Objective:To investigate the role of Gasdermin E (GSDME) -mediated keratinocyte pyroptosis induced by Cutibacterium acnes ( C.acnes) in the pathogenesis of acne. Methods:The human immortalized keratinocyte HaCaT cells were stimulated with heat-inactived C.acnes for 15 minutes to 24 hours, and Western blot analysis was performed to determine the expression of cleaved GSDME (GSDME-NT) in HaCaT cells at different time points. Skin tissue samples were collected from 5 acne patients and 4 healthy controls, who visited the Hospital for Skin Diseases, Chinese Academy of Medical Sciences from January 2 to December 1, 2024; additionally, 3 samples of acne cyst contents and 3 samples of normal follicle contents were collected. Immunohistochemical study and Western blot analysis were conducted to determine GSDME-NT expression in the epidermis. Enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of interleukin (IL) -1β and tumor necrosis factor (TNF) -α in acne cyst or normal follicle contents. GSDME-knockdown HaCaT cells were constructed by transfection with lentivirus carrying GSDME-shRNA, and HaCaT cells transfected with lentivirus carrying the nonsense sequence control (NC) served as controls; ELISA was performed to detect the levels of IL-1β and TNF-α in GSDME-knockdown HaCaT cells after C. acnes stimulation ( C. acnes + GSDME knockdown group) , as well as in the phosphate-buffered saline (PBS) + NC group, C. acnes + NC group, and PBS + GSDME knockdown group. Western blot analysis was conducted to determine the GSDME-NT expression in HaCaT cells pretreated with or without retinol after C. acnes stimulation. Results:The cleavage of GSDME in HaCaT cells began at 1 hour after in vitro C. acnes stimulation, and GSDME-NT could be detected at this time. Compared with the control epidermis, the proportion of GSDME-NT-positive HaCaT cells (9.34% ± 2.92% vs. 3.05% ± 1.14%, t = -3.47, P = 0.026) and GSDME-NT protein expression levels ( t = -3.51, P = 0.025) significantly increased in the lesional epidermis of acne patients. The levels of IL-1β and TNF-α were significantly higher in the acne cyst contents than in the normal follicle contents (IL-1β: 1 337.24 [1 182.32, 2 230.61] pg/ml vs. 0.00 [0.00, 108.21] pg/ml, Z = 1.99, P = 0.046; TNF-α: 811.31 [438.26, 817.73] pg/ml vs. 46.67 [12.41, 53.21] pg/ml, Z = 1.96, P = 0.049) . ELISA showed that the levels of IL-1β and TNF-α were significantly higher in the C. acnes + NC group (12.12 ± 3.07 pg/ml, 26.06 ± 1.57 pg/ml, respectively) than in the PBS + NC group (3.73 ± 2.24 pg/ml, 10.14 ± 0.79 pg/ml, P = 0.003, < 0.001, respectively) ; compared with the C. acnes + NC group, the levels of IL-1β and TNF-α significantly decreased in the C. acnes + GSDME knockdown group (3.38 ± 0.93 pg/ml, 12.67 ± 2.10 pg/ml, P = 0.003, < 0.001, respectively) . The GSDME-NT expression was significantly lower in the retinol + C. acnes group than in the C. acnes group ( P = 0.029) . Conclusion:C. acnes may induce GSDME-mediated pyroptosis in keratinocytes, thereby promoting the release of inflammatory factors and aggravating the inflammatory response in acne, while retinol may be able to inhibit this process.

Objective:To investigate the feasibility and safety of laparoscopic purse- string suture clamps combined with multi-functional seal caps for esophagojejunal Roux-en-Y anastomosis during total laparoscopic radical total gastrectomy (TLTG).Methods:This was a retrospective descriptive study of 42 patients with primary gastric malignancies who underwent TLTG at the First Affiliated Hospital of Nanjing Medical University that utilized laparoscopic purse-string suture clamps and multi-functional seal caps for esophagojejunal anastomosis between May, 2024 and January, 2025. The cohort included 33 males and 9 females, with a mean age of (67.7 ±9.5) years and a mean body mass index (BMI) of (23.9±2.9) kg/m 2. The American Society of Anesthesiologists (ASA) physical status classifications were I - II in 40 patients and III in 2 patients, and all patients were definitively diagnosed preoperatively via gastroscopy, dual-energy CT, and/or MRI. Tumor locations included the gastroesophageal junction (GEJ) in 28 cases (Siewert type II - III), the upper third of the stomach in 12 cases, and the middle third in 2 cases. The median distance of esophageal invasion was 1.3 cm, though in 10 cases this was ≥2 cm. Preoperative TNM staging was I-II in 17 patients and III in 25 patients. Surgical outcomes including operative time, anastomosis time, intraoperative blood loss, pathological results, and postoperative recovery were retrospectively analyzed. Results:All 42 operations were successful. The mean operative time was(212.5±26.4) minutes, and the average time from multi-functional seal cap placement to completion of the esophagojejunal anastomosis was (54.2±7.5) minutes. Mean intraoperative blood loss was (79.9±21.3) ml. Postoperative pathology confirmed R0 resection in all specimens, with a mean proximal esophageal margin distance of (2.1±1.6) cm. Furthermore, (51.9±15.1) lymph nodes on average were harvested from each patient; the mean time to oral intake was (149.5±41.4) hours; and the mean hospital stay was (11.3±5.4) days. Postoperative complications occurred in 6 patients: anastomotic leakage ( n=2), residual intra-abdominal infection ( n=1), pulmonary infection ( n=3), and Clavien-Dindo grade III or higher complications occurred in 2 patients. No recurrence, mortality, or anastomosis-related complications were observed within a median follow-up of 5.8 months (range 3.5-11.2). Conclusion:We find the application of the laparoscopic purse-string suture clamps and multi-functional seal caps for esophagojejunal anastomosis in TLTG to be safe and feasible, with satisfactory short-term outcomes.

Objective To analyze the correlation between serum interleukin-37(IL-37)and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)with disease severity in chronic obstructive pulmonary disease(COPD)patients with systemic inflammatory response syndrome(SIRS),and evaluate their combined predictive value for prognosis.Methods A total of 150 patients with COPD and SIRS in Zigong First People's Hospital from January 2023 to March 2024 were selected as the study group,and 150 patients with COPD were selected as the control group.The groups were compared for general data and serum IL-37 and NLRP3 levels upon admission.The serum IL-37 and NLRP3 levels of patients with different disease severities in the study group were compared to analyze their correlation with disease severity.28-day prognosis of both groups was compared,and the serum IL-37 and NLRP3 levels of patients with poor and good prognosis in the study group were analyzed.Univariate and multivariate Logistic regression was used to assess factors influencing poor prognosis in COPD patients with SIRS.The predictive value of serum IL-37 and NLRP3 for poor prognosis was evaluated,and their interactive effects on patient outcomes were analyzed.Results The study group's serum IL-37 and NLRP3 levels were higher upon admission compared to the control group(P<0.05);serum IL-37 and NLRP3 levels in extremely severe patients were higher than those in severe,moderate,and mild patients,with severe patients higher than moderate and mild patients,and moderate patients higher than mild patients(P<0.05);serum IL-37 and NLRP3 levels at admission were positively correlated with the disease severity of COPD patients with SIRS(P<0.05);patients with poor prognosis had higher serum IL-37 and NLRP3 levels upon admission compared to those with good prognosis(P<0.05);serum IL-37 and NLRP3 levels at admission were independent risk factors for poor prognosis in COPD patients with SIRS(P<0.05);the AUC for predicting poor prognosis using serum IL-37 and NLRP3 alone were 0.805 and 0.834,respectively,while the combined AUC was 0.920,which was higher than the individual AUCs(P<0.05);interaction analysis showed that high serum IL-37 and NLRP3 levels exhibited a positive super-multiplicative interaction in the prognosis of COPD patients with SIRS(P<0.05).Conclusion Serum IL-37 and NLRP3 levels in COPD patients with SIRS were positively correlated with disease severity,and the combined serum IL-37 and NLRP3 showed high predictive efficacy for patient prognosis.

The transition of cancer cells from epithelial state to mesenchymal state awarded hepatocellular carcinoma (HCC) stem cell properties and induced tumorigenicity, drug resistance, and high recurrence rate. Reversing the mesenchymal state to epithelial state by inducing mesenchymal-epithelial remodeling could inhibit the progression of HCC. Using high-throughput screening, chrysin was selected from natural products to reverse epithelial-mesenchymal transition (EMT) by selectively increasing CDH1 expression. The target identification suggested chrysin exerted its anti-HCC effect through covalently and specifically binding threonine 205 (Thr205) of alpha-enolase (ENO1). For the first time, we revealed that ENO1 bound β-catenin mRNA, and recruited YTHDF2 to identify the m6A modified β-catenin in the 3'-UTR region to degrade β-catenin mRNA. Eventually, the CDH1 gene expression was improved through the regulation of β-catenin mRNA. ENO1/β-catenin mRNA interaction might be a promising target for cellular plasticity reprogramming. Moreover, chrysin could mediate mesenchymal‒epithelial remodeling through increasing degradation of β-catenin mRNA by promoting the binding of ENO1 and β-catenin mRNA. To the best of our knowledge, chrysin is the first reported small molecule inducing β-catenin mRNA degradation through binding to ENO1. The water-soluble derivative of chrysin may be a natural product-derived lead compound for circumventing metastasis, recurrence, and drug resistance of HCC by mediating mesenchymal‒epithelial remodeling.

Objective:To investigate the role of Gasdermin E (GSDME) -mediated keratinocyte pyroptosis induced by Cutibacterium acnes ( C.acnes) in the pathogenesis of acne. Methods:The human immortalized keratinocyte HaCaT cells were stimulated with heat-inactived C.acnes for 15 minutes to 24 hours, and Western blot analysis was performed to determine the expression of cleaved GSDME (GSDME-NT) in HaCaT cells at different time points. Skin tissue samples were collected from 5 acne patients and 4 healthy controls, who visited the Hospital for Skin Diseases, Chinese Academy of Medical Sciences from January 2 to December 1, 2024; additionally, 3 samples of acne cyst contents and 3 samples of normal follicle contents were collected. Immunohistochemical study and Western blot analysis were conducted to determine GSDME-NT expression in the epidermis. Enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of interleukin (IL) -1β and tumor necrosis factor (TNF) -α in acne cyst or normal follicle contents. GSDME-knockdown HaCaT cells were constructed by transfection with lentivirus carrying GSDME-shRNA, and HaCaT cells transfected with lentivirus carrying the nonsense sequence control (NC) served as controls; ELISA was performed to detect the levels of IL-1β and TNF-α in GSDME-knockdown HaCaT cells after C. acnes stimulation ( C. acnes + GSDME knockdown group) , as well as in the phosphate-buffered saline (PBS) + NC group, C. acnes + NC group, and PBS + GSDME knockdown group. Western blot analysis was conducted to determine the GSDME-NT expression in HaCaT cells pretreated with or without retinol after C. acnes stimulation. Results:The cleavage of GSDME in HaCaT cells began at 1 hour after in vitro C. acnes stimulation, and GSDME-NT could be detected at this time. Compared with the control epidermis, the proportion of GSDME-NT-positive HaCaT cells (9.34% ± 2.92% vs. 3.05% ± 1.14%, t = -3.47, P = 0.026) and GSDME-NT protein expression levels ( t = -3.51, P = 0.025) significantly increased in the lesional epidermis of acne patients. The levels of IL-1β and TNF-α were significantly higher in the acne cyst contents than in the normal follicle contents (IL-1β: 1 337.24 [1 182.32, 2 230.61] pg/ml vs. 0.00 [0.00, 108.21] pg/ml, Z = 1.99, P = 0.046; TNF-α: 811.31 [438.26, 817.73] pg/ml vs. 46.67 [12.41, 53.21] pg/ml, Z = 1.96, P = 0.049) . ELISA showed that the levels of IL-1β and TNF-α were significantly higher in the C. acnes + NC group (12.12 ± 3.07 pg/ml, 26.06 ± 1.57 pg/ml, respectively) than in the PBS + NC group (3.73 ± 2.24 pg/ml, 10.14 ± 0.79 pg/ml, P = 0.003, < 0.001, respectively) ; compared with the C. acnes + NC group, the levels of IL-1β and TNF-α significantly decreased in the C. acnes + GSDME knockdown group (3.38 ± 0.93 pg/ml, 12.67 ± 2.10 pg/ml, P = 0.003, < 0.001, respectively) . The GSDME-NT expression was significantly lower in the retinol + C. acnes group than in the C. acnes group ( P = 0.029) . Conclusion:C. acnes may induce GSDME-mediated pyroptosis in keratinocytes, thereby promoting the release of inflammatory factors and aggravating the inflammatory response in acne, while retinol may be able to inhibit this process.

Objective:To investigate the feasibility and safety of laparoscopic purse- string suture clamps combined with multi-functional seal caps for esophagojejunal Roux-en-Y anastomosis during total laparoscopic radical total gastrectomy (TLTG).Methods:This was a retrospective descriptive study of 42 patients with primary gastric malignancies who underwent TLTG at the First Affiliated Hospital of Nanjing Medical University that utilized laparoscopic purse-string suture clamps and multi-functional seal caps for esophagojejunal anastomosis between May, 2024 and January, 2025. The cohort included 33 males and 9 females, with a mean age of (67.7 ±9.5) years and a mean body mass index (BMI) of (23.9±2.9) kg/m 2. The American Society of Anesthesiologists (ASA) physical status classifications were I - II in 40 patients and III in 2 patients, and all patients were definitively diagnosed preoperatively via gastroscopy, dual-energy CT, and/or MRI. Tumor locations included the gastroesophageal junction (GEJ) in 28 cases (Siewert type II - III), the upper third of the stomach in 12 cases, and the middle third in 2 cases. The median distance of esophageal invasion was 1.3 cm, though in 10 cases this was ≥2 cm. Preoperative TNM staging was I-II in 17 patients and III in 25 patients. Surgical outcomes including operative time, anastomosis time, intraoperative blood loss, pathological results, and postoperative recovery were retrospectively analyzed. Results:All 42 operations were successful. The mean operative time was(212.5±26.4) minutes, and the average time from multi-functional seal cap placement to completion of the esophagojejunal anastomosis was (54.2±7.5) minutes. Mean intraoperative blood loss was (79.9±21.3) ml. Postoperative pathology confirmed R0 resection in all specimens, with a mean proximal esophageal margin distance of (2.1±1.6) cm. Furthermore, (51.9±15.1) lymph nodes on average were harvested from each patient; the mean time to oral intake was (149.5±41.4) hours; and the mean hospital stay was (11.3±5.4) days. Postoperative complications occurred in 6 patients: anastomotic leakage ( n=2), residual intra-abdominal infection ( n=1), pulmonary infection ( n=3), and Clavien-Dindo grade III or higher complications occurred in 2 patients. No recurrence, mortality, or anastomosis-related complications were observed within a median follow-up of 5.8 months (range 3.5-11.2). Conclusion:We find the application of the laparoscopic purse-string suture clamps and multi-functional seal caps for esophagojejunal anastomosis in TLTG to be safe and feasible, with satisfactory short-term outcomes.

AIM:To investigate the effects and mechanism of long noncoding RNA PCED1B antisense strand 1(lncRNA PCED1B-AS1)on the proliferation,migration,invasion and apoptosis of papillary thyroid carcinoma(PTC)cells.METHODS:Human PTC cells were cultured in vitro.The expression of PCED1B-AS1 and fused in sarcoma(FUS)was measured by RT-qPCR.The effects of knockdown/overexpression of PCED1B-AS1/FUS on the migration and invasion of PTC cells were detected via Transwell assay.The effects of knockdown/overexpression of PCED1B-AS1/FUS on PTC cell proliferation were analysed via CCK-8 and plate colony assay.The effect of knockdown PCED1B-AS1 on PTC cell apoptosis was determined by flow cytometry.The target binding of PCED1B-AS1 and FUS was determined with bioin-formatics and RNA immunoprecipitation(RIP)experiments.Fluorescence in situ hybridization experiment was performed to verify whether PCED1B-AS1 colocalises with FUS.The mitogen-activated protein kinase(MAPK)signaling pathway-re-lated proteins were detected via Western blot.RESULTS:(1)PCED1B-AS1 expression was significantly higher and FUS expression was significantly lower in PTC cells compared with normal thyroid Nthy-ori3-1 cell(P<0.05).(2)Knockdown of PCED1B-AS1 and overexpression of FUS inhibited PTC cell migration,invasion and proliferation,and promoted apopto-sis(P<0.05).(3)Bioinformatics analysis and RIP assay verified the existence of targeted binding of PCED1B-AS1 to FUS(P<0.05).(4)PCED1B-AS1 and FUS colocalised in the cytoplasm.(5)Inhibition of PCED1B-AS1 decreased the expression of MAPK signaling pathway-related proteins p-ERK 1/2,p-JNK and p-P38(P<0.05).CONCLUSION:ln-cRNA PCED1B-AS1 inhibits the proliferation,migration and invasion,and promotes the apoptosis of PTC cells,and its mechanism may be related to the expression of FUS and the MAPK signaling pathway.

Objective To investigate the morphological and proteomic differences in exosomes(EXOs)during the stor-age of leukocyte-free apheresis platelets(LFA-Plt),evaluate the quality of platelets in storage and predict the function of EXOs at different storage periods.Methods EXOs were isolated by ultracentrifugation,then the morphological observation was performed by electron microscope.Particle size analysis and WB protein index detection were performed.4D Label-free quantitative proteomics technology was used to perform quantitative and bioinformatics analysis on identified proteins.Protein differential analysis on the LFA-Plt EXO between group day 3 and day 5 was performed,and GO function and KEGG path-way enrichment analysis on differential proteins was conducted.Results Cup shaped,CD9/TSG101 enriched and Calnexin(-)EXO was successfully obtained.The particle size(nm)of LFA-Plt EXO for day 3 and day 5 were(82.2±19.6)and(83.4±19.4)respectively,and the protein concentration(μ g/uL)were(0.55±0.13)and(0.51±0.08)respectively,with no statistically significant difference between two groups(P＞0.05).1 504 proteins were identified in all samples.GO func-tional enrichment analysis showed that the LFA-Plt EXO proteins were mainly concentrated in the cell membrane,extracel-lular domain and proteasome core complex,and were related to the binding ability of proteins,ATP,calcium ions and GTP,and mainly participated in processes such as redox,protein hydrolysis and signal transduction.KEGG functional annotation showed that the EXO proteins mainly participated in material transportation and catabolism,genetic information processing,and were closely related to human tumors and viral bacterial infections,affecting the metabolism of human immune system.Compared with day 3,day 5 EXO showed significant up-regulation in 16 proteins.The GO enrichment analysis showed that 16 upregulated proteins were mainly associated with adenosine homocysteine activity and 6-phosphofructose kinase activity,and were mainly involved in the metabolism of organic nitrogen compound.KEGG enrichment pathway analysis showed that the most important function of upregulated proteins was participating in signaling pathway for oocyte maturation mediated by progesterone.Conclusion Under the preparation and storage conditions of LFA-Plt in our center,platelet quality can be relatively stable.The functions of EXO proteins varies with different storage periods,which may affect the effectiveness of platelet transfusion.

Objective:To share the results of laparoscopic assisted proximal gastrectomy λ- shaped modified double tract reconstruction.Method:This study retrospectively included 3 patients during January 2024 from the Department of Gastric Surgery at the First Affiliated Hospital of Nanjing Medical University using the λ-shaped modified double tract reconstruction. The procedure of the λ-shaped modified double tract reconstruction is as follows. After completing proximal gastrectomy, the jejunum is transected 15 cm from the Treitz ligament. A suture is made 18-20 cm from the distal jejunum to mark the esophagojejunal anastomosis site. A circular stapler anvil is inserted through the distal jejunum, and the remaining end of the jejunum is turned to the right. The circular stapler is pierced through the marked site for an esophagojejunal end-to-end anastomosis, which is reinforced with a barbed suture continuously. A 60mm linear stapler is used to close the remaining end of the jejunum. We then mark the gastric side of the gastrojejunal anastomosis with suture in the middle of the anterior wall of the residual stomach, and mark the jejunal side of the gastrojejunal anastomosis at a distance of about 2 cm and 8 cm from the residual end of the distal jejunum. We make an opening of about 0.5 cm and use a 60 mm linear stapler to perform anastomosis on the jejunal side of the anterior wall of the residual stomach according to the markings, so that the distance between the esophagojejunal anastomosis and the gastrojejunal anastomosis is 10-12 cm. The common opening is closed with barbed wire. About 50 cm below the esophagojejunal anastomosis, the small intestine opening is anastomosed side to side using a circular stapler and the common opening is closed. Return the jejunum into the abdominal cavity to complete the reconstruction of the λ-shaped double tract reconstruction. We analyzed the surgery and postoperative conditions, including surgery time, anastomosis time, intraoperative bleeding, tumor size and pathology, postoperative mobilization, passage of gas and water intake time, discharge time, postoperative complications, and postoperative gastrointestinal imaging to observe the passage of food through the gastric and intestinal loops.Results:Three patients successfully received laparoscopic assisted proximal gastrectomy with λ-shaped modified double tract reconstruction. The surgical time was 155 minutes, 240 minutes, and 160 minutes, respectively; The postoperative time for first ambulation was 20 hours, 18 hours, and 26 hours, respectively. The time for passage of gas was 59 hours, 83 hours, and 75 hours, respectively. The drinking time was 66 hours, 87 hours, and 90 hours, respectively. The postoperative discharge days were all 7 days. No surgical related complications occurred. On the 6th day and 3 months after surgery, gastrointestinal angiography was performed. The contrast agent passed smoothly through the jejunal loop and residual stomach jejunal loop, and both sides were unobstructed. No contrast agent was found to retrograde to the esophagojejunal anastomosis.Conclusion:Laparoscopic assisted proximal gastrectomy with λ-shaped modified double tract reconstruction is safe and feasible, as it improves the diversion of food through the residual stomach while ensuring anti-reflux effects.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.