowel resection > 30 cm, postoperative mechanical ventilation > 7 days, postoperative vasoactive drug use > 3 days, serum albumin level on postoperative day 3 < 30 g/L, time to initiation of enteral nutrition > 7 days, time to full enteral nutrition > 21 days, and postoperative hospital stay > 40 days. Multivariate logistic regression analysis showed that preoperative hemodynamic instability (OR = 5.32, 95%CI: 1.84-15.39, P = 0.002), length of bowel resection > 30 cm (OR = 4.18, 95%CI: 1.51-11.56, P = 0.006), serum albumin on postoperative day 3 < 30 g/L (OR = 3.77, 95%CI: 1.42-10.00, P = 0.008), and postoperative mechanical ventilation > 7 days (OR = 3.25, 95%CI: 1.21-8.74, P = 0.019) were independent risk factors for postoperative complications in NEC patients (Table 2).
Table 2 Multivariate logistic regression analysis of factors associated with postoperative complications of neonatal necrotizing enterocolitis.
NEC is one of the most life-threatening gastrointestinal emergencies in the neonatal period, and is particularly common in preterm infants. The disease progresses rapidly, is associated with multiple complications, and has a high mortality rate, posing a serious threat to neonatal health[9,10]. In recent years, despite significant advances in perinatal medicine and neonatal intensive care, the overall incidence of NEC has not decreased significantly, severely affecting survival rates and long-term quality of life[11,12]. In extremely low- and very low-birth-weight infants, the incidence of NEC can reach 5%-10%, and approximately 20%-40% of affected infants require surgical intervention[13,14]. Postoperative complications remain highly prevalent among patients with NEC and are key factors affecting the prognosis. Therefore, exploring the risk factors for postoperative complications is of great clinical significance for optimizing treatment strategies and improving outcomes[15,16].
A large number of patients with NEC were admitted every year to the Department of Neonatology and Neonatal Surgery at the Children’s Hospital of Soochow University, a regional critical neonatal care center. This indicates that the hospital had extensive experience with surgical management. In the present study, 62 patients underwent surgery, and found that 45.16% experienced at least one complication after surgery. The most common complication was postoperative septic shock, affecting 25.81% of patients. This was followed by wound complications, which occurred in 14.52% of patients, and SBS, which occurred in 12.90% of patients. These findings were consistent with those of previous national and international studies. These studies have highlighted the high incidence of postoperative complications in patients with NEC. These findings are supported by[17,18]. These findings emphasize the complexity of postoperative management in this population. These studies also emphasized the challenges associated with postoperative management.
It should be noted that intestinal length in neonates varies substantially according to the gestational age and birth weight. Therefore, a fixed resection length may not fully reflect the functional bowel loss in different infants. In the present study, a threshold of > 30 cm was selected based on the distribution characteristics of this cohort, as previous studies have suggested that a residual bowel length below approximately 30 cm is associated with an increased risk of SBS and prolonged dependence on parenteral nutrition. Nevertheless, bowel resection and residual bowel lengths are not completely equivalent concepts, and future studies should incorporate standardized residual bowel measurements adjusted for gestational age. After analyzing the data, we found several factors associated with an increased risk of postoperative complications. These include blood pressure problems before surgery, surgery that takes more than 30 cm out of the bowel, and low blood albumin levels on postoperative day after surgery. We also found that patients who needed a machine to help them breathe for more than seven days after surgery had a higher risk of postoperative complications. The underlying mechanisms for these associations may be as follows. Preoperative hemodynamic instability may indicate severe sepsis. It also may indicate decompensated systemic inflammatory response syndrome. Such conditions are often accompanied by vasodilation. Capillary leakage syndrome was also observed. Myocardial depression is another characteristic feature of this disease. A marked reduction in the effective circulating volume may occur. This may reflect severe infection. It also may indicate circulatory dysfunction. Alternatively, this may reflect multiorgan involvement[19,20]. Surgery under this fragile physiological state reduces tolerance to surgical trauma, amplifies inflammatory and stress responses, delays tissue repair, promotes infection spread, and exacerbates organ dysfunction, thereby significantly increasing the risk of anastomotic leakage, intra-abdominal infection, and refractory septic shock[21,22]. Van Varsseveld et al[23] also reported that the preoperative cardiovascular status is closely related to surgical outcomes in extremely preterm NEC patients, which is consistent with the finding that preoperative hemodynamic instability is the strongest risk factor (OR = 5.32).
This highlights the importance of evaluating and optimizing circulatory function prior to surgery to improve tissue perfusion and organ reserve, creating a relatively stable physiological “window” to reduce postoperative complication risk. A bowel resection length > 30 cm was identified as the second most important risk factor (OR = 4.18). It should be noted that the threshold of bowel resection length > 30 cm used in this study was intended to reflect the extent of intestinal loss rather than serve as a direct surrogate for residual bowel length. We acknowledge that bowel resection and residual bowel lengths are not equivalent measures. Current literature suggests that a residual small bowel length of less than 30 cm is a critical determinant of SBS and long-term intestinal failure. In contrast, the amount of bowel resection does not fully account for individual variations in the total intestinal length related to gestational age, birth weight, and anatomical differences. Therefore, the observed association between resection length > 30 cm and postoperative complications should be interpreted as indicating more extensive surgical injury and reduced intestinal reserve, rather than directly predicting SBS. Future studies should incorporate standardized measurements of residual bowel length and evaluate their relationship with postoperative outcomes. Given the limited intestinal length in neonates, extensive resection results in greater surgical trauma and inflammatory burden, while significantly reducing the absorptive area for nutrients such as fats, fat-soluble vitamins, electrolytes, and fluids, with long-term implications[24]. Impairment of the intestinal mucosal barrier increases the risk of bacterial translocation, predisposing patients to SBS, infection, and a vicious cycle of complications, further increasing treatment difficulty and healthcare burden[25,26]. These findings emphasize adherence to “damage-control” and “intestinal-preservation” principles in NEC surgery, balancing the need to remove necrotic bowel while preserving viable intestine, particularly the ileocecal region and terminal ileum, to support postoperative intestinal function and nutrient absorption. Postoperative hypoalbuminemia (serum albumin level < 30 g/L on day 3) may arise from multiple mechanisms beyond nutritional depletion. Surgical trauma and systemic inflammation increase capillary permeability, resulting in the extravasation of albumin into the interstitial space. Aggressive fluid resuscitation may further dilute circulating albumin concentrations, while inflammatory cytokines suppress hepatic albumin synthesis[27,28]. Therefore, hypoalbuminemia reflects not only nutritional status but also the severity of systemic inflammatory responses. Recent studies have suggested that the CRP/albumin ratio (CAR), which combines inflammatory and nutritional information, may outperform either marker alone in predicting disease severity or the need for surgical intervention in NEC. Ghauri et al[29] demonstrated that an elevated CAR was associated with worse clinical outcomes in patients with NEC. Future studies should evaluate whether CAR has a superior predictive value for postoperative complications compared with albumin alone[30].
The presence of low albumin levels in the early postoperative period is an indication of not only nutritional depletion, but also a state of hypercatabolism and severe inflammation. This can result in reduced plasma colloid osmotic pressure, worsened tissue edema, impaired gut motility and absorption, and delayed enteral nutrition initiation and tolerance of enteral nutrition. As an important antioxidant and immune modulator, low albumin levels impair immune defense and delay wound healing and tissue repair, thereby increasing the risk of complications. Ghauri et al[29] proposed the CAR as a predictive marker for surgical intervention in NEC, highlighting the importance of inflammatory nutritional status in prognosis. Therefore, close monitoring of postoperative albumin levels is warranted along with timely nutritional support via enteral or parenteral routes. If necessary, albumin supplementation should be provided to improve the colloid osmotic pressure, reduce edema, enhance immunity, and support intestinal recovery. If a patient requires mechanical ventilation for more than 7 days after an operation, this can cause respiratory complications and may indicate severe infection. It can also lead to other problems such as problems with the heart or nervous system. Clinical management should focus on carefully assessing and maintaining respiratory function, using ventilation strategies to protect the lungs, and early weaning of patients to reduce ventilation-related complications. Interpretation of this finding requires caution, because the duration of postoperative mechanical ventilation may represent a marker of disease severity rather than a direct causal factor. Infants with severe systemic inflammation, hemodynamic instability, or multiple organ dysfunction are more likely to require prolonged ventilatory support and are at greater risk of postoperative complications. Therefore, reverse causality could not be completely excluded. Although multivariate regression was performed to adjust for major confounders, the retrospective design limited causal inference. Future prospective studies using stratified analyses or severity-adjusted models are needed to clarify this causal relationship. This study had several limitations. First, this was a retrospective single-center study with a relatively small sample size, which may limit the generalizability of the findings and introduce potential selection bias. Second, among the 62 infants included, only 28 experienced postoperative complications, and 15 variables were entered into the multivariate logistic regression model. The relatively low event-per-variable ratio may increase the risk of model overfitting and unstable coefficient estimates. Therefore, the identified risk factors should be interpreted with caution and require validation in larger multicenter cohorts. Third, bowel resection length, rather than residual bowel length, was analyzed, and the total remaining bowel length was not routinely recorded. Consequently, the relationship between bowel preservation and the subsequent development of SBS could not be fully evaluated. Fourth, although a multivariate regression was performed to adjust for potential confounders, the retrospective design precluded definitive causal inferences. In particular, the association between prolonged postoperative mechanical ventilation and postoperative complications may be influenced by reverse causality because infants with more severe disease are more likely to require prolonged ventilatory support and simultaneously experience adverse outcomes. Finally, preoperative hemodynamic instability was assessed according to clinical practice in the hospital center, and variations in definitions across institutions may have affected external reproducibility. Future prospective multicenter studies with larger sample sizes, standardized perioperative assessments, and longer follow-up periods are warranted to validate and extend these findings.
CONCLUSION
In summary, the risk of complications after surgery in patients with NEC is closely linked to their preoperative blood pressure, extent of bowel resection, and early postoperative recovery. Optimizing perioperative circulatory support, planning surgeries precisely, providing early nutritional support, and carefully managing respiration are essential for reducing the risk of complications and improving outcomes. This study is not without its limitations, which include a relatively small sample size, single-center design, and the potential for information and selection biases that are intrinsic to retrospective analyses. To gain a better understanding of the risk factors and mechanisms underlying postoperative complications in NEC, further additional multicenter studies. These studies should have larger sample sizes and better controls for confounding factors.
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Footnotes
Peer review: Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: China
Peer-review report’s classification
Scientific quality: Grade B, Grade C
Novelty: Grade B, Grade C
Creativity or innovation: Grade B, Grade B
Scientific significance: Grade C, Grade C
P-Reviewer: Inoue M, PhD, United States; Shiozaki A, PhD, Japan S-Editor: Wu S L-Editor: A P-Editor: Wang WB
