Identification of novel dual-target 4-hydroxyphenylpyruvate dioxygenase & phytoene dehydrogenase inhibitors via multiple virtual screening.

Two important plant enzymes are 4-hydroxyphenylpyruvate dioxygenase (HPPD; EC 1.13.11.27), which is necessary for biosynthesis of plastoquinone and tocopherols, and phytoene dehydrogenase (PDS; EC 1.3.99.26), which plays an important role in colour rendering. Dual-target proteins that inhibit pigment synthesis will prevent resistant weeds and improve the spectral characteristics of herbicides. This study introduces virtual screening of pharmacophores based on the complex structure of the two targets. A three-dimensional database was established by screening 1,492,858 compounds based on the Lipinski principle. HPPD&PDS dual-target receptor-ligand pharmacophore models were then constructed, and nine potential dual-target inhibitors were obtained through pharmacophore modeling, molecular docking, and molecular dynamics simulations. Ultimately, ADMET prediction software yielded three compounds with high potential as dual-target herbicides. The obtained nine inhibitors were stable when combined with both HPPD and PDS proteins. This study offers guidance for the development of HPPD&PDS dual-target inhibitors with novel skeletons.

Dual-recognition "turn-off-on" fluorescent Biosensor triphenylamine-based continuous detection of copper ion and glyphosate applicated in environment and living system.

Heavy metal Cu2+ emitted in industry and residues of glyphosate pesticides are pervasive in ecosystems, accumulated in water bodies and organisms' overtime, constituting hazard to human and ecological balance. The development of rapid, highly selective, reversibility and sensitive biosensor in vivo detection for Cu2+ and glyphosate was imminent. A novel dual-recognition fluorescence biosensor MPH was successfully synthesized based on triphenylamine, which demonstrated remarkable ratiometric fluorescence quenching toward Cu2+, while MPH-Cu2+ (1:1) ensemble exhibited ratiometric fluorescence restoration for glyphosate, both with observable color changes in daylight and UV lamp. The biosensor exhibited rapid, outstanding selectivity, anti-interference, and multiple cycles reversibility through "turn-off-on" fluorescence towards Cu2+ and glyphosate, respectively. Surprisingly, the clearly binding mechanisms of MPH to Cu2+ and MPH-Cu2+ ensemble to glyphosate were determined, respectively, based on the Job's plot, FT-IR, ESI-HRMS, 1H NMR titration and theoretical calculations of dynamics and thermodynamics. In addition, biosensor MPH demonstrated successful detection of Cu2+ and glyphosate across diverse environmental samples including tap water, extraction solutions of traditional Chinese medicine honeysuckle and soil samples. In the meantime, fluorescence imaging of Cu2+ and glyphosate at both micro and macro scales in various living organisms, such as rice roots, MCF-7 cells, zebrafish, and mice, were successfully achieved. Overall, this work was expected to become a promising and versatile fluorescence biosensor for rapid and reversible detection of Cu2+ and glyphosate both in vitro and vivo.

4-Hydroxyphenylpyruvate Dioxygenase Inhibitors: From Molecular Design to Synthesis.

Weed resistance is a critical issue in crop production. Among the known herbicides, 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors are crucial for addressing weed resistance. HPPD inhibitors constitute a pivotal aspect of contemporary crop protection strategies. The advantages of these herbicides are their broad weed spectrum, flexible application, and excellent compatibility with other herbicides. They also exhibit satisfactory crop selectivity and low toxicity and are environmentally friendly. An increasing number of new HPPD inhibitors have been designed by combining computer-aided drug design with conventional design approaches. Herein, the molecular design and structural features of innovative HPPD inhibitors are reviewed to guide the development of new HPPD inhibitors possessing an enhanced biological efficacy.

TCHH as a Novel Prognostic Biomarker for Patients with Gastric Cancer by Bioinformatics Analysis.

Background: This study aims to investigate the clinicopathological significance and prognostic value of Trichohyalin (TCHH) in gastric cancer patients through bioinformatics analysis. Materials and Methods: Data on TCHH expression and clinicopathological information were sourced from The Cancer Genome Atlas (TCGA). The Wilcoxon signed-rank test was used for evaluating the correlation between TCHH mRNA expression levels and clinicopathological features. The predictive significance of TCHH mRNA expression for overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in patients with gastric cancer was assessed using Cox regression models. Furthermore, measures of immune cell infiltration in gastric cancer were made, and studies of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were also carried out to investigate the possible roles of TCHH in patients with gastric cancer. Results: Compared to normal tissues, gastric cancer had a considerably higher expression of TCHH mRNA (P < 0.05). Wilcoxon analysis revealed a significant association between TCHH mRNA expression and the pathologic M stage (P = 0.017). High TPMT mRNA levels were also correlated with worse OS, DFS, and PFI in gastric cancer patients (both P < 0.05). TCHH showed significant negative correlations with the levels of NK CD56dim infiltration (r = -0.157, p = 0.002), Th17 cells infiltration (r = -0.235, P < 0.001), and Th2 infiltration (r = -0.195, P < 0.001). Furthermore, enrichment analysis indicated potential involvement in intermediate filament cytoskeleton organization, DNA methylation in gamete generation, cell-cell recognition, and G protein-coupled peptide receptor (GPCRs) activity. Conclusion: The level of TCHH mRNA may serve as a novel prognostic biomarker for gastric cancer patients.

Design, Synthesis, and Biological Activity of Novel Phenyltriazolinone PPO Inhibitors Containing Five-Membered Heterocycles.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) catalyzes the oxidation of protoporphyrinogen IX to protoporphyrin IX, which is a key step in the synthesis of porphyrins in vivo. PPO inhibitors use protoporphyrinogen oxidase as the target and block the biosynthesis process of porphyrin by inhibiting the activity of the enzyme, eventually leading to plant death. In this paper, phenyl triazolinone was used as the parent structure, and the five-membered heterocycle with good herbicidal activity was introduced by using the principle of substructure splicing. According to the principle of bioisosterism, the sulfur atoms on the thiophene ring were replaced with oxygen atoms. Finally, 33 phenyl triazolinones and their derivatives were designed and synthesized, and their characterizations and biological activities were investigated. The in vitro PPO inhibitory activity and greenhouse herbicidal activity of 33 target compounds were determined, and compound D4 with better activity was screened out. The crop safety determination, field weeding effect determination, weeding spectrum determination, and crop metabolism study were carried out. The results showed that compound D4 showed good safety to corn, soybean, wheat, and peanut but poor selectivity to cotton. The field weeding effect of this compound is comparable to that of the commercial herbicide sulfentrazone. The herbicidal spectrum experiment showed that compound D4 had a wide herbicidal spectrum and a good growth inhibition effect on dicotyledonous weeds. Molecular docking results showed that compound D4 forms a hydrogen bond with amino acid residue Arg-98 in the tobacco mitochondria (mtPPO)-active pocket and forms two π-π stacking interactions with Phe-392. This indicates that compound D4 has stronger PPO inhibitory activity. This indicates that compound D4 has wide prospects for development.

Massive continuous irrigation (MCI) and endoscopic debridement as an alternative treatment strategy for refractory abscess-fistula complexes.

OBJECTIVE: To evaluate the feasibility, safety, and efficacy of massive continuous irrigation (MCI) and endoscopic debridement for the treatment of refractory abscess-fistula complexes. METHODS: This was a retrospective single-center observational study involving 12 patients with refractory abscess-fistula complexes. All patients had experienced long-term treatment failure or had failed multiple treatment modalities. We used over two catheters and inserted them via the gastrointestinal (GI) tract or percutaneously to form a circulation pathway to achieve MCI of normal saline, endoscopic debridement was then performed. The treatment success rate, irrigation volume and treatment duration, time to abscess-fistula complex closure, intra-treatment complications, and recurrence rate were recorded. RESULTS: The treatment success rates were 100%. The median time of previous treatment was 32 days (range 7-912 days). The mean time from the use of the novel treatment strategy to abscess-fistula complex healing was 18.8 ± 11.0 days. The mean volume of irrigation was 10 804 ± 1669 mL/24 h. The mean irrigation time was 16.5 ± 9.2 days, and a median of two irrigation tubes (range 2-5) were used. No complications occurred either during or after the procedure. During the follow-up of 23.1 ± 18.1 months, no recurrence or adverse events were noted. CONCLUSIONS: MCI and endoscopic debridement may be a feasible, safe, and effective alternative treatment for refractory abscess-fistula complexes. Large prospective studies are needed to validate our results.

Design, Synthesis, and Bioactivity of Novel 2-(Arylformyl)cyclohexane-1,3-dione Derivatives as HPPD Inhibitors.

4-Hydroxyphenylpyruvate dioxygenase inhibitors (Echinochloa crus-galli 1.13.11.27, HPPD) have gained significant popularity as one of the best-selling herbicides worldwide. To identify highly effective HPPD inhibitors, a rational design approach utilizing bioisosterism was employed to create a series of 2-(arylformyl)cyclohexane-1,3-dione derivatives. A total of 29 novel compounds were synthesized and characterized through various techniques, including IR, 1H NMR, 13C NMR, and HRMS. Evaluation of their inhibitory activity against Arabidopsis thaliana HPPD (AtHPPD) revealed that certain derivatives exhibited superior potency compared to mesotrione (IC50 = 0.204 µM). Initial herbicidal activity tests demonstrated that compounds 27 and 28 were comparable to mesotrione in terms of weed control and crop safety, with compound 28 exhibiting enhanced safety in canola crops. Molecular docking analyses indicated that the quinoline rings of compounds 27 and 28 formed more stable π-π interactions with the amino acid residues Phe-360 and Phe-403 in the active cavity of AtHPPD, surpassing the benzene ring of mesotrione. Molecular dynamics simulations and molecular structure comparisons confirmed the robust binding capabilities of compounds 27 and 28 to AtHPPD. This study provides a valuable reference for the development of novel triketone herbicide structures, serving as a blueprint for future advancements in this field.

Design, synthesis and biological activity determination of novel phenylpyrazole protoporphyrinogen oxidase inhibitor herbicides.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is the last common enzyme in the biosynthetic pathway in the synthesis of heme and chlorophyll. The high-frequency use of PPO inhibitor herbicides has led to the gradual exposure of pesticide damage and resistance problems. In order to solve this kind of problem, there is an urgent need to develop new PPO inhibitor herbicides. In this paper, 16 phenylpyrazole derivatives were designed by the principle of active substructure splicing through the electron isosterism of five-membered heterocycles. Greenhouse herbicidal activity experiments and in vitro PPO activity experiments showed that the inhibitory effect of compound 9 on weed growth was comparable to that of pyraflufen-ethyl. Crop safety experiments and cumulative concentration experiments in crops showed that when the spraying concentration was 300 g ai/ha, wheat, corn, rice and other cereal crops were more tolerant to compound 9, among which wheat showed high tolerance, which was comparable to the crop safety of pyraflufen-ethyl. Herbicidal spectrum experiments showed that compound 9 had inhibitory activity against most weeds. Molecular docking results showed that compound 9 formed one hydrogen bond interaction with amino acid residue ARG-98 and two π-π stacking interactions with amino acid residue PHE-392, indicating that compound 9 had better herbicidal activity than pyraflufen-ethyl. It shows that compound 9 is expected to be a lead compound of phenylpyrazole PPO inhibitor herbicide and used as a herbicide in wheat field.

Endoscopic transgastric fenestration versus percutaneous drainage for management of (peri)pancreatic fluid collections adjacent to gastric wall (with video).

BACKGROUND: Percutaneous drainage (PCD) and endoscopic approaches have largely replaced surgical drainage as the initial approach for (peri) pancreatic fluid collections (PFC)s, while complications associated with endoscopic stent implantation are common. AIM: To introduce a novel endoscopic therapy named endoscopic transgastric fenestration (ETGF), which involves resection of tissue by endoscopic accessory between gastric and PFCs without stent implantation, and to evaluate its efficacy and safety compared with PCD for the management of PFCs adjacent to the gastric wall. METHODS: Patients diagnosed with PFCs adjacent to the gastric wall and who subsequently received ETGF or PCD were restrospectively enrolled. Indications for intervention were consistent with related guidelines. We analyzed patients baseline characteristics, technical and clinical success rate, recurrence and reintervention rate, procedure-related complications and adverse events. RESULTS: Seventy-two eligible patients were retrospectively identified (ETGF = 34, PCD = 38) from October 2017 to May 2021. Patients in the ETGF group had a significantly higher clinical success rate than those in the PCD group (97.1 vs 76.3%, P = 0.01). There were no statistically significant differences regarding recurrence, reintervention and incidence of complication between the two groups. While long-term catheter drainage was very common in the PCD group. CONCLUSION: Compared with PCD, ETGF has a higher clinical success rate in the management of PFCs adjacent to the gastric wall. ETGF is an alternative effective strategy for the treatment of PFCs adjacent to the gastric wall.

Design, Synthesis, and Biological Activity Determination of Novel Phenylpyrazole Protoporphyrinogen Oxidase Inhibitor Herbicides Containing Five-Membered Heterocycles.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitor herbicides have attracted widespread attention in recent years as ideal herbicides due to their high efficiency, low toxicity, and low pollution. In this article, 30 phenylpyrazole derivatives containing five-membered heterocycles were designed and synthesized according to the principle of bioelectronic isoarrangement and active substructure splicing. A series of structural characterizations were performed on the synthesized compounds. The herbicide activity in greenhouse was evaluated to determine their growth inhibition effect on weeds, their IC50 value through in vitro PPO enzyme activity measurement was calculated, and target compounds 2i and 3j that have herbicide effects comparable to pyraflufen-ethyl were selected. Crop safety experiments have shown that when the spraying concentration is 300 g of ai/ha, gramineous crops such as wheat, corn, and rice are more tolerant to compound 2i, with wheat exhibiting high tolerance, which is equivalent to the crop safety of pyraflufen-ethyl. Compound 2i can be used as a candidate herbicide for wheat, corn, and paddy fields, and the results are consistent with the cumulative concentration experiment. Molecular docking results showed that compound 2i interacted with the amino acid residue ARG-98 by forming two hydrogen bonds and interacted with the amino acid residue PHE-392 by forming two π-π stacking interactions, indicating that compound 2i has more excellent herbicidal activity than pyraflufen-ethyl and is expected to become a potential lead compound of phenylpyrazole PPO inhibitor herbicides.

Transgastric versus transrectal: Which access route is the best for NOTES gallbladder-preserving gallstone therapy?

OBJECTIVES: To compare the effectiveness and safety of transgastric and transrectal pure natural orifice transluminal endoscopic surgery (NOTES) for cholecystolithotomy. METHODS: This was a single-center retrospective comparative study of consecutive patients who underwent pure NOTES for either transrectal or transgastric gallbladder-preserving cholecystolithotomy between September 2017 and April 2020. Patients with symptomatic cholelithiasis were assigned for transrectal or transgastric NOTES based on the patients' choice. Treatment success, postoperative pain, peritonitis, time to resume normal diet, and duration of hospitalization were compared. RESULTS: The technical success rate was 100%. Forty-eight patients underwent successful NOTES cholecystolithotomy via the transrectal (n = 26) or transgastric route (n = 22). One (3.8%) patient in the transrectal NOTES group experienced postoperative abdominal pain compared to 6 (27.3%) in the transgastric NOTES group (P = 0.04). Fever and bile peritonitis developed in one (3.8%) patient in the transrectal NOTES group versus 8 (36.4%) in the transgastric NOTES group (P = 0.005). A postoperative fluid diet was commenced at 6 h with the transrectal approach versus on day 3 for the transgastric NOTES group. The mean postoperative hospitalization for transrectal and transgastric NOTES groups was 4.5 days versus 7 days (P = 0.001). Three patients in the transgastric NOTES group developed postoperative gastric fistula. CONCLUSIONS: Transrectal NOTES has advantages over transgastric NOTES, including preserved spatial orientation, relatively easier removal of specimens, early food intake, shorter hospitalization, fewer postoperative complications and less pain. Multicenter clinical trials with long-term follow-up are needed to confirm the safety and efficacy of both approaches.

Review on the Discovery of Novel Natural Herbicide Safeners.

The phytotoxicity of herbicides on crops is a major dilemma in agricultural production. Fortunately, the emergence of herbicide safeners is an excellent solution to this challenge, selectively enhancing the performance of herbicides in controlling weeds while reducing the phytotoxicity to crops. But owing to their potential toxicity, only a tiny proportion of safeners are commercially available. Natural products as safeners have been extensively explored, which are generally safe to mammals and cause little pollution to the environment. They are typically endogenous signal molecules or phytohormones, which are generally difficult to extract and synthesize, and exhibit relatively lower activity than commercial products. Therefore, it is necessary to adopt rational design approaches to modify the structure of natural safeners. This paper reviews the application, safener effects, structural characteristics, and modifications of natural safeners and provides insights on the discovery of natural products as potential safeners in the future.

Design, Synthesis, and Bioactivity of Novel Ester-Substituted Cyclohexenone Derivatives as Safeners.

Tembotrione, a 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor, has been widely used in many types of plants. Tembotrione has been reported for its likelihood of causing injury and plant death to certain corn hybrids. Safeners are co-applied with herbicides to protect certain crops without compromising weed control efficacy. Alternatively, herbicide safeners may effectively improve herbicide selectivity. To address tembotrione-induced Zea mays injury, a series of novel ester-substituted cyclohexenone derivatives were designed using the fragment splicing method. In total, 35 title compounds were synthesized via acylation reactions. All the compounds were characterized using infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry. The configuration of compound II-15 was confirmed using single-crystal X-ray diffraction. The bioactivity assay proved that tembotrione phytotoxicity to maize could be reduced by most title compounds. In particular, compound II-14 exhibited the highest activity against tembotrione. The molecular structure comparisons as well as absorption, distribution, metabolism, excretion, and toxicity predictions demonstrated that compound II-14 exhibited pharmacokinetic properties similar to those of the commercial safener isoxadifen-ethyl. The molecular docking model indicated that compound II-14 could prevent tembotrione from reaching or acting with Z. mays HPPD (PDB: 1SP8). Molecular dynamics simulations showed that compound II-14 maintained satisfactory stability with Z. mays HPPD. This research revealed that ester-substituted cyclohexenone derivatives can be developed as potential candidates for discovering novel herbicide safeners in the future.

Discovery of novel HPPD inhibitors: Virtual screening, molecular design, structure modification and biological evaluation.

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD, a Fe(II)/α-ketoglutarate dependent oxygenases), is a popular herbicide target. In this work, two pharmacophore models based on common molecular characteristics (HipHop) and receptor-ligand complex (CBP) were generated for virtual screening for HPPD inhibitors. About 1,000,000 molecules containing diketone structure from PubChem were filtered by Lipinski's rules to build a 3D database. Then the database was screened through combining HipHop model, CBP model, ADMET (absorption, distribution, metabolism, excretion and toxicity) prediction and molecular docking. Subsequently, based on the specific binding mode and affinity of HPPD inhibitors, 4 molecules with high -CDOCKER energy, good aqueous solubility and human safety predicative properties values were screened. From the screening results and combined with previous work, three novel HPPD inhibitors were designed and synthesized through fragment splicing and bioisosterism strategies. Compound IV-a exhibited similar inhibition of Arabidopsis thaliana HPPD (AtHPPD) and herbicidal activity as mesotrione. Crop selectivity showed that compound IV-a had better crop safety than mesotrione. Comparing the molecular properties, ADMET and molecular docking studies indicated that compounds IV-a exhibited better properties than mesotrione, which could be further modified as novel HPPD inhibitor herbicides.

Identification of 4-hydroxyphenylpyruvate dioxygenase inhibitors by virtual screening, molecular docking, molecular dynamic simulation.

BACKGROUND: 4-Hydroxyphenylpyruvate dioxygenase (HPPD) herbicides control broadleaf and gramineous weeds with better crop safety for corn, sorghum and wheat. Multiple screening models in silico have been established to obtain novel lead compounds as HPPD inhibition herbicides. RESULTS: Topomer comparative molecular field analysis (CoMFA) combined with topomer search technology and Bayesian, genetic approximation functions (GFA) and multiple linear regression (MLR) models generated by calculating different descriptors were constructed for the quinazolindione derivatives of HPPD inhibitors. The coefficient of determination (r2 ) of topomer CoMFA, MLR and GFA were 0.975, 0.970 and 0.968, respectively; all the models established displayed excellent accuracy and high predictive capacity. Five compounds with potential HPPD inhibition were obtained via screening fragment library combined with the validation of the above models and molecular docking studies. After molecular dynamics (MD) validation and absorption, distribution, metabolism, excretion and toxicity (ADMET) prediction, the compound 2-(2-amino-4-(4H-1,2,4-triazol-4-yl) benzoyl)-3-hydroxycyclohex-2-en-1-one not only exhibited stable interactions with the protein but also high solubility and low toxicity, and has potential as a novel HPPD inhibition herbicide. CONCLUSION: In this study, five compounds were obtained through multiple quantitative structure-activity relationship screening. Molecular docking and MD experiments showed that the constructed approach had good screening ability for HPPD inhibitors. This work provided molecular structural information for developing novel, highly efficient and low-toxicity HPPD inhibitors. © 2023 Society of Chemical Industry.

A novel isophorone-based fluorescent probe for recognition of Al3+ and its bioimaging in cells and plants.

In this work, a novel isophorone-based fluorescent probe H-1 was designed and synthesized. The probe H-1 could achieve highly selective detection of Al3+ through forming a 1:1 complex, with a recognition mechanism based on intramolecular charge transfer (ICT). The detection limit of the probe H-1 for Al3+ is as low as 8.25 × 10-8 M which was determined by fluorescent titration. It is confirmed that H-1 could be used not only for fluorescence spectrometry to detect Al3+ ions in actual water samples, but also for biological imaging to detect Al3+ ions in cells and plants.

Endoscopic retrograde appendicitis therapy (ERAT) vs appendectomy for acute uncomplicated appendicitis: A prospective multicenter randomized clinical trial.

OBJECTIVE: To compare the efficacy and feasibility of endoscopic retrograde appendicitis therapy (ERAT) with appendectomy for treating acute uncomplicated appendicitis. METHODS: This was a prospective multicenter randomized trial in which consecutive patients were randomized at a ratio of 1:1 to receive either ERAT or appendectomy. The outcomes included technical success rate, procedure time, postoperative pain relief, postoperative analgesic use, time to soft diet intake, length of postoperative hospital stay, postoperative complications, and recurrence rate. RESULTS: From August 2013 to December 2015, 110 patients with acute uncomplicated appendicitis were randomized to ERAT or appendectomy. The technical success rate was 94.55% for ERAT compared with 100% for appendectomy. Recurrence of appendicitis within 3-year follow-up occurred in 8 patients following ERAT. Postoperative abdominal pain was less frequent with ERAT than with appendectomy (21.15% [11/52] vs 87.27% [48/55], P < 0.001). Soft diet intake begun earlier after ERAT than appendectomy (6 h vs 48 h, P < 0.001), and post-procedure hospital stay was shorter (3 days vs 5 days, P < 0.001), as was the use of analgesics postoperatively (9.09% vs 49.09%, P < 0.001). CONCLUSIONS: ERAT is a feasible, safe, and effective alternative approach for the management of acute uncomplicated appendicitis. Compared with appendectomy, advantages of ERAT include no skin wound, organ preservation, reduced postoperative pain, early food intake, quick recovery, fewer postoperative complications, and shorter post-procedure hospitalization. The unsolved problem related to ERAT is the recurrence of appendicitis.

Laparoscopic resection is not superior to endoscopic resection for relative small gastric gastrointestinal stromal tumors: A propensity score-matched study.

Background and Aim: Endoscopic resection (ER) and laparoscopic resection (LAP) have been recommended for the treatment of gastric gastrointestinal stromal tumors (GISTs) less than 2 cm. However, the therapeutic approach for gastric GISTs between 2 and 5 cm in diameter is still under debate. In this retrospective study, we aimed to evaluate the feasibility, efficacy, and safety of ER for gastric GISTs (2-5 cm) compared with LAP. Methods: From January, 2011 to January, 2018, 197 patients with GISTs at our institution with tumor diameter between 2 and 5 cm were included in our study. Clinical baseline characteristics, histopathological results, and perioperative outcomes were collected and compared in all the patients. Propensity score matching (PSM) methods were used to balance baseline characteristics. Results: There was no significant difference in age (p = 0.246), gender (p = 0.572), tumor location (p = 0.333), pathological risk classification (p = 0.543), Ki-67 index (p = 0.212), and follow-up time (p = 0.831) in the ER and LAP groups. However, significance difference was found in times to liquid diet intake (4.45 ± 1.2 vs. 5.40 ± 1.5 days, p = 0.013) and hospital stays (7.72 ± 1.1 vs. 10.01 ± 1.3 days, p < 0.001). During the follow-up period, there was one recurrence in the ER group vs. two recurrences in the LAP group. After PSM, the tumor size was balanced between the two groups with 49 patients in each group. The times to liquid diet intake (4.18 ± 1.3 vs. 5.16 ± 1.6 days, p = 0.042) and hospital stay days (7.12 ± 1.1 vs. 9.94 ± 1.3, p < 0.0001) were still short in the ER group. Conclusions: ER is more associated with a quick postoperative recovery than LAP. ER could be an alternative approach for gastric GISTs (2-5 cm). However, the long-term follow-up outcomes are still unclear and random control trials are needed.