Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) globally, representing a major global health burden with limited disease-modifying therapies. Podocyte injury serves as the core pathological hallmark of DN, and conventional treatments targeting metabolic disorders or hemodynamic abnormalities fail to reverse the progressive decline of renal function. Accumulating evidence over the past decade has established that high glucose-induced podocyte pyroptosis—a pro-inflammatory form of programmed cell death—is a key driving force in DN progression. Its core molecular mechanism hinges on the activation of the TXNIP-NLRP3 inflammasome axis. Under sustained hyperglycemic conditions, excessive reactive oxygen species (ROS) are generated via pathways including the polyol pathway, advanced glycation end products (AGEs) accumulation, and mitochondrial dysfunction. Concurrently, methylglyoxal (a glucose metabolite) mediates post-translational modification of thioredoxin-interacting protein (TXNIP). These events collectively trigger the dissociation of TXNIP from thioredoxin (TRX), a redox-regulating protein. The free TXNIP then translocates to the mitochondria, where it binds to The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) and promotes inflammasome assembly. This assembly activates cysteine-aspartic acid protease 1 (caspase-1), which cleaves Gasdermin D (GSDMD) to generate its N-terminal fragment (GSDMD-NT). GSDMD-NT oligomerizes to form membrane pores, leading to podocyte swelling, rupture, and the release of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). These cytokines amplify local inflammatory responses, induce mesangial cell proliferation, and accelerate extracellular matrix deposition, ultimately exacerbating glomerulosclerosis. MCC950, a highly selective NLRP3 inhibitor, exerts its therapeutic effects through a multi-layered mechanism: it binds to the NACHT domain (NAIP, CIITA, HET-E and TP1 domain) of NLRP3 with nanomolar affinity, forming hydrogen bonds with key residues (Lys-42 and Asp-166) within the ATP-hydrolysis pocket to block ATP hydrolysis, thereby locking NLRP3 in an inactive conformational state. Additionally, MCC950 interferes with the protein-protein interaction between TXNIP and NLRP3 and regulates mitochondrial homeostasis to reduce ROS production. Preclinical studies have demonstrated that MCC950 dose-dependently reduces proteinuria, restores the expression of podocyte-specific markers (nephrin and Wilms tumor 1 protein, WT1), and alleviates podocyte foot process fusion and glomerulosclerosis in both streptozotocin (STZ)-induced type 1 diabetic models (characterized by absolute insulin deficiency) and db/db type 2 diabetic models (driven by insulin resistance). However, discrepancies in therapeutic outcomes exist across different models—some studies report exacerbated renal inflammation and fibrosis in STZ-induced models—which may stem from differences in disease pathogenesis, intervention timing (early vs. mid-stage disease), and dosing duration. Despite its promising preclinical efficacy, MCC950 faces significant translational challenges, including low oral bioavailability, insufficient podocyte targeting, potential hepatotoxicity, and drug-drug interactions with statins (commonly prescribed to diabetic patients for cardiovascular risk management). Furthermore, off-target effects such as the inhibition of carbonic anhydrase 2 have been identified, raising concerns about its safety profile. Nevertheless, its unique mechanism of action—directly blocking podocyte pyroptosis by targeting the TXNIP-NLRP3 axis—endows it with substantial translational value. In the future, strategies to overcome these barriers are expected to advance its clinical application: targeted delivery via nanocarriers (e.g., PLGA-PEG nanoparticles or nephrin antibody-conjugated systems) to enhance renal accumulation and podocyte specificity; precise patient stratification based on biomarkers such as serum IL-18 and renal TXNIP/NLRP3 expression to identify “inflammatory-phenotype” DN patients most likely to benefit; and combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors—whose metabolic benefits synergize with MCC950’s anti-inflammatory effects. These approaches hold great potential to break through clinical translation bottlenecks, offering a novel, precise anti-inflammatory treatment option for DN and addressing an unmet clinical need for therapies targeting the inflammatory underpinnings of the disease.

Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) globally, representing a major global health burden with limited disease-modifying therapies. Podocyte injury serves as the core pathological hallmark of DN, and conventional treatments targeting metabolic disorders or hemodynamic abnormalities fail to reverse the progressive decline of renal function. Accumulating evidence over the past decade has established that high glucose-induced podocyte pyroptosis—a pro-inflammatory form of programmed cell death—is a key driving force in DN progression. Its core molecular mechanism hinges on the activation of the TXNIP-NLRP3 inflammasome axis. Under sustained hyperglycemic conditions, excessive reactive oxygen species (ROS) are generated via pathways including the polyol pathway, advanced glycation end products (AGEs) accumulation, and mitochondrial dysfunction. Concurrently, methylglyoxal (a glucose metabolite) mediates post-translational modification of thioredoxin-interacting protein (TXNIP). These events collectively trigger the dissociation of TXNIP from thioredoxin (TRX), a redox-regulating protein. The free TXNIP then translocates to the mitochondria, where it binds to The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) and promotes inflammasome assembly. This assembly activates cysteine-aspartic acid protease 1 (caspase-1), which cleaves Gasdermin D (GSDMD) to generate its N-terminal fragment (GSDMD-NT). GSDMD-NT oligomerizes to form membrane pores, leading to podocyte swelling, rupture, and the release of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). These cytokines amplify local inflammatory responses, induce mesangial cell proliferation, and accelerate extracellular matrix deposition, ultimately exacerbating glomerulosclerosis. MCC950, a highly selective NLRP3 inhibitor, exerts its therapeutic effects through a multi-layered mechanism: it binds to the NACHT domain (NAIP, CIITA, HET-E and TP1 domain) of NLRP3 with nanomolar affinity, forming hydrogen bonds with key residues (Lys-42 and Asp-166) within the ATP-hydrolysis pocket to block ATP hydrolysis, thereby locking NLRP3 in an inactive conformational state. Additionally, MCC950 interferes with the protein-protein interaction between TXNIP and NLRP3 and regulates mitochondrial homeostasis to reduce ROS production. Preclinical studies have demonstrated that MCC950 dose-dependently reduces proteinuria, restores the expression of podocyte-specific markers (nephrin and Wilms tumor 1 protein, WT1), and alleviates podocyte foot process fusion and glomerulosclerosis in both streptozotocin (STZ)-induced type 1 diabetic models (characterized by absolute insulin deficiency) and db/db type 2 diabetic models (driven by insulin resistance). However, discrepancies in therapeutic outcomes exist across different models—some studies report exacerbated renal inflammation and fibrosis in STZ-induced models—which may stem from differences in disease pathogenesis, intervention timing (early vs. mid-stage disease), and dosing duration. Despite its promising preclinical efficacy, MCC950 faces significant translational challenges, including low oral bioavailability, insufficient podocyte targeting, potential hepatotoxicity, and drug-drug interactions with statins (commonly prescribed to diabetic patients for cardiovascular risk management). Furthermore, off-target effects such as the inhibition of carbonic anhydrase 2 have been identified, raising concerns about its safety profile. Nevertheless, its unique mechanism of action—directly blocking podocyte pyroptosis by targeting the TXNIP-NLRP3 axis—endows it with substantial translational value. In the future, strategies to overcome these barriers are expected to advance its clinical application: targeted delivery via nanocarriers (e.g., PLGA-PEG nanoparticles or nephrin antibody-conjugated systems) to enhance renal accumulation and podocyte specificity; precise patient stratification based on biomarkers such as serum IL-18 and renal TXNIP/NLRP3 expression to identify “inflammatory-phenotype” DN patients most likely to benefit; and combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors—whose metabolic benefits synergize with MCC950’s anti-inflammatory effects. These approaches hold great potential to break through clinical translation bottlenecks, offering a novel, precise anti-inflammatory treatment option for DN and addressing an unmet clinical need for therapies targeting the inflammatory underpinnings of the disease.

Objective:To study the expression of serum microRNA (miRNA)-335 and miRNA-375 in patients with papillary thyroid carcinoma (PTC) and their relationship with pathological features and prognosis.Methods:Using a case-control study method, 94 PTC patients admitted to Huaian Hospital of Huaian City from March 2021 to March 2023 were selected as PTC group. Another 73 healthy individuals who underwent physical examinations during the same period were selected as control group. Quantitative real-time PCR was used to determine the relative expression levels of serum miRNA-335 and miRNA-375. PTC patients were followed up until September 30, 2024, and the patient's prognosis was record. The relative expression levels of serum miRNA-335 and miRNA-375 were compared between the two groups, among different pathological features, and among patients with different prognoses. Multivariate logistic regression analysis was performed to identify independent risk factors for prognosis in PTC patients.Results:The relative expression level of serum miRNA-335 in the PTC group (2.35 ± 0.68) was higher than that in the control group (0.98 ± 0.04), while the relative expression level of miRNA-375 (0.65 ± 0.21) was lower than that in the control group (1.01 ± 0.02, P < 0.001). There was no statistically significant differences in the relative expression levels of serum miRNA-335 and miRNA-375 among PTC patients with different tumor diameters, tumor locations, tumor numbers, and vascular invasion ( P > 0.05). The relative expression level of serum miRNA-335 in TNM stages Ⅲ - Ⅳ was higher than that in stages Ⅰ - Ⅱ, while the relative expression level of miRNA-375 in TNM stages Ⅲ - Ⅳ was lower than that in stages Ⅰ - Ⅱ ( P < 0.001). The relative expression level of serum miRNA-335 of patients with lymph node metastasis was higher than that of patients without lymph node metastasis, while the relative expression level of serum miRNA-375 of patients with lymph node metastasis was lower than that of patients without lymph node metastasis ( P < 0.001). The relative expression level of serum miRNA-335 in the poor prognosis group was higher than that in the good prognosis group, while the relative expression level of miRNA-375 in the poor prognosis group was lower than that in the good prognosis group ( P < 0.001). Vascular invasion, lymph node metastasis, high expression of miRNA-335, and low expression of miRNA-375 were all independent risk factors for prognosis in PTC patients ( P < 0.05). Conclusion:Patients with PTC have high serum miRNA-335 expression and low miRNA-375 expression, and the expression of miRNA-335 and miRNA-375 is closely related to TNM staging, lymph node metastasis, and prognosis, which deserves clinical attention.

Aim To investigate the effect of eplerenone(EPL)on the alleviation of rheumatoid arthritis(RA)based on voltage-gated potassium channel 1.3(Kv1.3)/B-cell lymphoma-2(Bcl-2)/nuclear factor-κB(NF-κB)to inhibit macrophage M1 polarization in mice.Methods Bioinformatics technology was used to screen disease pathways and targets,and the binding affinity and stability of EPL-Kv1.3 complex system were calculated.A mouse model of RA was established and treated with EPL by intragastric administration for 42 days.The indicators reflecting drug remission of RA were recorded and detected.RAW264.7 cells were treated with EPL to detect the indicators reflecting the effect of drugs on macrophage M1 polarization,and to verify the upstream and downstream key targets of re-lated signaling pathways mediated by drugs.Results Bioinformatics analysis showed that the disease targets were mainly involved in inflammatory response and NF-κB signaling pathway,and EPL-Kv1.3 had high affinity and stable binding.In animal experiments,the detec-tion of anti-cyclic citrullinated peptide antibody(CCP-Ab)and joint score indicated the successful establish-ment of the model.Compared with the model group,EPL could reduce the toe redness and swelling score,alleviate the plantar redness and swelling,synovial swelling,and reduce fibrosis and inflammatory cell in-filtration in mice.The medium-dose and high-dose EPL groups reduced the HE staining score(P＜0.05,P＜0.01),and the high-dose EPL group reduced the serum RF in mice(P＜0.01).CCK-8 results showed that low,medium and high doses of EPL had no effect on the activity of RAW264.7 macrophages(P＞0.05).Compared with the model group,EPL treatment significantly reduced the contents of IL-6,TNF-α and NO in supernatant of the cells(P＜0.01),reduced the nuclear translocation of NF-KB-p65 in the high-dose EPL group,reduced the M1 polarization and increased the proportion of M2 polarization in the medium and high-dose EPL groups(P＜0.01).The mRNA levels of MyD88,IκB-α,NF-κB-p65,NF-KB-p50,IL-1 β and iNOS were significantly reduced in each dose group of EPL(P＜0.01).EPL significantly increased the pro-tein expression of Bcl-2(P＜0.01)and decreased the protein expression of Kv1.3,MyD88,p-IκB-α/IκB-α,p-p65/p65,IL-1 β and iNOS(P＜0.05).Conclusion EPL may play an immunomodulatory role in relieving RA in mice by regulating Kv1.3/Bcl-2/NF-κB path-way,reducing macrophage M1 polarization and amelio-rating macrophage-associated inflammatory response.

Objective:To explore whether perioperative oral probiotic therapy reduces infectious complications following pancreaticoduodenectomy (PD), aiming to obtain higher-level evidence for clinical practice.Methods:A total of 81 participants undergoing PD at the Department of Pancreatic and Metabolic Surgery, Nanjing Drum Tower Hospital & Affiliated Hospital of Medical School, Nanjing University, from May 2024 to December 2024 were enrolled in this single-center, prospective, randomized controlled trial. The participants were randomly divided into a probiotic treatment group and a control group (receiving conventional treatment without probiotics) using a random number method. The primary outcomes included the incidence of postoperative infectious complications and intra-abdominal infection, and the secondary outcomes were the recovery of gastrointestinal function, postoperative hospital stay, and duration and costs of antibiotic use. The hematological indicators including inflammation and immune markers on postoperative days (POD) 1, 3, 5, and 7 were also compared between these two groups.Results:Finally 72 cases (39 males and 33 females) were analyzed, with 36 patients in the probiotic treatment group and 36 patients in the control group. Compared to the control group, the probiotic treatment group showed statistically significant reductions in the incidence of infectious complications (33.3% vs. 66.7%, P=0.029), intra-abdominal infection (27.8% vs. 58.3%, P=0.030), and incidence of delayed gastric emptying (0 vs. 16.7%, P=0.033). Also, the probiotic treatment group exhibited significantly faster recovery in postoperative bowel movements and shorter time to defecation, liquid diet, and semi-liquid diet (all P<0.05). Additionally, the probiotic treatment group had significantly shorter hospital stay, reduced duration of antibiotic use, and lower antibiotic costs (all P<0.05). Finally, the probiotic treatment group had significantly higher lymphocyte counts on POD 1 ( P<0.05) and showed a significant downward trend in inflammatory markers such as interleukin-6 on PODs 3 and 5 and C-reactive protein on POD 7 (all P<0.05). Conclusions:Perioperative application of probiotic preparations in PD may reduce the incidence of postoperative infectious complications, especially intra-abdominal infection. Additionally, it can prevent delayed gastric emptying, promote the recovery of postoperative gastrointestinal function, shorten hospital stay, and reduce the use of antibiotics. These benefits may be related to the improvement of postoperative inflammatory status.

Lyase acylation is a post-translational modification of proteins that plays a key role in cellular function,gene transcription and cellular metabolism.Meanwhile,lysine acylation is also involved in mul-tiple biological processes in life forms,and its abnormality may be associated with the occurrence and de-velopment of many diseases.Therefore,prediction of lysine acylation sites is important for the diagnosis and treatment of diseases.Although biomedical experiments can detect lysine acylation sites with high precision,they are costly and time-consuming.To address this problem,researchers have developed more convenient and efficient computational methods as an alternative to traditional biomedical experi-mental techniques.In this study,we developed a prediction model iKcr-RG based on a deep learning ap-proach,which employs a two-branching strategy using both ResNet and BiGRU to extract both local and global feature information from the original sequence encoding.To further improve the performance of the model,we innovatively designed a feature fusion method.After these optimizations,this study demon-strates stronger robustness and stability in unbalanced data.In the independent dataset results,specificity(Sp),sensitivity(Sn),accuracy(Acc)and Matthews correlation coefficient(MCC)were 0.8109,0.7902,0.7940,and 0.4978 respectively.The iKcr-RG model was better than existing prediction mod-els in predicting lysine acylation sites,and this study provides new ideas and methods for the application of deep learning in bioinformatics.

Objective:To explore whether perioperative oral probiotic therapy reduces infectious complications following pancreaticoduodenectomy (PD), aiming to obtain higher-level evidence for clinical practice.Methods:A total of 81 participants undergoing PD at the Department of Pancreatic and Metabolic Surgery, Nanjing Drum Tower Hospital & Affiliated Hospital of Medical School, Nanjing University, from May 2024 to December 2024 were enrolled in this single-center, prospective, randomized controlled trial. The participants were randomly divided into a probiotic treatment group and a control group (receiving conventional treatment without probiotics) using a random number method. The primary outcomes included the incidence of postoperative infectious complications and intra-abdominal infection, and the secondary outcomes were the recovery of gastrointestinal function, postoperative hospital stay, and duration and costs of antibiotic use. The hematological indicators including inflammation and immune markers on postoperative days (POD) 1, 3, 5, and 7 were also compared between these two groups.Results:Finally 72 cases (39 males and 33 females) were analyzed, with 36 patients in the probiotic treatment group and 36 patients in the control group. Compared to the control group, the probiotic treatment group showed statistically significant reductions in the incidence of infectious complications (33.3% vs. 66.7%, P=0.029), intra-abdominal infection (27.8% vs. 58.3%, P=0.030), and incidence of delayed gastric emptying (0 vs. 16.7%, P=0.033). Also, the probiotic treatment group exhibited significantly faster recovery in postoperative bowel movements and shorter time to defecation, liquid diet, and semi-liquid diet (all P<0.05). Additionally, the probiotic treatment group had significantly shorter hospital stay, reduced duration of antibiotic use, and lower antibiotic costs (all P<0.05). Finally, the probiotic treatment group had significantly higher lymphocyte counts on POD 1 ( P<0.05) and showed a significant downward trend in inflammatory markers such as interleukin-6 on PODs 3 and 5 and C-reactive protein on POD 7 (all P<0.05). Conclusions:Perioperative application of probiotic preparations in PD may reduce the incidence of postoperative infectious complications, especially intra-abdominal infection. Additionally, it can prevent delayed gastric emptying, promote the recovery of postoperative gastrointestinal function, shorten hospital stay, and reduce the use of antibiotics. These benefits may be related to the improvement of postoperative inflammatory status.

Aim To investigate the effect of eplerenone(EPL)on the alleviation of rheumatoid arthritis(RA)based on voltage-gated potassium channel 1.3(Kv1.3)/B-cell lymphoma-2(Bcl-2)/nuclear factor-κB(NF-κB)to inhibit macrophage M1 polarization in mice.Methods Bioinformatics technology was used to screen disease pathways and targets,and the binding affinity and stability of EPL-Kv1.3 complex system were calculated.A mouse model of RA was established and treated with EPL by intragastric administration for 42 days.The indicators reflecting drug remission of RA were recorded and detected.RAW264.7 cells were treated with EPL to detect the indicators reflecting the effect of drugs on macrophage M1 polarization,and to verify the upstream and downstream key targets of re-lated signaling pathways mediated by drugs.Results Bioinformatics analysis showed that the disease targets were mainly involved in inflammatory response and NF-κB signaling pathway,and EPL-Kv1.3 had high affinity and stable binding.In animal experiments,the detec-tion of anti-cyclic citrullinated peptide antibody(CCP-Ab)and joint score indicated the successful establish-ment of the model.Compared with the model group,EPL could reduce the toe redness and swelling score,alleviate the plantar redness and swelling,synovial swelling,and reduce fibrosis and inflammatory cell in-filtration in mice.The medium-dose and high-dose EPL groups reduced the HE staining score(P＜0.05,P＜0.01),and the high-dose EPL group reduced the serum RF in mice(P＜0.01).CCK-8 results showed that low,medium and high doses of EPL had no effect on the activity of RAW264.7 macrophages(P＞0.05).Compared with the model group,EPL treatment significantly reduced the contents of IL-6,TNF-α and NO in supernatant of the cells(P＜0.01),reduced the nuclear translocation of NF-KB-p65 in the high-dose EPL group,reduced the M1 polarization and increased the proportion of M2 polarization in the medium and high-dose EPL groups(P＜0.01).The mRNA levels of MyD88,IκB-α,NF-κB-p65,NF-KB-p50,IL-1 β and iNOS were significantly reduced in each dose group of EPL(P＜0.01).EPL significantly increased the pro-tein expression of Bcl-2(P＜0.01)and decreased the protein expression of Kv1.3,MyD88,p-IκB-α/IκB-α,p-p65/p65,IL-1 β and iNOS(P＜0.05).Conclusion EPL may play an immunomodulatory role in relieving RA in mice by regulating Kv1.3/Bcl-2/NF-κB path-way,reducing macrophage M1 polarization and amelio-rating macrophage-associated inflammatory response.

Objective::Pulmonary hypertension secondary to left heart failure is associated with an abnormal response to exercise and poor prognosis. The objective of this study is to develop an algorithm by using data from cardiopulmonary exercise testing (CPET) to assess the severity of pulmonary hemodynamics and predict clinical worsening and mortality in patients with heart failure.Methods::From April 2017 to December 2018, a total of 102 patients with heart failure who underwent CPET and invasive right heart catheterization participated in this prospective study. All enrolled patients had their clinical characteristics, hemodynamic parameters, and CPET results. Based on the CPET data namely peak oxygen uptake, the minute ventilation/carbon dioxide production slope, resting end-tidal carbon dioxide, oxygen uptake/work rate flattening, exercise oscillatory ventilation, and oxygen uptake efficiency slope, a Heart Failure Cardiopulmonary Exercise (HFCE) score was developed. The total score was then calculated to categorize patients into 3 groups: low score (0-3) ( n = 31), intermediate score (4-7) ( n = 45), and high score (8-14) ( n = 26). Clinical events were defined as all-cause death and rehospitalization for heart failure, which were recorded and tracked for at least 12 months. Pearson’s correlation coefficients were calculated to assess the relationship between the HFCE score and hemodynamic parameters, 6-minute walk distance, and N-terminal-pro hormone brain natriuretic peptide. Cox proportional hazards regression analysis was used to identify independent predictors of clinical events. Survival curves for clinical events were generated using the Kaplan-Meier method and compared among the 3 groups with different HFCE scores with a log-rank test. Results::The high HFCE score group had a higher prevalence of New York Heart Association class Ⅲ-Ⅳ (high score vs. intermediate score vs. low score: 85% (22/26) vs. 56% (25/45) vs. 45% (14/31), P = 0.008), higher N-terminal-pro hormone brain natriuretic peptide levels (high score vs. intermediate score vs. low score: (3,039 ± 2,171) ng/L vs. (2,039 ± 2,353) ng/L vs. (1,438 ± 947) ng/L, P = 0.035), lower 6-minute walk distance (high score vs. intermediate score vs. low score: (312 ± 79) m vs. (362 ± 84) m vs. (363 ± 76) m, P = 0.042) compared to intermediate score or low score. The high HFCE score correlated well with high levels of pulmonary vascular resistance ( r = 0.539, P < 0.01), pulmonary artery wedge pressure ( r = 0.292, P < 0.01), and mean pulmonary artery pressure ( r = 0.474, P < 0.01), as well as low levels of cardiac output ( r = -0.357, P < 0.01). Moreover, 46 patients developed composed clinical events at 12 months. In the multivariate model, the HFCE score was an independent predictor of composed clinical events (hazard ratio = 1.142, 95% confidence interval: 1.041-1.253, P = 0.005). Kaplan-Meier analysis showed a significantly higher probability of composed clinical events in patients with a higher HFCE score ( P log-rank = 0.004). Conclusion::The HFCE score—obtained through CPET—provides valuable prognostic information by indicating the severity of hemodynamics in patients with pulmonary hypertension secondary to left heart failure. It can likely serve as a reliable predictor for clinical worsening and mortality.

Objectives: . Endotype-based interventions have shown promise in the treatment of patients with obstructive sleep apnea, and upper airway surgery is a key therapeutic option. However, responses to surgery vary among patients with obstructive sleep apnea. This study aims to examine changes in endotypic traits following upper airway surgery and to explore their association with surgical outcomes. Methods: . We prospectively recruited 25 patients with obstructive sleep apnea who visited a single sleep center for upper airway surgery. These patients underwent polysomnographic studies both before and after surgical intervention. During non-rapid eye movement and rapid eye movement sleep, we estimated endotypic traits—including collapsibility (Vpassive), arousal threshold, loop gain, and upper airway compensation—with the phenotyping using polysomnography method. Based on improvements in the apnea-hypopnea index, patients were classified as either responders or non-responders. We compared the preoperative endotypic traits between these groups using Mann-Whitney tests. Additionally, we compared changes in endotypic traits pre- and post-surgery between responders and non-responders using generalized linear mixed models. Results: . We identified 12 responders and 13 non-responders. Compared to non-responders, responders exhibited improved collapsibility during rapid eye movement sleep (22.3 vs. −8.2%eupnea in Vpassive, P=0.01), and their arousal threshold decreased during non-rapid eye movement sleep (−22.4%eupnea, P=0.02). No endotypic trait predicted surgical response; however, the apnea-hypopnea index during rapid eye movement sleep was higher among responders than non-responders (51.8/hr vs. 34.4/hr, P=0.05). Conclusion . Upper airway surgery significantly reduced collapsibility during rapid eye movement sleep in responders. The target pathology for upper airway surgery is a compromised upper airway during rapid eye movement sleep.