Yang J, Zhang CZ, Wang JJ, Zhang J. Metabolic improvement effects of jejunoileal side-to-side anastomosis in patients with type 2 diabetes and the glucagon-like peptide-1 mechanism. World J Diabetes 2025; 16(4): 103567 [DOI: 10.4239/wjd.v16.i4.103567]
Corresponding Author of This Article
Jing Zhang, MD, Central Laboratory, The First College of Clinical Medical Science, China Three Gorges University and Yichang Central People’s Hospital, No. 183 Yiling Avenue, Yichang 443000, Hubei Province, China. zhangjing@ctgu.edu.cn
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Editorial
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Jian Yang, Cheng-Zhi Zhang, Jiao-Jiao Wang, Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University and Yichang Central People’s Hospital, Yichang 443000, Hubei Province, China
Jian Yang, Cheng-Zhi Zhang, Jiao-Jiao Wang, Jing Zhang, Hubei Key Laboratory of Ischemic Cardiovascular Disease, Yichang 443000, Hubei Province, China
Jian Yang, Cheng-Zhi Zhang, Jiao-Jiao Wang, Jing Zhang, Hubei Provincial Clinical Research Center for Ischemic Cardiovascular Disease, Yichang 443000, Hubei Province, China
Cheng-Zhi Zhang, Jiao-Jiao Wang, Jing Zhang, Central Laboratory, The First College of Clinical Medical Science, China Three Gorges University and Yichang Central People’s Hospital, Yichang 443000, Hubei Province, China
Author contributions: Yang J, Zhang J, and Zhang CZ wrote the original draft and contributed to conceptualization, reviewing, and editing; Zhang CZ and Yang J made equal and significant intellectual contributions to this work; Wang JJ was responsible for creating the illustrations and tables; All authors read and approved the final version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 82471616, No. 82170418 and No. 82271618; Natural Science Foundation of Hubei Province, No. 2022CFA015; Central Guiding Local Science and Technology Development Project, No. 2022BGE237; Key Research and Development Program of Hubei Province, No. 2022BCE001 and No. 2023BCB139; and Hubei Provincial Health Commission Project, No. WJ2023M151.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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/
Corresponding author: Jing Zhang, MD, Central Laboratory, The First College of Clinical Medical Science, China Three Gorges University and Yichang Central People’s Hospital, No. 183 Yiling Avenue, Yichang 443000, Hubei Province, China. zhangjing@ctgu.edu.cn
Received: November 28, 2024 Revised: January 6, 2025 Accepted: January 14, 2025 Published online: April 15, 2025 Processing time: 97 Days and 13.6 Hours
Abstract
Wang et al explored the metabolic improvement effects of jejunoileal side-to-side anastomosis in patients with type 2 diabetes mellitus (T2DM), focusing on its multitarget metabolic regulatory potential through enhanced secretion of glucagon-like peptide-1. This surgical procedure alters the direction of nutrient flow, activates distal ileal L cells, and increases endogenous glucagon-like peptide-1 levels, supporting glucose homeostasis, enhancing insulin sensitivity, regulating body weight, and improving cardiovascular health. This structural adjustment transforms the gastrointestinal tract into an active endocrine regulatory organ, providing a pathway for metabolic improvement in patients with T2DM and other complex metabolic disorders. Although this procedure demonstrates significant metabolic improvements within 3-6 months after surgery, integrating hormone level measurements, metabolic marker analysis, and long-term follow-up has become crucial for exploring the complex mechanisms of T2DM in the field of metabolic surgery and T2DM management. Multidisciplinary collaboration involving support from endocrinology, nutrition, and rehabilitation teams before and after surgery is becoming increasingly vital in the long-term management of patients with T2DM. This collaboration optimizes surgical outcomes and enhances metabolic management. Side-to-side anastomosis shows potential in the multitarget metabolic management of T2DM, providing an additional intervention option for patients with T2DM and metabolic disorders.
Core Tip: Type 2 diabetes mellitus (T2DM) remains a global health challenge with rising prevalence and complications. Metabolic surgery, particularly jejunoileal side-to-side anastomosis, offers promising outcomes by enhancing glucagon-like peptide-1 secretion and improving glucose homeostasis and weight management. This innovative procedure transforms the gastrointestinal tract into an active metabolic regulator, thus addressing the multifaceted nature of T2DM. Multidisciplinary collaboration involving endocrinologists, nutritionists, and rehabilitation specialists optimizes outcomes and long-term management. Although metabolic surgery shows significant short-term benefits, further high-quality studies are required to assess its long-term efficacy. Personalized approaches that incorporate patient preferences and comprehensive follow-up are essential for optimal T2DM care.
Citation: Yang J, Zhang CZ, Wang JJ, Zhang J. Metabolic improvement effects of jejunoileal side-to-side anastomosis in patients with type 2 diabetes and the glucagon-like peptide-1 mechanism. World J Diabetes 2025; 16(4): 103567
We carefully read the study by Wang et al[1] on laparoscopic jejunoileal side-to-side anastomosis in type 2 diabetes mellitus (T2DM). The patients who underwent side-to-side jejunoileal anastomosis between 2020 and 2023 were reviewed, and strict inclusion and exclusion criteria were established. The inclusion criteria were as follows: (1) Age ≤ 75 years; (2) Body mass index (BMI) ≤ 32.5 kg/m²; (3) Peak C-peptide release twice the baseline; (4) Fasting C-peptide levels ≥ 1/2 of the lower normal limit; (5) Negative results for autoimmune diabetes antibodies; and (6) The absence of severe comorbidities or complications that would affect the surgical indications. The exclusion criteria were: (1) A history of hyperosmolar diabetic coma or diabetic ketoacidosis; (2) Severe infections; (3) Previous surgery or trauma; (4) Age < 18 years, women with pregnancy or lactation, or long-term use of antibiotics (< 6 months); (5) Severe liver or renal dysfunction, cardiovascular diseases, or infectious diseases; and (6) Malignant tumors or a history of kidney disease.
The surgeries were performed under general anesthesia. The patients were positioned in the supine position, and standard abdominal disinfection and positioning procedures were applied. A total of 78 patients were included in the study, and follow-up was conducted through outpatient visits, telephone, and WeChat at 3 months and 6 months postoperatively. They emphasized the role of gastrointestinal surgical interventions in achieving multitarget metabolic control, with postoperative improvements in glucose levels, blood lipids, and purine metabolism compared with preoperative values. These findings advocate surgery as an adjunctive approach for T2DM management.
The aging population, accelerated urbanization, and unhealthy lifestyles are attributed to the increased number of individuals affected by T2DM. Currently, there are various hypoglycemic medications for the treatment of T2DM. However, the long-term efficacy is often limited by poor patient compliance, reduced drug tolerance, and chronic complications of T2DM, which result in a continued rise in T2DM-related mortality and disability rates[2]. This finding underscores the need to develop new medications and alternative therapies for T2DM. As shown by Wang et al[1], jejunoileal side-to-side anastomosis resulted in significant metabolic improvement even at 6 months postoperatively. This study suggests that surgical management may be a viable option in certain populations with T2DM.
Bariatric surgery was first proposed by Pories et al[3], and relevant procedures include Roux-en-Y gastric bypass (RYGB), vertical sleeve gastrectomy (VSG), and jejunoileal side-to-side anastomosis, with the first two being the most frequently used surgical techniques. These procedures have been shown to lower blood glucose levels, improve insulin function, and delay complications associated with T2DM[4]. These effects may be mediated through postoperative changes in gastrointestinal structure, which influence nutrient absorption, modulate insulin sensitivity (such as hepatic insulin sensitivity and insulin secretion), and involve complex interorgan interactions (including gut-derived insulinotropic factors and bile acids)[5].
During follow-up periods of 1-5 years after surgery, 30%-60% of patients with T2DM experience sustained remission[6]. As the follow-up period increases, approximately 30% of patients remain affected by T2DM in the long term[7]. Despite relapse, most patients experience a period of better disease control, at least 5-15 years, compared with baseline levels[7-9]. Although there is recurrence, favorable changes have occurred in disease trajectories, including cardiovascular metabolic risk factors, diabetic nephropathy, and diabetic retinopathy[10,11]. Thus, surgical options for T2DM may become a novel therapeutic approach. However, more stringent preoperative evaluation, careful selection of surgical techniques, and comprehensive postoperative follow-up are necessary. Finally, given the large number of patients with T2DM, future treatments based on healthy lifestyles and dietary management are likely to be one of the most effective approaches.
EPIDEMIC TREND OF T2DM AND POTENTIAL ROLE OF METABOLIC SURGERY IN MANAGEMENT
Over the past three decades, the incidence and complications of T2DM have increased significantly. According to the global burden of disease study in 2013, T2DM (all types) was identified as the ninth-leading cause of shortened life expectancy[12]. It is estimated that by 2040, the global number of patients with T2DM will exceed 642 million, with developing countries, such as China and India, being the primary affected regions[13]. In China, a large-scale survey estimated that approximately 50.1% of adults are classified as having impaired fasting glucose, whereas approximately 11.6% of adults are diagnosed with T2DM. Compared to other regions, the onset of T2DM in Asia tends to occur at a younger age, with a relatively lower BMI[14]. However, the prevalence of T2DM increases with the incidence of obesity[15]. According to a global obesity prevalence survey, by 2025 the obesity rate is expected to reach 18% in males and 21% in females worldwide[16]. Previous studies have indicated that an increase in BMI is associated with a higher incidence of T2DM[15]. The dual epidemic of obesity and T2DM may represent a future trend.
The continued increase in T2DM and obesity is driven by multiple factors, including population aging, urbanization, unhealthy dietary habits, and sedentary lifestyles with prolonged periods of inactivity. Genetic and epigenetic factors, as well as lifestyle choices, play significant roles[13]. Insulin resistance and pancreatic cell dysfunction are the recognized causes of T2DM. Additionally, elevated BMI is closely associated with insulin resistance and metabolic abnormalities[17].
A variety of medications with good clinical efficacy have been developed for T2DM, including glucagon-like peptide (GLP)-1 receptor agonists and metformin. Prescription medications, along with dietary and exercise therapies, remain the cornerstone of current T2DM treatments. In China, only 25% of patients with T2DM receive treatment, and among those, only 39.7% have good control of glycated hemoglobin (HbA1c) levels[18]. This indicates that beyond basic therapies, additional work is necessary, such as addressing whether patients with T2DM have good treatment awareness, adherence to treatment, and presence of personalized treatment approaches and whether patients adjust their treatment in a timely manner or consider alternative treatment options at an early stage. As noted by Wang et al[1], patients with T2DM often experience poor adherence to treatment and suffer from side effects of medication, which contribute to suboptimal treatment outcomes. Currently, multiple pieces of evidence indicate that gastrointestinal management is an effective therapeutic target for T2DM.
Metabolic surgery related to the gastrointestinal tract has shown excellent postoperative blood glucose management, as indicated in a retrospective cohort study involving 4434 patients. The median disease-free time following RYGB surgery was 8.3 years[7]. RYGB alters gastric volume and gastrointestinal structure, allowing food to bypass the stomach and directly enter the jejunum. Additionally, the VSG procedure has been increasing in frequency and compared with RYGB offers a simpler surgical approach while providing similar therapeutic outcomes. These processes promote the rapid flow of nutrients into the intestine, stimulating an increase in hormone secretion and elevated blood bile acid levels.
A parallel randomized trial found that both treatments had similar effects on blood glucose control. However, another randomized controlled trial found that RYGB surgery had better weight loss outcomes and required fewer medications compared to VSG surgery[5,19]. Additionally, a meta-analysis of several observational studies indicated that metabolic surgery significantly reduced the incidence of cardiovascular events[20]. A single-center retrospective study found that RYGB surgery reduced patients’ blood glucose levels and decreased the incidence of microvascular and macrovascular complications[10].
A study that combined two randomized controlled trial cohorts and 12 observational studies found that compared with the non-surgical group the relative risk of diabetic retinopathy in the metabolic surgery group was reduced by approximately 83%[21]. In addition, a study that included three randomized controlled trials and seven observational studies indicated that metabolic surgery reduced the risk of nephropathy, retinopathy, and neuropathic complications by 74%[20].
In recent years, laparoscopic jejunoileal side-to-side anastomosis has become a viable treatment option for patients with T2DM with normal or high BMI. This procedure involves jejunoileal side-to-side anastomosis, which allows intestinal contents to quickly reach the distal ileum, stimulating the release of GLP-1 and achieving blood glucose control and improving metabolic outcomes[1,22]. As shown by Wang et al[1], patients at 6 months after surgery exhibited reductions in body weight, fasting blood glucose, postprandial blood glucose, and HbA1c levels compared with preoperative values. These data demonstrate the positive effects of surgical management in T2DM. It is evident that this surgical approach demonstrates significant metabolic management capabilities within the 6-month postoperative follow-up period.
However, long-term follow-up is still needed to confirm the true benefits. For example, a retrospective cohort study conducted a 14-year follow-up on patients with T2DM who underwent weight loss surgery. The results showed that 136 patients (32%) experienced a recurrence of T2DM. These patients may have the following characteristics: A longer duration of T2DM; more complex disease; or higher preoperative HbA1c levels. Additionally, the study also indicated that factors such as age, dietary habits, and whether patients received multidisciplinary management postoperatively were closely associated with the recurrence of T2DM[11,23].
METABOLIC REGULATORY POTENTIAL OF JEJUNOILEAL ANASTOMOSIS AND APPLICATION OF MULTIDISCIPLINARY COLLABORATION IN T2DM MANAGEMENT
The concept of strategically altering intestinal anatomy through jejunoileal anastomosis represents a paradigm shift. Unlike traditional pharmacological approaches that target a single pathway, such as glucose absorption or insulin sensitivity, jejunoileal anastomosis utilizes structural modifications to contribute to weight management, GLP-1 release, and appetite reduction. This innovative procedure reprograms the gastrointestinal tract to actively regulate specific endocrine and metabolic pathways, thereby addressing T2DM as a multifaceted disease involving complex metabolic dysfunctions, rather than treating it as a singular condition[22].
For example, the RYGB procedure alters the gastrointestinal anatomical arrangement, allowing nutrients to stimulate the activity of L cells more quickly. In addition, studies have indicated that the number of L cells increases in patients after RYGB surgery[24]. L cells are one of the factors that induce GLP-1 secretion[25]. Jejunoileal side-to-side anastomosis has been shown to enhance the secretion of endogenous GLP-1[22]. GLP-1 is a gut-derived insulinotropic hormone that plays a key role in glucose homeostasis by enhancing glucose-dependent insulin secretion and reducing postprandial blood glucose peaks[26].
GLP-1 binds to its receptor, activating adenylate cyclase, which leads to an increase in cyclic adenosine monophosphate levels. This, in turn, activates protein kinase A (PKA), promoting the exocytosis of insulin granules and enhancing insulin secretion[27]. In addition to the PKA signaling pathway, GLP-1 can also induce insulin release through the Epac signaling pathway (exchange protein directly activated by cyclic adenosine monophosphate). In β cells, the Epac protein stimulates the release of calcium from the endoplasmic reticulum, and the increase in intracellular calcium concentration enhances insulin secretion[28].
GLP-1 can stimulate insulin gene expression. It induces PKA activation, which increases the nuclear translocation of PDX1. PDX1 then binds to the insulin promoter, initiating insulin expression and synthesis[27]. GLP-1 is associated with delayed gastric emptying and increased satiety, which may aid in weight management. This is particularly beneficial for patients with T2DM, as weight control supports metabolic stability[29].
GLP-1 is associated with cardiovascular and renal effects. Studies on GLP-1 receptor agonists have shown that they can lower blood pressure, improve lipid profiles, and exert anti-inflammatory effects[30]. Although these effects primarily stem from pharmacological studies, enhanced endogenous GLP-1 secretion after surgery may offer similar benefits. As previously reported, weight loss surgery induces changes in the gastrointestinal anatomy, thereby stimulating L cells to release GLP-1. GLP-1 receptors are present in locations such as the vascular endothelium and coronary arteries. Activation of GLP-1 receptors can improve endothelial dysfunction, thereby protecting the blood vessels[31].
Weight loss surgery can alter the gastrointestinal anatomy, thereby affecting the absorption of lipid substances. This adjustment leads to changes in high-density lipoprotein, PON1 levels, inflammation, and thrombotic markers, ultimately providing cardiovascular protection[32,33]. In summary, the ability of surgical interventions to modify intestinal anatomy and enhance endogenous GLP-1 secretion underscores their transformative potential in the treatment of T2DM (Figure 1).
Figure 1 Effects of metabolic surgery on different target organs.
RYGB: Roux-en-Y gastric bypass; VSG: Vertical sleeve gastrectomy; GLP-1: Glucagon-like peptide-1.
Traditional metabolic surgeries, such as RYGB, are typically limited to patients with obesity (BMI: 35.0-39.9 kg/m²) or patients with insufficient control by other methods (BMI: 30.0-34.9 kg/m²). In contrast, the BMI range for those undergoing jejunoileal anastomosis is lower at 24-32 kg/m²[1,22]. Of course, the different definitions of obesity provided by the World Health Organization in various regions also need to be considered[6]. If its efficacy and safety are confirmed in a broader population, this surgery could become an alternative option, allowing clinicians to offer metabolic surgical interventions to patients with T2DM seeking overall metabolic improvement. This would mark a significant advancement in personalized T2DM management.
In recent years, with the growing popularity of various bariatric or gastrointestinal operations, multiple clinical trials have provided evidence that these can control obesity and manage blood glucose levels. However, behind the impressive data, it is important to note that these procedures alter the gastrointestinal anatomy and adjust the endocrine state, highlighting issues related to the complexity of the technique, the underlying mechanisms, and safety concerns. In the past, the level of understanding that surgical specialists had of the procedure largely determined patient prognosis[34].
In recent years, the quality of surgery has significantly improved with the involvement of training, professional certification, and multidisciplinary teams. This included preoperative comprehensive assessments conducted by a multidisciplinary team, including endocrinologists, surgeons, internists, and specialized nutrition teams (Table 1). An example of this is the multidisciplinary management of gastric bypass at Avicenne Hospital. First, the surgical indications and contraindications are assessed by the surgeon. This is followed by consultations with an endocrinologist and a nutritionist, assessing factors such as BMI, blood lipids, HbA1c, blood pressure, thyroid hormones, cortisol levels, and nutritional status. If abnormalities are detected during the assessment, the relevant specialists will make adjustments or provide treatment before conducting a re-evaluation for surgery[35].
Table 1 Multidisciplinary team management for metabolic surgery.
Division of roles and responsibilities; integration of multidisciplinary expertise; timely data sharing; regular discussions; patient-centered decision-making; digital process implementation; digital management integration
Develop personalized exercise plans based on age, gender, and health status; provide cognitive-behavioral support for adherence to exercise routines
Registered dietitian
Design structured, personalized diets; recommend adaptive postoperative diets; perform dietary adjustments at 1, 3, 6, and 12 months post-surgery during the first year
Psychologist
Provide effective communication and encouragement; offer postoperative psychological support; address issues related to lifestyle and appearance changes; treat conditions such as depression
The complexity of T2DM and the variability in postoperative individual prognosis indicate that close postoperative follow-up is required to ensure the effectiveness of treatment. For example, postoperative patients should continue to remain in contact with a multidisciplinary team. Endocrinologists play a crucial role in optimizing preoperative and postoperative metabolic management, ensuring stable blood glucose levels, and adjusting hormones and medications as a patient’s metabolic condition evolves. For example, oral antidiabetic medications or GLP-1 receptor agonists are paused preoperatively. Postoperatively, the use of sulfonylureas and other similar drugs is avoided[23].
Nutritionists play a key role by developing dietary plans to compensate for the altered nutrient absorption patterns after surgery, emphasizing low-glycemic, nutrient-dense foods to support blood glucose control and prevent nutritional deficiencies. Diabetes educators and care coordinators play a critical role in bridging the gap between patients and clinical teams. They provide guidance on self-monitoring, lifestyle modification, and follow-up protocols to enhance adherence and ensure the continuity of care.
Finally, physiotherapists and exercise specialists design exercise programs to enhance insulin sensitivity, support weight management, and improve cardiovascular health, thereby promoting overall metabolic stability and maximizing the long-term benefits of surgical interventions. This collaborative support system provides patients with the comprehensive resources needed to adapt to physiological changes following surgery, enhancing both physical and psychological resilience.
A randomized controlled study explored the effects of multidisciplinary diabetes care (MDC) or MDC combined with laparoscopic adjustable gastric banding (LAGB) on blood glucose control in patients with T2DM who were not obese. The endocrinologist regularly followed up on the patients’ HbA1c levels (with a target control below 7%) and adjusted medications as necessary. The nutritionist designed personalized dietary plans and monitored the patients’ dietary adherence every 6 months, making adjustments as needed. The exercise rehabilitation specialist recommended that patients engage in at least 150 min of moderate-intensity exercise per week, adjusting the exercise plan based on BMI or other comorbidities, while emphasizing the importance of physical activity. The diabetes educator provided patients with knowledge on disease management. The surgical specialist conducted preoperative screening and provided long-term postoperative follow-up. By integrating expertise from various disciplines, team members share patient data, hold regular meetings, and adjust the plan in a timely manner. Ultimately, among the patients receiving LAGB combined with MDC, 12 out of 23 (52%) achieved diabetes remission. In contrast, only 2 out of 25 (8%) patients receiving MDC alone achieved remission[36].
Similarly, long-term multidisciplinary follow-up after surgery is key to the patient’s long-term recovery. This includes postoperative blood glucose monitoring, continuous nutritional assessments, exercise training, and when necessary psychological evaluations. Additionally, annual screenings for diabetes-related complications are conducted, including necessary fundoscopy by an ophthalmologist, cardiac function assessments by a cardiologist, and specialized tests by a nephrologist[23]. This comprehensive approach significantly improved patient outcomes and fostered a more personalized model of metabolic health management, better addressing the complexities of T2DM.
CONCLUSION
The prevalence of T2DM and its complications has reached unprecedented levels in the past few decades, presenting an extraordinary challenge to global public health. Several large-scale studies have emphasized that effective weight management, combined with regular physical activity and a healthy diet, is essential as a foundation for other therapeutic strategies in patients with T2DM[37]. Lifestyle modifications, social support, and individualized pharmacotherapy are crucial for controlling the progression of T2DM and reducing complications.
Metabolic surgeries, including RYGB, LAGB, and jejunoileal side-to-side anastomosis, have become promising options for achieving long-term blood glucose control and reducing complications. Various treatment options, including pharmacotherapy and metabolic surgery, are available to both clinicians and patients. Incorporating multidisciplinary inputs and patient preferences is recommended when selecting the most appropriate therapeutic approach. However, this is based on a strict evaluation of the patient’s condition. When compared with pharmacotherapy, does surgery provide the greatest and most enduring benefits for patients? High-quality randomized controlled trials or prospective studies are required to evaluate the long-term effects of surgery.
In summary, the treatment of T2DM requires multidisciplinary collaboration, combining lifestyle interventions, personalized pharmacotherapy, or metabolic surgery to bring the maximum benefit to the patients. Through high-quality randomized controlled trials and prospective studies, metabolic surgery is expected to become a key component in the management of T2DM in the future, offering patients the hope of long-term metabolic improvement.
Footnotes
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Endocrinology and metabolism
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade B, Grade B, Grade C, Grade D
Novelty: Grade B, Grade B, Grade B, Grade C
Creativity or Innovation: Grade B, Grade B, Grade B, Grade C
Scientific Significance: Grade A, Grade B, Grade B, Grade C
P-Reviewer: Ji W; Yu X; Zhang RX S-Editor: Fan M L-Editor: Filipodia P-Editor: Zhao S
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