BackgroundPolycystic ovary syndrome (PCOS) significantly impairs physical and mental health, quality of life, and fertility in women of reproductive age. Strategies to enhance fertility in PCOS have been prioritised in International Guidelines. Whilst Guidelines recommend Letrozole in first line ovulation induction (OI), therapeutic interventions to optimise endocrine and metabolic PCOS features prior to OI have not been adequately researched despite potential to improve live birth and pregnancy outcomes. Whilst both a calorie-restricted (CR) diet and metformin interventions may offer benefits in the context, evidence is limited including for live birth rates, and pregnancy outcomes. Therefore, this study will aim aims to compare the effects of a CR diet versus metformin on live birth, endocrine, reproductive, and metabolic parameters as well as pregnancy outcomes in women with PCOS and overweight/obesity.MethodThis multicenter, randomized (1:1) comparative effectiveness trial will evaluate and compare the effects of a CR diet versus metformin, administered for 12 weeks prior to OI, on live birth, endocrine, metabolic, reproductive, and pregnancy outcomes in women with PCOS and overweight/obesity. The primary analysis will follow the intention-to-treat principle, including all participants who underwent randomization.DiscussionThis trial investigates the comparative efficacy of a CR diet versus metformin over a 12-week period prior to OI therapy in women with PCOS and overweight/obesity. Early therapeutic intervention holds significant potential to disrupt the pathophysiological cycle characterized by hyperandrogenism, excessive adiposity, and insulin resistance for improving fertility and pregnancy outcomes.Clinical trial registrationClinicalTrials.gov, identifier NCT06049186.

Background:Although small-size (T1, solid nodule with maximum diameter <3 cm) non-small cell lung cancer (NSCLC) is generally associated with a favorable prognosis, a notable subset of patients present with distant metastasis, a paradox that conventional staging fails to address. Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters and the systemic immune-inflammation index (SII) are linked to NSCLC progression, but their associations with distant metastasis in small-size NSCLC remain unclear. This study aimed to investigate these correlations to identify reliable metastatic risk factors for small-size NSCLC. Methods:This retrospective study enrolled 243 cases of pathologically confirmed T1 solid NSCLC, including 114 with and 129 without distant metastasis, who underwent 18F-FDG PET/CT within two weeks before tumor resection or biopsy. PET/CT metabolic parameters including standardized uptake value peak (SUVpeak), standardized uptake value maximum (SUVmax), standardized uptake value mean (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and coefficient of variation (COV) at various SUV thresholds (1.0, 1.5, 2.0, and 2.5) were assessed for primary lesions. Inflammation factors including SII were measured one day prior to surgery or biopsy. Patients were randomized into modeling (n=182) and validation (n=61) cohorts (3:1). Univariate/multivariate logistic regression analyses identified independent risk factors for metastasis correlations between metabolic parameters and serum inflammation markers were analyzed. Results:In the modeling cohort, high SUVpeak, SUVmean, SUVmax, MTV, TLG, and COV were significantly associated with distant metastasis (all P<0.05), except COV at SUV 1.0 (P=0.65). Multivariate regression confirmed COV at an SUV threshold of 2.0 (COV2.0) >0.33 as an independent risk factor [hazard ratio (HR) =3.03, P=0.01]. SII >641.68 was also identified as an independent inflammation-related risk factor (HR =2.84, P=0.003). COV2.0 was positively correlated with SII [odds ratio (OR) =4.55, P=0.03]. The co-high COV2.0/SII status was identified as an independent risk factor for metastasis (HR =5.08, P<0.001). In the independent validation cohort, the metastasis rate in the co-high COV2.0/SII group was 84.20% (16/19), significantly higher than the non-metastasis rate (15.80%, 3/19, P=0.043). The metastasis rate in the co-low COV2.0/SII group was only 17.90% (5/28, P<0.001). No clinicopathological features (age, gender, histological subtype, tumor diameter, smoking history) were associated with metastasis (all P>0.05). Conclusions:Enhanced glycolysis accompanied by a corresponding systemic immune response plays a critical role in T1 NSCLC metastasis. The combined assessment of 18F-FDG PET/CT-derived COV2.0 and serum SII may aid in evaluating the risk of distant metastasis in small-size NSCLC, thereby informing more rational treatment and follow-up strategies for lung cancer.

Cisplatin resistance remains a primary challenge in the clinical management of non-small cell lung cancer (NSCLC), yet the regulatory targets underlying this resistance remain largely unknown. It is well established that cisplatin kills tumor cells through the induction of DNA damage and the accumulation of reactive oxygen species (ROS), which exacerbate DNA damage. Here, we identify the glycolytic metabolic enzyme PGAM1, and specifically its elevated activity in cisplatin-resistant tumors, as a pivotal metabolic driver of this resistance. Y119 phosphorylation, which reflects increased PGAM1 activity, is significantly elevated in NSCLC patient tissues and further amplified in cisplatin-resistant cell lines. Mutation of the PGAM1 Y119 phosphorylation site (Y119F) resensitizes resistant cells to cisplatin both in vitro and in vivo. Mechanistically, Y119-phosphorylated PGAM1 enhances flux through the pentose phosphate pathway (PPP) and the serine synthesis pathway (SSP). This metabolic reprogramming promotes nucleotide biosynthesis and NADPH generation, thereby alleviating cisplatin-induced DNA damage and oxidative stress. In vivo, a PGAM1-derived pY119-mimetic cell-permeable peptide (Y119E-TAT) that competitively disrupts PGAM1 binding to its histidine kinase, thereby inhibiting PGAM1 activity, potently inhibits cisplatin-resistant NSCLC tumor growth. Together, these findings reveal a novel mechanism by which PGAM1 Y119 phosphorylation drives chemoresistance and suggest that targeting this phosphorylation event represents a potential therapeutic strategy to overcome cisplatin resistance in NSCLC.

BACKGROUND:To investigate the impact of 1-hour plasma glucose (1 h-PG) on the metabolic characteristics and pregnancy outcomes in polycystic ovary syndrome (PCOS). METHODS:This multicenter study analyzed 970 PCOS patients (2019-2025), including 289 undergoing assisted reproductive technology (198 successful deliveries). Participants were stratified by glucose tolerance: Group 1 (normal: fasting PG [FPG] ≤ 6.1, 1 h-PG < 8.6, 2-hour PG [2 h-PG] <7.8 mmol/L); Group 2 (isolated 1 h-prediabetes: 8.6 ≤ 1 h-PG < 11.6, FPG ≤ 6.1, 2 h-PG < 7.8 mmol/L); Group 3 (traditional 2 h-prediabetes: 7.8 ≤ 2 h-PG ≤ 11.1, FPG ≤ 6.1 mmol/L). Data included anthropometrics, metabolic biomarkers, sex hormones, and pregnancy outcomes were compared across three groups. RESULTS:PCOS with isolated 1 h-prediabetes (Group 2) had a more unfavorable metabolic profile with regard to metabolic traits, but were not significantly different from those of the traditional 2 h-prediabetes (Group 3). The adjusted odds ratios (ORs) for hypertension, hyperlipidemia, metabolic syndrome (MetS), and hyperuricemia in PCOS with Group 2 were 1.451 (1.013-2.079, P = 0.042), 1.706 (1.188-2.450, P = 0.004), 2.957 (1.755-4.981, P < 0.001), 1.890 (1.327-2.692, P < 0.001), respectively. For pregnancy outcomes, PCOS in Group 2 were more likely to progress to gestational diabetes mellitus (GDM) than those of Group 1, which was similarly observed in Group 3. The adjusted OR for GDM in the Group 2 was 4.065 (1.530-10.800, P = 0.005). CONCLUSIONS:Our study demonstrated that similar to 2 h-PG, elevated 1 h-PG was associated with different metabolic disorders and GDM. Therefore, 1 h-PG may serve as an additional marker of adverse metabolic status in women with PCOS.

Background Endometriosis-associated ovarian cancer is a distinct form of epithelial ovarian cancer that arises from the malignant transformation of benign endometriotic lesions. While epithelial-mesenchymal transition is acknowledged as a crucial process in the progression of endometriosis-associated ovarian cancer, the upstream regulatory mechanisms and key molecular drivers are not fully understood.Methods Differentially expressed genes between benign endometriosis and endometriosis-associated ovarian cancer (EAOC) tissues were identified using Gene Expression Omnibus datasets. The functional role of stromal cell-derived factor-1 (SDF-1) was investigated through in vitro overexpression and knockdown models. Mechanistic studies focused on SDF-1 interaction with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and regulation of epithelial-mesenchymal transition (EMT)-associated proteins. A retrospective analysis of 38 EAOC patients was performed to evaluate the association between SDF-1 expression and prognosis.Results SDF-1 expression was significantly elevated in EAOC tissues compared with benign endometriosis and correlated with EMT-related phenotypes. Functional assays demonstrated that SDF-1 enhanced cellular migration and invasion capacities. Mechanistically, SDF-1 induced EMT through activation of the PI3K/AKT signaling pathway. Clinically, high SDF-1 expression was associated with reduced overall survival and increased recurrence risk. Multivariate Cox regression analysis identified SDF-1 as an independent adverse prognostic factor in EAOC.Conclusions This study systematically elucidates the critical role of SDF-1 in the malignant transformation of endometriosis to EAOC. SDF-1 promotes tumor invasion and metastasis via PI3K/AKT-mediated induction of EMT. These findings highlight SDF-1 as a promising biomarker for early diagnosis and a potential therapeutic target, offering novel avenues for precision management of EAOC.

Background:Accurate prediction of the visceral pleural invasion (VPI) status in stage I peripheral non-small cell lung cancers (NSCLCs) may help patients benefit from surgery and chemotherapy strategies. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is a combination of CT and FDG PET that reflects not only the FDG PET-associated metabolic features but also the CT-associated anatomic features. The FDG PET/CT radiomics-based model has demonstrated greater accuracy in the diagnosis, prognosis, and treatment evaluation of tumors compared with those based on CT only, including in NSCLCs. This study aimed to develop an FDG PET/CT-based VPI prediction (VPIP) index for peripheral subpleural NSCLCs ≤3 cm to help design a more rational treatment strategy for small-size NSCLCs. Methods:This retrospective study included 2,383 patients with peripheral subpleural NSCLCs ≤3 cm between August 2016 and February 2022 diagnosed at Shanghai Chest Hospital. The patients were randomly assigned to the modeling and validation cohorts in a 3:1 ratio. Further, 1,691 PET and 1,691 CT radiomics features of tumors were extracted using the Multi-Modality Radiomics software on the syngo.via workstation. The t-test combined with least absolute shrinkage and selection operator regression was used for feature selection. The regression coefficients were used to formulate the VPIP index. The predictive performance of the VPIP index in both cohorts was assessed using the area under the receiver operating characteristic curve (AUC) and compared using the DeLong test. Results:Eventually, 6 PET and 10 CT features were selected to formulate the FDG PET/CT-based VPIP index. The predictive accuracy of the PET/CT-based VPIP index, with a threshold >-1.13 for VPI, was 83.4% and 83.7% in the modeling and validation cohorts, respectively. This accuracy was substantially higher than that based on PET alone (formulated by 15 PET radiomics features) or CT alone (formulated by 12 CT radiomics features) in both the modeling (AUC, 0.926 vs. 0.906 vs. 0.921) and validation cohorts (AUC, 0.918 vs. 0.892 vs. 0.905) (P=0.00-0.01). Conclusions:The VPIP index formulated in this study based on FDG PET/CT in peripheral subpleural NSCLCs ≤3 cm may help develop more rational surgery strategies for small-size NSCLCs.

BACKGROUND:Cervical cancer is a prevalent form of cancer in women, and the inhibition of ferroptosis has been shown to promote the progression of cervical cancer tumours. This study aimed to investigate the role of PIN1 in regulating ferroptosis in cervical cancer, focusing on its ability to modulate the cGAS-STING pathway and the potential involvement of USP34 as an upstream regulator of PIN1. METHODS:PIN1-overexpressing and PIN1-knockdown cell lines were constructed. In addition to activating p-STING via PIN1 knockdown and inhibiting p-STING via PIN1 overexpression, cell activity was evaluated via CCK8, EdU, transwell and flow cytometry assays. The expression of USP34, PIN1, cGAS, p-STING, and STING was analysed through qRT-PCR and immunofluorescence. Western blot analysis was used to detect the regulatory effects of USP34, PIN1, cGAS, p-STING, and STING, as well as SUMOylation. Ferroptosis was detected by ROS immunofluorescence, the mitochondrial membrane potential, and mitochondrial electron microscopy. Furthermore, PIN1-knockdown cells were used to construct xenograft tumours in BALB/c male nude mice, and the relevant verification experiments were performed in vivo. RESULTS:PIN1 can increase the proliferation and invasion of cervical cancer cells by significantly inhibiting ferroptosis. The mechanism by which PIN1 promotes cancer is inhibition of the cGAS-STING pathway. Additionally, we found that USP34 could increase the expression of PIN1 via SUMOylation in cervical cancer cells. CONCLUSION:This study confirmed that USP34 could upregulate PIN1 expression and SUMOylation, thereby inhibiting ferroptosis by suppressing the cGAS-STING pathway and in turn promoting the progression of cervical cancer.

Background: Anterior mediastinal masses are relatively uncommon, and mediastinal lymphomas are the malignancies most likely to be confused with thymic epithelial tumors (TETs). The aim of this study was to investigate whether the combination of (18)fluorine-fluorodeoxyglucose positron emission tomography-computed tomography (F-18-FDG PET-CT) findings and clinical parameters is useful in differentiating lymphoma from TETs in anterior mediastinal masses.Methods: This retrospective study consecutively included 304 patients with anterior mediastinal masses (244 TETs and 60 lymphomas) who underwent(18)F-FDG PET-CT 1 to 2 weeks before tumor resection or biopsy between August 2016 and March 2022. The correlations between the maximum standardized uptake value (SUVmax) of tumors and clinical parameters of patients with histology subtypes were analyzed. Receiver operating characteristic curve analysis was used to obtain the optimal cutoff values of age, lactate dehydrogenase (LDH), tumor size, and SUVmax to predict lymphoma. Logistic regression analysis was used to identify potential predictive factors for lymphoma.Results: Lymphoma was significantly associated with younger patient age, higher LDH level, larger tumor size, and higher SUVmax compared to TETs (P<0.001). In the modeling cohort, age <= 40.5 years, LDH level >= 197 U/I, tumor size >= 10.72 cm, and SUVmax >= 11.95 were identified as independent predictors for lymphoma with odds ratios of 20.14 [95% confidence interval (CI): 6.02-67.40; P<0.001], 4.89 (95% CI: 1.27-18.89; P=0.021), 8.82 (95% CI: 2.31-33.69; P=0.001), and 30.01 (95% CI: 6.59-136.72; P<0.001), respectively. The accuracy of age, LDH, tumor size, and SUVmax in predicting lymphoma was 84.8%, 67.8%, 85.2%, and 78.3% respectively. The combination of the four above parameters could improve the predictive accuracy to 89.1%, and in the validation cohort, this combination increased the predictive accuracy to 87.8%. Conclusions: SUVmax on F-18-FDG PET-CT has the potential ability to discriminate lymphomas from TETs in the diagnosis of anterior mediastinal masses, and the combination of SUVmax with clinical parameters can improve the diagnostic accuracy. This combination may therefore may be helpful in avoiding unnecessary operation in patients with anterior mediastinal lymphomas.

(1) Background: polycystic ovarian syndrome (PCOS) is a heterogeneous syndrome with a constellation of cardiometabolic risk factors. We aimed to investigate if the association of body fat mass (BFM) and skeletal muscle mass (SMM) with cardiometabolic risk differed in PCOS subtypes. (2) Methods: 401 participants (245 PCOS and 156 controls) were assessed for anthropometric measurements, glucose–lipid profiles, reproductive hormones and body composition with propensity score-matched (PSM) analysis. The association of the cardiometabolic risk score (z score, calculated based on levels of obesity and gluco-lipid measurements) with BFM (estimated by trunk BFM/Height2) and SMM (estimated by SMM/Height2) was calculated. (3) Results: Trunk BFM/Height2 and SMM/Height2 were both positively associated with cardiometabolic risk in PCOS (trunk BFM/Height2, OR 2.33, 95% CI 1.49–3.65; SMM/Height2, OR 2.05, 95% CI 1.12–3.76). SMM/Height2 associated with increased cardiometabolic risk in obese PCOS (BMI ≥ 28 kg/m2, OR 2.27, 95% CI 1.15–4.47). For those with lower BMI (<28 kg/m2), trunk BFM/Height2 showed a higher OR in both groups (PCOS, OR 2.12, 95% CI 1.06–4.24; control 2.04, 95% CI 1.04–4.02). Moreover, distinct associations among BMI-stratified groups were validated in hierarchical clustering identifying metabolic and reproductive clusters. (4) Conclusions: BFM and SMM are synergistically associated with higher cardiometabolic risk in PCOS women. Although BFM contributes to increased cardiometabolic risk, SMM also plays a primary role in obese PCOS. Our results highlight the importance of body composition in the management of PCOS.

BACKGROUND:Accurate, noninvasive, and reliable assessment of epidermal growth factor receptor (EGFR) mutation status and EGFR molecular subtypes is essential for treatment plan selection and individualized therapy in lung adenocarcinoma (LUAD). Radiomics models based on 18F-FDG PET/CT have great potential in identifying EGFR mutation status and EGFR subtypes in patients with LUAD. The validation of multi-center data, model visualization, and interpretation are significantly important for the management, application and trust of machine learning predictive models. However, few EGFR-related research involved model visualization and interpretation, and multi-center trial. PURPOSE:To develop explainable optimal predictive models based on handcrafted radiomics features (HRFs) extracted from multi-center 18F-FDG PET/CT to predict EGFR mutation status and molecular subtypes in LUAD. METHODS:Baseline 18F-FDG PET/CT images of 383 LUAD patients from three hospitals and one public data set were collected. Further, 1808 HRFs were extracted from the primary tumor regions using Pyradiomics. Predictive models were built based on cross-combination of seven feature selection methods and seven machine learning algorithms. Yellowbrick and explainable artificial intelligence technology were used for model visualization and interpretation. Receiver operating characteristic curve, classification report and confusion matrix were used for model performance evaluation. Clinical applicability of the optimal models was assessed by decision curve analysis. RESULTS:STACK feature selection method combined with light gradient boosting machine (LGBM) reached optimal performance in identifying EGFR mutation status ([area under the curve] AUC = 0.81 in the internal test cohort; AUC = 0.62 in the external test cohort). Random forest feature selection method combined with LGBM reached optimal performance in predicting EGFR mutation molecular subtypes (AUC = 0.89 in the internal test cohort; AUC = 0.61 in the external test cohort). CONCLUSIONS:Explainable machine learning models combined with radiomics features extracted from multi-center/scanner 18F-FDG PET/CT have certain potential to identify EGFR mutation status and subtypes in LUAD, which might be helpful to the treatment of LUAD.

To observe the effects of liraglutide on abdominal fat distribution in Chinese subjects with obesity in 12 weeks, and further to explore the correlation between abdominal fat content and glucose metabolism after monotherapy. This study recruited 71 obese subjects. All the subjects have received liraglutide monotherapy (0.6 mg-1.8 mg/d) for 12 weeks. Clinical assessment, laboratory assays and magnetic resonance imaging (MRI) examination were accessed at baseline and after 12 weeks treatment. MRI was applied to measure abdominal fat distribution, calculated by proton-density fat fraction (PDFF). After 12 weeks of liraglutide monotherapy, body weight in the obese participants decreased significantly (P < 0.001). Fasting blood glucose (FBG) levels, 2 h post-load blood glucose (2hPBG) levels, and glycosylated hemoglobin (HbA1c) were remarkably improved after liraglutide monotherapy (all P < 0.001). Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were significantly reduced after liraglutide monotheraphy (both P < 0.001). There was a notable reduction in liver fat content (LFC) after liraglutide monotherapy (P < 0.001). In the further analysis, LFC was greater in obese subjects with impaired glucose regulation (IGR) at baseline compared to those with normal glucose tolerance (NGT) (P = 0.002). The LFC reduction in IGR group was significantly greater than those in NGT group after liraglutide treatment (P < 0.001). Pearson correlation analysis showed that reduction of LFC was significantly correlated with improvement of FBG (r = 0.587, P < 0.001) and HbA1c (r = 0.607, P < 0.001) in obese patients. LFC was significantly reduced after liraglutide monotherapy for 12 weeks in subjects with obesity. The LFC reduction is likely to be associated with IGR remission in obese subjects.

BackgroundThe first-line treatment for polycystic ovary syndrome (PCOS) is lifestyle modification. However, it is currently unknown whether digital medicine can assist patients with PCOS in maintaining a healthy lifestyle while alleviating PCOS symptoms. ObjectiveThis study aims to evaluate the efficacy of WeChat-based digital intervention versus metformin treatment in women with PCOS and insulin resistance. MethodsA total of 80 women with PCOS and insulin resistance were recruited from an endocrinology clinic and randomly assigned to receive either a WeChat-based digital intervention (n=40, 50%) or metformin (n=40, 50%) for 12 weeks. The WeChat-based digital intervention consisted of 3 modules; a coach assisted the patients in using the intervention. The primary outcome was the change in a homeostatic model assessment for insulin resistance. At baseline and after the 12-week intervention, anthropometric parameters, menstruation frequency, sex hormone levels, metabolic factors, and body fat distribution were measured in the clinic. Furthermore, self-assessed web-based questionnaires on diet, exercise, sleep, anxiety, and depression were obtained. ResultsA total of 72 participants completed the follow-up (for a 90% follow-up rate), including 35 of 40 (88%) participants from the digital intervention group and 37 of 40 (93%) participants from the metformin group. The homeostatic model assessment for insulin resistance in the digital intervention group was significantly improved after 12 weeks of treatment with a mean change of –0.93 (95% CI –1.64 to –0.23), but no statistical difference was observed between the groups (least squares mean difference –0.20; 95% CI –0.98 to 0.58; P=.62). Both digital intervention and metformin treatment significantly improved menstruation frequency (digital intervention: P<.001; metformin: P<.001) and reduced body weight (digital intervention: P<.001; metformin: P<.001) and total fat mass (digital intervention: P<.001; metformin: P<.001). Furthermore, the digital intervention had a significant advantage over metformin in improving waist circumference (least squares mean difference –1.84; 95% CI –3.44 to –0.24; P=.03), waist-to-hip ratio (least squares mean difference –0.02; 95% CI –0.03 to 0.00; P=.03), total fat mass (least squares mean difference –1.59; 95% CI –2.88 to –0.30; P=.02), and dehydroepiandrosterone sulfate (least squares mean difference –69.73; 95% CI –129.70 to –9.75; P=.02). In terms of safety, the main adverse events were sensations of hunger in the digital intervention group (2/40, 5%) and gastrointestinal adverse events in the metformin group (12/40, 30%). ConclusionsOur data suggest that digital intervention is an effective treatment option for patients with PCOS, with an efficacy comparable to that of metformin, and that it can also alleviate the negative effects of medications and make it easier and more efficient to adhere to lifestyle treatments. WeChat-based digital interventions have the potential to provide a new path for the improvement and health of women with PCOS in China. Trial RegistrationClinicalTrials.gov NCT05386706; https://clinicaltrials.gov/study/NCT05386706

Introduction & Objective: Recent studies have shown that liver fat content (LFC) is associated with impaired glucose metabolism and insulin resistance in the obesity. It has been established that GLP-1RA could significantly reduce LFC in patients with T2DM. This study aimed to observe the effects of liraglutide on abdominal fat distribution and glucose metabolism in Chinese subjects with obesity for 12 weeks, and further explore the correlation between abdominal fat content and glucose profiles. Methods: This study recruited 71 obese patients (BMI≥28 kg/m²). All the patients have received liraglutide monotherapy for 12 weeks, and received anthropometric measurement, OGTT (Oral glucose tolerance test) and MRI examination at baseline and after 12 weeks treatment. The association between the glycemic metabolism and abdominal fat content was further analysed. Results: After 12 weeks of liraglutide monotherapy, body weight in the obese participants decreased significantly (P=0.014). Fasting blood glucose (FBG), 2h postprandial blood glucose (2hPBG), HbA1c, HOMA-IR were remarkably improved (all P<0.001). TC and LDL-c were sharply reduced (P=0.004, P=0.027 respectively). LFC was strikingly more in subjects with impaired glucose regulation (IGR) group compared to those with normal glucose tolerance (NGT) at baseline (P=0.002). The decreased LFC in IGR group was significantly greater after liraglutide treatment than those with NGT (P<0.001). Linear regression analysis showed that HOMA-IR at baseline was the independent marker for LFC reduction after liraglutide treatment (B: 0.634; 95%CI:0.100-1.168, P=0.021). Conclusion: Liraglutide monotherapy for 12 weeks significantly reduced LFC in patients with obesity. The LFC reduction may serve as one of possible mechanisms of blood glucose improvement in obese patients. Disclosure M. Du: None. J. Yue: None. Y. Qi: None. S. He: None. X. Lu: None. M. Yang: None. L. Wang: None. Q. Lu: None. J. Ma: None.

Purpose: Approximately 20% of patients with type I endometrial cancer (EC) of the uterus experience recurrence and metastasis. However, existing data do not provide sufficient evidence for the utility of protein levels as prognostic biomarkers in type I EC. This study aims to determine whether epiplakin1 (EPPK1) and progesterone receptor (PR) play a role in the recurrence and metastasis of type I EC. Methods: Following the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) for assessing the quality of biomarker research results, a retrospective analysis was conducted on clinical information and tissue samples of type I EC patients. Protein expression data and clinical data for type I EC were downloaded from The Cancer Proteome Atlas (TCPA) database. We utilized the Kaplan -Meier (K -M) method and Cox proportional hazards regression analyses to evaluate whether epiplakin1 (EPPK1), progesterone receptor (PR) and certain clinical parameters can serve as independent prognostic factors. The Immune Cell Abundance Identifier (ImmuCellAI) and Cancer Immunome Atlas (TCIA) were employed to predict responses to immunotherapy. Immunohistochemistry was carried out to assess the expression of EPPK1 in type I EC. Results: Type I EC patients with high EPPK1 and low PR expression had higher International Federation of Gynecology and Obstetrics (FIGO) stage, recurrence, and metastasis rates. Furthermore, EPPK1 was identified as an independent prognostic factor, and low expression of EPPK1 was predominantly observed in the POLE ultramutated (POLEmut) group, indicating a favorable prognosis. Additionally, the high EPPK1 expression group had a lower Immune Prognostic Score (IPS), suggesting that the high -expression group may not benefit from immune checkpoint inhibitors. Conclusion: High expression of EPPK1 is an independent prognostic factor in type I EC patients with low PR expression. It can identify a subgroup of patients at high risk of recurrence. A more aggressive treatment approach is recommended for these patients.

Introduction/Background Iparomlimab and tuvonralimab (QL1706), a bifunctional PD-1/CTLA-4 dual blocker, showed preliminary efficacy in patients with cervical cancer in phase 1 trial. Methodology This multi-center, open-label, single-arm, phase 2 trial (NCT05557565) recruited immune checkpoint inhibitors naïve patients with recurrent or metastatic cervical cancer (r/m CC) who failed first-line platinum-based chemotherapy with or without bevacizumab, regardless of PD-L1 status. Intravenous injection of iparomlimab and tuvonralimab 5.0 mg/kg every three weeks was administered. The primary endpoint was objective response rate (ORR) evaluated by the independent review committee (IRC). Results As of April 28, 2023, 148 participants were included in the full analysis set. Eastern Cooperative Oncology Group Performance Status scored 1 in 109 (73.6%) patients. Fifty-nine (39.9%) patients received prior bevacizumab. Fifty-five patients (37.2%) had received ≥2 lines of prior treatment. Median follow-up was 11.0 (0.7, 15.5) months. Per IRC, ORR was 33.8% (95% confidence interval [CI]: 26.2%-42.0%), and disease control rate was 64.9% (95% CI: 56.6%-72.5%). Median progression-free survival achieved 5.4 month (95% CI: 3.9–6.9). Median overall survival was not reached. ORR was 25.6% (95% CI: 13.5–41.2) and 37.1% (95% CI: 27.9%-47.1%) in patients with combined positive score (CPS) <1 (n=43) and with CPS≥1 (n=105), respectively. Treatment-related adverse events (TRAE) occurred in 104 (70.3%) patients. TRAE of grade ≥3 occurred in 36 (24.3%) patients, and the most common were anemia (4.1%), gamma-glutamyl transferase increased (2.7%), and lipase increased (2.7%). Three (2.0%) participants had TRAE leading to treatment discontinuation. Nine (6.1%) participants died due to treatment-emergent adverse events, which were all unrelated to the treatment. Conclusion Iparomlimab and tuvonralimab showed promising efficacy and manageable safety in patients with r/m CC who failed first-line chemotherapy. A phase 3 trial (NCT05446883) evaluating iparomlimab and tuvonralimab plus chemotherapy as first-line treatment for r/m CC is ongoing. Disclosures The presenting author, Jihong Liu, and the co-authors Hanmei Lou, Yun Zhou, Dapeng Li, Hongping Zhang, Mingjun Zhang, Lihua Wang, Huijun Cheng, Zi Liu, Wei Duan, and Mei Feng, declare that they have no conflict of interest. The co-authors Chao Wang, Shilin Xue, Hui Li, and Xiaoyan Kang are full-time employees of the company Qilu Pharmaceutical Co., Ltd.

OBJECTIVES:To investigated whether the basal F-18-FDG PET/CT could evaluate the prognosis or the benefit from adjuvant chemotherapy after surgery of patients with early-stage NSCLC with visceral pleural invasion. MATERIALS AND METHODS:A total of 116 patients with stage IB (T2, ≤ 3 cm with VPI, N0, M0) NSCLC underwent tumor resection and F-18-FDG PET/CT 1-3 weeks before surgery and were followed up for 1-79 months after surgery. SUVpeak, SUVmax, SUVmean, MTV, and TLG of tumors were obtained. The primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. ROC curve analysis, Cox regression test, and the Kaplan-Meier method were used for statistical analysis. RESULTS:High SUVs, TLG, and MTV were associated with postoperative progression of NSCLC (the area under the ROC curve: 0.695 to 0.750, P < .001). The increase of SUVs, TLG or MTV was associated with short postoperative PFS (P < .001) while an increase in TLG (P = .016) or MTV (P = .018) was associated with short postoperative OS. TLG > 16.81 was an independent indicator of both the short PFS (HR = 5.534, P = .002) and the short OS (HR = 5.075, P = .031). Further, adjuvant chemotherapy was associated with longer PFS in NSCLCs with TLG > 16.81 (treated vs. untreated: 63 vs. 52 months; HR = 2.242, P = .022) rather than those with TLG ≤ 16.81. CONCLUSION:SUV-based parameters on F-18-FDG PET/CT have the potential to evaluate the prognosis and benefit from adjuvant chemotherapy after tumor resection in stage IB (T2, ≤ 3 cm with VPI, N0, M0) NSCLC and therefore may be helpful for lung cancer treatment.